Nabarro, J D
A personal series of 256 cases of acromegaly/gigantism seen over a 20-year period from 1963 is described. The insidious nature of the condition resulted in delay in diagnosis which was often made by a doctor when seeing the patient for an unrelated problem. Other features which commonly led to the diagnosis being made were headache, change in appearance, carpal tunnel syndrome, amenorrhoea and diabetes. The Hardy system for grading the radiological appearance of the pituitary tumour was used. Widely invasive tumours were not common but tended to occur in patients with younger age of onset and high GH levels. The occurrence of various symptoms and clinical features was noted and the changes resulting from reducing the GH level to normal. The incidence of hypertension, but not of coronary artery disease, is increased and the blood pressure may be reduced following successful treatment. The effects on the upper and lower respiratory tract are reported as well as sleep apnoea and problems associated with anaesthesia. Skin manifestations included sweating, pigmented skin tags, acanthosis nigricans and cutis verticis gyrata. In the skeletal system the incidence of kyphoscoliosis and osteoarthritis especially of the hip is reported: the question of hip replacement is discussed. Diabetes mellitus disappeared in most cases if the acromegaly was cured. In men but not in women the incidence of colloid nodular goitre was increased as was hyperthyroidism in middle-aged women. In two patients a parathyroid adenoma was present: hypercalcaemia was present in five additional patients, but the cause was not determined. The common occurrence of amenorrhoea in the younger women was noted, it was not always associated with hyperprolactinaemia, and often responded to successful treatment of the acromegaly. The association of acromegaly with hirsutism and galactorrhoea is confirmed. The incidence of impotence and loss of libid in the men is discussed: in a proportion of those in whom the
Full Text Available Abstract Acromegaly is an acquired disorder related to excessive production of growth hormone (GH and characterized by progressive somatic disfigurement (mainly involving the face and extremities and systemic manifestations. The prevalence is estimated at 1:140,000–250,000. It is most often diagnosed in middle-aged adults (average age 40 years, men and women equally affected. Due to insidious onset and slow progression, acromegaly is often diagnosed four to more than ten years after its onset. The main clinical features are broadened extremities (hands and feet, widened thickened and stubby fingers, and thickened soft tissue. The facial aspect is characteristic and includes a widened and thickened nose, prominent cheekbones, forehead bulges, thick lips and marked facial lines. The forehead and overlying skin is thickened, sometimes leading to frontal bossing. There is a tendency towards mandibular overgrowth with prognathism, maxillary widening, tooth separation and jaw malocclusion. The disease also has rheumatologic, cardiovascular, respiratory and metabolic consequences which determine its prognosis. In the majority of cases, acromegaly is related to a pituitary adenoma, either purely GH-secreting (60% or mixed. In very rare cases, acromegaly is due to ectopic secretion of growth-hormone-releasing hormone (GHRH responsible for pituitary hyperplasia. The clinical diagnosis is confirmed biochemically by an increased serum GH concentration following an oral glucose tolerance test (OGTT and by detection of increased levels of insulin-like growth factor-I (IGF-I. Assessment of tumor volume and extension is based on imaging studies. Echocardiography and sleep apnea testing are used to determine the clinical impact of acromegaly. Treatment is aimed at correcting (or preventing tumor compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. Transsphenoidal surgery is often the first-line treatment
Acromegaly is a rare disorder caused by autonomous oversecretion of growth hormone mostly by pituitary adenoma. Untreated acromegaly leads to significantly increased morbidity and mortality and impaired quality of life. Early diagnosis and treatment is therefore essential for improvement of patients prognosis and management of acromegaly should be concentrated in specialized centres. Present article summarizes current view on diagnosis and treatment of acromegaly.
de Herder, Wouter W
Pierre Marie coined the term 'acromegaly' in 1886 and linked it to a distinct clinical disease with a characteristic clinical picture. However, Pierre Marie was not the first physician to give a full record of the clinical picture of acromegaly; others had preceded him, like the Dutch physician Johannes Wier. After Marie, pituitary enlargement was noted in almost all patients with acromegaly. Subsequently it was discovered that pituitary hyperfunction caused by a pituitary tumour was indeed the cause of acromegaly. The cause of acromegaly could be further determined after the discovery of growth hormone (GH) and insulin-like growth factor I (IGF-I) and after demonstrating an association with GH hypersecretion and elevated circulating IGF-I. From the beginning of the 20th century, acromegaly could be treated by pituitary surgery and/or radiotherapy. After 1970, medical therapies were introduced that could control acromegaly. First, dopamine agonists were introduced, followed by somatostatin analogues and GH receptor blockers.
Acromegaly is a rare disease caused due to hyper secretion of growth hormone. Most of the cases of acromegaly are caused by pitutary adenoma which can be microadenoma or macroadenomas. These adenomas are never malignant, but can have significant morbidity and mortality. We report a 35 year old female patient presented herewith classical presentation of acromegaly with chief complain of weight gain, excessive sweating , widening of both hands and feet and was diagnosed as a case of acromega...
Murrant, N J; Gatland, D J
Death from respiratory causes in acromegaly is three times more common than in the general population and is most often the result of upper airways obstruction, although less commonly pulmonary dysfunction and disturbance of the central nervous system may occur. These factors may be found alone or in combination. Despite several reports of laryngeal involvement, upper airway obstruction in acromegaly is usually regarded as being due to macroglossia and pharyngeal soft tissue hypertrophy. We present four cases of acromegaly in which tracheostomy was required for laryngeal obstruction, with a review of the literature concerning the nature of respiratory problems in acromegaly.
Ludecke, D.K.; Tolis, G.T.
This book contains five sections, each consisting of several papers. The section headings are: Biochemistry and Physiology of GH and Growth Factors, Pathology of Acromegaly, Clinical Endocrinology of Acromegaly, Nonsurgical Therapy of Acromegaly, and Surgical Therapy of Acromegaly.
A. Muhammad (Ammar); S.J.C.M.M. Neggers (Bas); A-J. van der Lely (Aart-Jan)
textabstractIntroduction: Acromegaly is a rare disorder in which, due to the high incidence of secondary hypogonadism, pregnancies are relatively rare. However, some women with acromegaly do get pregnant, which brings along questions about medication, complications and follow-up. This review tries
Vitale, G; Pivonello, R; Lombardi, G; Colao, A
Cardiovascular morbidity and mortality are increased in acromegaly. In fact, GH and IGF-I excess induces a specific cardiomyopathy. The early stage of acromegaly is characterized by the hyperkinetic syndrome (high heart rate and increased systolic output). Frequently, concentric biventricular hypertrophy and diastolic dysfunction occur in acromegaly, leading to an impaired systolic function ending in heart failure if the disease is untreated or unsuccessfully untreated. Besides, abnormalities of cardiac rhythm and of valves have been also described in acromegaly. The coexistence of other complications, such as arterial hypertension and diabetes, aggravates the acromegalic cardiomyopathy. The suppression of GH/IGF-I following an efficacious therapy could decrease left ventricular mass and improve cardiac function. In conclusion, a careful evaluation of cardiac function, morphology and activity seems to be mandatory in acromegaly.
Acromegaly is a rare disease characterized by excess secretion of growth hormone (GH) and increased circulating insulin-like growth factor 1 (IGF-1) concentrations. The disease is associated with increased morbidity and premature mortality, but these effects can be reduced if GH levels are decreased to <2.5 μg\\/l and IGF-1 levels are normalized. Therapy for acromegaly is targeted at decreasing GH and IGF-1 levels, ameliorating patients\\' symptoms and decreasing any local compressive effects of the pituitary adenoma. The therapeutic options for acromegaly include surgery, radiotherapy and medical therapies, such as dopamine agonists, somatostatin receptor ligands and the GH receptor antagonist pegvisomant. Medical therapy is currently most widely used as secondary treatment for persistent or recurrent acromegaly following noncurative surgery, although it is increasingly used as primary therapy. This Review provides an overview of current and future pharmacological therapies for patients with acromegaly.
Full Text Available This paper outlines the present status of medical therapy of acromegaly. Indications for permanent postoperative treatment, postirradiation treamtent to bridge the interval until remission as well as primary medical therapy are elaborated. Therapeutic efficacy of the different available drugs—somatostatin receptor ligands (SRLs, dopamine agonists, and the GH antagonist Pegvisomant—is discussed, as are the indications for and efficacy of their respective combinations. Information on their mechanism of action, and some pharmakokinetic data are included. Special emphasis is given to the difficulties to define remission criteria of acromegaly due to technical assay problems. An algorithm for medical therapy in acromegaly is provided.
Hannon, A M; Thompson, C J; Sherlock, M
Acromegaly is a clinical syndrome which results from growth hormone excess. Uncontrolled acromegaly is associated with cardiovascular mortality, due to an excess of risk factors including diabetes mellitus, hypertension and cardiomegaly. Diabetes mellitus is a frequent complication of acromegaly with a prevalence of 12-37%. This review will provide an overview of a number of aspects of diabetes mellitus and glucose intolerance in acromegaly including the following: 1. Epidemiology and pathophysiology of abnormalities of glucose homeostasis 2. The impact of different management options for acromegaly on glucose homeostasis 3. The management options for diabetes mellitus in patients with acromegaly RECENT FINDINGS: Growth hormone and IGF-1 have complex effects on glucose metabolism. Insulin resistance, hyperinsulinaemia and increased gluconeogenesis combine to produce a metabolic milieu which leads to the development of diabetes in acromegaly. Treatment of acromegaly should ameliorate abnormalities of glucose metabolism, due to reversal of insulin resistance and a reduction in gluconeogenesis. Recent advances in medical therapy of acromegaly have varying impacts on glucose homeostasis. These adverse effects influence management choices in patients with acromegaly who also have diabetes mellitus or glucose intolerance. The underlying mechanisms of disorders of glucose metabolism in patients with acromegaly are complex. The aim of treatment of acromegaly is normalisation of GH/IGF-1 with reduction of co-morbidities. The choice of therapy for acromegaly should consider the impact of therapy on several factors including glucose metabolism.
Full Text Available Acromegaly is a rare disease caused due to hyper secretion of growth hormone. Most of the cases of acromegaly are caused by pitutary adenoma which can be microadenoma or macroadenomas. These adenomas are never malignant, but can have significant morbidity and mortality. We report a 35 year old female patient presented herewith classical presentation of acromegaly with chief complain of weight gain, excessive sweating , widening of both hands and feet and was diagnosed as a case of acromegaly due to macroadenoma of pirtutary gland, on the basis of typical clinical features and hormonal parameters also radiological findings. Patient underwent transsphenoidal surgical resection of macroadenoma and recovered completely from the disease. Early recognition and diagnosis will help to avoid the complications of disease.
Gaya Thanabalasingham; Grossman, Ashley B.
Acromegaly is characterized by chronic, excess secretion of growth hormone (GH) from a pituitary adenoma, and elevated hepatic insulin-like growth factor 1 (IGF-1) levels. Significant progress has been made in the development of medical therapies to achieve biochemical and symptomatic control in acromegaly. In this review we discuss the three currently available medical therapies, which include somatostatin analogs, dopamine agonists and pegvisomant. We describe a step-wise approach in which ...
Said Azzoug; Farida Chentli
Introduction: Although growth hormone (GH) has been implicated in the pathogenesis of diabetic retinopathy (DR), DR is deemed to be rare in patients with GH excess. Our aim was to study its prevalence in subjects with acromegaly suffering from diabetes mellitus (DM), to analyze its characteristics, and to look for predictive factors such as age at diagnosis, GH concentration and duration, DM duration, DM control, and family background. Materials and Methods: Forty patients with acromegaly and...
Tatiana Hotimsky Millner
Full Text Available Pegvisomant is a new drug that blocks growth hormone peripheralreceptors, allowing normalization of insulin-like growth factor-1levels and consequently of clinical symptoms, reducing morbidityand mortality associated with acromegaly in almost all patients.Its introduction made us review the literature aiming to comparethe currently available therapies for acromegaly and theirrespective advantages and disadvantages. The treatmentalgorithms for this disease were reviewed considering that thedifferent existing therapies allow more adequate individualizationto each specific case, and addressing cost, availability, efficacyand safety.
Crowley, R K
BACKGROUND: Acromegaly secondary to growth hormone-releasing hormone (GHRH) excess is rare. AIMS\\/CASE DESCRIPTION: We report two patients with acromegaly who were diagnosed with sellar gangliocytomas that were immunopositive for GHRH. Tumour tissue persisted after debulking surgery and in the second case this was associated with persistent growth hormone hypersecretion, successfully suppressed by a somatostatin analogue. CONCLUSIONS: The development of functional pituitary adenomas in association with sellar gangliocytomas is poorly understood. We present a brief discussion of the possible aetiology of these unusual pituitary tumours.
Arias, Miguel A; Pachón, Marta; Rodríguez-Padial, Luis
Cases of sudden cardiac death have been reported in patients with acromegaly. Malignant ventricular arrhythmias may play an important role in this fatal complication, but the exact mechanisms are not well understood. We report on an acromegalic patient presenting with documented recurrent syncopal ventricular tachycardia.
Muhammad, Ammar; Neggers, Sebastian J; van der Lely, Aart J
Acromegaly is a rare disorder in which, due to the high incidence of secondary hypogonadism, pregnancies are relatively rare. However, some women with acromegaly do get pregnant, which brings along questions about medication, complications and follow-up. This review tries to address these issues and provide the reader with practical information. This review summarizes published data. Acromegaly is a disorder that is characterized by changes in growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin concentrations and actions. All these hormones are important in pregnancy as well. In principle, the fetal-placental collaboration between mother and child more-or-less takes over the control over GH and IGF-1, not only in normal physiology but also to a certain extend in acromegaly. When medication for the high GH levels or actions is continued during pregnancy, both dopamine agonists, somatostatin analogs and GH receptor antagonists have been used and the available data suggest that there are no adverse consequences on mother or fetus to date. However, it is strongly advised to stop any medical intervention during pregnancy until more data are available on the safety of these compounds. Also, medical treatment is not needed as tumor size and disease activity are not reported to escape.
Wassenaar, Monica Johanna Elisabeth
This thesis describes the long-term consequences of growth hormone and insulin-like growth factor I excess in patients cured from acromegaly for a mean duration of 17 years. Regarding the considerable prevalence of diverse morbidity in these patients, during the active phase of the disease but even
Wassenaar, Monica Johanna Elisabeth
This thesis describes the long-term consequences of growth hormone and insulin-like growth factor I excess in patients cured from acromegaly for a mean duration of 17 years. Regarding the considerable prevalence of diverse morbidity in these patients, during the active phase of the disease but even
Full Text Available Abstract Radiotherapy (RT remains an effective treatment in patients with acromegaly refractory to medical and/or surgical interventions, with durable tumor control and biochemical remission; however, there are still concerns about delayed biochemical effect and potential late toxicity of radiation treatment, especially high rates of hypopituitarism. Stereotactic radiotherapy has been developed as a more accurate technique of irradiation with more precise tumour localization and consequently a reduction in the volume of normal tissue, particularly the brain, irradiated to high radiation doses. Radiation can be delivered in a single fraction by stereotactic radiosurgery (SRS or as fractionated stereotactic radiotherapy (FSRT in which smaller doses are delivered over 5-6 weeks in 25-30 treatments. A review of the recent literature suggests that pituitary irradiation is an effective treatment for acromegaly. Stereotactic techniques for GH-secreting pituitary tumors are discussed with the aim to define the efficacy and potential adverse effects of each of these techniques.
Full Text Available Acromegaly is characterized by chronic, excess secretion of growth hormone (GH from a pituitary adenoma, and elevated hepatic insulin-like growth factor 1 (IGF-1 levels. Significant progress has been made in the development of medical therapies to achieve biochemical and symptomatic control in acromegaly. In this review we discuss the three currently available medical therapies, which include somatostatin analogs, dopamine agonists and pegvisomant. We describe a step-wise approach in which a somatostatin analog is followed by the addition of a dopamine agonist, and then if required the addition of or replacement by pegvisomant. New somatostatin agonists such as pasireotide, and the introduction of new orally-acting somatostatin agonists, should increase the therapeutic choices available in the near future.
Thanabalasingham, Gaya; Grossman, Ashley B
Acromegaly is characterized by chronic, excess secretion of growth hormone (GH) from a pituitary adenoma, and elevated hepatic insulin-like growth factor 1 (IGF-1) levels. Significant progress has been made in the development of medical therapies to achieve biochemical and symptomatic control in acromegaly. In this review we discuss the three currently available medical therapies, which include somatostatin analogs, dopamine agonists and pegvisomant. We describe a step-wise approach in which a somatostatin analog is followed by the addition of a dopamine agonist, and then if required the addition of or replacement by pegvisomant. New somatostatin agonists such as pasireotide, and the introduction of new orally-acting somatostatin agonists, should increase the therapeutic choices available in the near future.
Prolonged overproduction of growth hormone, like insulin-like growth factor-1 hypersecretion leads to acromegaly in adults. This is associated with several co-morbidities and increased mortality. Despite typical clinical features and modern diagnostic tools, it often takes years to diagnose from the onset of the disease. The aims of the treatment are to reduce or control tumour growth, inhibit growth hormone hypersecretion, normalize insulin-like growth factor-1 levels, treat co-morbidities and, therefore, reduce mortality. There are three approaches for therapy: surgery, medical management (dopamine agonists, somatostatin analogues and growth hormone receptor antagonist), and radiotherapy. Efficient therapy of the disease is based on the appropriate multidisciplinary team management. The review provides a summary of medical treatment for acromegaly.
Kuhn, Emmanuelle; Chanson, Philippe
Acromegaly, a rare disease due to growth hormone (GH) hypersecretion by a pituitary adenoma, is associated with severe comorbidity and premature death if not adequately treated. The usual first-line treatment is surgery. Various drugs, including somatostatin receptor ligands, dopamine agonists and GH receptor antagonists, are now available for use if surgery fails to suppress GH/IGF-I hypersecretion. Cabergoline, now the preferred dopamine agonist for treating hyperprolactinemia, is also used off-label for treating acromegaly. Cabergoline monotherapy is reported to normalize IGF-I levels in more than one-third of patients with acromegaly. When a somatostatin receptor ligand proves ineffective, cabergoline add-on therapy normalizes the IGF-I level in 40-50% of patients. Finally, when combined with the GH receptor antagonist pegvisomant in patients with mild uncontrolled disease, cabergoline helps to achieve normal IGF-I levels while avoiding the need for high-dose pegvisomant. Cabergoline is also inexpensive and well tolerated; in particular, it does not appear to promote heart valve disease.
Full Text Available Introduction: Although growth hormone (GH has been implicated in the pathogenesis of diabetic retinopathy (DR, DR is deemed to be rare in patients with GH excess. Our aim was to study its prevalence in subjects with acromegaly suffering from diabetes mellitus (DM, to analyze its characteristics, and to look for predictive factors such as age at diagnosis, GH concentration and duration, DM duration, DM control, and family background. Materials and Methods: Forty patients with acromegaly and DM (21 males, 19 females, median age = 50 years, underwent a systematic ophthalmological examination with dilated funduscopy to seek diabetic retinopathy. Results: Among this population, 05 (12.5% had DR. It was at an early stage or background retinopathy in 3 cases and at a more advanced stage or proliferative retinopathy in 2 cases. We did not find any correlation with age at diagnosis, GH levels and duration, DM duration and family history of DM, but poor glycemic control seems to play a role although statistical analysis showed borderline significance. Conclusion: From this study, we conclude that prevalence of DR in patients with acromegaly is 12.5%, and it is slight or moderate. Among studied factors, only poor glycemic control seems to be implicated in its development.
Hart, T B; Radow, S K; Blackard, W G; Tucker, H S; Cooper, K R
Previous case reports have shown an association between acromegaly and the sleep apnea syndrome (SAS). Some of the patients described had central SAS, raising the possibility that an elevation of the growth hormone (GH) level may cause a defect in respiratory drive. We determined the prevalence of SAS in 21 patients with a history of acromegaly. We separated them into two groups based on serum GH concentrations. Ten patients had active acromegaly (mean GH concentration, 62.2 ng/mL; range, 12.6 to 148 ng/mL), while 11 patients had inactive acromegaly (mean GH, 3.2 ng/mL; range, 0.7 to 6.4 ng/mL). Four of the ten patients with active acromegaly had SAS; none of the 11 patients with inactive acromegaly had SAS. Three patients with SAS had the purely obstructive type, and one had the mixed central and obstructive type. The hypercapnic ventilatory response was normal in all patients tested and was not influenced by the GH level. We conclude that SAS is associated with active acromegaly and that the GH level does not affect the hypercapnic ventilatory response. The absence of SAS in successfully treated patients suggests that it may resolve after a normal GH level is restored.
John D. Rolston
Full Text Available Acromegaly is debilitating disease occasionally refractory to surgical and medical treatment. Stereotactic radiosurgery, and in particular Gamma Knife surgery (GKS, has proven to be an effective noninvasive adjunct to traditional treatments, leading to disease remission in a substantial proportion of patients. Such remission holds the promise of eliminating the need for expensive medications, along with side effects, as well as sparing patients the damaging sequelae of uncontrolled acromegaly. Numerous studies of radiosurgical treatments for acromegaly have been carried out. These illustrate an overall remission rate over 40%. Morbidity from radiosurgery is infrequent but can include cranial nerve palsies and hypopituitarism. Overall, stereotactic radiosurgery is a promising therapy for patients with acromegaly and deserves further study to refine its role in the treatment of affected patients.
Wittmann, A L
The tongues of two patients with macroglossia were examined at autopsy. One of the patients had acromegaly and the other had hypothyroidism. To evaluate the size of the enlarged tongues, the average weight of the tongue in the human adult was determined first in a series of 20 unselected autopsies, 10 males and 10 females (ages 44 to 85). The weight of the tongue was greater in males than in females and was directly correlated with the height of the subject. Cachexia had relatively little effect on the weight. In acromegaly (case 21) and myxedema (case 22) the tongue was enlarged by at least 50%. Histopathology showed enlargement of muscle fibers especially anteriorly in acromegaly and hypothyroidism, thickening of the epithelium and increased subepithelial and interstitial connective tissue. Incidental findings included venous thrombi and telangiectasia in the subepithelial connective tissue in both hypothyroidism and acromegaly and a corpus amylaceum and two islands of hyaline cartilage in the tongue of hypothyroidism.
Kopff, B; Mucha, S; Wolffenbuttel, B H; Drzewoski, J
Abnormalities of glucose metabolism are a common feature of acromegaly. Overt diabetes mellitus develops in about 10-15% of patients. We present an unusual complication of acromegaly: a 37-year old man with a 2-year history of acromegaly developed diabetic ketoacidosis 3 weeks after transsphenoidal
Kopff, B; Mucha, S; Wolffenbuttel, B H; Drzewoski, J
Abnormalities of glucose metabolism are a common feature of acromegaly. Overt diabetes mellitus develops in about 10-15% of patients. We present an unusual complication of acromegaly: a 37-year old man with a 2-year history of acromegaly developed diabetic ketoacidosis 3 weeks after transsphenoidal
Ferramosca, B; Bianchi, D; Serra, D; Savini, R; Villecco, A S; Bugiardini, R
Acromegaly involves cardiovascular complications mostly due to the presence of hypertension, diabetes and atherosclerosis. However the appearance of cardiac decompensation and arrhythmias in the absence of predisposing factors tends to support the hypothesis of a specific myocardiopathy caused by excess GH. In order to assess the existence and course of subclinical cardiac alterations, 8 acromegaly patients were examined: 4 males and 4 females aged 31-56 with GH levels of 24-70 ng/ml (M + CD X 47 +/- 16) and no cardiovascular symptoms. One of the patients had moderate hypertension and 2 reduced glucose tolerance. The basal ECG showed sporadic ventricular extrasystoles in 2 cases and alterations compatible with left ventricular hypertrophy in another, while the effort ECG produced an asymptomatic depression of the ST segment in the hypertensive patient. The chest X-ray was normal in all cases. The echocardiography study investigated: the thickness of the interventricular septum (IVS = 13.9 +/- 2.8 mm), the thickness of the posterior wall of the left ventricle (LPW = 10.6 +/- 2.9 mm), the septum/posterior wall ratio (IVS/LPW = 1.3 +/- 0.2 the diastolic diameter (DD = 15.4 +/- 11.4 mm), the fraction of shortening (FS = 39.1 +/- 14.5%), the ejection fraction (EF = 64.1 +/- 18.4%) and revealed asymmetrical septal hypertrophy in 3 cases, concentric hypertrophy in another two. In two cases the DD and EF were distinctly altered. The patients were re-examined 2-4 years after surgical or radiation treatment. GH levels (M +/- SD = 10.3 +/- 10.1 ng/ml) were normal in 4 cases and still high, though lower in another two. The remaining two patients had borderline GH levels with high Sm-C. The ECG and chest X-ray were unchanged while echocardiography revealed a significant deterioration in heart function as far as DD (56.4 +/- 10.8 mm, p less than 0.05) were concerned with frankly pathological results in 4 and 3 cases respectively. These data confirm the view that most acromegalic
Pickett, J B; Layzer, R B; Levin, S R; Scheider, V; Campbell, M J; Sumner, A J
Seventeen consecutive acromegalic patients were evaluated for evidence of neuromuscular dysfunction and followed for 1 year after hypophysectomy. Before treatment, four patients had both a myopathy and the carpal tunnel syndrome, five had myopathy alone, four had carpal tunnel syndrome alone, and four had neither. The myopathy was caracterized by mild, strictly promixal weakness and flabbiness of muscles; electromyography revealed typical myopathic abnormalities, but serum enzymes and muscle biopsy usually were normal. The presence of myopathy or the carpal tunnel syndrrome could not be correlated with the magnitude of growth hormone elevation or any secondary endocrine derangement, but myopathy was associated with a longer duration of acromegaly. Carpal tunnel symptoms usually improved in the first 6 weeks after hypophysectomy, while myopathy improved more slowly and sometimes was detectable 1 year later.
Siddiqui, N I; Chowdhury, K S; Rahman, S; Sarker, C B; Rahman, K M
A fifty years old woman hailing from Purbadhala of Netrokona district complaining of gradual enlargement of hands, feet, nose and other acral parts of the body for about last eight years. She noticed coarsening of the skin and gradual protrusion of her lower jaw. She complained of headache, vertigo, frequent passage of urine, increased thirst, weight loss and fatiguability. She was found hypertensive having blood pressure 200/110 mm of Hg. Her appearance was coarse with rough skin. There were enlargement of hands, feet, nose, lower jaw with prognathism and enlargement of other acral parts. Investigations revealed high plasma glucose level, both fasting and 2 hrs. after glucose, high level of growth hormone, failure of suppression of growth hormone during OGTT. Thyroid function tests of the patient were found normal with increased heel pad size and enlarged sella turcica in all diameters. She was diagnosed as a case of acromegaly due to growth hormone hypersecretion.
Holdaway, I M; Rajasoorya, C
Acromegaly is a consequence of chronic growth hormone (GH) excess, due in the majority of cases to a GH-secreting pituitary adenoma, and occurring with a population prevalence of 60 per million and an incidence of 3-4 per million per year. Males and females appear to be equally affected with an average age of presentation of 44 years. Younger patients may have more aggressive tumours and higher GH concentrations. There is co-existent hyperprolactinaemia in about one third of cases, and a variable proportion of [figure: see text] tumours appear to have activating mutations of the gsp gene or other genetic abnormalities. Acute complications such as carpal tunnel syndrome, sweating and obstructive sleep apnoea are usually readily reversible with treatment of the condition, but chronic complications such as hypertension, diabetes and heart disease are less readily corrected and post-treatment GH levels of acromegaly leading to increased morbidity and mortality from the disorder, with observed-to-expected mortality ratios ranging from 1.6-3.3 and only approaching unity in those with growth hormone levels < 2.5 ug/L following treatment. Prognostic factors include in some studies the presence of diabetes and [table: see text] hypertension prior to diagnosis as well as measures of exposure to excessive growth hormone derived from the product of preoperative serum GH and the time from first symptoms to treatment. Overall, however, the most important prognostic variable appears to be the serum GH concentration achieved by treatment, with an increasing consensus that this needs to be < 2.5 ug/L (5 mU/L) to achieve cure of the condition.
McCabe, John; Ayuk, John; Sherlock, Mark
Acromegaly is a rare condition characterized by excessive secretion of growth hormone (GH), which is almost always due to a pituitary adenoma. Acromegaly is associated with significant morbidity such as hypertension, type 2 diabetes, cardiomyopathy, obstructive sleep apnoea, malignancy and musculoskeletal abnormalities. Acromegaly has also been associated with increased mortality in several retrospective studies. This review will focus on the epidemiological data relating to mortality rates in acromegaly, the relationship between acromegaly and malignancy, the role of GH and insulin-like growth factor-I in assessing the risk of future mortality, and the impact of radiotherapy and hypopituitarism on mortality.
Malicka, Joanna; Świrska, Joanna; Nowakowski, Andrzej
In the majority of cases, acromegaly is sporadic. However, it can also occur in a familial setting as a component of MEN-1, MEN-4, Carney complex (CNC) or as the extremely rare syndrome of isolated familial somatotropinoma (IFS), the latter belonging to familial isolated pituitary adenomas (FIPA). The diagnosis of IFS is based on the recognition of acromegaly/gigantism in at least two family members, given that the family is not affected by MEN-1, MEN-4 or CNC. The authors present a case study of two sisters: a 56 year-old patient (case no. 1) and a 61 year-old patient (case no. 2). In both sisters, acromegaly was recognised in the course of pituitary macroadenoma. Neither of the sisters showed features of MEN-1, MEN-4 or Carney complex. The authors suppose that the presented cases are manifestations of IFS. However, this diagnosis has not been confirmed yet because of the poor availability of genetic tests.
Vilar, Lucio; Vilar, Clarice Freitas; Lyra, Ruy; Lyra, Raissa; Naves, Luciana A
Acromegaly is a rare and underdiagnosed disorder caused, in more than 95% of cases, by a growth hormone (GH)-secreting pituitary adenoma. The GH hypersecretion leads to overproduction of insulin-like growth factor 1 (IGF-1) which results in a multisystem disease characterized by somatic overgrowth, multiple comorbidities, physical disfigurement, and increased mortality. This article aims to review the clinical features of acromegaly at diagnosis. Acromegaly affects both males and females equally and the average age at diagnosis ranges from 40 to 50 years (up to 5% of cases acromegaly is often diagnosed five to more than ten years after its onset. The typical coarsening of facial features include furrowing of fronthead, pronounced brow protrusion, enlargement of the nose and the ears, thickening of the lips, skin wrinkles and nasolabial folds, as well as mandibular prognathism that leads to dental malocclusion and increased interdental spacing. Excessive growth of hands and feet (predominantly due to soft tissue swelling) is present in the vast majority of acromegalic patients. Gigantism accounts for up to 5% of cases and occurs when the excess of GH becomes manifest in the young, before the epiphyseal fusion. The disease also has rheumatologic, cardiovascular, respiratory, neoplastic, neurological, and metabolic manifestations which negatively impact its prognosis and patients quality of life. Less than 15% of acromegalic patients actively seek medical attention for change in appearance or enlargement of the extremities. The presentation of acromegaly is more often related to its systemic comorbidities or to local tumor effects.
Baum, H; Lüdecke, D K; Herrmann, H D
50 patients with acromegaly and carpal tunnel syndrome have been examined electrophysiologically before and after transnasal operation of the pituitary adenoma. 32 of the 50 patients (64%) had symptoms of carpal tunnel syndrome. 13 of them had neurological deficits. 28 of the examined patients had pathological neurographical findings only. About 1 week post-operatively DL was decreased in 43%; in 10 out of 13 patients with neurological deficits DL decreased. GH was normalized in 80% and reduced to 5-10 micrograms/l in a further 10%. The investigation did not show whether the carpal tunnel syndrome only depended on a GH increase or on other factors also such as e.g., on the duration of symptoms or tissue changes. None of the patients had the transversal carpal ligament operated on. The coincidence between acromegaly and carpal tunnel syndrome was 64%. In 3 cases the carpal tunnel syndrome was the leading sign to the diagnosis of acromegaly.
Eastman, R C; Gorden, P; Glatstein, E; Roth, J
Conventional megavoltage irradiation of GH-secreting tumors has predictable effects on tumor mass, GH, and pituitary function. 1. Further growth of the tumor is prevented in more than 99% of patients, with only a fraction of a percent of patients requiring subsequent surgery for tumor mass effects. 2. GH falls predictably with time. By 2 years GH falls by about 50% from the baseline level, and by 5 years by about 75% from the baseline level. The initial GH elevation and the size and erosive features of the sella turcica do not affect the percent decrease in GH from the baseline elevation. 3. With prolonged follow-up, further decrease in GH is seen at 10 and 15 years, with the fraction of surviving patients achieving GH levels less than 5 ng/mL approaching 90% after 15 years in our experience. Gender, previous surgery, and hyperprolactinemia do not seem to affect the response to treatment. Patients with initial GH greater than 100 ng/mL are significantly less likely to achieve GH values less than 5 ng/mL during long-term follow-up. 4. Hypopituitarism is a predictable outcome of treatment, is delayed, and may be more likely in patients who have had surgery prior to irradiation. There is no evidence that this complication is more common in patients with acromegaly than in patients with other pituitary adenomas receiving similar treatment. 5. Vision loss due to megavoltage irradiation--using modern techniques and limiting the total dose to 4680 rad given in 25 fractions over 35 days, with individual fractions not exceeding 180 rad--is extremely rare. The reported cases have occurred almost entirely in patients who have received larger doses or higher fractional doses. The theory that patients with acromegaly are prone to radiation-induced injury to the CNS and optic nerves and chiasm because of small vessel disease is not supported by a review of the reported cases. 6. Brain necrosis and secondary neoplasms induced by irradiation are extremely rare. 7. Although
Buchfelder, Michael; Feulner, Julian
Surgical removal of as much tumor mass as possible is usually considered the first step of treatment in acromegaly, unless the patients are unfit for surgery or refuse an operation. To date, in almost all cases, minimally invasive, transsphenoidal microscopic or endoscopic approaches are used. Whether a curative approach is feasible or a debulking procedure is planned, can be anticipated on the basis of preoperative magnetic resonance imaging. It mostly depends on localization, size, and the invasive character of the lesion. The surgical results depend on tumor-related factors such as size, extension, the presence or absence of invasion, and the magnitude of IGF-1 and growth hormone oversecretion, respectively. However, even surgeon-related factors such as experience and case load of the centers have been shown to strongly affect surgical results and complication rates. A reoperation can be considered at various stages in the treatment algorithm. There are several new technical gadgets which might aid in the surgical procedure: navigation, the Doppler probe, and variants of intraoperative imaging.
Hannah-Shmouni, Fady; Trivellin, Giampaolo; Stratakis, Constantine A
Gigantism and acromegaly are rare disorders that are caused by excessive GH secretion and/or high levels of its mediator, IGF-1. Gigantism occurs when excess GH or IGF-1 lead to increased linear growth, before the end of puberty and epiphyseal closure. The majority of cases arise from a benign GH-secreting pituitary adenoma, with an incidence of pituitary gigantism and acromegaly of approximately 8 and 11 per million person-years, respectively. Over the past two decades, our increasing understanding of the molecular and genetic etiologies of pituitary gigantism and acromegaly yielded several genetic causes, including multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, pituitary adenoma association due to defects in familial succinate dehydrogenase genes, and the recently identified X-linked acrogigantism. The early diagnosis of these conditions helps guide early intervention, screening, and genetic counseling of patients and their family members. In this review, we provide a concise and up-to-date discussion on the genetics of gigantism and acromegaly. Published by Elsevier Ltd.
López Gavilanez, Enrique; Guerrero Franco, Kempis; Solórzano Zambrano, Narcisa; Navarro Chávez, Manuel; López Estrella, Camilo; Vaca Burbano, Luis; Marriott Díaz, Eduardo
To assess the epidemiology of acromegaly in the city of Guayaquil, Ecuador, and to compare our results to those reported in the literature. An analysis was made of retrospective and prospective data from all patients with acromegaly attending endocrinology clinics at the 4 main hospitals of the public health network of Guayaquil from January 2000 to December 2014. Age at diagnosis, estimated delay in diagnosis, imaging studies of pituitary gland, basal growth hormone (GH) level, GH after an oral glucose tolerance test (OGTT-GH), and serum levels of insulin-like growth factor 1 (IGF-1) were recorded. Incidence and prevalence of the disease were estimated using information from the 2010 census of population and housing. Forty-eight cases were recorded in the study period in 17 males (35.4%) and 31 females (64.5%); M/F ratio=1.8:1. Mean age at diagnosis was 47.3±16.8 years (range 18-86). Delay in diagnosis was 7.3±6.3 years (range 1-30). Mean age at diagnosis was 47.9±18.2 years in males and 46.3±15.8 years in females. Delay in diagnosis was 10.2±7.9 and 5.7±3.9 years in males and females, respectively. Prevalence of acromegaly is 18.7 cases per million inhabitants, and incidence of acromegaly 1.3 cases per million people per year. Acromegaly predominates in females, and is diagnosed in the fourth decade with a delay of approximately 8 years, usually even longer in males. Incidence and prevalence are lower than reported in international series. The disease is underdiagnosed and underreported in Ecuador. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.
Belinda George; Vinay, D; J Moolechery; Mathew, V; Anantharaman, R.; Ayyar, V; Bantwal, G
Introduction: Acromegaly is associated with enlargement of all organs including the gastro intestinal system. However, there are no previous reports of occurrence of megaduodenum in patients with acromegaly. Discussion: We present the case of a 47 year old male who was diagnosed to have acromegaly 13 years ago and had undergone transsphenoidal surgery twice with incomplete removal of the pituitary macro-adenoma and received radiotherapy following the second surgery. Patient has been on replac...
Gloria Lugo; Lara Pena; Fernando Cordido
Acromegaly and gigantism are due to excess GH production, usually as a result of a pituitary adenoma. The incidence of acromegaly is 5 cases per million per year and the prevalence is 60 cases per million. Clinical manifestations in each patient depend on the levels of GH and IGF-I, age, tumor size, and the delay in diagnosis. Manifestations of acromegaly are varied and include acral and soft tissue overgrowth, joint pain, diabetes mellitus, hypertension, and heart and respiratory failure. Ac...
Akoglu, Gulsen; Metin, Ahmet; Emre, Selma; Ersoy, Reyhan; Cakir, Bekir
Background: Acromegaly is a systemic syndrome caused by overproduction of growth hormone. The syndrome affects cutaneous, endocrine, cardiovascular, skeletal, and respiratory systems. Cutaneous manifestations of acromegaly are various, usually being the first presenting findings of the disease. Methods: Dermatological examinations of 49 patients of acromegaly who were followed-up at a tertiary referral hospital.Results: The study included 27 (55.1%) female and 22 (44.9%) male patients. The on...
Petrossians, Patrick; Daly, Adrian F; Natchev, Emil; Maione, Luigi; Blijdorp, Karin; Sahnoun-Fathallah, Mona; Auriemma, Renata; Diallo, Alpha M; Hulting, Anna-Lena; Ferone, Diego; Hana, Vaclav; Filipponi, Silvia; Sievers, Caroline; Nogueira, Claudia; Fajardo-Montañana, Carmen; Carvalho, Davide; Hana, Vaclav; Stalla, Günter K; Jaffrain-Réa, Marie-Lise; Delemer, Brigitte; Colao, Annamaria; Brue, Thierry; Neggers, Sebastian J C M M; Zacharieva, Sabina; Chanson, Philippe
Acromegaly is a rare disorder caused by chronic growth hormone (GH) hypersecretion. While diagnostic and therapeutic methods have advanced, little information exists on trends in acromegaly characteristics over time. The Liège Acromegaly Survey (LAS) Database, a relational database, is designed to assess the profile of acromegaly patients at diagnosis and during long-term follow-up at multiple treatment centers. The following results were obtained at diagnosis. The study population consisted of 3173 acromegaly patients from ten countries; 54.5% were female. Males were significantly younger at diagnosis than females (43.5 vs 46.4 years; P 3100 patients is the largest international acromegaly database and shows clinically relevant trends in the characteristics of acromegaly at diagnosis. PMID:28733467
Pasireotide (Signifor(®), Signifor(®) LAR) is a somatostatin analogue recently approved for the treatment of acromegaly. Unlike the first-generation agents, octreotide and lanreotide, which bind preferentially to somatostatin receptor (SSTR)-2, pasireotide binds to multiple SSTRs. This article reviews the clinical use and summarizes the pharmacological properties of intramuscular pasireotide in the treatment of acromegaly. The efficacy of pasireotide 40 mg every 28 days was superior to that of intramuscular octreotide 20 mg every 28 days with regard to biochemical control in a 12-month, phase III trial in medically naive patients. Similarly, in a 6-month, phase III trial in patients with acromegaly inadequately controlled with somatostatin analogues for at least 6 months, the efficacy of pasireotide 40 or 60 mg was superior to that of continued octreotide 30 mg or lanreotide autogel 120 mg (each drug was administered once every 28 days) with regard to biochemical control. The tolerability profile of intramuscular pasireotide is generally similar to that of first-generation agents, except for a higher incidence of hyperglycaemia-related adverse events with pasireotide. In clinical trials, the risk of developing pasireotide-associated hyperglycaemia was numerically greater in patients categorized as diabetic or prediabetic at baseline than in those with normal glucose tolerance. Careful monitoring of glycaemic status is required prior to and during pasireotide treatment and antidiabetic therapy should be commenced as indicated. Thus, in the treatment of acromegaly, pasireotide may be a more effective somatostatin analogue than other approved agents of the same class; however, the increased risk of hyperglycaemia needs to be considered and proactively managed.
Buchfelder, Michael; Schlaffer, Sven-Martin
Surgical extraction of as much tumour mass as possible is considered the first step of treatment in acromegaly in many centers. In this article the potential benefits, disadvantages and limitations of operative acromegaly treatment are reviewed. Pertinent literature was selected to provide a review covering current indications, techniques and results of operations for acromegaly. The rapid reduction of tumour volume is an asset of surgery. To date, in almost all patients, minimally invasive, transsphenoidal microscopic or endoscopic approaches are employed. Whether a curative approach is feasible or a debulking procedure is planned, can be anticipated on the basis of preoperative magnetic resonance imaging. The radicality of adenoma resection essentially depends on localization, size and invasive character of the tumour. The normalization rates of growth hormone and IGF-1 secretion, respectively, depend on tumour-related factors such as size, extension, the presence or absence of invasion and the magnitude of IGF-1 and growth hormone oversecretion. However, also surgeon-related factors such as experience and patient load of the centers have been shown to strongly affect surgical results and the rate of complications. As compared to most medical treatments, surgery is relatively cheap since the costs occur only once and not repeatedly. There are several new technical gadgets which aid in the surgical procedure: navigation and variants of intraoperative imaging. For the mentioned reasons, current algorithms of acromegaly management suggest an initial operation, unless the patients are unfit for surgery, refuse an operation or only an unsatisfactory resection is anticipated. A few suggestions are made when a re-operation could be considered.
L K Dzeranova
Full Text Available Sleep-disordered breathing is higly prevalent in acromegaly, disturbing patients quality of life and increasing the risk of acute cardiovascular compications. Presented clinical case discusses key considerations for timely diagnosis of sleep apnea syndrome and treatment planning. The case of 41 y.o. woman with newly diagnosed acromegaly and concomitant sleep apnea is typical for this disease.
Main, K M; Lindholm, J; Vandeweghe, M
The biochemical assessment of disease activity in acromegaly still presents a problem, especially in treated patients with mild clinical symptoms. We therefore examined the diagnostic value of the measurement of urinary growth hormone (GH) excretion in seventy unselected patients with acromegaly...
Epidemiology of acromegaly in Spain does not differ from that reported in other published series. Prevalence rate is approximately 60 cases per million, peak incidence occurs in middle age, more women are affected (61%), and there is a substantial delay between occurrence of the first symptoms and diagnosis. Studies REA (Spanish Acromegaly Registry) and OASIS analyzed the epidemiology, clinical characteristics, and management of the disease in Spain. Surgery, performed in more than 80% of patients, has been (and continues to be) the main treatment for the past four decades. In the past decade, however, more patients have received somatostatin analogs (SSAs) as first-line treatment. Use of radiation therapy has significantly decreased in recent decades. Somatostatin analogs (SSAs) are the most commonly used drugs, administered to 85% of patients; however, only 12%-15% continue on drug treatment alone. The surgical remission rate was 38.4% in the last decade, with a significant improvement over decades. Preoperative treatment with SSAs has no influence on surgical cure rates. Second-line therapies used after surgical failure in the past decade included SSAs in 49% of patients, repeat surgery in 27%, radiotherapy in 11%, pegvisomant in 15%, and dopamine agonists in 5%. Mean cost of acromegaly treatment was 9.668€ (data estimated in 2009 and adjusted in 2010), of which 71% was due to the cost of SSAs. Patients treated with pegvisomant have a more aggressive form of the disease and higher comorbidity rates.
Full Text Available Acromegaly and gigantism are due to excess GH production, usually as a result of a pituitary adenoma. The incidence of acromegaly is 5 cases per million per year and the prevalence is 60 cases per million. Clinical manifestations in each patient depend on the levels of GH and IGF-I, age, tumor size, and the delay in diagnosis. Manifestations of acromegaly are varied and include acral and soft tissue overgrowth, joint pain, diabetes mellitus, hypertension, and heart and respiratory failure. Acromegaly is a disabling disease that is associated with increased morbidity and reduced life expectancy. The diagnosis is based primarily on clinical features and confirmed by measuring GH levels after oral glucose loading and the estimation of IGF-I. It has been suggested that the rate of mortality in patients with acromegaly is correlated with the degree of control of GH. Adequately treated, the relative mortality risk can be markedly reduced towards normal.
Mazziotti, Gherardo; Marzullo, Paolo; Doga, Mauro; Aimaretti, Gianluca; Giustina, Andrea
Growth hormone deficiency (GHD) of the adult is characterized by reduced quality of life (QoL) and physical fitness, skeletal fragility, and increased weight and cardiovascular risk. Hypopituitarism may develop in patients after definitive treatment of acromegaly, but an exact prevalence of GHD in this population is still uncertain owing to limited awareness and the scarce and conflicting data available on this topic. Because acromegaly and GHD may yield adverse consequences on similar target systems, the final outcomes of some complications of acromegaly may be further affected by the occurrence of GHD. However, it is still largely unknown whether patients with post-acromegaly GHD may benefit from GH replacement. We review the diagnostic, clinical, and therapeutic aspects of GHD in adult patients treated for acromegaly. Copyright © 2014 Elsevier Ltd. All rights reserved.
Lugo, Gloria; Pena, Lara; Cordido, Fernando
Acromegaly and gigantism are due to excess GH production, usually as a result of a pituitary adenoma. The incidence of acromegaly is 5 cases per million per year and the prevalence is 60 cases per million. Clinical manifestations in each patient depend on the levels of GH and IGF-I, age, tumor size, and the delay in diagnosis. Manifestations of acromegaly are varied and include acral and soft tissue overgrowth, joint pain, diabetes mellitus, hypertension, and heart and respiratory failure. Acromegaly is a disabling disease that is associated with increased morbidity and reduced life expectancy. The diagnosis is based primarily on clinical features and confirmed by measuring GH levels after oral glucose loading and the estimation of IGF-I. It has been suggested that the rate of mortality in patients with acromegaly is correlated with the degree of control of GH. Adequately treated, the relative mortality risk can be markedly reduced towards normal.
Andersen, Marianne; Hagen, Casper; Frystyk, Jan
OBJECTIVES: Patients with prolactinomas and patients with acromegaly often have heterogenous adenomas. In this study we have focused on patients with prolactinomas who developed acromegaly and acromegalic patients with hyperprolactinaemia. Our hypothesis is that some patients with hyperprolactina......OBJECTIVES: Patients with prolactinomas and patients with acromegaly often have heterogenous adenomas. In this study we have focused on patients with prolactinomas who developed acromegaly and acromegalic patients with hyperprolactinaemia. Our hypothesis is that some patients...... with hyperprolactinaemia may develop clinical acromegaly. METHODS: We have included patients examined at department M, Odense University Hospital between 1996 and 2001. Seventy-eight patients with prolactinomas, 65 females and 13 males, with a median age (range) of 30 Years (14-74) and 47 Years (20-66), respectively, were...
Lugo, Gloria; Pena, Lara; Cordido, Fernando
Acromegaly and gigantism are due to excess GH production, usually as a result of a pituitary adenoma. The incidence of acromegaly is 5 cases per million per year and the prevalence is 60 cases per million. Clinical manifestations in each patient depend on the levels of GH and IGF-I, age, tumor size, and the delay in diagnosis. Manifestations of acromegaly are varied and include acral and soft tissue overgrowth, joint pain, diabetes mellitus, hypertension, and heart and respiratory failure. Acromegaly is a disabling disease that is associated with increased morbidity and reduced life expectancy. The diagnosis is based primarily on clinical features and confirmed by measuring GH levels after oral glucose loading and the estimation of IGF-I. It has been suggested that the rate of mortality in patients with acromegaly is correlated with the degree of control of GH. Adequately treated, the relative mortality risk can be markedly reduced towards normal. PMID:22518126
Andersen, Marianne; Hagen, Casper; Frystyk, Jan
OBJECTIVES: Patients with prolactinomas and patients with acromegaly often have heterogenous adenomas. In this study we have focused on patients with prolactinomas who developed acromegaly and acromegalic patients with hyperprolactinaemia. Our hypothesis is that some patients with hyperprolactina......OBJECTIVES: Patients with prolactinomas and patients with acromegaly often have heterogenous adenomas. In this study we have focused on patients with prolactinomas who developed acromegaly and acromegalic patients with hyperprolactinaemia. Our hypothesis is that some patients...... with hyperprolactinaemia may develop clinical acromegaly. METHODS: We have included patients examined at department M, Odense University Hospital between 1996 and 2001. Seventy-eight patients with prolactinomas, 65 females and 13 males, with a median age (range) of 30 Years (14-74) and 47 Years (20-66), respectively, were...
Claessen, Kim M J A; Mazziotti, Gherardo; Biermasz, Nienke R; Giustina, Andrea
Acromegaly is a chronic, progressive disease caused by a growth hormone (GH)-producing pituitary adenoma, resulting in elevated GH and insulin-like growth factor 1 concentrations. Following appropriate therapy (surgery, radiotherapy and/or medical treatment), many systemic GH-induced comorbid conditions improve considerably. Unfortunately, despite biochemical control, acromegaly patients suffer from a high prevalence of late manifestations of transient GH excess, significantly impairing their quality of life. In this overview article, we summarize the pathophysiology, diagnosis, clinical picture, disease course and management of skeletal complications of acromegaly, focusing on vertebral fractures and arthropathy.
Tirosh, Amit; Shimon, Ilan
In acromegaly the long-term exposure to high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels may result in specific complications in different human organs, including the thyroid gland and the colon. We will review here the evidence available regarding the characteristic thyroid and colon complications in acromegaly. This review summarizes the published data observing noncancerous structural abnormalities (thyroid nodules, colonic polyps) and thyroid and colon cancer in patients diagnosed with acromegaly. Thyroid micro-carcinomas are probably over-diagnosed among acromegalic patients. In regard to colon cancer, there is no sufficient data to suggest that colon cancer risk is higher in acromegaly compared to the general population.
Full Text Available Introduction: Acromegaly is associated with enlargement of all organs including the gastro intestinal system. However, there are no previous reports of occurrence of megaduodenum in patients with acromegaly. Discussion: We present the case of a 47 year old male who was diagnosed to have acromegaly 13 years ago and had undergone transsphenoidal surgery twice with incomplete removal of the pituitary macro-adenoma and received radiotherapy following the second surgery. Patient has been on replacement therapy for hypocortisolism, hypothyroidism and hypogonadism since 10 years. Post glucose growth hormone level continued to remain unsuppressed; however, patient never received any medical therapy for acromegaly. He was evaluated with esophago-gastro-duodenoscopy for recurrent abdominal pain and distension, which showed an elongated and tortuous megaduodenum. These findings were verified with a barium study which revealed dilated stomach, first and second part of duodenum with no evidence of a distal obstruction. Conclusions: We report this finding in view of the rare association.
Noor Rafhati Adyani Abdullah
Full Text Available Pachydermoperiostosis is a very rare osteoarthrodermopathic disorder whose clinical and radiographic presentations may mimic those of acromegaly. In the evaluation of patients with acromegaloid appearances, pachydermoperiostosis should be considered as a differential diagnosis. In this article, we report a 17-year-old boy who presented with 2-year history of acral enlargement and facial appearance changes associated with joint pain and excessive sweating. He had been investigated extensively for acromegaly, and the final diagnosis was pachydermoperiostosis.
Lombardi, G; Colao, A; Ferone, D; Marzullo, P; Landi, M L; Longobardi, S; Iervolino, E; Cuocolo, A; Fazio, S; Merola, B; Sacca, L
Patients with acromegaly have significant morbidity and mortality, associated with cardiovascular disease. Acromegaly is often complicated by other diseases such as diabetes mellitus, hypertension, and coronary artery disease, so the existence of acromegalic cardiomyopathy remains uncertain. Cardiac performance was investigated in patients with uncomplicated acromegaly. A subgroup of hypertensive acromegalics was also studied. In addition, the effects of chronic octreotide therapy or surgery on cardiac structure and function in acromegaly were studied. Twenty-six patients and 15 healthy controls underwent gated blood-pool cardiac scintigraphy and echocardiography at rest and during exercise. Echocardiography was repeated after 6 months of octreotide therapy (n = 11). Cardiac scintigraphy was repeated after 12 and 24 months of octreotide therapy (n = 10) or 12 to 24 months after surgery (n = 8). ECG, blood pressure, and heart rate were monitored during cardiac scintigraphy. Left ventricular mass (LVM) was calculated from the findings of the echocardiography. Serum growth hormone (GH) levels and plasma insulin-like growth factor-1 (IGF-1) levels were monitored. LVM index was significantly higher (P cardiac function were similar. Chronic octreotide decreased GH and IGF-1 levels and improved the structural abnormalities as measured by echocardiography. Chronic octreotide or surgery did not alter cardiac function parameters. Thus, important changes in cardiac structure and function occur in uncomplicated acromegaly, and improvements can be demonstrated after chronic octreotide therapy. Heart disease in acromegaly appears to be secondary to high circulating GH levels.
Akoglu, Gulsen; Metin, Ahmet; Emre, Selma; Ersoy, Reyhan; Cakir, Bekir
Acromegaly is a systemic syndrome caused by overproduction of growth hormone. The syndrome affects cutaneous, endocrine, cardiovascular, skeletal, and respiratory systems. Cutaneous manifestations of acromegaly are various, usually being the first presenting findings of the disease. Forty-nine patients with acromegaly, followed-up at a tertiary referral hospital, underwent dermatological examination. There were 27 (55.1%) female and 22 (44.9%) male patients. The age at onset of the disease was older in females than males (P=0.045). Most patients had acral enlargements, large triangular nose, coarse face, thickened lower lip, and prognathism. Fourteen (28.6%) patients had multiple cherry angiomas, five (10.2%) had varicose veins in lower limbs, and two (4.1%) had psoriasis. In conclusion, a wide spectrum of cutaneous symptoms and features may be associated with acromegaly. Detailed dermatological examination of patients with acromegaly should be an essential component of systemic evaluation. Future prospective studies investigating the relationships between changes in skin signs, hormone levels, and response to treatments may help understand details of skin involvement in acromegaly.
Dutta, P.; Das, S; Bhansali, A; S K Bhadada; B V Rajesh; Reddy, K. S.; Vaiphei, K; K. K. Mukherjee; Pathak, A.; Shah, V N
Background: Though cardiac involvement is common in acromegaly, overt congestive heart failure is uncommon. Materials and Methods: This is retrospective analysis of hospital record between 1996 and 2007. We analyzed records of 150 consecutive patients with acromegaly. We included the patients with acromegaly those who had overt congestive heart failure either at presentation or during the course of illness for the present analysis. The diagnosis of acromegaly and congestive cardiac failure we...
Hong, Jae Won; Ku, Cheol Ryong; Kim, Sun Ho; Lee, Eun Jig
Acromegaly is a slowly progressive disease caused by excessive growth hormone (GH), which is related to a GH secreting pituitary tumor in most cases. Herein, we describe the epidemiology, clinical characteristics, and treatment of acromegaly in Korea with a literature review. The average annual incidence of acromegaly in Korea was 3.9 cases per million people, which was within the range of previous Western studies. The primary treatment for acromegaly was also transsphenoidal adenomectomy, wh...
Full Text Available McCune-Albright syndrome is characterized by polyostatic fibrous dysplasia, brown spots on the skin (café au lait pigmentation and autonomous endocrine hyperfunction. Early puberty and other endocrinological manifestations, such as acromegaly, gigantism and hypercortisolism are widely observed in the syndrome. Acromegaly is seen in 20% of patients. We report a case of acromegaly accompanied with this syndrome.
Dreval, A V; Trigolosova, I V; Misnikova, I V; Kovalyova, Y A; Tishenina, R S; Barsukov, I A; Vinogradova, A V; Wolffenbuttel, B H R
Early carbohydrate metabolism disorders (ECMDs) and diabetes mellitus (DM) are frequently associated with acromegaly. We aimed to assess the prevalence of ECMDs in patients with acromegaly and to compare the results with those in adults without acromegaly using two population-based epidemiologic
Dreval, A V; Trigolosova, I V; Misnikova, I V; Kovalyova, Y A; Tishenina, R S; Barsukov, I A; Vinogradova, A V; Wolffenbuttel, B H R
Early carbohydrate metabolism disorders (ECMDs) and diabetes mellitus (DM) are frequently associated with acromegaly. We aimed to assess the prevalence of ECMDs in patients with acromegaly and to compare the results with those in adults without acromegaly using two population-based epidemiologic sur
Annamalai, Anand K; Gayton, Emma L; Webb, Alison; Halsall, David J; Rice, Caiomhe; Ibram, Ferda; Chaudhry, Afzal N; Simpson, Helen L; Berman, Laurence; Gurnell, Mark
Several studies have suggested an increased prevalence of benign and malignant tumors in acromegaly, particularly colonic neoplasms. The gallbladder's epithelial similarity to the colon raises the possibility that gallbladder polyps (GBP) may occur more frequently in acromegaly. Thirty-one patients with newly diagnosed acromegaly (14 females, 17 males; mean age 54.7 yr, range 27-76 yr) were referred to our center between 2004 and 2008. All had pituitary adenomas and were treated with somatostatin analogs prior to transsphenoidal surgery. Biliary ultrasonography was performed at the time of referral. In a retrospective case-cohort study, we compared the prevalence of GBP in these scans with those of 13,234 consecutive patients (age range 20-80 yr) presenting at the hospital for abdominal/biliary ultrasound during the same time interval. Associations between GH and IGF-I levels and GBP in acromegaly were also examined. There was a higher prevalence of GBP in patients with acromegaly compared with controls (29.03 vs 4.62%, P = 0.000008); relative risk was 6.29 (95% confidence interval 3.61-10.96). Eight of nine patients with acromegaly and GBP were older than 50 yr of age. GH levels were higher in those with GBP (median 30.8 μg/liter, interquartile range 10.9-39.1) than those without (8.2 μg/liter, interquartile range 6.0-16.0), but IGF-I levels were comparable. This is the first study to demonstrate an increased prevalence of GBP in patients with newly diagnosed acromegaly. Further studies are required to determine whether these patients are at increased risk of developing gallbladder carcinoma and to define the role, if any, of biliary ultrasound surveillance.
Salenave, Sylvie; Boyce, Alison M.; Collins, Michael T.
Background: McCune-Albright syndrome (MAS) includes the triad of poly/monostotic fibrous dysplasia, café-au-lait spots, and hyperfunctioning endocrinopathies. Acromegaly affects around 20% of MAS patients. Aims: The objective was to review all reported cases of acromegaly associated with MAS. Methods: All studies and case reports of acromegaly in patients with MAS were systematically sought in the world literature up to January 2013. We also included new data (from three unreported cases) and updated data on 23 previously reported patients from our two centers. Results: We reviewed the cases of 112 patients (65 males). Mean age at diagnosis of acromegaly was 24.4 years (range, 3–64). Among the 40 pediatric patients, 23 (57%) had precocious puberty. GH/IGF-1 excess was suggested by accelerated growth in 85% of pediatric cases. Acromegaly was almost always associated with skull base fibrous dysplasia. Modern imaging techniques (computed tomography or magnetic resonance imaging) revealed an adenoma in 54% of the patients (macroadenoma in more than two-thirds). Median GH levels and mean IGF-1 SD score at diagnosis were 57 μg/L (2.8 to 291 μg/L) and 8 (2.3 to 24), respectively. Hyperprolactinemia was present in 81% (mean, 149 μg/L; range, 21–600). Pituitary surgery, performed in 25 cases, very rarely cured the GH/IGF-1 excess. Somatostatin analogs improved GH/IGF-1 levels in most patients but achieved control of acromegaly in only 17 (30%) of 56 patients. Pegvisomant achieved normal IGF-1 levels in 10 of 13 cases. Conclusion: Acromegaly, which is present in 20–30% of patients with MAS, raises particular diagnostic and therapeutic issues. PMID:24517150
Keskin, F E; Yetkin, D O; Ozkaya, H M; Haliloglu, O; Sadri, S; Gazioglu, N; Tanrıover, N; Ak, H; Hatipoglu, E; Kadıoglu, P
To reveal the variety of symptoms experienced by patients before acromegaly diagnosis and to emphasize unneeded surgeries that patients undergo related to acromegaly prior to diagnosis of the disease. In total, 490 consecutive adult patients with acromegaly who were treated at our institution between 1998 and 2014 were included in this cross-sectional study, of which 313 could be contacted. Participants were questioned about their complaints at initial consultation and at the time of diagnosis, the first medical professional who they consulted, interval between onset and diagnosis, and surgeries they had undergone. This study included 313 participants, of whom 181 were women. The mean age was 48.8 ± 12.0 years. Patients most frequently presented with acral growth of hands and feet (32.6%) and headache (26.2%). Internists were the medical specialists who were most frequently first consulted (29.4%) then neurosurgeons (11.8%). Acromegaly was generally diagnosed by endocrinologists (55%), followed by neurosurgeons (23%). The median elapsed period prior to diagnosis was 24 months, interquartile range 6.0-48.0 months. Some 45.7% had undergone surgery; 35.2% were related to acromegaly symptoms: head and throat surgery (12.8%), nose surgery (9.3%), thyroidectomy (6.4%), carpal tunnel surgery (4.8%). The delay period for patients who had an operation prior to acromegaly diagnosis was significantly longer than for those who had no operations (p Acromegaly patients mostly present to internal medicine professionals. Surgeries related to acromegaly complications and symptoms before diagnosis cause a long delay period before diagnosis. Medical staff must be more aware of the clinical aspects of acromegaly.
Vitale, G; Pivonello, R; Galderisi, M; D'Errico, A; Spinelli, L; Lupoli, G; Lombardi, G; Colao, A
Cardiac involvement is common in acromegaly. Evidence for cardiac hypertrophy, dilation and diastolic filling abnormalities has been widely reported in literature. Generally, ventricular hypertrophy is revealed by echocardiography but early data referred increased cardiac size by standard X-ray. Besides, echocardiography investigates cardiac function and value disease. There are new technologic advances in ultrasonic imaging. Pulsed Tissue Doppler is a new non-invasive ultrasound tool which extends Doppler applications beyond the analysis of intra-cardiac flow velocities until the quantitative assessment of the regional myocardial left ventricular wall motion, measuring directly velocities and time intervals of myocardium. The radionuclide techniques permit to study better the cardiac performance. In fact, diastolic as well as systolic function can be assessed at rest and at peak exercise by equilibrium radionuclide angiography. This method has a main advantage of providing direct evaluation of ventricular function, being operator independent. Coronary artery disease has been poorly studied mainly because of the necessity to perform invasive procedures. Only a few cases have been reported with heart failure study by coronarography and having alterations of perfusion which ameliorated after somatostatin analog treatment. More recently, a few data have been presented using perfusional scintigraphy in acromegaly, even if coronary artery disease does not seem very frequent in acromegaly. Doppler analysis of carotid arteries can be also performed to investigate atherosclerosis: however, patients with active acromegaly have endothelial dysfunction more than clear-cut atherosclerotic plaques. In conclusion, careful assessments of cardiac function, morphology and activity need in patients with acromegaly.
Wildemberg, Luiz Eduardo; Gadelha, Mônica R
Acromegaly is a chronic disease with high morbidity and enhanced mortality if left untreated. Treatment options include surgery, medical therapy (somatostatin analogues (SA), dopamine agonists (DA) and growth hormone receptor antagonists) and radiotherapy. Despite these treatment options, "real-life" studies have shown that approximately 50% of patients are not controlled. In this scenario, a next-generation SA, pasireotide, has recently been approved for the treatment of acromegaly. 1) pasireotide's pharmacokinetics and pharmacodynamics; 2) pasireotide's anti-secretory and anti-proliferative effects, from preclinical studies up to phase III clinical trials; and 3) the adverse effects of pasireotide, focusing on hyperglycemia; 4) biomarkers of response to SA treatment. surgery is the primary treatment for most patients with acromegaly; however, approximately half of them will need adjuvant therapy. At present, the decision of this adjuvant treatment is made on a "trial-and-error" fashion. Nevertheless, in recent years, efforts have been made to establish biomarkers for the response to drugs involved in the treatment of acromegaly, which will change the treatment of acromegaly towards a more personalized therapeutic decision-making process. In the near future, the establishment of pasireotide response biomarkers will allow us to identify good candidates for first-line medical monotherapy with pasireotide.
Yu Mi Kang
Full Text Available Acromegaly is a slowly progressing condition resulting from excess growth hormone (GH, generally caused by a GH-secreting pituitary adenoma. Cancer is the third most common cause of mortality in patients with acromegaly, and insulin-like growth factor 1 (IGF-1 is known to influence tumor formation by increasing cell proliferation and inhibiting apoptosis. Multiple myeloma (MM is a plasma cell neoplasm, and previous studies have suggested the possible role of IGF-1 in its development of MM. However, no cases of acromegaly accompanied with MM have been reported in Asia to date. We here report the case of a 58-year-old woman with acromegaly accompanied with MM who presented with longstanding acromegalic manifestations resulting from a GH-secreting pituitary adenoma and also exhibited anemia, a reversed albumin/globulin ratio, and plasmacytosis on bone marrow examination. Because IGF-1 has been suggested to play an important role in the development and progression of MM, the patient promptly underwent surgical removal of the pituitary adenoma via a transsphenoidal approach. Since there is currently no consensus on therapeutic guidelines and suggested prognosis for MM with acromegaly, long-term follow-up of such cases is needed.
Atkinson, R L; Dimond, R C; Howard, W J; Earll, J M
6 patients with active acromegaly were treated with 10 mg of medroxyprogesterone acetate (MPA) every 6 hours daily for 2 weeks to 6 months. Oral glucose tolerance tests, growth hormone (GH) levels, and insulin tolerance tests (ITT) were done before and during MPA treatment. Basal GH levels varied widely during control and therapy periods; no significant lowering of GH levels occurred during treatment. Carbohydrate tolerance was not significantly affected by MPA therapy, although 5 out of 6 patients had deterioration at least once during treatment. Blood glucose response to ITT was unchanged by MPA. MPA did not affect the clinical features of acromegaly. There was no consistent effect of MPA on insulin-induced or arginine-induced GH secretion. It is concluded that MPA is not an effective agent for treating acromegaly.
... disease: Colon polyps Excess hair growth in females ( hirsutism ) Type 2 diabetes Weight gain (unintentional) Exams and ... rest of the pituitary gland is working normally. Treatment Surgery to remove the pituitary tumor that is ...
... leaks and, rarely, meningitis. Cerebrospinal fluid bathes the brain and can leak from the nose if the incision area doesn’t heal well. Meningitis is a bacterial or viral infection of the meninges, the outer covering of the brain. Even when surgery is successful and hormone levels ...
Abdullah, Noor Rafhati Adyani; Jason, Wong Lok Chin; Nasruddin, Azraai Bahari
Pachydermoperiostosis is a very rare osteoarthrodermopathic disorder whose clinical and radiographic presentations may mimic those of acromegaly. In the evaluation of patients with acromegaloid appearances, pachydermoperiostosis should be considered as a differential diagnosis. In this article, we report a 17-year-old boy who presented with 2-year history of acral enlargement and facial appearance changes associated with joint pain and excessive sweating. He had been investigated extensively for acromegaly, and the final diagnosis was pachydermoperiostosis. There is a broad range of differential diagnosis for acromegaloid features such as acromegaly, pseudoacromegaly with severe insulin resistance, Marfan's syndrome, McCune-Albright and a rare condition called pachydermoperiostosis.Once a patient is suspected to have acromegaly, the first step is biochemical testing to confirm the clinical diagnosis, followed by radiologic testing to determine the cause of the excess growth hormone (GH) secretion. The cause is a somatotroph adenoma of the pituitary in over 95 percent of cases.The first step is measurement of a serum insulin-like growth factor 1 (IGF1). A normal serum IGF1 concentration is strong evidence that the patient does not have acromegaly.If the serum IGF1 concentration is high (or equivocal), serum GH should be measured after oral glucose administration. Inadequate suppression of GH after a glucose load confirms the diagnosis of acromegaly.Once the presence of excess GH secretion is confirmed, the next step is pituitary magnetic resonance imaging (MRI).Atypical presentation warrants revision of the diagnosis. This patient presented with clubbing with no gigantism, which is expected in adolescent acromegalics as the growth spurt and epiphyseal plate closure have not taken place yet.
Anoun, Nadia; El Ouahabi, Hanan
Somatotroph adenomas are rare in the aging population. Diagnosis of somatotroph adenomas is often long delayed and they are characterized by atypical clinical picture. Their diagnostic criteria are similar to those used for younger patients. Surgery, if possible, is the treatment of choice for acromegaly in the elderly. Somatostatin analogues have shown to be effective in these patients. Prognosis is inversely correlated with patient's age, duration of disease and last GH level under treatment. Beside evolution of disease, age is a major determinant of mortality. We report three cases of elderly patients with acromegaly aged 75, 70 and 66 years respectively with a literature review.
Capatina, Cristina; Wass, John A H
Acromegaly (ACM) is a chronic, progressive disorder caused by the persistent hypersecretion of GH, in the vast majority of cases secreted by a pituitary adenoma. The consequent increase in IGF1 (a GH-induced liver protein) is responsible for most clinical features and for the systemic complications associated with increased mortality. The clinical diagnosis, based on symptoms related to GH excess or the presence of a pituitary mass, is often delayed many years because of the slow progression of the disease. Initial testing relies on measuring the serum IGF1 concentration. The oral glucose tolerance test with concomitant GH measurement is the gold-standard diagnostic test. The therapeutic options for ACM are surgery, medical treatment, and radiotherapy (RT). The outcome of surgery is very good for microadenomas (80-90% cure rate), but at least half of the macroadenomas (most frequently encountered in ACM patients) are not cured surgically. Somatostatin analogs are mainly indicated after surgical failure. Currently their routine use as primary therapy is not recommended. Dopamine agonists are useful in a minority of cases. Pegvisomant is indicated for patients refractory to surgery and other medical treatments. RT is employed sparingly, in cases of persistent disease activity despite other treatments, due to its long-term side effects. With complex, combined treatment, at least three-quarters of the cases are controlled according to current criteria. With proper control of the disease, the specific complications are partially improved and the mortality rate is close to that of the background population.
