... your blood pressure and water and salt balance. Addison disease happens if the adrenal glands don't make ... A problem with your immune system usually causes Addison disease. The immune system mistakenly attacks your own tissues, ...
Symptoms of Addison disease include: Chronic diarrhea, nausea, and vomiting Darkening of the skin in some places Dehydration Dizziness when standing up Low-grade fever Extreme weakness , fatigue , and slow, sluggish movement Darker ...
The clinical signs and symptoms of primary adrenal insufficiency are unspecific often causing a delayed diagnosis or even misdiagnosis. In the diagnostic work-up the short synacthen test is regarded as the gold standard. Hydrocortisone and fludrocortisone are the preferred therapy for Addison's disease. The management and surveillance of therapy requires experience and several aspects need to be followed to prevent side effects which might occur due to overtreatment or undertreatment. Very important aspects in therapy are the repeated teaching of the patient and relatives, the issuing of an emergency steroid card and the prescription of a glucocorticoid emergency set. Acute adrenal failure (adrenal crisis), which might be the first manifestation of adrenal insufficiency, is a life-threatening situation requiring immediate glucocorticoid administration and fluid substitution. The most common causes for an adrenal crisis are gastrointestinal infections and fever and discontinuation of glucocorticoid therapy. This article gives an up-to-date overview of diagnostic and therapeutic aspects of Addison's disease.
Addison's disease Diagnosis Your doctor will talk to you first about your medical history and your signs and ... If your doctor thinks that you may have Addison's disease, you may undergo some of the following tests: ...
Mor, F; Green, P; Wysenbeek, A J
Since the first description of primary adrenocortical insufficiency by Thomas Addison in 1855 several large series of patients with Addison's disease have been published. The common signs and symptoms include: weakness, hyperpigmentation, weight loss, gastrointestinal complaints, and hypotension. It is rare for patients with Addison's disease to present with musculoskeletal symptoms including flexion contractures, hyperkalaemic neuromyopathy, Guillain-Barré syndrome, migratory myalgia, sciati...
... of potassium and low levels of sodium. What causes Addison’s disease? Addison’s disease is caused by injury to your ... example, a problem with your pituitary gland can cause secondary Addison’s disease. Or, you may develop Addison’s disease if you ...
Afroz, S; Bain, S
Adrenal insufficiency is a rare disease, but is life threatening when overlooked. Addison's disease may be an acquired form of adrenal insufficiency due to the destruction or dysfunction of the adrenal cortex. It affects both glucocorticoid and mineralocorticoid function. Main presenting symptoms of Addison's disease such as fatigue, anorexia, vomiting and convulsion often mimics central nervous system (CNS) infections. We describe a case of Addison's disease who was initially misdiagnosed as a case of meningo-encephalitis subsequently renal tubular acidosis and finally Addison's disease. Addison's disease can remain unrecognized until acute crisis and sometimes it may be misdiagnosed.
Takahashi, Kentaro; Kagami, Shin-Ichiro; Kawashima, Hirotoshi; Kashiwakuma, Daisuke; Suzuki, Yoshio; Iwamoto, Itsuo
We herein describe a second Japanese case of sarcoidosis presenting Addison's disease. A 52-year-old man was diagnosed with sarcoidosis based on clinical and laboratory findings, including bilateral hilar lymphadenopathy and elevated levels of serum angiotensin-converting enzyme and lysozyme, as well as the presence of noncaseating epithelioid granulomas. The patient also exhibited general fatigue, pigmentation, weight loss, hypotension and hyponatremia, suggestive of chronic adrenocortical insufficiency. An endocrine examination confirmed primary adrenocortical insufficiency. This case suggests the direct involvement of sarcoid granuloma in the adrenal glands.
Napier, Catherine; Pearce, Simon H S
Addison's disease is a rare autoimmune disorder. In the developed world, autoimmune adrenalitis is the commonest cause of primary adrenal insufficiency, where the majority of patients have circulating antibodies against the key steroidogenic enzyme 21-hydroxylase. A complex interplay of genetic, immunological and environmental factors culminates in symptomatic adrenocortical insufficiency, with symptoms typically developing over months to years. Biochemical evaluation and further targeted investigations must confirm primary adrenal failure and establish the underlying aetiology. The diagnosis of adrenocortical insufficiency will necessitate lifelong glucocorticoid and mineralocorticoid replacement therapy, aiming to emulate physiological patterns of hormone secretion to achieve well-being and good quality of life. Education of patients and healthcare professionals is essential to minimise the risk of a life-threatening adrenal crisis, which must be promptly recognised and aggressively managed when it does occur. This article provides an overview of our current understanding of the natural history and underlying genetic and immunological basis of this condition. Future research may reveal novel therapeutic strategies for patient management. Until then, optimisation of pharmacological intervention and continued emphasis on education and empowerment of patients should underpin the management of individuals with autoimmune Addison's disease. Copyright © 2012. Published by Elsevier Masson SAS.
Puttanna, Amar; Cunningham, Alana Rosaleen; Dainty, Philip
Addison's disease is a relatively rare endocrine condition resulting from adrenal insufficiency due to various causes. Weight loss is a common feature; however, patients may be seen by a variety of specialists, even requiring acute admission before the diagnosis is made. Addison's disease is commonly associated with other autoimmune diseases. In some cases such as autoimmune polyendocrine syndromes (APS) types 1 and 2, these associations are more commonly found. We present a case of one such ...
Puttanna, Amar; Cunningham, Alana Rosaleen; Dainty, Philip
Addison's disease is a relatively rare endocrine condition resulting from adrenal insufficiency due to various causes. Weight loss is a common feature; however, patients may be seen by a variety of specialists, even requiring acute admission before the diagnosis is made. Addison's disease is commonly associated with other autoimmune diseases. In some cases such as autoimmune polyendocrine syndromes (APS) types 1 and 2, these associations are more commonly found. We present a case of one such patient who presented to the acute medical team having been referred to the gastrointestinal services in the previous year for persistent vomiting and weight loss. On review of history, the cause of vomiting and weight loss was questioned and combined with subsequent biochemical testing a diagnosis of Addison's disease was made. The patient was also noted to have other associated endocrine and autoimmune conditions.
Jul 17, 2013 ... Case Study: An unusual coexistence of Addison's disease and phaeochromocytoma. 164 ... strongly positive. ... Department of Endocrinology and Metabolism, Ondokuz Mayis University Medical School, Samsun, Turkey.
... common in particular ethnic groups? Genetic Changes The cause of autoimmune Addison disease is complex and not completely understood. A combination ... is not caused by an autoimmune reaction. Other causes include infections that ... adrenal glands. Addison disease can also be one of several features of ...
Cosimo, Caterina; Franco, Ciro
Addisonian crises, a rare but life-threatening event in pregnant women, may accompany stressful conditions such as labor, puerperium, infection, hyperemesis gravidarum or surgery. A 36-year-old woman, primigravida, with Addison's disease, diagnosed when she was 10 year-old and treated with cortisone and fludrocortisone. The therapy was regulated to avoid adrenal crisis during pregnancy. The woman underwent to caesarean section at 38th week and gave birth to a normal baby. The successful management of pregnant women with Addison's disease, regarding her state and that of the foetus, reassures those women that nowadays Addison's disease and pregnancy are not incompatible when proper monitoring and management is provided.
Napier, Catherine; Pearce, Simon H S
The purpose of this article is to review the current therapy of Addison's disease and to highlight recent developments in this field. Conventional steroid replacement for Addison's disease consists of twice or three-times daily oral hydrocortisone and once-daily fludrocortisone; however, new treatment modalities such as modified-released hydrocortisone and continuous subcutaneous hydrocortisone infusion have recently been developed. These offer the potential for closer simulation of the physiological serum cortisol rhythm. Two studies have also looked at modifying the natural history of adrenal failure using adrenocorticotropic hormone (ACTH) stimulation and immunomodulatory therapies, leading to the concept of residual adrenal function in some Addison's disease patients. Following more than 60 years with no significant innovation in the management of Addison's disease, these new approaches hold promise for improved patient health and better quality of life in the future.
Winters, Stephen J; Vitaz, Todd; Nowacki, Michael R; Craddock, Durrett C; Silverman, Craig
A 60-year-old man with Addison's disease, primary hypothyroidism and type 2 diabetes mellitus who was treated with stable doses of hydrocortisone and fludrocortisone developed increasing skin pigmentation and a bitemporal hemianopia. The plasma ACTH level was 14,464 pg/mL, and an invasive pituitary macroadenoma with suprasellar extension was found on magnetic resonance imaging leading to transnasal-transsphenoidal adenomectomy. The tumor demonstrated features of an eosinophilic adenoma and stained uniformly for ACTH. Residual tumor was treated with stereotactic radiotherapy. This case and the 13 cases published previously indicate that primary adrenal failure may predispose to corticotroph hyperplasia, and in some patients to the development of an invasive corticotroph adenoma. The ACTH level should be measured, and a pituitary magnetic resonance imaging is indicated when skin pigmentation increases in a patient with primary adrenal failure who is receiving customary treatment with glucocorticoids and mineralocorticoids.
Perry, M.C.; Eason, R.J.; Croxson, M.S.
The important contribution computerised tomography played in the diagnosis of tuberculous Addison's disease is described. While conventional radiographic methods of demonstrating this disease are often unhelpful, C.T. is an excellent technique for demonstrating the morphology of normal and abnormal adrenal glands
Oliveira, Diana; Lages, Adriana; Paiva, Sandra; Carrilho, Francisco
Addison's disease, or primary adrenocortical insufficiency, is a long-term, potentially severe, rare endocrine disorder. In pregnancy, it is even rarer. We report the case of a 30-year-old pregnant patient with Addison's disease, referred to Obstetrics-Endocrinology specialty consult at 14 weeks gestation. She had been to the emergency department of her local hospital various times during the first trimester presenting with a clinical scenario suggestive of glucocorticoid under-replacement (nausea, persistent vomiting and hypotension), but this was interpreted as normal pregnancy symptoms. Hydrocortisone dose was adjusted, and the patient maintained regular follow-up. No complications were reported for the remainder of gestation and delivery. Pregnant patients with Addison's disease should be monitored during gestation and in the peripartum period by multidisciplinary teams. Adjustments in glucocorticoid and mineralocorticoid replacement therapy are often necessary, and monitoring should be based mainly on clinical findings, which becomes increasingly difficult during pregnancy. Patient education and specialized monitoring are key to avoiding complications from under- or over-replacement therapy in this period. An increase in glucocorticoid replacement dose is expected to be necessary during pregnancy in a woman with Addison's disease.Patient education regarding steroid cover and symptoms of acute adrenal crisis are fundamental.Monitoring in this period is challenging and remains mainly clinical.The increase in hydrocortisone dose often obviates the need to increase fludrocortisone dose.
Bhattacharjee, Rana; Sharma, A; Rays, A; Thakur, I; Sarkar, D; Mandal, B; Mookerjee, S K; Chatterjee, S K; Chowdhury, Pradip Roy
Primary hypoadrenalism has various causes and protean manifestation. We report a young female patient who presented with severe muscle spasm as her primary complaint. On evaluation she was found to be a case of Addison's disease secondary to adrenal tuberculosis. Her muscle spasm disappeared rapidly with replacement dose of glucocorticoid.