Valkusz, Zsuzsanna; Tóth, Miklós; Boda, Judit; Nagy, Endre; Julesz, János
The authors review the historical and epidemiological aspects, clinical features and complications of acromegaly while emphasizing the importance of the early diagnosis and treatment. Acromegaly is a rare and mostly sporadic disorder due to excessive production of growth hormone. It is characterized by progressive somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. The prevalence is estimated between 40 and 125 cases/million. Generally, it is diagnosed in middle-aged adults (mean age 40 years, men and women equally affected). Due to its insidious onset and slow progression, acromegaly is often diagnosed 7 to more than 10 years after its onset. The disease has cardiovascular, rheumatological, respiratory and metabolic consequences which highly determine its prognosis. Acromegaly is associated with a number of complications resulting in a two- or four-fold increase of mortality and a decrease of life expectancy by about 10 years. The major causes of death include cardiovascular and cerebrovascular events, respiratory diseases and malignancies. The duration of the disease before the introduction of effective therapy may be a major predictor of increased mortality mainly due to complications . The early diagnosis is important for timely commencement of treatment and for prevention of serious complications of the disease.
Kałuzny, Marcin; Bolanowski, Marek
The authors present numerous historical descriptions of persons who might suffered from gigantism or acromegaly. The oldest medical data of patients, initial attempts of causal neurosurgical treatment, history of growth hormone, insulin-like growth factor-1, growth hormone releasing hormone and somatostatin discovery is reported. The highest contemporary living persons are also listed.
Mazziotti, Gherardo; Cimino, Vincenzo; De Menis, Ernesto; Bonadonna, Stefania; Bugari, Giovanna; De Marinis, Laura; Veldhuis, Johannes D; Giustina, Andrea
In healthy subjects, parathyroid hormone (PTH) is secreted in a dual fashion, with low-amplitude and high-frequency pulses superimposed on tonic secretion. These 2 components of PTH secretion seem to have different effects on target organs. The aim of our study was to evaluate whether growth hormone excess in acromegaly may modify the spontaneous pulsatility of PTH. Five male patients with newly diagnosed active acromegaly and 8 healthy subjects were evaluated by 3-minute blood sampling for 6 hours. Plasma PTH concentrations were evaluated by multiparameter deconvolution analysis. Plasma PTH release profiles were also subjected to an approximate entropy (ApEn) estimate, which provides an ensemble measure of the serial regularity or orderliness of the release process. In acromegalic patients, baseline serum PTH values were not significantly different from those measured in the healthy subjects, as well as tonic PTH secretion rate, number of bursts, fractional pulsatile PTH secretion, and ApEn ratio. Conversely, PTH pulse half-duration was significantly longer in acromegalic patients vs healthy subjects (11.8+/-0.95 vs 6.9+/-1.6 minutes; P=.05), whereas PTH pulse mass showed a tendency (P=.06) to be significantly greater in acromegalic patients. These preliminary data suggest that growth hormone excess may affect PTH secretory dynamics in patients with acromegaly. Potentially negative bone effects of the modifications of PTH secretory pattern in acromegaly should be investigated.
Full Text Available Kari L Edling,1 Anthony P Heaney1,21Department of Medicine, 2Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USAAbstract: Acromegaly is caused by pituitary somatotroph hypersecretion of growth hormone leading to elevated hepatic-derived and local levels of insulin-like growth factor-1. It is associated with increased morbidity and mortality due primarily to cardiovascular disease and diabetes mellitus. Normalization of growth hormone and insulin-like growth factor-1 levels has been associated with decreased morbidity from metabolic and cardiovascular effects, as well as reduced overall mortality in epidemiologic studies. Many patients experience a delay in obtaining a diagnosis, have pituitary macroadenomas at presentation, and accordingly, a significant number will not be cured by tumor surgical resection alone. Adjunctive radiation therapy cannot always offer biochemical and clinical disease control and carries a 40% risk of partial or total pituitary failure in the medium term. Several monotherapies or combination medical therapies are currently available for both primary and adjuvant acromegaly treatment, and include long-acting somatostatin analogs, the growth hormone receptor antagonist pegvisomant, and dopamine agonists. Next generation somatostatin analogs and new drug delivery methods of existing agents are in ongoing clinical studies. This paper will review current and novel therapies under development for acromegaly.Keywords: acromegaly, growth hormone, pituitary tumors, somatostatin analog, pasireotide, pegvisomant
Găloiu, S; Poiană, C
Acromegaly is a rare disease most frequently due to a GH secreting pituitary adenoma. Without an appropriate therapy, life of patients with acromegaly can be shortened with ten years. Pituitary surgery is usually the first line therapy for GH secreting pituitary adenomas. A meta-analysis proved that mortality is much lower in operated patients, even uncured, than the entire group of patients and is similar with the general population in patients with GH30% utilization of SRAs reported a lower mortality ratio than studies with lower percentages of SRA administration. Although therapy with DA has long been used in patients with acromegaly, there are no studies reporting its effect on mortality, but its efficacy is limited by the low remission rate obtained. The use of conventional external radiotherapy, although with good remission rate in time, was linked with increased mortality, mostly due to cerebrovascular diseases. Mortality in acromegaly can be reduced to expected levels from general population by using modern therapies either in monotherapy or by using multimodal approaches in experienced centers.
Full Text Available Acromegaly is diagnosed clinically by the universal presence of acral enlargement and typical coarse facies. We report a short, elderly female developing acromegalic facies for last 10 years without acral overgrowth. She is a patient of primary hypothyroidism, well controlled for last 20 years. Acromegaly was proven by high level of serum insulin like growth factor-1 (IGF-1 and elevated and nonsuppressed level of growth hormone (GH, with other hormonal profile being undisturbed. She had mild insulin resistance and systemic hypertension in absence of any visual field defect. Magnetic resonance imaging (MRI of brain revealed pituitary hyperplasia without any detectable adenoma. No source of ectopic secretion of GH or growth hormone releasing hormone (GHRH could be localized. Therefore, atypical presentation of acromegaly needs high degree of suspicion even if some of the common features are lacking. Here, we have biochemically proved acromegaly with typical facies, short stature but no acral overgrowth and pituitary adenoma despite longstanding disease activity, and thus eluding diagnosis for years.
Kyriakakis, Nikolaos; Chau, Vincent; Lynch, Julie; Orme, Steve M; Murray, Robert D
The novel formulation of lanreotide, lanreotide (LAN) autogel (ATG), has been available in Europe since 2001 and USA from 2006 for the treatment of acromegaly. It is one of only two clinically available somatostatin analogs available for use in acromegaly. Data relating to the use of ATG in acromegaly, specifically relating to comparison to octreotide (OCT) LAR and patient acceptability and preference, have been slow to accumulate. We performed a comprehensive review of the original literature relating to development, pharmacokinetics, acceptability and clinical efficacy of ATG. LAN ATG is a novel formulation of LAN consequent on self-assembly of nanotubules in water. Diffusion between molecules within the nanotubules and surrounding tissue fluid in vivo leads to pseudo first-order pharmacokinetics. Efficacy is equivalent to the alternate long-acting somatostatin analog, OCT LAR, normalizing growth hormone and IGF-I levels in around 60 and 50% respectively. Control of tumor growth is observed in over 95% of patients, with 64% seeing a clinically significant reduction in tumor size. ATG is provided in a prefilled syringe for deep subcutaneous injection, allowing self-injection, and may be administered up to 8 weeks greatly improving convenience for the patient. The data strongly support consideration of ATG as the medical therapy of choice for patients with acromegaly.
Scacchi, Massimo; Andrioli, Massimiliano; Carzaniga, Chiara; Vitale, Giovanni; Moro, Mirella; Poggi, Luca; Pecori Giraldi, Francesca; Fatti, Letizia M; Cavagnini, Francesco
Ultrasound-elastography (US-E) appears to be a helpful tool for the diagnosis of thyroid cancer. In acromegaly, the prevalence of thyroid cancer is still debated. The aims of this study were to evaluate thyroid nodules in acromegaly and to establish the accuracy of US-E in providing information on their nature, using cytological analysis as a reference. US-E was applied to 90 nodules detected in 25 acromegalic patients and to 94 nodules found in 31 non-acromegalic goitrous subjects. The lesions were classified according to the elasticity scores (ES) as soft (ES 1-2) or hard (ES 3-4). Fine needle aspiration cytology could be performed in 60.8% of hard nodules in acromegalics and in 86.7% of hard nodules in controls. The prevalence of hard nodules was significantly higher in the whole group of acromegalic patients than in controls (56.8 vs 16.0%, P<0.0001). The prevalence of hard nodules in patients with active acromegaly (68.9%) was greater, though not to a statistically significant extent, than that observed in cured (44.4%) and controlled (52.5%) patients. Cytology revealed malignancy or suspect malignancy in four of the nodules of non-acromegalic subjects and in none of the nodules of acromegalic patients. This study has demonstrated a high prevalence of stiff thyroid nodules in acromegaly, greater than that found in non-acromegalic goitrous subjects. In acromegalics, hard nodules appeared not to be malignant on cytopathological examination and are probably of fibrous nature. Thus, US-E appears to be of limited value for the diagnosis of thyroid cancer in acromegaly.
Gurbulak, Sabriye; Akin, Fulya; Yerlikaya, Emrah; Yaylali, Guzin F; Topsakal, Senay; Tanriverdi, Halil; Akdag, Beyza; Kaptanoglu, Bunyamin
Adiponectin is an adipocytes-derived hormone which has been shown to possess insulin-sensitizing, antiatherogenic, and anti-inflammatory properties. In acromegaly, the data on adiponectin is contradictory. The relationship between adiponectin levels and cardiac parameters has not been studied. The aim of this study was to find out how adiponectin levels were affected in acromegalic patients and the relationship between adiponectin levels and cardiac parameters. We included 30 subjects (15 male, 15 female), diagnosed with acromegaly and 30 healthy (10 male, 20 female) subjects. Serum glucose, insulin, GH, IGF-1 and adiponectin levels were obtained and the insulin resistance of the subjects was calculated. Echocardiographic studies of the subjects were performed. We determined that adiponectin levels were significantly higher in the acromegalic group than the control group. In the acromegalic group, there was no statistically significant relation between serum adiponectin and growth hormone (GH), or insulin-like growth factor-1 (IGF-1) levels (p = 0.3, p = 0.1). We demonstrated that cardiac function and structure are affected by acromegaly. IVST, PWT, LVMI, E/A ratio, DT, ET, IVRT, VPR, and LVESV values were increased and the results were statistically significant. In the acromegalic group, adiponectin levels were positively related with left ventricle mass index (LVMI) but this correlation was found to be statistically weak (p = 0.03). In our study, there was a positive correlation between VAI and LVM. We also could not find any correlation between VAI and adiponectin levels. Although insulin resistance and high insulin levels occur in active acromegaly patients, adiponectin levels were higher in our study as a consequence of GH lowering therapies. Our study showed that adiponectin levels may be an indicator of the cardiac involvement acromegaly. However, the usage of serum adiponectin levels in acromegalic patients as an indicator of cardiac involvement should be
Melmed, S; Casanueva, F.F.; Klibanski, A; Bronstein, M. D.; Chanson, P.; Lamberts, S. W.; Strasburger, C. J.; Wass, J. A. H.; Giustina, A
In March 2011, the Acromegaly Consensus Group met to revise and update the guidelines on the diagnosis and treatment of acromegaly complications. The meeting was sponsored by the Pituitary Society and the European Neuroendocrinology Association and included experts skilled in the management of acromegaly. Complications considered included cardiovascular, endocrine and metabolic, sleep apnea, bone diseases, and mortality. Outcomes in selected, related clinical conditions were also considered, ...
Hatipoglu, Esra; Yuruyen, Mehmet; Keskin, Ela; Yavuzer, Hakan; Niyazoglu, Mutlu; Doventas, Alper; Erdincler, Deniz Suna; Beger, Tanju; Kadioglu, Pinar; Gundogdu, Sadi
Cognitive and functional geriatric assessment may change in acromegaly. Herein we aimed to determine at which points geriatric assessment of the cases with acromegaly differs from that of general elderly population. In this comparative cross-sectional study, a total of 30 cases with acromegaly (controlled n = 14, uncontrolled n = 16) and 30 gender and body-mass index-matched cases without acromegaly (control group, CG) above 60 years old were included. Cognitive functions were evaluated on the basis of the mini-mental state exam (MMSE). Affective status was determined using the geriatric depression scale. Activities of daily living (ADL) were ranked according to the Barthel index while instrumental activities of daily living (IADL) were graded on the basis of the Lawton scale. Nutritional status was evaluated using the mini-nutritional assessment (MNA). Body composition was measured through bioimpedance analysis. Functional mobility was determined using the Timed Up and Go test (TUG) and muscle strength with the handgrip strength test. Scores on the MMSE were significantly lower in the elderly cases with acromegaly than in the cases without acromegaly (p acromegaly group than in the CG (p = 0.04). Total MNA scores were significantly lower in cases with acromegaly than in the CG (p = 0.006). More subjects in the acromegaly group (33%) were at greater risk of malnutrition than in the CG (3%) (p = 0.003). There was greater moderate functional impairment based on Barthel ADL in the acromegaly group than in the CG (p = 0.04). Acromegaly may impair cognitive functions, functional mobility and instrumental daily living activities in the geriatric population. With acromegaly, the risk of malnutrition may also increase. Copyright © 2014 Elsevier Ltd. All rights reserved.
Resmini, Eugenia; Sambo, Marcel; Blanco, Concepción; Calvo, Fernando; Pazos, Fernando; Fernández-Catalina, Pablo; Martínez de Icaya, Purificación; Páramo, Concepción; Fajardo, Carmen; Marazuela, Mónica; Álvarez-Escolá, Cristina; Díez, Juan Jose; Perea, Verónica
Acromegaly is a rare disease with nonspecific symptoms with acral enlargement being almost universally present at diagnosis. The estimated prevalence is 40–125 cases/million but targeted universal screening studies have found a higher prevalence (about 10 fold). The aim of the ACROSAHS study was to investigate the prevalence of acromegaly and acromegaly comorbidities in patients with sleep apnea symptoms and acral enlargement. ACROSAHS was a Spanish prospective non-interventional epidemiological study in 13 Hospital sleep referral units. Facial and acral enlargement symptoms including: ring size and shoe size increase, tongue, lips and jaws enlargement, paresthesia or carpal tunnel syndrome and widening of tooth spaces, as well as other typical acromegaly comorbidities were recorded with a self-administered questionnaire of patients who attended a first visit for sleep apnea symptoms between 09/2013 and 07/2014. Serum insulin-like growth factor type 1 (IGF1) was measured in patients with ≥1 acral symptom to determine the prevalence of acromegaly. Of the 1557 patients enrolled, 1477 with complete data (72% male) were analyzed. 530 patients (36%) reported at least 1 acral enlargement symptom and were tested for IGF-1, 41 were above range, persisted in 7, and among those, 2 cases of acromegaly were diagnosed (prevalence of at least 1.35 cases/1000). Overall, 1019 patients (69%) had ≥2 acromegaly symptoms and should have been screened according to guidelines; moreover 373 patients (25%) had ≥1 symptom of acral enlargement plus ≥3 other acromegaly symptoms. In conclusion, in patients with sleep apnea symptoms and acral enlargement, we found an acromegaly prevalence of at least 1.35 cases per 1000 and a high prevalence of typical acromegaly symptoms. It is important that sleep specialists are aware of acromegaly symptoms to aid with acromegaly diagnosis. PMID:28898247
Petrossians, Patrick; Tichomirowa, Maria A; Stevenaert, Achile; Martin, Didier; Daly, Adrian F; Beckers, Albert
Acromegaly is a chronic rare disease associated with negative pathological effects on multiple systems and organs. We designed a new informatics tool to study data from patients with acromegaly, the Liege Acromegaly Survey (LAS). This relational database permits the inclusion of anonymous historical and prospective data on patients and includes pathophysiology, clinical features, responses to therapy and long term outcomes of acromegaly. We deployed the LAS in a validation study at a single center in order to study the characteristics of patients with acromegaly diagnosed at our center from 1970-2011. A total of 290 patients with acromegaly were included (147 males and 143 females). There was a linear relationship between age at diagnosis and the date of diagnosis, indicating that older patients are being diagnosed with acromegaly more frequently. A majority presented with macroadenomas (77.5%) and the median diameter was 14 mm. Patients with macroadenomas were significantly younger than patients with microadenomas (P=0.01). GH values at diagnosis decreased with the age of the patients (P=0.01) and there was a correlation between GH values and tumor size at diagnosis (P=0.02). No correlation existed between insulin-like growth factor 1 (IGF-1) levels and tumor characteristics. The prevalence of diabetes was 21.4% in this population and 41.0% had hypertension. The presence of hypertension and diabetes were significantly associated with one another (P<0.001). There was a linear relation between initial GH and IGF-1 levels at diagnosis and those obtained during SSA analog treatment and the lowest GH and IGF-1 values following SSA therapy were obtained in older patients (GH: P<0.001; IGF-1: P<0.001). The LAS is a new relational database that is feasible to use in the clinical research setting and permits ready pooling of anonymous patient data from multiple study sites to undertake robust statistical analyses of clinical and therapeutic characteristics.
Dreval, A V; Trigolosova, I V; Misnikova, I V; Kovalyova, Y A; Tishenina, R S; Barsukov, I A; Vinogradova, A V; Wolffenbuttel, B H R
Early carbohydrate metabolism disorders (ECMDs) and diabetes mellitus (DM) are frequently associated with acromegaly. We aimed to assess the prevalence of ECMDs in patients with acromegaly and to compare the results with those in adults without acromegaly using two population-based epidemiologic surveys. We evaluated 97 patients with acromegaly in several phases of their disease (mean age, 56 years and estimated duration of acromegaly, 12.5 years). An oral glucose tolerance test was done in those not yet diagnosed with DM to reveal asymptomatic DM or ECMDs (impaired glucose tolerance+impaired fasting glucose). Comparisons were made between patients with acromegaly and participants from the general adult population (n=435) and an adult population with multiple type 2 diabetes risk factors (n=314), matched for gender, age and BMI. DM was diagnosed in 51 patients with acromegaly (52.5%) and 14.3% of the general population (Pacromegaly than in the general population and in the high-risk group; only 22% of patients with acromegaly were normoglycaemic. The prevalence of newly diagnosed ECMDs or DM was 1.3-1.5 times higher in patients with acromegaly compared with the high-risk group. Patients with acromegaly having ECMDs or DM were older, more obese and had longer disease duration and higher IGF1 levels (Z-score). Logistic regression showed that the severity of glucose derangement was predicted by age, BMI and IGF1 levels. In patients with acromegaly, the prevalence of DM and ECMDs considerably exceeds that of the general population and of a high-risk group, and development of DM depends on age, BMI and IGF1 levels.
Leporati, Paola; Fonte, Rodolfo; de Martinis, Luca; Zambelli, Alberto; Magri, Flavia; Pavesi, Lorenzo; Rotondi, Mario; Chiovato, Luca
Acromegaly is a rare disease associated with an increased risk of developing cancer. We report the case of a 72-year-old man who was diagnosed with acromegaly (IGF-1 770 ng/ml) and breast cancer. Four years before he suffered from a colon-rectal cancer. Pituitary surgery and octreotide-LAR treatment failed to control acromegaly. Normalization of IGF-1 (97 ng/ml) was obtained with pegvisomant therapy. Four years after breast cancer surgery, 2 pulmonary metastases were detected at chest CT. The patient was started on anastrozole, but, contrary to medical advice, he stopped pegvisomant treatment (IGF-I 453 ng/ml). Four months later, chest CT revealed an increase in size of the metastatic lesion of the left lung. The patient was shifted from anastrozole to tamoxifen and was restarted on pegvisomant, with normalization of serum IGF-1 levels (90 ng/ml). Four months later, a reduction in size of the metastatic lesion of the left lung was detected by CT. Subsequent CT scans throughout a 24-month follow-up showed a further reduction in size and then a stabilization of the metastasis. This is the first report of a male patient with acromegaly and breast cancer. The clinical course of breast cancer was closely related to the metabolic control of acromegaly. The rapid progression of metastatic lesion was temporally related to stopping pegvisomant treatment and paralleled a rise in serum IGF-1 levels. Normalization of IGF-1 after re-starting pegvisomant impressively reduced the progression of metastatic breast lesions. Control of acromegaly is mandatory in acromegalic patients with cancer.
Marro, B. [Service de Neuroradiologie, Batiment Babinsky, Hopital Salpetriere, 47, Bd de l`Hopital, F-75013 Paris (France); Zouaoui, A. [Service de Neuroradiologie, Batiment Babinsky, Hopital Salpetriere, 47, Bd de l`Hopital, F-75013 Paris (France); Sahel, M. [Service de Neuroradiologie, Batiment Babinsky, Hopital Salpetriere, 47, Bd de l`Hopital, F-75013 Paris (France); Crozat, N. [Service de Neuroradiologie, Batiment Babinsky, Hopital Salpetriere, 47, Bd de l`Hopital, F-75013 Paris (France); Gerber, S. [Service de Neuroradiologie, Batiment Babinsky, Hopital Salpetriere, 47, Bd de l`Hopital, F-75013 Paris (France); Sourour, N. [Service de Neuroradiologie, Batiment Babinsky, Hopital Salpetriere, 47, Bd de l`Hopital, F-75013 Paris (France); Sag, K. [Service de Neuroradiologie, Batiment Babinsky, Hopital Salpetriere, 47, Bd de l`Hopital, F-75013 Paris (France); Marsault, C. [Service de Neuroradiologie, Batiment Babinsky, Hopital Salpetriere, 47, Bd de l`Hopital, F-75013 Paris (France)
Adenomas causing acromegaly represent at least a quarter of pituitary adenomas. We studied 12 patients presenting with active acromegaly due to a pituitary adenoma with a 1.5 T superconductive MRI unit. All had T1-weighted sagittal and coronal sections before and after Gd-DTPA; six had coronal T2-weighted images. Surgical correlation was obtained in seven patients. Histologically, there were eight growth hormone (GH)-secreting and three mixed [GH and prolactin (PRL) secreting] adenomas, and one secreting GH, PRL and follicle-stimulating hormone. Macroadenomas (10) were more frequent than microadenomas (2). No correlation was found between serum GH and tumour size. There were nine adenomas in the lateral part of the pituitary gland; seven showed lateral or infrasellar invasion. Homogeneous, isointense signal on T1- and T2-weighted images was observed in six cases. Heterogeneous adenomas had cystic or necrotic components. (orig.). With 5 figs., 3 tabs.
A news article is presented which discusses a new use for proton therapy. As physicians and physicists continue to refine the clinical applications for charged particles, they can point to at least one notable success story: the treatment of acromegaly, a disorder that afflicts an estimated 250 persons in the United States each year. Bernard Kliman, MD, reported at the annual Endocrine Society meeting in Indianapolis that his group at Harvard Medical School, Boston, and the Harvard cyclotron has cured 479 (85.5%) of 560 patients with acromegaly or gigantism. Cure is defined as reducing growth hormone level to less than 5 ..mu..g/L and shrinking the soft tissue growth characteristic of the disease.
Macleod, A.F.; Clarke, D.G.; Pambakian, H.; Lowy, C.; Sonksen, P.H.; Collins, C.D. (Saint Thomas' Hospital, London (UK))
Despite hypophysectomy as the primary treatment in acromegaly, external radiotherapy maintains a role as a relatively slow but effective therapy for inadequately treated patients or those unsuitable for operation. Over the last 25 years the authors' regimen has differed from published series in that they give a larger dose per fraction, with fewer treatments. They have analysed the efficacy and side-effects of this regimen in 27 subjects with acromegaly. Growth hormone levels have fallen by, on average, 27% per year in the first five years, 83% of subjects achieving a basal growth hormone of <10mU/1. The acute and chronic side-effects of irradiation are discussed, including the relevance of estimates of biological potency, for example Time Dose Fraction (TDF). One patient suffered visual loss that was most likely to be secondary to the radiotherapy. Histological appearances of the pituitary fossa in five subjects previously treated with radiotherapy are reported. (author).
Abe, M; Tabuchi, K; Fujii, K; Oda, K; Ishimoto, S
Acromegaly is often associated with neuromuscular disorders. Most of them are caused by compression of nerves with hypertrophic bone and soft tissues or complications of diabetes mellitus. Myopathy has rarely been reported in the Japanese literature. We report two cases with myopathy out of 14 cases of acromegaly. Case 1 is a 62-year-old woman who developed muscle weakness and atrophy in the shoulder girdle, pelvic girdle and femoral regions after a 10-year history of acromegaly. She showed positive Gowers' sign and normal DTRs. Basal growth hormone (GH) level in plasma was 1076 ng/ml. Electromyograms (EMG) obtained from the deltoid and rectus femoris muscles revealed typical myopathic abnormalities; an excess of small-amplitude, short-duration, polyphasic motor unit potentials. Histological examinations of the rectus femoris muscle showed diffuse atrophy of both type I and type II fibers. She also had bilateral carpal tunnel syndrome and bilateral tarsal tunnel syndrome, which were confirmed by nerve conduction studies of median nerves and posterior tibial nerves. A cranial computed tomography (CT) scan demonstrated sellar mass with suprasellar extension. She underwent transsphenoidal adenomectomy and radiation therapy. GH level lowered to 29 ng/ml, however, myopathy remained unchanged for 3 years after the surgery. Case 2 is a 38-year-old woman who had undergone partial removal of a pituitary adenoma 9 years after the onset of acromegaly. Basal GH level in plasma before the surgery had been 1694 ng/ml and was still high after the surgery (100-505 ng/ml). The patient developed proximal muscle weakness and atrophy 4 years after the surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
Benfante, A; Ciresi, A; Bellia, M; Cannizzaro, F; Bellia, V; Giordano, C; Scichilone, N
Acromegaly is an insidious disorder caused by a pituitary growth hormone (GH)-secreting adenoma resulting in high circulating levels of GH and insulin-like growth factor I (IGF-I). Respiratory disorders are common complications in acromegaly, and can severely impact on quality of life, eventually affecting mortality. The present study aimed to explore structural and functional lung alterations of acromegalic subjects. We enrolled 10 consecutive patients (M/F: 5/5) affected by acromegaly. In all patients, magnetic resonance imaging (MRI) revealed the presence of pituitary tumor. All patients underwent clinical, lung functional, biological, and radiological assessments. Ten healthy age-matched subjects also served as controls. No statistically significant differences in lung function were detected between acromegalic and healthy subjects (p ≥ 0.05 for all analyses). However, the diffusing capacity for CO (TLCO) was significantly lower in the acromegalic group than in healthy subjects (TLCO% predicted: 78.1 ± 16 vs. 90 ± 6 %, respectively, p = 0.04; KCO% predicted: 77 ± 16 vs. 93 ± 5 %, p = 0.02, respectively). None of the lung function parameters correlated with duration of the disease, or with inflammatory marker of the airways. In acromegalics, biological (exhaled NO concentrations) and imaging (total lung volume, TLV, and mean lung density, MLD) evaluations were within normal values. The TLV measured by HRCT was 3540 ± 1555 ml in acromegalics, and the MLD was -711 ± 73 HU. None of the lung functional, radiological, and biological findings correlated with GH or IGF-I levels, and no correlation was found with duration of disease. In the current study, lung function evaluation allowed to detect early involvement of lung parenchyma, as assessed by TLCO and KCO, even in the absence of parenchymal density alterations of the lung by HRCT. These findings suggest to routinely include the carbon monoxide diffusing capacity in the lung function assessment for an
Dusková, J; Chlumská, A; Vilikusová, E; Marek, J; Sprincl, L
A 38-year old man deceased after being operated on recurring pituitary adenoma removed 13 years ago. Autopsy showed a massive spread of tumour on dura and in subarachnoid space. Growth hormone producing cells were found prevailing in the primary tumour as well as in secondaries by immunohistochemistry and immunofluorescence which concurred with acromegaly. Many cells produced prolactin. The tumour spreading discontinually in subdural and subarachnoid space was taken for a carcinoma.
Cuevas-Ramos, Daniel; Carmichael, John D.; Cooper, Odelia; Bonert, Vivien S.; Gertych, Arkadiusz; Mamelak, Adam N.
Context: GH-secreting pituitary adenomas exhibit heterogeneous natural history ranging from small tumors to large aggressive adenomas. Objective: To rigorously classify an acromegaly patient cohort defined by clinical, radiological, histopathological, and outcome characteristics. Design: Cross-sectional study. Setting: Tertiary referral pituitary center. Patients: Subjects were selected from a pituitary tumor research registry that includes 1178 patients with pituitary disease. Cluster analysis was performed on 338 acromegaly patients. Interventions: None. Main Outcome Measures: Biochemically active disease with elevated IGF-1 levels at follow-up. Results: Cluster analysis of all patients yielded 292 who were rigorously classified to three acromegaly types. Type 1 (50%) comprised older patients with the longest follow-up and most favorable outcomes, characterized by densely granulated, nonaggressive microadenomas and macroadenomas. Type 1 tumors extend to the sphenoid sinus more frequently than suprasellar extension (concave tumor image) and express abundant immunoreactive p21 and somatostatin receptor 2. Type 2 (19%) comprised noninvasive, densely or sparsely granulated macroadenomas, without significant extension (flat tumor image), with intermediate biochemical outcome. Type 3 (31%) was characterized by sparsely granulated aggressive macroadenomas and comprised patients with adverse therapeutic outcomes, despite receiving more treatments. These tumors extend to both the sphenoid sinus and suprasellar regions with commonly encountered optic chiasm compression (“peanut” magnetic resonance image), with low tumor p21 and somatostatin receptor 2 expression. Conclusions: After validation, this classification may be useful to accurately identify acromegaly patients with distinctive patterns of disease aggressiveness and outcome, as well as to provide an accurate tool for selection criteria in clinical studies. PMID:25250634
Piatt, J.H. Jr.; Blue, J.M.; Schold, S.C. Jr.; Burger, P.C.
A case of glioblastoma multiforme that occurred 14 years after radiotherapy for acromegaly is presented. The striking correspondence between the anatomy of the tumor and the geometry of the radiation ports is suggestive of a causal relationship. Previously reported cases of radiation-associated glioma are reviewed, and a brief appraisal of the evidence for induction of these lesions by radiation is presented. The differentiation of radiation-associated neoplasms from radionecrosis is also discussed.
Cushing’s syndrome, induced by an endogenous or exogenous cortisol excess, and acromegaly, the clinical syndrome caused by growth hormone (GH) excess in adulthood, as well as the disease induced by GH deficiency (GHD), represent perfect models for the evaluation of the effects induced by chronic exposure in vivo, respectively, to cortisol and GH/IGF-1 excess or deficiency on the complex structure of the tendons as well as on the related post-traumatic repair mechanism. Although the literature...
De Sousa Avinash
Full Text Available Depression is one of the commonest disorders encountered in general hospital psychiatry. Acromegaly is a condition with excessive growth hormone secretion that may at times present with oversychopathology. We present the case of a 33-year-old lady with depression and acromegaly that successfully resolved after treatment with escitalopram and cognitive therapy.
A. Giustina (Andrea); P. Chanson (Philippe); M.D. Bronstein; A. Klibanski; S.W.J. Lamberts (Steven); F.F. Casanueva; P. Trainer; E. Ghigo (Ezio); K.K.Y. Ho; S. Melmed (Shlomo)
textabstractObjective: The Acromegaly Consensus Group met in April 2009 to revisit the guidelines on criteria for cure as defined in 2000. Participants: Participants included 74 neurosurgeons and endocrinologists with extensive experience of treating acromegaly. Evidence/Consensus Process: Relevant
S.E. Franck (Sanne); A. Muhammad (Ammar); A-J. van der Lely (Aart-Jan); S.J.C.M.M. Neggers (Bas)
textabstractTreatment of acromegaly with monotherapy long-acting somatostatin analogues (LA-SSA) as primary treatment or after neurosurgery can only achieve complete normalization of insulin-like growth factor I (IGF-I) in roughly 40 % of patients. Recently, one of the acromegaly consensus groups
S.E. Franck; A. Muhammad; A-J. van der Lely (Aart-Jan); S.J.C.M.M. Neggers (Bas)
textabstractTreatment of acromegaly with monotherapy long-acting somatostatin analogues (LA-SSA) as primary treatment or after neurosurgery can only achieve complete normalization of insulin-like growth factor I (IGF-I) in roughly 40 % of patients. Recently, one of the acromegaly consensus groups ha
A. Giustina (Andrea); P. Chanson (Philippe); M.D. Bronstein; A. Klibanski; S.W.J. Lamberts (Steven); F.F. Casanueva; P. Trainer; E. Ghigo (Ezio); K.K.Y. Ho; S. Melmed (Shlomo)
textabstractObjective: The Acromegaly Consensus Group met in April 2009 to revisit the guidelines on criteria for cure as defined in 2000. Participants: Participants included 74 neurosurgeons and endocrinologists with extensive experience of treating acromegaly. Evidence/Consensus Process: Relevant
Silverstein, Julie M
Acromegaly is a rare and insidious disease characterized by the overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF1) and is most commonly due to a pituitary adenoma. Patients with acromegaly who experience prolonged exposure to elevated levels of GH and IGF1 have an increased mortality risk and progressive worsening of disease-related comorbidities. Multimodal treatment with surgery, medical therapy, and radiotherapy provides biochemical control, defined by recent acromegaly clinical guidelines from the Endocrine Society as a reduction of GH levels to acromegaly, even those without clinical symptoms of disease, require long-term monitoring of GH and IGF1 levels if the benefits associated with biochemical control are to be maintained and the risk of developing recurrent disease is to be abated. However, suboptimal monitoring is common in patients with acromegaly, and this can have negative health effects due to delays in detection of recurrent disease and implementation of appropriate treatment. Because of the significant health consequences associated with prolonged exposure to elevated levels of GH and IGF1, optimal monitoring in patients with acromegaly is needed. This review article will discuss the biochemical assessments used for therapeutic monitoring in acromegaly, the importance of monitoring after surgery and medical therapy or radiotherapy, the consequences of suboptimal monitoring, and the need for improved monitoring algorithms for patients with acromegaly. PMID:26381160
Hannon, Mark J; Barkan, Ariel L; Drake, William M
Radiotherapy has, historically, played a central role in the management of acromegaly, and the last 30 years have seen substantial improvements in the technology used in the delivery of radiation therapy. More recently, the introduction of highly targeted radiotherapy, or 'radiosurgery', has further increased the therapeutic options available in the management of secretory pituitary tumors. Despite these developments, improvements in primary surgical outcomes, an increase in the range and effectiveness of medical therapy options, and long-term safety concerns have combined to dictate that, although still deployed in selected cases, the use of radiotherapy in the management of acromegaly has declined steadily over the past 2 decades. In this article, we review some of the main studies that have documented the efficacy of pituitary radiotherapy on growth hormone hypersecretion and summarize the data around its potential deleterious effects, including hypopituitarism, cranial nerve damage, and the development of radiation-related intracerebral tumors. We also give practical recommendations to guide its future use in patients with acromegaly, generally, as a third-line intervention after neurosurgical intervention in combination with various medical therapy options.
Biermasz, Nienke R; Romijn, Johannes A; Pereira, Alberto M; Roelfsema, Ferdinand
Acromegaly is associated with considerable morbidity and excess mortality; however, after effective treatment, both morbidity and mortality risks improve. Growth hormone excess in acromegaly can be controlled in many patients by pharmacotherapy alone, and with a combination of transsphenoidal surgery and pharmacotherapy in almost all patients. Since the clinical introduction of pegvisomant, a growth hormone-receptor antagonist, the role of radiotherapy is restricted. This review focuses on the treatment options for acromegaly (e.g., surgery, radiotherapy and pharmacotherapy with the depot preparations of the somatostatin analogues octreotide long-acting release formulation, lanreotide slow-release formulation and lanreotide Autogel, the growth hormone antagonist pegvisomant and the dopamine agonist cabergoline). Pharmacological characteristics of these drugs and the clinical and adverse effects are discussed individually and in relation to the other treatment modalities. The evidence for biochemical goals aimed at during medical treatment and the costs of pharmacotherapy are discussed. A new treatment algorithm is proposed, in which the choice between primary medical treatment and primary surgery is individualised, dependent on adenoma size and extension, patient factors (age, preference for therapy, contraindication for surgery), surgical experience of the centre and octreotide sensitivity of the adenoma. The high cost of lifelong medical treatment, especially of pegvisomant, must be weighed against the cost of a single surgical procedure.
Melgar, Virgilio; Espinosa, Etual; Cuenca, Dalia; Valle, Vanessa; Mercado, Moisés
Acromegaly is a rare condition characterized by the excessive secretion of growth hormone (GH), usually by a pituitary adenoma. The clinical manifestations of acromegaly include enlarged hands, feet and face, headaches, arthralgias, fatigue and hyperhydrosis. This condition is also associated with comorbidities such as hypertension and diabetes in a significant proportion of patients and frequently compromises life quality and life expectancy. The biochemical diagnosis of acromegaly rests on the demonstration of an autonomous secretion of GH by means of the measurement of glucose-suppressed GH levels and the serum concentration of insulin like growth factor type 1 (IGF-1). The localizing method of choice is magnetic resonance image of the selar area, which in 70 % of the cases reveals the presence of a macroadenoma. Even though the primary treatment is usually the transsphenoidal resection of the adenoma, the majority of patients require a multimodal intervention that includes radiotherapy, as well as pharmacological therapy with somatostatin analogs and dopamine agonists. The latter approach has resulted in a significant reduction in mortality and in an improvement in the quality of life.
Fang, Hongjuan; Xu, Jian; Wu, Huanwen; Fan, Hong; Zhong, Liyong
Abstract Klinefelter syndrome (KS) is the most common chromosomal aneuploidy in male population, which demonstrates an unusual association with acromegaly. We herein present a rare case involving the confirmation of KS 2 years after surgical treatment for acromegaly. A 27-year-old man presented with an acromegalic appearance. Endocrinological examination revealed a high growth hormone (GH) concentration, low testosterone concentration, and high follicle-stimulating hormone and luteinizing hormone concentration. Brain imaging revealed a 9 × 6 × 7− mm sellar low-density nodule suggestive of a microadenoma. Trans-sphenoidal surgery was undertaken, and immunohistochemistry revealed GH positivity. Two years after surgery, the patient underwent examination for infertility. He presented with diminished pubic hair, and small and firm testes. Hormonal assay revealed hypergonadotrophic hypogonadism on the basis of decreased serum total testosterone (acromegaly is rare, and the association between them remains unclear, we suggest that complete pituitary hormonal screening and conventional pituitary MRI should be essential for patients with KS to screen for pituitary tumor. PMID:27124035
Arosio, M; Porretti, S; Epaminonda, P; Giavoli, C; Gebbia, C; Penati, C; Beck-Peccoz, P; Peracchi, M
GH increases hypothalamic somatostatin (SS) synthesis and secretion but it is unknown if chronic GH excess, as found in acromegaly, may influence circulating SS levels, that are mainly of enteropancreatic source and affect several gastrointestinal functions, including motility. Circulating SS occurs in several post-translational forms including somatostatin-14 (SS-14), somatostatin-28 (SS-28) and other small peptides. The aim of the present study was to characterize the fasting and postprandial pattern of plasma circulating somatostatin in normal subjects and patients with acromegaly. Fasting total SS and SS-28 levels were measured in 32 subjects, 16 acromegalic patients with a new diagnosis (A) (8 F, 8 M, median age 48) and 16 matched healthy volunteers (C) (8 F, 8 M, median age 45). SS was also determined after a standard solid-liquid meal (550 kCal) in 24 of the subjects (12 C and 12 A). Fasting SS and SS-28 were significantly higher in acromegalic patients as compared to healthy subjects. In the former, a positive correlation was found between IGF-I and SS levels (r = 0.525 p acromegaly. Excess GH/IGF-I could be a causal factor in somatostatin hypersecretion. Conceivably this abnormality might play a role in some alterations of gastrointestinal function of acromegalic patients such as prolonged bowel transit.
Krysiak, Robert; Okopień, Bogusław; Marek, Bogdan
Acromegaly is a relatively rare disease caused by excess secretion of growth hormone, usually from a pituitary somatotrope adenoma. Most of the tumors causing acromegaly are sporadic but in some cases the disease results from the presence of an inherited endocrine syndrome including type 1 multiple endocrine neoplasia, McCune-Albright syndrome and Carney complex. Because of the slow evolution of signs and symptoms, acromegaly can be a diagnostic challenge. The disease is characterised by significantly increased morbidity and mortality, both of which are secondary to the involvement of multiple organ systems. This prompts the need for the rapid and accurate recognition and management of this disorder. Acromegaly is diagnosed on the basis of clinical picture, hormonal assays and radiologic imaging of the pituitary gland. This article reviews the etiology, histopathological picture, clinical features and current diagnostic strategies in acromegaly and prognosis in this disorder.
Unubol, Mustafa; Eryilmaz, Ufuk; Guney, Engin; Ture, Mevlut; Akgullu, Cagdas
Acromegaly is a rare condition caused by a pituitary adenoma that secretes growth hormone. The mortality rate is 72 % higher in patients with acromegaly than in the general population according to meta-analyses. Mortality analysis has shown as many as 60 % of acromegalic patients die due to cardiovascular disease. Sudden cardiac death may occur in patients with acromegaly and malignant ventricular arrhythmia may play an important role in this fatal complication; however, the precise mechanism is not fully known. QT dispersion (dQT) is an electrophysiological factor known to be associated with a tendency for ventricular arrhythmia and sudden cardiac death. This study aimed to evaluate dQT as an early predictor of ventricular tachyarrhythmia, as sudden cardiac death commonly occurs in acromegalic patients. This cross-sectional case-control study enrolled 20 patients (10 female and 10 male) with acromegaly and 20 healthy controls (11 female and 9 male) after exclusion criteria were applied. Each participant underwent 12-lead electrocardiography, including ≥3 QRS complexes, at a speed of 25 mm/s after a 15-min rest. In each participant, the QT interval (beginning of the Q wave to the end of the T wave) was corrected (QTc) for heart rate using Bazett's formula [Formula: see text] QTc dispersion (dQTc) (QTc max - QTc min) was also calculated. There was no significant difference in median dQTc between the acromegalic patients (0.79 s) and the controls (0.45 s) (p > 0.05). Active acromegalic patients (n = 14) were estimated to have a median dQTc of 0.82 s, after excluding from the analysis six patients that were under full biochemical control, and that had randomly obtained growth hormone levels acromegaly might have an elevated risk for ventricular arrhythmia. We think that a non-invasive, simple and inexpensive marker-measurement of dQT-as part of cardiac monitoring could be valuable for screening complications in acromegalic patients.
Juan Francisco Martín-Rodríguez
Full Text Available Patients with active untreated acromegaly show mild to moderate neurocognitive disorders that are associated to chronic exposure to growth hormone (GH and insulin-like growth factor (IGF-I hypersecretion. However, it is unknown whether these disorders improve after controlling GH/IGF-I hypersecretion. The aim of this study was to compare neurocognitive functions of patients who successfully underwent GH-secreting adenoma transsphenoidal surgery (cured patients with patients with naive acromegaly. In addition, we wanted to determine the impact of different clinical and biochemical variables on neurocognitive status in patients with active disease and after long-term cure. A battery of six standardized neuropsychological tests assessed attention, memory and executive functioning. In addition, a quantitative electroencephalography with Low-Resolution Electromagnetic Tomography (LORETA solution was performed to obtain information about the neurophysiological state of the patients. Neurocognitive data was compared to that of a healthy control group. Multiple linear regression analysis was also conducted using clinical and hormonal parameters to obtain a set of independent predictors of neurocognitive state before and after cure. Both groups of patients scored significantly poorer than the healthy controls on memory tests, especially those assessing visual and verbal recall. Patients with cured acromegaly did not obtain better cognitive measures than naïve patients. Furthermore memory deficits were associated with decreased beta activity in left medial temporal cortex in both groups of patients. Regression analysis showed longer duration of untreated acromegaly was associated with more severe neurocognitive complications, regardless of the diagnostic group, whereas GH levels at the time of assessment was related to neurocognitive outcome only in naïve patients. Longer duration of post-operative biochemical remission of acromegaly was associated with
Ilhan, Muzaffer; Toptas-Hekimoglu, Bahar; Yaylim, Ilhan; Turgut, Seda; Turan, Saime; Karaman, Ozcan; Tasan, Ertugrul
Objective. The genetic structural alterations in the majority of somatotroph adenomas are not clarified and the search for novel candidate genes is still a challenge. We aimed to investigate possible associations between vitamin D receptor (VDR) polymorphisms and acromegaly. Design, Patients, and Methods. 52 acromegaly patients (mean age 45.7 ± 1.9 years) and 83 controls (mean age 43.1 ± 2.6 years) were recruited to the study. VDR polymorphism was determined by polymerase chain reaction-based restriction fragment length polymorphism methods. Results. The distribution of VDR genotypes showed a significant difference in the frequencies of VDR FokI genotypes between patients and controls (P = 0.034). VDR FokI ff genotype was significantly decreased in acromegaly patients (P = 0.035) and carriers of FokI Ff genotype had a 1.5-fold increased risk for acromegaly (OR: 1.5, 95% CI: 1.07–2.1; P = 0.020). IGF1 levels after treatment were significantly higher in patients carrying the Ff genotype compared to carrying ff genotype (P = 0.0049). 25(OH)D3 levels were significantly lower in acromegaly patients (P < 0.001). Conclusions. Our study suggests that VDR FokI genotypes might affect the development of acromegaly and VDR polymorphisms may play a role in the course of acromegaly as a consequence of altering hormonal status. PMID:25839036
Full Text Available Objective. The genetic structural alterations in the majority of somatotroph adenomas are not clarified and the search for novel candidate genes is still a challenge. We aimed to investigate possible associations between vitamin D receptor (VDR polymorphisms and acromegaly. Design, Patients, and Methods. 52 acromegaly patients (mean age 45.7±1.9 years and 83 controls (mean age 43.1±2.6 years were recruited to the study. VDR polymorphism was determined by polymerase chain reaction-based restriction fragment length polymorphism methods. Results. The distribution of VDR genotypes showed a significant difference in the frequencies of VDR FokI genotypes between patients and controls (P=0.034. VDR FokI ff genotype was significantly decreased in acromegaly patients (P=0.035 and carriers of FokI Ff genotype had a 1.5-fold increased risk for acromegaly (OR: 1.5, 95% CI: 1.07–2.1; P=0.020. IGF1 levels after treatment were significantly higher in patients carrying the Ff genotype compared to carrying ff genotype (P=0.0049. 25(OHD3 levels were significantly lower in acromegaly patients (P<0.001. Conclusions. Our study suggests that VDR FokI genotypes might affect the development of acromegaly and VDR polymorphisms may play a role in the course of acromegaly as a consequence of altering hormonal status.
Shanik, Michael H
Acromegaly is a rare disease characterized by hypersecretion of growth hormone (GH), typically from a benign pituitary somatotroph adenoma, that leads to subsequent hypersecretion of insulin-like growth factor 1 (IGF-1). Patients with acromegaly have an increased risk of mortality and progressive worsening of comorbidities. Surgery, medical therapy, and radiotherapy are currently available treatment approaches for patients with acromegaly, with overall therapeutic goals of lowering GH levels and achieving normal IGF-1 levels, reducing tumor size, improving comorbidities, and minimizing mortality risk. Although surgery can lead to biochemical remission in some patients with acromegaly, many patients will continue to have uncontrolled disease and require additional treatment. We reviewed recently published reports and present a summary of the safety and efficacy of current treatment modalities for patients with acromegaly. A substantial proportion of patients who receive medical therapy or radiotherapy will have persistently elevated GH and/or IGF-1. Because of the serious health consequences of continued elevation of GH and IGF-1, there is a need to improve therapeutic approaches to optimize biochemical control, particularly in high-need patient populations for whom current treatment options provide limited benefit. This review discusses current treatment options for patients with acromegaly, limitations associated with each treatment approach, and areas within the current treatment algorithm, as well as patient populations for which improved therapeutic options are needed. Novel agents in development were also highlighted, which have the potential to improve management of patients with uncontrolled or persistent acromegaly.
Pivonello, Rosario; Auriemma, Renata S; Grasso, Ludovica F S; Pivonello, Claudia; Simeoli, Chiara; Patalano, Roberta; Galdiero, Mariano; Colao, Annamaria
Acromegaly is associated with an enhanced mortality, with cardiovascular and respiratory complications representing not only the most frequent comorbidities but also two of the main causes of deaths, whereas a minor role is played by metabolic complications, and particularly diabetes mellitus. The most prevalent cardiovascular complications of acromegaly include a cardiomyopathy, characterized by cardiac hypertrophy and diastolic and systolic dysfunction together with arterial hypertension, cardiac rhythm disorders and valve diseases, as well as vascular endothelial dysfunction. Biochemical control of acromegaly significantly improves cardiovascular disease, albeit completely recovering to normal mainly in young patients with short disease duration. Respiratory complications, represented mainly by sleep-breathing disorders, particularly sleep apnea, and respiratory insufficiency, frequently occur at the early stage of the disease and, although their severity decreases with disease control, this improvement does not often change the indication for a specific therapy directed to improve respiratory function. Metabolic complications, including glucose and lipid disorders, are variably reported in acromegaly. Treatments of acromegaly may influence glucose metabolism, and the presence of diabetes mellitus in acromegaly may affect the choice of treatments, so that glucose homeostasis is worth being monitored during the entire course of the disease. Early diagnosis and prompt treatment of acromegaly, aimed at obtaining a strict control of hormone excess, are the best strategy to limit the development or reverse the complications and prevent the premature mortality.
Kaldrymidis, Dimitrios; Papadakis, Georgios; Tsakonas, Georgios; Kaldrymidis, Philippos; Flaskas, Theofanis; Seretis, Andreas; Pantazi, Eleni; Kostoglou-Athanassiou, Ifigenia; Peppa, Melpomeni; Roussou, Paraskevi; Diamanti-Kandarakis, Evanthia
Several studies have suggested that patients with acromegaly have an increased risk of thyroid, colorectal, breast and prostate cancers. In this study we determined the prevalence of malignant neoplasms in patients with acromegaly. Cancer risk was evaluated in a cohort of 110 patients (M/F 48/62, age 58.63±13.8 years, range 30-86) with acromegaly. Mean age at diagnosis of acromegaly was 46.37±13.11 years. Mean period of time since diagnosis of acromegaly was 12.26+9.6 years. From 110 patients, cancer was diagnosed in 26 (23.6%) patients. Thyroid cancer was the most common cancer and was diagnosed in 13 patients (11.8%); other cancers encountered were gastric cancer (N=2), endometrial cancer (N-2), and breast cancer, colon cancer, prostate cancer (N-2), myelodysplastic syndrome, renal cell carcinoma, lung cancer and pancreatic carcinoma, one case each. Age, gender, age at the time of diagnosis of acromegaly, tumor size of pituitary adenoma and duration of disease were not associated with cancer development. This study suggests that patients with acromegaly have an increased risk of thyroid cancer and therefore they should undergo regular screening with hormonal and ultrasound evaluation of the thyroid and FNAB when required.
Lieberman, S A; Hoffman, A R
Acromegalic patients suffer from a number of cardiovascular, metabolic, and rheumatologic problems, and they may also have an increased incidence of malignancy. We reviewed the literature concerning the reversibility of acromegalic complications. Hypertension, myocardial hypertrophy, left ventricular dysfunction and some rheumatologic abnormalities often continue despite successful treatment of the acromegaly. In contrast, glucose intolerance, soft tissue changes, and carpal tunnel syndrome usually resolve when the acromegaly is cured. Studies of the incidence and mortality of cancer in acromegaly are conflicting, but several suggest an increased incidence of colorectal cancer.
Full Text Available Malignancy is an important cause of mortality in acromegaly. Hematological malignancies are very rare in acromegaly. Here, we report an 80-year-old patient with acromegaly and multiple myeloma. Patient died within a month of diagnosis. Previous studies have shown that growth hormone and somatomedin-C activate B lymphocyte and somatomedin-C receptors are found in multiple myeloma cells. Possible effects of growth hormone and somatomedin-C on multiple myeloma progression are discussed in the light of the relevant literature. Turk Jem 2013; 17: 75-7
Full Text Available Introduction: Many of the treatment modalities recommended for acromegaly are either too expensive or not available in large parts of India. There is a dearth of treatment and outcome data in Indian patients. Aims and Objectives: The purpose of this study was to analyze the treatment modalities used and the respective outcomes which include remission, recurrence, hypopituitarism, other complications, and mortality. Materials and Methods: This is a retrospective data analysis of 15 acromegaly patients treated at a tertiary care hospital in eastern India. A remission criteria of nadir growth hormone level <1 μg/dl after Oral Glucose tolerance test (OGTT and normal age related IGF-1 levels was used. Results: All patients (100% had macroadenomas. Surgery could not be done in five (33%; three (19.8% refused, two (13.2% had comorbidities. Transsphenoidal surgery (TSS achieved remission in four out of ten (40%. Conventional radiotherapy (CRT failed in all five patients and caused hypopituitarisn in three (60%. Cabergoline (CAB either alone or following surgery achieved remission in one out of four (25% though symptomatic relief and tolerability were remarkable. One patient (7% had pituitary apoplexy with remission, two patients (14.3% died due to CVA. Conclusions: TSS remains the treatment of choice in acromegaly, though in macroadenomas the success is limited. A sizeable proportion of patients refuse or are unfit for surgery. As most of the recommended options are very costly or unavailable, alternative treatment options generally used are CRT or CAB which have limited efficacy. Incidence of hypopituitarism, following CRT is very high.
Muller, Alex F; Van Der Lely, Aart Jan
The treatment of acromegaly has changed considerably over the last few decades. In the late 1970s, the introduction of the dopamine receptor agonists made it possible to reduce growth hormone (GH) secretion by somatotropinomas for the first time. Thereafter, the introduction of the somatostatin analogues in the early 1980s had major implications. Recently, the first data on the use of genetically engineered human GH receptor (GHR) antagonists that block GH actions have become available. These GHR antagonists reduce both the biochemical abnormalities of acromegaly, as well as improve clinical signs and symptomatology. In this article we firstly review available data on dopamine agonists. Currently these compounds should be considered in patients with a mixed GH-prolactin secreting pituitary adenoma and/or those in whom pre-treatment insulin-like growth factor (IGF)-I concentrations are below 750 microg/L. We then discuss the somatostatin analogues. These compounds are capable of achieving biochemical control of GH and IGF-I in 50-60% of patients and tumour shrinkage in some 30%. In particular, candidates for treatment with these compounds are those patients who have undergone an unsuccessful transsphenoidal operation or who await the therapeutic effect of external pituitary irradiation. In selected patients primary medical therapy with somatostatin analogues is certainly a feasible option. To date, pegvisomant is the only available member of a new class of drugs that was especially designed to block the GHR. Pegvisomant is the most effective treatment for normalising IGF-I concentrations and appears to have a good safety profile. However, liver function tests should be regularly monitored and tumour size should be closely followed. Finally, we propose a treatment algorithm for acromegaly.
Daly, A F; Petrossians, P; Beckers, A
Historical data indicate that pituitary tumors represent 10% of intracranial tumors, while adenomas are noted in approximately 14-23% of normal subjects on autopsy or magnetic resonance imaging (MRI). About 2.5% of these tumors stain positive for GH in histopathologic studies. In contrast, the prevalence of clinically diagnosed acromegaly is lower at 36-69 per million population. Ongoing studies indicate that the actual prevalence of acromegaly in the community may be higher than previous epidemiologic data suggest. Acromegaly can occur both sporadically and in the setting of familial conditions, such as multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC). Isolated familial somatotropinoma has been described and newer data suggest that acromegaly may also occur in non-MEN1/CNC families in combination with other pituitary tumor phenotypes.
Shohael Mahmud Arafat
Full Text Available Acromegaly is characterized by chronic hypersecretion of growth hormone (GH and is associated with increased mortality rate because of the potential complications such as cardiovascular disease, respiratory disease, or malignancy, which are probably caused by the long-term exposure of tissues to excess GH, for at least 10 years, before diagnosis and treatment. Here we are reporting a case of acromegaly who initially presented with features of left ventricular failure for which she got herself admitted in CCU and was treated conservatively. Later on, after clinical examination and investigations she was diagnosed as a case of mitral regurgitation due to cardiomyopathy caused by acromegaly. After the successful transsphenoidal resection of the pituitary microadenoma, the level of GH was normalized and heart failure improved. Key words: acromegaly; heart failure; Pituitary microadenoma. DOI: http://dx.doi.org/10.3329/bsmmuj.v4i2.8644 BSMMU J 2011; 4(2:122-124
Jae Won Hong
Full Text Available Acromegaly is a slowly progressive disease caused by excessive growth hormone (GH, which is related to a GH secreting pituitary tumor in most cases. Herein, we describe the epidemiology, clinical characteristics, and treatment of acromegaly in Korea with a literature review. The average annual incidence of acromegaly in Korea was 3.9 cases per million people, which was within the range of previous Western studies. The primary treatment for acromegaly was also transsphenoidal adenomectomy, which accounted for 90.4% of patients whose primary therapeutic options were known. The overall surgical remission rates were 89%, 87%, 64%, 70%, and 50% for modified Hardy classification I, II, IIIA, IIIB, and IV, respectively. An updated and larger study regarding the treatment outcome of medical/radiotherapy in Korean acromegalic patients is needed.
Crespo, Iris; Valassi, Elena; Webb, Susan M
In recent years, health-related quality of life (QoL) has been considered an important outcome for clinical management of acromegaly. Poor QoL has been described in acromegalic patients with active disease as well as after endocrine cure. It is known that acromegaly determines many physical problems and psychological dysfunctions that unavoidably impact on patients' QoL. Moreover, there is evidence that factors, such as radiotherapy or post-treatment GH deficiency also impair QoL in patients diagnosed with acromegaly. Thus, including the assessment of QoL in daily clinical practice has become fundamental to understand the consequences of acromegaly and the impact on the patients' daily life.
Maffezzoni, Filippo; Formenti, Anna Maria; Mazziotti, Gherardo; Frara, Stefano; Giustina, Andrea
Acromegaly is a relatively rare condition of growth hormone (GH) excess associated with significant morbidity and, when left untreated, high mortality. Therapy for acromegaly is targeted at decreasing GH and insulin-like growth hormone 1 levels, ameliorating patients' symptoms and decreasing any local compressive effects of the pituitary adenoma. The therapeutic options for acromegaly include surgery, medical therapies (such as dopamine agonists, somatostatin receptor ligands and the GH receptor antagonist pegvisomant) and radiotherapy. However, despite all these treatments option, approximately 50% of patients are not adequately controlled. In this paper, the authors discuss: 1) efficacy and safety of current medical therapy 2) the efficacy and safety of the new multireceptor-targeted somatostatin ligand pasireotide 3) medical treatments currently under clinical investigation (oral octreotide, ITF2984, ATL1103), and 4) preliminary data on the use of new injectable and transdermal/transmucosal formulations of octreotide. This expert opinion supports the need for new therapeutic agents and modalities for patients with acromegaly.
Full Text Available Pituitary apoplexy is a rare clinical syndrome characterized by sudden onset of headache and vomiting, accompanied by visual disturbance or ocular motility impairment and pituitary insufficiency. Pituitary apoplexy presenting with these symptoms is seen in approximately 3% of patients with surgically treated pituitary adenomas. In acromegalic patients, apoplexy can be related to some provocating factors and rarely may be spontaneous. We present the case of an acromegalic patient with spontaneous remission after apoplexy. A 39-year-old male patient had transsphenoidal microsurgery for acromegaly in 1994 but remission was not achieved. After a 10-year period without follow-up, he experienced severe headache, nausea, vomiting, photophobia, and visual disturbance in July 2005 and scheduled an appointment with an ophthalmologist. His complaints ceased spontaneously within weeks. In October 2005, sellar MRI examination revealed a 3x2.5 cm mass of adenomatous tissue with necrosis. On admission to our clinic in November 2005, visual acuity, visual fields, and ocular motility, were normal; but results of laboratory tests revealed panhypopituitarism. He was thought to have apoplexy of a growth hormone secreting tumor, and hormone replacement therapy was initiated for panhypopituitarism. Because his symptoms had regressed, surgery was not considered. On rare occasions, acromegaly spontaneously remits after apoplexy, resulting in improved control of the functional adenoma without surgical intervention. Turk Jem 2008; 12: 80-2
Full Text Available Case summary A 14-year-old, neutered male European shorthair cat was evaluated for a routine health check. The owner did not report any clinical signs except for respiratory stridor. On physical examination the main findings were broad facial features and increased interdental spaces. On haematology, a mild, non-regenerative anaemia was detected, whereas the serum biochemistry profile and urinalysis were unremarkable. The serum glucose concentration was within the reference interval. Serum insulin-like growth factor-1 concentration was markedly elevated (>1600 ng/ml. The basal serum growth hormone concentration was elevated and decreased only mildly after somatostatin administration. Basal serum insulin concentration was high, and the insulin concentration increased considerably after glucose loading, consistent with insulin resistance. CT scanning of the skull showed an enlarged pituitary gland and increased skull bone thickness. The final diagnosis was acromegaly. Relevance and novel information These findings demonstrate that acromegaly should be pursued and suspected in cats other than those with diabetes mellitus.
Bronstein, Marcello D.; Oscar D. Bruno; Abreu, Alin; Mangupli, Ruth; Mercado, Moisés
Introduction Evidence-based treatment guidelines have undoubtedly advanced medical practice and supported optimal management of acromegaly, but their application may be hampered by limited access to the latest treatment options. Methods In this retrospective, narrative review, the authors revisited existing treatment guidelines for acromegaly in Latin America. These were considered in conjunction with published evidence chosen at the authors’ discretion. Findings In a socially and economicall...
Oshino, Satoru; Nishino, Akio; Suzuki, Tsuyoshi; Arita, Hideyuki; Tateishi, Akihiro; Matsumoto, Katsumi; Shimokawa, Toshio; Kinoshita, Manabu; Yoshimine, Toshiki; Saitoh, Youichi
The prevalence of cerebral aneurysm was retrospectively investigated in 208 patients with acromegaly relative to the rate of cerebral aneurysm in a group of control subjects. Neuroradiological examinations of the cerebral vascular system were conducted in 208 acromegaly patients (101 men; mean age, 48.8 years). The prevalence of cerebral aneurysm in the acromegaly patients was compared to that in a control group consisting of 7,390 subjects who underwent "brain checkup" between 2006 and 2008 (mean age, 51.6 years). In the acromegaly group, cerebral aneurysm was detected in 4.3 % of patients. By sex, the prevalence was 6.9 % in males, a significantly proportion than that in the control group with an odds ratio of 4.40. The prevalence in females did not differ between the two groups. In the acromegaly group, the rate of hypertension was significantly higher in the patients with aneurysm compared to those without aneurysm. Multiple logistic regression identified acromegaly as a significant factor related to the prevalence of cerebral aneurysm in all male subjects; other factors, such as age, hypertension and smoking, were not found to be significant. A significantly higher prevalence of cerebral aneurysm was detected in male patients with acromegaly. This finding indicates that excess growth hormone or insulin-like growth factor 1 affects the cerebral vascular wall, resulting in aneurysm formation. In addition to known systematic complications in the cardiovascular, respiratory, metabolic, and other systems, the risk of cerebral aneurysm should be considered in the management of acromegaly.
Siegel, Sonja; Streetz-van der Werf, Christine; Schott, Jennifer S; Nolte, Kay; Karges, Wolfram; Kreitschmann-Andermahr, Ilonka
The aim of this study was to systematically assess health care utilisation, diagnostic delay and psychosocial impairment in patients with acromegaly in rural versus urban health care environments. 41 patients with acromegaly were questioned to time lapse of symptom onset, first seeking medical advice and time of acromegaly diagnosis. Quality of life (QoL), and psychosocial impairment (depression, daytime sleepiness, sleep disturbances, disturbances of body image) were measured by self-assessment questionnaires. Patients were grouped into living in rural health care environments (RHCE, n = 22 patients) or urban health care environments (UHCE, n = 19 patients) using data on population density from the German Federal Statistical Office. RHCE patients waited significantly longer (2.5 vs. 0.89 years; p = .025) after symptom onset before seeking medical advice, but diagnosis of acromegaly was established at least as quickly as in UHCE (1.45 vs. 2.74 years; n.s.). There was a consistent trend toward more psychosocial impairment in UHCE which reached significance for sleep disturbances (p = .004). For all patients significant correlations between time delay of diagnostic process (defined as first visit to the doctor because of acromegaly-related symptoms and establishment of acromegaly diagnosis) and psychological QoL, depression, daytime sleepiness, sleep disorders and body image emerged. Patients with acromegaly in UHCE experienced more psychosocial impairment than patients in RHCE. The correlation of significantly increased psychosocial impairment and delay of diagnosis by the physician may reflect long-lasting embitterment in patients with acromegaly and should be considered during psychosocial counselling.
Maione, Luigi; Brue, Thierry; Beckers, Albert; Delemer, Brigitte; Petrossians, Patrick; Borson-Chazot, Françoise; Chabre, Olivier; François, Patrick; Bertherat, Jérôme; Cortet-Rudelli, Christine; Chanson, Philippe
Acromegaly is a rare disease associated with chronic multisystem complications. National registries have been created in several countries. The French Registry contains data on acromegaly epidemiology, management and comorbidities recorded over more than three decades, retrospectively until 1999 and prospectively from 1999 to 2012. Data could be analyzed for 999 of the 1034 patients included in the registry (46% males). Disease control, defined as IGF-I normalization (adjusted for age and sex), was achieved in 75% of patients at the last follow-up visit. Half the patients with uncontrolled disease had IGF-I levels below 1.5 times the upper limit of normal (ULN). The proportion of patients with surgically cured disease did not change markedly over time, whereas the proportion of patients with uncontrolled disease fell and the proportion of patients with medically controlled disease rose. Cardiovascular, metabolic, respiratory and rheumatologic comorbidities and their outcomes were recorded for most patients, and no noteworthy overall deterioration was noted over time. Cancer occurred in 10% of patients, for a standardized incidence ratio of 1.34 (95% CI: 0.94-1.87) in men and 1.24 (0.77-1.73) in women. Forty-one patients died during follow-up, for a standardized mortality ratio of 1.05 (0.70-1.42). Most deaths were due to cancer. The majority of patients with acromegaly now have successful disease control thanks to the multistep management. The incidence of comorbidities following diagnosis of acromegaly is very low. Life expectancy is now close to that of the general population, probably owing to better management of the GH/IGF-I excess and comorbidities. © 2017 European Society of Endocrinology.
Roug, Anne Stidsholt; Rasmussen, Åse Krogh; Juhler, M;
To evaluate the effect of fractionated stereotactic radiotherapy (FSRT) in acromegaly in a retrospective analysis.......To evaluate the effect of fractionated stereotactic radiotherapy (FSRT) in acromegaly in a retrospective analysis....
Manuylova, Ekaterina; Calvi, Laura M; Hastings, Catherine; Vates, G Edward; Johnson, Mahlon D; Cave, William T
Summary Co-secretion of growth hormone (GH) and prolactin (PRL) from a single pituitary adenoma is common. In fact, up to 25% of patients with acromegaly may have PRL co-secretion. The prevalence of acromegaly among patients with a newly diagnosed prolactinoma is unknown. Given the possibility of mixed GH and PRL co-secretion, the current recommendation is to obtain an insulin-like growth factor-1 (IGF-1) in patients with prolactinoma at the initial diagnosis. Long-term follow-up of IGF-1 is not routinely done. Here, we report two cases of well-controlled prolactinoma on dopamine agonists with the development of acromegaly 10–20 years after the initial diagnoses. In both patients, a mixed PRL/GH-cosecreting adenoma was confirmed on the pathology examination after transsphenoidal surgery (TSS). Therefore, periodic routine measurements of IGF-1 should be considered regardless of the duration and biochemical control of prolactinoma. Learning points: Acromegaly can develop in patients with well-controlled prolactinoma on dopamine agonists. The interval between prolactinoma and acromegaly diagnoses can be several decades. Periodic screening of patients with prolactinoma for growth hormone excess should be considered and can lead to an early diagnosis of acromegaly before the development of complications. PMID:27855229
Fieffe, Sandrine; Morange, Isabelle; Petrossians, Patrick; Chanson, Philippe; Rohmer, Vincent; Cortet, Christine; Borson-Chazot, Françoise; Brue, Thierry; Delemer, Brigitte
The French Acromegaly Registry records data of acromegalic patients' since 1992 in French, Belgian (Liège), and Swiss (Lausanne) centers. We studied the prevalence of diabetes in this population looking for risk factors. Patients from one of the centers (Reims) were then analyzed more thoroughly. This study has been conducted on all the patients recorded from 1999 until 2004 (519 patients). Evolution of cohorts' was reassessed in 2009. Of the different variables recorded in the registry: age, sex, body mass index (BMI), duration of acromegaly, GH, IGF1 and prolactin levels, pituitary tumor size, hormonal deficiencies, presence, duration and treatment of diabetes, hypertension, and rheumatological disease were analyzed. The prevalence of diabetes in the registry was 22.3%. Diabetic patients were older and had a higher BMI. Compared with the data of the French Social Security, acromegalic patients showed a more precocious apparition of diabetes and prevalence was higher in each age group. Compared with non-diabetic acromegalic subjects, diabetic patients had a more prolonged evolution of acromegaly before diagnosis. The levels of GH and IGF1 were not significantly different between the two groups. Only hypertension was significantly more frequent in diabetic patients. In our population, the prevalence of diabetes was estimated to be 22.3%. The GH and IGF1 levels did not appear as predictive factors for the presence of diabetes. On the contrary, age, BMI, and hypertension were significant risk factors as in the general population of type 2 diabetics.
Hee Kyung Kim; Ji Shin Lee; Min Ho Park; Jin Seong Cho; Jee Hee Yoon; Soo Jeong Kim; Ho-Cheol Kang
Introduction Several studies have reported a high frequency of papillary thyroid cancer (PTC) in patients with acromegaly. The aim of this study was to determine the prevalence and predictors of thyroid cancer in patients with acromegaly and to investigate the frequency of the BRAF V600E mutation in PTC patients with and without acromegaly. Materials and Methods We conducted a retrospective study of 60 patients with acromegaly. Thyroid ultrasonography (US) and US-guided fine needle aspiration...
Kameyama, S; Tanaka, R; Hasegawa, A; Tamura, T; Kuroki, M
Median nerve conduction was studied in 16 acromegalic patients with asymptomatic carpal tunnel syndrome (CTS) to examine the incidence of subclinical CTS. Thirteen patients (81%) and 23 hands (72%) demonstrated subclinical CTS, 10 bilaterally and three unilaterally in the dominant hand. The incidence reflects the greater sensitivity of the inching method for detecting focal conduction abnormalities. Two of three patients without subclinical CTS showed normal plasma somatomedin-C concentration despite growth hormone hypersecretion. Following adenomectomy, nerve conduction normalized in only six hands (26%). The postoperative persistence of the conduction delay implies that irreversible narrowing of the carpal tunnel rather than reversible soft tissue edema is the principal cause of CTS associated with acromegaly.
Sosa, Ernesto; Espinosa-de-los-Monteros, Ana Laura; González, Baldomero; Vargas, Guadalupe; Mier, Fernando; Mercado, Moisés
Treatment of acromegaly with somastostatin analogues, albeit highly effective, is not curative and its elevated cost represents a major disadvantage. Hereby we describe our Center's experience using a fixed, 20 mg q.4 weeks- dose of octreotide LAR. 97 patients, 69 females, 71 with macroadenomas, treated with 20-mg im injections of octreotide LAR every 4 weeks, in 23 as primary therapy. No dose escalation was allowed. Patients were evaluated with GH and IGF-1 levels at 4 weeks after the third injection; thereafter, assessments occurred at 3 to 6 months intervals. In 27 unselected patients, evaluations were also performed 6 weeks after the SA injection. A GH concentration 10 ng/mL was associated with a poor response. A biochemical control rate comparable with other published series it is feasible to reach with the treatment with a fixed dose of 20 mg.
Jensen, Jonna Gintberg; Høi, Henriette Brahe
for participation. An Interview guide was used, and interviews were conducted until data saturation was achieved. Interviews were recorded, and transcription was performed by the researcher. The patients’ statements were categorized by Eriksson's disease, care and life disorders and the three operational levels...... from Kvale’s analysis model were used. The research project's most spectacular findings were that: 1 ) The patients didn’t experience that caregivers had knowledge of the disease and symptoms 2 ) Other patients with Acromegaly were an important source of information 3) Being a teaching object...... for junior doctors was informative educational. Subsequently various initiatives were undertaken to optimize nursing. Among other things, hiring a specialist chief nurse, an informative theme evening for the staff, preparation of a short-term record for documentation, endocrinology training program...
Kim, Jung Hee; Hur, Kyu Yeon; Lee, Jung Hyun; Lee, Ji Hyun; Se, Young-Bem; Kim, Hey In; Lee, Seung Hoon; Nam, Do-Hyun; Kim, Seong Yeon; Kim, Kwang-Won; Kong, Doo-Sik; Kim, Yong Hwy
Endoscopic transsphenoidal surgery has recently been introduced in pituitary surgery. We investigated outcomes and complications of endoscopic surgery in 2 referral centers in Korea. We enrolled 134 patients with acromegaly (microadenomas, n = 15; macroadenomas, n = 119) who underwent endoscopic transsphenoidal surgery at Seoul National University Hospital (n = 74) and Samsung Medical Center (n = 60) between January 2009 and March 2016. Remission was defined as having a normal insulin-like growth factor-1 and a suppressed growth hormone (GH) <1 ng/mL during an oral glucose tolerance test. Remission was achieved in 73.1% of patients, including 13 of 15 microadenoma patients (86.7%) and 86 of 119 macroadenoma patients (72.3%). A multivariate analysis to determine a predictor of biochemical remission demonstrated that absence of cavernous sinus invasion and immediate postoperative GH levels <2.5 ng/dL were significant predictors of remission (adjusted odds ratio [OR], 5.14; 95% confidence interval [CI], 1.52-17.3 and OR, 9.60; 95% CI, 3.41-26.9, respectively). After surgery, normal pituitary function was maintained in 34 patients (25.4%). Sixty-four patients (47.7%) presented complete (n = 59, 44.0%) or incomplete (n = 5, 3.7%) recovery of pituitary function. Hypopituitarism persisted in 20 patients (14.9%) and worsened in 16 patients (11.9%). Postoperatively, transient diabetes insipidus was reported in 52 patients (38.8%) but only persisted in 2 patients (1.5%). Other postoperative complications were epistaxis (n = 2), cerebral fluid leakage (n = 4), infection (n = 1), and intracerebral hemorrhage (n = 1). Endoscopic transsphenoidal surgery for acromegaly presented high remission rates and a low incidence of endocrine deficits and complications. Regardless of surgical techniques, invasive pituitary tumors were associated with poor outcome. Copyright © 2017 Elsevier Inc. All rights reserved.
Erdur, Fatih M; Kilic, Türker; Peker, Selcuk; Celik, Ozlem; Kadioglu, Pinar
We aimed to evaluate the efficacy and reliability of gamma-knife radiosurgery (GKR) in 22 patients with acromegaly at the Endocrinology-Metabolism Clinic of Cerrahpasa Medical School. We collected data retrospectively from hospital records on disease activity and other pituitary functions, pituitary MRI and visual fields, before GKR and 6, 12, 24, 36, 48 and 60 months after GKR. The median follow-up duration after GKR was 60 months (interquartile range [IQR]: 24-60 months). The remission rate was 54.5% after the 60 months of follow-up. The median growth hormone (GH) level at 60 months after GKR (0.99 ng/mL [IQR: 0.36-2.2]) was significantly lower than the median GH level before GKR (5.65 ng/mL [IQR: 3.85-7.2] (p=0.002). The median insulin-like growth factor-1 (IGF-1) level 60 months after GKR (221.5 ng/mL [IQR: 149-535]) was significantly lower than the median IGF-1 level before GKR (582.5 ng/mL [IQR: 515-655]) (p=0.008). Tumour growth was well controlled in 20 patients (95.2%). Six patients (28.6%) developed new-onset hypopituitarism. We concluded that GKR is an effective adjuvant treatment to control tumour growth, lower GH and IGF-1 levels, and to increase remission rates in patients with acromegaly who were refractory to surgical and medical treatment. Copyright © 2011 Elsevier Ltd. All rights reserved.
Full Text Available Background: Though cardiac involvement is common in acromegaly, overt congestive heart failure is uncommon. Materials and Methods: This is retrospective analysis of hospital record between 1996 and 2007. We analyzed records of 150 consecutive patients with acromegaly. We included the patients with acromegaly those who had overt congestive heart failure either at presentation or during the course of illness for the present analysis. The diagnosis of acromegaly and congestive cardiac failure were based on standard criteria. Results:Out of 150 patients with acromegaly, 6 patients had overt CHF (4.0%, of which 4 presented with the features of CHF and 2 developed during the course of illness. Three patients had hypertension and 1 had diabetes. Baseline echocardiography showed severe biventricular dysfunction and global hypokinesia in all. Angiography showed dilated hypokinetic left ventricle with normal coronaries in 3, it was confirmed at autopsy in 1. Three underwent trans-sphenoidal surgery, 1 received somatostatin analogue as primary treatment modality. Normalization of growth hormone and IGF-1 led to improvement in cardiac function in 1, 1 patient lost to follow up, and 4 died during the course of illness. In 1 patient, autopsy was performed and cardiac specimen revealed normal coronaries, concentric ventricular hypertrophy, and dilatation with myofibrolysis and interfascicular fibrosis. Conclusion:Prevalence of overt CHF is 4% in present series. Overt CHF carries poor prognosis and hence, this complication should be recognized at earliest, and medical management to normalized cardiac function should be given utmost priority.
Full Text Available Acromegaly is a rare endocrine disorder characterized by the manifestations of sustained hypersecretion of growth hormone and concomitant elevations in circulating concentrations of insulin-like growth factor-1. It has been reported that patients with acromegaly are at the increased risk of developing malignant tumors, particularly colorectal cancer. Gastrointestinal stromal tumors are mesenchymal tumors of the digestive tract. An association between gastrointestinal stromal tumors and insulin-like growth factor system has been reported. Here, we report a patient diagnosed with synchronous acromegaly and gastrointestinal stromal tumor. A 59-year-old man with iron deficiency anemia presented with enlarged hands, coarse facial feature and several skin tags. Thyroid function tests were within normal range. Growth hormone was 5.14 ng/mL, insulin-like growth factor-1 was 820 ng/mL, and no growth hormone suppression was observed on 75g oral glucose tolerance test. Pituitary magnetic resonance imaging revealed microadenoma, and the patient was diagnosed with acromegaly. Upper gastrointestinal tract endoscopy revealed an ulcerovegetan mass in the duodenum and the results of the histopathologcal analysis was consistent with gastrointestinal stromal tumor. The association of synchronous and asynchronous gastrointestinal stromal tumors with other malignancies have been reported. The most common accompanying neoplasms are colorectal and gastric adenocarcinomas, as well as pancreatic tumors. However, in the literature, the number of reported cases of synchronous acromegaly and gastrointestinal stromal tumor are limited, and there are no sufficient data on this association. Turk Jem 2014; 2: 52-55
Iuliano, Sherry L; Laws, Edward R
To present case studies of a 36-year-old woman and a 73-year-old man who presented with the syndrome of acromegaly, and to provide primary care nurse practitioners (NPs) with the understanding of the clinical and laboratory features needed for early recognition and treatment of this fascinating disease. A comprehensive review of published literature on acromegaly is presented. The findings discussed include the history, physical examination, and diagnostic studies of two patients presenting in different ways. They both saw multiple healthcare providers, and had symptoms and signs eventually leading to the diagnosis of acromegaly. Acromegaly is the result of excessive amounts of growth hormone (GH) and insulin-like growth factor type 1 (IGF-1), almost always caused by a benign adenoma of the pituitary gland. This leads to coarse facial features, soft tissue swelling (including the tongue), enlargement of the hands and feet, respiratory problems, hypertension, diabetes mellitus, carpal tunnel syndrome, and osteoarthritis. Early recognition and appropriate referral can reverse some of the signs and symptoms over time, and lead to decreased mortality and a markedly improved quality of life. These cases exemplify the challenges faced by NPs and other healthcare providers in diagnosing patients with acromegaly. ©2013 The Author(s) ©2013 American Association of Nurse Practitioners.
Hochberg, Irit; Tran, Quynh T.; Barkan, Ariel L.; Saltiel, Alan R.; Chandler, William F.; Bridges, Dave
To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. PMID:26087292
Hochberg, Irit; Tran, Quynh T; Barkan, Ariel L; Saltiel, Alan R; Chandler, William F; Bridges, Dave
To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly.
Störmann, Sylvère; Gutt, Bodo; Roemmler-Zehrer, Josefine; Bidlingmaier, Martin; Huber, Rudolf M; Schopohl, Jochen; Angstwurm, Matthias W
Acromegaly is associated with increased mortality due to respiratory disease. To date, lung function in patients with acromegaly has only been assessed in small studies, with contradicting results. We assessed lung function parameters in a large cohort of patients with acromegaly. Lung function of acromegaly patients was prospectively assessed using spirometry, blood gas analysis and body plethysmography. Biochemical indicators of acromegaly were assessed through measurement of growth hormone and IGF-I levels. This study was performed at the endocrinology outpatient clinic of a tertiary referral center in Germany. We prospectively tested lung function of 109 acromegaly patients (53 male, 56 female; aged 24-82 years; 80 with active acromegaly) without severe acute or chronic pulmonary disease. We compared lung volume, air flow, airway resistance and blood gases to normative data. Acromegaly patients had greater lung volumes (maximal vital capacity, intra-thoracic gas volume and residual volume: P acromegaly. Female patients had significantly altered lung function in terms of subclinical airway obstruction. In our cross-sectional analysis of lung function in 109 patients with acromegaly, lung volumes were increased compared to healthy controls. Additionally, female patients showed signs of subclinical airway obstruction. There was no difference between patients with active acromegaly compared with patients biochemically in remission. © 2017 European Society of Endocrinology.
Mempel, E; Rap, Z; Jurkiewicz, J; Kuciński, L
The authors report results of surgical treatment of 30 patients treated by cryohypophysectomy by the stereotactic method through the nose and sphenoid sinus in the years 1967-1979. The material included 28 cases of acromegaly and 2 cases of gigantism. The pathological manifestations in acromegaly and gigantism were analysed for demonstration which of them can regress after surgical treatment. The results of hormonal determinations, particularly the levels of growth hormone, 17-KS and hydroxysteroids, as well as blood glucose curves, were compared before and after cryohypophysectomy and their normalization was observed after the operation. There was principally no need for substitutive treatment after surgical treatment with the exception of 4 cases in which this treatment was given during several postoperative months. The indications to this method of therapy include cases of acromegaly and gigantism with presence of active intrasellar adenomas. Patients should be referred for treatment early before development of skeletal deformities.
Gosau, Martin; Vogel, Corinna; Moralis, Antonios; Proff, Peter; Kleinheinz, Johannes; Driemel, Oliver
A 22-year-old man presented for orthodontic surgery because of mandibular prognathism. Clinical symptoms suggested acromegaly, and diagnosis was verified by an endocrinologist as well as by radiograph. Bilateral mandibular prognathism often represents the first and most striking physical characteristic of acromegaly; usually, it is also the main reason why patients seek help from orthodontists or maxillo-facial surgeons. This case report recapitulates the clinical and histopathological findings in pituitary growth hormone (GH) adenomas and emphasises their importance in surgical orthodontic planning. Mandibular prognatism, macroglossia and abnormal growth of hands and feet represent strong indicators for the diagnosis of acromegaly. This disease and its complications not only affect the entire body but increase mortality if the pituitary gland tumour remains untreated.
Full Text Available Co-secretion of growth hormone (GH and prolactin (PRL from a single pituitary adenoma is common. In fact, up to 25% of patients with acromegaly may have PRL co-secretion. The prevalence of acromegaly among patients with a newly diagnosed prolactinoma is unknown. Given the possibility of mixed GH and PRL co-secretion, the current recommendation is to obtain an insulin-like growth factor-1 (IGF-1 in patients with prolactinoma at the initial diagnosis. Long-term follow-up of IGF-1 is not routinely done. Here, we report two cases of well-controlled prolactinoma on dopamine agonists with the development of acromegaly 10–20 years after the initial diagnoses. In both patients, a mixed PRL/GH-cosecreting adenoma was confirmed on the pathology examination after transsphenoidal surgery (TSS. Therefore, periodic routine measurements of IGF-1 should be considered regardless of the duration and biochemical control of prolactinoma.
Balos Tuncer, Burcu; Canigur Bavbek, Nehir; Ozkan, Cigdem; Tuncer, Cumhur; Eroglu Altinova, Alev; Gungor, Kahraman; Akturk, Mujde; Balos Toruner, Fusun
The aim of this study was to assess differences in craniofacial characteristics, upper spine and pharyngeal airway morphology in patients with acromegaly compared with healthy individuals. Twenty-one patients with acromegaly were compared with 22 controls by linear and angular measurements on cephalograms. The differences between the mean values of cephalometric parameters were analyzed with Mann-Whitney U-test. With respect to controls, anterior (pacromegaly. Craniofacial changes were predominantly found in the frontal bone (pacromegaly exhibited diminished dimensions at nasal (pacromegaly. Current results point to the importance of the reduced airway dimensions and that dentists and/or orthodontists should be aware of the cranial or dental abnormalities in patients with acromegaly.
Full Text Available CONTEXT: In patients with acromegaly, cardiovascular complications are the main cause of death; sudden death has been associated with ventricular tachyarrhythmias. In other patients with life-threatening malignant ventricular tachyarrhythmias, surgical placement of an implantable cardioverter-defibrillator (ICD has proved highly effective in reducing sudden death rates. CASE REPORT: The present article reports the case of a 50-year-old male acromegalic patient who presented symptoms of syncope induced by ventricular tachycardia. An ICD was surgically implanted and a pituitary adenoma, which was responsible for the acromegaly, was completely removed in the same procedure. The surgery was successful and the ventricular arrhythmias were effectively terminated. During six months of follow-up, no documented arrhythmic episodes occurred. CONCLUSION: In patients with acromegaly, malignant ventricular tachyarrhythmia might be effectively controlled by implantation of an ICD and surgical removal of the pituitary adenoma.
Full Text Available A 45-year-old man presented with binocular diplopia in primary gaze for 1 year. Orthoptic evaluation showed 10-prism diopter right eye hypotropia and 6-prism diopter right eye esotropia. The elevation and abduction of the right eye were mechanically restricted. This was associated with systemic features suggestive of acromegaly. Magnetic resonance imaging (MRI of the brain demonstrated a pituitary macroadenoma. An elevated serum insulin-like growth factor I level and the failure of growth hormone suppression after an oral glucose load biochemically confirmed the diagnosis of acromegaly. Computed tomography (CT of the orbit demonstrated bilateral symmetrical enlargement of the medial rectus and inferior rectus muscle bellies. All tests regarding Graves-Basedow disease were negative. Although rare, diplopia due to a restrictive extraocular myopathy could be the presenting symptom of acromegaly.
Full Text Available Abstract A 22-year-old man presented for orthodontic surgery because of mandibular prognathism. Clinical symptoms suggested acromegaly, and diagnosis was verified by an endocrinologist as well as by radiograph. Bilateral mandibular prognathism often represents the first and most striking physical characteristic of acromegaly; usually, it is also the main reason why patients seek help from orthodontists or maxillo-facial surgeons. This case report recapitulates the clinical and histopathological findings in pituitary growth hormone (GH adenomas and emphasises their importance in surgical orthodontic planning. Mandibular prognatism, macroglossia and abnormal growth of hands and feet represent strong indicators for the diagnosis of acromegaly. This disease and its complications not only affect the entire body but increase mortality if the pituitary gland tumour remains untreated.
Murai, Atsuko; Nishii, Naohito; Morita, Takehito; Yuki, Masashi
Two intact female dogs were admitted for growing mammary tumors. They had symptoms of acromegaly including weight gain, enlargement of the head, excessive skin folds, and inspiratory stridor. Serum concentrations of growth hormone (GH), insulin-like growth factor-I (IGF-I), and insulin were elevated in the two cases. From these findings, both dogs were diagnosed with acromegaly. In case 1, the GH, IGF-I, and insulin levels subsided after removal of the focal benign mammary tumors and ovariohysterectomy. In case 2, those levels subsided after removal of only focal mammary carcinoma. In both cases, immunohistochemical investigations for GH were positive in the mammary tumor cells but not in the normal mammary glands. We concluded that GH-producing mammary tumors caused the present acromegaly.
Vitale, Giovanni; Pivonello, Rosario; Lombardi, Gaetano; Colao, Annamaria
Cardiovascular disease is claimed to be one of the most severe complications of acromegaly, contributing significantly to mortality in this disease. In fact, an excess of growth hormone (GH) and insulin-like growth factor 1 (IGF-I) causes a specific derangement of cardiomyocytes, leading to abnormalities in cardiac muscle structure and function, inducing a specific cardiomyopathy. In the early phase of acromegaly the excess of GH and IGF-I induces a hyperkinetic syndrome, characterized by increased heart rate and increased systolic output. Concentric hypertrophy is the most common feature of cardiac involvement in acromegaly, found in more than two thirds of patients at diagnosis. This abnormality is commonly associated with diastolic dysfunction and eventually with impaired systolic function ending in heart failure, if the GH/IGF-I excess is left untreated. In addition, abnormalities of cardiac rhythm and of heart valves have also been described in acromegaly. The coexistence of other complications, such as arterial hypertension and diabetes mellitus, aggravates acromegalic cardiomyopathy. Successful control of acromegaly induces a decrease in left ventricular mass and an improvement in diastolic function, while the effects of GH/IGF-I suppression on systolic function are more variable. However, since cardiovascular alterations in young patients with short disease duration are milder than in those with longer disease duration, it is likely to be easier to reverse and/or arrest acromegalic cardiomyopathy in young patients with early-onset disease. In conclusion, careful assessments of cardiac function, morphology, and activity are required in patients with acromegaly. An early diagnosis and prompt effective treatment are important in order to reverse acromegalic cardiomyopathy.
Cuevas-Ramos, Daniel; Fleseriu, Maria
Morbidity and mortality rates in patients with active acromegaly are higher than the general population. Adequate biochemical control restores mortality to normal rates. Now, medical therapy has an increasingly important role in the treatment of patients with acromegaly. Somatostatin receptor ligands (SRLs) are considered the standard medical therapy, either after surgery or as a first-line therapy when surgery is deemed ineffective or is contraindicated. Overall, octreotide and lanreotide are first-generation SRLs and are effective in ~20%-70% of patients. Pegvisomant, a growth hormone receptor antagonist, controls insulin-like growth factor 1 in 65%-90% of cases. Consequently, a subset of patients (nonresponders) requires other treatment options. Drug combination therapy offers the potential for more efficacious disease control. However, the development of new medical therapies remains essential. Here, emphasis is placed on new medical therapies to control acromegaly. There is a focus on pasireotide long-acting release (LAR) (Signifor LAR®), which was approved in 2014 by the US Food and Drug Administration and the European Medicine Agency for the treatment of acromegaly. Pasireotide LAR is a long-acting somatostatin multireceptor ligand. In a Phase III clinical trial in patients with acromegaly (naïve to medical therapy or uncontrolled on a maximum dose of first-generation SRLs), 40 and 60 mg of intramuscular pasireotide LAR achieved better biochemical disease control than octreotide LAR, and tumor shrinkage was noted in both pasireotide groups. Pasireotide LAR tolerability was similar to other SRLs, except for a greater frequency and degree of hyperglycemia and diabetes mellitus. Baseline glucose may predict hyperglycemia occurrence after treatment, and careful monitoring of glycemic status and appropriate treatment is required. A precise definition of patients with acromegaly who will derive the greatest therapeutic benefit from pasireotide LAR remains to be
O. Akha; R Rajabian; R. Aboutorabi; S. Teymouri
Abstract Although impaired glucose tolerance affects 36% and overt diabetes mellitus can be seen in 30% of cases with acromegaly, diabetic ketoacidosis is rarely reported in patients with this disease. We present an unusual complication of acromegaly: a 22 year old woman with amenorrhea (6 month ago) and blurred vision of left eye (4 month ago) referred to Ghaem neurology clinic in Mashhad. With a growth hormone (GH) level of =100ng/ml, Insulin like growth factor-1 (IGF-1) =1560 ng/ml and pit...
Muhammad, A; van der Lely, A J; Neggers, S J C M M
In almost every patient, acromegaly is caused by a growth hormone secreting pituitary adenoma. Clinical features are the result of excessive growth hormone secretion and the consecutive excess in insulin-like growth factor I levels. This results in somatic overgrowth and metabolic disturbances with a higher morbidity and mortality than in the general population. With optimal disease management, mortality can be reduced to that seen in the general population. The current treatment of acromegaly is based on a combination of surgery, radiotherapy and medical therapy. This review provides an overview of the current and upcoming therapies with a focus on medical therapy.
Yoshizawa, Toshihiko; Iwazaki, Masayuki; Jitsuiki, Kei; Ishikawa, Kouhei; Ohsaka, Hiromichi; Yanagawa, Youichi
A 61-year-old man with gigantism and acromegaly choked and fell into a coma. Immediate tracheal intubation resulted in a return of his consciousness. Enhanced computed tomography indicated that the trachea and left main bronchus were compressed by the thoracic spine and sternum. He required tracheotomy and positive end-expiratory pressure to maintain his pulmonary function. This is the first case of suffocation due to a thoracic deformity associated with acromegaly. Physicians should focus on clearing the tracheal airway using computed tomography to elucidate the anatomical relationship between the trachea and surrounding structures in acromegalic patients suffering from dyspnea.
Muzaffer Ilhan; Bahar Toptas-Hekimoglu; Ilhan Yaylim; Seda Turgut; Saime Turan; Ozcan Karaman; Ertugrul Tasan
Objective. The genetic structural alterations in the majority of somatotroph adenomas are not clarified and the search for novel candidate genes is still a challenge. We aimed to investigate possible associations between vitamin D receptor (VDR) polymorphisms and acromegaly. Design, Patients, and Methods. 52 acromegaly patients (mean age 45.7 ± 1.9 years) and 83 controls (mean age 43.1 ± 2.6 years) were recruited to the study. VDR polymorphism was determined by polymerase chain reaction-based...
Colak, A; Yılmaz, H; Temel, Y; Demirpence, M; Simsek, N; Karademirci, İ; Bozkurt, U; Yasar, E
Acromegaly is associated with increased cardiovascular morbidity and mortality. The data about the evaluation of coagulation and fibrinolysis in acromegalic patients are very limited and to our knowledge, platelet function analysis has never been investigated. So, we aimed to investigate the levels of protein C, protein S, fibrinogen, antithrombin 3 and platelet function analysis in patients with acromegaly. Thirty-nine patients with active acromegaly and 35 healthy subjects were included in the study. Plasma glucose and lipid profile, fibrinogen levels, GH and IGF-1 levels and protein C, protein S and antithrombin III activities were measured in all study subjects. Also, platelet function analysis was evaluated with collagen/ADP and collagen-epinephrine-closure times. Demographic characteristics of the patient and the control were similar. As expected, fasting blood glucose levels and serum GH and IGF-1 levels were significantly higher in the patient group compared with the control group (pglc: 0.002, pGH: 0.006, pIGF-1: 0.001, respectively). But lipid parameters were similar between the two groups. While serum fibrinogen and antithrombin III levels were found to be significantly higher in acromegaly group (p fibrinogen: 0.005 and pantithrombin III: 0.001), protein S and protein C activity values were significantly lower in the patient group (p protein S: 0.001, p protein C: 0.001). Also significantly enhanced platelet function (measured by collagen/ADP- and collagen/epinephrine-closure times) was demonstrated in acromegaly (p col-ADP: 0.002, p col-epinephrine: 0.002). The results did not change, when we excluded six patients with type 2 diabetes in the acromegaly group. There was a negative correlation between serum GH levels and protein S (r: -0.25, p: 0.04)) and protein C (r: -0.26, p: 0.04) values. Likewise, there was a negative correlation between IGF-1 levels and protein C values (r: -0.39, p: 0.002), protein S values (r: -0.39, p: 0.001), collagen
Full Text Available Objective. Single-session radiosurgery with Gamma Knife (GK may be a potential adjuvant treatment in acromegaly. We analyzed the safety and efficacy of GK in patients who had previously received maximal surgical debulking at our hospital. Methods. The study was a retrospective analysis of hormonal, radiological, and ophthalmologic data collected in a predefined protocol from 1994 to 2009. The mean age at treatment was 42.3 years (range 22–67 yy. 103 acromegalic patients participated in the study. The median follow-up was 71 months (IQ range 43–107. All patients were treated with GK for residual or recurrent GH-secreting adenoma. Results. Sixty-three patients (61.2% reached the main outcome of the study. The rate of remission was 58.3% at 5 years (95% CI 47.6–69.0%. Other 15 patients (14.6% were in remission after GK while on treatment with somatostatin analogues. No serious side effects occurred after GK. Eight patients (7.8% experienced a new deficit of pituitary function. New cases of hypogonadism, hypothyroidism, and hypoadrenalism occurred in 4 of 77 patients (5.2%, 3 of 95 patients (3.2%, and 6 of 100 patients at risk (6.0%, respectively. Conclusion. In a highly selected group of acromegalic patients, GK treatment had good efficacy and safety.
Dal, Jakob; Lundby Høyer, Katrine; Pedersen, Steen Bønløkke;
CONTEXT: Somatostatin analogues (SA) used in acromegaly to suppress GH secretion and tumor growth also suppress insulin secretion and may impact GH signaling. OBJECTIVE: To compare GH and insulin signaling after intravenous GH exposure in acromegalic patients controlled by surgery (n=9) or SA (n=9...... MEASURES: GH and insulin signalling in muscle and fat. GH and IGF-I in serum and interstitial fluid; insulin and FFA in serum. RESULTS: The groups were comparable as regards GH and IGF-I. The SA group exhibited higher FFA and glucose levels; basal SOCS1 mRNA in fat was increased in the SA group...... and correlated positively with SA dose (r(2)= 0.54, P=0.04). GH-induced GH signalling (pSTAT5b) in muscle occurred in both groups together with increased expression of SOCS and CISH genes. GH-induced pAKTthr(308) was observed in SA patients. In both groups mRNA expression of PTEN, a suppressor of insulin...
Manara, Renzo; Bommarito, Giulia; Rizzati, Silvia; Briani, Chiara; Della Puppa, Alessandro; Citton, Valentina; Zanchetta, Eva; Zerbo, Fabio; Ermani, Mario; Martini, Chiara; Mantero, Franco; Sicolo, Nicola; Maffei, Pietro; Scaroni, Carla
Herniation of cerebellar tonsils (CTH) might occur in acromegaly patients and improve after acromegaly treatment. Our study investigated CTH prevalence in acromegaly, its relationship with clinical, laboratory and neuroimaging findings and its possible pathogenesis and clinical impact. 150 acromegaly patients (median-age 56 years, age-range 21-88, 83 females) underwent brain magnetic resonance imaging (MRI). Clinical data, laboratory and pituitary adenoma imaging findings were recorded. CTH, posterior cranial fossa area, tentorial angle, clivus, supraocciput and Twining's line length were measured in acromegaly patients and controls, who included MRI of 115 consecutive subjects with headache or transient neurological deficits (control group-1) and 24 symptomatic classic Chiari 1 malformation patients (control group-2). Acromegaly patients were interviewed for symptoms known to be related with CTH. 22/150 acromegaly patients (15 %) and 8/115 control group-1 subjects presented with CTH (p = 0.04). In acromegaly patients, CTH correlated positively with younger age and inversely with GH-receptor antagonist treatment. Control group-2 had a shorter clivus than CTH acromegaly patients (40.4 ± 3.2 mm vs 42.5 ± 3.3 mm, p < 0.05), while posterior fossa measures did not differ among acromegaly subgroups (with and without CTH) and control group-1. Headache and vision problems were more frequent in CTH acromegaly patients (p < 0.05); two acromegaly patients presented with imaging and neurological signs of syringomyelia. Despite no signs of posterior fossa underdevelopment or cranial constriction, CTH is more frequent in acromegaly patients and seems to contribute to some disabling neurological symptoms.
Mercado, Moisés; Espinosa, Etual; Ramírez, Claudia
Acromegaly is a chronic systemic disorder caused in the vast majority of cases by a GH-secreting pituitary adenoma and resulting in significant morbidity and mortality if left untreated. The treatment of choice is the trans-sphenoidal resection of the adenoma, and although 80% of patients with microadenomas or confined macroadenomas achieve biochemical remission, the surgical success rate for patients harboring tumors with extrasellar extension is below 50%. Thus, a considerable proportion of patients will require some form of adjuvant treatment. Acromegaly can be approached pharmacologically by inhibiting GH secretion by the tumor (somatostatin analogues, dopamine agonists) or by antagonizing GH actions at its target tissues (GH receptor antagonists). The primary pharmacological treatment of acromegaly is increasingly gaining acceptance by both physicians and patients. The decision to use primary pharmacological treatment has to take into account the clinical characteristics of the patient (presence of comorbidities that significantly increase the surgical risk) and the biological nature of the adenoma (tumor size and location), as well as other aspects such as the availability of a pituitary surgeon and the cost of medications. This review provides a critical summary and update of the pharmacological treatment of acromegaly focusing both, on well-established agents and strategies as well as on novel compounds that are currently being developed.
Chihara, K; Kaji, H; Minamitani, N; Kodama, H; Kita, T; Goto, B; Chiba, T; Coy, D H; Fujita, T
Vasoactive intestinal polypeptide (VIP) was administered as an iv bolus of 1 micrograms/kg BW to 8 acromegalic patients and in doses of 0.5 and 1 microgram/kg BW to 15 normal volunteers. Both systolic and diastolic blood pressures decreased, and pulse rate increased transiently after VIP injection. VIP stimulated PRL release from the anterior pituitary in normal subjects. Plasma PRL responses to VIP in women were dose dependent and larger than those in men. On the other hand, plasma GH levels rose markedly after VIP injection in all 6 patients with untreated acromegaly. In 2 patients studied after transsphenoidal microadenomectomy, there was no plasma GH response to VIP. In 2 other patients with inactive acromegaly as well as in normal subjects, VIP failed to affect plasma GH levels. In all 6 patients with active acromegaly, LRH (1-2 micrograms/kg BW, iv) did not increase plasma GH levels, but TRH (5-10 micrograms/kg BW, iv) caused significant increases in plasma GH, the magnitude of which was not similar to that of increases seen after VIP injection. Paradoxical GH responses to TRH were not observed in patients in the inactive phase after transsphenoidal surgery. These findings suggest that VIP stimulates GH release in vivo in acromegalic patients. A VIP test as well as a TRH test offer promise as simple and reliable techniques to evaluate the activity of acromegaly, particularly after transsphenoidal surgery.
Duarte, Felipe H; Jallad, Raquel S; Bronstein, Marcello D
Despite recent advances in acromegaly treatment by surgery, drugs, and radiotherapy, hormonal control is still not achieved by some patients. The impairment of IGF-1 generation by estrogens in growth hormone deficient patients is well known. Patients on oral estrogens need higher growth hormone doses in order to achieve normal IGF-1 values. In the past, estrogens were one of the first drugs used to treat acromegaly. Nevertheless, due to the high doses used and the obvious side effects in male patients, this strategy was sidelined with the development of more specific drugs, as somatostatin receptor ligands and dopamine agonists. In the last 15 years, the antagonist of growth hormone receptor became available, making possible IGF-1 control of the majority of patients on this particular drug. However, due to its high cost, pegvisomant is still not available in many centers around the world. In this setting, the effect of estrogens and also of selective estrogen receptor modulators on IGF-1 control was reviewed, and proved to be an ancillary tool in the management of acromegaly. This review describes data concerning their efficacy and place in the treatment algorithm of acromegaly.
Tobi, M; Cats, A; Maliakkal, BJ; Kinzie, JL; Maliakkal, R; Dullaart, RPF; Luk, GD
Zollinger-Ellison syndrome (ZES) and acromegaly are two hypersecretory states in which colorectal neoplasia has been described, but the incidence in the former condition may not be increased. We describe four patients with colorectal neoplasia associated with the ZES and review other published
Abucham, Julio; Bronstein, Marcello D; Dias, Monike L
Although fertility is frequently impaired in women with acromegaly, pregnancy is apparently becoming more common due to improvement in acromegaly treatment as well as in fertility therapy. As a result, several studies on pregnancy in patients with acromegaly have been published in recent years adding new and relevant information to the preexisting literature. Also, new GH assays with selective specificities and the knowledge of the expression of the various GH genes have allowed a better understanding of somatotrophic axis function during pregnancy. In this review, we show that pregnancy in women with acromegaly is generally safe, usually with tumoral and hormonal stability. Although the paucity of data limits evidence-based recommendations for preconception counseling and pregnancy surveillance, controlling tumor size and hormonal activity before pregnancy is highly recommended to ensure better outcomes, and surgical control should be attempted when feasible. Treatment interruption at pregnancy confirmation has also proven to be safe, as drugs are not formally allowed to be used during pregnancy. Drug exposure (somatostatin analogs) during early or whole pregnancy might increase the chance of a lower birth weight. Aggressive disease is uncommon and may urge individual decisions such as surgery or drug treatment during pregnancy or lactation. © 2017 European Society of Endocrinology.
Murray B. Gordon
Full Text Available Introduction. Frequent colonoscopy screenings are critical for early diagnosis of colon cancer in patients with acromegaly. Case Presentations. We performed a retrospective analysis of the incidental diagnoses of colon cancer from the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734. Colon cancer was identified in 2 patients (4.5%. Case 1 patient was a 36-year-old male with acromegaly who underwent transsphenoidal surgery to remove the pituitary adenoma. After surgery, the patient underwent routine colonoscopy screening, which revealed a 40 mm tubular adenoma in the descending colon. A T1N1a carcinoma was surgically removed, and 1 of 22 lymph nodes was positive for metastatic disease, leading to a diagnosis of stage 3 colon cancer. Case 2 patient was a 50-year-old male with acromegaly who underwent transsphenoidal surgery to remove a 2 cm pituitary adenoma. The patient reported severe cramping and lower abdominal pain, and an invasive 8.1 cm3 grade 2 adenocarcinoma with signet rings was identified in the ascending colon and removed. Of the 37 lymph nodes, 34 were positive for the presence of tumor cells, and stage 3c colon cancer was confirmed. Conclusion. Current guidelines for colonoscopy screening at the time of diagnosis of acromegaly and at appropriate follow-up intervals should be followed.
Tobi, M; Cats, A; Maliakkal, BJ; Kinzie, JL; Maliakkal, R; Dullaart, RPF; Luk, GD
Zollinger-Ellison syndrome (ZES) and acromegaly are two hypersecretory states in which colorectal neoplasia has been described, but the incidence in the former condition may not be increased. We describe four patients with colorectal neoplasia associated with the ZES and review other published cases
Nakhle, Samer; Ludlam, William H.
Introduction. Frequent colonoscopy screenings are critical for early diagnosis of colon cancer in patients with acromegaly. Case Presentations. We performed a retrospective analysis of the incidental diagnoses of colon cancer from the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734). Colon cancer was identified in 2 patients (4.5%). Case 1 patient was a 36-year-old male with acromegaly who underwent transsphenoidal surgery to remove the pituitary adenoma. After surgery, the patient underwent routine colonoscopy screening, which revealed a 40 mm tubular adenoma in the descending colon. A T1N1a carcinoma was surgically removed, and 1 of 22 lymph nodes was positive for metastatic disease, leading to a diagnosis of stage 3 colon cancer. Case 2 patient was a 50-year-old male with acromegaly who underwent transsphenoidal surgery to remove a 2 cm pituitary adenoma. The patient reported severe cramping and lower abdominal pain, and an invasive 8.1 cm3 grade 2 adenocarcinoma with signet rings was identified in the ascending colon and removed. Of the 37 lymph nodes, 34 were positive for the presence of tumor cells, and stage 3c colon cancer was confirmed. Conclusion. Current guidelines for colonoscopy screening at the time of diagnosis of acromegaly and at appropriate follow-up intervals should be followed. PMID:28025627
Turan, Onur; Akinci, Barış; Ikiz, Ahmet Omer; Itil, Oya; Oztura, Ibrahim; Ada, Emel; Akdeniz, Bahri; Yener, Serkan; Kaya, Murat; Gedik, Arzu; Comlekci, Abdurrahman
Acromegaly is a multisystemic disorder caused by excessive secretion of growth hormone (GH). Sleep-disordered breathing (SDB) such as sleep apnea syndrome (SAS) may occur in acromegaly. The aim of study was to assess the presence of sleep disorders and evaluate the systemic complications on respiratory, cardiovascular, and upper airway systems in acromegalic patients. The study group consisted of 30 acromegaly outpatients. GH and insulin-like growth factor 1 (IGF-1) measurements were obtained; body pletysmography, arterial blood gas analysis, tissue-doppler imaging, echocardiography, polysomnography, otorhinolaryngologic examination, and head-neck computed tomography were performed. Sixteen female (53.3%) and 14 male (46.7%) acromegalic patients had a mean age of 51.1 ± 13.2. GH was supressed in 19 patients (63.3%) when 11 had active acromegaly (36.7%). There were 17 patients with SAS (62.9%) (7: mild, 3:intermediate, 7:severe SAS) and average AHI was 16/h. Sixteen patients had predominantly obstructive SAS while one patient had predominantly central SAS. SAS was statistically more frequent in males than females (P = .015). The mean neck circumference was significantly longer in patients with SAS (P = .048). In SAS patients,the soft palate was elongated and thickened,which was statistically significant (P = .014 and P = .05).Vallecula-to-tongue distance was statistically longer in acromegalic patients with SAS (P = .007).There was a positive correlation between tonsil size,vallecula-to-tongue distance and AHI (r = 0.432, P = .045 and r = 0.512, P = .021, respectively). SDB seems to be common and clinically important in patients with acromegaly, particularly in men. The most frequent type of apnea in acromegalics is obstructive. Hormonal activity of acromegaly does not seem to have an effect on the development of SAS. Despite its high prevalence, SAS is frequently under-assessed in patients with acromegaly. Systemic
Joanna Elżbieta Malicka
Full Text Available Background . The prevalence of adenomas which cause acromegaly is estimated at 50–70 mln people. They secrete excess of growth hormone and increase the risk of benign and malignant tumours. Intestinal tumours are considered the most common types of lesion. In order to diagnose them early, a colonoscopic examination should be performed every 2–3 years. Objectives. The aim of the study was to estimate the frequency of the performed colonoscopies in acromegaly patients, and to assess their applicability in the detection of neoplastic lesions of the colon. Material and methods . The study involved 69 patients with acromegaly (26 M, 43 F, aged 26–83 years (mean 58.9 ± 11.0. The authors analyzed medical records and the results of additional tests. Results . Colonoscopy was performed in 30 patients (43.5% of cases, was well tolerated and without serious complications. 70% of colonoscopies revealed polyps of the colon and 6.7% revealed colon carcinoma. In 9 patients (30% of conducted studies colonoscopy examination showed no pathological changes. Only in 4 cases the test was performed more than once. Conclusions . Current recommendations regarding colonoscopic examinations in all acromegaly patients are implemented in less than half of the cases. Recommendations relating to colonoscopy being repeated every 2–3 years are followed occasionally. Colonoscopy is a diagnostic test of great significance. In 70% of cases it enables the detection and removal of pathological lesions of the colon. As a low-invasive, safe and well-tolerated examination it should be performed in all patients. GPs should make acromegaly patients aware of the importance of colonoscopy and refer them for periodic follow-up examinations.
Bhansali, A; Upreti, V; Dutta, P; Mukherjee, K K; Nahar, U; Santosh, R; Das, S; Walia, R; Pathak, A
Adolescent acromegaly is a rare disorder and these patients present with tall stature/gigantism, tumor mass effects and menstrual irregularities. 34 consecutive (26 males) patients having onset of disease prior to 21 years of age were included in this retrospective analysis. Their clinical features and treatment outcome were studied. Mean age and lag time at presentation were 21.6 +/- 3.9 years and 5.1 +/- 3.5 years respectively. Common presenting manifestations included acral enlargement, tumor mass effects and menstrual irregularities. Mean height at presentation was 174.6 +/- 13.7 cms (range: 150-210 cm) and one third had gigantism (height > or =97th percentile, WHO growth charts). Hypertension and glucose intolerance were seen in 15% and 23.5% respectively. Mean nadir GH after glucose load was 58.2 +/- 13.7 ng/ml and IGF -1 was 534.8 +/- 132.8 ng/ml. Half of the patients had concomitant hyperprolactinemia. Almost all (97%) had macroadenoma and anterior pituitary hormone deficiencies were frequent (75%). Patients with gigantism were younger (19.6 +/- 4.9 vs. 22.6 +/- 2.9 years; p = 0.001), had higher GH values (66.68 +/- 27.22 vs. 53.98 +/- 15.99 ng/ml; p = 0.04) and hypogonadism was more common (90.9% vs. 56.5%, p = 0.03) than those with normal stature. 32 patients (94.1%) were treated primarily with surgery, 7 (21.9%) received post operative radiotherapy. Mean duration of follow up was 33.1 +/- 10.1 months. Only 30% had nadir GH values of <1 ng/ml. One third of adolescent patients had acrogigantism. These patients were younger, had higher GH levels and concurrent hypogonadism was more common. Cure could be achieved only in about one third of the patients.
Bernabeu, I; Alvarez-Escolá, C; Paniagua, A E; Lucas, T; Pavón, I; Cabezas-Agrícola, J M; Casanueva, F F; Marazuela, M
Combination with cabergoline may offer additional benefits to acromegalic patients on pegvisomant monotherapy. We evaluated the safety and efficacy profile of this combination and investigated the determinants of response. An observational, retrospective, cross-sectional study. Fourteen acromegalic patients (9 females), who were partially resistant to somatostatin analogs and on pegvisomant monotherapy. Cabergoline was added because of the presence of persistent mildly increased IGF-I. The mean follow-up time was 18.3 ± 10.4 months. The efficacy and safety profile was assessed. The influence of clinical and biochemical characteristics on treatment efficacy was studied. IGF-I levels returned to normal in 4 patients (28%) at the end of the study. In addition, some decline in IGF-I levels was observed in a further 5 patients. The % IGF-I decreased from 158 ± 64% to 124 ± 44% (p = 0.001). The average change in IGF-I was -18 ± 27% (range -67 to +24%). Lower baseline IGF-I (p = 0.007), female gender (p = 0.013), lower body weight (p = 0.031), and higher prolactin (PRL) levels (p = 0.007) were associated with a better response to combination therapy. There were no significant severe adverse events. Significant tumour shrinkage was observed in 1 patient. Combination therapy with pegvisomant and cabergoline could provide better control of IGF-I in some patients with acromegaly. Baseline IGF-I levels, female gender, body weight, and PRL levels affect the response to this combination therapy.
Danilowicz, Karina; Day, Patricia Fainstein; Marcos P. Manavela; Herrera, Carlos Javier; Deheza, María Laura; Isaac, Gabriel; Juri, Ariel; Katz, Debora; Oscar D. Bruno
Introduction Acromegaly is a rare disease with a large burden due its associated comorbidities and the life-long management required. Since the occurrence and severity of associated complications are related to length of exposure to the excess growth hormone seen in acromegaly, early diagnosis is imperative. The delay in diagnosis, however, can be long, and may be the result of a lack of disease awareness and screening programs. Since acromegaly is an uncommon disease, finding ways to increas...
Brummelman, Pauline; Koerts, Janneke; Dullaart, Robin P. F.; van den Berg, Gerrit; Tucha, Oliver; Wolffenbuttel, Bruce H R; van Beek, Andre P.
Background In untreated acromegaly patients, decreased cognitive functioning is reported to be associated with the degree of growth hormone (GH) and IGF-1 excess. Whether previous GH excess or current medical treatment for acromegaly specifically affects cognition remains unclear. The aim of this study was to compare cognitive functioning of patients who are treated for acromegaly with patients with non-functioning pituitary adenomas (NFA). In addition, we assessed the influence of prolonged ...
Burton, Tanya; Le Nestour, Elisabeth; Neary, Maureen; Ludlam, William H.
Purpose Incidence and prevalence estimates of acromegaly in the United States (US) are limited. Most existing reports are based on European data sources. The objective of this study was to estimate the annual incidence and prevalence of acromegaly in a large US managed care population, overall and stratified by age, sex, and geographic region, using data from 2008 to 2012. Methods Using administrative claims data, commercial health plan enrollees were identified with acromegaly if they had tw...
Giustina, Andrea; Chanson, Philippe; Kleinberg, David; Bronstein, Marcello D; Clemmons, David R; Klibanski, Anne; van der Lely, Aart J; Strasburger, Christian J; Lamberts, Steven W; Ho, Ken K Y; Casanueva, Felipe F; Melmed, Shlomo
In March 2013, the Acromegaly Consensus Group met to revise and update guidelines for the medical treatment of acromegaly. The meeting comprised experts skilled in the medical management of acromegaly. The group considered treatment goals covering biochemical, clinical and tumour volume outcomes, and the place in guidelines of somatostatin receptor ligands, growth hormone receptor antagonists and dopamine agonists, and alternative modalities for treatment including combination therapy and novel treatments. This document represents the conclusions of the workshop consensus.
Zarool-Hassan, Redzuan; Conaglen, Helen M; Conaglen, John V; Elston, Marianne S
INTRODUCTION Chronic excess growth hormone production results in acromegaly, a condition associated with widespread physical changes, including soft tissue and bony overgrowth. When untreated, acromegaly reduces life expectancy. Patients usually remain undiagnosed for years after the onset of symptoms, by which stage irreversible physical changes have often occurred. METHOD A cross-sectional questionnaire study involving patients with acromegaly from the Waikato Endocrine Unit and the New Zealand Acromegaly Society evaluated features of acromegaly that were present before diagnosis. The aim of this study was to identify acromegaly features that were most prevalent to promote increased awareness about the disease by healthcare providers. RESULTS 81 participants were included. The main pre-diagnosis physical changes participants reported were acral changes, alterations in facial features and oral symptoms. For some, these features were present for more than 10 years before the acromegaly diagnosis. Multiple co-morbidities associated with acromegaly were reported. Two-thirds of the participants felt that an earlier diagnosis was possible. Most participants were in contact with General Practitioners (GPs) and/or dentists before diagnosis. Endocrinologists had the highest diagnosis rate, followed by GPs. Dentists had a low diagnosis rate despite a high prevalence of oral symptoms among study participants. CONCLUSION Increased awareness of acromegaly among primary care clinicians is important as they are the first-point-of-contact with the healthcare system for most patients. Health professionals' early recognition of symptoms and signs of acromegaly would reduce delays in time-to-diagnosis, enable earlier treatment and may improve outcomes for patients with acromegaly. MESH KEYWORDS Acromegaly; symptoms; delayed diagnosis; clinicians; primary healthcare.
Full Text Available Acromegaly is a rare disease that, in the majority of cases, is due to the presence of a benign growth hormone (GH- producing tumor of the pituitary. Growth hormone has profound effects on linear bone growth, bone metabolism, and bone mass. In acromegaly, the skeletal effects of chronic GH excess have been mainly addressed by evaluating bone mineral density (BMD. Most data were obtained in patients with active acromegaly, and apparently high or normal BMD was observed in the absence of hypogonadism. The Autors describe a case of patient affected by acromegaly without hypogonadism with serious osteoporosis and biological signs of osteomalacia.
Ilhan, M M; Alkan, A; Aralasmak, A; Akkoyunlu, M E; Kart, L; Tasan, E
Objective: We examined brain diffusion changes of patients with acromegaly. We searched whether there are differences in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values between remission and non-remission patients with acromegaly and investigated any effect of time of hormone exposure on diffusion metrics. Methods: The values of FA and ADC were calculated in a total of 35 patients with acromegaly and 28 control subjects. Patients were subdivided into remission and non-remission groups. We looked at brain FA and ADC differences among the groups and looked for any relation between the diffusion changes and time of hormone exposure among the patients with acromegaly. Results: We found decreased FA and increased ADC values in some of the growth hormone responsive areas. There were no significant brain diffusion changes between remission and non-remission groups. The most affected areas were the hypothalamus, parietal white matter and pre-motor cortex in patients with acromegaly. In terms of hormone exposure time among the patients with acromegaly, there was no effect of disease duration on brain microstructural changes. Conclusion: All patients with acromegaly showed increased brain diffusion with no relation to disease duration and treatment status. We suggested that in patients with acromegaly, brain damage had already occurred in the subclinical period before symptom onset. Advances in knowledge: This study contributes to the understanding of the mechanisms in acromegaly. PMID:24734977
Martín-Rodríguez, Juan Francisco; Madrazo-Atutxa, Ainara; Venegas-Moreno, Eva; Benito-López, Pedro; Gálvez, María Ángeles; Cano, David A.; Tinahones, Francisco J.; Torres-Vela, Elena; Soto-Moreno, Alfonso; Leal-Cerro, Alfonso
Patients with active untreated acromegaly show mild to moderate neurocognitive disorders that are associated to chronic exposure to growth hormone (GH) and insulin-like growth factor (IGF-I) hypersecretion. However, it is unknown whether these disorders improve after controlling GH/IGF-I hypersecretion. The aim of this study was to compare neurocognitive functions of patients who successfully underwent GH-secreting adenoma transsphenoidal surgery (cured patients) with patients with naive acromegaly. In addition, we wanted to determine the impact of different clinical and biochemical variables on neurocognitive status in patients with active disease and after long-term cure. A battery of six standardized neuropsychological tests assessed attention, memory and executive functioning. In addition, a quantitative electroencephalography with Low-Resolution Electromagnetic Tomography (LORETA) solution was performed to obtain information about the neurophysiological state of the patients. Neurocognitive data was compared to that of a healthy control group. Multiple linear regression analysis was also conducted using clinical and hormonal parameters to obtain a set of independent predictors of neurocognitive state before and after cure. Both groups of patients scored significantly poorer than the healthy controls on memory tests, especially those assessing visual and verbal recall. Patients with cured acromegaly did not obtain better cognitive measures than naïve patients. Furthermore memory deficits were associated with decreased beta activity in left medial temporal cortex in both groups of patients. Regression analysis showed longer duration of untreated acromegaly was associated with more severe neurocognitive complications, regardless of the diagnostic group, whereas GH levels at the time of assessment was related to neurocognitive outcome only in naïve patients. Longer duration of post-operative biochemical remission of acromegaly was associated with better
Full Text Available Daniel Cuevas-Ramos,1 Maria Fleseriu2,3 1Department of Endocrinology and Metabolism, Neuroendocrinology Clinic, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; 2Department of Medicine (Endocrinology, 3Department of Neurological Surgery, Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA Abstract: Morbidity and mortality rates in patients with active acromegaly are higher than the general population. Adequate biochemical control restores mortality to normal rates. Now, medical therapy has an increasingly important role in the treatment of patients with acromegaly. Somatostatin receptor ligands (SRLs are considered the standard medical therapy, either after surgery or as a first-line therapy when surgery is deemed ineffective or is contraindicated. Overall, octreotide and lanreotide are first-generation SRLs and are effective in ~20%–70% of patients. Pegvisomant, a growth hormone receptor antagonist, controls insulin-like growth factor 1 in 65%–90% of cases. Consequently, a subset of patients (nonresponders requires other treatment options. Drug combination therapy offers the potential for more efficacious disease control. However, the development of new medical therapies remains essential. Here, emphasis is placed on new medical therapies to control acromegaly. There is a focus on pasireotide long-acting release (LAR (Signifor LAR®, which was approved in 2014 by the US Food and Drug Administration and the European Medicine Agency for the treatment of acromegaly. Pasireotide LAR is a long-acting somatostatin multireceptor ligand. In a Phase III clinical trial in patients with acromegaly (naïve to medical therapy or uncontrolled on a maximum dose of first-generation SRLs, 40 and 60 mg of intramuscular pasireotide LAR achieved better biochemical disease control than octreotide LAR, and tumor shrinkage was noted in both pasireotide groups. Pasireotide LAR tolerability
Broder, Michael S; Chang, Eunice; Ludlam, William H; Neary, Maureen P; Carmichael, John D
To establish a baseline pattern of care across academic and community settings, it is important to examine the contemporary treatment of acromegaly. We characterized medical treatment patterns for acromegaly in the US to develop a basis for tracking concordance with guidelines. Acromegaly patients were identified in two commercial claims databases for this retrospective analysis. Study subjects had ≥2 medical claims with acromegaly (ICD-9-CM code 253.0) and ≥1 claim for pharmacotherapy (bromocriptine, cabergoline, octreotide SA, octreotide LAR, lanreotide, or pegvisomant) in the study timeframe (1 January 2002-31 December 2013). Patients were considered newly treated if they were continuously enrolled for ≥6 months before first observed treatment and had no claim for pharmacologic treatment during that time. Outcomes included various pharmacotherapies, including combination treatments, and differences between lines of therapy. A total of 3150 patients had ≥1 pharmacotherapy (mean age: 46.5 years; 50.1% were female); 1471 were newly treated. Somatostatin receptor ligands (SRLs) were the most common drug class used first line (57.2%); cabergoline (27.8%) was the most common treatment, followed by octreotide LAR (22.3%) and lanreotide (19.7%). SRLs were also the most commonly used second-line (42.8%) and third-line pharmacotherapies (43.9%), with combination therapy (23.2%) and octreotide LAR (19.8%) as the most commonly used treatments, respectively. This study, representing the largest claims-based analysis of acromegaly to date, used two databases across a 12 year period to examine complex treatment patterns in a difficult-to-study disease. Although wide variation in acromegaly treatment patterns exists in US clinical practice, in first-line, second-line, and third-line therapy, SRL was the most commonly used drug class. Drug combinations also varied considerably across lines of therapy. The switching between different monotherapies and varied use of drugs
Reid, Tirissa J.; Post, Kalmon D.; Bruce, Jeffrey N.; Kanibir, M. Nabi; Reyes-Vidal, Carlos M.; Freda, Pamela U.
BACKGROUND Traditionally, acromegaly evaded diagnosis until in its clinically obvious later stages when treatment is more difficult. Over the last 25 years diagnostic tests have improved, but whether clinical disease detection also improved was unknown so we tested if disease severity at diagnosis had changed from 1981 to 2006. METHODS Data on 324 consecutive acromegaly patients presenting from 1981–2006 at two New York City hospitals were collected by retrospective review (n=324) and by interview (n=200). The main complaint, acromegaly-associated co-morbidities, signs, symptoms, healthcare providers visited, pre-operative growth hormone (GH) and insulin-like growth factor I (IGF-I) levels and pituitary tumor size at diagnosis were compared in patients presenting in the earlier vs. later halves of the time period. RESULTS Times from symptom onset to diagnosis were 5.9 yr. (early) vs. 5.2 yr. (late)(p=ns). At diagnosis, 96% of early and late groups had facial feature changes and/or hand/foot enlargement. Co-morbidities included hypertension (HTN) 37 % (early) vs. 36% (late), carpal tunnel syndrome (24 vs. 24%), sleep apnea (13 vs. 29%)(p acromegaly patients were unchanged from 1981–2006. Most patients still have marked manifestations of acromegaly at diagnosis suggesting that acromegaly remains clinically under-recognized. Healthcare professionals should more commonly consider acromegaly, which can lead to earlier diagnosis and better treatment outcome. PMID:19473180
Calderón, María Del Rosario; Delgado, Elvira; García Campos, Francisco
Acromegaly is a clinical syndrome caused by the excessive production of growth hormone. It is associated with high morbidity and significantly increased mortality, mainly due to cardiovascular and respiratory complications, and cancer. Mortality is reduced to that of the general population following successful treatment, in other words, when insulin-like growth factor (IGF-I) and growth hormone values return to normal levels. Not all tumours associated with this syndrome benefit from cost-effective early diagnosis programmes. An in-depth knowledge on the part of clinicians of the morbidity and mortality associated with acromegaly, allowing them in many cases to anticipate the expected clinical course of the disease, is the best therapeutic and follow-up strategy in these patients. Copyright © 2016 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.
Kleinberg, D L
Acromegaly is a disease that shortens life expectancy (1-3) and causes severe systemic problems during life (4). It can arise and be recognized quickly if the onset is rapid, as in gigantism. Unfortunately there is usually a delay in diagnosis, on average 9 yr (4). The longer the delay the more likely patients are to develop partially or completely irreversible systemic problems, such as sleep apnea (5) and arthritis. Although some of the signs and co-morbidities of acromegaly are permanent, there is good evidence that cure of the disease reverses early mortality (3, 6, 7). It has been estimated that life expectancy is shortened by about 10 yr overall, and longer when diabetes or heart disease are already present at the time of diagnosis.
Idowu Olufemi Emmanuel
Full Text Available The management of acromegaly caused by an uncommon growth hormone-secreting pituitary adenoma can be challenging in low-resource African subregion. We conducted a study over a 2-year period to describe the results and challenges following surgical treatment of this rare condition in our centre. The clinical outcome was defined as successful based on the surgeon′s intraoperative observation, postoperative neuroimaging findings and neuroendocrinological results. A total of three patients (two males and one female aged 19-32 years were included. Visual impairment was the main presenting symptom in all the three patients. The postoperative period was uneventful. Acromegaly is an uncommon disorder in our region. Surgery is the treatment of choice in low-resource practice.
Full Text Available Our aim is to describe a case of acromegaly that was associated with symptomatic Rathke′s cyst. We describe a young male student without any significant family history who presented with clinical and biochemical features consistent with growth hormone excess, which was confirmed with dynamic testing. He also described a persistent headache predating symptoms of growth hormone excess by 4 years. Magnetic resonance imaging (MRI of the pituitary showed a large sellar mass which was thought to be a somatotroph adenoma. Trans-sphenoidal surgery was performed; however, a colloid lesion was identified by the neurosurgeon that proved to be a Rathke′s cyst. The association of acromegaly with Rathke′s cyst is very rare, with less than 10 cases found to be reported on review of literature. This is the first report from India.
Arya, K R; Krishna, K; Chadda, M
The common dermatological manifestations seen in 34 cases of acromegaly were changes in facial appearance, enlargement of hands and feet, intolerance to heat and sweating, carpal tunnel syndrome, hirsutism, acrochordons and acanthosis nigricans. The mean estimated age of onset was 32.8 years in males and 31.7 years in females, while the mean age at the time of diagnosis was 38.6 years and 36.1 years for males and females respectively, with a slight male preponderance noted.
Full Text Available Abstract Acromegaly is a chronic disease with an important impact on patients, Health Related Quality of Life (HRQoL. The ability to effectively measure Health Related Quality of Life is central to describing the impacts of disease or treatment upon the patient, therefore the importance of having a disease specific questionnaire for acromegaly. For the development of the AcroQoL questionnaire different sources of information were used: first a literature search was performed to identify relevant papers describing the impact of acromegaly in HRQoL, second the main domains of impact on HRQoL were identified by 10 experts endocrinologists, and third ten in-depth semi-structured interviews were conducted in acromegalic patients to identify domains and items related to the self-perceived impact of acromegaly in patients' life. After a proper qualitative analysis a preliminary 38 item questionnaire was obtained. Rasch analysis concluded with a final 22 item questionnaire. The measurement properties (validity and reliability of the resulting final questionnaire were tested and compared using standard procedures (Cronbach's Alpha and item-total correlation. The evaluation of the item parameters confirmed the construct validity of the new instrument. Responsiveness to change was assessed in a small sample of 32 acromegalic patients with active disease in Spain who were administered the AcroQoL and the generic questionnaire EuroQoL 5-D. The results showed a statistically significant relationship between all the dimensions of AcroQoL and the VAS (visual analogic scale of EQ-5D. An improvement in the global score of AcroQoL was related to a global improvement in the VAS of the EQ-5D. Following the current recommended standard methodology the Spanish questionnaire was translated into eleven other languages.
Sasagawa, Yasuo; Tachibana, Osamu; Doai, Mariko; Hayashi, Yasuhiko; Tonami, Hisao; Iizuka, Hideaki; Nakada, Mitsutoshi
Acromegaly is a systemic disease which causes multiple bony alterations. Some authors reported that acromegalic patients have risk factors for an intraoperative vascular injury due to the specific anatomical features of their sphenoid sinus. The objective of our study was to analyze the anatomic characteristics of sphenoid sinus in acromegalic patients compared with controls, by evaluation of computed tomography (CT) findings. We examined 45 acromegalic (acromegaly group) and 45 non-acromegalic patients (control group) with pituitary adenomas who were matched for sex, age, height, tumor size, and cavernous sinus invasion (Knosp grade). Preoperative CT of the pituitary region including the sphenoid sinus was used to evaluate the following anatomic characteristics: type of sphenoid sinus (sellar or pre-sellar/conchal); intrasphenoid septa (non/single or multiple); carotid artery protrusion; carotid artery dehiscence; intercarotid distance. Sixteen acromegalic patients (35.5 %) and 6 controls (13.3 %) had carotid artery protrusion. Additionally, 10 acromegalic patients (22.2 %) and 3 controls (6.6 %) had carotid artery dehiscence. Carotid artery protrusion and dehiscence were more frequent in the acromegaly group than in control group (p = 0.013 and 0.035, respectively). Other anatomic characteristics (type of sphenoid sinus, intrasphenoid septa, and intracarotid distance) showed no significant differences between acromegaly and control groups. Our study suggests that carotid artery protrusion and dehiscence occur more frequently among acromegalic patients, compared with non-acromegalic patients. It is important for surgeons to be aware of these anatomic variations to avoid vital complications, such as carotid injuries, during surgery.
Kawakubo, A; Ariyoshi, S; Fukui, S; Shimada, M; Haseba, S; Gotoh, Y
A rare anesthetic experience of a 30-year-old woman with acromegaly complicated with Basedow's disease is reported. After the thyroid function was successfully controlled by drug therapy, resection of pituitary adenoma was performed under general anesthesia. Anesthesia was induced and maintained with NLA. No problem was observed during the operation and postoperative period. Careful attention should be paid to the management of circulation, respiration, metabolism and endocrinium through the perioperative period.
Oldfield, Edward H; Jane, John A; Thorner, Michael O; Pledger, Carrie L; Sheehan, Jason P; Vance, Mary Lee
OBJECTIVE The relationship between growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in patients with acromegaly as serial levels drop over time after treatment has not been examined previously. Knowledge of this relationship is important to correlate pretreatment levels that best predict response to treatment. To examine the correlation between GH and IGF-1 and IGF-1 z-scores over a wide range of GH levels, the authors examined serial GH and IGF-1 levels at intervals before and after surgery and radiosurgery for acromegaly. METHODS This retrospective analysis correlates 414 pairs of GH and IGF-1 values in 93 patients with acromegaly. RESULTS Absolute IGF-1 levels increase linearly with GH levels only up to a GH of 4 ng/ml, and with IGF-1 z-scores only to a GH level of 1 ng/ml. Between GH levels of 1 and 10 ng/ml, increases in IGF-1 z-scores relative to changes in GH diminish and then plateau at GH concentrations of about 10 ng/ml. From patient to patient there is a wide range of threshold GH levels beyond which IGF-1 increases are no longer linear, GH levels at which the IGF-1 response plateaus, IGF-1 levels at similar GH values after the IGF-1 response plateaus, and of IGF-1 levels at similar GH levels. CONCLUSIONS In acromegaly, although IGF-1 levels represent a combination of the integrated effects of GH secretion and GH action, the tumor produces GH, not IGF-1. Nonlinearity between GH and IGF-1 occurs at GH levels far below those previously recognized. To monitor tumor activity and tumor viability requires measurement of GH levels.
Tani, Y.; Tanaka, N.; Isoya, Eiji [Dept. of Orthopaedic Surgery, Soseikai General Hospital, Kyoto (Japan)
A 39-year-old man with acromegaly exhibited locking of metacarpophalangeal (MCP) joints of both index fingers. Large osteophytes were found at the metacarpal heads by radiography and computerized tomography (CT). Magnetic resonance (MR) images revealed hypertrophy of volar plates. We suggest that these characteristic acromegalic features caused locking of MCP joints. Surgery was required on one of the joints to release the locking. (orig.)
Rosenstock, J.; Doyle, F.H.; Joplin, G.F.; Jung, R.T.; Mashiter, K. (Hammersmith Hospital, London (UK). Postgraduate Medical School)
A brief case history is presented of a patient, who, after yttrium-90 implantation, showed a complete clinical and hormonal remission of her acromegaly, maintaining normal pituitary function. The remarkable feature was the rapid disappearance of her attacks of somnolence within 96 hours of pituitary implantation, despite persistence of nocturnal snoring and well before any remodelling of soft tissues could have occurred. This response suggests that her daytime somnolence had a narcoleptic component.
Iwasaki, N; Masuko, T; Ishikawa, J; Minami, A
Although carpal tunnel syndrome is frequent in acromegaly, few acromegalics will be encountered by most hand surgeons. This paper considers the treatment of four cases of acromegaly in whom carpal tunnel syndrome arose, to discuss aspects of management of carpal tunnel syndrome in this patient group.
Devoitille, A; Beckers, A; Piérard, L A
Acromegaly is a disease characterized by chronic growth hormone hypersecretion. Cardiovascular complications represent the main cause of death. We present here a rare case of dilated cardiomyopathy whose diagnosis revealed an acromegaly. This will provide the opportunity to review an uncommon disease and its recently reassessed prevalence.
Camilo, Gustavo B; Carvalho, Alysson R S; Machado, Dequitier C; Mogami, Roberto; Melo, Pedro L
Objective: Our purpose was to compare the findings of CT pulmonary densitovolumetry and pulmonary function in patients with active acromegaly and controlled acromegaly and, secondarily, to correlate these findings. Methods: 11 patients with active acromegaly, 18 patients with controlled acromegaly and 17 control subjects, all non-smokers, underwent quantification of lung volume using multidetector CT (Q-MDCT) and pulmonary function tests. Results: Patients with active acromegaly had larger total lung mass (TLM) values than the controls and larger amounts of non-aerated compartments than the other two groups. Patients with active acromegaly also had larger amounts of poorly aerated compartments than the other two groups, a difference that was observed in both total lung volume (TLV) and TLM. TLV as measured by inspiratory Q-MDCT correlated significantly with total lung capacity, whereas TLV measured using expiratory Q-MDCT correlated significantly with functional residual capacity. Conclusion: Patients with active acromegaly have more lung mass and larger amounts of non-aerated and poorly aerated compartments. There is a relationship between the findings of CT pulmonary densitovolumetry and pulmonary function test parameters. Advances in knowledge: Although the nature of our results demands further investigation, our data suggest that both CT pulmonary densitovolumetry and pulmonary function tests can be used as useful tools for patients with acromegaly by assisting in the prediction of disease activity. PMID:26246281
Brummelman, Pauline; Koerts, Janneke; Dullaart, Robin P. F.; van den Berg, Gerrit; Tucha, Oliver; Wolffenbuttel, Bruce H. R.; van Beek, Andre P.
Background In untreated acromegaly patients, decreased cognitive functioning is reported to be associated with the degree of growth hormone (GH) and IGF-1 excess. Whether previous GH excess or current medical treatment for acromegaly specifically affects cognition remains unclear. The aim of this
Camilo, Gustavo B; Carvalho, Alysson R S; Machado, Dequitier C; Mogami, Roberto; Melo, Pedro L; Lopes, Agnaldo J
Our purpose was to compare the findings of CT pulmonary densitovolumetry and pulmonary function in patients with active acromegaly and controlled acromegaly and, secondarily, to correlate these findings. 11 patients with active acromegaly, 18 patients with controlled acromegaly and 17 control subjects, all non-smokers, underwent quantification of lung volume using multidetector CT (Q-MDCT) and pulmonary function tests. Patients with active acromegaly had larger total lung mass (TLM) values than the controls and larger amounts of non-aerated compartments than the other two groups. Patients with active acromegaly also had larger amounts of poorly aerated compartments than the other two groups, a difference that was observed in both total lung volume (TLV) and TLM. TLV as measured by inspiratory Q-MDCT correlated significantly with total lung capacity, whereas TLV measured using expiratory Q-MDCT correlated significantly with functional residual capacity. Patients with active acromegaly have more lung mass and larger amounts of non-aerated and poorly aerated compartments. There is a relationship between the findings of CT pulmonary densitovolumetry and pulmonary function test parameters. Although the nature of our results demands further investigation, our data suggest that both CT pulmonary densitovolumetry and pulmonary function tests can be used as useful tools for patients with acromegaly by assisting in the prediction of disease activity.
Brummelman, Pauline; Koerts, Janneke; Dullaart, Robin P. F.; van den Berg, Gerrit; Tucha, Oliver; Wolffenbuttel, Bruce H. R.; van Beek, Andre P.
Background In untreated acromegaly patients, decreased cognitive functioning is reported to be associated with the degree of growth hormone (GH) and IGF-1 excess. Whether previous GH excess or current medical treatment for acromegaly specifically affects cognition remains unclear. The aim of this st
Fang, Hongjuan; Xu, Jian; Wu, Huanwen; Fan, Hong; Zhong, Liyong
Klinefelter syndrome (KS) is the most common chromosomal aneuploidy in male population, which demonstrates an unusual association with acromegaly. We herein present a rare case involving the confirmation of KS 2 years after surgical treatment for acromegaly.A 27-year-old man presented with an acromegalic appearance. Endocrinological examination revealed a high growth hormone (GH) concentration, low testosterone concentration, and high follicle-stimulating hormone and luteinizing hormone concentration. Brain imaging revealed a 9 × 6 × 7- mm sellar low-density nodule suggestive of a microadenoma. Trans-sphenoidal surgery was undertaken, and immunohistochemistry revealed GH positivity. Two years after surgery, the patient underwent examination for infertility. He presented with diminished pubic hair, and small and firm testes. Hormonal assay revealed hypergonadotrophic hypogonadism on the basis of decreased serum total testosterone (syndrome itself. As the simultaneous occurrence of KS and acromegaly is rare, and the association between them remains unclear, we suggest that complete pituitary hormonal screening and conventional pituitary MRI should be essential for patients with KS to screen for pituitary tumor.