Sun, Zhong-Hua; Nomura, Kaoru; Toraya, Shohzoh; Ujihara, Makoto; Horiba, Nobuo; Suda, Toshihiro; Tsushima, Toshio; Demura, Hiroshi; Kono, Atsushi
Adrenal computed tomographic (CT) scanning was conducted in twelve patients with Addison's disease during the clinical course. In tuberculous Addison's disease (n=8), three of four patients examined during the first two years after disease onset had bilaterally enlarged adrenals, while one of four had a unilaterally enlarged one. At least one adrenal gland was enlarged after onset in all six patients examined during the first four years. Thereafter, the adrenal glands was atrophied bilaterally, in contrast to adrenal glands in idiopathic Addison's disease which was atrophied bilaterally from disease onset (n=2). Adrenal calcification was a less sensitive clue in tracing pathogenesis, i.e., adrenal calcification was observed in five of eight patients with tuberculous Addison's disease, but not idiopathic patients. Thus, adrenal CT scanning could show the etiology of Addison's disease (infection or autoimmunity) and the phase of Addison's disease secondary to tuberculosis, which may be clinically important for initiating antituberculous treatment. (author)
Chaudhuri, Sayani; Rao, Karthik N; Patil, Navin; Ommurugan, Balaji; Varghese, George
Over past two decades there has been significant improvement in medical field in elucidating the underlying pathophysiology and genetics of Addison's disease. Adrenal insufficiency (Addison's disease) is a rare disease with an incidence of 0.8/100,000 cases. The diagnosis may be delayed if the clinical presentation mimics a gastrointestinal disorder or psychiatric illness. We report a case of Addison's disease presenting as acute pain in abdomen mimicking clinical presentation of acute pancreatitis.
Royo Gómez, M; Olmos Jiménez, M J; Rodríguez Arnao, M D; Roldán Martín, M B
Addison's disease or primary adrenal insufficiency is a rare disease in children. The signs and symptoms at diagnosis are frequently non-specific and insidious. Since adrenal crisis represents an emergency, it is important to be aware and to have a high degree of suspicion of the disorder in order to achieve an early diagnosis and treatment. We present a retrospective study describing the epidemiological, clinical and etiological data at diagnosis of five patients with Addison's disease followed up in our hospital. Dehydration, hyponatremia and skin hyperpigmentation were the most prevalent signs and symptoms at onset of the disease. The patients had low serum cortisol levels and positive adrenal antibodies. One patient with negative antibodies presented with a polyglandular syndrome. Copyright © 2012 Asociación Española de Pediatría. Published by Elsevier España, S.L. All rights reserved.
Ross, A H; Haider, S; Bailey, C C
To report three cases of Nonarteritic anterior ischaemic optic neuropathy (NAAION) in patients with Addison's disease. We present a retrospective review of patients presenting with NAAION with underlying Addison's disease. Three eyes of two young patients presented with NAAION. Both patients had underlying Addison's disease with episodes of prolonged hypotension. To our knowledge, this is the first published report of NAAION associated with Addison's disease. As hypotension may be one of the few situations, in which NAAION may be treatable and the visual loss reversible, it is important to recognize and treat sustained episodes of hypotension in these individuals.
Lambacher, Bianca; Wittek, Thomas
A 4.75-year old Simmental cow was presented with symptoms of colic and ileus. The clinical signs and blood analysis resulted in the diagnosis of suspected primary hypoadrenocorticism (Addison's disease). Although Addison's disease has been frequently described in other domestic mammals, to our knowledge, this disease has not previously been reported in cattle.
The prevalence of Addison's disease in South Africa is lower than in Western countries. This is concerning, since patients could be dying, undiagnosed. Enhanced awareness of this highly treatable condition is warranted. The epidemiology, aetiology, clinical presentation, screening and management of Addison's disease ...
Full Text Available Abstract Background Addison's disease, also known as hypoadrenocorticism, has been reported in many individual dogs, although some breeds exhibit a greater incidence than the population as a whole. Addison's is presumed to be an autoimmune mediated hereditary defect but the mode of inheritance remains unclear. In particular, the heritability and mode of inheritance have not been defined for the Portuguese Water Dog although Addison's is known to be prevalent in the breed. Results The analyses present clear evidence that establishes Addison's disease as an inherited disorder in the Portuguese Water Dog with an estimate of heritability of 0.49 (± 0.16; there were no differences in risk for disease across sexes (p > 0.49. Further, the complex segregation analysis provides suggestive evidence that Addison's disease in the Portuguese Water Dog is inherited under the control of a single, autosomal recessive locus. Conclusion The high heritability and mode of inheritance of Addison's disease in the Portuguese Water Dog should enable the detection of segregating markers in a genome-wide scan and the identification of a locus linked to Addison's. Though the confirmation of Addison's disease as an autosomal recessive disorder must wait until the gene is identified, breeders of these dogs may wish to keep the present findings in mind as they plan their breeding programs to select against producing affected dogs.
Oberbauer, A M; Bell, J S; Belanger, J M; Famula, T R
Addison's disease, also known as hypoadrenocorticism, has been reported in many individual dogs, although some breeds exhibit a greater incidence than the population as a whole. Addison's is presumed to be an autoimmune mediated hereditary defect but the mode of inheritance remains unclear. In particular, the heritability and mode of inheritance have not been defined for the Portuguese Water Dog although Addison's is known to be prevalent in the breed. The analyses present clear evidence that establishes Addison's disease as an inherited disorder in the Portuguese Water Dog with an estimate of heritability of 0.49 (+/- 0.16); there were no differences in risk for disease across sexes (p > 0.49). Further, the complex segregation analysis provides suggestive evidence that Addison's disease in the Portuguese Water Dog is inherited under the control of a single, autosomal recessive locus. The high heritability and mode of inheritance of Addison's disease in the Portuguese Water Dog should enable the detection of segregating markers in a genome-wide scan and the identification of a locus linked to Addison's. Though the confirmation of Addison's disease as an autosomal recessive disorder must wait until the gene is identified, breeders of these dogs may wish to keep the present findings in mind as they plan their breeding programs to select against producing affected dogs.
Chronic adrenal insufficiency, known as Addison's disease, presents with a constellation of symptoms and signs. The neuropsychiatric aspect of this condition is not fully understood and not much has been documented about it in the English literature. This article presents a case of a 41-year old male patient who presented initially with depression after a recent life stressor. After his condition escalated and therapy continued to fail, the medical team revised its diagnosis to Addison's disease. Neuropsychiatric symptoms could be the first presentation of Addison's disease, and thus should be kept in mind whenever such a case presents to the physician.
Husebye, Eystein S; Løvås, Kristian
Autoimmune Addison's disease and autoimmune ovarian insufficiency are caused by selective targeting by T and B lymphocytes to the steroidogenic apparatus in these organs. Autoantibodies toward 21-hydroxylase are a clinically useful marker for autoimmune Addison's disease. Autoantibodies to 21-hydroxylase are found in premature ovarian insufficiency, but others also can be present, notably antibodies against side-chain cleavage enzyme. The autoimmune response primarily targets the theca cells, yielding elevated concentrations of inhibin, which is emerging as a useful diagnostic marker for autoimmune etiology of ovarian insufficiency. Little is known about its immunogenetics, but in contrast to Addison's disease, several experimental models of autoimmune premature ovarian insufficiency are available for study.
Zhang, Zhuo-li; Wang, Yu; Zhou, Wei; Hao, Yan-jie
Addison's disease is an autoimmune process. However, Addison's disease associated with connective tissue diseases (CTD) is only occasionally reported. Here, we report six cases of Addison's disease secondary to a variety of CTD, which include systemic lupus erythematosus, Takayasu arteritis, systemic sclerosis, ankylosing spondylitis (AS) and antiphospholipid antibody syndrome. The association of Addison's disease with Takayasu arteritis and AS is reported for the first time. We also found high prevalence of hypothyroidism as concomitant autoimmune disorder. Our case series highlight the autoimmune features of Addison's disease. Therefore, we suggest considering adrenal dysfunction in patients with CTD.
Yamauchi, Teiyu; Yashiro, Naofumi; Iio, Masahiro
The computed tomography (CT) findings of the adrenal glands were described in six patients with Addison's disease. Three of four patients due to tuberculosis showed calcification in bilateral adrenal glands. In all three, non-calcified portions of left adrenal glands were identified by CT. One showed bilaterally enlarged adrenal glands. Bilateral adrenal glands were small in a patient with idiopatic Addison's disease. One patient of metastatic infiltration of the adrenal glands showed nodular masses in bilateral adrenal beds. CT findings were useful to clarify the etiology of Addison's patients. (author)
Addison's disease is a rare condition. Its onset of symptoms most often is nonspecific contributing to a diagnostic and therapeutic delay. Acute renal failure can be the first manifestation of this disease. We report the case of a patient with Addison's disease who was initially treated for acute renal failure due to multiple myeloma and whose diagnosis was adjusted thereafter. Patient's condition dramatically improved after treatment with intravenous rehydration; injectable hydrocortisone.
Bratland, Eirik; Husebye, Eystein S
Autoimmune adrenocortical failure, or Addison's disease, is a prototypical organ-specific autoimmune disorder. In common with related autoimmune endocrinopathies, Addison's disease is only manageable to a certain extent with replacement therapy being the only treatment option. Unfortunately, the available therapy does not restore the physiological hormone levels and biorhythm. The key to progress in treating and preventing autoimmune Addison's disease lies in improving our understanding of the predisposing factors, the mechanisms responsible for the progression of the disease, and the interactions between adrenal antigens and effector cells and molecules of the immune system. The aim of the present review is to summarize the current knowledge on the role of T cells and cellular immunity in the pathogenesis of autoimmune Addison's disease. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Pulzer, A; Burger-Stritt, S; Hahner, S
Adrenal insufficiency, a rare disorder which is characterized by the inadequate production or absence of adrenal hormones, may be classified as primary adrenal insufficiency in case of direct affection of the adrenal glands or secondary adrenal insufficiency, which is mostly due to pituitary or hypothalamic disease. Primary adrenal insufficiency affects 11 of 100,000 individuals. Clinical symptoms are mainly nonspecific and include fatigue, weight loss, and hypotension. The diagnostic test of choice is dynamic testing with synthetic ACTH. Patients suffering from chronic adrenal insufficiency require lifelong hormone supplementation. Education in dose adaption during physical and mental stress or emergency situations is essential to prevent life-threatening adrenal crises. Patients with adrenal insufficiency should carry an emergency card and emergency kit with them.
Srinivasan, B; Patel, M; Ethunandan, M; Ilankovan, V
Melanoma accounts for 5% of all skin cancers. The risk of metastasis is related to the thickness of the tumour, and can affect local, regional and distant sites. Adrenal metastasis from melanoma of the head and neck is uncommon and often asymptomatic. Addison's disease as a presentation of metastatic melanoma is extremely rare and we are unaware of previous reports in the world literature. We report a case of a patient with metastatic melanoma presenting with signs and symptoms of Addison's disease.
INTRODUCTION: Corticoid therapy is well-known to improve the symptoms of psoriasis. Addison's disease is an autoimmune disease which leads to a loss of cortisol production in the adrenal glands. This case report describes a patient with wide-spread psoriasis for 34 years who was cured when Addison's disease was detected and substitution to reach normal biological cortisol levels was introduced. CASE REPORT: A 59-year-old man was diagnosed with Addison's disease. He had been tired for several years and had had difficulties in continuing his work. His brother had Addison's disease and recommended him to make a screen for the disease. Synacthen test diagnosed Addison's disease with a clear deficiency of cortisol production. After substitution with hydrocortisone the patient's constitution improved rapidly and he felt no longer tired during work. At the same time, all skin lesions of psoriasis disappeared as well as aches in several joints, both symptoms having been present for a couple of decades. Previously, salves of cortisol had been used to reduce the symptoms of psoriasis, but now, 1-2 years later, after the treatment of Addison's disease, no symptoms in the skin or joints have reoccurred. CONCLUSIONS: This report illustrates that Addison's disease, although a rare condition, should be kept in mind before treatment of psoriasis is started. Especially if other symptoms such as fatigue are present, a screening test of serum cortisol in the morning should be liberally made. The report also illustrates a need of examining corticoid levels in patients with psoriasis compared to the general population.
Erichsen, Martina M; Husebye, Eystein S; Michelsen, Trond M; Dahl, Alv A; Løvås, Kristian
Females with primary adrenal insufficiency (Addison's disease) have reduced levels of circulating androgens, which are allegedly important for sexual functioning. The aim was to determine peripheral androgen status, sexual functioning, and birth rates in Addison's disease females. In a postal survey, all 269 females in the Norwegian Addison's registry were invited to complete the Sexual Activity Questionnaire (SAQ) and registration of childbirths. Blood samples were analyzed for 5alpha-androstane-3alpha,17beta-diol-3-glucuronide (3alpha-Diol-G) and compared with blood donor levels. The SAQ scores were compared with 740 age-matched controls from the general population and 234 women subjected to risk-reducing salpingo-oophorectomy. Fertility was estimated as standardized incidence ratio for birth; the expected number of births was estimated from population statistics. The SAQ was completed by 174 (65%) of the Addison's patients. Those not taking DHEA had significantly lower 3alpha-Diol-G levels than blood donors (mean, 0.53 vs. 2.2 ng/ml; P Addison's disease females were equally sexually active as the controls, but they reported significantly higher pleasure and less discomfort. They reported lower pleasure but less discomfort than the risk-reducing salpingo-oophorectomy women. The fertility was significantly reduced in females with Addison's disease; 54 children were born to mothers with established diagnosis (87.5 expected), yielding a standardized incidence ratio for birth of 0.69 (confidence interval, 0.52-0.86). Despite androgen depletion, females with Addison's disease do not report impaired sexuality. The fertility is reduced after the diagnosis is made; the reasons for this remain unknown.
Rodrigo Antonio Brandão Neto
Full Text Available CONTEXT: Erythema induratum of Bazin (EIB is considered to be a tuberculid reaction and consists of recurrent painful nodules. The differential diagnosis includes diseases like nodular vasculitis, perniosis, polyarteritis nodosa and erythema nodosum. CASE REPORT: We report the case of a woman with EIB who developed Addison's disease during treatment with anti-tuberculosis drugs with good response to glucocorticoid replacement. The diagnosis was obtained through the clinical picture, positive tuberculin test and positive BCG (bacillus Calmette-Guérin test on the histological sample. Anti-tuberculosis drugs and glucocorticoid replacement led to disappearance of the signs and symptoms. CONCLUSIONS: This is the first description of an association between EIB and Addison's disease. It should be borne in mind that tuberculosis is an important etiological factor for Addison's disease.
Full Text Available A 28-year-old man diagnosed with primary adrenal insufficiency (Addison's disease in 2002. Following diagnosis, replacement therapy with hydrocortisone and fludrocortisone was indicated. Hydrocortisone replacement therapy was unsuccessful, and increased ACTH levels as high as 996 pg/dl were observed on outpatient follow-up. A pituitary MRI revealed a pituitary microadenoma. These findings raised three possibilities: (1 treatment is insufficient; (2 there is no relationship between Addison's disease and pituitary microadenoma; and (3 the microadenoma is similar to Nelson's syndrome. This latter is the most satisfactory explanation of this patient's clinical picture.
Choudhary, Sandeep; Alam, Anwer; Dewan, Vivek; Yadav, Dinesh; Dubey, N K
Addison's disease is most commonly due to autoimmune adrenalitis and tuberculosis and refers to primary hypoadrenalism caused by a total or near total destruction or dysfunction of both adrenal cortices. Usual manifestations involve chronic fatigue, muscle weakness, loss of appetite, nausea, vomiting, diarrhea, hypotension and hyperpigmentation of skin. We herein report a case of primary adrenal insufficiency presenting with fever and seizures in an 11-yr-old boy. His symptoms resolved after starting specific therapy. This kind of presentation of Addison's disease is rather unusual.
White, K G
Jane Austen's letters describe a two-year deterioration into bed-ridden exhaustion, with unusual colouring, bilious attacks and rheumatic pains. In 1964, Zachary Cope postulated tubercular Addison's to explain her symptoms and her relatively pain-free illness. Literary scholars later countered this posthumous diagnosis on grounds that are not well substantiated, while medical authors supported his conclusion. Important symptoms reported by contemporary Addison's patients-mental confusion, generalised pain and suffering, weight loss and anorexia-are absent from Jane Austen's letters. Thus, by listening to the patient's perspective, we can conclude it is unlikely that Addison's disease caused Jane Austen's demise. Disseminated bovine tuberculosis would offer a coherent explanation for her symptoms, so that Cope's original suggestion of infective tuberculosis as the cause of her illness may have been correct.
Bøe Wolff, A S; Oftedal, B; Johansson, S
Autoimmune Addison's disease (AAD) is often associated with other components in autoimmune polyendocrine syndromes (APS). Whereas APS I is caused by mutations in the AIRE gene, the susceptibility genes for AAD and APS II are unclear. In the present study, we investigated whether polymorphisms...
Sowden, J. M.; Borsey, D. Q.
A 44 year old man with longstanding diabetes mellitus gave a 6-month history of periodic attacks of flaccid quadriplegia. Following one of these episodes he was admitted for assessment. In view of persistent hyperkalaemia, hypoadrenalism was suspected and Addison's disease was confirmed biochemically. Adrenal replacement therapy restored the potassium levels to normal and resulted in no further attacks of paralysis. PMID:2594601
Biagi, Federico; Campanella, Jonia; Soriani, Alessandra; Vailati, Alberto; Corazza, Gino R
It is well known that coeliac disease is associated with autoimmune endocrine diseases, such as autoimmune thyroid disease and insulin-dependent diabetes mellitus. Recently, coeliac disease has been shown in approximately 10% of patients with autoimmune Addison's disease. Addison's disease is the most common cause of primary adrenocortical insufficiency and it shares several clinical features with coeliac disease. Although hyperpigmentation and hypotension are the most specific signs, gastrointestinal symptoms are common and can be the first complaints of the patients. The aim of our study was to investigate the prevalence of coeliac disease in Italian patients with Addison's disease. Seventeen consecutive patients affected by Addison's disease (14 F, mean age 53.9 years, range 26-79 years) were enrolled in the study. Eleven of them were affected by Addison's disease associated with autoimmune thyroid disease and/or insulin-dependent diabetes mellitus; the other 6 patients were suffering from isolated Addison's disease. Diagnosis had been performed at the age of 40.5 years (range 23-55). Steroid treatment had already been started in 16 of the patients. Endomysial antibodies were tested in all of them and a duodenal biopsy was taken in those found to be positive for antiendomysial antibody (EMA). One out of 17 patients was found to be EMA positive. Duodenal biopsy confirmed the diagnosis of coeliac disease by showing subtotal villous atrophy. Although we studied only a small sample, our preliminary results confirmed that Addison's disease is associated with coeliac disease, being present in 5.9% of patients with Addison's disease. Since the symptoms can be similar and treatment of Addison's disease can mask coeliac disease, this association should always be actively investigated.
Eriksson, D.; Bianchi, Matteo; Landegren, Nils; Nordin, Jessika; Dalin, Frida; Mathioudaki, Argyri; Eriksson, G. N.; Hultin-Rosenberg, Lina; Dahlqvist, Johanna; Zetterqvist, H.; Karlsson, Andreas; Hallgren, Anna; Farias, F. H. G.; Murén, Eva; Ahlgren, Kerstin M.
BackgroundAutoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addisons disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. MethodsTo understand the genetic background of Addisons disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected se...
Anna A. Kasperlik-Zaluska
Full Text Available This study aimed at comparing two groups of patients with Addison's disease: A, including 180 patients described in 1991 and B, consisting of 138 patients registered since 1991. The incidence of coexisting autoimmune disorders was evaluated and etiological factors were analyzed. Immunological and imaging studies (computed tomography in group B were performed. Adrenal autoantibodies were examined by an indirect immunofluorescence technique in group A, and by the assay measuring autoantibodies against steroid 21-hydroxylase in group B. Adrenal autoantibodies were revealed in 37% of patients examined by the immunofluorescence method and in 63% investigated by the modern technique. Tuberculosis was found in 52 patients in the group A and in two patients in the group B; metastatic infiltrations of the adrenals in CT were detected in 16 patients. Probable autoimmune Addison's disease was diagnosed in 125/180 patients (69% in the group A and in 116/138 patients (84% in the group B.
Kasperlik-Zaluska, Anna A.; Czarnocka, Barbara; Jeske, Wojciech; Papierska, Lucyna
This study aimed at comparing two groups of patients with Addison's disease: A, including 180 patients described in 1991 and B, consisting of 138 patients registered since 1991. The incidence of coexisting autoimmune disorders was evaluated and etiological factors were analyzed. Immunological and imaging studies (computed tomography in group B) were performed. Adrenal autoantibodies were examined by an indirect immunofluorescence technique in group A, and by the assay measuring autoantibodies against steroid 21-hydroxylase in group B. Adrenal autoantibodies were revealed in 37% of patients examined by the immunofluorescence method and in 63% investigated by the modern technique. Tuberculosis was found in 52 patients in the group A and in two patients in the group B; metastatic infiltrations of the adrenals in CT were detected in 16 patients. Probable autoimmune Addison's disease was diagnosed in 125/180 patients (69%) in the group A and in 116/138 patients (84%) in the group B. PMID:21188237
Meyer, G; Hackemann, A; Penna-Martinez, M; Badenhoop, K
Several studies have shown a reduced quality of life in patients with Addison's disease, but little is known about the potential influences. We determined the quality of life in 200 patients with Addison's disease using an Addison's disease-specific quality-of-life questionnaire. Data about first symptoms, time to diagnosis and current medication were collected by questionnaires. With increasing latency between first symptoms and diagnosis of adrenal insufficiency, the quality of life decreased in highly significant manner (pdisease (p=0.05), atrophic gastritis (p=0.01) and primary ovarian failure (p=0.01) were highly correlated with reduced scores. Quality of life was significantly lower in female patients and in those with manifestation at older ages. With more autoimmune comorbidities, the quality of life scores dropped. The most important factor, however, was latency between first symptoms and diagnosis that affected patients' quality of life even years after manifestation of the disease. These results confirm and extend previous observations and emphasize the importance of a timely diagnosis. Therefore, medical awareness for this rare but easily treatable disorder needs to be sharpened. © Georg Thieme Verlag KG Stuttgart · New York.