The approach to a patient with acromegaly and persistent disease after surgery requires a complex diagnostic assessment. Acromegaly is a chronic and insidious disease that is associated with multisystem comorbidities, including cardiovascular disease, hypertension, sleep apnea syndrome, colon polyposis, arthropathy, and metabolic complications including glucose intolerance and type 2 diabetes mellitus. Patients also have a variety of signs and symptoms, including headache, arthralgias, carpal tunnel syndrome, sweating, fatigue, and psychological issues that impact significantly on quality of life. The recommended approach to the evaluation of the postoperative patient includes a biochemical assessment, with measurement of serum IGF-I along with a glucose-suppressed GH value, radiological assessment to determine location of residual tumor and presence of mass effects, a physical examination for evidence of skeletal and soft tissue overgrowth and related signs of acromegaly, and a thorough clinical assessment for the presence of comorbidities. Repeat surgery is indicated if there is residual tumor that is surgically accessible and there may be a chance for surgical cure, or if there are persistent mass effects upon the optic chiasm. Otherwise, medical therapy is indicated, utilizing somatostatin analogs, dopamine agonists, and pegvisomant, a GH receptor antagonist. Radiation therapy is usually relegated to situations where medical therapy is ineffective or poorly tolerated or where patients would prefer not to sustain the cost of long-term medical therapy. The choice of therapy requires close dialog among endocrinologists, neurosurgeons, radiation therapists, and neuroophthalmologists for optimal care of patients.
Barkan, Ariel; Bronstein, Marcello D; Bruno, Oscar D; Cob, Alejandro; Espinosa-de-los-Monteros, Ana Laura; Gadelha, Monica R; Garavito, Gloria; Guitelman, Mirtha; Mangupli, Ruth; Mercado, Moisés; Portocarrero, Lesly; Sheppard, Michael
Although there are international guidelines orienting physicians on how to manage patients with acromegaly, such guidelines should be adapted for use in distinct regions of the world. A panel of neuroendocrinologists convened in Mexico City in August of 2007 to discuss specific considerations in Latin America. Of major discussion was the laboratory evaluation of acromegaly, which requires the use of appropriate tests and the adoption of local institutional standards. As a general rule to ensure diagnosis, the patient's GH level during an oral glucose tolerance test and IGF-1 level should be evaluated. Furthermore, to guide treatment decisions, both GH and IGF-1 assessments are required. The treatment of patients with acromegaly in Latin America is influenced by local issues of cost, availability and expertise of pituitary neurosurgeons, which should dictate therapeutic choices. Such treatment has undergone profound changes because of the introduction of effective medical interventions that may be used after surgical debulking or as first-line medical therapy in selected cases. Surgical resection remains the mainstay of therapy for small pituitary adenomas (microadenomas), potentially resectable macroadenomas and invasive adenomas causing visual defects. Radiotherapy may be indicated in selected cases when no disease control is achieved despite optimal surgical debulking and medical therapy, when there is no access to somatostatin analogues, or when local issues of cost preclude other therapies. Since not all the diagnostic tools and treatment options are available in all Latin American countries, physicians need to adapt their clinical management decisions to the available local resources and therapeutic options.
Dos Santos Silva, Cintia Marques; Lima, G A B; Volschan, I C M; Gottlieb, I; Kasuki, L; Neto, L Vieira; Gadelha, M R
The aims of this study are to determine the prevalence of coronary atherosclerosis in acromegalic patients and to investigate the relationship between the coronary artery calcium score (CS) and acromegaly status and clinical parameters [Framingham risk score (FRS)]. Fifty-six acromegalic patients and paired non-acromegalic volunteers were stratified according to the FRS into low-, intermediate-, and high-risk groups. CS was assessed using multidetector computed tomography. The patients were considered to have controlled or active acromegaly at the time they were submitted to evaluation. Sixty-six percent of acromegalic patients exhibited arterial hypertension, 36 % had diabetes mellitus, and 34 % had hypercholesterolemia. The median FRS and the median risk for cardiovascular event within the next 10 years were similar in the acromegalics and the controls. The median total CS and CS >75th percentile didn't differ significantly between these groups. In patients with controlled acromegaly, a low, intermediate, or high FRS risk was observed in 86, 14, and 0 %, respectively. In patients with active disease, a low, intermediate, or high FRS risk was verified in 94, 3, and 3 %, respectively, and differences between the controlled and active groups were not significant. Seventy-two percent of the patients had total CS = 0, and there were no differences between the controlled and active groups. The risk of coronary artery disease in acromegalic patients, determined according to FRS and CS, is low despite the high prevalence of metabolic abnormalities.
Colao, Annamaria; Ferone, Diego; Marzullo, Paolo; Lombardi, Gaetano
This review focuses on the systemic complications of acromegaly. Mortality in this disease is increased mostly because of cardiovascular and respiratory diseases, although currently neoplastic complications have been questioned as a relevant cause of increased risk of death. Biventricular hypertrophy, occurring independently of hypertension and metabolic complications, is the most frequent cardiac complication. Diastolic and systolic dysfunction develops along with disease duration; and other cardiac disorders, such as arrhythmias, valve disease, hypertension, atherosclerosis, and endothelial dysfunction, are also common in acromegaly. Control of acromegaly by surgery or pharmacotherapy, especially somatostatin analogs, improves cardiovascular morbidity. Respiratory disorders, sleep apnea, and ventilatory dysfunction are also important contributors in increasing mortality and are advantageously benefitted by controlling GH and IGF-I hypersecretion. An increased risk of colonic polyps, which more frequently recur in patients not controlled after treatment, has been reported by several independent investigations, although malignancies in other organs have also been described, but less convincingly than at the gastrointestinal level. Finally, the most important cause of morbidity and functional disability of the disease is arthropathy, which can be reversed at an initial stage, but not if the disease is left untreated for several years.
Izzard, Ashley S; Emerson, Michael; Prehar, Sukhpal; Neyses, Ludwig; Trainer, Peter; List, Edward O; Kopchick, John J; Heagerty, Anthony M
Although, it is accepted that there is an excess of cardiovascular mortality in acromegaly, it is uncertain whether this is due to the direct effects of growth hormone-induced-cardiomyopathy or is a consequence of atherosclerosis secondary to the metabolic syndrome often observed in this condition. Direct comparison of a mouse model of acromegaly to a mouse model of Laron's syndrome allowed us to carry out detailed phenotyping and better understand the role GH plays in the circulatory system. Transgenic mice that overexpress the growth hormone gene (GH) developed gigantism, including insulin resistance and higher blood pressures commensurate with increased body mass. In these giant mice, the hearts were hypertrophied but haemodynamic studies suggested contractile function was normal. Segments of small arteries mounted in a pressure myograph showed vascular wall hypertrophy but a preserved lumen diameter. Vascular contractile function was normal. Mice in which the GH receptor gene was disrupted or 'knocked out' were dwarf and had low blood pressure, small hearts and blood vessels but a normally functioning circulation. Correlations of body mass with cardiovascular parameters suggested that blood pressure and structural characteristics develop in line with body size. In this transgenic mouse model of acromegaly, there is cardiac and vascular hypertrophy commensurate with GH excess but normal function. Our findings support the contention that the excess mortality in this condition may be due to the development of hypertrophic cardiomyopathy rather than increased rates of atherosclerotic coronary artery disease.
Schiavon, F; Maffei, P; Martini, C; De Carlo, E; Fais, C; Todesco, S; Sicolo, N
Although wide range investigations on the heart and great vessels have been reported in acromegaly, the field of microcirculation is still largely vacant. The nailfold is a window through which we can observe in vivo the vascular bed. This study investigates through nailfold capillaroscopy the morphology of cutaneous microcirculation in acromegaly in relationship with the usual hormonal parameters of disease activity. Twenty-five acromegalic patients and 26 normal subjects, age and sex matched, were studied. A subgroup of acromegalics (8 patients) was considered in stable remission, and the remaining 17 had active disease. Capillaroscopy was performed in each subject by in vivo computer aided stereomicroscopy (magnification, x400). The following morphological parameters were calculated: the number of tortuous loops, meandering capillaries, and capillaries per millimeter; avascular areas; visibility of subpapillary plexus; the capillary length; and intercapillary distance. We were unable to perform the exam in 4 of 25 patients because visibility was poor. The capillary number and length were significantly reduced in acromegalics compared to controls [8.9 +/- 1.5 vs. 10.3 +/- 1.2 no./mm (P = 0.0010) and 174 +/- 49 vs. 255 +/- 24 microm (P acromegaly, morphological alterations also affect the peripheral microcirculation, which seems to be influenced by the activity of the disease. We believe that nailfold capillaroscopy may represent an additional useful tool in the follow-up of acromegalic patients.
Gadelha, Monica R; Wildemberg, Luiz Eduardo; Bronstein, Marcello D; Gatto, Federico; Ferone, Diego
First-generation somatostatin receptors ligands (SRL) are the mainstay in the medical treatment of acromegaly, however the percentage of patients controlled with these drugs significantly varies in the different studies. Many factors are involved in the resistance to SRL. In this review, we update the physiology of somatostatin and its receptors (sst), the use of SRL in the treatment of acromegaly and the factors involved in the response to these drugs. The SRL act through interaction with the sst, which up to now have been characterized as five subtypes. The first-generation SRL, octreotide and lanreotide, are considered sst2 specific and have biochemical response rates varying from 20 to 70%. Tumor volume reduction can be found in 36-75% of patients. Several factors may determine the response to these drugs, such as sst, AIP, E-cadherin, ZAC1, filamin A and β-arrestin expression in the somatotropinomas. In patients resistant to first-generation SRL, alternative medical treatment options include: SRL high dose regimens, SRL in combination with cabergoline or pegvisomant, or the use of pasireotide. Pasireotide is a next-generation SRL with a broader pattern of interaction with sst. In the light of the recent increase of treatment options in acromegaly and the deeper knowledge of the determinants of response to the current first-line therapy, a shift from a trial-and-error treatment to a personalized one could be possible.
Imamura, H; Isu, T; Iwasaki, Y; Sugimoto, S; Abe, H; Tashiro, K
Four cases of carpal tunnel syndrome in acromegaly were reported. These 4 cases were found in 21 acromegalies (19%). Besides change of features, they complained bilateral sensory disturbances of their hands. After transsphenoidal removal of pituitary adenoma, GH levels returned to the normal range and sensory disturbances were improved in all cases. Mechanism of carpal tunnel syndrome in acromegaly is that edematous synovial tissues compress the median nerve because oversecretion of growth hormone causes increase of sodium and water retention in the extracellular fluid. The patient who showes high basal level of growth hormone and/or acromegalic pattern by various tolerance tests does not always have the carpal tunnel syndrome. But this syndrome is apt to be found in active acromegaly. So the detection of the symptom showed by this activity such as hypersudation in our cases leads to the early diagnosis of acromegaly.
Boguszewski, Cesar Luiz; Ayuk, John
Based on experimental and animal models, epidemiological data from non-acromegaly populations, and longitudinal and cross-sectional cohorts of patients with acromegaly, a potential association between acromegaly and cancer has long been hypothesized, in particular colorectal cancer, and, to a lesser extent, breast, thyroid and prostate cancers. The exact mechanisms underlying this potential association have not been fully elucidated. Results from studies examining cancer incidence and mortality in acromegaly have been inconsistent, with some demonstrating increased risk, whereas others show no increase. This article reviews the existing data relating to cancer risk and mortality in acromegaly, exploring the limitations of study designs and the impact of changes in disease control and patient outcomes over time. © 2016 European Society of Endocrinology.
Mammis, Antonios; Eloy, Jean Anderson; Liu, James K
Giants have been a subject of fascination throughout history. Whereas descriptions of giants have existed in the lay literature for millennia, the first attempt at a medical description was published by Johannes Wier in 1567. However, it was Pierre Marie, in 1886, who established the term "acromegaly" for the first time and established a distinct clinical diagnosis with clear clinical descriptions in 2 patients with the characteristic presentation. Multiple autopsy findings revealed a consistent correlation between acromegaly and pituitary enlargement. In 1909, Harvey Cushing postulated a “hormone of growth" as the underlying pathophysiological trigger involved in pituitary hypersecretion in patients with acromegaly. This theory was supported by his observations of clinical remission in patients with acromegaly in whom he had performed hypophysectomy. In this paper, the authors present some of the early accounts of acromegaly and gigantism, and describe its historical evolution as a medical and surgical entity.
Jiang, He-Jiun; Hung, Wei-Wen; Hsiao, Pi-Jung
Acromegaly is always complicated with comorbidities and increased mortality. The disease activity and mortality outcomes are highly correlated to the level of growth hormone and insulin-like growth factor 1. A variety of clinical manifestations of acromegaly have been reported. We present a unique case where a 49-year-old male was diagnosed with acromegaly with a first manifestation as an episode of diabetic ketoacidosis. Because he refused any suggestion of treatment, a recurrent episode of diabetic ketoacidosis with pituitary apoplexy occurred. A huge B-cell lymphoma displaying as a huge facial mass followed within 1 year of the diagnosis of acromegaly. Death from advanced cancer ensued 3 years later. This clinical experience strongly reinforces the urgency of controlling growth hormone and insulin-like growth factor 1 as soon as possible once acromegaly is diagnosed.
Sue, Mariko; Yoshihara, Aya; Okubo, Yoichiro; Ishikawa, Mayumi; Ando, Yasuyo; Hiroi, Naoki; Shibuya, Kazutoshi; Yoshino, Gen
Acromegaly is characterized by chronic hypersecretion of growth hormone (GH) and is associated with increased mortality rate because of the potential complications such as cardiovascular disease, respiratory disease, or malignancy, which are probably caused by the long-term exposure of tissues to excess GH, for at least 10 years, before diagnosis and treatment. A 22-year-old man with a 2-month history of fatigue was admitted to our hospital because of chest discomfort, dyspnea, and pitting edema of the lower limbs experienced over a 1-month period. On admission, his height and body weight were 186 cm and 138.5 kg, respectively, with a BMI of 39.8 kg/m(2). He showed acromegalic features and elevated serum GH and IGF-1 levels, which were 11.5 ng/mL and 960 ng/mL, respectively. There was no GH suppression in the 75-g oral glucose tolerance test. Pituitary magnetic resonance imaging (MRI) revealed microadenoma. Chest X-ray revealed cardiomegaly, and echocardiogram showed dilated left ventricular (LV) cavity and diffuse hypokinesis with extremely decreased ejection fraction (EF). He was diagnosed as having acromegaly with congestive heart failure from diastolic cardiomyopathy. After the successful transsphenoidal resection of the pituitary adenoma, the level of GH was normalized. However, the cardiac dysfunction did not show any improvement even after the administration of β-blockers, angiotensin-converting enzyme inhibitor (ACE-I), or diuretics. The patient was re-hospitalized, and he died of cardiac failure at the age of 25 years. Patients with acromegaly have been reported to have about 30% higher mortality rate, and cardiovascular disease accounts for 60% of the deaths. We report a case of a patient with juvenile acromegaly who was diagnosed with severe cardiac failure at the time of diagnosis and failed to recover cardiac function even after the successful resection of the pituitary adenoma. Immediate diagnosis and treatment are required for better control of
Hong, A R; Kim, J H; Kim, S W; Kim, S Y; Shin, C S
Lumbar spine trabecular bone score (TBS) was significantly decreased in active acromegaly patients. TBS may be useful to assess the skeletal fragility in acromegaly in which bone mineral density (BMD) is not sufficient to represent bone strength and explain the high incidence of fragility fractures in acromegaly patients. Although the data on BMD are controversial, patients with acromegaly have an increased risk of fragility fracture. We examined the lumbar spine TBS to explain the skeletal deterioration in acromegaly patients. We included 14 men and 19 women acromegaly patients who underwent dual-energy X-ray absorptiometry at the time of diagnosis from 2000 to 2014 at Seoul National University Hospital. Ninety-nine age-, sex- and body mass index-matched controls were recruited. Biochemical parameters, lumbar spine TBS, and BMD at all sites were measured. Gonadal status was evaluated at diagnosis. Lumbar spine TBS was lower in acromegaly patients than in controls in both genders (1.345 ± 0.121 vs. 1.427 ± 0.087, P = 0.005 in men; 1.356 ± 0.082 vs. 1.431 ± 0.071, P = 0.001 in women). In contrast, BMD at all sites did not differ between the two groups. Hypogonadal acromegaly patients (men, n = 9; women, n = 12) had lower TBS values compared with controls both in men and women (all P acromegaly patients, lumbar spine TBS was lower than in women controls only (P = 0.041). Skeletal microarchitecture was deteriorated in acromegaly patients as assessed by TBS, which seems to be a consequence of growth hormone excess as well as hypogonadism, especially in women.
Full Text Available Background. Cardiovascular complications are known to be the main determinants of reduced life expectancy and decreased quality of life in acromegaly patients. Our study aimed to provide insight into the cardiovascular changes that occur in acromegaly patients and to investigate the correlative risk factors. Methods. A total of 108 patients definitively diagnosed with acromegaly and 108 controls matched for age and gender were recruited into study and control groups, respectively. Standard echocardiography was performed on all of the participants, and data were collected and analyzed. Results. All acromegaly patients presented with structural cardiac changes, including a larger heart cavity, thicker myocardial walls, and increased great vessel diameters compared with the control group. Additionally, the acromegaly patients presented with reduced diastolic function. Aging and increased body mass index (BMI were correlated with myocardial hypertrophy and diastolic dysfunction; a longer disease duration was correlated with larger great vessel diameters. Conclusions. Ageing and increased BMI are independent risk factors for acromegalic cardiomyopathy, and a long disease duration results in the expansion of great vessels. Increased efforts should be made to diagnose acromegaly at an early stage and to advise acromegaly patients to maintain a healthy weight.
Guo, Xiaopeng; Gao, Lu; Zhang, Shuo; Li, Yilin; Wu, Yue; Fang, Ligang; Deng, Kan; Yao, Yong; Lian, Wei; Wang, Renzhi; Xing, Bing
Background. Cardiovascular complications are known to be the main determinants of reduced life expectancy and decreased quality of life in acromegaly patients. Our study aimed to provide insight into the cardiovascular changes that occur in acromegaly patients and to investigate the correlative risk factors. Methods. A total of 108 patients definitively diagnosed with acromegaly and 108 controls matched for age and gender were recruited into study and control groups, respectively. Standard echocardiography was performed on all of the participants, and data were collected and analyzed. Results. All acromegaly patients presented with structural cardiac changes, including a larger heart cavity, thicker myocardial walls, and increased great vessel diameters compared with the control group. Additionally, the acromegaly patients presented with reduced diastolic function. Aging and increased body mass index (BMI) were correlated with myocardial hypertrophy and diastolic dysfunction; a longer disease duration was correlated with larger great vessel diameters. Conclusions. Ageing and increased BMI are independent risk factors for acromegalic cardiomyopathy, and a long disease duration results in the expansion of great vessels. Increased efforts should be made to diagnose acromegaly at an early stage and to advise acromegaly patients to maintain a healthy weight.
Cooper, Timothy; Dziegielewski, Peter T; Singh, Praby; Seemann, Robert
To present a case of bilateral vocal fold immobility (BVCI) in a patient with acromegaly and review the current literature describing this presentation. Case report and literature review. Academic tertiary care center. English language literature search of online journal databases. A 56-year-old man presented with 3 months of progressive stridor and shortness of breath. Transnasal flexible endoscopy revealed BVCI. A tracheostomy was performed to secure his airway. Further history was suggestive of acromegaly and imaging demonstrated a pituitary macroadenoma. The diagnosis of acromegaly was made. The patient was treated with octreotide followed by an endoscopic trans sphenoidal resection of the pituitary adenoma. Sixteen months after his initial presentation, a right laser arytenoidectomy was performed and the patient was subsequently decannulated. In the literature to date, 11 cases of BVCI in acromegaly have been reported. These patients often present with stridor and require a tracheostomy. With treatment of their acromegaly, these patients may regain vocal fold mobility and may be decannulated. Acromegaly with BVCI is a rare presentation. Acute management of the airway of patients with acromegaly presenting with BVCI typically requires a tracheostomy. A period of 15 months should be allowed for restoration of vocal fold mobility before airway opening procedures are considered. Copyright Â© 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
Suda, Kentaro; Fukuoka, Hidenori; Iguchi, Genzo; Hirota, Yushi; Nishizawa, Hitoshi; Bando, Hironori; Matsumoto, Ryusaku; Takahashi, Michiko; Sakaguchi, Kazuhiko; Takahashi, Yutaka
The prevalence of acromegaly is estimated to be 8-24/100,000, but several recent studies suggest it is underestimated. In particular, acromegaly is considered more prevalent in patients with type 2 diabetes mellitus (T2DM) than in the normal population. This study aimed to evaluate the prevalence of acromegaly in hospitalized patients with T2DM. A total of 327 hospitalized patients with T2DM were recruited as subjects. If serum insulin-like growth factor 1 (IGF-1) levels were found to be elevated, random GH level was measured or oral glucose tolerance test (OGTT) was performed. Five patients with elevated serum IGF-1 levels and random GH level or inadequate suppression of GH in the OGTT underwent pituitary magnetic resonance imaging. Of those patients, pituitary adenoma was detected in 2 patients. These 2 patients were diagnosed with acromegaly, as they also exhibited mild acromegalic features. Intriguingly, both these patients exhibited severe macroangiopathy and an absence of microangiopathy. The prevalence of acromegaly in the hospitalized patients with T2DM in this study was therefore 0.6%, suggesting a higher prevalence than that predicted. Although a large-scale prospective study is required to clarify the precise prevalence of acromegaly in hospitalized patients with T2DM, the present study shows that it is useful to screen hospitalized patients with T2DM for acromegaly by measuring their serum IGF-1 level.
Christofides, Elena A
In acromegaly, achieving biochemical control (growth hormone [GH] level acromegaly is challenging because it is rooted in observing subtle clinical manifestations, and it is typical for acromegaly to evolve for up to 10 years before it is recognized. This results in chronic exposure to elevated levels of GH and IGF-1 and delay in patients receiving appropriate treatment, which consequently increases mortality risk. In this review, the clinical impact of elevated GH and IGF-1 levels, the effectiveness of current therapies, and the potential role of novel treatments for acromegaly will be discussed. Clinical burden of acromegaly and benefits associated with management of GH and IGF-1 levels will be reviewed. Major treatment paradigms in acromegaly include surgery, medical therapy, and radiotherapy. With medical therapies, such as somatostatin analogs, dopamine agonists, and GH receptor antagonists, a substantial proportion of patients achieve reduced GH and normalized IGF-1 levels. In addition, signs and symptoms, quality of life, and comorbidities have also been reported to improve to varying degrees in patients who achieve biochemical control. Currently, there are several innovative therapies in development to improve patient outcomes, patient use, and access. Timely biochemical control of acromegaly ensures that the patient can ultimately improve morbidity and mortality from this disease and its extensive consequences. PMID:27471378
Gurel, Michelle H; Bruening, Paul R; Rhodes, Christine; Lomax, Kathleen G
Acromegaly is a chronic condition resulting from a growth hormone-secreting pituitary tumor that can substantially impact patients' physical and emotional well-being. We sought to understand the impact of acromegaly on disease-related concerns and treatment choices from the patient perspective. The path to diagnosis, current disease management, interactions with the treating health care providers (HCPs), and support networks were also assessed. Acromegaly patients were recruited primarily from a patient support group (Acromegaly Community). In Phase I, ten patients participated over the course of 5 days in a moderated online discussion board and they answered questions about their disease. In Phase II, a separate nine-patient cohort participated in face-to-face interviews conducted during an acromegaly patient conference. Data were summarized qualitatively by grouping similar answers and quotations. Nineteen acromegaly patients were recruited across the two cohorts, and both groups shared similar concerns. They demonstrated a notable interest in understanding their disease and its treatment. Patients were focused on the impact of the disease on their life, and they expressed a desire to get beyond reminders of their disease. The patients described long journeys to a correct diagnosis and relief at having a name for their condition. Many shared a sense of shock at needing pituitary surgery and felt unsatisfied by the treatment decision process, motivating them to discuss it with other patients. Patients not connected to a patient support group reported feeling helpless and lonely. Most patients shared a desire to improve their general knowledge about acromegaly to spare others their protracted diagnostic period. Patients also reported hesitancy in asking questions or sharing details about the disease's impact on their lives with their HCPs. Acromegaly can be a life-changing diagnosis with profound, ongoing effects on patients' lives. Patients struggle with many
Zoicas, F; Kleindienst, A; Mayr, B; Buchfelder, M; Megele, R; Schöfl, C
Early diagnosis of acromegaly prevents irreversible comorbidities and facilitates surgical cure. Carpal tunnel syndrome (CTS) is common in acromegaly and patients have often undergone surgery for CTS prior to the diagnosis of acromegaly. We hypothesized that screening CTS-patients for acromegaly could facilitate active case-finding. We prospectively enrolled 196 patients [135 women, 56.9 (range 23-103) years] who presented with CTS for surgery. Patients were asked about 6 symptoms suggestive of acromegaly using a questionnaire calculating a symptom score (0-6 points), and insulin-like-growth factor 1 (IGF-1) was measured. If IGF-1 was increased, IGF-1 measurement was repeated, and random growth hormone (GH) and/or an oral glucose tolerance test (OGTT) with assessment of GH-suppression were performed. The mean symptom score was 1.7±1.3 points. Three patients reported the maximal symptom score of 6 points, but none of them had an increased IGF-1. There was no correlation between the symptom score and IGF-1-SDS (standard deviation score) (r=0.026; p=0.71). Four patients had an IGF-1>2 SDS. In 2 patients acromegaly was ruled out using random GH and OGTT. One patient had normal IGF-1 and random GH at follow-up. One patient refused further diagnostics. In this prospective cohort of patients with CTS, the observed frequency of acromegaly was at most 0.51% (95% CI 0.03 to 2.83%). In this prospective study, none of the 196 patients with CTS had proven acromegaly. Thus, we see no evidence to justify general screening of patients with CTS for acromegaly.
Scaroni, C; Selice, R; Benedini, S; De Menis, E; Arosio, M; Ronchi, C; Gasperi, M; Manetti, L; Arnaldi, G; Polenta, B; Boscaro, M; Albiger, N; Martino, E; Mantero, F
Acromegaly is associated with a greater morbidity and higher incidence of tumors, possibly due to the permissive role of elevated GH and IGF-I levels. In the general population, adrenal masses are frequently discovered (prevalence 1-5%) at computed tomography (CT). We evaluated the prevalence of adrenal lesions in patients with acromegaly. We studied 94 acromegalic patients, 54 females (mean age 55.0+/-16.0 yr) and 40 males (mean age 50+/-14 yr) referred to 5 Endocrinology Units between 2001-2003; 49 had active disease and 45 had been treated with surgery and/or were controlled with medical therapy. Abdominal CT showed adrenal lesions in 27 patients; 9 of them had unilateral masses (10%) with benign features (diameter 0.5-3 cm) and 18 had hyperplasia (14 monolateral and 4 bilateral), with no significant differences between patients with active vs controlled disease, and with no correlation between prevalence of masses and duration of disease, GH and IGF-I levels. Hormone study (urinary free cortisol, catecholamines/metanephrines, upright plasma renin activity and aldosterone, morning plasma ACTH and low-dose dexamethasone suppression test) disclosed no major endocrine alterations. During a 1-yr follow-up, the adrenal masses increased in size in 3 cases and 1 patient also developed subclinical Cushing's syndrome. Adrenal lesions seem more frequent in acromegaly than in the general population, but no single factor (GH/IGF-I levels or disease duration) predicts them. The masses appear to be benign and nonhypersecreting, but a longer follow-up is recommended to disclose any changes in their morphofunctional state.
Frara, Stefano; Maffezzoni, Filippo; Mazziotti, Gherardo; Giustina, Andrea
Acromegaly is an insidious disorder characterized by excess secretion of growth hormone (GH) and elevated circulating levels of insulin-like growth factor-I (IGF-I), generally caused by a pituitary adenoma. It is a rare disease associated with an average 10-year reduction in life expectancy due to metabolic, cardiovascular, and cerebrovascular comorbidities and reduced quality of life caused by paresthesias, fatigue, osteoarthralgia, or bone fractures. In 2000, Cortina Consensus Conference established general criteria for diagnosis and biochemical control of acromegaly, which have been revised in recent years, adapting them to emerging clinical evidences as well as the evolving assay techniques. Authors have proposed a binary definition of cure for acromegaly, where both GH and IGF-I are important determinants: the former is more linked to the presence of residual adenomatous tissue, while the latter to the peripheral activity of the disease. Control of tumor growth and complications is also an essential goal of treatment. Surgical, medical, and radiotherapy approaches are all valid alternatives. The surgical option is, however, unsuccessful in about 50% of patients. Somatostatin analogs (SRLs), octreotide LAR, and lanreotide ATG can inhibit cell growth, besides their beneficial effects on GH hypersecretion and on most comorbidities. Pasireotide is a new multireceptor-targeted SRL with reported superior biochemical efficacy to octreotide, due to higher affinity for SSTR-5, but potentially causing detrimental effects on glucose homeostasis. Pegvisomant could be a valid choice in all patients resistant to SRLs. It is a competitive GH antagonist, which efficaciously blocks IGF-I production, inhibiting the dimerization of GH receptor. Normal IGF-I levels represent, therefore, its only relevant efficacy endpoint, while only few cases of tumor growth on pegvisomant have been reported, so far.
Witek, Przemysław; Mucha, Sławomir; Ruchała, Marek
Despite the known importance of somatostatin analogues (SSAs) in the treatment of acromegaly, patient satisfaction leading to preferences for specific SSAs have received little attention so far. This open, prospective, observational, multicentre patient-reported outcome study included adult patients with acromegaly, who switched from another SSA to lanreotide Autogel (new and previous devices) at least two months prior to enrolment. The observation period was around 12 months. The primary outcome assessed was overall treatment satisfaction, measured using the five-point Likert scale. The secondary outcomes were: 1) treatment effectiveness, in terms of symptom control; 2) technical problems related to treatment administration, measured by the Visual Analog Scale (VAS); and 3) ease and safety of lanreotide Autogel delivery (new device vs. previous device). Of the 102 patients who completed the study, 97 (95.1%) were "completely or rather satisfied" with lanreotide Autogel therapy, four (3.9%) were "neither satisfied nor dissatisfied", and one (1%) was "rather dissatisfied". Symptom control was reported as "excellent" or "good" by 88-89% of patients throughout the study. Patients reported fewer technical problems related to administration of lanreotide Autogel (final mean VAS: 5.3) compared to previous SSAs (mean VAS: 37.6). Of the 31 patients treated with lanreotide Autogel using the previous device followed by the new device, 64.5% reported the new device as improved. Lanreotide Autogel therapy resulted in greater patient satisfaction with overall acromegaly management, when compared to previous SSAs. The new lanreotide Autogel device was found to be easier to use than the previous one. (Endokrynol Pol 2016; 67 (6): 572-579).
Fathalla, Hussein; Cusimano, Michael D; Di Ieva, Antonio; Lee, John; Alsharif, Omar; Goguen, Jeannette; Zhang, Stanley; Smyth, Harley
Transsphenoidal surgery in the setting of acromegaly is quite challenging due to increased soft tissue mass, bony overgrowth, and bleeding. There is a debate on the endoscopic versus microscopic approach for these patients. The purpose of our study is to compare the outcomes for acromegaly after transsphenoidal surgery using both techniques. Retrospective review of 65 acromegalic patients who underwent transsphenoidal surgery in our department. Clinical remission was defined as resolution of typical acromegalic symptoms. Radiological resection was defined by volumetric criteria, and biochemical remission was defined as by the 2010 consensus on the criteria for remission of acromegaly. There was no significant difference in age, preoperative endocrine status, percent of macro adenomas, suprasellar, or infrasellar extension between both groups. Patients were assigned to both groups based on our existing referral pattern. Endoscopic approach was performed in 42 patients, while the microscopic approach was performed in 23 patients. No significant difference in remission rates was found between both groups (45.2 vs. 34.7 %, p = 0.40). The endoscopic group, however, had a significantly higher rate of gross total resections (61 vs. 42 %, p = 0.05). There was also a trend towards higher rates of gross total resections when cavernous sinus was present (48 vs. 14.2 %, p = 0.09). Postoperative diabetes insipidus occurred more in microscopic patients (34.7 vs. 17 %, p = 0.05), otherwise there was no significant difference in rates of complications. The median follow-up period was 56.6 months (range 6-156, mean 66.1). There is no significant difference in the rates of biochemical remission between the endoscopic and microscopic techniques. The endoscope technique, however, seems to be superior in achieving gross total resection especially with tumors invading the cavernous sinus.
Full Text Available The common dermatological manifestations seen in 34 cases of acromegaly were changes in facial appearance, enlargement of hands and feet, intolerance to heat and sweating, carpal tunnel syndrome, hirsutism, acrochordons and acanthosis nigricans. The mean estimated age of onset was 32.8 years in males and 31.7 years in females, while the mean age at the time of diagnosis was 38.6 years and 36.1 years for males and females respectively, with a slight male preponderance noted.
Here we commemorate the character and academic authority of Prof. Zabiholah Gorban (1903-2006), the founder of Shiraz medical school. No doubt, in the scope of history of contemporary medicine, he has been efficient and effective. With respect to this fact, his article on a rare case described in Acta anatomica published in Iran in 1966, entitled (Observations on a giant skeleton) is browsed and reviewed. A case named Siah Khan with combined acromegaly and gigantism that appears to have letters to say still after nearly half a century.
Gheorghiu, Monica Livia
Purpose Treatment of acromegaly has undergone important progress in the last 20 years mainly due to the development of new medical options and advances in surgical techniques. Pituitary surgery is usually first-line therapy, and medical treatment is indicated for persistent disease, while radiation (RT) is often used as third-line therapy. The benefits of RT (tumor volume control and decreased hormonal secretion) are hampered by the long latency of the effect and the high risk of adverse effects. Stereotactic RT methods have been developed with the aim to provide more precise targeting of the tumor with better control of the radiation dose received by the adjacent brain structures. The purpose of this review is to present the updates in the efficacy and safety of pituitary RT in acromegalic patients, with an emphasis on the new stereotactic radiation techniques. Methods A systematic review was performed using PubMed and articles/abstracts and reviews detailing RT in acromegaly from 2000 to 2016 were included. Results Stereotactic radiosurgery and fractionated stereotactic RT (FSRT) for patients with persistent active acromegaly after surgery and/or during medical therapy provide comparable high rates of tumor control, i.e. stable or decrease in size of the tumor in 93-100% of patients at 5-10 years and endocrinological remission in 40-60% of patients at 5 years. Hypofractionated RT is an optimal option for tumors located near the optic structures, due to its lower toxicity for the optic nerves compared to single-dose radiosurgery. The rate of new hypopituitarism varies from 10 to 50% at 5 years and increases with the duration of follow-up. The risk for other radiation-induced complications is usually low (0-5% for new visual deficits, cranial nerves damage or brain radionecrosis and 0-1% for secondary brain tumors) and risk of stroke may be higher in FSRT. Conclusion Although the use of radiotherapy in patients with acromegaly has decreased with advances in
Colao, Annamaria; Auriemma, Renata S; Pivonello, Rosario; Galdiero, Mariano; Lombardi, Gaetano
This chapter discusses the effects of biochemical control of acromegaly on cardiovascular diseases, metabolic complications, respiratory abnormalities, malignancies and bone alterations. Acromegaly is associated with increased morbidity and mortality for cardiovascular and respiratory complications, whereas neoplasms seem to be a minor cause of increased risk of death. Other associated diseases are osteoarthritis, carpal tunnel syndrome, fatigue, visual abnormalities and reproductive disorders. Acromegaly results in premature death because of prolonged elevation of GH an IGF-I levels, and a strong biochemical control improves well-being and restores life expectancy to normal. The main goals of medical treatment of acromegaly include normalization of biochemical markers of disease activity, improvement in signs and symptoms of the disease, removal or reduction of tumor mass and preservation of pituitary function.
Astaf'eva, L I; Kalinin, P L; Kadashev, B A
Acromegaly is a severe disease associated with chronic overproduction of the growth hormone (GH) and insulin-like growth factor-1 (IGF-1), which is caused in most cases by pituitary adenoma. The main causes of mortality in acromegaly are cardiovascular diseases, respiratory diseases, and cancers. At present, the most effective treatment for acromegaly is surgical pituitary adenomectomy. Complete resection of pituitary tumors leads to the normalization of GH and IGF-1 levels, regression of symptoms, and a reduction in the risk of death. The article discusses the current criteria for diagnosis and remission of acromegaly after surgical adenomectomy as well as postoperative monitoring issues aligned with the recent guidelines of the Russian and international endocrinology associations.
Full Text Available McCune-Albright syndrome (MAS is characterized by a triad of poly/monostotic fibrous dysplasia, café-au-lait macules, and hyperfunctioning endocrinopathies, including growth hormone (GH excess. Acromegaly, as a manifestation of endocrine hyperfunction with MAS is uncommon. We report a 34-year-old man with MAS and acromegaly, in whom surgical removal of the pituitary tumour has been technically difficult because of bone deformities. A combination of a long-acting somatostatin analogue (Sandostatin LAR and external irradiation were therefore used as treatment. Acromegaly associated with MAS is very rarely seen, and has been the subject of approximately 70 published reports. We present a case of acromegaly associated with MAS and a brief survey of relevant literature. Turk Jem 2009; 13: 13-5
Kim, Soo Kyoung; Kim, Bo Ra; Kim, Kyongyoung; Kim, Sungsu; Jung, Jung Hwa; Hahm, Jong Ryeal; Jung, Jaehoon
Endocrine diseases are frequently accompanied by diabetes mellitus and treatment of an underlying endocrine disease often improves glucose control. The co-occurrence of acromegaly and Cushing's syndrome is extremely rare. We herein describe a patient who showed a dramatic improvement in glucose control following treatment for co-existing acromegaly and Cushing's syndrome. An adrenal mass was incidentally discovered during a routine evaluation of a 56-year-old woman who was subsequently diagnosed with acromegaly and a unilateral cortisol-producing adrenal adenoma. Her blood glucose was poorly controlled despite receiving high-dose insulin therapy. After undergoing adrenalectomy for Cushing's syndrome, her insulin dosage was decreased by almost 50%. The insulin treatment was discontinued following the treatment of acromegaly.
Full Text Available Abstract Although impaired glucose tolerance affects 36% and overt diabetes mellitus can be seen in 30% of cases with acromegaly, diabetic ketoacidosis is rarely reported in patients with this disease. We present an unusual complication of acromegaly: a 22 year old woman with amenorrhea (6 month ago and blurred vision of left eye (4 month ago referred to Ghaem neurology clinic in Mashhad. With a growth hormone (GH level of =100ng/ml, Insulin like growth factor-1 (IGF-1 =1560 ng/ml and pituitary macro adenoma in magnetic resonance imaging (MRI, she was candidated for surgery. A few hours before surgery she had dyspnea, loss of consciousness, fever and with blood sugar (BS =500 mg/ml, Hco3=2.4, PH=7.06 and keton in urine. Diabetic ketoacidosis was diagnosed. The patient was treated with high dose of insulin (500 IU/day and hydration. After octerotide administration the need for insulin decreased and after pituitary adenectomy, there was no need for insulin therapy and the patient was discharged on metformin (one tablet per day.
Full Text Available In the present retrospective study we determined the frequency of glucose intolerance in active untreated acromegaly, and searched for risk factors possibly supporting the emergence of the diabetic condition. Among 43 patients, 8 (19%; 95% CI: 8-33% had diabetes mellitus and 2 (5%; 1-16% impaired glucose tolerance. No impaired fasting glycemia was demonstrable. The frequency of diabetes was on average 4.5 times higher than in the general Slovak population. Ten factors suspected to support progression to glucose intolerance were studied by comparing the frequency of glucose intolerance between patients with present and absent risk factors. A family history of diabetes and arterial hypertension proved to have a significant promoting effect (P<0.05, chi-square test. A significant association with female gender was demonstrated only after pooling our data with literature data. Concomitant prolactin hypersecretion had a nonsignificant promoting effect. In conclusion, the association of active untreated acromegaly with each of the three categories of glucose intolerance (including impaired fasting glycemia, not yet studied in this connection was defined as a confidence interval, thus permitting a sound comparison with the findings of future studies. Besides a family history of diabetes, female gender and arterial hypertension were defined as additional, not yet described risk factors.
Arafah, B U; Brodkey, J S; Kaufman, B; Velasco, M; Manni, A; Pearson, O H
Twenty-five patients with acromegaly and 3 patients with gigantism underwent transsphenoidal microsurgery in an attempt to remove the tumor and preserve normal pituitary function whenever possible. An adenoma was identified and removed in 27 of 28 patients. Evaluation 3--6 months postoperatively revealed a GH level less than 5 ng/ml in 29 patients, 5--10 ng/ml in 4 patients and 11--29 ng/ml in 4 other patients. Dynamics of GH secretion were normal in 11 patients who had normal pituitary function and are considered cured. Two patients with low or undetectable GH levels are also considered cured at the expense of being hypopituitary. Three of 7 patients with normal basal GH levels but abnormal dynamics of GH secretion relapsed within 1 yr. Eleven of the 13 patients considered cured did not have extrasellar extension, while 14 of the 15 patients not cured had extrasellar extension. Five patients who were not cured with surgery received radiation therapy. Three patients were treated with an ergot derivative, Lergotrile mesylate, after surgery and radiation therapy failed to normalize GH levels. Transsphenoidal microsurgery is an optimal form of therapy for patients with acromegaly or gigantism, especially those with no extrasellar extension. Dynamics of GH secretion are very useful in evaluating the completeness of adenoma removal.
Learned-Miller, Erik; Lu, Qifeng; Paisley, Angela; Trainer, Peter; Blanz, Volker; Dedden, Katrin; Miller, Ralph
Acromegaly is a rare disorder which affects about 50 of every million people. The disease typically causes swelling of the hands, feet, and face, and eventually permanent changes to areas such as the jaw, brow ridge, and cheek bones. The disease is often missed by physicians and progresses beyond where it might if it were identified and treated earlier. We consider a semi-automated approach to detecting acromegaly, using a novel combination of support vector machines (SVMs) and a morphable model. Our training set consists of 24 frontal photographs of acromegalic patients and 25 of disease-free subjects. We modelled each subject's face in an analysis-by-synthesis loop using the three-dimensional morphable face model of Blanz and Vetter. The model parameters capture many features of the 3D shape of the subject's head from just a single photograph, and are used directly for classification. We report encouraging results of a classifier built from the training set of real human subjects.
Burton, Tanya; Le Nestour, Elisabeth; Bancroft, Tim; Neary, Maureen
Acromegaly is a rare, chronic, and debilitating disease that results from excessive growth hormone production. Clinically, this disease is associated with enlargement of soft tissue, excessive skeletal growth, and increased risk of cardiovascular disease. Acromegaly is often diagnosed late, when a wide range of comorbidities may already be present. First-line therapy for acromegaly is typically surgery; but a number of highly-specific pharmacological agents have recently enabled a more aggres...
Bex, Marie; Abs, Roger; T'Sjoen, Guy; Mockel, Lean; Velkeniers, Brigitte; Muermans, Katja; Maiter, Dominique
Objectives: To constitute a registry on acromegaly, AcroBel, to evaluate the epidemiology and quality of care of acromegaly in Belgium and Luxembourg. Design: A nationwide survey from June 2003 till September 2004 aiming to collect data from all patients with acromegaly who had visited the participating endocrine clinics after 1 January 2000. Methods: Retrospective data collection coupled to a visit within the survey period, allowing sampling of metabolic parameters and centralised dete...
Abreu, Alin; Tovar, Alejandro Pinzón; Castellanos, Rafael; Valenzuela, Alex; Giraldo, Claudia Milena Gómez; Pinedo, Alejandro Castellanos; Guerrero, Doly Pantoja; Barrera, Carlos Alfonso Builes; Franco, Humberto Ignacio; Ribeiro-Oliveira, Antônio; VILAR, Lucio; Jallad, Raquel S.; Duarte, Felipe Gaia; Gadelha, Mônica; Boguszewski, Cesar Luiz
Introduction Acromegaly is a rare, insidious disease resulting from the overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), and is associated with a range of comorbidities. The extent of associated complications and mortality risk is related to length of exposure to the excess GH and IGF-1, thus early diagnosis and treatment is imperative. Unfortunately, acromegaly is often diagnosed late, when patients already have a wide range of comorbidities. The presence of co...
Bahena-García Ana; Tamez-Pérez Héctor E; Gómez de Ossio María D; Gutiérrez-Hermosillo Hugo; Tamez-Peña Alejandra L
Abstract Introduction In the patient with acromegaly, pituitary surgery is the therapeutic standard. Despite undergoing surgery, a significant number of patients with acromegaly continue to have uncontrolled growth hormone secretion. These patients require other treatments such as external irradiation and/or drug therapy. Case presentation We present the clinical and laboratory responses to six months of treatment with rosiglitazone in four cases. In all four cases, the patients had persisten...
Akdeniz, Bahri; Gedik, Arzu; Turan, Onur; Ozpelit, Ebru; Ikiz, Ahmet Omer; Itil, Oya; Badak, Ozer; Baris, Nezihi; Cömlekçi, Abdurrahman
Left ventricular diastolic dysfunction (LVDD) develops in the early stages of acromegaly. The purpose of this study was to identify LVDD analyzing by new echocardiograpic criteria as well as to evaluate determinants of the LVDD in acromegaly. This cross-sectional study examined 42 patients with acromegaly; 16 in active disease (AA) and 26 cured/ well controlled (CA), and compared them with 30 healthy controls (CG). Ventricular systolic and diastolic functions were studied by conventional and tissue Doppler imaging based on the E/Em ratio and myocardial performance index (MPI). Other clinical parameters possibly contributing to LVDD in acromegaly were also investigated. The prevalence of LV hypertrophy (33%) and LVDD (35.7%) were increased in acromegaly, however, there were no differences between the AA and CA groups. Acromegalic patients had higher LV volumes and LV mass, and septal E/Em ratio compared to CG, whereas LV ejection fraction and MPI were not different. The presence of acromegaly (r = 0.29, P = 0.013), diabetes mellitus (DM) (r = 0.41, P < 0.001), hypertension (r = 0.35, P = 0.002), and sleep apnea (r = 0.56, P = 0.003) were found to be correlated with LVDD, whereas duration and activity of acromegaly were not. In regression analysis, advanced age (OR: 8.53, P = 0.006) and DM (OR: 25.9, P = 0.007) were found to be independent risk factors for LVDD. The risk of LVDD according to new criteria increases in acromegaly. However, it seems to be related to the presence of DM and advanced age and is independent of disease duration and activity.
Banerji, Deepu; Das, Nitu K.; Sharma, Siddhiraj; Jindal, Yogesh; Vijendra K Jain; Behari, Sanjay
Context: Functional growth hormone producing adenomas have long-term deleterious effects on the visual apparatus, the cardiovascular and musculoskeletal systems, and often predispose to malignancies. Since persistence of acromegaly affects outcome and quality of life, therapeutic interventions become mandatory. Aim: This study represents an analysis of long-term clinical and endocrinal outcome of 115 patients of acromegaly after surgical management. Setting and Design: Tertiary care retrospec...
Wolinski, K; Stangierski, A; Dyrda, K; Nowicka, K; Pelka, M; Iqbal, A; Car, A; Lazizi, M; Bednarek, N; Czarnywojtek, A; Gurgul, E; Ruchala, M
Acromegaly is a chronic disease resulting from pathological oversecretion of growth hormone and subsequently insulin growth factor-1. Several complications of the disease have been reported, including cardiovascular diseases, respiratory disorders but also increased risk of benign and malignant neoplasms. The aim of the study was to evaluate the risk of malignant neoplasms in the patients with acromegaly in comparison with the control group. Medical documentation of acromegalic patients treated in one medical center between 2005 and 2016 has been analyzed. Results were compared with sex- and age-matched group of subjects with prolactinomas and hormonally inactive pituitary lesions hospitalized in the same department. Two hundred patients with acromegaly were included. Control group was composed of 145 patients. Any malignant neoplasm in anamnesis was present in 27 (13.5 %) patients with acromegaly and six (4.1 %) subjects from control group (p = 0.003). Thyroid cancer was present in 14 (7.0 %) patients with acromegaly and two (1.4 %) in control group (p = 0.02). Breast cancer was present in seven women (5.4 % of women) in acromegaly group but none of subjects in control group (p = 0.02). Colon cancer-4 (2.0 %) patients in acromegaly group and 0 in control group (p = 0.14). Malignant neoplasms are significantly more common in patients with acromegaly. Particularly, risk of thyroid cancer was increased over fivefold. Systematic screening for neoplastic diseases should be important part of follow-up in these patients. Further case-control studies are strongly indicated to evaluate which neoplasms are more common in acromegalic patients and what is the exact risk of malignancy.
V N Azizyan
Full Text Available In this article we describe a spontaneous remission of acromegaly of intraoperative bleeding, with subsequent hemorrhage into the tumor. The cases of spontaneous remission of acromegaly described in the literature have been associated mainly with hemorrhage or ischemic apoplexy pituitary adenoma without surgical intervention. Most often, both processes, especially hemorrhage are accompanied by the development of panhypopituitarism. Cases in which there was a normalization of only growth hormone isolated.
Cordes Uwe; Both Stefan; Wuster Christian; Omran Wael; Reisch Robert
Abstract Introduction The first-line treatment for acromegaly is transsphenoidal surgery. In approximately 50% of patients, however, a cure is not possible with surgery and alternatives are needed. Somatostatin analog therapy is the recommended first-line treatment in patients with such cases. Here we provide the first report of a high-dose lanreotide primary therapy in patients with acromegaly. Case presentation Six patients who were not suitable for surgery were given 60 mg of lanreotide (A...
Topsakal, S; Akin, F; Turgut, S; Yaylali, G F; Herek, D; Ayada, C
Acromegaly is characterized by excess growth hormone and insulin-like growth factor-1 concentrations. There is conflicting evidence as to whether acromegaly is associated with an increased risk of atherosclerosis. Apelin is an adipose tissue-derived peptide that may be associated with hyperinsulinemia. Fetuin-A is a hepatocyte produced plasma glycoprotein that has an important role as a calcification inhibitor. The aim of this study was to examine apelin, fetuin-A, and procalcitonin concentrations and to assess their relationship with carotid intima medial thickness (cIMT) in subjects with acromegaly. Apelin, fetuin-A, and procalcitonin serum concentrations were measured in 37 (20 inactive and 17 active) subjects with acromegaly and 30 control subjects, along with carotid intima medial thickness. The concentrations of apelin, fetuin-A, and procalcitonin were increased in subjects with acromegaly. There were significant correlations between apelin, fetuin-A, and procalcitonin in subjects with acromegaly. Carotid intima medial thickness values were similar between control subjects and subjects with acromegaly. Carotid intima medial thickness was not increased in subjects with acromegaly. It is possible that the increased apelin and fetuin-A concentrations observed play a protective role against the development of atherosclerosis in subjects with acromegaly. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Full Text Available Acromegaly is a disorder caused by the excess production of pituitary growth hormone and is characterized by the enlargement of the hands, feet and head. Increased morbidity and mortality with acromegaly is associated with cardiovascular complications, hypertension, glucose intolerance, cardiomyopathy and coronary artery disease. We report a case of acromegaly, which presented with ST-segment elevation acute myocardial infarction. The patient received successful primary transluminal coronary angioplasty with stent implantation. Acromegaly was suspected from typical appearance, and confirmed with hormonal examination and imaging of the pituitary mass. We discuss this case in comparison with previous literature.
Tagliafico, A; Resmini, E; Ferone, D; Martinoli, C
The purpose of this article is to summarise the early musculoskeletal complications of acromegaly. Some of the early signs of acromegaly may be evaluated by the musculoskeletal radiologist. In the early stage of disease, peripheral nerve enlargement associated with carpal tunnel syndrome or cubital tunnel syndrome and thickening of retinacula, such as A1 pulley in trigger finger, represent the features that may be seen by radiologists and are worthy of an endocrinological evaluation. Due to the insidious nature of the disease, the diagnosis of acromegaly is significantly delayed. Few and nonspecific symptoms characterise the initial phases of the disease, and therefore, most patients will have generally consulted many specialists (most frequently musculoskeletal radiologists) before an adequate endocrinological assessment is performed. For this reason, initial clinical signs are much more important than symptoms for an early diagnosis of acromegaly. The first and most important therapeutic approach to acromegaly is early diagnosis, whereas the therapeutic goals are to eliminate morbidity and reduce mortality to the expected age- and sex-adjusted rates and prevent the development of systemic complications. Musculoskeletal radiologists should be aware that these features may be early manifestations of acromegaly. When both radiological and clinical abnormalities are present, an endocrinological workup is useful to diagnose the disease in an early phase.
Alibas, H; Gogas Yavuz, D; Kahraman Koytak, P; Uygur, M; Tanridag, T; Uluc, K
Acromegaly is known to affect peripheral nervous system (PNS) causing carpal tunnel syndrome (CTS) and polyneuropathy. The frequency of these disorders and the evaluation methods vary among studies. In the present study, we aimed to examine PNS of acromegaly patients under somatostatin analogue (SSA) therapy. Forty-eight acromegaly patients (26 F/22 M, 45.58 ± 11.6 years) under SSA treatment and 44 healthy controls (25 F/19 M, 47.46 ± 8.7 years) were assessed by symptom questionnaires, neurologic examination and electrophysiological studies. 87.5 % of the acromegaly patients had at least one abnormal finding regarding PNS. With the incorporation of palm-wrist median nerve conduction velocity method, we detected CTS in 50 % of patients. Polyneuropathy was less frequent (29.2 %). Both conditions were independent from the coexisting diabetes mellitus (p = 0.22 for CTS, p = 0.71 for polyneuropathy). Polyneuropathy but not CTS was more common among biochemically uncontrolled acromegaly patients rather than those under control (p = 0.03; p = 0.68, respectively). Our findings emphasize the high prevalence of peripheral nervous system involvement in acromegaly patients under SSA therapy and importance of neurological evaluation of these patients. Early diagnosis and treatment of the disease may reduce the PNS involvement.
Tritos, Nicholas A; Biller, Beverly M K
To review published data on pegvisomant and its therapeutic role in acromegaly. Electronic searches of the published literature were conducted using the keywords: acromegaly, growth hormone (GH) receptor (antagonist), pegvisomant, therapy. Relevant articles (n = 141) were retrieved and considered for inclusion in this manuscript. Pegvisomant is a genetically engineered, recombinant growth hormone receptor antagonist, which is effective in normalizing serum insulin-like growth factor 1 (IGF-1) levels in the majority of patients with acromegaly and ameliorating symptoms and signs associated with GH excess. Pegvisomant does not have direct antiproliferative effects on the underlying somatotroph pituitary adenoma, which is the etiology of GH excess in the vast majority of patients with acromegaly. Therefore, patients receiving pegvisomant monotherapy require regular pituitary imaging in order to monitor for possible increase in tumor size. Adverse events in patients on pegvisomant therapy include skin rashes, lipohypertrophy at injection sites, and idiosyncratic liver toxicity (generally asymptomatic transaminitis that is reversible upon drug discontinuation), thus necessitating regular patient monitoring. Pegvisomant is an effective therapeutic agent in patients with acromegaly who are not in remission after undergoing pituitary surgery. It mitigates excess GH action, as demonstrated by IGF-1 normalization, but has no direct effects on pituitary tumors causing acromegaly. Regular surveillance for possible tumor growth and adverse effects (hepatotoxicity, skin manifestations) is warranted.
Broder, M S; Neary, M P; Chang, E; Cherepanov, D; Katznelson, L
The economic burden of acromegaly in the US has been largely unknown. We describe the prevalence of treatment patterns, complication rates, and associated healthcare utilization and costs of acromegaly in the US. Patients were identified between 1/1/2002 and 12/31/2009 in claims databases. During 1-year after each continuously-enrolled patient's first acromegaly claim, pharmacy and medical claims were used to estimate outcomes. Regression models were used to adjust outcomes. There were 2,171 acromegaly patients (mean age: 45.3 years; 49.7% female); 77.8% received the majority of their care from non-endocrinologists. Pharmacologic treatment was used by 30.8% of patients: octreotide-LAR in 18.6%, dopamine agonists in 9.8%, short-acting octreotide in 4.7%, pegvisomant in 4.1%, and lanreotide in 1.2%; 56% had biochemical monitoring. Comorbidities were common, ranging from 6.6% (colon neoplasms) to 25.6% (musculoskeletal abnormalities). Mean healthcare costs were $24,900. Adjusted analyses indicated comorbidities increased the odds of hospitalization: by 76% for musculoskeletal abnormalities; 193% for cardiovascular abnormalities; and 56% for sleep apnea (p acromegaly patients. Cardiovascular complications nearly tripled the odds of hospitalization (OR 2.93) and increased annual mean cost by $13,331. Adequate management of this disease may be able to reduce health care utilization and cost associated with these complications and with acromegaly in general.
Selek, Alev; Cetinarslan, Berrin; Gurbuz, Yesim; Tarkun, Ilhan; Canturk, Zeynep; Cabuk, Burak
The purpose of this study was to evaluate aromatase enzyme expression in growth hormone (GH) secreting adenomas and comparison with prolactinomas, nonfunctional adenomas, and normal pituitary tissues. Also the impact of its expression on clinical and prognostic features was evaluated. 38 acromegaly, 26 prolactinoma, and 31 nonfunctional pituitary adenoma and 11 normal pituitary gland samples from autopsies were included. Aromatase and estrogen receptor-alpha (ERα) were evaluated by Immunohistochemical method; demographic, pre- and postoperative features of the patients were noted. Aromatase was expressed in varying degrees in all cases in study including controls. Aromatase expression in patients with acromegaly was significantly higher than patients with prolactinoma, nonfunctional adenoma, and controls (p = 0.04, p = 0.01 and p acromegaly, aromatase expression was negatively correlated with ER-alpha (p = 0.02, r = -0.34). Also, Ki-67 immunohistochemical results were negatively correlated with aromatase expression (p = 0.03, r = -0.27) while positively correlated with ER expression (p acromegaly. In patients with acromegaly and prolactinoma, aromatase expression was negatively correlated with Ki-67 score, and also it was higher in patients with complete postoperative remission than without remission. Therefore, aromatase expression may be a good prognostic marker predominantly in acromegaly.
Ali Riza Koksal
Full Text Available An increase in the prevalence of colorectal polyps and cancer is reported in patients with acromegaly. This trial is designed to determine whether there is an increase in the prevalence of colorectal polyps/cancer in Turkish acromegaly patients. Sixty-six patients, who were under follow-up with the diagnosis of acromegaly and underwent total colonoscopic examination, were enrolled in the study. Sixty-five age- and gender-matched patients with nonspecific complaints were selected as control. The mean age of acromegalic patients was 51.5±12.8 years of whom 27 (40.9% were females. In 20 (30.3% of the patients with acromegaly a total of 65 colorectal polyps were detected. Forty-seven (72.3% of the polyps were detected at the rectosigmoid region. In 8 (12.3% of the 65 control patients a total of 17 polyps were found. There was a statistically significant difference between the groups (P=0.018. At the logistic regression analysis we found that the risk for colon polyps increased 3.2-fold in the presence of acromegaly, irrespective of age and gender (OR: 3.191, 95% CI: 1.25–8.13. In conclusion, patients who were followed up with the diagnosis of acromegaly should be taken to the colonoscopic surveillance program and all polyps detected should be excised in order to protect them from colorectal cancer.
Vandeva, Silvia; Yaneva, Maria; Natchev, Emil; Elenkova, Atanaska; Kalinov, Krasimir; Zacharieva, Sabina
Various factors influence quality of life (QoL) in acromegaly. Whether disease control and treatment approach are related to QoL is still a matter of debate. The aim of the present study was to evaluate QoL in patients with acromegaly using the disease-specific Acromegaly Quality of Life Questionnaire in respect to disease activity, treatment modalities, and other factors. We studied 212 patients with acromegaly in a cross-sectional manner over a 6-year period in a single tertiary center. As a second step, seventy of the patients who were with active disease at baseline were followed up prospectively and 45 of them were in remission at re-evaluation. In regard to the cross-sectional group, active acromegaly independently predicted worse appearance scores. Prior radiotherapy and older age were independent negative predictors of all scales. Female gender negatively predicted all scales except the appearance domain. Longer duration of remission predicted worse personal relations scores in biochemically controlled patients. The use of somatostatin analog (SSA) was associated with worse personal relations scores, while higher IGF-1 index predicted worse appearance scores in patients with active acromegaly. In the prospective group, achievement of remission independently predicted improvement of the total scale. Lower corresponding baseline scores predicted improvement of the total, physical, and appearance scales, while the absence of hypopituitarism independently predicted improvement of the appearance scale. The use of SSA was associated with improvement of the total and appearance scores. In conclusion, QoL is a multifactorial issue that needs an individualized approach for detection and management.
Cheng, Sonia; Gomez, Karen; Serri, Omar; Chik, Constance; Ezzat, Shereen
Background The risk and mortality due to cancer in patients with acromegaly have been previously investigated. Although GH/IGF-1 excess provides a probable pathophysiological explanation, the degree of IGF-1 excess and the role in acromegaly-associated neoplasms of diabetes, a common comorbidity in acromegaly with known association with cancer, remains unclear. Methods Acromegalic patients treated in three Canadian referral centers (Toronto, Montreal, Edmonton) were included. All available clinical information was recorded including: age, initial and last percentage of the upper limit of normal (%ULN) IGF-1 levels, comorbidities and other neoplasms (benign and malignant). Results 408 cases were assessed. 185 were women (45.3%), 126 (30.9%) developed extra-pituitary neoplasms: 55 malignant and 71 benign. The most frequent anatomic site was the gastrointestinal tract (46 [11.3%]), followed by head and neck (36 [8.8%]) and multiple locations (14 [3.4%]). 106 (26.0%) cases had diabetes. Initial IGF-1 was significantly higher in men older than 50 (380.15 vs. 284.78, p = 0.001) when compared to men younger than 50. Diabetics showed significantly higher initial IGF-1 (389.38 vs. 285.27, p = 0.009), as did diabetics older than 50 compared with those without diabetes. 45.3% (48/106) of cases with diabetes developed extra-pituitary neoplasms vs. 24.3% (71/292) without diabetes (p = 0.001, OR: 2.576 95%CI 1.615–4.108). 22.6% (24/106) of cases with diabetes developed malignant tumors vs. 9.2% (27/292), (p < 0.001, OR 2.873, 95%CI 1.572–5.250). Conclusions These data suggest that acromegalic patients with diabetes are more likely to develop extra-pituitary neoplasms and their initial IGF-1 levels are higher. The contribution of IGF-1 vs. diabetes alone or in combination in the development of extra-pituitary neoplasms warrants further investigation. PMID:25996963
Full Text Available The risk and mortality due to cancer in patients with acromegaly have been previously investigated. Although GH/IGF-1 excess provides a probable pathophysiological explanation, the degree of IGF-1 excess and the role in acromegaly-associated neoplasms of diabetes, a common comorbidity in acromegaly with known association with cancer, remains unclear.Acromegalic patients treated in three Canadian referral centers (Toronto, Montreal, Edmonton were included. All available clinical information was recorded including: age, initial and last percentage of the upper limit of normal (%ULN IGF-1 levels, comorbidities and other neoplasms (benign and malignant.408 cases were assessed. 185 were women (45.3%, 126 (30.9% developed extra-pituitary neoplasms: 55 malignant and 71 benign. The most frequent anatomic site was the gastrointestinal tract (46 [11.3%], followed by head and neck (36 [8.8%] and multiple locations (14 [3.4%]. 106 (26.0% cases had diabetes. Initial IGF-1 was significantly higher in men older than 50 (380.15 vs. 284.78, p = 0.001 when compared to men younger than 50. Diabetics showed significantly higher initial IGF-1 (389.38 vs. 285.27, p = 0.009, as did diabetics older than 50 compared with those without diabetes. 45.3% (48/106 of cases with diabetes developed extra-pituitary neoplasms vs. 24.3% (71/292 without diabetes (p = 0.001, OR: 2.576 95%CI 1.615-4.108. 22.6% (24/106 of cases with diabetes developed malignant tumors vs. 9.2% (27/292, (p < 0.001, OR 2.873, 95%CI 1.572-5.250.These data suggest that acromegalic patients with diabetes are more likely to develop extra-pituitary neoplasms and their initial IGF-1 levels are higher. The contribution of IGF-1 vs. diabetes alone or in combination in the development of extra-pituitary neoplasms warrants further investigation.
Full Text Available Michelle H Gurel,1 Paul R Bruening,2 Christine Rhodes,2 Kathleen G Lomax31Neuroendocrine Clinical Center, Massachusetts General Hospital, Boston, MA, USA; 2Nicholas Research Associates International, New York, NY, USA; 3Medical Affairs, Ipsen Biopharmaceuticals, Inc., Basking Ridge, NJ, USAPurpose: Acromegaly is a chronic condition resulting from a growth hormone-secreting pituitary tumor that can substantially impact patients' physical and emotional well-being. We sought to understand the impact of acromegaly on disease-related concerns and treatment choices from the patient perspective. The path to diagnosis, current disease management, interactions with the treating health care providers (HCPs, and support networks were also assessed.Methods: Acromegaly patients were recruited primarily from a patient support group (Acromegaly Community. In Phase I, ten patients participated over the course of 5 days in a moderated online discussion board and they answered questions about their disease. In Phase II, a separate nine-patient cohort participated in face-to-face interviews conducted during an acromegaly patient conference. Data were summarized qualitatively by grouping similar answers and quotations.Results: Nineteen acromegaly patients were recruited across the two cohorts, and both groups shared similar concerns. They demonstrated a notable interest in understanding their disease and its treatment. Patients were focused on the impact of the disease on their life, and they expressed a desire to get beyond reminders of their disease. The patients described long journeys to a correct diagnosis and relief at having a name for their condition. Many shared a sense of shock at needing pituitary surgery and felt unsatisfied by the treatment decision process, motivating them to discuss it with other patients. Patients not connected to a patient support group reported feeling helpless and lonely. Most patients shared a desire to improve their general
Kim, Hee Kyung; Lee, Ji Shin; Park, Min Ho; Cho, Jin Seong; Yoon, Jee Hee; Kim, Soo Jeong; Kang, Ho-Cheol
Introduction Several studies have reported a high frequency of papillary thyroid cancer (PTC) in patients with acromegaly. The aim of this study was to determine the prevalence and predictors of thyroid cancer in patients with acromegaly and to investigate the frequency of the BRAFV600E mutation in PTC patients with and without acromegaly. Materials and Methods We conducted a retrospective study of 60 patients with acromegaly. Thyroid ultrasonography (US) and US-guided fine needle aspiration were performed on nodules with sonographic features of malignancy. We selected 16 patients with non-acromegalic PTC as a control group. The BRAFV600E mutation was analyzed in paraffin-embedded surgical specimens of PTC by real-time polymerase chain reaction, and tumor specimens from patients with PTC were stained immunohistochemically with an antibody against insulin-like growth factor-1 receptor β (IGF-1Rβ). Results Thyroid cancer was found in 15 (25.0%) patients. No differences in age, sex, initial growth hormone (GH) and IGF-1 percentage of the upper limit of normal values or treatment modalities were observed between patients with and without PTC. Acromegaly was active in 12 of 15 patients at the time of PTC diagnosis; uncontrolled acromegaly had a significantly higher frequency in the PTC group (60%) than in the non-PTC group (28.9%) (p = 0.030). The BRAFV600E mutation was present in only 9.1% (1/11) of PTC patients with acromegaly, although 62.5% (10/16) of control patients with PTC had the mutation (p = 0.007). IGF-1Rβ immunostaining showed moderate-to-strong staining in all malignant PTC cells in patients with and without acromegaly. Significantly less staining for IGF-1Rβ was observed in normal adjacent thyroid tissues of PTC patients with acromegaly compared with those without (p = 0.014). Conclusion The prevalence of PTC in acromegalic patients was high (25%). An uncontrolled hyperactive GH-IGF-1 axis may play a dominant role in the development of PTC
Hee Kyung Kim
Full Text Available INTRODUCTION: Several studies have reported a high frequency of papillary thyroid cancer (PTC in patients with acromegaly. The aim of this study was to determine the prevalence and predictors of thyroid cancer in patients with acromegaly and to investigate the frequency of the BRAFV600E mutation in PTC patients with and without acromegaly. MATERIALS AND METHODS: We conducted a retrospective study of 60 patients with acromegaly. Thyroid ultrasonography (US and US-guided fine needle aspiration were performed on nodules with sonographic features of malignancy. We selected 16 patients with non-acromegalic PTC as a control group. The BRAFV600E mutation was analyzed in paraffin-embedded surgical specimens of PTC by real-time polymerase chain reaction, and tumor specimens from patients with PTC were stained immunohistochemically with an antibody against insulin-like growth factor-1 receptor β (IGF-1Rβ. RESULTS: Thyroid cancer was found in 15 (25.0% patients. No differences in age, sex, initial growth hormone (GH and IGF-1 percentage of the upper limit of normal values or treatment modalities were observed between patients with and without PTC. Acromegaly was active in 12 of 15 patients at the time of PTC diagnosis; uncontrolled acromegaly had a significantly higher frequency in the PTC group (60% than in the non-PTC group (28.9% (p = 0.030. The BRAFV600E mutation was present in only 9.1% (1/11 of PTC patients with acromegaly, although 62.5% (10/16 of control patients with PTC had the mutation (p = 0.007. IGF-1Rβ immunostaining showed moderate-to-strong staining in all malignant PTC cells in patients with and without acromegaly. Significantly less staining for IGF-1Rβ was observed in normal adjacent thyroid tissues of PTC patients with acromegaly compared with those without (p = 0.014. CONCLUSION: The prevalence of PTC in acromegalic patients was high (25%. An uncontrolled hyperactive GH-IGF-1 axis may play a dominant role in the
Yagi, Takakaza; Kawakami, Masayoshi; Takada, Kenji
A male (30 years five months) who complained of mandibular prominence and masticatory dysfunction was diagnosed as a mandibular prognathic with acromegaly after cephalometric and endocrine examinations. The level of growth hormone (GH) subsequent to a transsphenoidal hypophysectomy had been controlled by medicines for about five years. Surgical orthodontic correction improved his occlusion and profile, but magnetic resonance imaging detected a recurrent adenoma in the cranial base during the retention period. The recurrence resulted in slight prognathic changes of the patient with a high level of GH. This is a case report of the treatment of an acromegalic patient discussing growth considerations that could influence the orthodontic treatment plan and long-term stability.
Galanti, G; Cappelli, B; Diricatti, G; Mininni, S; Vono, M C; Gensini, G F
The aim of this study was to establish the existence of primary acromegalic cardiomyopathy different from the cardiovascular complications often associated with acromegaly. Thirty-four acromegalic patients, referred to our non-invasive laboratory and divided into two groups on the basis of the presence of hypertension, underwent echocardiographic studies. A control group of 34 subjects individually matched with the patients for age, sex, and blood pressure values was also studied. To evaluate cardiac function during exercise, the normotensive acromegalics, the control group, and a group of 9 athletes with left ventricular mass comparable to that of the acromegalic subjects underwent a handgrip test. Cardiac mass was increased in all patients; hypertensive patients had a greater increase than normotensive patients (144.9 +/- 38 vs 120.9 +/- 20.8 g/m, p cardiac hypertrophy caused by GH hyperincretion does not improve acromegalic heart activity: diastolic function, although normal at rest, appears deficient during isometric exercise.