Renner, F.; Graninger, W.
One of the major causes of chronic adrenal insufficiency (Addison's disease) is tuberculous adrenalopathy. Since sonography and computed tomography have become generally available in recent years and are of potential help in the diagnosis of this disease the merits of these methods are discussed in the light of 2 cases of adrenal tuberculosis, followed by a review of the literature. Adrenal calcification is the most significant, although not specific sign of adrenal insufficiency due to tuberculosis. Computed tomography has proven to be the method of choice in the non-invasive diagnosis of tuberculous adrenalopathy and in the monitoring of tuberculostatic treatment in this disease. Sonography is helpful as a preliminary investigation. (Author)
Mozolevska, Viktoriya; Schwartz, Anna; Cheung, David; Shaikh, Bilal; Bhagirath, Kapil M; Jassal, Davinder S
Addison's disease is often accompanied by a number of cardiovascular manifestations. We report the case of a 30-year-old man who presented with a new onset dilated cardiomyopathy due to Addison's disease. The clinical presentation, treatment, and outcomes of this rare hormone mediated cardiac disorder are reviewed.
Likhari, Taruna; Magzoub, Saeed; Griffiths, Melanie J; Buch, Harit N
Background Addison's disease may present with recurrent hypoglycaemia in subjects with type 1 diabetes mellitus. There are no data, however, on the prevalence of Addison's disease presenting with recurrent hypoglycaemia in patients with diabetes mellitus. Methods Three year retrospective study of diabetic patients with “unexplained” recurrent hypoglycaemia investigated with a short Synacthen test to exclude adrenocortical insufficiency. Results 95 patients with type 1 diabetes mellitus were studied. Addison's disease was identified as the cause of recurrent hypoglycaemia in one patient with type 1 diabetes mellitus. Conclusion Addison's disease is a relatively rare but remedial cause of recurrent hypoglycaemia in patients with type 1 diabetes mellitus. A low threshold for investigating patients with type 1 diabetes mellitus and recurrent hypoglycaemia to detect Addison's disease is therefore suggested. PMID:17551075
Likhari, Taruna; Magzoub, Saeed; Griffiths, Melanie J; Buch, Harit N; Gama, R
Addison's disease may present with recurrent hypoglycaemia in subjects with type 1 diabetes mellitus. There are no data, however, on the prevalence of Addison's disease presenting with recurrent hypoglycaemia in patients with diabetes mellitus. Three year retrospective study of diabetic patients with "unexplained" recurrent hypoglycaemia investigated with a short Synacthen test to exclude adrenocortical insufficiency. 95 patients with type 1 diabetes mellitus were studied. Addison's disease was identified as the cause of recurrent hypoglycaemia in one patient with type 1 diabetes mellitus. Addison's disease is a relatively rare but remedial cause of recurrent hypoglycaemia in patients with type 1 diabetes mellitus. A low threshold for investigating patients with type 1 diabetes mellitus and recurrent hypoglycaemia to detect Addison's disease is therefore suggested.
Cronin, C C
Acute adrenal crisis in patients with unrecognized chronic adrenocortical failure is difficult to diagnose and potentially fatal. We describe 2 patients with acute adrenal crisis whose diagnoses were hindered because of concomitant glucocorticoid treatment. Acute adrenal insufficiency is primarily a state of mineralocorticoid deficiency. Prednisolone and prednisone, the most frequently prescribed anti-inflammatory corticosteroid agents, have minimal mineralocorticoid activity. Several conditions that may be treated with pharmacological glucocorticoids are associated with an increased risk of Addison disease. An acute adrenal crisis, against which concurrent glucocorticoid therapy does not confer adequate protection, may develop in such patients.
Brandão Neto, Rodrigo Antonio; de Carvalho, Jozélio Freire
Autoimmune adrenalitis, or autoimmune Addison disease (AAD), is the most prevalent cause of primary adrenal insufficiency in the developed world. AAD is rare and can easily be misdiagnosed as other conditions. The diagnosis depends on demonstrating inappropriately low cortisol production and the presence of high titers of adrenal cortex autoantibodies (ACAs), along with excluding other causes of adrenal failure using other tests as necessary. The treatment corticosteroid replacement, and the prognosis following the treatment is the same as the normal population. Spontaneous recovery of adrenal function has been described but is rare. Copyright © 2014 Elsevier B.V. All rights reserved.
Eriksson, D; Bianchi, M; Landegren, N; Nordin, J; Dalin, F; Mathioudaki, A; Eriksson, G N; Hultin-Rosenberg, L; Dahlqvist, J; Zetterqvist, H; Karlsson, Å; Hallgren, Å; Farias, F H G; Murén, E; Ahlgren, K M; Lobell, A; Andersson, G; Tandre, K; Dahlqvist, S R; Söderkvist, P; Rönnblom, L; Hulting, A-L; Wahlberg, J; Ekwall, O; Dahlqvist, P; Meadows, J R S; Bensing, S; Lindblad-Toh, K; Kämpe, O; Pielberg, G R
Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls. We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10 -15 , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex. Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment. © 2016 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.
Gan, Earn H; Pearce, Simon H
The treatment for autoimmune Addison's disease (AAD) has remained virtually unchanged in the last 60 years. Most patients have symptoms that are relatively well controlled with exogenous steroid replacement, but there may be persistent symptoms, recurrent adrenal crisis and poor quality of life, despite good compliance with optimal current treatments. Treatment with conventional exogenous steroid therapy is also associated with premature mortality, increased cardiovascular risk and complications related to excessive steroid replacement. Hence, novel therapeutic approaches have emerged in the last decade attempting to improve the long-term outcome and quality of life of patients with AAD. This review discusses the recent developments in treatment innovations for AAD, including the novel exogenous steroid formulations with the intention of mimicking the physiological biorhythm of cortisol secretion. Our group has also carried out a few studies attempting to restore endogenous glucocorticoid production via immunomodulatory and regenerative medicine approaches. The recent advances in the understanding of adrenocortical stem cell biology, and adrenal plasticity will also be discussed to help comprehend the science behind the therapeutic approaches adopted. © 2017 European Society of Endocrinology.
Namikawa, Hiroki; Takemoto, Yasuhiko; Kainuma, Shigeto; Umeda, Sakurako; Makuuchi, Ayako; Fukumoto, Kazuo; Kobayashi, Masanori; Kinuhata, Shigeki; Isaka, Yoshihiro; Toyoda, Hiromitsu; Kamata, Noriko; Tochino, Yoshihiro; Hiura, Yoshikazu; Morimura, Mina; Shuto, Taichi
We herein report a case of Addison's disease caused by tuberculosis characterized by atypical hyperpigmentation, noted as exacerbation of the pigmentation of freckles and the occurrence of new freckles, that was diagnosed in the presence of active pulmonary tuberculosis. The clinical condition of the patient was markedly ameliorated by the administration of hydrocortisone and anti-tuberculosis agents. When exacerbation of the pigmentation of the freckles and/or the occurrence of new freckles are noted, Addison's disease should be considered as part of the differential diagnosis. In addition, the presence of active tuberculosis needs to be assumed whenever we treat patients with Addison's disease caused by tuberculosis, despite its rarity.
Hellesen, Alexander; Bratland, Eirik; Husebye, Eystein S
Autoimmunity against the adrenal cortex is the leading cause of Addison's disease in industrialized countries, with prevalence estimates ranging from 93-220 per million in Europe. The immune-mediated attack on adrenocortical cells cripples their ability to synthesize vital steroid hormones and necessitates life-long hormone replacement therapy. The autoimmune disease etiology is multifactorial involving variants in immune genes and environmental factors. Recently, we have come to appreciate that the adrenocortical cell itself is an active player in the autoimmune process. Here we summarize the complex interplay between the immune system and the adrenal cortex and highlight unanswered questions and gaps in our current understanding of the disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
Full Text Available Introduction: Primary adrenal insufficiency is a rare disease, especially in pediatric age. Case report: We report the case of a teenager with astenia with four months’ evolution, causing repeated visits to the emergency department during the previous month due gastrointestinal symptoms and a ten kilograms weight loss. In admission the patient had a reasonable general condition, hydrated and without cutaneous hyperpigmentation. Laboratory results showed hyponatremia, increased levels of corticotropin with normal cortisol levels, increased levels of renin with decreased aldosterone levels and presence of antissuprarrenal antibodies, allowing the diagnosis of autoimmune primary adrenal insufficiency. The boy started treatment with hydrocortisone and fludrocortisone with favorable response. Discussion/conclusions: The diagnosis of Addison’s disease requires a high degree of suspicion due its unspecific symptomatology. This disease often presents gastrointestinal symptoms. Thus, towards a patient with hyponatremia accompanied by constitutional and gastrointestinal symptoms, we must always consider this diagnosis.
Preto, Clara; Correia, Joana; Pinheiro, Marina; Barroso, Fábio; Leite, Sara; Fernandes, Alexandre; Cardoso, Helena; Borges, Teresa
Introduction: Primary adrenal insufficiency is a rare disease, especially in pediatric age. Case report: We report the case of a teenager with astenia with four months’ evolution, causing repeated visits to the emergency department during the previous month due gastrointestinal symptoms and a ten kilograms weight loss. In admission the patient had a reasonable general condition, hydrated and without cutaneous hyperpigmentation. Laboratory results showed hyponatremia, increased levels of corti...
Løvås, Kristian; Curran, Suzanne; Oksnes, Marianne; Husebye, Eystein S; Huppert, Felicia A; Chatterjee, V Krishna K
Patients with Addison's disease reproducibly self-report impairment in specific dimensions of general well-being questionnaires, suggesting particular deficiencies in health-related quality-of-life (HRQoL). We sought to develop an Addison's disease-specific questionnaire (AddiQoL) that could better quantify altered well-being and treatment effects. Design, Setting, Patients, Intervention, and Outcomes: We reviewed the literature to identify HRQoL issues in Addison's disease and interviewed patients and their partners in-depth to explore various symptom domains. A list of items was generated, and nine expert clinicians and five expert patients assessed the list for impact and clarity. A preliminary questionnaire was presented to 100 Addison's outpatients; the number of items was reduced after analysis of the distribution of the responses. The final questionnaire responses were assessed by Cronbach's alpha and Rasch analysis. Published studies of HRQoL in Addison's disease indicated reduced vitality and general health perception and limitations in physical and emotional functioning. In-depth interviews of 14 patients and seven partners emphasized the impact of the disease on the emotional domain. Seventy HRQoL items were generated; after the expert consultation process and pretesting in 100 patients, the number of items was reduced to 36. Eighty-six patients completed the final questionnaire; the responses showed high internal consistency with Cronbach's alpha 0.95 and Person Separation Index 0.94 (Rasch analysis). We envisage AddiQoL having utility in trials of hormone replacement and management of patients with Addison's disease, analogous to similar questionnaires in GH deficiency (AGHDA) and acromegaly (AcroQoL).