Kaku, T; Nakashima, Y; Ichiyasu, H; Soejima, M; Baba, K; Kuroiwa, A
A 57-year-old woman with acromegaly associated with mitral chordal rupture is reported. She was noted to have abnormal development in the size of her hands and feet in childhood. She occasionally suffered from shortness of breath on exertion and nocturnal dyspnea for several years, and was diagnosed and treated as having congestive heart failure due to valvular heart disease. On admission to our hospital, chordal rupture was suspected on the basis of M-mode and two-dimensional echocardiography. Seven years after discharge, she died of congestive heart failure. On autopsy, the heart weight and ventricular wall thickness were increased. Rupture of the posterior chordae was confirmed, but evidence of an old myocardial infarction was not found. There was severe interstitial fibrosis in the left ventricular wall. A possible etiology of the chordal rupture in this case was thought to be the excessive stretching caused by the disproportional visceromegaly of the heart.
Shahnaz Ahmad Mir
Full Text Available Introduction: Pituitary apoplexy is an uncommon event and usually occurs in non-functioning pituitary tumors. Among the functioning tumors, prolactinomas are the ones most likely to apoplexy. Apoplexy in growth hormone (GH producing adenomas is a very rare event with less than thirty cases reported worldwide. Objective: To describe a case of spontaneous pituitary apoplexy in acromegaly. Case Report: A 55 year old smoker male presented to the our outpatient clinic in 2004 with complaints of gradual onset increase in the size of hands and feet, bilateral knee pain, increased sweating and blurring of vision. Investigations uncovered diabetes mellitus by a casual blood glucose of 243 mg/dl and HbA1c of 8.5%. Growth hormone suppression test using 75 gram oral glucose showed a 60 minute growth hormone of 105 ng/ml. Magnetic resonance imaging of the sellar region showed a 12.0 mm × 10.0 mm pituitary adenoma. The patient was planned for transsphenoidal tumor decompression. However, the patient was lost to follow up. Eight-years later, he presented in the emergency department of our institute with sudden onset headache, vomiting and decreased level of consciousness of one day duration. CT scan of the head with focus on the sella was suggestive of apoplexy which was later confirmed by the MRI of the sellar region. Conclusion: Although acromegaly can remit following apoplexy of the responsible pituitary adenoma, long term follow up is needed for early detection of the development of deficiency of pituitary hormones which may occur over years following the event as well as to detect tumor regrowth which again may occur several years later.
Reyes-Vidal, Carlos M.; Mojahed, Hamed; Shen, Wei; Jin, Zhezhen; Arias-Mendoza, Fernando; Fernandez, Jean Carlos; Gallagher, Dympna; Bruce, Jeffrey N.; Post, Kalmon D.
Context: GH and IGF-I have important roles in the maintenance of substrate metabolism and body composition. However, when in excess in acromegaly, the lipolytic and insulin antagonistic effects of GH may alter adipose tissue (AT) deposition. Objectives: The purpose of this study was to examine the effect of surgery for acromegaly on AT distribution and ectopic lipid deposition in liver and muscle. Design: This was a prospective study before and up to 2 years after pituitary surgery. Setting: The setting was an academic pituitary center. Patients: Participants were 23 patients with newly diagnosed, untreated acromegaly. Main Outcome Measures: We determined visceral (VAT), subcutaneous (SAT), and intermuscular adipose tissue (IMAT), and skeletal muscle compartments by total-body magnetic resonance imaging, intrahepatic and intramyocellular lipid by proton magnetic resonance spectroscopy, and serum endocrine, metabolic, and cardiovascular risk markers. Results: VAT and SAT masses were lower than predicted in active acromegaly, but increased after surgery in male and female subjects along with lowering of GH, IGF-I, and insulin resistance. VAT and SAT increased to a greater extent in men than in women. Skeletal muscle mass decreased in men. IMAT was higher in active acromegaly and decreased in women after surgery. Intrahepatic lipid increased, but intramyocellular lipid did not change after surgery. Conclusions: Acromegaly may present a unique type of lipodystrophy characterized by reduced storage of AT in central depots and a shift of excess lipid to IMAT. After surgery, this pattern partially reverses, but differentially in men and women. These findings have implications for understanding the role of GH in body composition and metabolic risk in acromegaly and other clinical settings of GH use. PMID:26037515
Cansu, Güven Barış; Yılmaz, Nusret; Yanıkoğlu, Atakan; Özdem, Sebahat; Yıldırım, Aytül Belgi; Süleymanlar, Gültekin; Altunbaş, Hasan Ali
Early diagnosis and treatment of cardiovascular diseases, the most frequent cause of morbidity and mortality in acromegaly, may be an efficient approach to extending the lifespan of affected patients. Therefore, it is crucial to determine any cardiovascular diseases in the subclinical period. The study objectives were to determine markers of subclinical atherosclerosis and asses heart structure and function. This was a cross-sectional, single-center study of 53 patients with acromegaly and 22 age- and sex-matched healthy individuals. Carotid intima-media thickness (CIMT), pulse-wave velocity (PWV), and echocardiographic data were compared between these groups. CIMT and PWV were higher in the acromegaly group than in the healthy group (P = .008 and P = .002, respectively). Echocardiography showed that left ventricular diastolic dysfunction was present in 11.3% of patients. Left ventricular mass index and left atrial volume index were higher in the patients (P = .016 and Pacromegaly and the control group. Our results showed that subclinical atherosclerosis (i.e., CIMT and PWV markers) and heart structure and function were worse in patients with acromegaly than in healthy individuals. Because there were no differences in these parameters between patients with controlled and uncontrolled acromegaly, our results suggest that the structural and functional changes do not reverse with biochemical control. AA = active acromegaly BSA = body surface area CA = biochemically controlled acromegaly CH = concentric hypertrophy CIMT = carotid intima-media thickness DBP = diastolic blood pressure DM = diabetes mellitus ECHO = echocardiography EDV = enddiastolic volume EF = ejection fraction ESV = endsystolic volume GH = growth hormone HC = healthy control HL = hyperlipidemia HT = hypertension IGF-1 = insulin-like growth factor 1 LA = left atrial LAV = left atrial volume LAVI = left atrial volume index LV = left ventricular LVDD = left ventricular diastolic dysfunction LVEF = left
Altinova, Alev Eroglu; Ozkan, Cigdem; Akturk, Mujde; Gulbahar, Ozlem; Yalcin, Muhittin; Cakir, Nuri; Toruner, Fusun Balos
Free 25-hydroxyvitamin D [25(OH)D] is suggested to be important in the determination of vitamin D deficiency, since vitamin D-binding protein (VDBP) may affect total 25(OH)D levels. There are no data about free 25(OH)D concentrations in acromegaly. We aimed to investigate serum VDBP and total and free 25(OH)D levels in patients with acromegaly in comparison with control subjects. We recruited 54 patients with acromegaly and 32 control subjects who were similar according to age, gender, and body mass index. Serum VDBP levels were found to be increased in patients with acromegaly compared to control subjects [90.35 (72.45-111.10) vs. 69.52 (63.89-80.13) mg/l, p = 0.001]. There was statistically no significant difference in serum total 25(OH)D levels between the patients with acromegaly and control subjects [18.63 (13.35-27.73) vs. 22.51 (19.20-28.96) ng/ml, p = 0.05]. Free 25(OH)D levels were significantly decreased in patients with acromegaly compared to control subjects [14.55 (10.45-21.45) vs. 17.75 (15.30-23.75) pg/ml, p = 0.03]. Free 25(OH)D levels correlated positively with total 25(OH)D (p = 0.0001) and HDL cholesterol (p = 0.04) and negatively with fasting blood glucose (p = 0.04). Our findings indicate that VDBP is increased and free 25(OH)D is decreased in acromegaly, while there is no significant alteration in total 25(OH)D.
Full Text Available Elena A Christofides Endocrinology Associates, Inc., Columbus, OH, USA Abstract: In acromegaly, achieving biochemical control (growth hormone [GH] level <1.0 ng/mL and age- and sex-normalized levels of insulin-like growth factor 1 [IGF-1] through timely diagnosis and appropriate treatment provides an opportunity to improve patient outcomes. Diagnosis of acromegaly is challenging because it is rooted in observing subtle clinical manifestations, and it is typical for acromegaly to evolve for up to 10 years before it is recognized. This results in chronic exposure to elevated levels of GH and IGF-1 and delay in patients receiving appropriate treatment, which consequently increases mortality risk. In this review, the clinical impact of elevated GH and IGF-1 levels, the effectiveness of current therapies, and the potential role of novel treatments for acromegaly will be discussed. Clinical burden of acromegaly and benefits associated with management of GH and IGF-1 levels will be reviewed. Major treatment paradigms in acromegaly include surgery, medical therapy, and radiotherapy. With medical therapies, such as somatostatin analogs, dopamine agonists, and GH receptor antagonists, a substantial proportion of patients achieve reduced GH and normalized IGF-1 levels. In addition, signs and symptoms, quality of life, and comorbidities have also been reported to improve to varying degrees in patients who achieve biochemical control. Currently, there are several innovative therapies in development to improve patient outcomes, patient use, and access. Timely biochemical control of acromegaly ensures that the patient can ultimately improve morbidity and mortality from this disease and its extensive consequences. Keywords: disease burden, growth hormone, insulin-like growth factor 1, medical therapy, pituitary
A number of retrospective studies report that patients with acromegaly have increased morbidity and premature mortality, with standardized mortality ratios (SMR) of 1.3-3. Many patients with acromegaly develop hypopituitarism as a result of the pituitary adenoma itself or therapies such as surgery and radiotherapy. Pituitary radiotherapy and hypopituitarism have also been associated with an increased SMR.
Pendleton, C.; Adams, H.; Salvatori, R.; Wand, G.; Quinones-Hinojosa, A.
A review of Dr. Cushing's surgical cases at Johns Hopkins Hospital revealed new information about his early operative experience with acromegaly. Although in 1912 Cushing published selective case studies regarding this work, a review of all his operations for acromegaly during his early years has ne
Hoevenaren, I.A.; Wagenmakers, M.A.E.M.; Roerink, S.H.P.P.; Netea-Maier, R.T.; Ulrich, D.J.O.; Maal, T.J.J.
BACKGROUND: Acral overgrowth is a highly common clinical sign in patients with active acromegaly. To what extent this overgrowth persists after long-term remission of acromegaly is largely unknown. Using the new imaging technique of three-dimensional (3D) stereophotogrammetry, it is possible to
De Heide, L. J. M.; Van den Berg, G.; Wolthuis, A.; Van Schelven, W. D.
in acromegaly, the overproduction of growth hormone is usually caused by a pituitary adenoma. We report a 74-year-old woman with acromegaly caused by ectopic overproduction of growth hormone-releasing hormone (GHRH), a rare diagnosis. The GHRH appeared to be produced by a carcinoid tumour of the
Pendleton, C.; Adams, H.; Salvatori, R.; Wand, G.; Quinones-Hinojosa, A.
A review of Dr. Cushing's surgical cases at Johns Hopkins Hospital revealed new information about his early operative experience with acromegaly. Although in 1912 Cushing published selective case studies regarding this work, a review of all his operations for acromegaly during his early years has ne
De Heide, L. J. M.; Van den Berg, G.; Wolthuis, A.; Van Schelven, W. D.
in acromegaly, the overproduction of growth hormone is usually caused by a pituitary adenoma. We report a 74-year-old woman with acromegaly caused by ectopic overproduction of growth hormone-releasing hormone (GHRH), a rare diagnosis. The GHRH appeared to be produced by a carcinoid tumour of the lun
Yedinak, Chris G; Fleseriu, Maria
Pituitary adenomas (PAs) represent 15 % of all brain tumors. One-sixth of these are reported to cause acromegaly via excess growth hormone secretion. These tumors have been associated with multiple comorbidities, including neuropsychiatric and cognitive dysfunction. We aimed to assess patient perception of cognitive deficits and the relationship of cognitive changes to active acromegaly (AA) versus controlled acromegaly (CA) versus non-functional PAs (NFPA). A modified FACT-Cog survey was used, which focused on the prevalence and severity of perceived dysfunction in five areas of cognitive function: ability to learn, concentration/distractibility, mental agility, memory and recall, and verbal recall. Patient perception of current health and health change over the previous 12 months was also assessed. The overall perceived prevalence and severity of cognitive dysfunction were the highest among NFPA groups, particularly in the areas of mental agility, verbal recall, and memory/recall. Patients with AA reported greater prevalence and severity of dysfunction with respect to concentration/distractibility and ability to learn. Patients with AA reported the best overall current health, though patients with CA reported the greatest improvement in health over the previous year. These findings may indicate that PAs can affect cognitive function regardless of whether excess growth hormone is present. Acromegaly and NFPA patients perceive specific areas of cognitive dysfunction that may require further evaluation and treatment. Further research may be useful regarding patient quality of life, patient functionality during normal daily activities, and perceived dysfunction despite biological disease control.
Hyae Min Lee
Full Text Available The leading cause of morbidity and mortality in patients with acromegaly is cardiovascular complications. Myocardial exposure to excessive growth hormone can cause ventricular hypertrophy, hypertension, arrhythmia, and diastolic dysfunction. However, congestive heart failure as a result of systolic dysfunction is observed only rarely in patients with acromegaly. Most cases of acromegaly exhibit high levels of serum insulin-like growth factor-1 (IGF-1. Acromegaly with normal IGF-1 levels is rare and difficult to diagnose. Here, we report a rare case of an acromegalic patient whose first clinical manifestation was severe congestive heart failure, despite normal IGF-1 levels. We diagnosed acromegaly using a glucose-loading growth hormone suppression test. Cardiac function and myocardial hypertrophy improved 6 months after transsphenoidal resection of a pituitary adenoma.
Lee, Hyae Min; Lee, Sun Hee; Yang, In Ho; Hwang, In Kyoung; Hwang, You Cheol; Ahn, Kyu Jeung; Chung, Ho Yeon; Hwang, Hui Jeong; Jeong, In Kyung
The leading cause of morbidity and mortality in patients with acromegaly is cardiovascular complications. Myocardial exposure to excessive growth hormone can cause ventricular hypertrophy, hypertension, arrhythmia, and diastolic dysfunction. However, congestive heart failure as a result of systolic dysfunction is observed only rarely in patients with acromegaly. Most cases of acromegaly exhibit high levels of serum insulin-like growth factor-1 (IGF-1). Acromegaly with normal IGF-1 levels is rare and difficult to diagnose. Here, we report a rare case of an acromegalic patient whose first clinical manifestation was severe congestive heart failure, despite normal IGF-1 levels. We diagnosed acromegaly using a glucose-loading growth hormone suppression test. Cardiac function and myocardial hypertrophy improved 6 months after transsphenoidal resection of a pituitary adenoma.
Wijayaratne, Dilushi Rowena; Arambewela, M H; Dalugama, Chamara; Wijesundera, Dishni; Somasundaram, Noel; Katulanda, Prasad
Acromegaly is an endocrine disorder arising from excessive serum growth hormone levels in adulthood and is characterized by progressive somatic enlargement. Biochemical confirmation is achieved by demonstration of elevated baseline serum growth hormone levels which are not suppressed during an oral glucose tolerance test, and by increased levels of serum insulin-like growth factor-1. The serum insulin-like growth factor-1 level provides an assessment of integrated growth hormone secretion and is recommended for diagnosis, monitoring, and screening of acromegaly. We report a case of a patient with acromegaly secondary to a pituitary microadenoma who presented with low insulin-like growth factor-1. An 83-year-old Sinhalese woman presented to our hospital with an enlarging multinodular goiter. She was observed to have macroglossia, thickened coarse skin, acral enlargement, and newly detected, uncontrolled diabetes. A diagnosis of acromegaly was suspected. She did not complain of recent headaches, vomiting, visual difficulties, or galactorrhea and was clinically euthyroid. Her pulse rate was 84 beats/min, and her blood pressure was 150/90 mmHg. A visual field assessment did not reveal a defect. Her random growth hormone levels were 149 mU/L (acromegaly with a paradoxical rise of growth hormone. Her serum age-specific insulin-like growth factor-1 level was below normal at 124.7 ng/ml (normal range 150-350 ng/ml). Her serum insulin-like growth factor-1 level, measured after glycemic control was achieved with metformin and insulin, was elevated, which is characteristic of acromegaly. Magnetic resonance imaging of her pituitary revealed a pituitary microadenoma. Acromegaly secondary to a growth hormone-secreting pituitary microadenoma was confirmed. Systemic illnesses, including catabolic states, hepatic or renal failure, malnutrition, and diabetes mellitus, are known to decrease insulin-like growth factor-1 levels and may result in false-negative values in patients with
Helen M. Conaglen
Full Text Available Purpose. Excess growth hormone secretion in adults results in acromegaly, a condition in which multiple physical changes occur including bony and soft tissue overgrowth. Over time these changes can markedly alter a person’s appearance. The aim of this study was to compare body image disturbance in patients with acromegaly to those with nonfunctioning pituitary adenomas (NFAs and controls and assess the impact of obesity in these groups. Methods. A cross-sectional survey including quality of life, body image disturbance, anxiety and depression measures, growth hormone, and BMI measurement was carried out. Results. The groups did not differ with respect to body image disturbance. However separate analysis of obese participants demonstrated relationships between mood scales, body image disturbance, and pain issues, particularly for acromegaly patients. Conclusions. While the primary hypothesis that acromegaly might be associated with body image disturbance was not borne out, we have shown that obesity together with acromegaly and NFA can be associated with body image issues, suggesting that BMI rather than primary diagnosis might better indicate whether patients might experience body image disturbance problems.
Freda, Pamela U; Reyes, Carlos M; Conwell, Irene M; Sundeen, Robert E; Wardlaw, Sharon L
The orexigenic peptide, ghrelin, is regulated by acute and chronic nutritional state. Although exogenously administered ghrelin stimulates pituitary GH secretion, little is known about the role of ghrelin in endogenous GH secretion or how high GH and IGF-I levels in acromegaly could affect ghrelin secretion and vice versa. Therefore, we evaluated fasting and post oral glucose tolerance test serum ghrelin levels in 19 patients with active acromegaly at baseline and after either surgery in 9 of these or administration of long-acting octreotide (Sandostatin LAR) in the other 10 patients. After surgical cure, fasting ghrelin rose from 312 +/- 56 pg/ml to 548 +/- 97 pg/ml (P = 0.013). Fasting serum ghrelin levels were higher in all patients after surgery and ranged between 112% and 349% of presurgery levels. Ghrelin levels fell significantly during long-acting octreotide therapy from 447 +/- 34 pg/ml to 206 +/- 15 pg/ml (P acromegaly; lowered serum levels of ghrelin in active acromegaly rise along with the postsurgery normalization of GH and IGF-I and improved insulin resistance. In contrast to surgical therapy, long-acting octreotide therapy persistently suppressed serum ghrelin levels. It remains to be determined whether altered circulating ghrelin concentrations could impact on body composition changes in acromegaly.
Aihara, K; Nishi, Y; Hatano, S; Kihara, M; Ohta, M; Sakoda, K; Uozumi, T; Usui, T
This study was designed to evaluate trace metal metabolism in patients with known abnormalities of human growth hormone (hGH). The mean concentration of zinc in plasma and urine decreased in patients with hGH deficiency after hGH injection, whereas, after adenomectomy, in patients with acromegaly, zinc increased in plasma, remained the same in erythrocytes, and decreased in urine. There was a negative correlation between plasma zinc and serum hGH levels and a positive correlation between urinary zinc excretion and serum hGH levels in acromegaly. In hGH deficiency, the copper content remained unchanged in plasma and erythrocytes and rose in urine after treatment; however, in acromegaly, the copper content increased in plasma and remained unchanged in erythrocytes and urine after surgery. The mean concentration of erythrocyte manganese did not change significantly after treatment in patients with hGH deficiency or acromegaly, but the pre-hGH treatment level of erythrocyte manganese in hGH deficiency was lower than in the controls. Plasma selenium concentrations were decreased in hGH deficiency and increased in acromegaly patients after therapy. These results suggest that hGH affects the metabolism of zinc, copper, manganese, and selenium.
Bozok Cetintas, Vildan; Zengi, Ayhan; Tetik, Asli; Karadeniz, Muammer; Ergonen, Faruk; Kucukaslan, Ali Sahin; Tamsel, Sadik; Kosova, Buket; Sahin, Serap Baydur; Saygılı, Fusun; Eroglu, Zuhal
Acromegaly is a syndrome that results when the pituitary gland produces excess growth hormone after epiphyseal closure at puberty. Usually, subjects with acromegaly exhibit a 2- to 3-fold higher mortality rate from diseases that are associated with cardiovascular complications when compared to the normal population. In this study, we therefore aimed to evaluate whether a well-established cardiovascular risk factor, the Apolipoprotein E (Apo E) genotype, contributes to increased risk of cardiovascular complications in subjects with acromegaly. A total of 102 unrelated acromegaly subjects were prospectively included into this case-control association study and constituted our study group. The study group was comparable by age and gender with 200 unrelated healthy subjects constituting our control group. Genomic DNA was isolated from the peripheral blood leukocytes of all subjects and Apo E genotype (codon 112/158) was assessed by melting temperature analyses after using a real-time PCR protocol. The Apolipoprotein E4 allele was found at a significantly higher frequency in the study group when compared with the control group (P = 0.032). Subjects with the E2 allele, on the other hand, had significantly increased values in body mass index (P = 0.004), waist circumference (P = 0.001), C-reactive protein (CRP) (P acromegaly since it is concurrently present with other cardiovascular risk factors such as the left-side carotid intima media thickness and CRP.
Krug, Sebastian; Boch, Michael; Rexin, Peter; Pfestroff, Andreas; Gress, Thomas; Michl, Patrick; Rinke, Anja
Pulmonary neuroendocrine tumors (NET) form a heterogeneous group of rare diseases. In these tumors, paraneoplastic syndromes have been described to drive the course of the disease, among them acromegaly induced by paraneoplastic secretion of growth hormone-releasing hormone (GHRH). We report the case of a 43 years old patient initially diagnosed with acromegaly accompanied by weight gain and acral enlargement. Subsequently, further diagnostic work-up identified a solitary pulmonary neuroendocrine tumor (NET). Laboratory tests revealed markedly increased growth hormone (GH) and insulin-like growth factor 1 (IGF-1) without GHRH elevation in the absence of pituitary pathologies confirming the paraneoplastic origin of clinical presentation with acromegaly. Curative surgery was performed leading to normalization of the elevated hormone levels and improvement of the clinical symptoms. Immunohistochemically, a typical carcinoid (TC) was seen with low proliferation index and abundant IGF-1 expression. The association of acromegaly and pulmonary NET has only rarely been reported. We present an individual case of paraneoplastic GH- and IGF-1 secretion in a patient with pulmonary NET. Based on their rarity, the knowledge of paraneoplastic syndromes occurring in patients with pulmonary NET such as acromegaly due to paraneoplastic GH- and IGF-1 secretion is mandatory to adequately diagnose and treat these patients.
Full Text Available Hirsuitism though not uncommon (24%, is not considered to be a prominent feature of acromegaly because of its lack of specificity and occurrence. Hirsuitism is very common in women of reproductive age (5-7% and has been classically associated with polycystic ovarian syndrome (PCOS. Twenty-eight year lady with 3 year duration of hirsuitism (Modified Ferriman Gallwey score-24/36 , features of insulin resistance (acanthosis, subtle features of acromegaloidism (woody nose and bulbous lips was diagnosed to have acromegaly in view of elevated IGF-1 (1344 ng/ml; normal: 116-358 ng/ml, basal (45.1 ng/ml and post glucose growth hormone (39.94 ng/ml and MRI brain showing pituitary macroadenoma. Very high serum androstenedione (>10 ng/ml; normal 0.5-3.5 ng/ml, elevated testosterone (0.91 ng/ml, normal <0.8 and normal dehydroepiandrosterone sulphate (DHEAS (284 mcg/dl, normal 35-430 mcg/dl along with polycystic ovaries on ultrasonography lead to diagnosis of associated PCOS. She was also diagnosed to have diabetes. This case presentation intends to highlight that hirsuitism may rarely be the only prominent feature of acromegaly. A lookout for subtle features of acromegaly in all patients with hirsuitism and going for biochemical evaluation (even at the risk of investigating many patients of insulin resistance and acromegloidism may help us pick up more patients of acromegaly at an earlier stage thus help in reducing disease morbidity.
Soszynski, P.; Slowinska-Srzednicka, J.; Zgliczynski, S. (Medical Center for Postgraduate Education, Warsaw (Poland))
Arterial hypertension is common in acromegaly, but the pathogenesis of this complication remains unknown. To determine the role of an endogenous Na,K pump inhibitor/digoxin-like substance (DLS) in the pathogenesis of hypertension in acromegaly 76 subjects: 28 with acromegaly, 20 with essential hypertension and 28 healthy controls were studied. Serum DLS was measured with the use of radioimmunoassay and bioassay by the inhibition of digoxin-sensitive erythrocyte 86-Rb uptake. In acromegaly, the activity of DLS was significantly increased and plasma renin activity decreased in the hypertensive group, as compared with that of the normotensive group and controls. Moreover, DLS was elevated in the low-renin group of essential hypertension, as compared with that of the normal/high-renin group or controls. The activity of DLS correlated positively with mean arterial pressure and negatively with plasma renin activity, but not with growth hormone levels. In conclusion, an endogenous sodium pump inhibitor/digoxin-like substance may play a role in the pathogenesis of low-renin hypertension in acromegaly.
Vazquez-Martinez, Rafael; Martinez-Fuentes, Antonio J; Pulido, Marina R; Jimenez-Reina, Luis; Quintero, Ana; Leal-Cerro, Alfonso; Soto, Alfonso; Webb, Susan M; Sucunza, Nuria; Bartumeus, Frederic; Benito-Lopez, Pedro; Galvez-Moreno, Maria A; Castaño, Justo P; Malagon, Maria M
Rab proteins regulate the sequential steps of intracellular membrane transport. Alterations of these GTPases and their associated proteins are emerging as the underlying cause for several human diseases involving dysregulated secretory activities. Herein we investigated the role of Rab18, which negatively regulates hormone secretion by interacting with secretory granules, in relation to the altered functioning of tumoral pituitary somatotropes causing acromegaly. A total of 18 patients diagnosed with pituitary tumors causing acromegaly (nine patients) or nonfunctioning adenomas (nine patients) underwent endoscopic transsphenoidal surgery. Adenomas were subsequently processed to evaluate Rab18 production in relation to GH secretion. We found that somatotropinoma cells are characterized by a high secretory activity concomitantly with a remarkably reduced Rab18 expression (15%) and protein content levels (30%), as compared with cells from nonfunctioning pituitary adenomas derived from patients with normal or reduced GH plasma levels (100%). Furthermore, immunoelectron microscopy revealed that Rab18 association with the surface of GH-containing secretory granules was significantly lower in somatotropes from acromegalies than nonfunctioning pituitary adenomas. Finally, we provide evidence that modulation of Rab18 gene expression can revert substantially the hypersecretory activity of cells because Rab18 overexpression reduced by 40% the capacity of cells from acromegalies to respond to GHRH stimulation. These results suggest that molecular alterations affecting individual components of the secretory granule traffic machinery can contribute to maintain a high level of GH in plasma. Accordingly, Rab18 constitutes a valuable target as a diagnostic, prognostic, and/or therapeutic tool for human acromegaly.
Full Text Available Abstract Introduction In the patient with acromegaly, pituitary surgery is the therapeutic standard. Despite undergoing surgery, a significant number of patients with acromegaly continue to have uncontrolled growth hormone secretion. These patients require other treatments such as external irradiation and/or drug therapy. Case presentation We present the clinical and laboratory responses to six months of treatment with rosiglitazone in four cases. In all four cases, the patients had persistent growth hormone overproduction despite previous surgical treatment and other conventional therapy. Case 1 is a 57-year-old Caucasian woman, case 2 is a 51-year-old Hispanic man, case 3 is a 32-year-old Hispanic woman, and case 4 is a 36-year-old Hispanic man. In three of these patients, basal and nadir growth hormone and insulin-like growth factor 1 levels were significantly decreased (P P Conclusion Rosiglitazone could be a treatment option in select patients with acromegaly.
Zieliński, Grzegorz; Maksymowicz, Maria; Podgórski, Jan; Olszewski, Włodzimierz T
Double pituitary adenomas are very rare and present up to 1 % of pituitary adenomas in unselected autopsy series and up to 2 % in large surgical series. We report a case of a 47-year-old man presented slight clinical features of acromegaly with 2 years duration. Endocrine evaluation confirmed active acromegaly and revealed adrenocorticotropin hormone-dependent hypercortisolemia. Preoperative magnetic resonance imaging of the pituitary demonstrated clearly separated double microadenomas with different intensity. The patient underwent transsphenoidal surgery and both tumors were completely removed and were fixed separately. The histological and ultrastructural examination confirmed coincidence of the double, clearly separated pituitary adenomas in one gland. Postoperative function of the hypothalamo-hypophyseal axis was normalized. We conclude from this case and a literature review that double endocrinologically active pituitary adenomas leading to acromegaly and Cushing's disease may occur. Additionally, a review of the literature regarding multiple pituitary adenomas has also been performed.
Lindberg-Larsen, Rune; Møller, Niels; Schmitz, Ole
CONTEXT: Pegvisomant is a specific GH receptor antagonist that is able to normalize serum IGF-I concentrations in most patients with acromegaly. The impact of pegvisomant on insulin sensitivity and substrate metabolism is less well described. PATIENTS AND METHODS: We assessed basal and insulin......-stimulated (euglycemic clamp) substrate metabolism in seven patients with active acromegaly before and after 4-wk pegvisomant treatment (15 mg/d) in an open design. RESULTS: After pegvisomant, IGF-I decreased, whereas GH increased (IGF-I, 621 +/- 82 vs. 247 +/- 33 microg/liter, P = 0.02; GH, 5.3 +/- 1.5 vs. 10.8 +/- 3...... vs. 1563 +/- 101 kcal/24 h, P = 0.03), but the rate of lipid oxidation did not change significantly. CONCLUSIONS: 1) Pegvisomant treatment for 4 wk improves peripheral and hepatic insulin sensitivity in acromegaly. 2) This is associated with a decrease in resting energy expenditure, whereas free...
Ueland, Thor; Ebbesen, Ebbe Nils; Thomsen, Jesper Skovhus;
of these growth factors in relation to biomechanical properties in acromegaly. MATERIALS AND METHODS: Trabecular bone biomechanical competence (compression test), apparent density (peripheral quantitative computed tomography, pQCT), and bone matrix contents of calcium (HCl hydrolysis) and IGFs (guanidinium......-HCl extraction) were measured in iliac crest biopsies from 13 patients with active acromegaly (two women and 11 men, aged 21-61 years) and 21 age- and sex-matched controls (four women and 17 men, aged 23-64 years). RESULTS: Trabecular bone pQCT was reduced in acromegalic patients compared with controls (P = 0...... bone content of IGF-I, IGFBP-3, or osteocalcin. However, IGF-II and IGFBP-5 content was decreased (P acromegaly, supporting previous observations...
Full Text Available More than 99% of patients with acromegaly harbor a growth hormone (GH secreting pituitary adenoma. As the time from onset of signs/symptoms to diagnosis of acromegaly is long (symptom onset to diagnosis is often 4-10 years, pituitary adenomas that cause GH excess are often large and are nearly always visible on conventional magnetic resonance imaging (MRI. However, in rare circumstances, acromegalic patients without an ectopic source will not have imaging evidence of a pituitary adenoma. Management of these patients poses special challenge, and once ectopic source of GH/growth-hormone-releasing hormone (GHRH is ruled out, an exploration of pituitary might be useful. We herein report a case of acromegaly with imaging evidence of sellar floor osteoma, but no pituitary adenoma, and negative work up for an ectopic source of GH/GHRH tumor, and on surgical exploration pituitary adenoma could be identified and removed and confirmed on histopathologic examination.
Szcześniak, Dorota; Jawiarczyk-Przybyłowska, Aleksandra; Rymaszewska, Joanna
Acromegaly is a rare and chronic disease, most often caused by a pituitary adenoma. Excessive secretion of the growth hormone (GH) leads to hepatic secretion of insulin-like growth factor-1 (IGF-1), which in turn causes characteristic changes in the patient's appearance, many skeletal deformities and metabolic disorders. In addition to somatic symptoms, acromegalic patients demonstrate psychosocial and personality deficits, as well as common co-occurrence of mental disorders. There are few studies investigating acromegaly in Poland. In recent years, the concept of quality of life has become fundamental to understanding health problems. Studies dealing with acromegaly likewise tend to include assessments of quality of life of patients suffering from this endocrinopathy.
Ramírez-Rentería, Claudia; Hernández-Ramírez, Laura C; Portocarrero-Ortiz, Lesly; Vargas, Guadalupe; Melgar, Virgilio; Espinosa, Etual; Espinosa-de-Los-Monteros, Ana Laura; Sosa, Ernesto; González, Baldomero; Zúñiga, Sergio; Unterländer, Martina; Burger, Joachim; Stals, Karen; Bussell, Anne-Marie; Ellard, Sian; Dang, Mary; Iacovazzo, Donato; Kapur, Sonal; Gabrovska, Plamena; Radian, Serban; Roncaroli, Federico; Korbonits, Márta; Mercado, Moisés
Although aryl hydrocarbon receptor-interacting protein (AIP) mutations are rare in sporadic acromegaly, their prevalence among young patients is nonnegligible. The objectives of this study were to evaluate the frequency of AIP mutations in a cohort of Mexican patients with acromegaly with disease onset before the age of 30 and to search for molecular abnormalities in the AIP gene in teeth obtained from the "Tampico Giant". Peripheral blood DNA from 71 patients with acromegaly (51 females) with disease onset T (p.Arg304Ter), well-known truncating mutation was identified; in one of these two cases and her identical twin sister, the mutation proved to be a de novo event, since neither of their parents were found to be carriers. In the remaining three patients, new mutations were identified: a frameshift mutation (c.976_977insC, p.Gly326AfsTer), an in-frame deletion (c.872_877del, p.Val291_Leu292del) and a nonsense mutation (c.868A > T, p.Lys290Ter), which are predicted to be pathogenic based on in silico analysis. Patients with AIP mutations tended to have an earlier onset of acromegaly and harboured larger and more invasive tumours. A previously described genetic variant of unknown significance (c.869C > T, p.Ala299Val) was identified in DNA from the Tampico Giant. The prevalence of AIP mutations in young Mexican patients with acromegaly is similar to that of European cohorts. Our results support the need for genetic evaluation of patients with early onset acromegaly.
Bihan, Hélène; Espinosa, Consuelo; Valdes-Socin, Hernan; Salenave, Sylvie; Young, Jacques; Levasseur, Suzanne; Assayag, Patrick; Beckers, Albert; Chanson, Philippe
Cardiovascular complications are a major cause of morbidity and mortality in patients with acromegaly. Normalization of GH secretion is associated with an improvement in structural and functional cardiac abnormalities. However, the long-term cardiac effects of treatment for acromegaly have not been studied in patients who have already developed chronic congestive heart failure (CHF). We reviewed the charts of 330 consecutive patients with acromegaly treated in two French and Belgian centers since 1985. Ten patients with both acromegaly and CHF (eight men, two women, mean age 49.7 yr) were studied retrospectively. One of them was excluded because CHF was due to severe aortic stenosis.CHF (New York Heart Association stages III-IV and echocardiography showing dilated hypokinetic cardiomyopathy with left ventricular systolic dysfunction and a left ventricular ejection fraction less than 45%) was diagnosed before, concomitantly, or after acromegaly in, respectively, two, five, and two patients. Three patients were referred with terminal heart failure requiring transplantation.One patient had transient CHF associated with a hypertensive crisis. The other eight patients had symptomatic chronic CHF. Control of GH hypersecretion failed, totally or partially, in three patients: one had a long-term survival, and the two others died at 1 and 5 yr. Good GH control was achieved in five patients: four of these are still alive 2-16 yr after diagnosis of CHF, their clinical status is stable or improved, and their quality of life is good. Overall, the 1- and 5-yr mortality (or transplantation) rates for patients with chronic symptomatic CHF were 25% (2 of 8 patients) and 37.5% (3 of 8 patients), respectively. In conclusion, less than 3% of acromegalic patients developed CHF in this study. Although effective treatment of acromegaly improved short-term cardiovascular status, its impact on long-term survival is questionable.
Matsumoto, Ryusaku; Fukuoka, Hidenori; Iguchi, Genzo; Odake, Yukiko; Yoshida, Kenichi; Bando, Hironori; Suda, Kentaro; Nishizawa, Hitoshi; Takahashi, Michiko; Yamada, Shozo; Ogawa, Wataru; Takahashi, Yutaka
Objective Patients with acromegaly exhibit reduced life expectancy and increased prevalence of age-related diseases, such as diabetes, hypertension, and cardiovascular disease. However, the underlying mechanism has not been fully elucidated. Telomere shortening is reportedly associated with reduced life expectancy and increased prevalence of these age-related diseases. Methods We measured telomere length in patients with acromegaly using quantitative PCR method. The effect of GH and IGF-I on telomere length and cellular senescence was examined in human skin fibroblasts. Results Patients with acromegaly exhibited shorter telomere length than age-, sex-, smoking-, and diabetes-matched control patients with non-functioning pituitary adenoma (0.62 ± 0.23 vs. 0.75 ± 0.35, respectively, P = 0.047). In addition, telomere length in acromegaly was negatively correlated with the disease duration (R2 = 0.210, P = 0.003). In vitro analysis revealed that not GH but IGF-I induced telomere shortening in human skin fibroblasts. Furthermore, IGF-I-treated cells showed increased senescence-associated β-galactosidase activity and expression of p53 and p21 protein. IGF-I-treated cells reached the Hayflick limit earlier than GH- or vehicle-treated cells, indicating that IGF-I induces cellular senescence. Conclusion Shortened telomeres in acromegaly and cellular senescence induced by IGF-I can explain, in part, the underlying mechanisms by which acromegaly exhibits an increased morbidity and mortality in association with the excess secretion of IGF-I. PMID:26448623
Dal, Jakob; Feldt-Rasmussen, Ulla; Andersen, Marianne; Kristensen, Lars Ø; Laurberg, Peter; Pedersen, Lars; Dekkers, Olaf M; Sørensen, Henrik Toft; Jørgensen, Jens Otto L
Valid data on acromegaly incidence, complications and mortality are scarce. The Danish Health Care System enables nationwide studies with complete follow-up and linkage among health-related databases to assess acromegaly incidence, prevalence, complications and mortality in a population-based cohort study. All incident cases of acromegaly in Denmark (1991-2010) were identified from health registries and validated by chart review. We estimated the annual incidence rate of acromegaly per 10(6) person-years (py) with 95% confidence intervals (95% CIs). For every patient, 10 persons were sampled from the general population as a comparison cohort. Cox regression and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used. Mean age at diagnosis (48.7 years (CI: 95%: 47.2-50.1)) and annual incidence rate (3.8 cases/10(6) persons (95% CI: 3.6-4.1)) among the 405 cases remained stable. The prevalence in 2010 was 85 cases/10(6) persons. The patients were at increased risk of diabetes mellitus (HR: 4.0 (95% CI: 2.7-5.8)), heart failure (HR: 2.5 (95% CI: 1.4-4.5)), venous thromboembolism (HR: 2.3 (95% CI: 1.1-5.0)), sleep apnoea (HR: 11.7 (95% CI: 7.0-19.4)) and arthropathy (HR: 2.1 (95% CI: 1.6-2.6)). The complication risk was also increased before the diagnosis of acromegaly. Overall mortality risk was elevated (HR: 1.3 (95% CI: 1.0-1.7)) but uninfluenced by treatment modality. (i) The incidence rate and age at diagnosis of acromegaly have been stable over decades, and the prevalence is higher than previously reported. (ii) The risk of complications is very high even before the diagnosis. (iii) Mortality risk remains elevated but uninfluenced by mode of treatment. © 2016 European Society of Endocrinology.
Sardella, Chiara; Cappellani, Daniele; Urbani, Claudio; Manetti, Luca; Marconcini, Giulia; Tomisti, Luca; Lupi, Isabella; Rossi, Giuseppe; Scattina, Ilaria; Lombardi, Martina; Di Bello, Vitantonio; Marcocci, Claudio; Martino, Enio; Bogazzi, Fausto
The primary objective of this study is to identify the predictors of comorbidities and major adverse cardiovascular events (MACE) that can develop after diagnosis of acromegaly. The role of therapy for acromegaly in the event of such complications was also evaluated. Retrospective cohort study was conducted on 200 consecutive acromegalic patients in a tertiary referral center. The following outcomes were evaluated: diabetes, hypertension and MACE. Each patient was included in the analysis of a specific outcome, unless they were affected when acromegaly was diagnosed, and further classified as follows: (i) in remission after adenomectomy (Hx), (ii) controlled by somatostatin analogues (SSA) (SSAc) or (iii) not controlled by SSA (SSAnc). Data were evaluated using Cox regression analysis. After diagnosis of acromegaly, diabetes occurred in 40.8% of patients. The SSAnc group had a three-fold higher risk of diabetes (HR: 3.32, P = 0.006), whereas the SSAc group had a 1.4-fold higher risk of diabetes (HR: 1.43, P = 0.38) compared with the Hx group. Hypertension occurred in 35.5% of patients, after diagnosis. The determinants of hypertension were age (HR: 1.06, P = 0.01) and BMI (HR: 1.05, P = 0.01). MACE occurred in 11.8% of patients, after diagnosis. Age (HR: 1.09, P = 0.005) and smoking habit (HR: 5.95, P = 0.01) were predictors of MACE. Conversely, therapy for acromegaly did not influence hypertension or MACE. After diagnosis of acromegaly, control of the disease (irrespective of the type of treatment) and lifestyle are predictors of comorbidities and major adverse cardiovascular events. © 2016 European Society of Endocrinology.
Anterior hypopituitarism is a common complication of head trauma, with a prevalence of 30% to 70% among long-term survivors. This is a much higher frequency than previously thought and suggests that most cases of post-traumatic hypopituitarism remain undiagnosed and untreated. Symptoms of hypopituitarism are very unspecific and very similar to those in traumatic brain injury patients in general, which makes hypopituitarism difficult to diagnose. The factors that predict the likelihood of developing hypopituitarism following traumatic brain injury remain poorly understood. The incidence of a specific hormone deficiency is variable, with growth hormone deficiency reported in 18% to 23% of cases. A 23-year-old Hispanic man with a 2-year history of hypertension and diabetes presented with severe closed-head trauma producing diffuse axonal injury, subarachnoid hemorrhage and a brain concussion. A computed tomography scan showed a pituitary macroadenoma. The patient has clinical features of acromegaly and gigantism without other pituitary hyperfunctional manifestations or mass effect syndrome. A short-term post-traumatic laboratory test showed high levels of insulin like growth factor 1 and growth hormone, which are compatible with a growth hormone-producing pituitary tumor. At the third month post-trauma, the patient's levels of insulin like growth factor 1 had decreased to low normal levels, with basal low levels of growth hormone. A glucose tolerance test completely suppressed the growth hormone, which confirmed resolution of acromegaly. An insulin tolerance test showed lack of stimulation of growth hormone and cortisol, demonstrating hypopituitarism of both axes. Even though hypopituitarism is a frequent complication of traumatic brain injury, there are no reports in the literature, to the best of my knowledge, of patients with hyperfunctional pituitary adenomas, such as growth hormone-producing adenoma, that resolved after head trauma. A clear protocol has not yet
Mykytyuk, M R
Examined 76 (26 men and 50 women) patients with active acromegaly aged 20 to 70 years, average age (48.22 ± 12.19). Echocardiographic signs of hypertrophy of the left ventricular (LVH) revealed by 63.2% of patients, including 46%--concentric LVH. Found that high levels of pituitary growth hormone (GH) and insulin like growth factor-1 (IGF-1) were independent predictors of LVH. Influence of GH and IGF-1 on the formation of LVH-mediated through anthropometric parameters and levels of systolic and diastolic blood pressure, which are predictors in patients with acromegaly LVH.
Castañeda Pascual, M; Navarro García, C; Batllori Gastón, M; Anadón Senac, María P; Arrondo Nicolás, J; Martín Vizcaíno, M P
An excess of growth hormone is responsible for the phenotypical characteristics of acromegaly. Tissue hypertrophy and growth also affect the airway, potentially making perioperative management difficult. If tests to foresee the likelihood of difficult airway have limitations affecting their sensitivity, specificity and predictive value even in the normal population, their reliability in patients with acromegaly is still more doubtful. At this time, videoassisted or optical laryngoscopes can offer a way to facilitate intubation in these patients. We report 3 cases in which the AirTraq optical laryngoscope was used to gain a full view of the vocal cords in acromegalic patients scheduled for pituitary surgery by the transsphenoidal route.
Jungheim, K; Badenhoop, K; Ottmann, O G; Usadel, K H
Hypothalamic disease often affects the patients' personality and this also applies to pituitary tumors with suprasellar extension. We report on a patient with a 12-year history of recurrent acromegaly, treated with three transphenoidal operations, single field radiation therapy and bromocriptine/octreotide administration. During the course of follow-up she presented with self-inflicted anemia and Kleine-Levin syndrome (hypersomnia, hyperphagia and hypersexuality). Furthermore, she developed post-radiation necrosis within the right temporal lobe. Whether her neurological and personality disorders result - at least partially - from the acromegaly or the temporal lobe necrosis remains unclear.
El Aziz, Siham; Chadli, Asma; Obbiba, Atika; El Ghomari, Hassan; Farouqi, Ahmed
A 56-years-old woman was referred to our unit for partially treated acromegaly. She had a high level of insulin growth factor. She did not complain of any pulmonary symptoms and was a non-smoker. Physical examination revealed clinical features of acromegaly. She had a 13 mm pituitary adenoma and was proposed for surgical intervention. Her chest X-ray showed a right paracardiac tumor. Computed tomography scan revealed a large right-sided fowler tumor. Pituitary surgery was cancelled and lobect...
Silverstein, Julie M
Cushing's disease (CD) and acromegaly are characterized by excessive hormone secretion resulting in comorbidities such as impaired glucose metabolism, diabetes and hypertension. Pasireotide is a new-generation, multireceptor-targeted somatostatin receptor ligand approved for CD (subcutaneous [SC] injection formulation) and acromegaly (long-acting release [LAR] formulation). In clinical studies of pasireotide, hyperglycemia-related adverse events (AEs) were frequently observed. This review highlights differences in reported rates of hyperglycemia in pasireotide trials and discusses risk factors for and management of pasireotide-associated hyperglycemia. Clinical trials evaluating pasireotide in patients with CD or acromegaly were reviewed. The frequency of hyperglycemia-related AEs was lower in patients with acromegaly treated with pasireotide LAR (57.3-67.0 %) than in patients with CD treated with pasireotide SC (68.4-73.0 %). Fewer patients with acromegaly treated with pasireotide LAR discontinued therapy because of hyperglycemia-related AEs (Colao et al. in J Clin Endocrinol Metab 99(3):791-799, 2014, 3.4 %; Gadelha et al. in Lancet Diabetes Endocrinol 2(11):875-884, 2014, 4.0 %) than did patients with CD treated with pasireotide SC (Boscaro et al. in Pituitary 17(4):320-326, 2014, 5.3 %; Colao et al. in N Engl J Med 366(10):914-924, 2012, 6.0 %). Hyperglycemia-related AEs occurred in 40.0 % of patients with acromegaly treated with pasireotide SC, and 10.0 % discontinued treatment because of hyperglycemia. Ongoing studies evaluating pasireotide LAR in patients with CD and management of pasireotide-induced hyperglycemia in patients with CD or acromegaly (ClinicalTrials.gov identifiers NCT01374906 and NCT02060383, respectively) will address these key safety issues. Disease pathophysiology, drug formulation, and physician experience potentially influence the differences in reported rates of pasireotide-induced hyperglycemia in CD and acromegaly
Hara, Tomomi; Kanasaki, Haruhiko; Oride, Aki; Moriyama, Masayuki; Kyo, Satoru
We report a case of a woman who was incidentally diagnosed with acromegaly after referral for prolonged post-partum amenorrhea. A 25-year-old woman, gravida 2 para 1, had a normal transvaginal delivery and breastfeeding had been discontinued more than a year after delivery. Thereafter, spontaneous menstruation did not restart and she underwent hormonal therapy. Subsequently, she was referred to our university hospital for prolonged amenorrhea. Hormonal examination revealed severe hypogonadotropic hypogonadism (luteinizing hormone 0.5 mIU/mL, follicle-stimulating hormone acromegaly. © 2016 Japan Society of Obstetrics and Gynecology.
Malgo, F; Hamdy, N A T; Rabelink, T J; Kroon, H M; Claessen, K M J A; Pereira, A M; Biermasz, N R; Appelman-Dijkstra, N M
Acromegaly is a rare disease caused by excess growth hormone (GH) production by the pituitary adenoma. The skeletal complications of GH and IGF-1 excess include increased bone turnover, increased cortical bone mass and deteriorated microarchitecture of trabecular bone, associated with a high risk of vertebral fractures in the presence of relatively normal bone mineral density (BMD). We aimed to evaluate tissue-level properties of bone using impact microindentation (IMI) in well-controlled patients with acromegaly aged ≥18 years compared to 44 controls from the outpatient clinic of the Centre for Bone Quality. In this cross-sectional study, bone material strength index (BMSi) was measured in 48 acromegaly patients and 44 controls with impact microindentation using the osteoprobe. Mean age of acromegaly patients (54% male) was 60.2 years (range 37.9-76.5), and 60.5 years (range 39.8-78.6) in controls (50% male). Patients with acromegaly and control patients had comparable BMI (28.2 kg/m(2) ± 4.7 vs 26.6 kg/m(2) ± 4.3, P = 0.087) and comparable BMD at the lumbar spine (1.04 g/cm(2) ± 0.21 vs 1.03 g/cm(2) ± 0.13, P = 0.850) and at the femoral neck (0.84 g/cm(2) ± 0.16 vs 0.80 g/cm(2) ± 0.09, P = 0.246). BMSi was significantly lower in acromegaly patients than that in controls (79.4 ± 0.7 vs 83.2 ± 0.7; P acromegaly after reversal of long-term exposure to pathologically high GH and IGF-1 levels. Our findings also suggest that methods other than DXA should be considered to evaluate bone fragility in patients with acromegaly. © 2017 European Society of Endocrinology.
Madsen, Michael; Fisker, Sanne; Feldt-Rasmussen, Ulla;
OBJECTIVE: To investigate whether pegvisomant treatment in acromegaly induces gradual elevations in endogenous serum growth hormone (GH) levels and whether serum pegvisomant levels predict the therapeutic outcome. PATIENTS AND METHODS: Seventeen patients (6 women), mean age 46·3 years (range: 23...... correlated with baseline growth hormone levels, whereas no associations between serum pegvisomant and either dose, gender, age or body weight were found. CONCLUSIONS: (1) Serum GH levels increased initially, but remained stable during prolonged pegvisomant treatment in patients with acromegaly, (2) serum...
Maiza, Jean-Christophe; Castillo-Ros, Stéphane; Matta, Maria; Bennet, Antoine; Caron, Philippe
We present the case of a 51-year old female patient with acromegaly that was resistant to somatostatin analogs and dopamine agonists. The patient was diagnosed with breast cancer requiring treatment with the anti-estrogen tamoxifen. Prior to initiating the treatment with tamoxifen, the IGF-I level was very high at 415% of the upper limit of normal for the patient's age and sex. During the tamoxifen treatment, the level of IGF-I dropped spectacularly down to normal levels. This observation highlights the effect of an anti-estrogen treatment in certain female patients with acromegaly.
Full Text Available In patients with active acromegaly after pituitary surgery, somatostatin analogues are effective in controlling the disease and can even be curative in some cases. After treatment discontinuation, the likelihood of disease recurrence is high. However, a small subset of patients remains symptom-free after discontinuation, with normalized growth hormone (GH and insulin-like growth factor (IGF1 levels. The characteristics of patients most likely to achieve sustained remission after treatment discontinuation are not well understood, although limited evidence suggests that sustained remission is more likely in patients with lower GH and IGF1 levels before treatment withdrawal, in those who respond well to low-dose treatment, in those without evidence of adenoma on an MRI scan and/or in patients who receive long-term treatment. In this report, we describe the case of a 56-year-old female patient treated with lanreotide Autogel for 11 years. Treatment was successfully discontinued, and the patient is currently disease-free on all relevant parameters (clinical, biochemical and tumour status. The successful outcome in this case adds to the small body of literature suggesting that some well-selected patients who receive long-term treatment with somatostatin analogues may achieve sustained remission.
Pumarino, H; Oviedo, S; Michelsen, H; Campino, C
50 patients with autonomous growth hormone excess (48 with adult acromegaly and 2 with gigantism) were studied between 1966 to 1986 (2.38 pts/year). Characteristic clinical presentation, an increase in growth hormone (GH) uninhibited by glucose, and/or hyperphosphemia and hyperhydroxiprolinuria were present in all patients. No cases of hypercalcemia were recorded. Phosphemia was increased in 55.8%, alkaline phosphatases in 61.7%, calciuria in 26.9% and hydroxyprolinuria in 74.2% of the patients. Basal GH was over 5 ng/ml (89.9 DS +/- 170.9) in 42 pts, and in 37 was not suppressed after glucose administration, 38% had an increased (paradoxical response) and 62% a flat response (less than 50% change of basal values). TRH test was performed in 14 patients, 8 presented an increase in GH titer. Hyperprolactinemia was seen in 4 of 12 patients in whom this hormone was measured. The size of the sella turcica was increased in 93%, and although the larger sellar size correlated to higher levels of GH, correlation was not significant. 20% of the pts had rheumatological disease, 14% goiter, 12% cardiac disease, 26.5% had diastolic hypertension and 4% renal lithiasis (hypercalciuric pts). 38% had hyperglycemia with a diabetic glucose tolerance test and 18% had non-diabetic abnormal glucose tolerance test.
Dusková, J; Marek, J; Povýsil, C
Woman 75-year-old treated 30 years for syndrome of acromegaly refused pituitary surgery and irradiation. Five years and nine months before death she had a colon carcinoma successfully removed. Multinodular hyperfunctional goitre was treated with carbimazole. For six last years of life corticosteroids were given as a replacement therapy. Her cause of death was the heart failure due to acromegalic heart disease. In autopsy a large intrasellar and extrasellar pituitary adenoma without rests of nonneoplastic tissue was found. Nevertheless the target peripheral endocrine glands except ovaries, were not atrophic. A multinodular goitre and diffuse adrenocortical hyperplasia were revealed. Histology, and immunohistochemistry demonstrated that mot neoplastic cells were producing GH and ACTH, dispersly Prl, scattered cells were positive for beta-subunit of FSH, LH, TSH. Electron microscopy proved most of the cells to be densely granulated. We classify the adenoma according to the newly proposed WHO pituitary tumours classification (1) as plurihormonal, hyperfunctional, extrasellar, typical adenoma from densely granulated cells. We conclude that in plurihormonal adenomas with dominant (in the case referred acromegalic) symptomatology the additional hormonal production should be monitored as a possible source of important complications.
Cadieux, R J; Kales, A; Santen, R J; Bixler, E O; Gordon, R
Two acromegalic patients presented with the additional complaint of excessive daytime sleepiness. Subsequent sleep laboratory evaluation revealed that each patient had concurrent obstructive sleep apnea. In each patient, endoscopic examination of the upper airway revealed that on inspiration, the soft tissue of the posterior and lateral hypopharynx invaginated into the laryngeal vestibule before any posterior movement of the tongue. Neither enlargement of the tongue nor in movement in relation to respiration appeared to be the primary factors in the etiology of the upper airway obstruction. After tracheostomy, both the obstructive sleep apnea and excessive daytime sleepiness were eliminated. Our case reports indicate that the treatment and prognosis of patients with acromegaly are affected when sleep apnea is concurrently diagnosed. When a patient is suspected of being acromegalic and also complains of excessive daytime sleepiness, obtaining a through sleep history from the patient as well as from the bed partner is essential. If sleep apnea is then diagnosed, a tracheostomy should be considered an initial and continuing part of the overall treatment plan.
Khaleeli, A A; Levy, R D; Edwards, R H; McPhail, G; Mills, K R; Round, J M; Betteridge, D J
A study of the neuromuscular features of acromegaly was performed in six patients. Clinical assessment was supplemented by quadriceps force measurements, plasma creatine kinase (CK) activities, electromyography (EMG) and nerve conduction studies. Muscle mass was measured by urinary creatinine/height indices (CHI) and cross sectional area (CSA) of thighs and calves on computed tomography. Quadriceps force/unit cross sectional area was derived. Needle biopsies of vastus lateralis were studied by histochemical and ultrastructural methods. Mean fibre area (MFA) and fibre type proportions were measured. Most of the subjects studied had muscle pain and proximal muscle weakness confirmed by quadriceps force measurements. This occurred in the absence of muscle wasting, as shown by cross sectional area measurements and normal or raised creatinine/height indices. "Myopathic" features were demonstrated by needle biopsy in half the patients and occasionally by electromyography and raised plasma creatine kinase activity. Abnormalities on needle biopsy included variation in fibre size, type 2 fibre atrophy and large type 1 MFA relative to type 2 MFA. Electronmicroscopy showed the non-specific findings of increased glycogen accumulation, excess lipofuscin pigment and myofilament loss.
Full Text Available Acromegaly is a complex disease that requires the intervention of a multidisciplinary team. The most frequent clinical manifestations are growing of distal parts of the body and some areas of the face. Patients may also present arterial hypertension, diabetes mellitus, colonic polyps, cardiomegaly, neurological and endocrine changes secondary to the presence of a GH-secreting tumor in pituitary or extrapituitary origin, or eutopic hypothalamic GHRH hypersecretion and peripheral GHRH hypersecretion. Surgery is the first treatment used for most patients, regardless of the cause. In the great majority of cases, pituitary tumor can be removed through a transsphenoidal approach. Craniotomy is reserved for those cases with giant tumors, particularly when they grow toward the middle or posterior cranial fossa. Best surgical results are obtained when the tumor is confined into the sella turcica or if it has a regular suprasellar extension. When the disease cannot be controlled with surgery, medical treatment is indicated. Somatostatin analogues are included as the first line of medication, followed by dopamine agonist and growth hormone receptors antagonists. Radiation therapy can be also indicated in two main forms for residual tumor with medically refractory patients: radiosurgery for small tumors or fractionated stereotactic radiotherapy for larger ones.
De Menis, E; Giustina, A; Colao, A; Degli Uberti, E; Ghigo, E; Minuto, F; Bogazzi, F; Drigo, R; Cattaneo, A; Aimaretti, G
In 2007 the Italian COM.E.T.A. (COMorbidities Evaluation and Treatment in Acromegaly) study group started to assess the application in a clinical setting of the Versailles criteria for management of acromegaly complications by a first questionnaire focusing on cardiovascular co-morbidities. A further questionnaire on sleep apnea syndrome (SAS) was delivered by the COM.E.T.A. study group to 107 endocrine centers in Italy. The results of our survey suggest that SAS is a well-known comorbidity even if its estimated prevalence is lower than in the literature. Polysomnography is the preferred tool for diagnosis. Control of SAS is considered relevant both for quality of life and co-morbidities. Continuous positive airway pressure is the cornerstone of therapy, but patients' acceptance may be critical. Control of GH/IGF-I secretion is important to improve SAS. Management of SAS requires cooperation between specialists.
Kyriakakis, Nikolaos; Trouillas, Jacqueline; Dang, Mary N; Lynch, Julie; Belchetz, Paul; Korbonits, Márta
Summary A male patient presented at the age of 30 with classic clinical features of acromegaly and was found to have elevated growth hormone levels, not suppressing during an oral glucose tolerance test. His acromegaly was originally considered to be of pituitary origin, based on a CT scan, which was interpreted as showing a pituitary macroadenoma. Despite two trans-sphenoidal surgeries, cranial radiotherapy and periods of treatment with bromocriptine and octreotide, his acromegaly remained active clinically and biochemically. A lung mass was discovered incidentally on a chest X-ray performed as part of a routine pre-assessment for spinal surgery 5 years following the initial presentation. This was confirmed to be a bronchial carcinoid tumour, which was strongly positive for growth hormone-releasing hormone (GHRH) and somatostatin receptor type 2 by immunohistochemistry. The re-examination of the pituitary specimens asserted the diagnosis of pituitary GH hyperplasia. Complete resolution of the patient’s acromegaly was achieved following right lower and middle lobectomy. Seventeen years following the successful resection of the bronchial carcinoid tumour the patient remains under annual endocrine follow-up for monitoring of the hypopituitarism he developed after the original interventions to his pituitary gland, while there has been no evidence of active acromegaly or recurrence of the carcinoid tumour. Ectopic acromegaly is extremely rare, accounting for <1% of all cases of acromegaly. Our case highlights the diagnostic challenges differentiating between ectopic acromegaly and acromegaly of pituitary origin and emphasises the importance of avoiding unnecessary pituitary surgery and radiotherapy. The role of laboratory investigations, imaging and histology as diagnostic tools is discussed. Learning points: Ectopic acromegaly is rare, accounting for less than 1% of all cases of acromegaly. Ectopic acromegaly is almost always due to extra-pituitary GHRH secretion
Ilter, A; Kırış, A; Kaplan, Ş; Kutlu, M; Şahin, M; Erem, C; Civan, N; Kangül, F
The aim of this study was to evaluate atrial electromechanical delay (EMD), P wave dispersion (Pwd), and left atrial (LA) mechanical functions in patients with active acromegaly. Twenty-three patients with active acromegaly and 27 age- and sex-matched controls were included in this study. All atrial electromechanical interval parameters (PA lateral, PA septum, PA tricuspid, interatrial EMD, intra-LA EMD, and intra-right atrial EMD) were measured from mitral lateral annulus, mitral septal annulus, and right ventricular tricuspid annulus by tissue Doppler imaging. LA volumes were measured by the disk method in the apical four-chamber view and were indexed to the body surface area. Mechanical function parameters of LA were calculated. Pwd was performed by 12-lead electrocardiograms. Atrial electromechanical intervals (PA lateral, PA septum, PA tricuspid, interatrial EMD, intra-LA EMD, and intra-right atrial EMD) and Pwd were similar between patients with acromegaly and control subjects (all p > 0.05). LA volumes (maximum, minimum, and presystolic) and LA mechanical functions were not significantly different between the groups (all p > 0.05). Additionally, serum levels of growth hormone and insulin-like growth factor-1 were not correlated with atrial electromechanical parameters and LA mechanical functions. Atrial electrical conduction times were not prolonged and LA mechanical functions were not impaired in patients with active acromegaly compared with controls. And the prevalence of supraventricular arrhythmia risk may not increase in this population.
Biermasz, Nienke R; Roelfsema, Ferdinand; Pereira, Alberto M; Romijn, Johannes A
The introduction of effective pharmacological treatments has changed the management of acromegaly. However, chronic, life-long treatment with somatostatin analogues and/or growth hormone receptor antagonists is very expensive. We estimated the costs of treatment algorithms to control acromegaly from a Dutch perspective. We used the following assumptions: after the diagnosis of acromegaly there is a mean remaining lifespan of approximately 33 years; the success rates of surgery and somatostatin analogues in controlling the disease are approximately 60%; and the lifelong costs of different algorithms to control acromegaly in 100 patients ranged from 43 million euros (primary surgery and secondary somatostatin analogues) to 57 million euros (primary somatostatin analogues and secondary surgery) and even reached 95 million euros (medical treatment only). In algorithms that include trans-sphenoidal surgery, the lifetime treatment costs are almost 46-59% cheaper per 100 patients than in algorithms with medical treatment but without trans-sphenoidal surgery. Algorithms with primary surgery and secondary somatostatin analogs are 30% cheaper per 100 patients than algorithms with primary somatostatin analogues and secondary surgery. Per 100 patients, algorithms including lanreotide Autogel are 14-34% more expensive than algorithms including octreotide long-acting release. These life-long costs should be taken into consideration when making choices between treatment algorithms.
WANG Xian-ling; DOU Jing-tao; L(U) Zhao-hui; ZHONG Wen-wen; BA Jian-ming; JIN Du; LU Ju-ming; PAN Chang-yu; MU Yi-ming
Background Subclinical apoplexy of pituitary functional adenoma can cause spontaneous remission of hormone hypersecretion.The typical presence of pituitary growth hormone (GH) adenoma is gigantism and/or acromegaly.We investigated the clinical characteristics of patients with spontaneous partial remission of acromegaly or gigantism due to subclinical apoplexy of GH adenoma.Methods Six patients with spontaneous remission of acromegaly or gigantism were enrolled.The clinical characteristics,endocrinological evaluation and imageological characteristics were retrospectively analyzed.Results In these cases,the initial clinical presences were diabetes mellitus or hypogonadism.No abrupt headache,vomiting,visual function impairment,or conscious disturbance had ever been complained of.The base levels of GH and insulin growth factor-1 (IGF-1) were normal or higher,but nadir GH levels were all still ＞1 μg/L in 75 g oral glucose tolerance test.Magnetic resonance imaging detected enlarged sella,partial empty sella and compressed pituitary.The transsphenoidal surgery was performed in 2 cases,and the other patients were conservatively managed.All the patients were in clinical remission.Conclusions When the clinical presences,endocrine evaluation,biochemical examination and imageology indicate spontaneous remission of GH hypersecretion in patients with gigantism or acromegaly,the diagnosis of subclinical apoplexy of pituitary GH adenoma should be presumed.To these patients,conservative therapy may be appropriate.
Thuesen, L; Christensen, S E; Weeke, J; Orskov, H; Henningsen, P
Cardiac function was studied by echocardiography in 12 patients with active acromegaly and in 12 age- and sex-matched healthy control subjects. None of the patients had cardiovascular diseases or other endocrine diseases than acromegaly. The patients had a mean age of 39 +/- 5 years and were short-term acromegalic with a mean duration of disease of 6 +/- 3 years. Mean left ventricular mass was 163 +/- 43 g/m2 in the acromegalic group versus 120 +/- 24 g/m2 in the control group. Preload (the diastolic diameter of the left ventricle) was within normal limits, while afterload (end-systolic meridional wall stress) was significantly decreased in the acromegalic group. Myocardial contractility assessed as fractional shortening of the left ventricle was 39.9 +/- 3.6% in the acromegalic group versus 32.9 +/- 5.1% in the control group, and cardiac output was increased by 52% in the acromegalic group because of increased heart rate and stroke volume. We suggest that augmented peripheral blood flow is responsible for the condition of cardiac hyperkinesia in short-term acromegaly and involved in the development of hypertension, which is a frequent complication of long-term acromegaly.
Wang, Xian-Ling; Dou, Jing-Tao; Lü, Zhao-Hui; Zhong, Wen-Wen; Ba, Jian-Ming; Jin, Du; Lu, Ju-Ming; Pan, Chang-Yu; Mu, Yi-Ming
Subclinical apoplexy of pituitary functional adenoma can cause spontaneous remission of hormone hypersecretion. The typical presence of pituitary growth hormone (GH) adenoma is gigantism and/or acromegaly. We investigated the clinical characteristics of patients with spontaneous partial remission of acromegaly or gigantism due to subclinical apoplexy of GH adenoma. Six patients with spontaneous remission of acromegaly or gigantism were enrolled. The clinical characteristics, endocrinological evaluation and imageological characteristics were retrospectively analyzed. In these cases, the initial clinical presences were diabetes mellitus or hypogonadism. No abrupt headache, vomiting, visual function impairment, or conscious disturbance had ever been complained of. The base levels of GH and insulin growth factor-1 (IGF-1) were normal or higher, but nadir GH levels were all still > 1 µg/L in 75 g oral glucose tolerance test. Magnetic resonance imaging detected enlarged sella, partial empty sella and compressed pituitary. The transsphenoidal surgery was performed in 2 cases, and the other patients were conservatively managed. All the patients were in clinical remission. When the clinical presences, endocrine evaluation, biochemical examination and imageology indicate spontaneous remission of GH hypersecretion in patients with gigantism or acromegaly, the diagnosis of subclinical apoplexy of pituitary GH adenoma should be presumed. To these patients, conservative therapy may be appropriate.
Radian, Serban; Diekmann, Yoan; Gabrovska, Plamena; Holland, Brendan; Bradley, Lisa; Wallace, Helen; Stals, Karen; Bussell, Anna-Marie; McGurren, Karen; Cuesta, Martin; Ryan, Anthony W; Herincs, Maria; Hernández-Ramírez, Laura C; Holland, Aidan; Samuels, Jade; Aflorei, Elena Daniela; Barry, Sayka; Dénes, Judit; Pernicova, Ida; Stiles, Craig E; Trivellin, Giampaolo; McCloskey, Ronan; Ajzensztejn, Michal; Abid, Noina; Akker, Scott A; Mercado, Moises; Cohen, Mark; Thakker, Rajesh V; Baldeweg, Stephanie; Barkan, Ariel; Musat, Madalina; Levy, Miles; Orme, Stephen M; Unterländer, Martina; Burger, Joachim; Kumar, Ajith V; Ellard, Sian; McPartlin, Joseph; McManus, Ross; Linden, Gerard J; Atkinson, Brew; Balding, David J; Agha, Amar; Thompson, Chris J; Hunter, Steven J; Thomas, Mark G; Morrison, Patrick J; Korbonits, Márta
The aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304(*) (or p.R304(*) ; NM_003977.3:c.910C>T, p.Arg304Ter) identified in Northern Ireland (NI) predisposes to acromegaly/gigantism; its population health impact remains unexplored. We measured R304(*) carrier frequency in 936 Mid Ulster, 1,000 Greater Belfast (both in NI) and 2,094 Republic of Ireland (ROI) volunteers and in 116 NI or ROI acromegaly/gigantism patients. Carrier frequencies were 0.0064 in Mid Ulster (95%CI = 0.0027-0.013; P = 0.0005 vs. ROI), 0.001 in Greater Belfast (0.00011-0.0047) and zero in ROI (0-0.0014). R304(*) prevalence was elevated in acromegaly/gigantism patients in NI (11/87, 12.6%, P acromegaly/gigantism cases. tMRCA is consistent with historical/folklore accounts of Irish giants. Forward simulations predict many undetected carriers; geographically targeted population screening improves asymptomatic carrier identification, complementing clinical testing of patients/relatives. We generated disease awareness locally, necessary for early diagnosis and improved outcomes of AIP-related disease. © 2016 The Authors. **Human Mutation published by Wiley Periodicals, Inc.
Yarman, S. [Div. of Endocrinology, Metabolism and Nutrition, Istanbul Univ., Istanbul (Turkey); Minareci, Oe. [Dept. of Radiology, Medical Faculty of Istanbul Univ., Istanbul (Turkey)
Simultaneous occurrence of an intracranial meningioma and a growth hormone (GH)-producing pituitary adenoma is exceedingly rare, as is coexistence of an empty sella and acromegaly. We report all these rare entities in the same patient. We evaluated the role of inferior petrosal sinus sampling for lateralisation of an adenoma in this patient. (orig.)
Ribeiro-Oliveira, Antônio; Barkan, Ariel
Acromegaly is a chronic disease characterized by the presence of a pituitary growth hormone (GH)-producing tumour, excessive secretion of growth hormone, raised levels of insulin-like growth factor I (IGF-I) and characteristic clinical presentation of acral enlargement. Over the past two decades, major advances have occurred in the understanding of some aspects of acromegaly--such as the biology of pituitary tumours, the physiology, molecular mechanisms of GH secretion and IGF-I generation, and the pathogenesis of comorbidities. Moreover, new approaches to diagnosis and surveillance (both in terms of screening and follow-up) of acromegaly have led to increases in the number of patients diagnosed with active disease, many of whom would previously have been missed. The development of sensitive assays for detecting plasma GH and IGF-I levels, as well as the widespread use of MRI for visualization of small tumours, have been major contributing factors to these improvements. Treatment advances have resulted in improved cure rates and disease control through novel neurosurgical techniques and pharmacological approaches. This Review summarizes and discusses the changes in our understanding of the epidemiology, diagnosis, treatment, and follow-up of acromegaly and its comorbidities.
Chemla, Denis; Attal, Pierre; Maione, Luigi; Veyer, Anne-Sophie; Mroue, Ghassan; Baud, Dany; Salenave, Sylvie; Kamenicky, Peter; Bobin, Serge; Chanson, Philippe
Successful treatment of acromegaly improves disease-related cardiovascular mortality and morbidity, but its effects on autonomic modulation of the heart rate are unknown. We documented treatment-induced changes in time-domain heart rate variability, taking into account the confounding effects of obstructive sleep apnea. Sixteen consecutive patients (12 males, aged 43 ± 12 y) with newly diagnosed acromegaly underwent overnight (12:00-7:00 am) cardiac Holter recordings coupled with polysomnography. Data were obtained before and 10 ± 6 months after successful treatment of acromegaly. IGF-1 levels fell from 807 ± 333 to 207 ± 69 μg/L and normalized in all patients. Seven patients (44%) had obstructive sleep apnea (apnea-hypopnea index 33 ± 21/h) at baseline. Treatment had no significant effect on polysomnographic indices. After treatment, increases were noted in the normal-to-normal heart period (NN), SD-NN, the percentage of NN differing from the previous NN by greater than 50 msec, and the root mean square of successive differences in NN (each P rate variability results were not influenced by the type of treatment, and there was no relationship between changes in NN and changes in the apnea-hypopnea index (P = .58). Early after successful treatment of acromegaly, we observed increased parasympathetic modulation/decreased sympathetic modulation of the nighttime heart rate, an effect that seems unrelated to changes in sleep apnea status. Treatments aimed at normalizing IGF-1 may improve cardiovascular homeostasis through improved cardiac autonomic nervous system modulation.
Rick, Jonathan W; Jahangiri, Arman; Flanigan, Patrick M; Aghi, Manish K
Acromegaly is a rare disease that is associated with many co-morbidities. This condition also causes progressive deformity of the skull which includes frontal bossing and cranial thickening. Surgical and/or medical management can cure this condition in many patients, but it is not understood if patients cured of acromegaly experience regression of their skull deformities. We performed a retrospective analysis on patients treated at our dedicated pituitary center from 2009 to 2014. We looked at all MRI images taken during the treatment of these patients and recorded measurements on eight skull dimensions. We then analyzed these measurements for changes over time. 29 patients underwent curative treatment for acromegaly within our timeframe. The mean age for this population was 45.0 years old (range 19-70) and 55.2 % (n = 16) were female. All of these patients were treated with a transsphenoidal resection for a somatotropic pituitary adenoma. 9 (31.1%) of these patients required further medical therapy to be cured. We found statically significant variation in the coronal width of the sella turcica after therapy, which is likely attributable to changes from transsphenoidal surgery. None of the other dimensions had significant variation over time after cure. Patients cured of acromegaly should not expect natural regression of their skull deformities. Our study suggests that both frontal bossing and cranial thickening do not return to normal after cure.
Conclusion: Early postoperative GH values may be used to predict long-term cure. A value of ≤1.5 ng/ml at 6 h following surgery may predict long-term cure in two-thirds of the patients with acromegaly who undergo TSS.
Roerink, S.; Marsman, D.; Bon, A. van; Netea-Maier, R.T.
We present a case of a 46-year-old transgender male who, during his female-to-male transition, presented with a pituitary apoplexy at the emergency department of a general hospital in the Netherlands. During admission, it turned out that he also suffered from acromegaly due to a growth hormone secre
Herlitz, H.; Jonsson, O.; Bengtsson, B.-Aa. (Departments of Nephrology, Urology and Endocrinology, University of Goeteborg, Goeteborg (Sweden))
We investigated the relationship between mean plasma growth hormone (GH) concentration and cellular sodium transport in untreated and treated acromegaly. Seventeen patients (age 55 [+-] 3 years) with active acromegaly were studied with respect to plasma GH (mean of 24 h GH profile) and erythrocyte electrolyte content as well as transmembrane sodium transport. The patients were reinvestigated two weeks after successful surgery (N = 14) and again after one year (N = 13). Erythrocyte electrolytes were analyzed by flame photometry and sodium influx and efflux rate constant determined by in vitro incubation using a modified Keyne's formula. In patients with active acromegaly there was a significant positive correlation between IGF-1 and cellular sodium transport, while GH tended to show a negative relatonship to the same parameter. After successful treatment, both IGF-1 and GH disclosed a positive relationship to cellular sodium transport. After one year, a significant increase in erythrocyte sodium content was seen in the patients compared to the preoperative situation. In conclusion, if this is a generalized phenomonen the results are compatible with a sodium-retaining effect of GH via stimulation of transmembrane sodium transport. In active acromegaly this may be counteracted by a sodium transport inhibitor giving the reverse relationship between GH and cellular sodium transport. (au).
Roerink, S.H.P.P.; Lindert, E.J. van; Ven, A.C. van de
In this double case report, we present two special cases of pituitary apoplexy. First, we describe a patient with growth hormone deficiency despite clinical suspicion of acromegaly. Imaging showed evidence of a recent pituitary apoplexy, which might have caused spontaneous remission of the acromegal
Tabur, S; Sezen, H; Korkmaz, H; Ozkaya, M; Akarsu, E
The present study aimed to evaluate the activity of prolidase in controlled acromegaly patients and its association with oxidative stress. 25 acromegalic patients in remission who were followed in our outpatient clinic and 31 healthy controls were enrolled in the study. Serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), total antioxidative status (TAS), total oxidative stress (TOS), total free sulfhydryl (-SH), paraoxonase (PON), arylesterase (ARE), lipid hydroperoxide (LOOH) and prolidase activity levels were measured. Percent ratio of TOS to TAS level was accepted as oxidative stress index (OSI). Serum prolidase activity, TOS, OSI, and LOOH levels were significantly higher in acromegaly patients compared to the healthy control group (pacromegaly patients compared to the healthy control group (p=0.002). Prolidase activity were positively correlated with TOS, OSI, LOOH and negatively correlated with -SH in patients with acromegaly (r=0.471, pacromegaly patients. These results suggest that extracellular matrix changes continue eventhough the disease is controlled, and elevated oxidative stress is involved in the increased prolidase activity in acromegaly patients.
P.U. Freda (Pamela); L. Katznelson (Laurence); A-J. van der Lely (Aart-Jan); F. Reyes; S. Zhao (Shouhao); D. Rabinowitz (Daniel)
textabstractContext: Although considerable data exist on the use of long-acting somatostatin analogs to treat acromegaly, their reported efficacy differs substantially among trials. Objective: We conducted a meta-analysis to derive definitive estimates of their efficacy for biochemical control and
Full Text Available Ferdinand Roelfsema, Nienke R Biermasz, Alberto M Pereira, Johannes A RomijnDepartment of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, The NetherlandsBackground: In acromegaly, expert surgery is curative in only about 60% of patients. Postoperative radiation therapy is associated with a high incidence of hypopituitarism and its effect on growth hormone (GH production is slow, so that adjuvant medical treatment becomes of importance in the management of many patients.Objective: To delineate the role of lanreotide in the treatment of acromegaly.Methods: Search of Medline, Embase, and Web of Science databases for clinical studies of lanreotide in acromegaly.Results: Treatment with lanreotide slow release and lanreotide Autogel® normalized GH and insulin-like growth factor-I (IGF-I concentrations in about 50% of patients. The efficacy of 120 mg lanreotide Autogel® on GH and IGF-I levels was comparable with that of 20 mg octreotide LAR. There were no differences in improvement of cardiac function, decrease in pancreatic β-cell function, or occurrence of side effects, including cholelithiasis, between octreotide LAR and lanreotide Autogel®. When postoperative treatment with somatostatin analogs does not result in normalization of serum IGF-I and GH levels after noncurative surgery, pegvisomant alone or in combination with somatostatin analogs can control these levels in a substantial number of patients.Keywords: acromegaly, lanreotide, somatostatin analog, growth hormone, pegvisomant
Agarwal, Purnima; Rai, Praveer; Jain, Manoj; Mishra, Shambhavi; Singh, Uttam; Gupta, Sushil Kumar
Background: There are conflicting data regarding the prevalence of colorectal polyp in patients with acromegaly. Subjects and Methods: Consecutive forty-seven acromegalic patients (21 men, 26 women), with a mean age of (40 ± 12 years) attending endocrinology outpatient department underwent full colonoscopy. All the patients underwent clinical and biochemical evaluation (glucose suppressed growth hormone (GH), Insulin-like growth factor-1 [IGF-1], fasting insulin, and glucose). The control group (n = 120) for colonoscopy was adult subjects undergoing evaluation for symptoms of irritable bowel syndrome. Clinical and biochemical parameters in acromegalic patients with colonic polyp were compared to those without a polyp. Results: Patients with acromegaly had significantly higher prevalence of colonic polyp as compared to control subjects (10.6% vs. 0.8%). None of the patients with polyp had skin tags. There was no significant difference between subjects with and without colonic polyp in duration of illness, basal, and glucose-suppressed GH and most recent IGF-1. Fasting blood sugar was significantly higher (P acromegaly as compared to control have a higher prevalence of colonic polyps. There was no association of polyps seen with age, BMI, skin tags, homeostasis model assessment of insulin resistance index, duration of disease, and basal and glucose-suppressed GH and IGF-1 levels. There were no specific predictive factors detected. Screening full colonoscopy is recommended in all cases with acromegaly. PMID:27366708
Broder, Michael S; Chang, Eunice; Cherepanov, Dasha; Neary, Maureen P; Ludlam, William H
Acromegaly, a rare endocrine disorder, results from excessive growth hormone secretion, leading to multisystem-associated morbidities. Using 2 large nationwide databases, we estimated the annual incidence and prevalence of acromegaly in the U.S. We used 2008 to 2013 data from the Truven Health MarketScan(®) Commercial Claims and Encounters Database and IMS Health PharMetrics healthcare insurance claims databases, with health plan enrollees acromegaly (International Classification of Diseases, 9th Revision, Clinical Modification Code [ICD-9CM] 253.0), or 1 claim with acromegaly and 1 claim for pituitary tumor, pituitary surgery, or cranial stereotactic radiosurgery. Annual incidence was calculated for each year from 2009 to 2013, and prevalence in 2013. Estimates were stratified by age and sex. Incidence was up to 11.7 cases per million person-years (PMPY) in MarketScan and 9.6 cases PMPY in PharMetrics. Rates were similar by sex but typically lowest in ≤17 year olds and higher in >24 year olds. The prevalence estimates were 87.8 and 71.0 per million per year in MarketScan and PharMetrics, respectively. Prevalence consistently increased with age but was similar by sex in each database. The current U.S. incidence of acromegaly may be up to 4 times higher and prevalence may be up to 50% higher than previously reported in European studies. Our findings correspond with the estimates reported by a recent U.S. study that used a single managed care database, supporting the robustness of these estimates in this population. Our study indicates there are approximately 3,000 new cases of acromegaly per year, with a prevalence of about 25,000 acromegaly patients in the U.S. CT = computed tomography GH = growth hormone IGF-1 = insulin-like growth factor 1 ICD-9-CM Code = International Classification of Diseases, 9th Revision, Clinical Modification Codes MRI = magnetic resonance imaging PMPY = per million person-years.
Muhammad, Ammar; Delhanty, Patric J D; Huisman, Martin; Visser, Jenny A; Jan van der Lelij, Aart; Neggers, Sebastian J C M M
Data on plasma acylated ghrelin (AG) and unacylated ghrelin (UAG) levels in acromegaly are limited. High AG/UAG ratios are linked with type 2 diabetes, obesity, and hyperphagia (e.g., in Prader-Willi syndrome). To assess fasting plasma AG and UAG levels, and the AG/UAG ratio in acromegaly patients receiving combination treatment of long-acting somatostatin analogs (LA-SSAs) and pegvisomant (PEGV; n = 60). We used as controls acromegaly patients whose disease was controlled with PEGV monotherapy and medically naïve patients with active acromegaly. Fasting venous blood samples were collected and directly stabilized to inhibit deacylation of AG. Plasma AG and UAG levels were determined by double-antibody sandwich enzyme immunoassay, and the AG/UAG ratio was calculated. Plasma AG and UAG levels were significantly lower in patients with acromegaly receiving combination treatment [median, interquartile range (IQR): AG: 8.5 pg/mL, 2.9 to 21.1 pg/mL; UAG: 26.9 pg/mL, 11.2 to 42.1 pg/mL] compared with patients using PEGV alone [AG: 60.5 pg/mL (IQR, 58.8 to 77.4 pg/mL); UAG: 153.7 pg/mL (IQR, 127.3 to 196.0 pg/mL)] and medically naïve patients with acromegaly [AG: 24.0 pg/mL (IQR, 12.6 to 49.7 pg/mL); UAG: 56.3 pg/mL (IQR, 43.4 to 61.5 pg/mL)]. However, AG/UAG ratios were similar in all groups. Although plasma AG and UAG are suppressed during combination treatment with LA-SSAs and PEGV, the AG/UAG ratio remained similar. This shows that SSAs decrease both AG and UAG levels, which suggests that they do not alter metabolism significantly in acromegaly patients.
Yaron, Marianna; Izkhakov, Elena; Sack, Jessica; Azzam, Ibrahim; Osher, Etty; Tordjman, Karen; Stern, Naftali; Greenman, Yona
Acromegaly is associated with increased cardiovascular morbidity and mortality when inadequately treated, which may be secondary to associated comorbidities or to direct IGF-1 effects on the cardiovascular system. By using a control group carefully matched for traditional cardiovascular risk factors, we aimed to assess the direct contribution of disease activity and IGF-1 levels to arterial damage as assessed by measurements of arterial stiffness and endothelial function. Twenty-nine subjects with acromegaly (11 males, 52 ± 14 year; 15 active acromegaly) and 24 matched controls underwent evaluation of large and small artery compliance using applanation tonometry, pulse wave velocity (PWV), augmentation index (Alx), carotid ultrasonography intima-media thickness, (IMT) and flow-mediated dilatation (FMD). IGF-1 expressed as times the upper limit of the normal range (x ULN) was 2.2 ± 1.1 in patients with active disease versus 0.7 ± 0.2 in patients in remission. Irrespective of disease activity, FMD was lower in patients with acromegaly than in control subjects, (3.4 ± 2.7 % in active acromegaly, 4.4 ± 3.3 % in controlled acromegaly and 7.5 ± 3.8 % in controls; p = 0.004). There were no significant differences in PWV, Alx, and IMT between groups. A positive correlation was found between IGF-1× ULN and IMT (r = 0.4; P = 0.02). Asymmetric dimethylarginine (ADMA), a novel cardiovascular risk factor, was positively correlated to arterial stiffness (r = 0.46; p = 0.017) and negatively with small vessel compliance (r = -0.44, p = 0.02). Patients with acromegaly have significantly impaired endothelial function as assessed by FMD, but other tested vascular parameters were similar to a control group that was adequately matched for cardiovascular risk factors.
Yarman, S; Yalın, G Y; Dogansen, S C; Canbaz, B; Tanrıkulu, S; Akyuz, F
Somatostatin analogs control GH/IGF-1 excess in acromegaly. Somatostatin receptors also mediate the complex effects of somatostatin on the gastrointestinal tract and may be defensive in inflammatory bowel diseases, such as ulcerative colitis. We present a patient who showed good response to long-acting octreotide (OCT-LAR) treatment in terms of both acromegaly and ulcerative colitis (UC). A 58-year-old female patient with diagnosis of acromegaly and ulcerative colitis was started on long-acting somatostatin treatment as a first-line treatment for acromegaly as she refused to undergo transsphenoidal surgery. During the follow-up period, a significant amelioration was also observed in the course of ulcerative colitis, and clinical remission of both diseases was achieved uneventfully. Somatostatin appears to be a promising candidate in the treatment of inflammatory bowel diseases. © 2016 John Wiley & Sons Ltd.
Akira Shimatsu; Akira Teramoto; Naomi Hizuka; Kazuo Kitai; Joaquim Ramis; Kazuo Chihara
.... However, its efficacy in Japanese patients has not been extensively evaluated. We examined the dose-response relationship and long-term efficacy and safety in Japanese patients with acromegaly or pituitary gigantism...
Trivellin, G.; Daly, A.F.; Faucz, F.R.; Yuan, B.; Rostomyan, L.; Larco, D.O.; Schernthaner-Reiter, M.H.; Szarek, E.; Leal, L.F.; Caberg, J.-H.; Castermans, E.; Villa, C.; Dimopoulos, A.; Chittiboina, P.; Xekouki, P.; Shah, N.; Metzger, D.; Lysy, P.A.; Ferrante, E.; Strebkova, N.; Mazerkina, N.; Zatelli, M.C.; Lodish, M.; Horvath, A.; de Alexandre, R. Bertollo; Manning, A.D.; Levy, I.; Keil, M.F.; de la Luz Sierra, M.; Palmeira, L.; Coppieters, W.; Georges, M.; Naves, L.A.; Jamar, M.; Bours, V.; Wu, T.J.; Choong, C.S.; Bertherat, J.; Chanson, P.; Kamenický, P.; Farrell, W.E.; Barlier, A.; Quezado, M.; Bjelobaba, I.; Stojilkovic, S.S.; Wess, J.; Costanzi, S.; Liu, P.; Lupski, J.R.; Beckers, A.; Stratakis, C.A.
BACKGROUND Increased secretion of growth hormone leads to gigantism in children and acromegaly in adults; the genetic causes of gigantism and acromegaly are poorly understood. METHODS We performed clinical and genetic studies of samples obtained from 43 patients with gigantism and then sequenced an implicated gene in samples from 248 patients with acromegaly. RESULTS We observed microduplication on chromosome Xq26.3 in samples from 13 patients with gigantism; of these samples, 4 were obtained from members of two unrelated kindreds, and 9 were from patients with sporadic cases. All the patients had disease onset during early childhood. Of the patients with gigantism who did not carry an Xq26.3 microduplication, none presented before the age of 5 years. Genomic characterization of the Xq26.3 region suggests that the microduplications are generated during chromosome replication and that they contain four protein-coding genes. Only one of these genes, GPR101, which encodes a G-protein–coupled receptor, was overexpressed in patients’ pituitary lesions. We identified a recurrent GPR101 mutation (p.E308D) in 11 of 248 patients with acromegaly, with the mutation found mostly in tumors. When the mutation was transfected into rat GH3 cells, it led to increased release of growth hormone and proliferation of growth hormone–producing cells. CONCLUSIONS We describe a pediatric disorder (which we have termed X-linked acrogigantism [X-LAG]) that is caused by an Xq26.3 genomic duplication and is characterized by early-onset gigantism resulting from an excess of growth hormone. Duplication of GPR101 probably causes X-LAG. We also found a recurrent mutation in GPR101 in some adults with acromegaly. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.) PMID:25470569
Trivellin, Giampaolo; Daly, Adrian F; Faucz, Fabio R; Yuan, Bo; Rostomyan, Liliya; Larco, Darwin O; Schernthaner-Reiter, Marie Helene; Szarek, Eva; Leal, Letícia F; Caberg, Jean-Hubert; Castermans, Emilie; Villa, Chiara; Dimopoulos, Aggeliki; Chittiboina, Prashant; Xekouki, Paraskevi; Shah, Nalini; Metzger, Daniel; Lysy, Philippe A; Ferrante, Emanuele; Strebkova, Natalia; Mazerkina, Nadia; Zatelli, Maria Chiara; Lodish, Maya; Horvath, Anelia; de Alexandre, Rodrigo Bertollo; Manning, Allison D; Levy, Isaac; Keil, Margaret F; Sierra, Maria de la Luz; Palmeira, Leonor; Coppieters, Wouter; Georges, Michel; Naves, Luciana A; Jamar, Mauricette; Bours, Vincent; Wu, T John; Choong, Catherine S; Bertherat, Jerome; Chanson, Philippe; Kamenický, Peter; Farrell, William E; Barlier, Anne; Quezado, Martha; Bjelobaba, Ivana; Stojilkovic, Stanko S; Wess, Jurgen; Costanzi, Stefano; Liu, Pengfei; Lupski, James R; Beckers, Albert; Stratakis, Constantine A
Increased secretion of growth hormone leads to gigantism in children and acromegaly in adults; the genetic causes of gigantism and acromegaly are poorly understood. We performed clinical and genetic studies of samples obtained from 43 patients with gigantism and then sequenced an implicated gene in samples from 248 patients with acromegaly. We observed microduplication on chromosome Xq26.3 in samples from 13 patients with gigantism; of these samples, 4 were obtained from members of two unrelated kindreds, and 9 were from patients with sporadic cases. All the patients had disease onset during early childhood. Of the patients with gigantism who did not carry an Xq26.3 microduplication, none presented before the age of 5 years. Genomic characterization of the Xq26.3 region suggests that the microduplications are generated during chromosome replication and that they contain four protein-coding genes. Only one of these genes, GPR101, which encodes a G-protein-coupled receptor, was overexpressed in patients' pituitary lesions. We identified a recurrent GPR101 mutation (p.E308D) in 11 of 248 patients with acromegaly, with the mutation found mostly in tumors. When the mutation was transfected into rat GH3 cells, it led to increased release of growth hormone and proliferation of growth hormone-producing cells. We describe a pediatric disorder (which we have termed X-linked acrogigantism [X-LAG]) that is caused by an Xq26.3 genomic duplication and is characterized by early-onset gigantism resulting from an excess of growth hormone. Duplication of GPR101 probably causes X-LAG. We also found a recurrent mutation in GPR101 in some adults with acromegaly. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).
Füchtbauer, Laila; Olsson, Daniel S; Bengtsson, Bengt-Åke; Norrman, Lise-Lott; Sunnerhagen, Katharina S; Johannsson, Gudmundur
Patients with acromegaly have decreased body fat (BF) and increased extracellular water (ECW) and muscle mass. Although there is a lack of systematic studies on muscle function, it is believed that patients with acromegaly may suffer from proximal muscle weakness despite their increased muscle mass. We studied body composition and muscle function in untreated acromegaly and after biochemical remission. Prospective observational study. Patients with acromegaly underwent measurements of muscle strength (dynamometers) and body composition (four-compartment model) at diagnosis (n = 48), 1 year after surgery (n = 29) and after long-term follow-up (median 11 years) (n = 24). Results were compared to healthy subjects. Untreated patients had increased body cell mass (113 ± 9% of predicted) and ECW (110 ± 20%) and decreased BF (67 ± 7.6%). At one-year follow-up, serum concentration of IGF-I was reduced and body composition had normalized. At baseline, isometric muscle strength in knee flexors and extensors was normal and concentric strength was modestly increased whereas grip strength and endurance was reduced. After one year, muscle strength was normal in both patients with still active disease and patients in remission. At long-term follow-up, all patients were in remission. Most muscle function tests remained normal, but isometric flexion and the fatigue index were increased to 153 ± 42% and 139 ± 28% of predicted values, respectively. Patients with untreated acromegaly had increased body cell mass and normal or modestly increased proximal muscle strength, whereas their grip strength was reduced. After biochemical improvement and remission, body composition was normalized, hand grip strength was increased, whereas proximal muscle fatigue increased. © 2017 European Society of Endocrinology.
Constantin, Tina; Tangpricha, Vin; Shah, Reshma; Oyesiku, Nelson M; Ioachimescu, Octavian C; Ritchie, James; Ioachimescu, Adriana G
Acromegaly has been associated with calcium-phosphate and bone turnover alterations. Controlled studies of these interactions are sparse. To evaluate calcium and bone metabolism in active and treated acromegaly. We conducted a controlled, prospective study at a tertiary referral center. We studied 22 patients with acromegaly referred for surgical or medical therapy (ACM) and 22 with nonfunctioning pituitary adenomas referred for surgery (control). Calcium (serum and urine), phosphorus, parathyroid hormone (PTH), 25-hydroxy- and 1,25-dihydroxy-vitamin D, bone turnover markers [serum C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP)], and cytokines [receptor activator of nuclear factor κB ligand (RANK-L) and osteoprotegerin (OPG)] at baseline and 3 to 6 months after treatment. At baseline, the ACM group had lower PTH levels than controls (36.3 ± 13.9 pg/mL vs 56.0 ± 19.9 pg/mL) and higher phosphorus (4.34 ± 0.71 mg/dL vs 3.55 ± 0.50 mg/dL) (P acromegaly, serum calcium (9.52 ± 0.43 mg/dL to 9.26 ± 0.28 mg/dL), phosphorus (4.34 ± 0.71 mg/dL to 3.90 ± 0.80 mg/dL), and CTX (0.91 ± 0.75 ng/mL to 0.63 ± 0.68 ng/mL) decreased, while PTH increased (36.3 ± 13.9 pg/mL to 48.9 ± 16.7 pg/mL) (P Acromegaly patients exhibited PTH-independent calcium-phosphate alterations and enhanced coupled bone formation and resorption. Within 6 months of treatment, bone resorption decreased, whereas RANK-L/OPG changes were inconsistent.
Strasburger, Christian J; Karavitaki, Niki; Störmann, Sylvère; Trainer, Peter J; Kreitschmann-Andermahr, Ilonka; Droste, Michael; Korbonits, Márta; Feldmann, Berit; Zopf, Kathrin; Sanderson, Violet Fazal; Schwicker, David; Gelbaum, Dana; Haviv, Asi; Bidlingmaier, Martin; Biermasz, Nienke R
Background Long-acting somatostatin analogues delivered parenterally are the most widely used medical treatment in acromegaly. This patient-reported outcomes survey was designed to assess the impact of chronic injections on subjects with acromegaly. Methods The survey was conducted in nine pituitary centres in Germany, UK and The Netherlands. The questionnaire was developed by endocrinologists and covered aspects of acromegaly symptoms, injection-related manifestations, emotional and daily life impact, treatment satisfaction and unmet medical needs. Results In total, 195 patients participated, of which 112 (57%) were on octreotide (Sandostatin LAR) and 83 (43%) on lanreotide (Somatuline Depot). The majority (>70%) of patients reported acromegaly symptoms despite treatment. A total of 52% of patients reported that their symptoms worsen towards the end of the dosing interval. Administration site pain lasting up to a week following injection was the most frequently reported injection-related symptom (70% of patients). Other injection site reactions included nodules (38%), swelling (28%), bruising (16%), scar tissue (8%) and inflammation (7%). Injection burden was similar between octreotide and lanreotide. Only a minority of patients received injections at home (17%) and 5% were self-injecting. Over a third of patients indicated a feeling of loss of independence due to the injections, and 16% reported repeated work loss days. Despite the physical, emotional and daily life impact of injections, patients were satisfied with their treatment, yet reported that modifications that would offer major improvement over current care would be ‘avoiding injections’ and ‘better symptom control’. Conclusion Lifelong injections of long-acting somatostatin analogues have significant burden on the functioning, well-being and daily lives of patients with acromegaly. PMID:26744896
Potorac, Iulia; Petrossians, Patrick; Daly, Adrian F; Alexopoulou, Orsalia; Borot, Sophie; Sahnoun-Fathallah, Mona; Castinetti, Frederic; Devuyst, France; Jaffrain-Rea, Marie-Lise; Briet, Claire; Luca, Florina; Lapoirie, Marion; Zoicas, Flavius; Simoneau, Isabelle; Diallo, Alpha M; Muhammad, Ammar; Kelestimur, Fahrettin; Nazzari, Elena; Centeno, Rogelio Garcia; Webb, Susan M; Nunes, Marie-Laure; Hana, Vaclav; Pascal-Vigneron, Véronique; Ilovayskaya, Irena; Nasybullina, Farida; Achir, Samia; Ferone, Diego; Neggers, Sebastian J C M M; Delemer, Brigitte; Petit, Jean-Michel; Schöfl, Christof; Raverot, Gerald; Goichot, Bernard; Rodien, Patrice; Corvilain, Bernard; Brue, Thierry; Schillo, Franck; Tshibanda, Luaba; Maiter, Dominique; Bonneville, Jean-François; Beckers, Albert
GH-secreting pituitary adenomas can be hypo-, iso- or hyper-intense on T2-weighted MRI sequences. We conducted the current multicenter study in a large population of patients with acromegaly to analyze the relationship between T2-weighted signal intensity on diagnostic MRI and hormonal and tumoral responses to somatostatin analogs (SSA) as primary monotherapy. Acromegaly patients receiving primary SSA for at least 3 months were included in the study. Hormonal, clinical and general MRI assessments were performed and assessed centrally. We included 120 patients with acromegaly. At diagnosis, 84, 17 and 19 tumors were T2-hypo-, iso- and hyper-intense, respectively. SSA treatment duration, cumulative and mean monthly doses were similar in the three groups. Patients with T2-hypo-intense adenomas had median SSA-induced decreases in GH and IGF-1 of 88% and 59% respectively, which were significantly greater than the decreases observed in the T2-iso- and hyper-intense groups (P < 0.001). Tumor shrinkage on SSA was also significantly greater in the T2-hypo-intense group (38%) compared with the T2-iso- and hyper-intense groups (8% and 3%, respectively; P < 0.0001). The response to SSA correlated with the calculated T2 intensity: the lower the T2-weighted intensity, the greater the decrease in random GH (P < 0.0001, r = 0.22), IGF-1 (P < 0.0001, r = 0.14) and adenoma volume (P < 0.0001, r = 0.33). The T2-weighted signal intensity of GH-secreting adenomas at diagnosis correlates with hormone reduction and tumor shrinkage in response to primary SSA treatment in acromegaly. This study supports its use as a generally available predictive tool at diagnosis that could help to guide subsequent treatment choices in acromegaly. © 2016 Society for Endocrinology.
Burness, Celeste B; Dhillon, Sohita; Keam, Susan J
Lanreotide Autogel(®) (ATG) [Somatuline(®) Autogel(®), Somatuline(®) Depot(®)] is a prolonged-release, supersaturated aqueous gel formulation of the somatostatin analogue lanreotide acetate that acts via somatostatin receptors to reduce both growth hormone and insulin-like growth factor-I levels. It is indicated for the treatment of patients with acromegaly who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy. This article reviews the clinical efficacy and tolerability of lanreotide ATG in the treatment of acromegaly, as well as summarizing its pharmacological properties. Results of clinical trials and extension studies of up to 4 years duration showed that deep subcutaneous lanreotide ATG was a generally effective treatment in treatment-naive and treatment-experienced adults with acromegaly. Lanreotide ATG provided hormonal control and improved both health-related quality of life and acromegaly symptoms in most patients; it also reduced tumour volume to a clinically significant extent in studies of primary therapy. Moreover, lanreotide ATG was generally no less effective than intramuscular lanreotide long-acting microparticles and was as effective as intramuscular octreotide long-acting release in switching or crossover studies, including those with standard or extended dosing intervals. Lanreotide ATG is generally well tolerated; the most frequently reported adverse events were mild or moderate transient gastrointestinal symptoms. Lanreotide ATG also has the advantage of being available in a convenient pre-filled syringe and is given subcutaneously rather than intramuscularly. Thus, lanreotide ATG continues to be a valuable option in the treatment of acromegaly, with potential advantages being ease of administration and longer dosing intervals in patients who have an adequate response to initial therapy.
Longobardi, S; Di Somma, C; Di Rella, F; Angelillo, N; Ferone, D; Colao, A; Merola, B; Lombardi, G
Acromegalic patients present an increase of osteoblastic and osteoclastic activity, showing a different effect on the axial and appendicular skeletal structures. At this regard controversial data about bone mineral density (BMD) have been published in literature. In fact an increase of BMD levels in femoral neck and Ward's triangle without any difference in lumbar spine has been described. On the other hand normal BMD levels at forearm and reduced BMD levels at lumbar spine were found. These patients seem to have a reduction of trabecular BMD similar to postmenopausal osteoporotic patients despite normal or slightly elevated cortical BMD. Recently, it has been described that cytokines, in particular tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1), are implicated in the pathogenetic mechanism of postmenopausal osteoporosis. Taking into account that growth hormone (GH) can increase TNF-alpha and IL-1 secretion by mononuclear blood cells, the evaluation of possible relationship between the reduced BMD at lumbar spine and circulating cytokines levels was carried out in acromegalic patients. In addition we evaluated the effect of acute octreotide administration on serum TNF-alpha and IL-I concentrations. Eleven patients with active acromegaly and eleven healthy age-, sex-, weight- and heightmatched subjects were enrolled in this study. BMD was significantly reduced at lumbar spine (0.80 +/- 0.29 g/cm2 vs 1.02 +/- 0.11 g/cm2; p affect bone turnover inducing an increase of cytokines acting by a paracrine/autocrine mechanism cannot be ruled out.
Summary In patients with active acromegaly after pituitary surgery, somatostatin analogues are effective in controlling the disease and can even be curative in some cases. After treatment discontinuation, the likelihood of disease recurrence is high. However, a small subset of patients remains symptom-free after discontinuation, with normalized growth hormone (GH) and insulin-like growth factor (IGF1) levels. The characteristics of patients most likely to achieve sustained remission after treatment discontinuation are not well understood, although limited evidence suggests that sustained remission is more likely in patients with lower GH and IGF1 levels before treatment withdrawal, in those who respond well to low-dose treatment, in those without evidence of adenoma on an MRI scan and/or in patients who receive long-term treatment. In this report, we describe the case of a 56-year-old female patient treated with lanreotide Autogel for 11 years. Treatment was successfully discontinued, and the patient is currently disease-free on all relevant parameters (clinical, biochemical and tumour status). The successful outcome in this case adds to the small body of literature suggesting that some well-selected patients who receive long-term treatment with somatostatin analogues may achieve sustained remission. Learning points: The probability of disease recurrence is high after discontinuation of treatment with somatostatin analogues. Current data indicate that remission after treatment discontinuation may be more likely in patients with low GH and IGF1 levels before treatment withdrawal, in those who respond well to low-dose treatment, in those without evidence of adenoma on MRI, and/or in patients receiving prolonged treatment. This case report suggests that prolonged treatment with somatostatin analogues can be curative in carefully selected patients. PMID:27933171
Şahin, Muhammed; Şahin, Alparslan; Kılınç, Faruk; Yüksel, Harun; Özkurt, Zeynep Gürsel; Türkcü, Fatih Mehmet; Pekkolay, Zafer; Soylu, Hikmet; Çaça, İhsan
Increased secretion of growth hormone and insulin-like growth factor-1 in acromegaly has various effects on multiple organs. However, the ocular effects of acromegaly have yet to be investigated in detail. The aim of the present study was to compare retina ganglion cell/inner plexiform layer (GCIPL) and peripapillary nerve fiber layer thickness (pRNFL) between patients with acromegaly and healthy control subjects using spectral domain optical coherence tomography (SD-OCT). This cross-sectional, comparative study included 18 patients with acromegaly and 20 control subjects. All participants underwent SD-OCT to measure pRNFL (in the seven peripapillary areas), GCIPL (in the nine ETDRS areas), and central macular thickness (CMT). Visual field (VF) examinations were performed using a Humphrey field analyzer in acromegalic patients. Measurements were compared between patients with acromegaly and control subjects. A total of 33 eyes of 18 patients with acromegaly and 40 eyes of 20 control subjects met the inclusion criteria of the present study. The overall calculated average pRNFL thickness was significantly lower in patients with acromegaly than in control subjects (P = 0.01), with pRNFL thickness significantly lower in the temporal superior and temporal inferior quadrants. Contrary to our expectations, pRNFL thickness in the nasal quadrant was similar between acromegalic and control subjects. The mean overall pRNFL thickness and superonasal, nasal, inferonasal, and inferotemporal quadrant pRNFL thicknesses were found to correlate with the mean deviation (MD) according to Spearman's correlation. However, other quadrants were not correlated with VF sensitivity. No significant difference in CMT values was observed (P = 0.6). GCIPL thickness was significantly lower in all quadrants of the inner and outer macula, except for central and inferior outer quadrants, in the acromegaly group than that in the control group (P acromegaly compared with that in control subjects
Kosma Wolinski; Agata Czarnywojtek; Marek Ruchala
INTRODUCTION: Acromegaly is a quite rare chronic disease caused by the increased secretion of growth hormone (GH) and subsequently insulin - like growth factor 1. Although cardiovascular diseases remains the most common cause of mortality among acromegalic patients, increased prevalence of malignant and benign neoplasms remains a matter of debate. The aim of this study is to evaluate the risk of thyroid nodular disease (TND) and thyroid cancer in patients with acromegaly. MATERIALS AND METHOD...
Zieliński, Grzegorz; Maksymowicz, Maria; Podgórski, Jan; Olszewski, Włodzimierz T
Double pituitary adenomas are very rare and present up to 1 % of pituitary adenomas in unselected autopsy series and up to 2 % in large surgical series. We report a case of a 47-year-old man presented slight clinical features of acromegaly with 2 years duration. Endocrine evaluation confirmed active acromegaly and revealed adrenocorticotropin hormone-dependent hypercortisolemia. Preoperative magnetic resonance imaging of the pituitary demonstrated clearly separated double microadenomas with d...
Naves, Luciana Ansaneli; Porto, Lara Benigno; Rosa, João Willy Corrêa; Casulari, Luiz Augusto; Rosa, José Wilson Corrêa
Geographical information systems (GIS) have emerged as a group of innovative software components useful for projects in epidemiology and planning in Health Care System. This is an original study to investigate environmental and geographical influences on epidemiology of acromegaly in Brazil. We aimed to validate a method to link an acromegaly registry with a GIS mapping program, to describe the spatial distribution of patients, to identify disease clusters and to evaluate if the access to Hea...
Lesén, Eva; Granfeldt, Daniel; Houchard, Aude; Dinet, Jérôme; Berthon, Anthony; Olsson, Daniel S; Björholt, Ingela; Johannsson, Gudmundur
Acromegaly is a complex endocrine disease with multiple comorbidities. Treatment to obtain biochemical remission includes surgery, medical therapy and radiation. We aimed to describe comorbidities, treatment patterns and cost-of-illness in patients with acromegaly in Sweden. A nationwide population-based study. Patients with acromegaly were identified and followed in national registers in Sweden. Longitudinal treatment patterns were assessed in patients diagnosed between July 2005 and December 2013. The cost-of-illness during 2013 was estimated from a societal perspective among patients diagnosed between 1987 and 2013. Among 358 patients with acromegaly (48% men, mean age at diagnosis 50.0 (s.d. 15.3) years) at least one comorbidity was reported in 81% (n = 290). The most common comorbidities were hypertension (40%, n = 142), neoplasms outside the pituitary (30%, n = 109), hypopituitarism (22%, n = 80) and diabetes mellitus (17%, n = 61). Acromegaly treatment was initiated on average 3.7 (s.d. 6.9) months after diagnosis. Among the 301 treated patients, the most common first-line treatments were surgery (60%, n = 180), somatostatin analogues (21%, n = 64) and dopamine agonists (14%, n = 41). After primary surgery, 24% (n = 44) received somatostatin analogues. The annual per-patient cost was €12 000; this was €8700 and €16 000 if diagnosed before or after July 2005, respectively. The cost-of-illness for acromegaly and its comorbidities was 77% from direct costs and 23% from production loss. The prevalence of comorbidity is high in patients with acromegaly. The most common first-line treatment in acromegalic patients was surgery followed by somatostatin analogues. The annual per-patient cost of acromegaly and its comorbidities was €12 000. © 2017 European Society of Endocrinology.
Karel Van Praet
Full Text Available Aortic regurgitation and dilatation of the aortic root and ascending aorta are severe complications of acromegaly. The current trend for management of an aortic root aneurysm is valve-sparing root replacement as well as restoring the diameter of the aortic sinotubular junction (STJ and annulus. Our case report supports the recommendation that in patients with acromegaly, severe aortic root involvement may indicate the need for surgery.
Lotti, Francesco; Rochira, Vincenzo; Pivonello, Rosario; Santi, Daniele; Galdiero, Mariano; Maseroli, Elisa; Balestrieri, Antonio; Faustini-Fustini, Marco; Peri, Alessandro; Sforza, Alessandra; Colao, Annamaria; Maggi, Mario; Corona, Giovanni
The prevalence of erectile dysfunction (ED) and its correlates in men with acromegaly has never been investigated. The aim of this study was to evaluate sexual function in men with acromegaly. Multicenter-based, retrospective analysis of a nonselected series of 57 acromegalic subjects (mean age: 52.7 ± 14.2 years) was performed. Acromegalic subjects reporting ED (n = 24) were compared with matched ED patients without acromegaly or pituitary disease (controls), selected from a cohort of more than 4,000 subjects enrolled in the Florence Sexual Medicine and Andrology Unit. Patients were interviewed using Structured Interview on Erectile Dysfunction (SIEDY) structured interview, a 13-item tool for the assessment of ED-related morbidities. Several clinical and biochemical parameters were taken. Penile color Doppler ultrasound (PCDU) was performed in a subgroup of 37 acromegalic subjects. ED was reported by 42.1% of acromegalic subjects. After adjusting for age and testosterone, acromegalic subjects with ED had a higher prevalence of hypertension and more often reported an impairment of sleep-related erections and a longer smoking habit. Accordingly, acromegaly-associated ED was characterized by a higher organic component and worse PCDU parameters. No relationship between ED and testosterone levels or other acromegaly-related parameters was found. However, acromegalic subjects with severe ED reported a longer disease duration. In a case-control analysis, comparing acromegalic subjects with ED-matched controls free from acromegaly (1:5 ratio), acromegalic men had a worse ED problem and a higher organic component of ED, as derived from SIEDY score. In line with these data, acromegalic patients with ED had a higher prevalence of major adverse cardiovascular events history at enrollment and lower PCDU parameters. Subjects with complicated acromegaly are at an increased risk of developing ED, especially those with cardiovascular morbidities. Our data suggest
Bolanowski, Marek; Daroszewski, Jacek; Medraś, Marek; Zadrozna-Sliwka, Beata
Acromegaly is a rare disease caused by growth hormone (GH) hypersecretion. GH and insulin-like growth factor-I (IGF-I) exert anabolic activity in bones. Nevertheless, bone mineral density (BMD) loss is not uncommon in patients with acromegaly. It is assumed to be due to hypogonadism associated with the acromegaly. The aim of the study was to examine BMD at various skeletal sites and bone turnover and to assess the influence of impaired gonadal function and disease activity on BMD and turnover changes in acromegaly. A total of 62 patients were studied (40 women, 22 men). Among the women, 22 had active disease and 18 were cured; 16 women had normal gonadal function, and 24 were hypogonadal. Altogether, 12 men presented with active acromegaly, and 10 were cured; normal gonadal function was found in 10 men, and hypogonadism was diagnosed in 12 men. Controls were 30 healthy subjects. Densitometry using dual-energy X-ray absorptiometry of the lumbar spine, proximal femur, forearm, and total body was carried out. Bone turnover was studied based on serum osteocalcin, C-terminal collagen type 1 crosslinks, and bone alkaline phosphatase concentration. A disadvantageous effect of acromegaly on bone density was associated with hypogonadism in the distal radius (in women), the proximal femur (in men), and the total body (both sexes). An anabolic effect of GH during active acromegaly was present in the proximal femur only in men. We confirmed increased bone turnover in the presence of acromegaly, and these changes were similar regarding the activity of the disease and the gonadal status.
Kyriakakis, Nikolaos; Trouillas, Jacqueline; Dang, Mary N; Lynch, Julie; Belchetz, Paul; Korbonits, Márta; Murray, Robert D
A male patient presented at the age of 30 with classic clinical features of acromegaly and was found to have elevated growth hormone levels, not suppressing during an oral glucose tolerance test. His acromegaly was originally considered to be of pituitary origin, based on a CT scan, which was interpreted as showing a pituitary macroadenoma. Despite two trans-sphenoidal surgeries, cranial radiotherapy and periods of treatment with bromocriptine and octreotide, his acromegaly remained active clinically and biochemically. A lung mass was discovered incidentally on a chest X-ray performed as part of a routine pre-assessment for spinal surgery 5 years following the initial presentation. This was confirmed to be a bronchial carcinoid tumour, which was strongly positive for growth hormone-releasing hormone (GHRH) and somatostatin receptor type 2 by immunohistochemistry. The re-examination of the pituitary specimens asserted the diagnosis of pituitary GH hyperplasia. Complete resolution of the patient's acromegaly was achieved following right lower and middle lobectomy. Seventeen years following the successful resection of the bronchial carcinoid tumour the patient remains under annual endocrine follow-up for monitoring of the hypopituitarism he developed after the original interventions to his pituitary gland, while there has been no evidence of active acromegaly or recurrence of the carcinoid tumour. Ectopic acromegaly is extremely rare, accounting for ectopic acromegaly and acromegaly of pituitary origin and emphasises the importance of avoiding unnecessary pituitary surgery and radiotherapy. The role of laboratory investigations, imaging and histology as diagnostic tools is discussed. Ectopic acromegaly is rare, accounting for less than 1% of all cases of acromegaly.Ectopic acromegaly is almost always due to extra-pituitary GHRH secretion, mainly from neuroendocrine tumours of pancreatic or bronchial origin.Differentiating between acromegaly of pituitary origin and
Chinezu, Laura; Vasiljevic, Alexandre; Trouillas, Jacqueline; Lapoirie, Marion; Jouanneau, Emmanuel; Raverot, Gérald
Silent somatotroph tumours are growth hormone (GH) immunoreactive (IR) pituitary tumours without clinical and biological signs of acromegaly. Their better characterisation is required to improve the diagnosis. Twenty-one silent somatotroph tumours were compared to 59 somatotroph tumours with acromegaly. Tumours in each group were classified into GH and plurihormonal (GH/prolactin (PRL)/±thyroid-stimulating hormone (TSH)) and into densely granulated (DG) and sparsely granulated (SG) types. The two groups were then compared with regards to proliferation (Ki-67, p53 indexes and mitotic count), differentiation (expression of somatostatin receptors SSTR2A-SSTR5 and transcription factor Pit-1) and secretory activity (% of GH- and PRL-IR cells). The silent somatotroph tumours represented 2% of all tested pituitary tumours combined. They were more frequent in women than in men (P = 0.002), more frequently plurihormonal and SG (P acromegaly. They all expressed SSTR2A, SSTR5 and Pit-1. The plurihormonal (GH/PRL/±TSH) tumours were mostly observed in women (sex ratio: 3/1) and in patients who were generally younger than those with acromegaly (P acromegaly. A low secretory activity of these tumours might explain the normal plasma values for GH and insulin-like growth factor 1 (IGF1) and the absence of clinical signs of acromegaly. © 2017 European Society of Endocrinology.
Lin, E; Wexler, TL; Nachtigall, L; Tritos, N; Swearingen, B; Hemphill, L; Loeffler, J; Biller, BMK; Klibanski, A; Miller, KK
Background Both growth hormone (GH) excess and GH deficiency are associated with body composition and biomarkers of cardiovascular risk in patients with pituitary disorders. However, the effects of developing GH deficiency after definitive treatment of acromegaly are largely unknown. Objective To determine whether development of GH deficiency after definitive therapy for acromegaly is associated with increased visceral adiposity and biomarkers of cardiovascular risk compared to GH sufficiency after definitive therapy for acromegaly. Design Cross-sectional Patients We studied three groups of subjects, all with a history of acromegaly (n=76): subjects with subsequent GH deficiency (GHD; n=31), subjects with subsequent GH sufficiency (GHS; n=25), and subjects with active acromegaly (AA; n=20). No study subjects were receiving somatostatin analogues, dopamine agonists or hGH. Measurements Body composition (by DXA), abdominal adipose tissue depots (by cross-sectional CT), total body water (by bioimpedance analysis) and carotid intima-media thickness (IMT) were measured. Fasting morning serum was collected for high-sensitivity C-reactive protein (hsCRP), lipids and lipoprotein levels. An oral glucose tolerance test was performed, and homeostasis model of assessment-insulin resistance (HOMA-IR) was calculated. Results Abdominal visceral adipose tissue, total adipose tissue, and total body fat were higher in subjects with GHD than GHS or AA (p acromegaly may adversely affect body composition and inflammatory biomarkers of cardiovascular risk but does not appear to adversely affect glucose homeostasis, lipids and lipoproteins, or other cardiovascular risk markers. PMID:22315983
Tiemensma, Jitske; Biermasz, Nienke R; van der Mast, Roos C; Wassenaar, Moniek J E; Middelkoop, Huub A M; Pereira, Alberto M; Romijn, Johannes A
Active acromegaly is associated with psychopathology, personality changes, and cognitive dysfunction. It is unknown whether, and to what extent, these effects are present after long-term cure of acromegaly. The aim of the study was to assess psychopathology, personality traits, and cognitive function in patients after long-term cure of acromegaly. This was a cross-sectional study. We studied 68 patients after long-term cure (13±1 yr) of acromegaly and 68 matched controls. We compared these data with 60 patients treated for nonfunctioning pituitary macroadenomas (NFMAs) and 60 matched controls. Psychopathology was assessed using the Apathy Scale, Irritability Scale, Hospital Anxiety and Depression Scale, and Mood and Anxiety Symptoms Questionnaire short-form, and personality was assessed by the Dimensional Assessment of Personality Pathology short-form (DAPPs). Cognitive function was assessed by 11 tests. Compared with matched controls, patients cured from acromegaly scored significantly worse on virtually all psychopathology questionnaires and on several subscales of the DAPPs. Compared with NFMA patients, patients cured from acromegaly scored worse on negative affect (P=0.050) and somatic arousal (P=0.009) and seven of 18 subscales of the DAPPs (Pmaladaptive personality traits but not cognitive dysfunction, compared with matched controls and patients treated for NFMA. These results suggest irreversible effects of previous GH excess, rather than effects of pituitary adenomas per se and/or their treatment, on the central nervous system.
Fukuda, Izumi; Hizuka, Naomi; Muraoka, Toko; Kurimoto, Makiko; Yamakado, Yu; Takano, Kazue; Ichihara, Atsuhiro
Untreated acromegaly is associated with a twofold to fourfold increased mortality risk compared to the population. Recently, new therapeutic modalities have been developed and may contribute to an improvement in treatment outcomes in patients with acromegaly. In the current study we determined the clinical features and recent therapeutic outcomes in patients with acromegaly. The initial symptoms, selected therapeutic modalities, and outcomes in 125 patients with acromegaly (M/F, 49/76, 19-86 years) who were admitted to our institution between 2001 and 2010 were analyzed using medical charts. The basal GH levels and IGF-I SD scores in the patients ranged from 0.17 to 90.21 μg/L and 1.9-13.6, respectively. Acral enlargement (face, hands, and feet) without overt complications was essential to the diagnosis in 49 % of the patients. In these cases, it required 5 years to establish the diagnosis of acromegaly after symptom onset. Twenty (16 %) and 13 (10 %) patients had diabetes mellitus and hypertension 6 years prior to the diagnosis of acromegaly, respectively. In 35 patients with microadenomas, the rate of controlled cases following transsphenoidal surgery was 93 %. In 90 patients with macroadenomas, the remission rate was 79 % with multidisciplinary treatment. In cases in which the tumor extended beyond the lateral tangent of the internal carotid artery (Knosp grade ≥3), the remission rate was 33-56 %. Improvements in surgical techniques and medical therapies may contribute to increased rates of controlled cases in patients with acromegaly, although advanced lateral extension of the tumor remains a critical determinant of the therapeutic outcome.
Joanna Elżbieta Malicka
Full Text Available Background . Acromegaly is a rare chronic disease with an excessive secretion of growth hormone, which leads to characteristic changes in appearance, organ and metabolic complications and neoplasms, which are a significant cause of shortened survival time. One of the most common consequences of acromegaly is disturbed carbohydrate metabolism. Objectives . The aim of this study was to assess the prevalence of disorders of carbohydrate tolerance and their relationship with the prevalence of malignant tumours in subjects with acromegaly. Material and methods. The study group comprised 69 patients with confirmed acromegaly (26 M, 43 F, aged 26–83 (mean 58.9 ± 11.0. Medical histories and the results of laboratory tests – plasma fasting glucose and oral glucose tolerance test, as well as the results of imaging and histopathological examinations performed in cases of suspected cancer lesions were analyzed. Results Disorders of carbohydrate tolerance were confirmed in a total of 46 patients (66.7%. 23 patients (33.3% had normal glucose tolerance. Diabetes was diagnosed in 22 patients (31.9%, while prediabetes was diagnosed in 24 (34.8% patients. In the analyzed group there were 6 cases of cancers, including 5 patients with concomitant diabetes, which represented a value significantly higher (p = 0.01 compared to patients without diabetes. The sixth case of cancer was detected in a woman with IGT . In patients with normal glucose tolerance there was no case of cancer. Conclusions . Among patients with acromegaly, disorders of carbohydrate tolerance occur in more than half of the cases, which confirms the need for active screening in this group of patients, in which a significant role is played by General Practitioners. General Practitioners should also consider the possibility of acromegaly in the differential diagnosis of glucose tolerance disorders detected in their patients. All patients with acromegaly, especially with concomitant diabetes or
Full Text Available Among multimodality treatments for acromegaly, the goals of surgical intervention are to balance maximal tumor resection while preserving normal pituitary function and maintaining patient safety. The resection of growth hormone-(GH- secreting pituitary adenomas in the hands of experienced surgeons results in hormonal remission in 50–70% of patients. Acromegalic patients often have medical comorbidities and anatomical variations complicating anesthesia and surgical management. Despite these challenges, complications such as CSF leak or new hypopituitarism following surgery remain uncommon. Over the past decade, endoscopic approaches to pituitary tumors have improved visualization and facilitated identification of additional tumor using angled telescopes. Patients with persistent acromegaly following surgery require continued medical and/or radiation-based interventions. The adjunctive use of stereotactic radiosurgery offers hormonal remission in 40–50% of patients. In this article, the current preoperative evaluation, indications for surgery, surgical approaches, role of radiosurgery, complications, and remission criteria following operative resection of GH adenomas are reviewed.
Shimatsu, A; Imura, H; Irie, M; Nakagawa, S; Goto, Y; Shimizu, N; Takeda, R; Kato, Y; Saito, S; Ibayashi, H
Sixty-four patients with active acromegaly and three patients with gigantism were treated with the long acting somatostatin analog SMS 201-995 (50-500 micrograms, sc, every 6-12 h or 150-880 micrograms daily by intermittent sc infusion, for up to 114 weeks). The fasting plasma GH levels were significantly suppressed (less than 50% of the values before treatment) in 49 patients and became normal in 18 patients. Suppression of GH secretion was associated with normalization of plasma somatomedin-C levels (14 out of 30 cases) and significant clinical improvement such as disappearance of headache and decrease of excessive sweating. Shrinkage of pituitary tumors as determined by computed tomography and/or magnetic resonance imaging studies occurred in 11 out of 40 cases. Side effects were minimal and tolerable. SMS 201-995 appears to be an effective agent for the treatment of acromegaly and gigantism.
Zampieri, P; Scanarini, M; Sicolo, N; Andrioli, G; Mingrino, S
Four cases of growth-hormone-secreting pituitary adenoma, with associated aspects of acromegaly and gigantism, are reported in patients aged 12-26. All of the patients had macroadenomas and were treated surgically, three by the transsphenoidal approach and one with a transfrontal craniotomy. Histologic examination revealed eosinophilic adenomas in three of the cases and a mixed eosinophilic--chromophobe adenoma in one, all with cellular irregularities (mitosis and cellular and nuclear polymorphism), local invasivity, or both. Because surgical treatment did not produce complete normalization of growth hormone levels, radiotherapy followed the operations in all four cases. In our opinion, the treatment of acromegalic gigantism poses more therapeutic problems than that of simple acromegaly, with combined treatment (surgical, radiation, and medical) often being necessary.
Pereira, Erlick A C; Turner, Martin R; Wass, John A H; Talbot, Kevin
We report a patient presenting with ALS in whom acromegaly was later confirmed. Insulin-like growth factor-1 (IGF-1) has been tried in the treatment of ALS and despite equivocal results from clinical trials, efforts have continued to try to harness the significant positive effects on motor neuron growth observed in vitro and in survival of mouse models of the disease. One subsequent study has reported an association between higher circulating serum IGF-1 levels and longer disease duration in ALS patients. Concern therefore arose in our case that treatment of the acromegaly with a somatostatin analogue might adversely affect the natural course of his ALS through lowering of potentially beneficial IGF-1 levels. Through clinical observation and prognostic modelling we suggest that this concern was unfounded. The potential interaction of these two rarely coincident disorders in our patient is discussed.
Orio, F; Iovino, M; Monteleone, P; Agrusta, M; Steardo, L; Lombardi, G
An extensive hypothalamic neurotransmitter impairment has been proposed in acromegaly. However, at the moment, the hypothalamic GABAergic system has been little investigated in this disorder. Since GABA has been shown to modulate growth hormone (GH) and prolactin (PRL) secretion in human subjects, it seemed reasonable to investigate hypothalamic GABAergic functioning through the assessment of basal GH and PRL responses to pharmacological activation of this system. 800 mg of sodium valproate (SV), a drug with GABA facilitating properties, were administered orally to 7 acromegalic patients and 9 healthy volunteers. Blood samples were collected before and after the drug administration for the measurement of plasma GH and PRL levels. SV induced a clear-cut rise in basal GH and a decrease in basal PRL in healthy subjects, but it did not induce any change in the basal levels of these hormones in acromegalics. These results suggest that the response of GH and PRL to SV in acromegaly is qualitatively different from normal controls.
Full Text Available Tongue enlargement and mandibular prognathism are clinically recognized in almost all patients with acromegaly. An acromegaly-like rat model recently developed by exogenous administration of insulin-like growth factor I (IGF-I was used to investigate morphological and histopathological changes in orofacial structures and to clarify whether these changes were reversible. Exogenous administration of IGF-I evoked specific enlargement of the tongue with identifiable histopathological changes (increased muscle bundle width, increased space between muscle bundles, and increased epithelial thickness, elongation of the mandibular alveolar bone and ascending ramus, and lateral expansion of the mandibular dental arch. Regarding histopathological changes in the mandibular condyle, the cartilaginous layer width, bone matrix ratio, and number of osteoblasts were all significantly greater in this rat model. After normalization of the circulating IGF-I level, tongue enlargement and histopathological changes in the tongue and mandibular condyle were reversible, whereas morphological skeletal changes in the mandible remained.
Iikubo, Masahiro; Kojima, Ikuho; Sakamoto, Maya; Kobayashi, Akane; Ikeda, Hidetoshi; Sasano, Takashi
Tongue enlargement and mandibular prognathism are clinically recognized in almost all patients with acromegaly. An acromegaly-like rat model recently developed by exogenous administration of insulin-like growth factor I (IGF-I) was used to investigate morphological and histopathological changes in orofacial structures and to clarify whether these changes were reversible. Exogenous administration of IGF-I evoked specific enlargement of the tongue with identifiable histopathological changes (increased muscle bundle width, increased space between muscle bundles, and increased epithelial thickness), elongation of the mandibular alveolar bone and ascending ramus, and lateral expansion of the mandibular dental arch. Regarding histopathological changes in the mandibular condyle, the cartilaginous layer width, bone matrix ratio, and number of osteoblasts were all significantly greater in this rat model. After normalization of the circulating IGF-I level, tongue enlargement and histopathological changes in the tongue and mandibular condyle were reversible, whereas morphological skeletal changes in the mandible remained.
Orosz, Andrea; Csajbók, Éva; Czékus, Csilla; Gavallér, Henriette; Magony, Sándor; Valkusz, Zsuzsanna; Várkonyi, Tamás T; Nemes, Attila; Baczkó, István; Forster, Tamás; Wittmann, Tibor; Papp, Julius Gy; Varró, András; Lengyel, Csaba
Cardiovascular diseases, including ventricular arrhythmias are responsible for increased mortality in patients with acromegaly. Acromegaly may cause repolarization abnormalities such as QT prolongation and impairment of repolarization reserve enhancing liability to arrhythmia. The aim of this study was to determine the short-term beat-to-beat QT variability in patients with acromegaly. Thirty acromegalic patients (23 women and 7 men, mean age±SD: 55.7±10.4 years) were compared with age- and sex-matched volunteers (mean age 51.3±7.6 years). Cardiac repolarization parameters including frequency corrected QT interval, PQ and QRS intervals, duration of terminal part of T waves (Tpeak-Tend) and short-term variability of QT interval were evaluated. All acromegalic patients and controls underwent transthoracic echocardiographic examination. Autonomic function was assessed by means of five standard cardiovascular reflex tests. Comparison of the two groups revealed no significant differences in the conventional ECG parameters of repolarization (QT: 401.1±30.6 ms vs 389.3±16.5 ms, corrected QT interval: 430.1±18.6 ms vs 425.6±17.3 ms, QT dispersion: 38.2±13.2 ms vs 36.6±10.2 ms; acromegaly vs control, respectively). However, short-term beat-to-beat QT variability was significantly increased in acromegalic patients (4.23±1.03 ms vs 3.02±0.80, Pacromegaly in spite of unchanged conventional parameters of ventricular repolarization. This enhanced temporal QT variability may be an early indicator of increased liability to arrhythmia.
Wijayaratne, Dilushi Rowena; Arambewela, M. H.; Dalugama, Chamara; Wijesundera, Dishni; Somasundaram, Noel; Katulanda, Prasad
Introduction Acromegaly is an endocrine disorder arising from excessive serum growth hormone levels in adulthood and is characterized by progressive somatic enlargement. Biochemical confirmation is achieved by demonstration of elevated baseline serum growth hormone levels which are not suppressed during an oral glucose tolerance test, and by increased levels of serum insulin-like growth factor-1. The serum insulin-like growth factor-1 level provides an assessment of integrated growth hormone ...
Mooney, Michael A.; Simon, Elias D.; Little, Andrew S.
The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036
Full Text Available Cynthia Plunkett, Ariel L BarkanDivision of Endocrinology, University of Michigan Medical Center, Ann Arbor, MI, USAAbstract: Patients with acromegaly (a condition of chronic growth hormone hypersecretion by a pituitary adenoma often require pharmacological treatment. Somatostatin analogs (SSAs such as pasireotide, lanreotide, and octreotide are frequently used as first-line medical therapy. As SSAs are delivered by regular subcutaneous or intramuscular injections, they can result in injection-related pain or anxiety and can be challenging to fit into patients’ lifestyles. When combined with the prolonged, debilitating psychological complications associated with acromegaly, these administration challenges can negatively impact compliance, adherence, and quality of life. Proactively managing patients’ expectations and providing appropriate, timely guidance are crucial for maximizing adherence, and ultimately, optimizing the treatment experience. As part of ongoing clinical research since 1997, our team at the University of Michigan has used SSAs to treat 30 patients with acromegaly. Based on our clinical experiences with multiple SSA administration regimens (long-acting intramuscular, long-acting deep subcutaneous, and twice-daily subcutaneous, we generated a dialog map that guides health care professionals through the many sensitive and complex patient communication issues surrounding this treatment process. Beginning with diagnosis, the dialog map includes discussion of treatment options, instruction on proper drug administration technique, and ensuring of appropriate follow-up care. At each step, we provide talking points that address the following: the patients’ clinical situation; their geographic, economic, and psychological concerns; and their inclination to communicate with clinicians. We have found that involving patients, nurses, and physicians as equal partners in the treatment process optimizes treatment initiation, adherence
Full Text Available Introduction: Patients with acromegaly can be treated with surgery, medical therapy and/or radiation therapy. For the patients not being cured with surgery, treatment with somatostatin analogues (SSAs is the primary therapy. SSA can be taken by self- or partner-administered injections in addition to being given by a nurse at a clinic. The aim was to assess if patients with acromegaly prefer self-injections and to investigate their attitudes towards long-term medical therapy. Method: All patients in the southern medical region of Sweden with a diagnosis of acromegaly and treated with SSA were eligible for the study (n = 24. The study is based on a questionnaire asking about the patients’ attitudes and preferences for injections with SSA, including their attitudes towards self-injection with SSA. Results: The patients’ (23 included median age was 68.5 years and the patients had been treated with SSA for 13 (1–38 years. One patient was currently self-injecting. All of the other patients were receiving injections from a nurse at a clinic. Three patients preferred self-injections, one preferred partner injections and 19 patients did not prefer self- or partner injections. The most frequent arguments to not preferring self-injections were ‘feeling more secure with an educated nurse’ and ‘preferring regular contact with a specialised nurse’. Conclusion: Patients with acromegaly prefer regular contact with the endocrine team to the independence offered by self-injections. These findings might mirror the patients’ desires for continuity and safety. We need to address patients’ concerns regarding injections with SSA and support them in their choices.
Radian, Serban; Diekmann, Yoan; Gabrovska, Plamena; Holland, Brendan; Bradley, Lisa; Wallace, Helen; Stals, Karen; Bussell, Anna‐Marie; McGurren, Karen; Cuesta, Martin; Ryan, Anthony W.; Herincs, Maria; Hernández‐Ramírez, Laura C.; Holland, Aidan; Samuels, Jade; Aflorei, Elena Daniela; Barry, Sayka; Dénes, Judit; Pernicova, Ida; Stiles, Craig E.; Trivellin, Giampaolo; McCloskey, Ronan; Ajzensztejn, Michal; Abid, Noina; Akker, Scott A.; Mercado, Moises; Cohen, Mark; Thakker, Rajesh V.; Baldeweg, Stephanie; Barkan, Ariel; Musat, Madalina; Levy, Miles; Orme, Stephen M.; Unterländer, Martina; Burger, Joachim; Kumar, Ajith V.; Ellard, Sian; McPartlin, Joseph; McManus, Ross; Linden, Gerard J.; Atkinson, Brew; Balding, David J.; Agha, Amar; Thompson, Chris J.; Hunter, Steven J.; Thomas, Mark G.; Morrison, Patrick J.
ABSTRACT The aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304* (or p.R304*; NM_003977.3:c.910C>T, p.Arg304Ter) identified in Northern Ireland (NI) predisposes to acromegaly/gigantism; its population health impact remains unexplored. We measured R304* carrier frequency in 936 Mid Ulster, 1,000 Greater Belfast (both in NI) and 2,094 Republic of Ireland (ROI) volunteers and in 116 NI or ROI acromegaly/gigantism patients. Carrier frequencies were 0.0064 in Mid Ulster (95%CI = 0.0027–0.013; P = 0.0005 vs. ROI), 0.001 in Greater Belfast (0.00011–0.0047) and zero in ROI (0–0.0014). R304* prevalence was elevated in acromegaly/gigantism patients in NI (11/87, 12.6%, P < 0.05), but not in ROI (2/29, 6.8%) versus non‐Irish patients (0–2.41%). Haploblock conservation supported a common ancestor for all the 18 identified Irish pedigrees (81 carriers, 30 affected). Time to most recent common ancestor (tMRCA) was 2550 (1,275–5,000) years. tMRCA‐based simulations predicted 432 (90–5,175) current carriers, including 86 affected (18–1,035) for 20% penetrance. In conclusion, R304* is frequent in Mid Ulster, resulting in numerous acromegaly/gigantism cases. tMRCA is consistent with historical/folklore accounts of Irish giants. Forward simulations predict many undetected carriers; geographically targeted population screening improves asymptomatic carrier identification, complementing clinical testing of patients/relatives. We generated disease awareness locally, necessary for early diagnosis and improved outcomes of AIP‐related disease. PMID:27650164
Jordi L Reverter
Full Text Available Data on the prevalence of benign and malignant nodular thyroid disease in patients with acromegaly is a matter of debate. In the last decade an increasing incidence of thyroid cancer has been reported. The aim of this study was to evaluate the prevalence of goiter, thyroid nodules and thyroid cancer in a large series of patients with acromegaly with a cross-sectional study with a control group. Six Spanish university hospitals participated. One hundred and twenty three patients (50% men; mean age 59±13 years; disease duration 6.7±7.2 years and 50 controls (51% males, mean age 58±15 years were studied. All participants underwent thyroid ultrasound and fine needle aspiration. Cytological analysis was performed in suspicious nodules between 0.5 and 1.0 cm and in all nodules greater than 1.0 cm. Goiter was more frequently found in patients than in controls (24.9 vs. 8.3%, respectively; p<0.001. Nodular thyroid disease as well as nodules greater than 1 cm were also more prevalent in acromegalic patients (64.6%, vs. 28.6%, p<0.05 and 53.3 vs. 28.6%, respectively; p<0.05, and all underwent fine needle aspiration. Suspicious cytology was detected in 4 patients and in none of the controls. After thyroidectomy, papillary thyroid carcinoma was confirmed in two cases (3.3% of patients with thyroid nodules, representing 1.6% of the entire group of patients with acromegaly (2.4% including a case with previously diagnosed papillary thyroid carcinoma. These data indicated that thyroid nodular disease and cancer are increased in acromegaly, thus justifying its routine ultrasound screening.
Definition and epidemiology The first historical description of acromegaly could be the story of David and Goliath described both in The Old Testament and in the Koran. Goliath was a giant, but David defeated him by sneaking up on him, maybe in his visual field defect, and hitting him with a stone in the forehead using a sling. The connection between gigantism and the pituitary, hence with the possibility of visual disturbances, was not recognized until 1884, published in a book by Fritzsc...
Cander, Soner; Oz Gul, Ozen; Ersoy, Canan; Erturk, Erdinc
AbstractIn acromegaly, transsphenoidal hypophysectomy is the primary treatment of choice. Medical treatment is performed on patients uncontrollable with surgery. Indications for primary medical treatment or medical treatment prior to surgery are limited to patients with macroadenoma with high risk for surgery due to cardiac and respiratory problems. Medical treatment is not applied on patients with microadenoma due to the high chance of cure with surgical option. Seventy-five years-old female...
U. A. Tsoy
Full Text Available Background: Obstructive sleep disordered breathing or obstructive sleep apnea (OSA is the most common respiratory impairment in acromegaly. OSA is bound up with heightened cardiovascular mortality. Aim: Тo study frequency, features, and structure of sleep disordered breathing in patients with newly diagnosed acromegaly and to elucidate the factors influencing their development. Materials and methods: 38 patients (10 men, 28 women, median age 53 (28-76 years, median body mass index (BMI 29 (19.9-44.3 kg/m² with newly diagnosed acromegaly were recruited into the study. All subjects underwent full polysomnography (Embla N7000, Natus, USA and Remlogica software (USA. Results: Sleep disordered breathing was found in 28 (73.7% patients. OSA was revealed in all cases, in 11 (39.3% subjects it was mixed. In 10 (35.7% patients OSA was mild, in 8 (28.6% moderate, and in 10 (35.7% severe. BMI (р<0.01, disease duration (р=0.003, and insulin-like growth factor-1 (IGF-1 level (р=0.04 were different in patients without OSA and patients with moderate-to-severe OSA. No difference was found in sex (р=0.4, age (р=0.064, and growth hormone level (р=0.6. Frequency of arterial hypertension, diabetes mellitus, and other glucose metabolism impairments was the same in subjects without OSA and with severe-to-moderate OSA. Conclusion: All patients with newly diagnosed acromegaly should undergo polysomnography. BMI, disease duration, and IGF-1 level are significant risk factors for OSA development. Correlation OSA with arterial hypertension and glucose metabolism impairments needs to be further investigated.