Objective: To examine the relationship between illness representations, coping behaviour and adaptive outcome in patients with Addison's disease (AD). Design: Cross-sectional. Following Leventhal's self-regulation model (Leventhal, Meyer & Nerenz, 1980), it was hypothesized that illness
Lee, Paul; Greenfield, Jerry R
Addison's disease is associated with low bone mineral density and increased risk of hip fractures. Causes are multifactorial, contributed by underlying adrenocortical hormonal deficiency, associated autoimmune endocrinopathies, electrolyte disturbances and, in some patients, supraphysiologic glucocorticoid replacement. Recent realization of physiologic cortisol production rate has revised downwards glucocorticoid replacement dosages. Meanwhile, new research has emerged suggesting complex interplay between sodium and calcium homoeostasis under the influence of mineralocorticoid and parathyroid hormone that may impact bone health. As the prevalence of Addison's disease is rising, and osteoporosis and fractures are associated with significant morbidity and increased mortality, attention to bone preservation in Addison's disease is of clinical relevance and importance. We suggest an approach to bone health in Addison's disease integrating physiologic adrenocortical hormonal replacement with electrolyte and mineral homoeostasis optimization. © 2015 John Wiley & Sons Ltd.
Smans, L.; Lentjes, E.G.W.M.; Hermus, A.R.; Zelissen, P.M.J.
OBJECTIVE: Patients with Addison's disease require lifelong treatment with glucocorticoids. At present, no glucocorticoid replacement therapy (GRT) can exactly mimic normal physiology. As a consequence, under- and especially overtreatment can occur. Suboptimal GRT may lead to various side effects.
Objective: To examine the relationship between illness representations, coping behaviour and adaptive outcome in patients with Addison's disease (AD). Design: Cross-sectional. Following Leventhal's self-regulation model (Leventhal, Meyer & Nerenz, 1980), it was hypothesized that illness representations are directly associated with coping and, via coping, with adaptive outcome. Method: The illness representations held by 63 patients with a diagnosis of Addison's disease were explored using a q...
Pozzi Mucelli, R.S.; Pozzi Mucelli, F.; Muner, G.
Addison's disease of the adrenal glands presents with different pathological findings depending on the stage. In the acute phase the adrenal glands are bilaterally enlarged while in the chronic phase the glands are small and calcified. A case of Addison's disease with follow-up over a period of a year by CT is reported. CT showed the evolution of the adrenal glands from bilateral masses to small calcified glands. The differential diagnostic problems in the acute phase are also discussed. (orig.)
Horn, Morten A; Erichsen, Martina M; Wolff, Anette S B; Månsson, Jan-Eric; Husebye, Eystein S; Tallaksen, Chantal M E; Skjeldal, Ola H
X-linked adrenoleukodystrophy is an important cause of Addison's disease in boys, but less is known about its contribution to Addison's disease in adult men. After surveying all known cases of X-linked adrenoleukodystrophy in Norway in a separate study, we aimed to look for any missed cases among the population of adult men with nonautoimmune Addison's disease. Among 153 adult men identified in a National Registry for Addison's Disease (75% of identified male cases of Addison's disease in Norway), those with negative indices for 21-hydroxylase autoantibodies were selected. Additionally, cases with low autoantibody indices (48-200) were selected. Sera from subjects included were analysed for levels of very long-chain fatty acids, which are diagnostic for X-linked adrenoleukodystrophy in men. Eighteen subjects had negative indices and 17 had low indices for 21-hydroxylase autoantibodies. None of those with low indices and only one of those with negative indices were found to have X-linked adrenoleukodystrophy; this subject had already been diagnosed because of the neurological symptoms. Cases of Addison's disease proved to be caused by X-linked adrenoleukodystrophy constitute 1·5% of all adult male cases in Norway; the proportion among nonautoimmune cases was 15%. We found X-linked adrenoleukodystrophy to be an uncommon cause of Addison's disease in adult men. However, this aetiological diagnosis has far-reaching consequences both for the patient and for his extended family. We therefore recommend that all adult men with nonautoimmune Addison's disease be analysed for levels of very long-chain fatty acids. © 2013 John Wiley & Sons Ltd.
Chen, Xiaoyan; Chen, Zhiye; Huang, Dehui; Liu, Xiaofeng; Gui, Qiuping; Yu, Shengyuan
We described a 38-year-old woman of rapidly progressive dementia with white matter encephalopathy and death. She had Addison's disease but the adrenal glands were hyperplastic. Brain magnetic resonance imaging revealed diffuse white matter lesion predominantly in the frontal lobe with band-like contrast enhancement. l-Methyl-11C-methionine positron emission tomography revealed accumulation of tracer in bilateral frontal lobes. Stereotactic biopsy demonstrated demyelination changes. A number of urinary organic acids were elevated. Adrenoleukodystrophy was diagnosed by elevated plasma very long chain fatty acid and ABCD1 gene mutation (C1544C/T). Adrenoleukodystrophy should be considered as a differential diagnosis in women with rapidly progressive white matter encephalopathy. Copyright © 2014 Elsevier B.V. All rights reserved.
Mascarenhas, Janice V; Jude, Edward B
Addison's disease accounts for the majority of cases of adrenal failure that are detected during hospital admissions. Unfortunately, prompt diagnosis of this condition is often delayed due to varied atypical manifestations and inadequate assessment at the time of presentation. We report a case of a 52-year-old woman who was detected to have hypotension during routine colonoscopy for evaluation of anaemia and progressive weight loss. During admission for evaluation of hypotension, she was also detected to have hyponatremia. Hyponatremia and hypotension failed to improve despite fluid resuscitation. Our endocrinological opinion was sought for and on further evaluation she was diagnosed with primary adrenal insufficiency. Glucocorticoid and mineralocorticoid replacement therapy were eventually instituted, which was followed by restoration of blood pressure and normalisation of serum sodium levels. 2014 BMJ Publishing Group Ltd.
Kocyigit, Ismail; Unal, Aydin; Tanriverdi, Fatih; Hayri Sipahioglu, Murat; Tokgoz, Bulent; Oymak, Oktay; Utas, Cengiz
Addison's disease is a rare disorder in patients with end-stage renal disease (ESRD). In patients, the diagnosis of Addison's disease is difficult in clinical practice because most of the clinical findings of this disease are similar to those of the renal failure. We present a 51-year-old male patient, who underwent hemodialysis therapy for 8 years, diagnosed with Addison's disease after having myalgia, skin hyperpigmentation, weight loss, sweating, and nausea for the past few weeks. The physical examination was completely normal except for muscle weakness, hyperpigmentation on labial mucosa and skin in a patient. The laboratory tests revealed anemia and hypoglycemia. Serum cortisol, adrenocorticotropic hormone (ACTH) levels, and ACTH stimulation test results were consistent with Addison's disease. Adrenal computerized tomography revealed bilateral atrophic glands. Additionally, it was found that elevated serum thyroid stimulating hormone levels and antithyroid peroxidase antibody titer were positive. Our purpose is to emphasize that physicians should be alert to the potential for additional different conditions particularly in terms of adrenal failure in patients with ESRD.
Erichsen, Martina M; Løvås, Kristian; Fougner, Kristian J; Svartberg, Johan; Hauge, Erik R; Bollerslev, Jens; Berg, Jens P; Mella, Bjarne; Husebye, Eystein S
Primary adrenal insufficiency (Addison's disease) is a rare autoimmune disease. Until recently, life expectancy in Addison's disease patients was considered normal. To determine the mortality rate in Addison's disease patients. i) Patients registered with Addison's disease in Norway during 1943-2005 were identified through search in hospital diagnosis registries. Scrutiny of the medical records provided diagnostic accuracy and age at diagnosis. ii) The patients who had died were identified from the National Directory of Residents. iii) Background mortality data were obtained from Statistics Norway, and standard mortality rate (SMR) calculated. iv) Death diagnoses were obtained from the Norwegian Death Cause Registry. Totally 811 patients with Addison's disease were identified, of whom 147 were deceased. Overall SMR was 1.15 (95% confidence intervals (CI) 0.96-1.35), similar in females (1.18 (0.92-1.44)) and males (1.10 (0.80-1.39)). Patients diagnosed before the age of 40 had significantly elevated SMR at 1.50 (95% CI 1.09-2.01), most pronounced in males (2.03 (1.19-2.86)). Acute adrenal failure was a major cause of death; infection and sudden death were more common than in the general population. The mean ages at death for females (75.7 years) and males (64.8 years) were 3.2 and 11.2 years less than the estimated life expectancy. Addison's disease is still a potentially lethal condition, with excess mortality in acute adrenal failure, infection, and sudden death in patients diagnosed at young age. Otherwise, the prognosis is excellent for patients with Addison's disease.
Wolff, A S B; Mitchell, A L; Cordell, H J; Short, A; Skinningsrud, B; Ollier, W; Badenhoop, K; Meyer, G; Falorni, A; Kampe, O; Undlien, D; Pearce, S H S; Husebye, E S
In common with several other autoimmune diseases, autoimmune Addison's disease (AAD) is thought to be caused by a combination of deleterious susceptibility polymorphisms in several genes, together with undefined environmental factors and stochastic events. To date, the strongest genomic association with AAD has been with alleles at the HLA locus, DR3-DQ2 and DR4. The contribution of other genetic variants has been inconsistent. We have studied the association of 16 single-nucleotide polymorphisms (SNPs) within the CD28-CTLA-4-ICOS genomic locus, in a cohort comprising 691 AAD patients of Norwegian and UK origin with matched controls. We have also performed a meta-analysis including 1002 patients from European countries. The G-allele of SNP rs231775 in CTLA-4 is associated with AAD in Norwegian patients (odds ratio (OR)=1.35 (confidence interval (CI) 1.10-1.66), P=0.004), but not in UK patients. The same allele is associated with AAD in the total European population (OR=1.37 (CI 1.13-1.66), P=0.002). A three-marker haplotype, comprising PROMOTER_1661, rs231726 and rs1896286 was found to be associated with AAD in the Norwegian cohort only (OR 2.43 (CI 1.68-3.51), P=0.00013). This study points to the CTLA-4 gene as a susceptibility locus for the development of AAD, and refines its mapping within the wider genomic locus.
van der Valk, Eline S.; Smans, Lisanne C C J; Hofstetter, Hedwig; Stubbe, Janine H.; de Vries, Marieke; Backx, Frank J G; Hermus, Ad R M M; Zelissen, Pierre M J
BACKGROUND: Health related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. OBJECTIVE: The aim of this study was to
Valk, E.S. Van der; Smans, L.C.C.J.; Hofstetter, H.; Stubbe, J.H.; Vries, M de; Backx, F.J.; Hermus, A.R.M.M.; Zelissen, P.M.J.
BACKGROUND: Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. OBJECTIVE: The aim of this study was to
Valk, E.S. van der; Smans, L.C.C.J.; Hofstetter, H.; Stubbe, J.H.; Vries, M. de; Backx, F.J.G.; Hermus, A.R.M.M.; Zelissen, P.M.J.