Orosz, Andrea; Csajbók, Éva; Czékus, Csilla; Gavallér, Henriette; Magony, Sándor; Valkusz, Zsuzsanna; Várkonyi, Tamás T.; Nemes, Attila; Baczkó, István; Forster, Tamás; Wittmann, Tibor; Papp, Julius Gy.; Varró, András; Lengyel, Csaba
Cardiovascular diseases, including ventricular arrhythmias are responsible for increased mortality in patients with acromegaly. Acromegaly may cause repolarization abnormalities such as QT prolongation and impairment of repolarization reserve enhancing liability to arrhythmia. The aim of this study was to determine the short-term beat-to-beat QT variability in patients with acromegaly. Thirty acromegalic patients (23 women and 7 men, mean age±SD: 55.7±10.4 years) were compared with age- and sex-matched volunteers (mean age 51.3±7.6 years). Cardiac repolarization parameters including frequency corrected QT interval, PQ and QRS intervals, duration of terminal part of T waves (Tpeak-Tend) and short-term variability of QT interval were evaluated. All acromegalic patients and controls underwent transthoracic echocardiographic examination. Autonomic function was assessed by means of five standard cardiovascular reflex tests. Comparison of the two groups revealed no significant differences in the conventional ECG parameters of repolarization (QT: 401.1±30.6 ms vs 389.3±16.5 ms, corrected QT interval: 430.1±18.6 ms vs 425.6±17.3 ms, QT dispersion: 38.2±13.2 ms vs 36.6±10.2 ms; acromegaly vs control, respectively). However, short-term beat-to-beat QT variability was significantly increased in acromegalic patients (4.23±1.03 ms vs 3.02±0.80, Pacromegaly in spite of unchanged conventional parameters of ventricular repolarization. This enhanced temporal QT variability may be an early indicator of increased liability to arrhythmia. PMID:25915951
Lim, Dawn Shao Ting; Fleseriu, Maria
Uncontrolled acromegaly results in approximately 2-fold excess mortality. Pituitary surgery is first-line therapy, and medical treatment is indicated for persistent disease. While cabergoline and pegvisomant are used in select patients, somatostatin receptor ligands (SRLs) remain the cornerstone of medical treatment. Management of patients poorly responsive to SRLs is therefore, challenging. The purpose of this review is to highlight the options for combination medical therapy in the treatment of acromegaly, with an emphasis on efficacy and safety. All original articles/abstracts detailing combination medical therapy in acromegaly were identified from a PubMed search. Studies reviewed included retrospective and open-label prospective studies. While the combination of SRL and cabergoline was generally well tolerated, a lower baseline insulin-like growth factor-1 (IGF-1) level was the best predictor of efficacy; this combination may be most effective in patients with mildly elevated IGF-1. SRL-pegvisomant combination normalized IGF-1 in the majority of patients; continued efficacy despite individual drug dosing reduction was also reported. The risk of significant liver enzyme elevation was, however, higher than that reported with SRL monotherapy; close monitoring is recommended. Data on pegvisomant-cabergoline combination is limited, but this may be an option in the setting of SRL intolerance. Reports on temozolomide used in combination with other medical therapies in patients with aggressive GH-secreting tumors are also summarized. While more prospective, randomized controlled trials on long-term efficacy and safety are needed, combination medical therapy remains a treatment strategy that should be considered for acromegaly patients poorly responsive to SRLs.
Colao, Annamaria; Auriemma, Renata S; Pivonello, Rosario
In nearly all cases, acromegaly is caused by excess GH from a pituitary adenoma, resulting in elevated circulating levels of GH and, subsequently, IGF-1. Treatment goals are to eliminate morbidity and restore the increased mortality to normal rates. Therapeutic strategies aim to minimize tumor mass and normalize GH and IGF-1 levels. Somatostatin analogues are the medical treatment of choice in acromegaly, as first-line or post-surgical therapy, and have proven efficacy in pituitary tumor volume reduction (TVR). Here we review the effects of somatostatin analogue therapy on pituitary tumor volume in patients with acromegaly. TVR with somatostatin analogues may be mediated by direct anti-proliferative effects via activation of somatostatin receptors, or by indirect effects, such as angiogenesis inhibition, and is more pronounced when they are administered as first-line therapy. Various studies of first-line treatment with octreotide LAR have shown significant TVR in ≥73% of patients. First-line treatment with lanreotide Autogel has shown evidence of TVR, although more studies are needed. In a recent randomized, double-blind, 12-month trial in 358 medical-treatment-naïve acromegaly patients, significant TVR was achieved by 81% of patients administered pasireotide LAR and 77% administered octreotide LAR. Pre-operative somatostatin analogue therapy may also induce TVR and improve post-operative disease control compared with surgery alone. TVR is progressive with prolonged treatment, and decreased IGF-1 levels may be its best predictor, followed by age and degree of GH decrease. However, TVR does not always correlate with degree of biochemical control. Somatostatin analogues (first- or second-line treatment) are the mainstay of medical therapy and, as first-line medical therapy, are associated with significant pituitary TVR in most patients.
Michael Anthony Mooney
Full Text Available The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment.
A V Dreval’
Full Text Available Aim of this study was to investigate efficiency and safety of OctreotidLong FS in patients with acromegaly. Materials and methods. 41 patients with acromegaly (8 – de novo and 33 patients after different somato statin analogs treatment was treated OctreotidLong FS one injection in 28 days. Growth hormone (GH, Insulin like Growth Factor 1 (IFG1, fasting glucose (FG and HbA1c were assess after 3, 6 and 12 month of therapy. Results. We found out the decreasing of GH and IGF1 from 12,8 (8,0–82,7 mU/ml to 3,8 (1,6–13,8 mU/ml ( p < 0,05 and %IGF1 increasing (% IGF1 from 231 (150–286% to 9,5 (−26–111% ( p < 0,05 in 8 de novo acromegalic patients. We also revealed that IGF1 didn’t change and GH decreased after 3 month (33 patients, 6 month (22 patients and 12 month (8 patients of OctreotidLong FS treatment. We didn’t observed negative effect of OctreotidLong FS treatment to carbohydrate metabolism in patients with acromegaly. Conclusion. The therapy of OctreotidLong FS leads to induce successful control of GH and IGFI in 50% de novo patients and didn’t change the number of patients with control of acromegaly after another somato statin analogs treatment. Carbohydrate metabolism also didn’t change after OctreotidLong FS treatment.
Polanco-Briceno, Susan; Glass, Daniel; Plunkett, Cindy
Purpose This study was designed to assess the awareness and utilization of resources to improve patients’ treatment experiences among endocrinologists who currently treat patients with acromegaly. Methods A total of 4,280 US endocrinologists were randomly selected from the CMS National Plan and Provider Enumeration System and were invited by mail to participate in a 20-minute online survey. In order to qualify, respondents had to be the primary physician making treatment decisions for at least one patient for their acromegaly. Results Results are based on responses from 126 physicians from primarily urban and suburban practices, with a median of five acromegaly patients. A total of 70% of patients are currently receiving drug therapy; among these, 91% are on octreotide (51%), lanreotide (29%), or pasireotide (11%), alone or in combination with another therapy. Nearly half of the respondents thought that the impact of patient adherence on therapy outcome for acromegaly was either not very (40%) or not at all (7%) significant. Respondents who believe patient adherence significantly impacts treatment outcome were significantly more likely to discuss automated adherence reminders (50% vs 26%; P=0.015), mobile administration programs (57% vs 35%; P=0.029), and symptom tracking (72% vs 42%; P=0.002). Overall, 44% of respondents routinely recommend education/emotional support programs, and 25% routinely recommend financial assistance programs. Respondents who believe patient adherence significantly impacts treatment outcome generally were more familiar with individual education and emotional support programs compared to those who do not, although they were not more likely to routinely refer patients to any of these resources. Conclusion There are unmet needs with respect to increasing awareness among physicians of the importance of patient adherence to therapy, resources available to patients, and how collaboration among patients, nurses, and physicians can improve
Zoppoli, Gabriele; Bianchi, Federico; Bruzzone, Andrea; Calvia, Alessandro; Oneto, Caterina; Passalia, Caterina; Balleari, Enrico; Bedognetti, Davide; Ponomareva, Elena; Nazzari, Elena; Castelletti, Lara; Castellan, Lucio; Minuto, Francesco; Ghio, Riccardo; Ferone, Diego
Polycythemia associated with acromegaly is usually caused by the systemic manifestations of the disease, such as sleep-apnea or concomitant erythropoietin-secreting kidney tumors. The recognition of underlying pathologies requires a thorough diagnostic process. We report a unique case of acromegaly with polycythemia, not caused by commonly described manifestations of the disease, and receding with octreotide therapy. The medical history of 141 acromegalic patients followed by the Endocrinology Unit of the San Martino University Hospital in Genoa has been also reviewed, together with the literature evidence for similar cases. The diagnostic workflow and 2-years follow-up of a 43-years old acromegalic, polycythemic man with a history of past smoking, moderate hypertension, and mental retardation are described. The hematological parameters of our cohort was retrospectively compared with those of a healthy, age/gender-related control group as well. Therapy with octreotide LAR, 20 mg i.m. q28d was begun soon after diagnosis of acromegaly in the polycythemic patient. Haematocrit level, hormonal setting, as well as pituitary tumor size and visual perimetry during treatment were recorded. Octreotide LAR treatment normalized hormonal alterations, as well as hematological parameters. Polycythemia has not recurred after 2 years of therapy. The median hemoglobin and hematocrit levels of the retrospectively analyzed cohort of acromegalic were significantly lower than normal ranges of a healthy, age/sex- related control population. In conclusions, polycythemia can be a direct, albeit rare, secondary manifestation of acromegaly, that must be considered during the diagnostic work-up of acromegalic patients presenting with such disorder.
Ferdinand Roelfsema, Nienke R Biermasz, Alberto M Pereira, Johannes A RomijnDepartment of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, The NetherlandsBackground: In acromegaly, expert surgery is curative in only about 60% of patients. Postoperative radiation therapy is associated with a high incidence of hypopituitarism and its effect on growth hormone (GH) production is slow, so that adjuvant medical treatment becomes of importance in the management of many patient...
Giustina, Andrea; Mazziotti, Gherardo; Cannavò, Salvatore; Castello, Roberto; Arnaldi, Giorgio; Bugari, Giovanna; Cozzi, Renato; Ferone, Diego; Formenti, Anna Maria; Gatti, Enza; Grottoli, Silvia; Maffei, Pietro; Maffezzoni, Filippo; Montini, Marcella; Terzolo, Massimo; Ghigo, Ezio
Increase in drug frequency or dose is recommended for acromegaly patients with partial response to long-acting somatostatin receptor ligands (SRLs). However, the efficacy and safety data with lanreotide (LAN) Autogel (LAN-ATG) at high dose (HD) or high frequency (HF) are still scanty. To evaluate the biochemical efficacy and safety of HF and HD LAN-ATG in patients with active acromegaly. Twenty-four-week prospective, multicenter, randomized, open-label trial. Thirty patients with active acromegaly, partial responders to SRLs, were randomized to HF (120 mg/21 days; 15 patients) or HD (180 mg/28 days; 15 patients) LAN-ATG. Normalization of serum insulin-like growth factor-I (IGF-I) and reduction in random growth hormone (GH) values < 1.0 µg/L, reduction in serum IGF-I and GH from baseline, differences in biochemical response between HF and HD LAN-ATG, adverse events. IGF-I decreased significantly (P = 0.007) during the 24-week treatment, with greater decrease in HD (P = 0.03) vs HF group (P = 0.08). Normalization in IGF-I values occurred in 27.6% of patients (P = 0.016 vs baseline), without a significant difference between HF and HD groups (P = 0.59). The decrease in serum IGF-I significantly correlated with serum LAN values (P = 0.04), and normalization of IGF-I was predicted by baseline IGF-I values (P = 0.02). Serum GH values did not change significantly (P = 0.22). Overall, 19 patients (63.3%) experienced adverse events, all being mild to moderate and transient, without differences between the two therapeutic arms. HF and HD LAN-ATG regimens are effective in normalizing IGF-I values in about one-third of patients with active acromegaly inadequately controlled by long-term conventional SRLs therapy.
Goto, Junko; Otsuka, Fumio; Inagaki, Kenichi; Tsukamoto, Naoko; Suzuki, Jiro; Miyoshi, Tomoko; Ogura, Toshio; Kamada, Yasuhiko; Makino, Hirofumi
We report a rare case of polycystic ovary syndrome (PCOS) complicated with acromegaly due to a growth hormone (GH)-producing pituitary adenoma. Complete removal of the pituitary adenoma successfully reduced circulating levels of GH and insulin-like growth factor (IGF)-1, which, in turn, resulted in the amelioration of gonadal dysfunction, hyperandrogenism, lutenizing hormone hypersecretion, and severe insulin resistance. This clinical complication suggests that activation of systemic GH-IGF-1 axis is potentially involved in the development of PCOS.
Full Text Available Background: There are conflicting data regarding the prevalence of colorectal polyp in patients with acromegaly. Subjects and Methods: Consecutive forty-seven acromegalic patients (21 men, 26 women, with a mean age of (40 ± 12 years attending endocrinology outpatient department underwent full colonoscopy. All the patients underwent clinical and biochemical evaluation (glucose suppressed growth hormone (GH, Insulin-like growth factor-1 [IGF-1], fasting insulin, and glucose. The control group (n = 120 for colonoscopy was adult subjects undergoing evaluation for symptoms of irritable bowel syndrome. Clinical and biochemical parameters in acromegalic patients with colonic polyp were compared to those without a polyp. Results: Patients with acromegaly had significantly higher prevalence of colonic polyp as compared to control subjects (10.6% vs. 0.8%. None of the patients with polyp had skin tags. There was no significant difference between subjects with and without colonic polyp in duration of illness, basal, and glucose-suppressed GH and most recent IGF-1. Fasting blood sugar was significantly higher (P < 0.05 in adenoma group after adjusting for age, body mass index (BMI, and insulin levels. Patients in adenoma group showed a trend toward male gender and younger age as compared to those without adenoma. Conclusions: Subjects with acromegaly as compared to control have a higher prevalence of colonic polyps. There was no association of polyps seen with age, BMI, skin tags, homeostasis model assessment of insulin resistance index, duration of disease, and basal and glucose-suppressed GH and IGF-1 levels. There were no specific predictive factors detected. Screening full colonoscopy is recommended in all cases with acromegaly.
Full Text Available Abstract Introduction The first-line treatment for acromegaly is transsphenoidal surgery. In approximately 50% of patients, however, a cure is not possible with surgery and alternatives are needed. Somatostatin analog therapy is the recommended first-line treatment in patients with such cases. Here we provide the first report of a high-dose lanreotide primary therapy in patients with acromegaly. Case presentation Six patients who were not suitable for surgery were given 60 mg of lanreotide (Autogel® every four weeks. All patients were German nationals and Caucasian. When the response of our patients was unsatisfactory, the dose was increased sequentially to 90 mg every four weeks, 120 mg every four weeks, 120 mg every three weeks and 180 mg every three weeks. Treatment duration was 12 to 24 months. In all cases, the lanreotide dose was 120 mg every 4 weeks or higher. In five of our patients, growth hormone (GH levels were successfully reduced (in three patients GH Tumor shrinkage or degeneration was observed in the five responding patients. No drug-related adverse events were noted. Conclusions These results suggest that lanreotide at high doses of 120 mg every four weeks or more is an effective first-line therapy for patients with acromegaly that surgery alone cannot treat.
van der Lely, A J; de Herder, W W; Lamberts, S W
Acromegaly was the first pituitary disease to be recognised as a clinical entity, although initially it was not clear whether the eosinophilic adenomas causing pituitary enlargement were causative or just a manifestation of the syndrome itself. Following the documented clinical improvement of patients with acromegaly after partial hypophysectomy, it was proven that the pituitary adenomas were aetiological. The treatment of acromegaly has changed during the last decades; the introduction of the somatostatin (SMS) analogue octreotide has had major implications. Octreotide was the first SMS analogue to become available for clinical use. It is generally well tolerated, but is associated with the development of gallstones in 15 to 20% of patients. Other adverse effects include transient injection-site pain, abdominal, diarrhoea, gastritis (long term therapy) and loss of scalp hair. No long haematological or biochemical adverse effects have been reported. Desensitisation to the beneficial effects of octreotide therapy is highly unusual. A long-acting formulation of octreotide is being studied, and should be available by the end of 1997.
Because growth hormone and IGF-1 both have regulatory roles in the cardiovascular system, patients with acromegaly often present with abnormalities of heart structure and function and the vascular system, which if left unmanaged can reduce life expectancy. Early symptoms of acromegalic cardiomyopathy (hyperkinetic syndrome) can be characterized by cardiac hypertrophy, increased heart rate, and increased systolic output. When left untreated, more pronounced hypertrophy, signs of diastolic dysfunction and insufficient systolic function on exertion arise, and can lead to systolic dysfunction at rest, and eventually heart failure with signs of dilative cardiomyopathy. Increasingly, evidence suggests that early diagnosis and treatment of acromegaly (before the age of 40 years) can help prevent the progression of cardiovascular disease, improve quality of life, and reduce the risk of premature mortality. This review focuses on management strategies for newly diagnosed patients with acromegaly and evidence of cardiovascular disease. The roles of surgery and medical treatment are discussed in the context of using optimal treatment strategies to help reverse cardiac hypertrophy and normalize other cardiac risk factors.
Watanobe, H; Tamura, T
It has been reported that neuropeptide Y (NPY) affects growth hormone (GH) secretion in several animal species. With respect to the role of NPY in regulating GH release in humans, one previous study has reported that NPY inhibited GH secretion from cultured GH-secreting pituitary adenoma cells in vitro. However, since it has yet to be explored whether NPY affects GH secretion in acromegaly in vivo, in this study we attempted to examine the effect of intravenous (i.v.) bolus injection of 100 microg of human NPY on plasma GH levels in 15 patients with active acromegaly, trying to find a possible correlation among GH responses to NPY, thyrotropin-releasing hormone (TRH;500 microg, i.v.), luteinizing hormone-releasing hormone (LHRH;100 microg, i.v.), and bromocriptine (Br;2.5 mg, per os). NPY significantly increased GH secretion (more than twice the basal level) in 4 (27%) patients, and all of them were responsive to LHRH and non-responsive to Br. In contrast, 3 (20%) acromegalics showed a significant decrease in GH levels (less than half the baseline) after NPY, and all these patients were responsive to both TRH and Br. From these results, we hypothesize that the NPY-induced increase in GH release may be a feature of somatotroph-like pituitary adenoma causing acromegaly, whereas the NPY-induced decrease in GH secretion may be a feature of lactotroph-like adenoma.
Matsubara, M; Odagaki, E; Morioka, T
Inhibition of plasma GH by dopaminergic agonists is one of the characteristics of the GH secretion in acromegaly. GRF is known to stimulate GH secretion in most patients with acromegaly. In order to elucidate the relationship between GRF and dopamine in regulating the secretion of GH in this disease, we examined plasma GH responses to dopamine (DA) infusion (4 micrograms/kg/min), GRF injection (100 micrograms i.v.), sulpiride (SP) injection (200 mg i.v.), a DA blocker, DA plus GRF and SP plus GRF in a 51-year-old male patient with acromegaly. Plasma GH was reduced to 14% of the initial level by iv infusion of DA, and was elevated to 158% by iv injection of GRF. No considerable change was observed in plasma GH by iv infusion of SP (114% of the initial level). GH release induced by GRF was remarkably reduced by simultaneous administration of DA (28% of the initial level), whereas SP administration did not affect GRF-induced GH release (154%). The marked reduction of GH release after DA plus GRF seems to suggest that the effect of DA on the GH regulation is stronger than that of GRF in this acromegalic patient. It is suggested also that endogenous DA may not play an inhibitory role in GH secretion in this case since DA blockade by SP did not raise basal GH levels and the GH response to GRF.
Godang, Kristin; Olarescu, Nicoleta Cristina; Bollerslev, Jens; Heck, Ansgar
Bone turnover is increased in acromegaly. Despite normalization of bone turnover after treatment, the risk for vertebral fractures remains increased. Gonadal status, but not BMD, is correlated with vertebral fractures. Trabecular bone score (TBS) is related to bone microarchitecture. The aim of this study is to assess the longitudinal change in TBS and BMD following treatment for acromegaly. DESIGN, SETTING, PATIENTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: This longitudinal study included 48 patients with acromegaly between 2005 and 2015. BMD, TBS, and markers for bone turnover (P1NP and CTX-1) were measured at baseline and following treatment. Following treatment, the mean TBS decreased by 3.0 (±7.0) %, whereas the BMD at the lumbar spine (LS) increased by 3.2 (±4.9) % (both Pacromegaly affects TBS and BMD at LS in different manners. The reduction of bone turnover markers predicts the increase in BMD but not the decrease in TBS. The DXA changes were more pronounced in men. Alterations in trabecular bone architecture may explain the persistent fracture risk despite the increase in BMD after disease control. © 2016 European Society of Endocrinology.
Carmichael, John D; Broder, Michael S; Cherepanov, Dasha; Chang, Eunice; Mamelak, Adam; Said, Qayyim; Neary, Maureen P; Bonert, Vivien
The study aim was to estimate the proportion of acromegaly patients with various comorbidities and to determine if biochemical control was associated with reduced proportion of cardiovascular risk factors. Data were from a single-center acromegaly registry. Study patients were followed for ≥12 months after initial treatment. Study period was from first to last insulin-like growth factor-I and growth hormone tests. Of 121 patients, 55% were female. Mean age at diagnosis was 42.4 (SD: 15.0). Mean study period was 8.8 (SD: 7.2) years. Macroadenomas were observed in 93 of 106 patients (87.7%), and microadenomas in 13 (12.3%). Initial treatment was surgery in 104 patients (86%), pharmacotherapy in 16 (13.2%), and radiation therapy in 1 (0.8%). Of 120 patients, 79 (65.8%) achieved control during the study period. New onset comorbidities (reported 6 months after study start) were uncommon (acromegaly compared to their controlled counterparts in this single-center registry. About a third of the patients remained uncontrolled after a mean of >8 years of treatment, demonstrating the difficulty of achieving control in some patients.
Fracassi, F; Zagnoli, L; Rosenberg, D; Furlanello, T; Caldin, M
Acromegaly results from the overproduction of growth hormone in adulthood and is characterised by overgrowth of soft tissue and/or bone as well as insulin resistance. There are few data indicating the risk factors associated with this disease in dogs or its clinicopathological features and sequelae. The objective of this retrospective study was to catalogue and assess these aspects of the disease in German shepherd dogs (GSDs) which were found to be over-represented among acromegalic dogs attending two veterinary referral clinics over a period of 7 years. Each acromegalic dog (AD) was compared with two breed/age/sex matched controls. Clinical signs of acromegaly included panting, polyuria/polydipsia, widened interdental spaces, weakness, inspiratory stridor, macroglossia, weight gain, redundant skin folds, thick coat, exophthalmos and mammary masses. Serum alkaline phosphatase, creatine-kinase, glucose, triglyceride, phosphate ion, and 'calcium per phosphate product' concentrations were significantly higher in acromegalic animals while haemoglobin concentration, blood urea nitrogen, sodium and chloride ion concentrations, and urinary specific gravity, osmolality and fractional excretion of phosphate were significantly lower. Although, in the majority of cases clinicopathological abnormalities resolved following ovariohysterectomy, in one dog, acromegalic signs abated and insulin-like growth factor-1 concentrations normalised only following the surgical excision of mammary tumours carried out 2 months after ovariohysterectomy. The findings of this study indicate that GSDs are predisposed to the development of acromegaly with a suspected inherited susceptibility.
Roelfsema, Ferdinand; Biermasz, Nienke R; Pereira, Alberto M; Romijn, Johannes A
Background In acromegaly, expert surgery is curative in only about 60% of patients. Postoperative radiation therapy is associated with a high incidence of hypopituitarism and its effect on growth hormone (GH) production is slow, so that adjuvant medical treatment becomes of importance in the management of many patients. Objective To delineate the role of lanreotide in the treatment of acromegaly. Methods Search of Medline, Embase, and Web of Science databases for clinical studies of lanreotide in acromegaly. Results Treatment with lanreotide slow release and lanreotide Autogel® normalized GH and insulin-like growth factor-I (IGF-I) concentrations in about 50% of patients. The efficacy of 120 mg lanreotide Autogel® on GH and IGF-I levels was comparable with that of 20 mg octreotide LAR. There were no differences in improvement of cardiac function, decrease in pancreatic β-cell function, or occurrence of side effects, including cholelithiasis, between octreotide LAR and lanreotide Autogel®. When postoperative treatment with somatostatin analogs does not result in normalization of serum IGF-I and GH levels after noncurative surgery, pegvisomant alone or in combination with somatostatin analogs can control these levels in a substantial number of patients. PMID:19707377
Höybye, C; Chandramouli, V; Efendic, S; Hulting, A-L; Landau, B R; Schumann, W C; Wajngot, A
The diabetogenic effect of excess growth hormone (GH) such as that in acromegaly is well known. However, the contribution of the various components to hepatic glucose production (HGP) is not completely understood. In this study we evaluated insulin resistance, HGP, gluconeogenesis (GNG), and glycogenolysis (GLY) in five patients with acromegaly before and after pituitary microsurgery. Insulin resistance was estimated by the HOMA index. HGP was measured using a primed continuous (6,6- 2H2) glucose infusion, and GNG was measured from 2 H enrichment at carbons 2 and 5 of blood glucose on ingestion of 2H2O. The ratio of these enrichments equals the fractional contribution of GNG to HGP, and GLY was calculated as the difference between HGP and GNG. All measurements were performed after 12 hours of fasting. Levels of GH and IGF-I decreased, as did the HOMA index (p<0.05). HGP was reduced from 11.4 micromol/kg/min to 9.7 micromol/kg/min (p=0.032). GNG contributed most to HGP. GNG was unchanged, whereas GLY's fraction decreased 29% (p=0.056) postoperatively. This pilot study indicates that GNG is the main contributor to HGP and that GLY is more sensitive than is GNG to the insulin resistance existing in acromegaly.
Krause, W; Rassner, G; Happle, R
The university museum for cultural history in the castle of Marburg has a portrait "Die grosse Barb", which represents a women suffering from acromegaly. She shows the typical pathologic alterations: thickening of the skin folds, thickening of the lips and the eyelids, growth of bones and cartilages, lengthening of the nose, enlargement of the ears, protrusion of the zygoma, mandible and the chin. Acromegaly is a consequence of enhanced secretion of growth hormone, which occurs also as a symptom of several syndromes, such as multiple endocrine neoplasia type 1, McCune-Albright-syndrome, and NAME syndrome (Carney complex type I). The most remarkable symptom of acromegaly is the gigantism. This occurs also in androgen-deficient states, such as the Klinefelter syndrome and some more genetic syndromes, of which the Simpson-Golabi-Behmel syndrome, the Sotos syndrome, the Marfan syndrome, the homocystinuria, and the fragile X-syndrome may be mentioned. Nothing is known on the further fate of the patient shown in the portrait. It is also unknown, whether she owes her position as a chambermaid to her gigantism, for it was a common use in courts to have people with abnormal body shapes in attendance.
de Herder, Wouter W
In 1886 Pierre Marie used the term "acromegaly" for the first time and gave a full description of the characteristic clinical picture. However several others had already given clear clinical descriptions before him and sometimes had given the disease other names. After 1886, it gradually became clear that pituitary enlargement (caused by a pituitary adenoma) was the cause and not the consequence of acromegaly, as initially thought. Pituitary adenomas could be found in the great majority of cases. It also became clear that acromegaly and gigantism were the same disease but occurring at different stages of life and not different diseases as initially thought. At the end of the 19th and beginning of the 20th century most information was derived from case descriptions and post-mortem examinations of patients with acromegaly or (famous) patients with gigantism. The stage was set for further research into the pathogenesis, diagnosis and therapy of acromegaly and gigantism.
Maffezzoni, Filippo; Maddalo, Michele; Frara, Stefano; Mezzone, Monica; Zorza, Ivan; Baruffaldi, Fabio; Doglietto, Francesco; Mazziotti, Gherardo; Maroldi, Roberto; Giustina, Andrea
Vertebral fractures are an emerging complication of acromegaly but their prediction is still difficult occurring even in patients with normal bone mineral density. In this study we evaluated the ability of high-resolution cone-beam computed tomography to provide information on skeletal abnormalities associated with vertebral fractures in acromegaly. 40 patients (24 females, 16 males; median age 57 years, range 25-72) and 21 healthy volunteers (10 females, 11 males; median age 60 years, range: 25-68) were evaluated for trabecular (bone volume/trabecular volume ratio, mean trabecular separation, and mean trabecular thickness) and cortical (thickness and porosity) parameters at distal radius using a high-resolution cone-beam computed tomography system. All acromegaly patients were evaluated for morphometric vertebral fractures and for mineral bone density by dual-energy X-ray absorptiometry at lumbar spine, total hip, femoral neck, and distal radius. Acromegaly patients with vertebral fractures (15 cases) had significantly (p cone-beam computed tomography at the distal radius may be useful to evaluate and predict the effects of acromegaly on bone microstructure.
Asa, S L; Scheithauer, B W; Bilbao, J M; Horvath, E; Ryan, N; Kovacs, K; Randall, R V; Laws, E R; Singer, W; Linfoot, J A
We report the histological, ultrastructural, and immunocytochemical features of six hypothalamic gangliocytomas associated with pituitary GH cell adenomas and/or acromegaly. In four patients, the gangliocytoma was intrasellar, and no hypothalamic investigation was performed; in two patients, autopsy confirmed hypothalamic involvement. Four patients had a gangliocytoma associated with pituitary GH cell adenoma and acromegaly; electron microscopy demonstrated an intimate association between neurons and adenomatous GH cells. One patient had a gangliocytoma and a GH cell adenoma but no clinical evidence of acromegaly. In the sixth patient, clinical and biochemical acromegaly was manifest, but no pituitary adenoma was demonstrated. Using immunocytochemistry, human pancreatic tumor GRF (hptGRF-40) was localized in the majority of neurons of all six gangliocytomas. The pituitary adenomas and nontumorous adenohypophyses were negative for hptGRF-40. In addition, somatostatin, glucagon, and GnRH were demonstrated within some neurons of several tumors; insulin and gastrin stains were equivocal. These findings confirm previous proposals of production of a GRF by such gangliocytomas. While the significance of other peptides found in some of the tumors is uncertain, the presence of hptGRF-40 in neurons of these gangliocytomas supports the theory that GRF excess is the mechanism responsible for over-production of GH and provides evidence for a syndrome of hypothalamic acromegaly.
Full Text Available Cardiovascular diseases, including ventricular arrhythmias are responsible for increased mortality in patients with acromegaly. Acromegaly may cause repolarization abnormalities such as QT prolongation and impairment of repolarization reserve enhancing liability to arrhythmia. The aim of this study was to determine the short-term beat-to-beat QT variability in patients with acromegaly. Thirty acromegalic patients (23 women and 7 men, mean age±SD: 55.7±10.4 years were compared with age- and sex-matched volunteers (mean age 51.3±7.6 years. Cardiac repolarization parameters including frequency corrected QT interval, PQ and QRS intervals, duration of terminal part of T waves (Tpeak-Tend and short-term variability of QT interval were evaluated. All acromegalic patients and controls underwent transthoracic echocardiographic examination. Autonomic function was assessed by means of five standard cardiovascular reflex tests. Comparison of the two groups revealed no significant differences in the conventional ECG parameters of repolarization (QT: 401.1±30.6 ms vs 389.3±16.5 ms, corrected QT interval: 430.1±18.6 ms vs 425.6±17.3 ms, QT dispersion: 38.2±13.2 ms vs 36.6±10.2 ms; acromegaly vs control, respectively. However, short-term beat-to-beat QT variability was significantly increased in acromegalic patients (4.23±1.03 ms vs 3.02±0.80, P<0.0001. There were significant differences between the two groups in the echocardiographic dimensions (left ventricular end diastolic diameter: 52.6±5.4 mm vs 48.0±3.9 mm, left ventricular end systolic diameter: 32.3±5.2 mm vs 29.1±4.4 mm, interventricular septum: 11.1±2.2 mm vs 8.8±0.7 mm, posterior wall of left ventricle: 10.8±1.4 mm vs 8.9±0.7 mm, P<0.05, respectively. Short-term beat-to-beat QT variability was elevated in patients with acromegaly in spite of unchanged conventional parameters of ventricular repolarization. This enhanced temporal QT variability may be an early indicator of increased
Full Text Available Purpose: To evaluate bone mineral density (BMD measurements and the presence of periodontitis in patients with acromegaly, as well as to inquire the impact of interfering factors. Material and Method: Forty-seven acromegalic patients with any accompanying condition known to affect calcium-bone metabolism and 60 age-matched healthy controls were included. Age, gender, duration and activity of acromegaly, past-present therapy options, pituitary hormone profiles, replacement therapies, and the results of periodontal analysis were recorded. Results: Eighteen patients were male (38.3%, 29 were female (61.7%. The mean age of the patients was 46.6±11.5 years, twenty-five (53.1% had active, 22 (46.8% had inactive acromegaly. The latter were older and had longer disease duration (p=0.04, p=0.003, respectively. Serum calcium and phosphorus levels, 24-hour urinary calcium excretion and BMD at the lumbar spine and femur neck insignificantly associated with disease activity (p>0.05. Osteoporosis was detected in 6 patients (12.76%. Periodontitis and advanced periodontitis were more common in control group (66.7% vs. 44.7%, (43.3% vs. 12.8% (p=0.022, p=0.0001, respectively. There was no difference in chronic periodontitis and severity between active and inactive groups (48% vs. 40.9%; p=0.279. No difference was noted in other study parameters, as well. Repeated measures analysis of variance demonstrated statistically insignificant distribution between GH change in time and periodontitis subgroups. Discussion: We demonstrated that acromegaly exerted no clear negative impact on vertebral BMD in the absence of overt hypogonadism. Regardless of disease activity, acromegaly cases exhibited lower rates of periodontitis with less severity which remained unchanged in the presence of accompanying metabolic disorders known to have negative impact on periodontal tissue. Chronic exposure to excess GH may have a protective role against periodontitis. Turk Jem 2015; 19: 42-48
Shimatsu, Akira; Teramoto, Akira; Hizuka, Naomi; Kitai, Kazuo; Ramis, Joaquim; Chihara, Kazuo
The somatostatin analog lanreotide Autogel has proven to be efficacious for treating acromegaly in international studies and in clinical practices around the world. However, its efficacy in Japanese patients has not been extensively evaluated. We examined the dose-response relationship and long-term efficacy and safety in Japanese patients with acromegaly or pituitary gigantism. In an open-label, parallel-group, dose-response study, 32 patients (29 with acromegaly, 3 with pituitary gigantism) received 5 injections of 60, 90, or 120 mg of lanreotide Autogel over 24 weeks. Four weeks after the first injection, 41% of patients achieved serum GH level of gigantism) received lanreotide Autogel once every 4 weeks for a total of 13 injections. Dosing was initiated with 90 mg and adjusted according to clinical responses at Weeks 16 and/or 32. At Week 52, 47% of patients had serum GH levels of gigantism.
Gadoth, N; Bechar, M; Seggev, J; Kushnir, M; Gilai, A
Severe sleep apnea was present in a patient with upper airway obstruction due to acromegaly. The study of orbicularis oculi reflex responses (OORR) disclosed a marked prolongation of the late response prior to tracheostomy. Following the surgical relief of upper airway obstruction, sleep apnea disappeared, and the latency of the late response of the OORR was dramatically reduced but failed to normalize. The OORR and especially its late response were normal in a patient with acromegaly who did not experience sleep apnea. In two patients with sleep apnea, but without acromegaly, the late responses of the OORR were abnormal. It is suggested that the presence of abnormal OORR in sleep apnea may reflect a basic defect in pontomedullary control of respiration during sleep.
Kreitschmann-Andermahr, Ilonka; Buchfelder, Michael; Kleist, Bernadette; Kohlmann, Johannes; Menzel, Christa; Buslei, Rolf; Kołtowska-Häggsträm, Maria; Strasburger, Christian; Siegel, Sonja
Even if treated, acromegaly has a considerable impact on patient quality of life (QoL); despite this, the exact clinical determinants of QoL in acromegaly are unknown. This study retrospectively examines a cohort of treated patients with acromegaly, with the aim of identifying these determinants. Retrospective survey analysis, with 165 patients included in the study. All patients completed a survey, which included demographic data and the clinical details of their disease, the Short Form-36 Health Survey (SF-36), the revised Beck Depression Inventory (BDI-II), and the Bern Embitterment Inventory (BEI). Stepwise regression was used to identify predictors of QoL. The strongest predictors of the physical component score of the SF-36 were (in order of declining strength of association): Delay between first presentation of the disease and diagnosis, body mass index (BMI), number of doctors visited before the diagnosis of acromegaly, and age at diagnosis. For the mental component score, the strongest predictors were: number of doctors visited, previous radiotherapy, and age at study entry; and, for the BDI-II score: number of doctors visited, previous radiotherapy, age at study entry, and employment status at the time of diagnosis. The following were predictors of the BEI score: number of doctors visited, and age at study entry. Diagnostic delay and lack of diagnostic acumen in medical care provision are strong predictors of poor QoL in patients with acromegaly. Other identified parameters are radiotherapy, age, BMI, and employment status. An efficient acromegaly service should address these aspects when devising disease management plans. BDI-II = Beck Depression Inventory II BEI = Bern Embitterment Inventory BMI = body mass index IGF-1 = insulin-like growth factor 1 MCS = mental component summary (score) PCS = physical component summary (score) QoL = quality of life SDS = standard deviation score SF-36 = Short Form-36 Health Survey.
Woliński, Kosma; Stangierski, Adam; Gurgul, Edyta; Bromińska, Barbara; Czarnywojtek, Agata; Lodyga, Martha; Ruchała, Marek
Acromegaly results from oversecretion of growth hormone and subsequently insulin growth factor-1. According to some authors, the disease can cause increased prevalence of nodular goitre and thyroid cancer (TC). However, the number of studies comparing acromegalic patients with control groups is low. We aimed to assess the prevalence of thyroid lesions in patients with acromegaly in comparison to an age- and sex-matched control group and to update the meta-analysis previously performed in our department by the same authors. We searched medical documentation of patients with acromegaly treated in our department between 2003 and 2013. The prevalence of thyroid abnormalities was compared with the group of patients with hormonally inactive adrenal incidentalomas. To perform the meta-analytic part of the paper we also searched ten databases to find relevant papers. Two hundred and five patients with acromegaly and 184 patients with incidentalomas were included. Any thyroid lesions were present in 77.6% of patients with acromegaly vs. 63.0% with incidentalomas (p = 0.002), multinodular goitre - 66.8% vs. 47.8% (p = 0.0002), and TC- 5.4% vs. 2.7% (p = 0.21) respectively. For thyroid lesions the pooled odds ratio (OR) was 3.1 (95% confidence interval [CI] 1.8-5.5), and for TCs the OR was 4.5 (95% CI 1.9-10.3). According to our results thyroid lesions were significantly more common in patients with acromegaly; in case of TC the difference was not significant. The updated meta-analysis showed significantly increased prevalence of both disorders. In conclusion, systematic thyroid examination should be an important part of follow-up in case of acromegalic patients. (Endokrynol Pol 2017; 68 (1): 2-6).
Seino, Y; Taminato, T; Goto, Y; Inoue, Y; Kadowaki, S; Hattori, M; Mori, K; Kato, Y; Matsukura, S; Imura, H
Plasma glucagon and insulin responses to L-arginine were compared in normal controls and patients with isolated growth hormone deficiency and acromegaly. Patients with isolated growth hormone deficiency were characterized by high plasma glucagon response and low plasma insulin response, whereas acromegalic patients showed exaggerated plasma glucagon response and almost normal insulin response. These results suggest that growth hormone is probably required for optimum function of the islets, and since hyperglucagonaemia was observed in both growth hormone deficiency and acromegaly, metabolic disturbances stemming from the respective primary diseases may affect glucagon secretion.
Reyes-Vidal, Carlos; Fernandez, Jean Carlos; Bruce, Jeffrey N.; Crisman, Celina; Conwell, Irene M.; Kostadinov, Jane; Geer, Eliza B.; Post, Kalmon D.
Context: Although epidemiological studies have found that GH and IGF-1 normalization reduce the excess mortality of active acromegaly to expected rates, cross-sectional data report some cardiovascular (CV) risk markers to be less favorable in remission than active acromegaly. Objective: The objective of the study was to test the hypothesis that remission of acromegaly after surgical therapy increases weight and adiposity and some CV risk markers and these changes are paralleled by a rise in ghrelin. Design: Forty-two adults with untreated, active acromegaly were studied prospectively. Changes in outcome measures from before to after surgery were assessed in 26 subjects achieving remission (normal IGF-1) and 16 with persistent active acromegaly (elevated IGF-1) after surgery. Setting: The study was conducted at tertiary referral centers for pituitary tumors. Main Outcome Measures: Endocrine, metabolic, and CV risk parameters, anthropometrics, and body composition by dual-energy X-ray absorptiometry were measured. Results: Remission increased total ghrelin, body weight, waist circumference, C-reactive protein, homocysteine, high-density lipoprotein, and leptin and reduced systolic blood pressure, homeostasis model assessment score, triglycerides, and lipoprotein (a) by 6 months and for 32 ± 4 months after surgery. The ghrelin rise correlated with the fall in the levels of GH, IGF-1, and insulin and insulin resistance. Weight, waist circumference, and ghrelin did not increase significantly in the persistent active acromegaly group. Total body fat, trunk fat, and perentage total body fat increased by 1 year after surgery in 15 remission subjects: the increase in body fat correlated with the rise in total ghrelin. Conclusions: Although most markers of CV risk improve with acromegaly remission after surgery, some markers and adiposity increase and are paralleled by a rise in total ghrelin, suggesting that these changes may be related. Understanding the mechanisms and
Huebsch, P. (Ludwig-Boltzmann-Institut fuer Radiologisch-Physikalische Tumordiagnostik, Vienna (Austria)); Kotzmann, H. (Universitaetsklinik fuer Innere Medizin 3, Vienna (Austria)); Svoboda, T. (Universitaetsklinik fuer Innere Medizin 3, Vienna (Austria)); Kainberger, F.M. (Ludwig-Boltzmann-Institut fuer Radiologisch-Physikalische Tumordiagnostik, Vienna (Austria)); Bankier, A. (Ludwig-Boltzmann-Institut fuer Radiologisch-Physikalische Tumordiagnostik, Vienna (Austria)); Seidl, G. (Ludwig-Boltzmann-Institut fuer Radiologisch-Physikalische Tumordiagnostik, Vienna (Austria))
Acromegaly is regarded as a cause for secondary osteoporosis, whereas recent papers suggest that growth hormone increases bone mineral density (BMD). In 16 patients with active acromegaly we found an increased BMD compared to normal controls in the lumbar spine and the proximal femur by means of dual energy X-ray absoptiometry. This increase in BMD was statistically significant in the femoral neck and in Ward's triangle (P=0.05). Moreover, no signs of osteoporosis were found radiologically. (orig.)
Full Text Available A male patient presented at the age of 30 with classic clinical features of acromegaly and was found to have elevated growth hormone levels, not suppressing during an oral glucose tolerance test. His acromegaly was originally considered to be of pituitary origin, based on a CT scan, which was interpreted as showing a pituitary macroadenoma. Despite two trans-sphenoidal surgeries, cranial radiotherapy and periods of treatment with bromocriptine and octreotide, his acromegaly remained active clinically and biochemically. A lung mass was discovered incidentally on a chest X-ray performed as part of a routine pre-assessment for spinal surgery 5 years following the initial presentation. This was confirmed to be a bronchial carcinoid tumour, which was strongly positive for growth hormone-releasing hormone (GHRH and somatostatin receptor type 2 by immunohistochemistry. The re-examination of the pituitary specimens asserted the diagnosis of pituitary GH hyperplasia. Complete resolution of the patient’s acromegaly was achieved following right lower and middle lobectomy. Seventeen years following the successful resection of the bronchial carcinoid tumour the patient remains under annual endocrine follow-up for monitoring of the hypopituitarism he developed after the original interventions to his pituitary gland, while there has been no evidence of active acromegaly or recurrence of the carcinoid tumour. Ectopic acromegaly is extremely rare, accounting for <1% of all cases of acromegaly. Our case highlights the diagnostic challenges differentiating between ectopic acromegaly and acromegaly of pituitary origin and emphasises the importance of avoiding unnecessary pituitary surgery and radiotherapy. The role of laboratory investigations, imaging and histology as diagnostic tools is discussed.
Parkinson, C; Kassem, M; Heickendorff, Lene
Active acromegaly is associated with increased biochemical markers of bone turnover. Pegvisomant is a GH receptor antagonist that normalizes serum IGF-I in 97% of patients with active acromegaly. We evaluated the effects of pegvisomant-induced serum IGF-I normalization on biochemical markers...... of bone and soft tissue turnover, as well as levels of PTH and vitamin D metabolites, in 16 patients (nine males; median age, 52 yr; range, 28-78 yr) with active acromegaly (serum IGF-I at least 30% above upper limit of an age-related reference range). Serum procollagen III amino-terminal propeptide...
Chanson, Philippe; Brue, Thierry; Delemer, Brigitte; Caron, Philippe; Borson-Chazot, Françoise; Zouater, Hichem
To monitor long-term pegvisomant treatment of patients with acromegaly in routine clinical practice. The French ACROSTUDY is part of the global ACROSTUDY, an observational post-authorization safety surveillance study of acromegaly treatment with pegvisomant. The median duration of follow-up of the 292 included patients was 5.2 years. Overall 272 (93%) patients received somatostatin analogues before initiation of pegvisomant. The most prescribed initial dose of pegvisomant (after possible administration of a loading dose) was 10mg/day and, starting from the 2nd year, the median dose was 20mg/day. Serum IGF-1 concentration decreased as soon as pegvisomant was started and after 5 years there was a 62% mean decrease in serum IGF-1 concentration. The percentage of patients with serum IGF-1 concentration within normal ranges (for age and sex) of the local laboratory shifted from 11% at start of pegvisomant to 43% at 6 months and 63% after 5 years. The last available imaging (242 patients) showed an increased or decreased tumor size in 4 and 10% of patients, respectively. Mean weight increased by 3 kg over the 5-year period (P<10(-3)). Mean fasting blood glucose significantly decreased over time (P<0.05), while HbA1c level remained unchanged. Tolerance profile was generally good and similar to that described in clinical studies. This analysis showed a significant decrease in IGF-1 levels throughout the follow-up period, and confirmed that pegvisomant treatment is safe in acromegaly. The results of this interim analysis remain to be confirmed by the final analysis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Yamada, Shozo; Fukuhara, Noriaki; Oyama, Kenichi; Takeshita, Akira; Takeuchi, Yasuharu
Acromegaly is a disorder characterized by hypersecretion of growth hormone caused by a growth hormone-secreting pituitary adenoma. To evaluate the long-term efficacy and safety of repeat transsphenoidal surgery for persistent or recurrent acromegaly. We retrospectively reviewed records for 53 acromegalic patients who underwent repeat transsphenoidal surgery for persistent or progressive acromegaly at Toranomon Hospital between 1987 and 2006. Multivariate logistic regression was performed to evaluate preoperative factors influencing the surgical outcome. Thirty-one patients (58.5%) met the criteria for cure on long-term follow-up endocrine findings. Furthermore, 17 patients were well controlled with normal insulin-like growth factor I levels without (2 patients) or with medication (15 patients), whereas insulin-like growth factor I levels were still above normal in 5 patients after postoperative adjuvant therapy. Only 1 patient was undergoing additional hormonal replacement after surgery, although transient cerebrospinal fluid leak, transient abducens nerve palsy, severe nasal bleeding, and pituitary abscess occurred in each patient, respectively. Multivariate analysis clarified that a favorable surgical outcome was achieved in patients without cavernous sinus invasion (hazard ratio 12.56), tumor segmentation (hazard ratio 5.82), or in those older than 40 years old (hazard ratio 3.21). Repeat surgery can be performed safely with an approximately 60% long-term cure rate in this series. Reoperation should therefore be considered for persistent or recurrent disease in acromegalic patients in whom adjuvant therapy is not effective enough or cannot be accepted. The careful study of initial or preoperative magnetic resonance imaging and the use of micro-Doppler, endoscope, and eye movement monitoring device during surgery can help increase cure rate with a lower complication rate.
Clemmons, David R; Chihara, Kazuo; Freda, Pamela U; Ho, Ken K Y; Klibanski, Anne; Melmed, Shlomo; Shalet, Stephen M; Strasburger, Christian J; Trainer, Peter J; Thorner, Michael O
Acromegaly is associated with significant morbidities and a 2- to 3-fold increase in mortality because of the excessive metabolic action of GH and IGF-I, a marker of GH output. Reductions in morbidity correspond with decreases in IGF-I, and mortality is lowered following normalization of IGF-I or GH levels. Therefore, this has become an important end point. Current guidelines for the treatment of acromegaly have not considered recent advances in medical therapy, in particular, the place of pegvisomant, a GH receptor antagonist. Treatment goals include normalizing biochemical markers, controlling tumor mass, preserving pituitary function, and relieving signs and symptoms. Surgery reduces tumor volume and is considered first-line therapy. Radiation reduces tumor volume and GH and IGF-I levels, but the onset of action is slow and hypopituitarism typically develops. Therefore, pharmacotherapy is often used following surgery or as first-line therapy for nonresectable tumors. Dopamine agonists can be considered in patients exhibiting minimal disease or those with GH-prolactin-cosecreting tumors but will not achieve hormone normalization in most patients. Somatostatin analogs effectively suppress GH and IGF-I in most patients, but intolerance (e.g. diarrhea, cramping, gallstones) can occur. Pegvisomant, the newest therapeutic option, blocks GH action at peripheral receptors, normalizes IGF-I levels, reduces signs and symptoms, and corrects metabolic defects. Pegvisomant does not appear to affect tumor size and has few adverse effects. Pegvisomant is the most effective drug treatment for acromegaly in normalizing IGF-I and producing a clinical response; it is the preferred agent in patients resistant to or intolerant of somatostatin analogs.
Portocarrero-Ortiz, Lesly A; Vergara-Lopez, Alma; Vidrio-Velazquez, Maricela; Uribe-Diaz, Ana María; García-Dominguez, Avril; Reza-Albarrán, Alfredo Adolfo; Cuevas-Ramos, Daniel; Melgar, Virgilio; Talavera, Juan; Rivera-Hernandez, Aleida de Jesus; Valencia-Méndez, Carla Valentina; Mercado, Moisés
Acromegaly is a systemic disorder caused by a GH-secreting pituitary adenoma. As with other rare diseases, acromegaly registries developed in various European countries have provided us with important information. The objective of the study was to analyze the epidemiological, clinical, biochemical, and therapeutic data from the Mexican Acromegaly Registry (MAR). The setting of the study was a nationwide patient registry. The MAR was created in 2009. It gathers data from 24 participating centers belonging to three different institutions using a specifically designed on-line platform. Only patients diagnosed after 1990 were included in the program. A total of 2057 patients (51% female, mean age at diagnosis 41.1 ± 24.5 y) have been registered for an estimated prevalence of 18 cases per 1 million inhabitants. Hypertension, glucose intolerance, diabetes, and dyslipidemia were present in 27%, 18.4%, 30%, and 24% of the patients, respectively. The IGF-1 level at diagnosis and the concomitant presence of hypertension were significantly associated with the development of diabetes. Transsphenoidal surgery was the primary treatment in 72% of the patients. Pharmacological treatment, mostly with somatostatin analogs, was administered primarily and adjunctively in 26% and 54% of the patients, respectively. Treatment choice varied among the three participating institutions, with the predominance of pharmacological therapy in two of them and of radiation therapy in the third. Therapeutic outcomes were similar to those reported in the European registries. The MAR is the largest and first non-European registry of the disease. Our findings highlight important within-country differences in treatment choice due to variations in the availability of resources.
Crespo, Iris; Santos, Alicia; Valassi, Elena; Pires, Patricia; Webb, Susan M; Resmini, Eugenia
Evaluation of cognitive function in acromegaly has revealed contradictory findings; some studies report normal cognition in patients with long-term cured acromegaly, while others show attention and memory deficits. Moreover, the presence of affective disorders in these patients is common. Our aim was to evaluate memory and decision making in acromegalic patients and explore their relationship with affective disorders like anxiety and depressive symptoms. Thirty-one patients with acromegaly (mean age 49.5 ± 8.5 years, 14 females and 17 males) and thirty-one healthy controls participated in this study. The Iowa Gambling Task (IGT), Rey Auditory Verbal Learning Test, State-Trait Anxiety Inventory, and Beck Depression Inventory-II (BDI-II) were used to evaluate decision making, verbal memory, anxiety, and depressive symptoms, respectively. Acromegalic patients showed impairments in delayed verbal memory (p < 0.05) and more anxiety and depressive symptoms (p < 0.05) than controls. In the IGT, acromegalic patients presented an altered decision-making strategy compared to controls, choosing a lower number of the safer cards (p < 0.05) and higher number of the riskier cards (p < 0.05). Moreover, multiple correlations between anxiety and depressive symptoms and performance in memory and decision making were found. Impaired delayed memory and decision making observed in acromegalic patients are related to anxiety and depressive symptoms. Providing emotional support to the patients could improve their cognitive function. A key clinical application of this research is the finding that depressive symptoms and anxiety are essentially modifiable factors.
Victor Jacobus Geraedts
Full Text Available IINTRODUCTION. Remission criteria of acromegaly are based on biochemical variables, i.e. normalization of increased hormone levels. However, the established reduction in Quality of Life (QoL is suggested to be independent of biochemical control. The aim of this study was to test which aspects predict Qol best in acromegaly. METHODS/Design. This is a prospective cohort study in 80 acromegalic patients, with a cross-sectional and longitudinal part. The main outcome measure was health-related quality of life (QoL, measured by a generic and a disease-specific questionnaire (the SF-36 and AcroQol. Main predictors were age, gender, biochemical control, disease characteristics, treatment modalities and psychopathology. RESULTS. Our cohort of 80 acromegalics had a mean age 54.7 ± 12.3 years with an average disease duration of 10.8 ± 10.0 years. Ratio macro-/microadenoma was 54/26. In adjusted mixed method models, we found that psychopathology significantly predicts QoL in acromegaly (in models including the variables age, gender, disease duration, tumor size, basal hormone levels, relevant treatment modalities and relevant comorbidities, with a higher degree of psychopathology indicating a lower QoL (depression vs. AcroQoL: B=-1.175, p<0.001, depression vs. SF36: B=-1.648, p<0.001, anxiety vs. AcroQoL: B=-0.399, p<0.001, anxiety vs. SF36: B=-0.661, p<0.001. The explained variances demonstrate superiority of psychopathology over biochemical control and other variables in predicting QoL in our models. DISCUSSION. Superiority of psychopathology over biochemical control calls for a more extensive approach regarding diagnosing depression and anxiety in pituitary adenomas to improve QoL. Depressive symptoms and anxiety are modifiable factors that might provide valuable targets for possible future treatment interventions.
Tutuncu, Yasemin; Berker, Dilek; Isik, Serhat; Ozuguz, Ufuk; Akbaba, Gulhan; Kucukler, Ferit Kerim; Aydin, Yusuf; Guler, Serdar
Long-acting somatostatin analogs are frequently used as adjuvant treatment of acromegaly patients after noncurative surgery. This sudy aims to compare the efficacy of octreotide long-acting release (OCT) and lanreotide Autogel (LAN) in acromegaly patients. Sixty-eight patients not cured by transsphenoidal endoscopic or microscopic pituitary surgery between 2003 and 2009 were retrospectively analyzed (25 men; 43 women; mean age 41.1 ± 10.9 years [range 18-65 years]). The patients were assigned randomly to OCT (n = 36) and LAN (n = 32) groups. Evaluations included insulin-like growth factor I (IGF-I) and growth hormone (GH) after oral glucose tolerance test (OGTT) 3, 6, 12 and 18 months after starting medical treatment; pituitary magnetic resonance imaging was performed before treatment and after 3 and 12 months. Patients achieving IGF-I levels within the age and gender normal range and GH level <1 μg/l following OGTT were considered a 'biochemical cure'. Mean IGF-I and GH values and tumor volumes (cm(3)) in the LAN and OCT groups were similar in the post-operative period before initiation of medical treatment. A statistically significant decrease in GH and IGF-I levels was obtained for both treatment groups at each follow-up visit compared to the previous value. Tumor shrinkage after 12 months of treatment was statistically significant in both groups but the percentage tumor shrinkage (28.5% vs. 34.9%, P = 0.166) and rate of patients achieving biochemical cure (63.9 and 78.1%, P = 0.454) were similar between OCT and LAN groups, respectively. OCT and LAN treatment options have similar efficacy for ensuring biochemical cure and tumor shrinkage in acromegaly patients who had noncurative surgery.
Lerat, Justine; Lacoste, Marie; Prechoux, Jean-Marc; Aubry, Karine; Nadalon, Sylvie; Ly, Kim Heang; Bessede, Jean-Pierre
A 61-year-old man with obstructive sleep apnea syndrome and normal BMI complained of dyspnea. Nasofibroscopy revealed a global and major oedema of the glottis and supraglottis and also a paralysis of the left vocal fold. CT-scan pointed out a spontaneous hyperdensity of the left arytenoid cartilage. A tracheostomy was performed. Clinical examination revealed large hands and macroglossy with high IGF1 rate. MRI confirmed a supracentimetric pituitary adenoma. To our knowledge, this is the first description of a case of acute respiratory distress due to unilateral larynx paralysis leading to acromegaly diagnosis. This is due to submucosal hypertrophy and vocal cord immobility.
Full Text Available Daphne T Adelman1, Karen JP Liebert2, Lisa B Nachtigall2, Michele Lamerson3, Bert Bakker31Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, 2Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA, 3Endocrinology Medical Affairs, Ipsen Biopharmaceuticals, Inc, Basking Ridge, NJ, USAAbstract: Acromegaly is a rare disease most often caused by the prolonged secretion of excess growth hormone from a pituitary adenoma. The disease is associated with multiple significant comorbidities and increased mortality. The delay to diagnosis is often long. This may be because of low disease awareness among health care professionals, the insidious onset of differentiating features, and because patients are likely to present with complaints typical of other conditions more frequently seen in primary care. Early identification of acromegaly facilitates prompt treatment initiation and may minimize the permanent effects of excess growth hormone. The primary treatment for many patients will be pituitary surgery, although not all patients will be eligible for surgery or achieve a surgical cure. If biochemical control is not achieved following surgery, other treatment options include medical therapy and radiation therapy. Improved biochemical control may only alleviate rather than reverse the associated comorbidities. Thus, lifelong monitoring of patient health is needed, with particular attention to the management of cardiovascular risk factors. It is additionally important to consider the impact of both disease and treatment on patients' quality of life and minimize that impact where possible, but particularly for chronic therapies. For the majority of patients, chronic therapy is likely to include somatostatin analog injections. In some circumstances, it may be possible to extend the dosing interval of the analog once good biochemical control is achieved. Additional convenience
Miodrag Krstic; Tamara Alempijevic; Bojan Stimec; Marjan Micev; Miroslav Milicevic; Dragan Micic; Goran Jankovic
Villous adenomas are benign epithelial lesions with malignant potential that can occur in any part of the gastrointestinal tract. We present a case of a middle age woman with acromegaly who was investigated for nonspecific gastrointestinal complaints. Ultrasonography and subsequent endosonography diagnosed a large (4.5 cm), hyperechoic, sessile polyp with numerous pedicles. An open cholecystectomy was performed and revealed a villous adenoma with several foci of carcinoma in situ. Detailed investigations showed no other tumors of the gastrointestinal tract. After five years of follow-up, the patient reports no complaints, and the results of laboratory testing and imaging studies are within the normal range.
Hennessey, J V; Jackson, I M
Pituitary adenomas are frequently encountered, benign intracranial tumours. Clinically classified according to their capacity to produce and secrete hormones, pituitary tumours are diagnosed from the clinical manifestations and biochemical findings of specific pituitary hormone overproduction or of impaired pituitary function due to pressure on normal pituitary cells, the pituitary stalk or the hypothalamus. Additionally, the tumour may result in neurological manifestations due to its effect as an intracranial space-occupying lesion. Pituitary adenomas may present acutely with pituitary apoplexy after intrapituitary haemorrhage or infarction. The subsequent hypofunction of the pituitary with concomitant neurological sequelae of an expanding intracranial mass are often associated with excruciating headache, diplopia and visual field defects. Gradually developing neurological deficits or secondary endocrine failure over several years may precede the recognition of non-secretory tumours (30-40% of pituitary adenomas) as well as some of the hormone-producing adenomas, especially when they expand beyond the confines of the sella turcica. Asymptomatic masses occur in the pituitary in 5-27% of unselected autopsy series. About 10-20% of pituitaries imaged as part of a brain study contain lesions 'consistent with a pituitary adenoma', with about half being pituitary adenomas ('incidentalomas'). Many advocate screening such cases for a wide spectrum of pituitary function abnormalities. Clinical judgement should be utilized to determine the extent of the work-up and the frequency of follow-up. Acromegaly, a clinical syndrome caused by excess growth hormone secretion, accounts for one-sixth of resected pituitary tumours. This disorder leads to chronic progressive disability and a shortened life span, with approximately 50% of untreated acromegalic patients experiencing premature death. The prevalence of acromegaly has been estimated to range from 50 to 70 per million, with the
Fatti, L M; Scacchi, M; Pincelli, A I; Lavezzi, E; Cavagnini, F
Respiratory disorders are common and important complications in acromegaly. Patients suffering from acromegaly display a 1.6-3.3 fold increase in mortality rate, which is due to respiratory disorders in 25% of cases. In these patients, mortality for lung disease is 2-3 fold higher than in the general population. Every portion of the respiratory system may be involved. Deformities of facial bones, edema and hypertrophy of the mucosae and pharyngeal and laryngeal cartilages, enlargement of the tongue and inspiratory collapse of the hypopharinx, all may contribute to respiratory alterations. Nasal polyps, "hormonal rhinitis", changes of the voice and snoring are common occurrences. Though rarely, a laryngocele may ensue. Pneumomegaly is frequently observed and, as suggested by functional studies, might be due to an increased number rather than volume of the alveoli. An obstructive respiratory syndrome caused by mucosal thickening of the upper airways and bronchi is observed in 25% of female and 70% of male patients. The sleep apnea syndrome (SAS) affects 60-70% of acromegalic patients. SAS may be of obstructive, central or mixed type. Obstructive SAS is the prevailing form in acromegaly. It is due to intermittent obstruction of upper airways with preserved activity of the respiratory center, as testified by the remarkable thoracic and abdominal respiratory efforts. The pathogenesis of the central type of SAS is more complex. Narrowing of the upper airways may induce reflex inhibition of the respiratory center. Moreover, increased GH levels and, possibly, defects in the somatostatinergic pathways, may increase the ventilatory response of the respiratory center to carbon dioxide, thereby leading to respiratory arrest. In the mixed type of SAS, the phenomena underlying the other two forms coexist. Oxygen desaturation concomitant with the apneic episodes accounts for the frequent nocturnal wakening and diurnal drowsiness. Among the clinical correlates of SAS, arterial
Clark, A.J.L.; Chahal, P.; Mashiter, K.; Joplin, G.F. (Royal Postgraduate Medical School, London (UK))
The authors have investigated the possibility that the increase in serum PRL levels observed in patients with acromegaly treated with external irradiation could be due to damage to the hypothalamus or portal vessels, by comparing the effects of yttrium-90 interstitial irradiation, which is highly localised and does not normally extend to the hypothalamus, in a similar series of patients. These results are consistent with the hypothesis; a less likely explanation is that an overgrowth of radio-resistant PRL-secreting tumour cells is occurring after external irradiation, but not after yttrium-90 implantation.
Abrams, Pascale; Alexopoulou, Orsalia; Abs, Roger; Maiter, Dominique; Verhelst, Johan
Background: Lanreotide-Autogel is a depot formulation of the somatostatin analog lanreotide used in the treatment of acromegaly. We investigated whether prolonging or shortening the interval between injections would offer any benefit. Subjects and methods: The interval was prolonged from once every 4 weeks to once every 6 weeks when patients (n = 9) had normal IGF-I and GH concentrations. When patients (n = 12) had still elevated IGF-I or GH on the maximal dose of 1.20 mg every 4 weeks, the i...
Tritos, Nicholas A; Johannsson, Gudmundur; Korbonits, Márta
CONTEXT: GH deficiency (GHD) may occur in adults with cured acromegaly (acroGHD). OBJECTIVE: Our objective was to examine the effectiveness and safety of GH replacement in acroGHD. DESIGN: This study was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database). SETTING...
Ozkaya, Mesut; Sayiner, Zeynel Abidin; Kiran, Gurkan; Gul, Kamile; Erkutlu, Ibrahim; Elboga, Umut
Acromegaly is a clinical syndrome caused by the overproduction of growth hormone (GH) and also known as a rare disease. Clinical, biochemical, and radiological features are often indistinguishable between GH-producing hypophysis adenomas and ectopic GH-releasing hormone (GHRH)-producing tumors. A 40-year-old woman presented to us with her growing feet, hands especially fingers, and enlarging nose. Biochemical diagnosis of acromegaly was made by measuring insulin-like growth factor-1 (IGF-1) level and glucose-suppressed GH estimation. Her spot IGF-1 level was 1300 ng/ml (90-226 ng/ml). The basal GH was 30 ng/l, and 60- and 120-min GH levels after 75-g oral glucose load were 29 and 40 ng/l, respectively. Magnetic resonance imaging (MRI) of pituitary was normal. There was no pituitary adenoma or pituitary hyperplasia. Extrapituitary ectopic hypersecretion of GH or GHRH-secreting tumor search was done by high-resolution computed tomography (CT) of chest and whole abdomen. Abdomen CT revealed 9.5 × 8 cm pelvic mass, which included calcific regions and solid component. The specimen's immunohistochemical staining with GH was positive but interestingly GHRH was negative. According to immunohistochemical staining, the patient's diagnosis was ectopic acromegaly due to a GH-secreting neuroendocrine-differentiated tumor developed from an ovarian mature cystic teratoma. Herein, we present excellent illustration of an unusual and confusing clinical scenario of ectopic acromegaly.
Arzamendi, Audrey E.; Shahlaie, Kiarash; Latchaw, Richard E.; Lechpammer, Mirna; Arzumanyan, Hasmik
Objective To describe the work-up and treatment of rare ectopic acromegaly caused by a biopsy-proven somatotroph pituitary adenoma located within the bony intersphenoid septum of a patient with empty sella syndrome (ESS). Methods We report the presentation, clinical course, diagnostic work-up, and lesion localization and treatment challenges encountered in a 55-year-old patient, with a brief review of relevant literature. Results A 55-year-old African-American man presented with acromegaly and ESS. Attempts to definitively localize the causative tumor were unsuccessful, though petrosal sinus sampling supported central growth hormone production and imaging suggested bone-enclosed subsellar pituitary tissue. Endoscopic endonasal transphenoidal exploration was undertaken with resection of a somatotroph pituitary microadenoma, and subsequent clinical improvement and biochemical remission. Retrospective review revealed the patient's pituitary to have been located ectopically within a unique bony intersphenoid septum. Conclusion This report describes the first known case of an ectopic pituitary adenoma located within the midline bony intersphenoid septum, which we postulate to have resulted from anomalous embryological pituitary migration. Intra-intersphenoid septal tumors should be considered in cases of apparent central acromegaly with ESS or absence of tumor tissue within the paranasal sinuses or other peripheral locations. Indexing Acromegaly, ESS, pituitary adenoma, sphenoid sinus septum. PMID:27468406
A-J. van der Lely (Aart-Jan); W.W. de Herder (Wouter); J.A.M.J.L. Janssen (Joop); S.W.J. Lamberts (Steven)
textabstractWe have studied the physiological and clinical relevance of measurements of serum total and free IGF-I and IGF-binding protein-3 (IGFBP-3) in 57 previously untreated patients with active acromegaly (32 males, 25 females; mean age 47 years) as compared with sex- and age-
S.J.C.M.M. Neggers (Bas); W.W. de Herder (Wouter); R.A. Feelders (Richard); A-J. van der Lely (Aart-Jan)
textabstractThe efficacy of combined treatment in active acromegaly with both long-acting somatostatin analogs (SRIF) and pegvisomant (PEG-V) has been well established. The aim was to describe the PEG-V dose reductions after the conversion from daily PEG-V to combination treatment. To clarify the in
Butz, Laura B; Sullivan, Stephen E; Chandler, William F; Barkan, Ariel L
Approximately 25 % of cases of clinically active acromegaly cases treated in our academic center between 1996 and 2000, were diagnosed in patients who had elevated plasma IGF-1 levels, but apparently "normal" 24-h mean plasma GH levels. The current study served to update the data for patients with acromegaly referred to our facility, after increasing awareness of this "normal" GH subpopulation throughout the medical community. A retrospective chart review was conducted on 157 patients with acromegaly who underwent resection of a confirmed somatotroph pituitary adenoma at the University of Michigan Health System between the dates of 1 Jan 2001 to 23 Sept 2015. Overall prevalence of acromegalic patients with "normal" GH levels, defined as GH 2 cm in the maximal diameter were encountered more frequently in the group with elevated GH (43 vs. 14 %, p acromegaly have "normal" GH, and therefore strengthens the growing body of evidence which supports the leading role of IGF-1 levels in diagnostic evaluation. At the present time, questions about the natural course of "micromegaly" and treatment benefits compared to the subpopulation with elevated GH levels remain unanswered, but research continues to build on our understanding of the heterogeneous population of individuals.
Andreassen, Mikkel; Faber, Jens Oscar; Kjær, Andreas;
Long-term treatment of acromegaly prevents aggravation and reverses associated heart disease. A previous study has shown a temporary increase in serum levels of the N-terminal fraction of pro B-type natriuretic peptide (NT-proBNP) suggesting an initial decline in cardiac function when treatment...