Background: Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. Objective: The aim of this study was to
Dantas, Thinali Sousa; Nascimento, Isabelly Vidal do; Verde, Maria Elisa Quezado Lima; Alves, Ana Paula Negreiros Nunes; Sousa, Fabrício Bitu; Mota, Mário Rogério Lima
Oral melanoacanthoma is a mucocutaneous, pigmented, rare, benign, and probably reactive lesion. This paper reports for the first time in the literature a case of multifocal oral melanoacanthoma in a patient diagnosed with Addison's disease and concomitant Graves' disease with hyperthyroidism. The patient presented with oral pigmented lesions, which were hypothesized to be mucosal pigmentation associated with Addison's disease. Due to their unusual clinical pattern, these oral lesions were biopsied and diagnosed as oral melanoacanthoma on histopathology and immunohistochemistry for HMB-45. At the moment of this report, the patient was being treated for her systemic conditions, but the lesions had not regressed. Reactive hyperpigmentation of the skin and mucous membranes may be found in Addison's disease and hyperthyroidism. This case reinforces the hypothesis of a reactive nature for oral melanoacanthoma and highlights the need for investigation of endocrine disorders in patients with multifocal oral melanoacanthoma.
Henry, Michelle; Thomas, Kevin G F; Ross, Ian L
Patients with Addison's disease frequently self-report memory and attention difficulties, even when on standard replacement therapy. However, few published studies examine, using objective measures and assessing across multiple domains, the cognitive functioning of Addison's disease patients relative to healthy controls. The primary aim of this study was to investigate whether the previously reported subjective cognitive deficits in Addison's disease are confirmed by objective measures. Conducting comprehensive neuropsychological assessments of patients with relatively rare clinical disorders, such as Addison's disease, is challenging because access to those patients is often limited, and because their medical condition might prevent extended testing sessions. Brief telephonic cognitive assessments are a useful tool in such circumstances. Hence, we administered the Brief Test of Adult Cognition by Telephone to 27 Addison's disease patients and 27 matched healthy controls. The instrument provides objective assessment of episodic memory, working memory, executive functioning, reasoning, and speed of processing. Statistical analyses confirmed that, as expected, patients performed significantly more poorly than controls on the episodic memory subtest. There were, however, no significant between-group differences on the attention, executive functioning, reasoning, and speed of processing subtests. Furthermore, patients with a longer duration of illness performed more poorly across all domains of cognition. We conclude that, for Addison's disease patients, previously reported subjective cognitive deficits are matched by objective impairment, but only in the domain of episodic memory. Future research might investigate (a) whether these memory deficits are material-specific (i.e., whether non-verbal memory is also affected), and (b) the neurobiological mechanisms underlying these deficits.
Hinz, Laura E; Kline, Gregory A; Dias, Valerian C
To present a case of symptomatic autoimmune adrenal insufficiency with initially normal serum cortisol and to caution about limitations of the current diagnostic algorithm for adrenal insufficiency, which does not reflect the pathophysiology of early disease. We describe the clinical presentation and relevant investigations of a patient ultimately found to have Addison's disease, which is followed by a focused review of the literature. A 41-year-old Caucasian woman with autoimmune hypothyroidism, premature ovarian failure, and microscopic colitis presented with nausea, salt craving, increased skin pigmentation, and postural hypotension. Initial bloodwork revealed a normal morning cortisol of level of 19.2 μg/dL (normal, 7.2 to 25 μg/dL) but an adrenocorticotropic hormone (ACTH) level 10 times normal, at 513.6 pg/mL (normal, <52.5 pg/mL). Her potassium was normal, but her aldosterone level was 4.12 ng/dL (normal, 12.3 to 62.5 ng/dL) and her renin activity was increased (23.0 mg/dL/hour; normal, <6.0 mg/dL/hour). Six weeks after initial presentation, she was found to have anti-adrenal antibodies. It was not until 10 weeks after her initial symptomatic presentation that her morning cortisol level was found to be subnormal and a formal diagnosis of adrenal insufficiency was made. The present case and literature review reveal that common diagnostic approaches will miss patients with (possibly symptomatic) early adrenal insufficiency. We suggest that serum ACTH level testing or tests of mineralocorticoid function be included in the initial step of investigation for suspected primary adrenal insufficiency.
Godswill, Okwuonu Chimezie; Odigie, Ojeh-Oziegbe
Coexistence of Addison's disease and systemic lupus erythematosus (SLE) is a rare occurrence with only few reported cases in the literature. We describe a 29-year-old woman who presented to us with clinical features of acute Addisonian crisis and SLE. Laboratory investigations were confirmatory of Addison's disease in a background of SLE. The patient made remarkable improvement on administration of steroids as replacement therapy for adrenal insufficiency and treatment of SLE. Clinicians need to have a high-index of suspicion of this possible coexistence in order to avoid the associated deleterious hemodynamic and metabolic consequences.
Hasik, J.; Kozal, H.; Kosowicz, J.; Hansz, J.
Radioimmunoassay of gastrin level in the blood was performed in 20 controls, 12 patients with duodenal ulcer, 13 patients with atrophic gastritis and 14 patients with Addison-Biermer's disease. Gastrin level in the serum of the patients with duodenal ulcer did not differ significantly from that of controls. In atrophic gastritis and particularly in Addison-Biermer's disease gastrin level was found to be several times higher. This is probably a result of chronic gastrin secretion stimulation which is normally inhibited by gastric juice. (author)
Rodrigo Antonio Brandão Neto
Full Text Available CONTEXT: Erythema induratum of Bazin (EIB is considered to be a tuberculid reaction and consists of recurrent painful nodules. The differential diagnosis includes diseases like nodular vasculitis, perniosis, polyarteritis nodosa and erythema nodosum. CASE REPORT: We report the case of a woman with EIB who developed Addison's disease during treatment with anti-tuberculosis drugs with good response to glucocorticoid replacement. The diagnosis was obtained through the clinical picture, positive tuberculin test and positive BCG (bacillus Calmette-Guérin test on the histological sample. Anti-tuberculosis drugs and glucocorticoid replacement led to disappearance of the signs and symptoms. CONCLUSIONS: This is the first description of an association between EIB and Addison's disease. It should be borne in mind that tuberculosis is an important etiological factor for Addison's disease.CONTEXTO: O eritema indurado de Bazin (EIB é considerado uma reação tuberculoide e consiste de nódulos dolorosos recorrentes. O diagnóstico diferencial inclui doenças como vasculite nodular, perniose, poliarterite nodosa e eritema nodoso. RELATO DE CASO: Nós reportamos o caso de uma mulher com EIB que desenvolveu doença de Addison durante tratamento com drogas tuberculostáticas e com boa resposta com reposição de glicocorticoide. O diagnóstico foi realizado pela apresentação clínica, teste tuberculínico positivo e positividade para BCG (bacilo Calmette-Guérin no espécime histológico. A reposição de glicocorticoides e drogas tuberculostáticas levou ao desaparecimento dos sinais e sintomas. CONCLUSÕES: Este é o primeiro caso reportando a associação entre EIB e doença de Addison. Tuberculose é um importante agente etiológico da doença de Addison.
Betterle, Corrado; Garelli, Silvia; Presotto, Fabio; Furmaniak, Jadwiga
Recent progress in the immunopathology field has greatly improved our understanding of the natural history of autoimmune diseases, particularly of Addison's disease. Addison's disease is known to be a chronic illness characterized by adrenocortical gland insufficiency that develops following a long and mainly asymptomatic period, characterized by the presence of circulating autoantibodies directed to adrenal cortex antigens. In this chapter we describe the groups of subjects at risk of developing Addison's disease, together with the diagnostic tests considered the most appropriate for evaluating adrenal function: determination of basal plasma adrenocorticotropic hormone (ACTH) levels, plasma renin activity, plasma aldosterone and cortisol levels, and cortisol levels after intravenous stimulation with ACTH (ACTH test). The employment of specific clinical, immunological and functional criteria in the subjects with autoantibodies to the adrenal cortex allows identifying those at risk of developing overt disease. The independent risk factors for the progression to adrenal failure have also been identified and they contribute to different risks of developing clinical Addison's disease. Based on the risk level, the subjects should be monitored over time to observe early signs of adrenal dysfunction, and start substitutive treatment as soon as possible. For patients presenting with high risk, prevention strategies and trials might be available. © 2016 S. Karger AG, Basel.
van der Valk, Eline S; Smans, Lisanne C C J; Hofstetter, Hedwig; Stubbe, Janine H; de Vries, Marieke; Backx, Frank J G; Hermus, Ad R M M; Zelissen, Pierre M J
Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. The aim of this study was to investigate the quality of life in Dutch patients with Addison's disease particularly regarding the presence of fatigue and the ability to be physically active. In this cross-sectional study, a postal survey was performed among Dutch patients with Addison's disease on stable glucocorticoid replacement therapy with hydrocortisone or cortisone acetate. For quality of life and physical activity assessment, patients completed general and health-related quality of life and physical activity questionnaires, and scores were compared to Dutch controls. A total of 328 patients with Addison's disease were studied. In patients with Addison's disease, only 45·7% met the standard of physical activity (Combinorm) compared to 67·8% of Dutch controls (P < 0·01). Forty-eight per cent of patients showed abnormal fatigue, while 61% had severe fatigue. The CIS fatigue scores were significantly higher compared to controls (P < 0·01). We found reduced general subjective health-related QoL scores in both male and female patients, especially in younger patients <65 years of age. Physical activity is decreased in patients with Addison's disease, combined with a reduced subjective health-related QoL and increased fatigue. © 2016 John Wiley & Sons Ltd.
Passanisi, Stefano; Timpanaro, Tiziana; Lo Presti, Donatella; Caruso-Nicoletti, Manuela
Primary adrenocortical insufficiency or Addison's disease is caused by a progressive destruction of the adrenal cortex, resulting into a reduction of glucocorticoids, mineralocorticoids, and androgens. Autoimmune Addison's disease is the most common etiological form, accounting for about 80% of all cases. We describe the case of a 16-year-old Caucasian boy affected by type-1 diabetes mellitus and autoimmune thyroiditis, who experienced recurrent hypoglycaemia as presenting symptom of Addison's disease. Hypoglycaemia is not a common presenting feature of Addison's disease, both in patients with type-1 diabetes mellitus and in non-diabetic patients. However, hypoglycaemia may occur in association with primary and secondary glucocorticoid deficiency as a result of an enhanced insulin sensitivity. Hypoglycaemia is the most common acute complication of insulin therapy in patients with type-1 diabetes mellitus. Addison's disease has been described in approximately 0.5% of patients with type-1 diabetes mellitus, being more frequent in females and occurring in middle-aged patients. An association among type-1 diabetes mellitus, autoimmune thyroiditis, and Addison's disease is found in the "Schmidt's syndrome", a rare disorder that may occur in the paediatric age. Our case suggests that the presence of Addison's disease should be taken into consideration in patients with type-1 diabetes mellitus and frequent episodes of hypoglycaemia. We wish to highlight that there are no specific indications to screen for the association between Addison's disease and type-1 diabetes mellitus, although an early diagnosis of Addison's disease in diabetic patients would prevent the morbidity and potential mortality of this association.
Elebrashy, Ibrahim; Yousief, Elham; Saif, Aasem
We report a case of Addison's disease presenting with recurrent deep venous thrombosis and thrombocytopenia and proved to have primary anti-phospholipid antibody syndrome. The case report highlights the shared autoimmune nature of both diseases.
Wulffraat, N. M.; Drexhage, H. A.; Bottazzo, G. F.; Wiersinga, W. M.; Jeucken, P.; van der Gaag, R.
The presence of serum immunoglobulins (Ig) blocking ACTH-induced adrenal DNA synthesis and/or cortisol production was studied in 25 patients with idiopathic Addison's disease. For this purpose guinea pig adrenal segments kept in organ culture were exposed to ACTH and graded concentrations of patient
Wilms, G.; Tits, J.; Vanstraelen, D.; Marchal, G.; Rigauts, H.; Baert, A.L.
In a patient with Addison's disease, who gave a history of a severe car accident, CT showed bilateral enlargement of the adrenal glands. MRI, by demonstrating paramagnetic T1 shortening due to methaemoglobin and haemosiderin on T2-weighted images, confirmed the haemorrhagic nature of the lesions. (orig.)
Jagannath, A.; Brill, P.W.; Winchester, P.
A 13-year-old girl developed Addison's disease during antituberculous therapy for presumed tuberculous ventriculitis. CT of the abdomen showed diffusely enlarged hypodense adrenals and a hypodense lesion in the lower pole of the left kidney. Biopsy of the renal lesion revealed caseating and noncaseating granolomas. (orig.)
Gan, Earn H; MacArthur, Katie; Mitchell, Anna L; Hughes, Beverly A; Perros, Petros; Ball, Stephen G; James, R Andrew; Quinton, Richard; Chen, Shu; Furmaniak, Jadwiga; Arlt, Wiebke; Pearce, Simon H S
Despite lifelong steroid hormone replacement, there is excess morbidity and mortality associated with autoimmune Addison's disease. In health, adrenocortical cells undergo continuous self-renewal from a population of subcapsular progenitor cells, under the influence of ACTH, suggesting a therapeutic possibility. We aimed to determine whether tetracosactide (synthetic ACTH1-24) could revive adrenal steroidogenic function in autoimmune Addison's disease. Thirteen patients (aged 16-65 y) with established autoimmune Addison's disease for more than 1 year were recruited at the Newcastle University Clinical Research Facility. The intervention included a 20-week study of regular sc tetracosactide (ACTH1-24) therapy. Serum and urine corticosteroids were measured during medication withdrawal at baseline and every 5 weeks during the study. Serum cortisol levels remained less than 100 nmol/L in 11 of 13 participants throughout the study. However, two women achieved peak serum cortisol concentrations greater than 400 nmol/L after 10 and 29 weeks of tetracosactide therapy, respectively, allowing withdrawal of corticosteroid replacement. Concurrently, urine glucocorticoid and mineralocorticoid metabolite excretion increased from subnormal to above the median of healthy controls. One of these responders remains well with improving peak serum cortisol (672 nmol/L) 28 months after stopping all treatments. The other responder showed a gradual reduction in serum cortisol and aldosterone over time, and steroid therapy was recommenced after a 28-week period without glucocorticoid replacement. This is the first study to demonstrate that established autoimmune Addison's disease is amenable to a regenerative medicine therapy approach.
caused by autoimmune destruction of adrenal gland cortex. Those with Addisons disease have a deficiency of cortisol and aldostreone. These deficiencies are accompanied by adrenal androgen depletion. A case report of 43 year old female is hereby reported. The patient presented with hyperpigmentation of nipples, ...
Baxter, M; Gorick, S; Swords, F M
Summary Addison's disease is a condition characterised by immune-mediated destruction of the adrenal glands leading to a requirement of lifelong replacement therapy with mineralocorticoid and glucocorticoid. We present a case of a 53-year-old man who presented at the age of 37 years with nausea, fatigue and dizziness. He was found to have postural hypotension and buccal pigmentation. His presenting cortisol level was 43 nmol/l with no response to Synacthen testing. He made an excellent response to conventional replacement therapy with hydrocortisone and fludrocortisone and then remained well for 16 years. On registering with a new endocrinologist, his hydrocortisone dose was revised downwards and pre- and post-dose serum cortisol levels were assessed. His pre-dose cortisol was surprisingly elevated, and so his dose was further reduced. Subsequent Synacthen testing was normal and has remained so for further 12 months. He is now asymptomatic without glucocorticoid therapy, although he continues on fludrocortisone 50 μg daily. His adrenal antibodies are positive, although his ACTH and renin levels remain elevated after treatment. Addison's disease is generally deemed to lead to irreversible cell-mediated immune destruction of the adrenal glands. For this reason, patients receive detailed counselling and education on the need for lifelong replacement therapy. To our knowledge, this is the third reported case of spontaneous recovery of the adrenal axis in Addison's disease. Recovery may therefore be more common than previously appreciated, which may have major implications for the treatment and monitoring of this condition, and for the education given to patients at diagnosis. Learning points Partial recovery from Addison's disease is possible although uncommon.Patients with long-term endocrine conditions on replacement therapy still benefit from regular clinical and biochemical assessment, to revisit optimal management.As further reports of adrenal axis recovery
Sahoo, Jaya Prakash; Selviambigapathy, Jayakumar; Kamalanathan, Sadishkumar; Nagarajan, K; Vivekanandan, Muthupillai
Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations.
Baxter, M; Gorick, S; Swords, F M
Addison's disease is a condition characterised by immune-mediated destruction of the adrenal glands leading to a requirement of lifelong replacement therapy with mineralocorticoid and glucocorticoid. We present a case of a 53-year-old man who presented at the age of 37 years with nausea, fatigue and dizziness. He was found to have postural hypotension and buccal pigmentation. His presenting cortisol level was 43 nmol/l with no response to Synacthen testing. He made an excellent response to conventional replacement therapy with hydrocortisone and fludrocortisone and then remained well for 16 years. On registering with a new endocrinologist, his hydrocortisone dose was revised downwards and pre- and post-dose serum cortisol levels were assessed. His pre-dose cortisol was surprisingly elevated, and so his dose was further reduced. Subsequent Synacthen testing was normal and has remained so for further 12 months. He is now asymptomatic without glucocorticoid therapy, although he continues on fludrocortisone 50 μg daily. His adrenal antibodies are positive, although his ACTH and renin levels remain elevated after treatment. Addison's disease is generally deemed to lead to irreversible cell-mediated immune destruction of the adrenal glands. For this reason, patients receive detailed counselling and education on the need for lifelong replacement therapy. To our knowledge, this is the third reported case of spontaneous recovery of the adrenal axis in Addison's disease. Recovery may therefore be more common than previously appreciated, which may have major implications for the treatment and monitoring of this condition, and for the education given to patients at diagnosis. Partial recovery from Addison's disease is possible although uncommon.Patients with long-term endocrine conditions on replacement therapy still benefit from regular clinical and biochemical assessment, to revisit optimal management.As further reports of adrenal axis recovery emerge, this may
Sahoo, Jaya Prakash; Selviambigapathy, Jayakumar; Kamalanathan, Sadishkumar; Nagarajan, K.; Vivekanandan, Muthupillai
Background: Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. Materials and Methods: This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Results: Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. Conclusions: The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations. PMID:27042409
Printha, K.; Hulathduwa, S. R.; Samarasinghe, K.; Suh, Y. H.; De Silva, K. R. D.
Background: Stress and depression shows possible links to neuronal death in hippocampus. Subiculum plays a prominent role in limbic stress integration and direct effect of corticosteroids on subicular neurons needs to be defined to assess its subsequent impact on hippocampal plasticity. Aim: This study was intended to assess apoptosis in subicular neurons of a young depressed suicide victim, where presumably stress induced excess of corticosteroids and a case of young Addison's disease with low level of corticosteroids. Materials and Method: Both bilateral adrenal glands (Addison's) and subiculum (both cases) were initially stained with hematoxylin and eosin; subicular neurons of both cases were examined for the degree of apoptosis using ‘ApopTag Kit’. Apoptotic cell counts were expressed as average number of labeled cells/mm2 and the results were analysed statistically using a non-parametric Mann–Whitney U test. Result: Apoptotic neurons were detected in the subicular region of both suicide and Addison victims, and it is statistically significant in both right and left between the cases (P Addison disease where the number of neuronal cell death between right and left was statistically insignificant (P > 0.05). Conclusion: The present study confirms the vulnerability of the subicular neurons to apoptosis, possibly due to corticosteroids in both ends of spectrum. PMID:20048453
Ross, I L; Levitt, N S; Blom, D J; Haarburger, D
Hypogonadism may complicate Addison's disease (primary hypoadrenalism), but prevalence and metabolic sequelae of hypogonadism in Addison's disease are poorly described. We recruited patients from the South African Addison's disease national registry who received stable replacement doses of hydrocortisone and had no acute illness. Male biochemical testosterone deficiency was defined as an early morning basal testosterone10 or 12 IU/l). Testosterone deficiency did not correlate with age, disease duration or hydrocortisone dose. Untreated male hypogonadal subjects had a higher (mean ± standard deviation) BMI compared to eugonadal subjects 29.2 ± 4.9 kg/m(2) vs. 24.7 ± 3.4 kg/m(2) (p=0.01) and a higher median (interquartile range) high-sensitive-CRP 6.4 (2.5-14.0) mg/l vs. 1.45 (0.6-2.8) mg/l (p=0.002). There were no differences between the 2 groups in lipids, lipoproteins and fasting glucose. The median (interquartile range) DHEAS was lower in the hypogonadal 0.31 (0.27-0.37) μmol/l, compared with the eugonadal group 0.75 (0.50-1.51) μmol/l (p=0.005). POF was documented in 11% of female patients. Male testosterone deficiency was highly prevalent in this cohort and was primarily due to secondary hypogonadism. Only BMI and hs-CRP were increased in untreated male hypogonadal subjects. Male and female hypogonadism appears to be a common complication of Addison's disease and may contribute to its morbidity. © Georg Thieme Verlag KG Stuttgart · New York.
Ma Ensen; Yang Zhigang; Li Yuan; Guo Yingkun; Deng Yuping; Zhang Xiaochun
Objective: To determine the characteristics of tuberculous Addison's disease on the axial and multiplanar reformatted (MPR) images of the multidetector-row computed tomography (MDCT). Materials and methods: The unenhanced and contrast-enhanced MDCT features in 19 patients with tuberculous Addison's disease were retrospectively assessed for the location, contour, size, calcification, attenuation, and enhancement patterns. The correlation between the duration of Addison's disease and the percentage of calcification presence was evaluated. Results: The adrenal glands were infected bilaterally in all of the 19 cases (100%, 38 glands). Enlargement of the glands appeared in 18 cases (94.7%, 36 glands) and the remaining one case (5.3%, two glands) showed atrophy bilaterally. Of the 36 enlarged adrenals, 13 (36.1%) had preserved contours, and the other 23 (63.9%) were mass-like. The size of the adrenals ranged from 0.6 to 4.8cm (mean 1.92+/-0.96cm). Calcification was revealed in 16 adrenals (16/38, 42.1%), increasing in incidence with disease progression. Fourteen of the 36 (38.9%) enlarged adrenals showed peripheral enhancement while the remaining 22 (61.1%) demonstrated heterogeneous enhancement. The ΔCT value, the attenuation measurement of mass-like lesions, was less in the central area (7+/-4HU) than that in the peripheral area (32+/-14HU) (P<0.01) between the unenhanced and contrast-enhanced scan. Conclusion: MDCT can reveal the characteristic morphology and CT attenuation in the tuberculous Addison's disease. Combined with its clinical presentations and biochemical findings, we can diagnose and stage adrenal tuberculosis with high specificity and accuracy on MDCT
Smans, Lisanne; Lentjes, Eef; Hermus, Ad; Zelissen, Pierre
Patients with Addison's disease require lifelong treatment with glucocorticoids. At present, no glucocorticoid replacement therapy (GRT) can exactly mimic normal physiology. As a consequence, under- and especially overtreatment can occur. Suboptimal GRT may lead to various side effects. The aim of this study was to investigate the use of salivary cortisol day curves (SCDC) in the individual adjustment of GRT in order to approach normal cortisol levels as closely as possible, reduce over- and underreplacement and study the short-term effects on quality of life (QoL). Twenty patients with Addison's disease were included in this prospective study. A SCDC was obtained and compared to normal controls; general and disease specific QoL-questionnaires were completed. Based on SCDC assessment of over- and undertreatment (calculated as duration (h) × magnitude (nmol/L) at different time points, glucocorticoid dose and regime were adjusted. After 4 weeks SCDC and QoL assessment were repeated and the effect of adjusting GRT was analysed. At baseline, underreplacement was present in 3 and overreplacement in 18 patients; total calculated overreplacement was 32.8 h.nmol/L. Overreplacement decreased significantly to 13.3 h. nmol/L (p =0.005) after adjustment of GRT. Overreplacement was found particularly in the afternoon and evening. After reducing overreplacement in the evening, complaints about sleep disturbances significantly decreased. Individual adjustment of GRT based on SCDC to approach normal cortisol concentrations during the day can reduce overreplacement, especially in the evening. This can lead to a reduction of sleep disturbances and fatigue in patients with Addison's disease. A SCDC is a simple and patient-friendly tool for adjusting GRT and can be useful in the follow-up of patients with Addison's disease.