S.J.C.M.M. Neggers (Bas); W.W. de Herder (Wouter); R.A. Feelders (Richard); A-J. van der Lely (Aart-Jan)
textabstractThe efficacy of combined treatment in active acromegaly with both long-acting somatostatin analogs (SRIF) and pegvisomant (PEG-V) has been well established. The aim was to describe the PEG-V dose reductions after the conversion from daily PEG-V to combination treatment. To clarify the
Dural, Muhammet; Kabakcı, Giray; Cınar, Neşe; Erbaş, Tomris; Canpolat, Uğur; Gürses, Kadri Murat; Tokgözoğlu, Lale; Oto, Ali; Kaya, Ergün Barış; Yorgun, Hikmet; Sahiner, Levent; Dağdelen, Selçuk; Aytemir, Kudret
Cardiovascular complications are the most common causes of morbidity and mortality in acromegaly. However, there is little data regarding cardiac autonomic functions in these patients. Herein, we aimed to investigate several parameters of cardiac autonomic functions in patients with acromegaly compared to healthy subjects. We enrolled 20 newly diagnosed acromegalic patients (55% female, age:45.7 ± 12.6 years) and 32 age- and gender-matched healthy subjects. All participants underwent 24 h Holter recording. Heart rate recovery (HRR) indices were calculated by subtracting 1st, 2nd and 3rd minute heart rates from maximal heart rate. All patients underwent heart rate variability (HRV) and QT dynamicity analysis. Baseline characteristics were similar except diabetes mellitus and hypertension among groups. Mean HRR1 (29.2 ± 12.3 vs 42.6 ± 6.5, p = 0.001), HRR2 (43.5 ± 15.6 vs 61.1 ± 10.8, p = 0.001) and HRR3 (46.4 ± 16.2 vs 65.8 ± 9.8, p = 0.001) values were significantly higher in control group. HRV parameters as, SDNN [standard deviation of all NN intervals] (p = 0.001), SDANN [SD of the 5 min mean RR intervals] (p = 0.001), RMSSD [root square of successive differences in RR interval] (p = 0.001), PNN50 [proportion of differences in successive NN intervals >50 ms] (p = 0.001) and high-frequency [HF] (p = 0.001) were significantly decreased in patients with acromegaly; but low frequency [LF] (p = 0.046) and LF/HF (p = 0.001) were significantly higher in acromegaly patients. QTec (p = 0.009), QTac/RR slope (p = 0.017) and QTec/RR slope (p = 0.01) were significantly higher in patients with acromegaly. Additionally, there were significant negative correlation of disease duration with HRR2, HRR3, SDNN, PNN50, RMSSD, variability index. Our study results suggest that cardiac autonomic functions are impaired in patients with acromegaly. Further large scale studies are needed to exhibit the prognostic significance of impaired autonomic functions in patients with
Jayasena, Channa N; Izzi-Engbeaya, Chioma; Narayanaswamy, Shakunthala; Modi, Manish; Clarke, Holly; Nijher, Gurjinder M K; Meeran, Karim; Dhillo, Waljit S
Cardiovascular complications represent the biggest cause of mortality in acromegaly. It is therefore important to optimally stratify acromegalic patients according to disease activity and complication risk. GH is secreted in a pulsatile manner from the pituitary gland, but GH pulsatility is not routinely assessed clinically. The coefficient of variation of serum GH (GHCV) during oral glucose tolerance test (OGTT) quantifies the variation of GH secretion in patients with acromegaly, but has not been reported previously. To investigate whether GHCV during OGTT is associated with clinical parameters predicted to relate with hypothalamo-pituitary dysfunction during acromegaly, such as radiotherapy treatment, pituitary deficiency and cardiac disease. GHCV was calculated during 584 OGTTs and compared with nadir serum GH and IGF-1 in 111 acromegalic patients treated at a single centre. Acromegalic patients treated with radiotherapy had a 37% lower level of GHCV when compared to the nonradiotherapy group (mean GHCV: 0·298 ± 0·015, no radiotherapy; 0·189 ± 0·007, radiotherapy; P < 0·001). Neither serum IGF-1 nor nadir GH was significantly altered in the radiotherapy group. Mean GHCV was 50% lower in the acromegalic patients with cardiac failure when compared to acromegalic patients with normal echocardiogram (0·161 ± 0·034 vs 0·297 ± 0·055; P < 0·05). Neither serum IGF-1 nor nadir GH was significantly altered during cardiac failure. Our preliminary data suggest that GHCV during OGTT may be reduced during acromegaly in patients with previous radiotherapy, pituitary deficiencies and cardiac disease. Larger studies are required to determine whether GHCV could provide help to assess the morbidity status of patients with treated acromegaly. © 2015 John Wiley & Sons Ltd.
Full Text Available INTRODUCTION: Acromegaly is a quite rare chronic disease caused by the increased secretion of growth hormone (GH and subsequently insulin - like growth factor 1. Although cardiovascular diseases remains the most common cause of mortality among acromegalic patients, increased prevalence of malignant and benign neoplasms remains a matter of debate. The aim of this study is to evaluate the risk of thyroid nodular disease (TND and thyroid cancer in patients with acromegaly. MATERIALS AND METHODS: PubMed, Cochrane Library, Scopus, Cinahl, Academic Search Complete, Web of Knowledge, PubMed Central, PubMed Central Canada and Clinical Key databases were searched to identify studies containing. Random-effects model was used to calculate pooled odds ratios and risk ratios of TND in acromegaly. Studies which not included control groups were systematically reviewed. RESULTS: TND was more frequent in acromegaly than in control groups (OR = 6.9, RR = 2.1. The pooled prevalence of TND was 59.2%. Also thyroid cancer (TC proved to be more common in acromegalic patients (OR = 7.5, RR = 7.2, prevalence was 4.3%. The pooled rate of malignancy (calculated per patient was equal to 8.7%. CONCLUSIONS: This study confirms that both TND and TC occur significantly more often in acromegalic patients than in general population. These results indicate that periodic thyroid ultrasound examination and careful evaluation of eventual lesions should be an important part of follow-up of patients with acromegaly.
Odake, Yukiko; Fukuoka, Hidenori; Yamamoto, Masaaki; Arisaka, Yoshifumi; Konishi, Junya; Yoshida, Kenichi; Matsumoto, Ryusaku; Bando, Hironori; Suda, Kentaro; Nishizawa, Hitoshi; Iguchi, Genzo; Yamada, Shozo; Ogawa, Wataru; Takahashi, Yutaka
Acromegaly is a disease associated with an increased risk for several kinds of neoplasms including colon and thyroid cancer. Although the association between acromegaly and pancreatic neoplasms has not been elucidated, it has recently been reported that GNAS gene mutations were found in 58% of intraductal papillary mucinous neoplasms (IPMNs), which are representative pancreatic cystic lesions, suggesting a link between IPMNs and acromegaly. To assess the prevalence of pancreatic cystic lesions in patients with acromegaly, we performed a retrospective cross-sectional single institute study. Thirty consecutive acromegalic patients (20 females and 10 males; mean age, 60.9 ± 11.9 years) who underwent abdominal contrast-enhanced computed tomography or magnetic resonance imaging between 2007 and 2015 at Kobe University Hospital were recruited. We also analyzed the relationship between presence of pancreatic cystic lesions and somatic GNAS mutations in pituitary tumors. Seventeen of 30 (56.7%) patients studied had pancreatic cystic lesions. Nine of 17 patients (52.9%) were diagnosed with IPMNs based on imaging findings. These results suggest that the prevalence of IPMNs may be higher in acromegalic patients in acromegalic patients than historically observed in control patients (up to 13.5%). In patients with pancreatic cystic lesions, the mean patient age was higher and the duration of disease was longer than in those without pancreatic cystic lesions (67.0 ± 2.3 vs. 53.0 ± 2.7 years, p lesions. These data demonstrate that old or long-suffering patients with acromegaly have a higher prevalence of pancreatic cystic lesions. Moreover, the prevalence of pancreatic cystic lesions may be increased in acromegalic patients.
Zawada, Natalia Bożena; Kunert-Radek, Jolanta; Pawlikowski, Marek; Pisarek, Hanna; Radek, Maciej
Non-functioning pituitary adenomas (NFPA) are often diagnosed late as invasive macroadenomas. The surgical resection is usually incomplete and about 50% of patients require additional surgery. Recent data suggest that somatostatin analogues (SSA), so important in the pharmacotherapy of acromegaly, can also be effective in the management of NFPA. We analysed data of patients who had been treated up to 10 years previously with SSA: 40 with acromegaly (23 - primary, 17 - recurrent tumours) and 22 with NFPA (4 - primary, 18 - recurrent tumours). Hormonal profile, dynamics of tumour size change, ophthalmic syndromes, somatostatin receptor (SSTR) scintigraphy, and immunohistochemistry of SSTR subtypes of operated tumours as well as side effects were investigated. Biochemical cure of acromegaly was achieved in 57.5% of patients, while reduction of tumour size was observed in 37% of patients and it was more frequent in not-operated cases. Regarding NFPA, stabilisation of tumour size was noticed in 68% of patients. Tumour shrinkage was reported in 9% of cases, but in 23% of the study group the adenoma size increased with indication for reoperation. The efficacy of SSA in NFPA is much lower in comparison to their well-established effects in the treatment of acromegaly. Stabilisation of tumour size, which is observed in the majority of NFPA, is significantly more frequent in comparison to the natural history of untreated NFPA and our previous studies as well. Analysis of SSTR subtypes is an argument in favour of introduction of novel broad-spectrum SSA that may be more effective in the treatment of NFPA. Referring to acromegaly, adenoma size decrease was reported more frequently in primary therapy. Considering recurrent tumours better outcomes were achieved in patients who were pre-treated with SSA before planned surgery. (Endokrynol Pol 2016; 67 (3): 292-298).
Kan, Emrah; Kan, Elif K; Okuyucu, Ali
To compare the central corneal thickness (CCT), intraocular pressure (IOP), and tear insulin-like growth factor 1 (IGF-1) levels between patients with acromegaly and a control group and to evaluate the possible effect of tear IGF-1 and duration of the disease on CCT and IOP. We included 31 patients with acromegaly (study group) and 40 age- and sex-matched controls in the study. Patients with acromegaly were divided into 2 subgroups based on disease status (active/inactive). All participants underwent complete ophthalmologic evaluation including CCT and IOP values. Basal tear samples were collected from both groups and tear IGF-1 levels were measured. The CCT, IOP, and tear IGF-1 levels were compared between groups and subgroups and the association between tear IGF-I levels and ocular parameters (CCT, IOP) and disease duration were also evaluated. Central corneal thickness, IOP, and tear IGF-1 levels did not show a significant difference between study and control groups. We also did not find a significant difference in terms of CCT, IOP, or tear IGF-1 levels between subgroups of patients. Correlation analysis did not show an association between the duration of disease and tear IGF-1 levels with CCT or IOP. There was no significant difference in tear IGF-1 levels between patients with acromegaly and controls. Additionally, there was no correlation between disease duration and tear IGF-1 levels with CCT or IOP levels. This lack of association may suggest that tear IGF-1 levels might not have an effect on CCT or IOP findings in patients with acromegaly.
Haliloglu, Ozlem; Dogangun, Burak; Ozcabi, Bahar; Kural, Hanife Ugur; Keskin, Fatma Ela; Ozkaya, Hande Mefkure; Pamukcu, Fatma Colkesen; Bektas, Elif; Poyraz, Burc Cagri; Buber, Hakan; Evliyaoglu, Olcay; Kadioglu, Pinar
To determine the physical status and intelligence scores of children of acromegalic mothers and to compare them with those of children from mothers without acromegaly. Six women with acromegaly who became pregnant under follow-up between 2010 and 2014 and their 16 children (group A) were assessed and compared with 16 children of healthy women (group B) and 15 children of women with prolactinoma (group C). The physical examinations of children were performed by the department of pediatric endocrinology and intelligence quotient (IQ) testing was undertaken by adult and pediatric psychiatry departments, using appropriate scales for their ages. Six of the 16 children (girls/boys: 7/9) were born after the diagnosis of acromegaly. Five of the 6 pregnancies occured when the patients were taking somatostatin analogs, none continued taking the drugs during pregnancy. The mean IQ of groups A, B, and C were 106.4 ± 12.5, 105.3 ± 12.5, and 103.2 ± 16.1 respectively (p > 0.05). The mean ages, birth percentiles, recent weight and height standard deviation scores were similar between groups (p > 0.05). Two siblings from group A and 1 child from group B were large for gestational age at birth. At recent follow-up, two children from group A were found tall for their age and one from group C was short for his age and was placed under the care of pediatric endocrinology clinic. Pregnancies in acromegaly seems to be uneventful and the general health status and IQ scores of children from women with and without acromegaly were found similar.
Villar-Taibo, Rocío; Ballesteros-Pomar, María D; Vidal-Casariego, Alfonso; Alvarez-San Martín, Rosa M; Kyriakos, Georgios; Cano-Rodríguez, Isidoro
Pituitary apoplexy is a rare but potentially life-threatening clinical syndrome characterized by ischemic infarction or hemorrhage into a pituitary tumor. The diagnosis of pituitary tumor apoplexy is frequently complicated because of the nonspecific nature of its signs and symptoms, which can mimic different neurological processes, including meningitis. Several factors have been associated with apoplexy, such as dopamine agonists, radiotherapy, or head trauma, but meningitis is a rarely reported cause. We describe the case of a 51-year-old woman with acromegaly due to a pituitary macroadenoma. Before surgical treatment, she arrived at Emergency with fever, nausea, vomiting and meningismus. Symptoms and laboratory tests suggested bacterial meningitis, and antibiotic therapy was initiated, with quick improvement. A computerized tomography (CT) scan at admission did not reveal any change in pituitary adenoma, but a few weeks later, magnetic resonance imaging (MRI) showed data of pituitary apoplexy with complete disappearance of the adenoma. Currently, her acromegaly is cured, but she developed hypopituitarism and diabetes insipidus following apoplexy. We question whether she really experienced meningitis leading to apoplexy or whether apoplexy was misinterpreted as meningitis. In conclusion, the relationship between meningitis and pituitary apoplexy may be bidirectional. Apoplexy can mimic viral or bacterial meningitis, but meningitis might cause apoplexy, as well. This fact highlights the importance of differential diagnosis when evaluating patients with pituitary adenomas and acute neurological symptoms.
Martín-Rodríguez, Juan F; Muñoz-Bravo, Jose L; Ibañez-Costa, Alejandro; Fernandez-Maza, Laura; Balcerzyk, Marcin; Leal-Campanario, Rocío; Luque, Raúl M; Castaño, Justo P; Venegas-Moreno, Eva; Soto-Moreno, Alfonso; Leal-Cerro, Alfonso; Cano, David A
Acromegaly is a disorder resulting from excessive production of growth hormone (GH) and consequent increase of insulin-like growth factor 1 (IGF-I), most frequently caused by pituitary adenomas. Elevated GH and IGF-I levels results in wide range of somatic, cardiovascular, endocrine, metabolic, and gastrointestinal morbidities. Subcutaneous implantation of the GH-secreting GC cell line in rats leads to the formation of tumors. GC tumor-bearing rats develop characteristics that resemble human acromegaly including gigantism and visceromegaly. However, GC tumors remain poorly characterized at a molecular level. In the present work, we report a detailed histological and molecular characterization of GC tumors using immunohistochemistry, molecular biology and imaging techniques. GC tumors display histopathological and molecular features of human GH-producing tumors, including hormone production, cell architecture, senescence activation and alterations in cell cycle gene expression. Furthermore, GC tumors cells displayed sensitivity to somatostatin analogues, drugs that are currently used in the treatment of human GH-producing adenomas, thus supporting the GC tumor model as a translational tool to evaluate therapeutic agents. The information obtained would help to maximize the usefulness of the GC rat model for research and preclinical studies in GH-secreting tumors.
Potorac, Iulia; Petrossians, Patrick; Daly, Adrian F; Schillo, Franck; Ben Slama, Claude; Nagi, Sonia; Sahnoun, Mouna; Brue, Thierry; Girard, Nadine; Chanson, Philippe; Nasser, Ghaidaa; Caron, Philippe; Bonneville, Fabrice; Raverot, Gérald; Lapras, Véronique; Cotton, François; Delemer, Brigitte; Higel, Brigitte; Boulin, Anne; Gaillard, Stéphan; Luca, Florina; Goichot, Bernard; Dietemann, Jean-Louis; Beckers, Albert; Bonneville, Jean-François
Responses of GH-secreting adenomas to multimodal management of acromegaly vary widely between patients. Understanding the behavioral patterns of GH-secreting adenomas by identifying factors predictive of their evolution is a research priority. The aim of this study was to clarify the relationship between the T2-weighted adenoma signal on diagnostic magnetic resonance imaging (MRI) in acromegaly and clinical and biological features at diagnosis. An international, multicenter, retrospective analysis was performed using a large population of 297 acromegalic patients recently diagnosed with available diagnostic MRI evaluations. The study was conducted at ten endocrine tertiary referral centers. Clinical and biochemical characteristics, and MRI signal findings were evaluated. T2-hypointense adenomas represented 52.9% of the series, were smaller than their T2-hyperintense and isointense counterparts (Pdiagnosis than women (P=0.067) and presented higher IGF1 values (P=0.01). Although in total, adenomas had a predominantly inferior extension in 45.8% of cases, in men this was more frequent (P<0.0001), whereas in women optic chiasm compression of macroadenomas occurred more often (P=0.0067). Most adenomas (45.1%) measured between 11 and 20 mm in maximal diameter and bigger adenomas were diagnosed at younger ages (P=0.0001). The T2-weighted signal differentiates GH-secreting adenomas into subgroups with particular behaviors. This raises the question of whether the T2-weighted signal could represent a factor in the classification of acromegalic patients in future studies.
Lopes, Agnaldo José; Ferreira, Arthur Sá; Walchan, Evelyn Mendes; Soares, Mauricio Santos; Bunn, Priscila Santos; Guimarães, Fernando Silva
To evaluate the effects of demographics and hormonal variations on knee muscle performance in patients with acromegaly and develop explanatory models of peripheral muscle function in these individuals. This was a cross-sectional study in which 53 acromegalics and 27 healthy subjects underwent knee isokinetic dynamometry to evaluate the peak torque value for leg extension at 75°/s (PTE75) and 240°/s (PTE240). Separate multivariable linear regression models for the prediction of PTE75 and PTE240 were tested using variables commonly used as predictors in the clinical setting and other specific variables related to acromegaly. The final prediction model for PTE75 (R(2)=0.888; adjusted R(2)=0.820, SE of bias=16.2Nm, p<0.001) was -0.221×growth hormone+36.791×sexmale=1-27.407×statusactive=1-0.690×age+148.071. The final prediction model for PTE240 (R(2)=0.816; adjusted R(2)=0.805, SE of bias=8.8Nm, p<0.001) was -0.174×growth hormone+12.522×sexmale=1-0.520×age+98.099. In acromegalics, high growth hormone levels, female gender, and older age are associated with reduced muscle strength and endurance. Additionally, active disease negatively affects peripheral muscle strength in these patients. Copyright © 2016 Elsevier B.V. All rights reserved.
Shimatsu, A; Imura, H; Irie, M; Nakagawa, S; Goto, Y; Shimizu, N; Takeda, R; Kato, Y; Saito, S; Ibayashi, H
Twenty-one patients with active acromegaly and two patients with pituitary gigantism were treated with the long-acting somatostatin analogue octreotide (100-600 micrograms/day, sc, two or three times daily or 300-1500 micrograms daily by intermittent sc infusion) for 9-63 months. There was rapid clinical improvement. The fasting plasma GH levels were significantly suppressed (less than 50% of the values before treatment) in 17 patients and were normalized (less than 5 ng/ml) in 6 patients (27.3%). Plasma IGF-I levels were lowered by 50% and were normalized in 7 out of 18 cases. The effect of octreotide on pituitary tumor size was evaluated in 13 patients. In 4 cases, the shrinkage of the pituitary tumor was detected by computed tomographic scans and/or magnetic resonance imaging studies. The drug was generally well tolerated. However, there were probably newly formed gallstones in two patients during the therapy. Our study suggests that octreotide is an effective and relatively safe new approach for treating active acromegaly and gigantism.
Takao, Masaki; Mori, Taisuke; Orikasa, Hideki; Oh, Haengphil; Suzuki, Kinuko; Koto, Atsuo; Yamazaki, Kazuto
A 44-year-old Japanese man with elevated growth hormone levels and gradual deterioration of mental and renal function was admitted to the hospital. With his deteriorated general condition and renal failure, the patient developed pulmonary thromboembolism and died of respiratory failure. Autopsy examination was conducted, which revealed abnormal accumulation or intracytoplasmic storage of lipid-rich material in the small blood vessels, kidney, heart, and nervous system. After postmortem pathologic studies, including light-microscopic histochemistry, electron microscopy, and biochemical analysis of the stored lipid contents, a final diagnosis of Fabry disease was made. Histopathologic examination revealed a unique vasculopathy characterized by the presence of abnormal intracytoplasmic lipid inclusions and vascular remodeling. With regard to the clinical presentation of acromegaly, hyperplasia but not adenomatous transformation of the acidophils of the anterior pituitary gland with immunohistochemical detection of growth hormone within the cells was noted. In this case, the complication of acromegaly with hyperplasia of the acidophilic cells of the anterior pituitary gland and the unique vasculopathy causing significant organ failure, mainly of the kidney, heart, and central nervous systems, possibly as a result of microcirculatory failure, are considered to be not incidental findings but to be intimately involved in the pathogenesis of Farby disease.
Jensen, A L; Thomsen, M K; Aaes, H; Andreasen, M; Søndergaard, J
Growth hormone (GH) has recently been shown to affect polymorphonuclear neutrophil granulocyte (PMN) function and to be secreted by mononuclear cells, indicating that the hormone may be active in an immunophysiologic network, acting as an endo- or paracrine priming agent. The purpose of the present study was to evaluate the chemotactic responsiveness of canine peripheral PMN in a dog with acromegaly, caused by spontaneous, progesterone-induced hypersecretion of GH and, secondary to this, a seven-fold increase in insulin-like growth factor I (IGF-I). The chemotactic responsiveness towards zymosan-activated serum (ZAS) and leukotriene B4 (LTB4) was evaluated at a time when the dog suffered from acromegaly and again 57 days after corrective surgery (ovariohysterectomy). The experiments showed that PMN from the patient exhibited enhanced chemotactic migration that appeared to be associated with the hypersomatotropic condition as judged from the reversibility of the phenomenon. The glucose intolerance and elevated serum alkaline phosphatase that were observed in the acromegalic dog were also shown to be reversible following surgery.
Sang Ouk Chin
Full Text Available A macroinvasive pituitary adenoma with plurihormonality usually causes acromegaly and hyperprolactinemia, and also accompanies with neurologic symptoms such as visual disturbances. However, its concurrent presentation with a rectal carcinoid tumor is rarely observed. This study reports the history, biochemical, colonoscopic and immunohistochemical results of a 48-year-old female with acromegaly and hyperprolactinemia. Despite the large size and invasive nature of the pituitary adenoma to adjacent anatomical structures, she did not complain of any neurologic symptoms such as visual disturbance or headache. Immunohistochemical staining of the surgical specimen from the pituitary adenoma revealed that the tumor cells were positive for growth hormone (GH, prolactin (PRL, and thyroid stimulating hormone (TSH. Staining for pituitary-specific transcription factor-1 (Pit-1 was shown to be strongly positive, which could have been possibly contributing to the plurihormonality of this adenoma. Colonoscopy found a rectal polyp that was identified to be a carcinoid tumor using immunohistochemical staining. A macroinvasive pituitary adenoma with concomitant rectal carcinoid tumor was secreting GH, PRL, and TSH, which were believed to be in association with over-expression of Pit-1. This is the first case report of double primary tumors comprising a plurihormonal pituitary macroadenoma and rectal carcinoid tumor.
Full Text Available Abstract Introduction Asymptomatic pituitary abnormalities occur in about 10% of cranial magnetic resonance imaging scans, but metastatic carcinoma of the pituitary gland is rare: 133 cases have been reported. Two thirds secreted either prolactin or adrenocorticotropic hormone, and another 24% were non-secreting. Case presentation A 42-year-old Caucasian man lived for 30 years after the diagnosis of a pituitary tumor whose clinical and biochemical features were those of acromegaly and hypogonadism. Radiotherapy, totaling 7300 rad, was administered to the sella over two courses. Growth hormone levels normalized, but he developed both thyroid and adrenal insufficiency, and replacement therapy was commenced. Fourteen years later, growth hormone levels again became elevated, and bromocriptine was commenced but led to side effects that could not be tolerated. An attempted surgical intervention failed, and octreotide and pergolide were used in succession. Twenty-seven years after the diagnosis, a mass from an excisional biopsy of below the angle of the mandible proved to be metastatic pituitary carcinoma. Immunohistochemical staining was positive for synaptophysin, growth hormone, and prolactin. One year later, an octreotide scan showed uptake at the sella, neck, and spleen. Our patient declined further active oncology treatment. Conclusions Metastatic pituitary carcinoma associated with acromegaly is particularly rare. To the best of our knowledge, this is the eighth such case and is the first report of growth hormone and prolactin present in the metastatic mass.
Tanaka, Sho; Haketa, Akira; Yamamuro, Shun; Suzuki, Toshiko; Kobayashi, Hiroki; Hatanaka, Yoshinari; Ueno, Takahiro; Fukuda, Noboru; Abe, Masanori; Yoshino, Atsuo; Soma, Masayoshi
Whether somatostatin analogs for acromegaly improve or worsen a patient's glycemic profile is controversial. A risk of hypoglycemia should be presumed, especially when patients receive insulin therapy, as the package inserts caution. However, a detailed clinical course of such a case has never been reported in research articles. An 80-year-old Japanese female diabetes patient treated with insulin therapy was diagnosed with acromegaly, and the somatostatin analog, lanreotide, was given. On day 4 of lanreotide treatment, repeated hypoglycemia as a result of exogenous insulin arose and the patient required inpatient care. After lanreotide treatment, the total daily insulin dose could be reduced, but her fasting C-peptide level decreased from 1.6 to 0.4 ng/mL, implying improved insulin resistance and impaired endogenous insulin secretion. In the present case, marked alteration surrounding lanreotide administration was observed; careful co-administration with insulin therapy is required, as the package insert cautions. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
Li, Z-Q; Quan, Z; Tian, H-L; Cheng, M
To investigate whether 3 months' preoperative treatment with lanreotide improved outcome in newly diagnosed patients with acromegaly resulting from invasive pituitary macroadenoma. After baseline evaluation, untreated patients were randomized to undergo direct transsphenoidal surgery or lanreotide treatment (30 mg via intramuscular injection every 2 weeks, increased to 30 mg/week at week 8 if growth hormone nadir > 2.5 μg/l), for 3 months prior to surgery. Tumour shrinkage following lanreotide treatment was analysed. Cure was evaluated at 3 months postsurgery by measuring growth hormone and insulinlike growth factor-1 (IGF-1) levels. Preoperative lanreotide treatment significantly reduced mean tumour size. Growth hormone and IGF-1 levels were lower in the pretreatment group than in the direct surgery group at 3 months postsurgery. According to combined growth hormone and IGF-1 levels, significantly more patients were cured by trans-sphenoidal surgery in the pretreatment group compared with the direct surgery group (11 of 24 and five of 25 patients, respectively). Lanreotide treatment for 3 months before trans-sphenoidal surgery effectively reduced tumour size, and improved surgical cure rate, in newly diagnosed patients with acromegaly resulting from invasive pituitary macroadenoma.
Full Text Available A 55 year-old male presented with multiple pus-discharging abscesses and sinuses and mutilating scarring on the gluteal region and back prevalent for the last ten years with exacerbations and remissions. Physical examination revealed acromegaly with frontal bossing, prognathism, a barrel chest and acral hypertrophy. Dermatological examination revealed cutis verticis gyrata, thick eyelids, a large triangular nose, a thickened lower lip, macroglossia, widely spaced teeth and widened skin pores with wet and oily skin. Hair was fine and nails were flat and wide. There were multiple inflammatory papules, tender nodules, draining sinuses, and grouped, polyporous comedones as well as multiple and extensive depressed and keloidal scars localized predominantly over the gluteal region with a few scattered lesions over the back. A computed tomography (CT scan showed widened sella turcica. His basal fasting growth hormone (GH levels were markedly raised (230 ng/mL; normal 1-5 ng/mL while the prolactin levels were moderately raised (87 ng/mL; normal 2-5 ng/mL. These findings were consistent with a diagnosis of acromegaly. The patient was put on antibiotics, nonsteroidal antiinflammatory drugs and isotretinoin at a dose of 1 mg/kg/day, which was increased to 1.5 mg/kg/day. Except for an initial mildly beneficial response, the skin lesions were largely resistant to high doses of isotretinoin at the end of four months.
Cote, David J; Iuliano, Sherry L; Smith, Timothy R; Laws, Edward R
This case report provides provocative and useful data regarding two aspects of acromegaly and its management. The patient, who is one of a pair of identical twins, has no known hereditary, genetic or otherwise potentially etiologic factors as compared to her unaffected sister. Secondly, transsphenoidal surgery, which was ultimately successful, was complicated by pneumococcal meningitis, an unusual event with only four previously reported patients, three of whom ended in death or major neurologic deficits. In this case, a 57-year-old woman gradually developed classical signs and symptoms of acromegaly while her identical twin sister remained normal with no evidence of endocrine disease. Endoscopic transsphenoidal surgery was complicated by the development of meningitis 25 days after surgery. This was controlled following a difficult hospital course. Streptococcus pneumoniae meningoencephalitis is a rare but life-threatening complication of transsphenoidal surgery. A high index of suspicion for incipient meningitis should be maintained when patients present with severe headache and increased intracranial pressure, even if they initially lack the typical symptoms and signs. Immediate and aggressive treatment is necessary to avoid significant neurologic deficit.
Dal, Jakob; Feldt-Rasmussen, Ulla; Andersen, Marianne
remained stable. The prevalence in 2010 was 85 cases/10(6) persons. The patients were at increased risk of diabetes mellitus (HR: 4.0 (95% CI: 2.7-5.8)), heart failure (HR: 2.5 (95% CI: 1.4-4.5)), venous thromboembolism (HR: 2.3 (95% CI: 1.1-5.0)), sleep apnoea (HR: 11.7 (95% CI: 7.0-19.4)) and arthropathy......-based cohort study. METHOD: All incident cases of acromegaly in Denmark (1991-2010) were identified from health registries and validated by chart review. We estimated the annual incidence rate of acromegaly per 10(6) person-years (py) with 95% confidence intervals (95% CIs). For every patient, 10 persons were...... sampled from the general population as a comparison cohort. Cox regression and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used. RESULTS: Mean age at diagnosis (48.7 years (CI: 95%: 47.2-50.1)) and annual incidence rate (3.8 cases/10(6) persons (95% CI: 3.6-4.1)) among the 405 cases...
Dal J; Skou N; Nielsen EH; Jørgensen JOL; Pedersen L
Jakob Dal,1 Nikolaj Skou,1 Eigil Husted Nielsen,2 Jens Otto Lunde Jørgensen,1 Lars Pedersen3 1Department of Endocrinology, Aarhus University Hospital, Aarhus, 2Department of Endocrinology, Aalborg University Hospital, Aalborg, 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Background: The incidence of acromegaly is uncertain, since population-based studies are few. In the absence of a specific acromegaly registry, the Danish National Registry of ...
Raikundalia, Milap D; Pines, Morgan J; Svider, Peter F; Baredes, Soly; Folbe, Adam J; Liu, James K; Eloy, Jean Anderson
Transsphenoidal surgery (TSS) is a common procedure for a variety of pituitary lesions. This procedure can be associated with complications related to the surgery or specific pathology. In this study, we evaluate inpatient postoperative complications among patients who underwent TSS for growth hormone adenomas using a nationally representative database, and compare patient characteristics and complications to patients who underwent TSS for other benign pituitary neoplasms. Analysis of the Nationwide Inpatient Sample revealed 13,070 TSS patients (including 892 with acromegaly) between 2002 and 2010. Complication rates, outcomes, patient demographics, hospital stay, and total charges were evaluated among TSS patients with and without acromegaly. There was an increase in TSS performed in both cohorts from 2002 to 2010. Acromegaly patients were younger, had shorter hospital stays, and incurred fewer charges. Acromegaly patients had a lower occurrence of postoperative urinary/renal complications (0.2% vs 1.1%), thromboembolic events (0% vs 0.4%), fluid/electrolyte abnormalities (5.7% vs 9.1%), and iatrogenic hypopituitarism (0.3% vs 1.1%) compared to other TSS patients (all p acromegaly patients was 2.6% vs 1.7% in non-acromegaly patients, a result that did not reach significance (p = 0.054). Upon comparison of inpatient hospitalizations for patients undergoing TSS for growth hormone adenomas and other benign pituitary neoplasms, acromegaly patients had a significantly lower occurrence of postoperative fluid/electrolyte abnormalities. Acromegaly patients had shorter hospitalizations and subsequently fewer total charges. © 2015 ARS-AAOA, LLC.
Salvatori, Roberto; Nachtigall, Lisa B.; Cook, David M.; Bonert, Vivien; Molitch, Mark E.; Blethen, Sandra; Chang, Stephen; ,
Surgical resection is often not curative in patients with acromegaly and long-acting somatostatin analogues (lanreotide or octreotide) are often needed. This study assessed the efficacy and safety of self- or partner-administration of lanreotide in patients with acromegaly. This was a six-month, single-arm, open-label study conducted at 13 endocrinology clinics. Fifty-nine patients received deep subcutaneous lanreotide injections every 28 days. Twelve patients started on 120 mg lanreotide and...
Lucas, T; Astorga, R; ,
Objective and design Depot somatostatin analogues are well accepted as either adjuvant or primary therapy for acromegaly, and their long dosage intervals facilitate adherence to treatment. Our objective was to evaluate whether lanreotide Autogel® 120 mg, every 4–8 weeks, was as effective in controlling acromegaly as lanreotide microparticles 30 mg, every 1–2 weeks. Patients design and measurements Patients who had used lanreotide microparticles 30 mg, ≥ 2 months prestudy, and had responded to...
Touskova, V; Klouckova, J; Durovcova, V; Lacinova, Z; Kavalkova, P; Trachta, P; Kosak, M; Mraz, M; Haluzikova, D; Hana, V; Marek, J; Krsek, M; Haluzik, M
We explored the effect of chronically elevated circulating levels of growth hormone (GH)/insulin-like-growth-factor-1 (IGF-1) on mRNA expression of GH/IGF-1/insulin axis components and p85alpha subunit of phosphoinositide-3-kinase (p85alpha) in subcutaneous adipose tissue (SCAT) of patients with active acromegaly and compared these findings with healthy control subjects in order to find its possible relationships with insulin resistance and body composition changes. Acromegaly group had significantly decreased percentage of truncal and whole body fat and increased homeostasis model assessment-insulin resistance (HOMA-IR). In SCAT, patients with acromegaly had significantly increased IGF-1 and IGF-binding protein-3 (IGFBP-3) expression that both positively correlated with serum GH. P85alpha expression in SCAT did not differ from control group. IGF-1 and IGFBP-3 expression in SCAT were not independently associated with percentage of truncal and whole body fat or with HOMA-IR while IGFBP-3 expression in SCAT was an independent predictor of insulin receptor as well as of p85alpha expression in SCAT. Our data suggest that GH overproduction in acromegaly group increases IGF-1 and IGFBP-3 expression in SCAT while it does not affect SCAT p85alpha expression. Increased IGF-1 or IGFBP-3 in SCAT of acromegaly group do not appear to contribute to systemic differences in insulin sensitivity but may have local regulatory effects in SCAT of patients with acromegaly.
Andela, Cornelie D; Biermasz, Nienke R; Kaptein, Adrian A; Pereira, Alberto M; Tiemensma, Jitske
Patients with acromegaly can be treated with surgery, radiotherapy and/or medical treatment. In general, patients' beliefs about medication are associated with illness perceptions, a contributory factor of Quality of Life (QoL). At present, there are no quantitative studies on medication beliefs in patients with acromegaly. Here, we aimed to examine possible associations between medication beliefs, illness perceptions, and QoL. Furthermore we aimed to explore whether illness perceptions of patients with remission of acromegaly receiving medical treatment differ from patients without medical treatment. Cross-sectional evaluation of 73 patients with remission of acromegaly (n = 28 patients with medication, n = 45 without medication). The Beliefs about Medicines Questionnaire (BMQ), Illness Perception Questionnaire-Revised (IPQ-R), EuroQoL-5D, and AcroQoL were used for the assessment. Stronger beliefs about the necessity of medical treatment and stronger concerns about the adverse effects were associated with attributing more symptoms to acromegaly, perceiving more negative consequences, and having a stronger belief in a cyclical timeline (BMQ, all P acromegaly tend to perceive a more chronic timeline of their disease, compared to patients with remission without medical treatment. These psychological factors need to be taken into account when treating patients and developing a psychosocial education program aiming to improve QoL. Copyright © 2015 Elsevier Ltd. All rights reserved.
Ajaj, W.; Goyen, M.; Herrmann, B.; Massing, S.; Goehde, S.; Lauenstein, T.; Ruehm, S.G. [University Hospital, Department of Diagnostic and Interventional Radiology, Essen (Germany)
This study assessed both two-dimensional (2D) TrueFISP imaging for quantifying tongue volume and real-time TrueFISP imaging for evaluating chewing and swallowing in healthy volunteers and patients with acromegaly. In 50 healthy volunteers, tongue volumes were measured using a 2D TrueFISP sequence. Chewing and swallowing were visualized using a real-time TrueFISP sequence. Ten patients with acromegaly were examined twice with the same magnetic resonance imaging protocol: once prior to therapy and a second time 6 months after therapy. Prior to therapy, healthy volunteers had an average tongue volume of 140 ml for men and 90 ml for women, and patients with acromegaly had an average tongue volume of 180 ml for men and 145 ml for women. However, 6 months after therapy the mean tongue volumes in patients with acromegaly had decreased to 154 ml in the men and to 125 ml in the women. The chewing and swallowing process was normal in all volunteers. Prior to therapy, just two patients showed a chewing and swallowing pathology, which disappeared after therapy. Patients with acromegaly had larger tongue volumes than healthy volunteers, and TrueFISP imaging proved feasible for visualizing chewing and swallowing in real time and is capable of detecting possible pathologies. Furthermore, TrueFISP imaging can be used to monitor therapeutic approaches in patients with acromegaly. (orig.)
Bonert Vivien S
Full Text Available Abstract Pituitary adenomas are associated with a variety of clinical manifestations resulting from excessive hormone secretion and tumor mass effects, and require a multidisciplinary management approach. This article discusses the treatment modalities for the management of patients with a prolactinoma, Cushing's disease and acromegaly, and summarizes the options for medical therapy in these patients. First-line treatment of prolactinomas is pharmacotherapy with dopamine agonists; recent reports of cardiac valve abnormalities associated with this class of medication in Parkinson's disease has prompted study in hyperprolactinemic populations. Patients with resistance to dopamine agonists may require other treatment. First-line treatment of Cushing's disease is pituitary surgery by a surgeon with experience in this condition. Current medical options for Cushing's disease block adrenal cortisol production, but do not treat the underlying disease. Pituitary-directed medical therapies are now being explored. In several small studies, the dopamine agonist cabergoline normalized urinary free cortisol in some patients. The multi-receptor targeted somatostatin analogue pasireotide (SOM230 shows promise as a pituitary-directed medical therapy in Cushing's disease; further studies will determine its efficacy and safety. Radiation therapy, with medical adrenal blockade while awaiting the effects of radiation, and bilateral adrenalectomy remain standard treatment options for patients not cured with pituitary surgery. In patients with acromegaly, surgery remains the first-line treatment option when the tumor is likely to be completely resected, or for debulking, especially when the tumor is compressing neurovisual structures. Primary therapy with somatostatin analogues has been used in some patients with large extrasellar tumors not amenable to surgical cure, patients at high surgical risk and patients who decline surgery. Pegvisomant is indicated in patients
Full Text Available Jakob Dal,1 Nikolaj Skou,1 Eigil Husted Nielsen,2 Jens Otto Lunde Jørgensen,1 Lars Pedersen3 1Department of Endocrinology, Aarhus University Hospital, Aarhus, 2Department of Endocrinology, Aalborg University Hospital, Aalborg, 3Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark Background: The incidence of acromegaly is uncertain, since population-based studies are few. In the absence of a specific acromegaly registry, the Danish National Registry of Patients (DNRP becomes a potential source of data for studying the epidemiology of acromegaly, by linking all hospital discharge diagnoses to the personal identification numbers of individual Danish inhabitants. The validity of the DNRP with respect to acromegaly, however, remains to be tested. The aim of this study was to validate the International Classification of Diseases (ICD codes for acromegaly (ICD-8: 25300, 25301. ICD-10: E22.0 as used in the DNRP, and to assess the influence of various registration patterns on the accuracy of registry data. Methods: We identified patients registered with ICD codes for the diagnosis of acromegaly or other pituitary disorders during the period 1991–2009. Data on the institutional origin of each registration and the number of relevant DNRP registrations were recorded, and systematic patient chart reviews were performed to confirm the diagnosis. Results: In total, 110 cases of acromegaly were confirmed, compared with 275 registered cases, yielding a positive predictive value (PPV of 40%. When restricting the search to the regional highly specialized department of endocrinology, the PPV increased to 53% with no loss of cases with confirmed acromegaly. With a requirement of at least one, two, or three DNRP registrations, the PPV increased, but with a concurrent loss of confirmed cases. Conclusion: The DNRP seems to be a useful source for identifying new cases of acromegaly, especially when restricting the search to a relevant
Yamazaki, Masanori; Sato, Ai; Nishio, Shin-ichi; Takeda, Teiji; Miyamoto, Takahide; Katai, Miyuki; Hashizume, Kiyoshi
A 33-year-old woman was hospitalized for examination of edematous laryngopharynx. She was acromegalic. A pituitary adenoma with elevated serum levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I) was detected, indicating acromegaly caused by GH-secreting pituitary adenoma. Multiple pigmented nevi were also noted without overt short stature and cubitus valgus. Chromosome analysis revealed that she had contracted Turner syndrome with 47,XXX/45,X/46,XX mosaicism. Transsphenoidal resection of the tumor decreased serum GH and IGF-I levels, but the edema was not improved. Both premature ovarian failure and hypertension appeared after surgery. This case may indicate the important relationships between GH/IGF-I and Turner syndrome.
Tourtelot, John B; Vesely, David L
A 7'3" basketball player was noted to have 2 to 3 times thicker tissue in his hands than 6'10" players by an endocrinologist sitting 10 rows above the player in a basketball arena. This led to the diagnosis of pituitary gigantism where the history revealed that he was 7'3" at 15 years of age. At age 19 when the acryl enlargement was noted, a diagnostic workup revealed elevated growth hormones and insulin-like growth factor 1 (IGF-1) with a 2 × 1.3 cm pituitary tumor. His history suggested that his epiphyseal plates had closed at age 15, and because he continued to produce IGF-1, he now has acromegaly. His elevated adrenocorticotropic hormone (ACTH) before surgery suggests that he also had preclinical Cushing's disease. After pituitary transsphenoidal surgery, all acryl enlargement in hands and ligaments disappeared. His growth hormone, IGF-1 and ACTH returned to normal 2 weeks after surgery.
Page, M D; Millward, M E; Taylor, A; Preece, M; Hourihan, M; Hall, R; Scanlon, M F
We have treated 16 acromegalic patients for up to 44 months with octreotide in varying doses. Growth hormone levels were suppressed in 14 patients with associated clinical improvement. IGF-1 levels were measured in 12 and fell into the normal range in 10. Prolactin was suppressed in six hyperprolactinaemic patients but was unaltered in normoprolactinaemic acromegalic patients. Post-prandial hyperglycaemia with impaired insulin secretion was noted in all patients, and one patient required oral hypoglycaemic agents. Octreotide did not affect thyroid function. CT scans from before and after six months of treatment demonstrated minimal tumour shrinkage in only two patients. Octreotide was well tolerated with no serious haematological or biochemical disturbance and no evidence of malabsorption. Two patients developed gallstones. Octreotide is effective in acromegaly. The development of gallstones is the only serious adverse event we have encountered.
P. Senthil Kumar
Full Text Available The purpose of the study was octreotide therapy in acromegaly is associated with an increased prevalence of gall stones, which may be the result of inhibition of gall bladder motility. Gall stone prevalence in untreated acromegalic patients relative to the general population is unknown, however and the presence of gall stones and gall bladder motility in these patients and in acromegalic patients receiving octreotide was therefore examined. Gall bladder emptying in untreated acromegalic subjects is impaired. Octreotide further increases post prandial residual gall bladder volume and this may be a factor in the increased gall stone prevalence seen in these patients. The results of octreotide therapy in acromegalic and the normal controls were compared using the marginal distribution of a stretched Brownian motion ( as ∗ ; = 1 4 − 2 4
Full Text Available Abstract Introduction Oxalate nephropathy has various etiologies and remains a rare cause of renal failure. To the best of our knowledge, we report the first case of oxalate nephropathy following octreotide therapy. Case presentation We report the case of a 78-year-old Caucasian man taking chronic octreotide treatment for acromegaly who presented with acute oxalate nephropathy after antibiotic therapy. The diagnosis was confirmed by urinary analysis and a kidney biopsy. The recovery of renal function was favorable after hydration and withdrawal of octreotide therapy. Conclusions Oxalate nephropathy should be suspected in patients at risk who present with acute kidney injury after prolonged antibiotic treatment. This diagnosis should be distinguished from immuno-allergic interstitial nephritis and requires specific care. The evolution of this condition may be favorable if the pathology is identified correctly. Octreotide therapy should be considered a risk factor for enteric oxaluria.
Ferraù, Francesco; Romeo, P D; Puglisi, S; Ragonese, M; Torre, M L; Scaroni, C; Occhi, G; De Menis, E; Arnaldi, G; Trimarchi, F; Cannavò, S
This multicentric study aimed to investigate the prevalence of the G protein-coupled receptor 101 (GPR101) p.E308D variant and aryl hydrocarbon receptor interacting protein (AIP) gene mutations in a representative cohort of Italian patients with acromegaly. 215 patients with GH-secreting pituitary adenomas, referred to 4 Italian referral centres for pituitary diseases, have been included. Three cases of gigantism were present. Five cases were classified as FIPA. All the patients have been screened for germline AIP gene mutations and GPR101 gene p.E308D variant. Heterozygous AIP gene variants have been found in 7 patients (3.2 %). Five patients carried an AIP mutation (2.3 %; 4 females): 3 patients harboured the p.R3O4Q mutation, one had the p.R304* mutation and the last one the IVS3+1G>A mutation. The prevalence of AIP mutations was 3.3 % and 2.8 % when considering only the patients diagnosed when they were <30 or <40-year old, respectively. Furthermore, 2.0 % of the patients with a pituitary macroadenoma and 4.2 % of patients resistant to somatostatin analogues treatment were found to harbour an AIP gene mutation. None of the patients was found to carry the GPR101 p.E308D variant. The prevalence of AIP gene mutations among our sporadic and familial acromegaly cases was similar to that one reported in previous studies, but lower when considering only the cases diagnosed before 40 years of age. The GPR101 p.E308D change is unlikely to have a role in somatotroph adenomas tumorigenesis, since none of our sporadic or familial patients tested positive for this variant.
Resmini, E; Murialdo, G; Giusti, M; Boschetti, M; Minuto, F; Ferone, D
We describe the case of an acromegalic patient primarily treated with octreotide LAR in whom the pituitary tumor disappeared after 18 months of treatment. A 68-yr-old woman, with clinical suspicion of acromegaly, was admitted to our Unit with the ultrasonographical evidence of cardiac hypertrophy, arrhythmias, right branch block and interatrial septum aneurism. She referred hands and feet enlargement since the age of 30 and facial disfigurements since the age of 50. At the age of 45 she underwent surgery for carpal tunnel syndrome and at the age of 61 an euthyroid nodular goiter was diagnosed. Hormonal evaluation showed elevated circulating GH levels (25+/-3.2 ng/ml), not suppressible after oral glucose load, and elevated IGF-I levels (646 ng/ml), whereas the remaining pituitary function was normal. Visual perimetry was normal, whereas magnetic resonance imaging (MRI) showed an intrasellar pituitary adenoma with maximal diameter of 9 mm. In order to improve cardiovascular function before surgery, the patient started octreotide LAR 20 mg every 4 weeks for 3 months. Then based on IGF-I values, the dose was adjusted to 30 mg. After 6 months a second MRI showed significant tumor reduction (>50% of baseline maximal diameter), GH and IGF-I were within the normal range and the patient continued the treatment. After one-year therapy, an improvement of cardiac alterations was recorded and the patient was referred to the neurosurgeon. However, she refused the operation. At 18-month follow-up, MRI showed the complete disappearance of direct and indirect signs of pituitary adenoma. To our knowledge, this is the first case of complete radiological remission of pituitary tumor during octreotide LAR treatment in acromegaly.
Full Text Available INTRODUCTION: Acromegaly is frequently associated with impaired glucose tolerance and/or diabetes. To evaluate the relationship between glucose metabolism and acromegaly disease, we evaluated 269 consecutive patients from two referral centres. METHODS: Clinical presentation, pituitary tumor size and invasiveness, and pituitary pathology were captured in a dedicated database. RESULTS: 131 women and 138 men with a mean age of 53.8 years were included. Of these, 201 (74.7% presented with a macroadenoma and 18 (6.7% with a microadenoma. Radiographic invasion was present in 91 cases (33.8%. Mean tumor diameter was 1.86 cm (0.2-4.6. Pituitary histopathologic findings revealed pure GH-producing somatotroph adenomas (SA in 147 patients, prolactin-production by mixed lactotroph (LA and SA or mammosomatotroph adenoma (MSA in 46 [22.4%], acidophil stem cell adenoma in 6 [2.9%], and other diagnoses in 6 [2.9%]. Medical treatment included octreotide in 96 [36.9%] and in combination with pegvisomant or dopamine agonists in 63 [24.2%]. Nearly 80% of patients achieved IGF-1 normalization. Importantly, patients with pure somatotroph adenomas were significantly more likely to present with abnormal glucose metabolism [48.7%] than those with mixed adenomas [9.7%] [p<0.001] independent of GH/IGF-1 levels or tumor invasiveness. Abnormal glucose metabolism and pituitary pathology also remained linked following IGF-1 normalization. Moreover patients with pure SA and abnormal glucose metabolism were significantly (p<0.001 less likely to achieve disease remission despite the same therapeutic strategies. Conversely, patients with mixed adenomas were more likely (OR: 2.766 (95% CI: 1.490-5.136 to achieve disease remission. CONCLUSIONS: Patients with pure somatotroph adenomas are more likely than those with mixed adenomas to exhibit abnormal glucose metabolism.
Turgut, Sebahat; Topsakal, Senay; Ata, Melek Tunç; Herek, Duygu; Akın, Fulya; Özkan, Şeyma; Turgut, Günfer
Background: Acromegaly is associated with increased morbidity and mortality related to cardiovascular diseases. Leptin (LEP) and Leptin Receptor (LEPR) gene polymorphisms can increase cardiovascular risks. The aim of this study was to investigate association between the frequencies of LEP and LEPR gene polymorphisms and subclinical atherosclerosis in acromegalic patients. Methods: Forty-four acromegalic patients and 30 controls were admitted to study. The polymorphisms were identified by using polymerase chain reaction from peripheral blood samples. The levels of systolic and diastolic blood pressure, BMI, fasting plasma glucose, fasting insulin, IGF-I, GH, IGFBP3, leptin, triglyceride, carotid Intima Media Thickness (cIMT) and HDL and LDL cholesterol concentrations were evaluated. Results: There was statistically significant difference between the LEPR genotypes of acromegalic patients (GG 11.4%, GA 52.3%, and AA 36.4%) and controls (GG 33.3%, GA 50%, and AA 16.7%) although their LEP genotype distribution was similar. In addition, the prevalence of the LEPR gene G and A alleles was significantly different between patients and controls. No significant difference was found among the G(-2548) A leptin genotypes of groups in terms of the clinical parameters. cIMT significantly increased homozygote LEPR GG genotype group compared to AA subjects in patients. But the other parameters were not different between LEPR genotypes groups of patients and controls. Conclusion: It can be said that the LEPR gene polymorphism may affect cIMT in patients. The reason is that LEPR GG genotype carriers may have more risk than other genotypes in the development of subclinical atherosclerosis in acromegaly. PMID:27563428
Full Text Available BACKGROUND: The long-acting somatostatin analogue octreotide is used either as an adjuvant or primary therapy to lower growth hormone (GH levels in patients with acromegaly and may also induce pituitary tumor shrinkage. OBJECTIVE: We performed a meta-analysis to accurately assess the effect of octreotide on pituitary tumor shrinkage. DATA SOURCES: A computerized Medline and Embase search was undertaken to identify potentially eligible studies. STUDY ELIGIBILITY CRITERIA: Eligibility criteria included treatment with octreotide, availability of numerical metrics on tumor shrinkage and clear definition of a clinically relevant reduction in tumor size. Primary endpoints included the proportion of patients with tumor shrinkage and mean percentage reduction in tumor volume. DATA EXTRACTION AND ANALYSIS: The electronic search identified 2202 articles. Of these, 41 studies fulfilling the eligibility criteria were selected for data extraction and analysis. In total, 1685 patients were included, ranging from 6 to 189 patients per trial. For the analysis of the effect of octreotide on pituitary tumor shrinkage a random effect model was used to account for differences in both effect size and sampling error. RESULTS: Octreotide was shown to induce tumor shrinkage in 53.0% [95% CI: 45.0%-61.0%] of treated patients. In patients treated with the LAR formulation of octreotide, this increased to 66.0%, [95% CI: 57.0%-74.0%. In the nine studies in which tumor shrinkage was quantified, the overall weighted mean percentage reduction in tumor size was 37.4% [95% CI: 22.4%-52.4%], rising to 50.6% [95% CI: 42.7%-58.4%] with octreotide LAR. LIMITATIONS: Most trials examined were open-label and had no control group. CONCLUSIONS: Octreotide LAR induces clinically relevant tumor shrinkage in more than half of patients with acromegaly.
Seravalle, G; Carzaniga, C; Attanasio, R; Grassi, G; Lonati, L; Facchini, C; Cozzi, R; Fatti, L M; Montini, M; Vitale, G; Sciortino, G; Damanti, S; Brambilla, G; Cavagnini, F; Mancia, G; Scacchi, M
Sympathovagal imbalance has been shown in acromegaly by indirect measurements of adrenergic tone. Data regarding direct measurement of sympathetic activity are lacking as yet. Aim of this study was to assess the adrenergic tone through direct recording of muscle sympathetic nerve activity (MSNA) in acromegalic patients. Fifteen patients (age 26-66 years, eight women) with newly diagnosed active acromegaly without hyperprolactinaemia, pituitary hormone deficiencies, obstructive sleep apnoea and cardiac hypertrophy, and 15 healthy subjects matched for age, sex and body mass index were recruited. After evaluating anthropometric and echocardiographic parameters, anterior pituitary function, glucose and lipid metabolism, and measuring plasma leptin, direct recording of sympathetic outflow via the microneurographic technique was performed. For similar anthropometric and metabolic parameters in patients and controls, HOMA index was significantly increased in the former (4·2 ± 2·39 vs 1·6 ± 0·19, P < 0·001). Surprisingly, this finding of insulin resistance was accompanied by a marked sympathetic inhibition (MSNA 18·3 ± 8·10 vs 37·3 ± 6·48 bursts/min, P < 0·0001, respectively in patients and controls). A reduction in plasma leptin (1·6 ± 1·04 vs 6·5 ± 2·01 μg/l, P < 0·0001) was also recorded in the patients. MSNA was positively correlated with leptin (P < 0·0001). Newly diagnosed acromegalic patients without cardiac hypertrophy display a decreased sympathetic outflow in spite of insulin resistance. This finding might be related to hypoleptinaemia. © 2012 Blackwell Publishing Ltd.
W K M G Amarawardena
Full Text Available The granulation pattern of somatotroph adenomas is well known to be associated with differing clinical and biochemical characteristics, and it has been shown that sparsely granulated tumours respond poorly to commonly used somatostatin receptor ligands (SRLs. We report a challenging case of acromegaly with a sparsely granulated tumour resistant to multiple modalities of treatment, ultimately achieving biochemical control with pasireotide. A 26-year-old lady presented with classical features of acromegaly, which was confirmed by an oral glucose tolerance test. Insulin-like growth factor 1 (IGF1 was 1710 μg/L (103–310 μg/L and mean growth hormone (GH was >600 U/L. MRI scan showed a 4 cm pituitary macroadenoma with suprasellar extension and right-sided cavernous sinus invasion. She underwent trans-sphenoidal pituitary surgery. Histology displayed moderate amounts of sparsely granular eosinophilic cytoplasm, staining only for GH. Postoperative investigations showed uncontrolled disease (IGF1:1474 μg/L, mean GH:228 U/L and residual tumour in the cavernous sinus. She received external beam fractionated radiation. Over the years, she received octreotide LAR (up to 30 mg, lanreotide (up to 120 mg two weekly, cabergoline, pegvisomant and stereotactic radiosurgery to no avail. Only pegvisomant resulted in an element of disease control; however, this had to be stopped due to abnormal liver function tests. Fifteen years after the diagnosis, she was started on pasireotide 40 mg monthly. Within a month, her IGF1 dropped and has remained within the normal range (103–310 μg/L. Pasireotide has been well tolerated, and there has been significant clinical improvement. Somatostatin receptor subtyping revealed a positivity score of two for both sst5 and sst2a subtypes.
Gordon, Rebecca J.; Bell, Jennifer; Chung, Wendy K.; David, Raphael; Oberfield, Sharon E.; Wardlaw, Sharon L.
Purpose Acromegaly in infancy is extremely rare. We describe a 32 year old woman who presented at 6 months of age with isolated macrocephaly, followed by accelerated linear growth. At 21 months of age, her head circumference was 55 cm (+5.5 SD), height was 97.6 cm (+4.4 SD) and weight was 20.6 kg (+6.2 SD). She had markedly elevated levels of growth hormone (GH) (135 ng/ml), IGF-1 (1540 ng/ml) and prolactin (370 ng/ml). A pituitary macroadenoma was surgically resected. Immunohistochemical staining was positive for GH. Post-operatively, she developed ACTH and TSH deficiency and diabetes insipidus. Methods Long term clinical follow-up and genetic testing with chromosomal microarray analysis. Results Despite GH deficiency, she grew well until 7 ½ years old, with subsequent decline in growth velocity, and received GH therapy for 5 years. Puberty was initiated with estrogen therapy. As an adult, she has no stigmata of acromegaly, with a height of 164.5 cm and non-acromegalic features. IGF-1 has remained in the low normal range. Prolactin has been mildly elevated. Serial MRIs have shown no evidence of tumor recurrence. She receives replacement therapy with hydrocortisone, levothyroxine and DDAVP. Chromosomal microarray analysis revealed that she has X-linked acrogigantism (X-LAG) due to a de novo duplication of Xq26.3 (516 kb). She recently became pregnant following ovarian stimulation and chorionic villus sampling revealed that she is carrying a male with the same duplication. Conclusion This report provides detailed long term clinical follow-up of a patient with X-LAG syndrome. PMID:27631333
Sagvand, Babak Torabi; Khairi, Shafaq; Haghshenas, Arezoo; Swearingen, Brooke; Tritos, Nicholas A; Miller, Karen K; Klibanski, Anne; Nachtigall, Lisa B
Long-acting somatostatin analogs are one of the main classes of medical therapy used for acromegaly and most patients require ongoing treatment. Few studies have evaluated the long-term efficacy and safety of lanreotide depot beyond 2 years. The goal of this study was to provide a long-term longitudinal assessment of efficacy and safety of lanreotide depot in lanreotide responders compared to a surgically cured control group. In this retrospective longitudinal case-control study, patients with acromegaly receiving lanreotide depot monotherapy continuously for at least 24 months (N = 24) and surgically cured patients (N = 39) were compared. Serum IGF-1, pituitary MRIs, lanreotide dose, co-morbidities and adverse effects were assessed longitudinally. In the lanreotide group, IGF-1 remained normal and unchanged over 6 years; comparable to the surgery only group. There was no difference in prevalence of normal IGF-1 between the lanreotide and surgery only groups at 6 months (100 vs. 97 %), 6 years (89 vs. 90 %) and at last follow-up (96 vs. 92 %). Tumor size remained stable (79 %) or decreased (21 %) in the lanreotide group. In the surgery only group, tumor size remained unchanged in all patients. Hemoglobin A1C did not differ between lanreotide and surgery only groups (baseline 5.8 vs. 6.1 %; last follow-up 6.0 vs. 5.7 %). Two (8 %) of the lanreotide and none of the surgery only group developed new diabetes mellitus. Lanreotide depot maintains normalization of IGF-1 in 89 % of responders after 6 years, comparable to surgically cured controls, and controlled tumor size in all without significant adverse effects.
Valassi, Elena; Brick, Danielle J.; Johnson, Jessica C.; Biller, Beverly M. K.; Klibanski, Anne; Miller, Karen K.
Objective To compare the response in quality of life (QoL) to growth hormone (GH) replacement in women with GH deficiency (GHD) and a history of acromegaly with that in women with GHD of other causes. Methods Fifty-five women with GHD were studied: 17 with prior acromegaly and 38 with other causes of GHD. We compared two 6-month, randomized, placebo-controlled studies of GH therapy in women with hypopituitarism conducted with use of the same design—one in women with a history of acromegaly and one in women with no prior acromegaly. QoL was assessed with the following questionnaires: the QoL-Assessment of Growth Hormone deficiency in Adults (AGHDA), the Symptom Questionnaire, and the 36-Item Short-Form Health Survey (SF-36). Results The 2 groups had comparable mean pretreatment age, body mass index, and QoL scores and comparable mean GH dose at 6 months (0.61 ± 0.30 versus 0.67 ± 0.27 mg daily). After 6 months of GH replacement therapy, women with GHD and prior acromegaly demonstrated a greater improvement in AGHDA score, four SF-36 subscales (Role Limitations due to Physical Health, Energy or Fatigue, Emotional Well-Being, and Social Functioning), and the Somatic Symptoms subscale of the Symptom Questionnaire than did women with GHD of other causes. Poorer pretreatment QoL was associated with a greater improvement in QoL after administration of GH. Conclusion In this study, GH replacement therapy improved QoL in women with GHD and a history of acromegaly but not in women with GHD due to other hypothalamic and pituitary disorders. Further studies are needed to determine the long-term risks versus benefits of GH replacement in patients who develop GHD after definitive treatment for acromegaly. PMID:22440981
Mewawalla, Prerna; Jaiswal, Gayatri; Moustakakis, Michael; Sankaranarayanan, Niranjan; Dasanu, Constantin A
Diabetic ketoacidosis is rarely encountered in acromegaly. We present a unique patient with refractory diabetic ketoacidosis (DKA) as a first presentation of acromegaly. In addition to an insulin drip and intravenous fluids, our patient was managed with octreotide therapy. As he developed acute renal failure in the context of renal hypoperfusion, continuous venovenous hemofiltration (CVVH) was instituted. After only three days of therapy, the growth hormone (GH) level dropped circa fourfold and insulin growth factor 1 (IGF-1) level dropped ninefold. We postulate a hypothetical role of CVVH in removal of plasma GH and IGF-1, similar to the clearance of other medium size molecules such as brain natriuretic peptide and procalcitonin. If this is confirmed in future studies, CVVH may have therapeutic implications for the above category of patients.
Andreassen, Mikkel; Faber, Jens; Kjær, Andreas;
of acromegaly is initiated. This was a three months prospective study investigating short-term cardiac effects of treatment in acromegalic patients. Cardiac function was evaluated by the gold standard method cardiac magnetic resonance imaging (CMRI) and circulating levels of B-type natriuretic peptides (BNP......Long-term treatment of acromegaly prevents aggravation and reverses associated heart disease. A previous study has shown a temporary increase in serum levels of the N-terminal fraction of pro B-type natriuretic peptide (NT-proBNP) suggesting an initial decline in cardiac function when treatment...... and NT-proBNP). CMRI was performed at baseline and after 3 months of treatment. Levels of IGF-I, BNP and NT-proBNP were measured after 0, 1, 2 and 3 months. Eight patients (5 males and 3 females, mean age 53 ± 12 years (range 30-70)) and 8 matched healthy control subjects were included. Median IGF-I Z...
Pendleton, Courtney; Adams, Hadie; Salvatori, Roberto; Wand, Gary; Quiñones-Hinojosa, Alfredo
A review of Dr. Cushing's surgical cases at Johns Hopkins Hospital revealed new information about his early operative experience with acromegaly. Although in 1912 Cushing published selective case studies regarding this work, a review of all his operations for acromegaly during his early years has never been reported. We uncovered 37 patients who Cushing treated with surgical intervention directed at the pituitary gland. Of these, nine patients who presented with symptoms of acromegaly, and one with symptoms of gigantism were selected for further review. Two patients underwent transfrontal 'omega incision' approaches, and the remaining eight underwent transsphenoidal approaches. Of the 10 patients, 6 were male. The mean age was 38.0 years. The mean hospital stay was 39.4 days. There was one inpatient death during primary interventions (10%) and three patients were deceased at the time of last follow-up (33%). The mean time to death, calculated from the date of the primary surgical intervention, and including inpatient and outpatient deaths, was 11.3 months. The mean time to last follow-up, calculated from the day of discharge, was 59.3 months. At the time of last follow-up, two patients reported resolution of headache; four patients reported continued visual deficits, and two patients reported ongoing changes in mental status. This review analyzes the outcomes for 10 patients who underwent surgical intervention for acromegaly or gigantism, and offers an explanation for Cushing's transition from the transfrontal "omega incision" to the transsphenoidal approach while practicing at the Johns Hopkins Hospital.
Niyazoglu, Mutlu; Sayitoglu, Muge; Firtina, Sinem; Hatipoglu, Esra; Gazioglu, Nurperi; Kadioglu, Pinar
Aryl hydrocarbon receptor-interacting protein (AIP) is associated with 15-20% of familial isolated pituitary adenomas and 50-80% of cases with AIP mutation exhibit a somatotropinoma. Herein we report clinical characteristics of a large family where AIP R304X variants have been identified. AIP mutation analysis was performed on a large (n = 52) Turkish family across six generations. Sella MRIs of 30 family members were obtained. Basal pituitary hormone levels were evaluated in 13 family members harboring an AIP mutation. Thirteen of 52 family members (25%) were found to have a heterozygous nonsense germline R304X mutation in the AIP gene. Seven of the 13 mutation carriers (53.8%) had current or previous history of pituitary adenoma. Of these 7 mutation carriers, all but one had somatotropinoma/somatolactotropinoma (85.7% of the pituitary adenomas). Of the 6 acromegaly patients with AIP mutation (F/M: 3/3) the mean age at diagnosis of acromegaly was 32 ± 10.3 years while the mean age of symptom onset was 24.8 ± 9.9 years. Three of the six (50%) acromegaly cases with AIP mutation within the family presented with a macroadenoma and none presented with gigantism. Biochemical disease control was achieved in 66.6% (4/6) of the mutation carriers with acromegaly after a mean follow-up period of 18.6 ± 17.6 years. Common phenotypic characteristics of familial pituitary adenoma or somatotropinoma due to AIP mutation vary between families or even between individuals within a family.
Gonzalez, Baldomero; Vargas, Guadalupe; Mendoza, Victoria; Nava, Mariana; Rojas, Moisés; Mercado, Moisés
Acromegaly is associated with an increased risk of colonic polyps. The magnitude of such risk is controversial, and the characteristics that distinguish patients who develop polyps from those who do not are not well established. This study was performed to determine the prevalence of colonic polyps upon the diagnosis of acromegaly and to compare the clinical and biochemical features of patients with and without polyps. Out of 165 patients who underwent a full colonoscopy upon diagnosis of acromegaly, 53 were found to harbor colonic lesions (cases), whereas the remaining 112 were used as controls. Demographic, clinical, and biochemical characteristics were compared between the 2 groups. The prevalence of colonic polyps was 32%, with an estimated relative risk of 6.21 (95% confidence interval [CI] 4.08-9.48). Adenomatous and nonadenomatous polyps were found in 22 and 31 patients, respectively. The most common location was the descending colon. Compared to patients without polyps, subjects with polyps were somewhat older and had significantly higher insulin-like growth factor-1 (IGF-1) levels and a higher prevalence of diabetes. Upon multivariate analysis, only IGF-1 level at diagnosis remained significantly associated with colonic polyps in general and with hyperplastic polyps in particular. Acromegaly is associated with an elevated risk of developing colonic polyps, particularly, distally located hyperplastic lesions. Except for a higher IGF-1 level at diagnosis, no distinctive clinical or biochemical features can be found among those who develop polyps compared to those who do not. CI = confidence interval GH = growth hormone IGF-1 = insulin-like growth factor 1 IQR = inter-quartile range RR = relative risk ULN = upper limit of normal.
de Oliveira Machado, Evelyn; Lima, Carlos Henrique Azeredo; Ogino, Liana Lumi; Kasuki, Leandro; Gadelha, Mônica R
Acromegaly is associated with significant morbidity and increased mortality, but has a variable severity phenotype. The presence of the exon 3-deleted isoform of the growth hormone receptor (d3-GHR) may influence the disease phenotype and treatment outcomes, including the frequency of biochemical discordance after medical treatment. The objective of this study was to analyze the influence of the d3-GHR isoform on clinical and biochemical characteristics and in the treatment outcomes of Brazilian multiethnic acromegaly patients. We retrospectively analyzed our acromegaly outpatient clinic databank and collected demographic, clinical, biochemical and treatment outcome data from those patients who agreed to participate in the study. A blood sample was collected from all patients, the DNA was extracted and the GHR isoforms were evaluated by PCR, with the full length (fl)-GHR represented by a 935-bp fragment and the d3-GHR represented by a 532-bp fragment. A total of 121 patients were included. Fifty-six patients (46.3 %) were full-length homozygous (fl/fl), 48 (39.7 %) were heterozygous (fl/d3) and 17 (14.0 %) were d3-GHR homozygous (d3/d3). There was no difference between patients homozygous for the fl isoform and those harboring at least one d3-GHR allele in the demographic, clinical and biochemical data or in the treatment outcomes, including somatostatin receptor ligands (SRL) monotherapy, combination therapy with SRL and cabergoline and pegvisomant treatment. There was also no difference between the groups for the frequency of GH and IGF-I discordance after medical treatment. GHR exon 3 genotyping appears to have no clinical significance, at least in Brazilian acromegaly patients.
Caron, Philippe J; Bevan, John S; Petersenn, Stephan; Houchard, Aude; Sert, Caroline; Webb, Susan M
To evaluate the effects of lanreotide Autogel on patient-reported outcomes and association with biochemical control, using PRIMARYS data. PRIMARYS was a 1-year, open-label study of lanreotide Autogel (Depot in USA) 120 mg every 4 weeks in 90 treatment-naïve patients with acromegaly. Symptoms were assessed using Patient-assessed Acromegaly Symptom Questionnaire (PASQ) and health-related quality of life (HRQoL) using the AcroQoL questionnaire. Correlations between PASQ and AcroQoL scores, and between PASQ/AcroQoL and growth hormone (GH)/insulin-like growth factor-1 (IGF-1) levels were also evaluated (post hoc). Acromegaly symptoms and HRQoL significantly improved from week 12 to week 48, with modest correlations at week 48 between PASQ total score (R = -0.55, p 50% of baseline standard deviation) in PASQ total score and >40% achieved a MID in AcroQoL global score (post hoc). Changes in PASQ scores were similar in biochemically controlled (GH levels ≤2.5 μg/L and normal IGF-1 levels) and uncontrolled groups, while changes in global and psychological AcroQoL scores were greater in the controlled group. There was no correlation between changes in PASQ or AcroQoL scores and changes in GH or IGF-1 levels. Primary treatment with lanreotide Autogel over 1 year was associated with rapid and sustained improvements in clinical signs and symptoms and HRQoL in patients with acromegaly. Improvements in HRQoL, but not symptoms, were greater in those achieving biochemical control (ClinicalTrials.gov: NCT00690898; EudraCT: 2007-000155-34).