Maki, Sara; Kramarz, Caroline; Maria Heister, Paula; Pasha, Kamran
Addison's disease is a rare endocrine disorder that frequently presents with non-specific symptoms, but may deteriorate rapidly into life-threatening Addisonian crisis if left untreated. Diagnosis can be difficult in patients without a suggestive medical history. We describe a case of a 37-year-old man who was admitted with acute kidney injury and hyperkalaemia, resistant to treatment with insulin/dextrose and calcium gluconate. On clinical examination, he was found to be hyperpigmented; a subsequent random serum cortisol of 49 nmol/L affirmed the preliminary diagnosis of Addison's disease. The patient's hyperkalaemia improved on treatment with hydrocortisone, and a follow-up morning adrenocorticotropic hormone of 1051 ng/L confirmed the diagnosis. 2016 BMJ Publishing Group Ltd.
John G. Skedros
Full Text Available This report describes a patient who had a series of daily interscalene nerve blocks to treat pain following a shoulder manipulation for postsurgical stiffness. She experienced acute respiratory compromise that persisted for many weeks. All typical and unusual causes of these symptoms were ruled out. Her treating pulmonologist theorized that the ipsilateral carotid body had been injured. However, it was subsequently determined that the constellation of symptoms and their prolonged duration were best explained by a poor stress response from Addison's disease coupled with exacerbation of early onset myasthenia gravis. This patient's case is not a typical reaction to interscalene nerve blocks, and thus preoperative testing would not be recommended for myasthenia gravis or Addison's disease without underlying suspicion. We describe this report to inform physicians to consider a workup for these diagnoses if a typical workup rules out all usual causes of complications from an interscalene block.
Skedros, John G; Kiser, Casey J; Mendenhall, Shaun D
This report describes a patient who had a series of daily interscalene nerve blocks to treat pain following a shoulder manipulation for postsurgical stiffness. She experienced acute respiratory compromise that persisted for many weeks. All typical and unusual causes of these symptoms were ruled out. Her treating pulmonologist theorized that the ipsilateral carotid body had been injured. However, it was subsequently determined that the constellation of symptoms and their prolonged duration were best explained by a poor stress response from Addison's disease coupled with exacerbation of early onset myasthenia gravis. This patient's case is not a typical reaction to interscalene nerve blocks, and thus preoperative testing would not be recommended for myasthenia gravis or Addison's disease without underlying suspicion. We describe this report to inform physicians to consider a workup for these diagnoses if a typical workup rules out all usual causes of complications from an interscalene block.
Ian Louis Ross
Full Text Available BACKGROUND: Addison's disease is a potentially life-threatening disorder, and prompt diagnosis, and introduction of steroid replacement has resulted in near normal life-expectancy. There are limited data describing the clinical presentation of Addison's disease in South Africa. It is hypothesised that patients may present in advanced state of ill-health, compared to Western countries. PATIENTS: A national database of patients was compiled from primary care, referral centres and private practices. 148 patients were enrolled (97 white, 34 mixed ancestry, 5 Asian and 12 black. METHODS: Demographic and clinical data were elicited using questionnaires. Biochemical data were obtained from folder reviews and laboratory archived results. RESULTS: The majority of the cohort was women (62%. The median and inter-quartile age range (IQR of patients at enrolment was 46.0 (32.0-61.0 years, with a wide range from 2.8-88.0 years. The median and IQR age at initial diagnosis was 34.0 (20.0-45.0 years (range 0.02-77.0 years, indicating that at the time of enrolment, the patients, on average, were diagnosed with Addison's disease 12 years previously. Hyperpigmentation was observed in 76%, nausea and vomiting occurred in more than 40%, and weight loss was noted in 25%. Loss of consciousness as a presenting feature was recorded in 20%. with a 95% confidence interval [CI] of (14-28% and shock occurred in 5% CI (1.5-8.5%. Case-finding was recorded at 3.1 per million. CONCLUSIONS: The usual constellation of hyperpigmentation, nausea, vomiting and weight loss suggests Addison's disease, but a significant proportion present with an advanced state of ill-health and Addisonian crises. A lower prevalence rate, compared to Western countries is suggested.
Jyothi, K S; George, Cyriac; Shaji, K S
Adrenoleukodystrophy (ALD) is an X-linked disorder with diverse clinical presentations. A 30-year-old male, previously diagnosed with Addison's disease, on steroid supplementation for 18 years, presented to us with manic symptoms for 4 years. He was found to have white matter hypodensities in computed tomography head and had white matter signal changes in magnetic resonance imaging, and therefore a diagnosis of ALD was made.
Pearce, Simon H S; Mitchell, Anna L; Bennett, Stuart; King, Phil; Chandran, Sukesh; Nag, Sath; Chen, Shu; Smith, Bernard Rees; Isaacs, John D; Vaidya, Bijay
A diagnosis of Addison's disease means lifelong dependence on daily glucocorticoid and mineralocorticoid therapy and is associated with increased morbidity and mortality as well as a risk of unexpected adrenal crisis. The objective of the study was to determine whether immunomodulatory therapy at an early stage of autoimmune Addison's disease could lead to preservation or improvement in adrenal steroidogenesis. This was an open-label, pilot study of B lymphocyte depletion therapy in new-onset idiopathic primary adrenal failure. Doses of iv rituximab (1 g) were given on d 1 and 15, after pretreatment with 125 mg iv methylprednisolone. Six patients (aged 17-47 yr; four females) were treated within 4 wk of the first diagnosis of idiopathic primary adrenal failure. Dynamic testing of adrenal function was performed every 3 months for at least 12 months. Serum cortisol levels declined rapidly and were less than 100 nmol/liter (3.6 μg/dl) in all patients by 3 months after B lymphocyte depletion. Serum cortisol and aldosterone concentrations remained low in five of the six patients throughout the follow-up period. However, a single patient had sustained improvement in both serum cortisol [peak 434 nmol/liter (15.7 μg/dl)] and aldosterone [peak 434 pmol/liter (15.7 ng/dl)] secretion. This patient was able to discontinue steroid medications 15 months after therapy and remains well, with improving serum cortisol levels 27 months after therapy. New-onset autoimmune Addison's disease should be considered as a potentially reversible condition in some patients. Future studies of immunomodulation in autoimmune Addison's disease may be warranted.
Ross, Ian Louis; Levitt, Naomi S
Addison's disease is a potentially life-threatening disorder, and prompt diagnosis, and introduction of steroid replacement has resulted in near normal life-expectancy. There are limited data describing the clinical presentation of Addison's disease in South Africa. It is hypothesised that patients may present in advanced state of ill-health, compared to Western countries. A national database of patients was compiled from primary care, referral centres and private practices. 148 patients were enrolled (97 white, 34 mixed ancestry, 5 Asian and 12 black). Demographic and clinical data were elicited using questionnaires. Biochemical data were obtained from folder reviews and laboratory archived results. The majority of the cohort was women (62%). The median and inter-quartile age range (IQR) of patients at enrolment was 46.0 (32.0-61.0) years, with a wide range from 2.8-88.0 years. The median and IQR age at initial diagnosis was 34.0 (20.0-45.0) years (range 0.02-77.0) years, indicating that at the time of enrolment, the patients, on average, were diagnosed with Addison's disease 12 years previously. Hyperpigmentation was observed in 76%, nausea and vomiting occurred in more than 40%, and weight loss was noted in 25%. Loss of consciousness as a presenting feature was recorded in 20%. with a 95% confidence interval [CI] of (14-28%) and shock occurred in 5% CI (1.5-8.5%). Case-finding was recorded at 3.1 per million. The usual constellation of hyperpigmentation, nausea, vomiting and weight loss suggests Addison's disease, but a significant proportion present with an advanced state of ill-health and Addisonian crises. A lower prevalence rate, compared to Western countries is suggested.
Thompson, Michael D; Kalmar, Eileen; Bowden, Sasigarn A
We present a case of rapidly progressing Addison's disease in adrenal crisis with severe hyponatraemia and absence of hyperkalaemia in a 10-year-old girl. She presented with 2 weeks of vomiting, fatigue and weight loss. Her serum electrolytes obtained 1 week prior to presentation were normal, except for mild hyponatraemia at 131 mmol/L, which dropped to 112 mmol/L on admission. She had normal serum potassium, low-serum osmolality, with elevated urine sodium and osmolality, indistinguishable from syndrome of inappropriate antidiuretic hormone (SIADH). Subsequently, Addison's disease was diagnosed on the basis of gingival hyperpigmentation and undetectable cortisol on adrenocorticotropic hormone stimulation test. She rapidly responded to stress dose hydrocortisone, followed by hydrocortisone and fludrocortisone replacement therapy. The absence of hyperkalaemia in the presence of severe hyponatraemia cannot rule out Addison's disease in children. The mechanism of hypo-osmolar hyponatraemia in primary adrenal insufficiency and clinical clues to differentiate it from SIADH are discussed. 2015 BMJ Publishing Group Ltd.
Inder, Warrick J; Meyer, Caroline; Hunt, Penny J
Addison's disease may be complicated by hypertension and less commonly by heart failure. We review the pathophysiology of the renin-angiotensin-aldosterone axis in Addison's disease and how this is altered in the setting of hypertension and heart failure. An essential first step in management in both conditions is optimizing glucocorticoid replacement and considering dose reduction if excessive. Following this, if a patient with Addison's disease remains hypertensive, the fludrocortisone dose should be reviewed and reduced if there are clinical and/or biochemical signs of mineralocorticoid excess. In the absence of such signs, where the renin is towards the upper end of the normal range or elevated, an angiotensin II (AII) receptor antagonist or angiotensin converting enzyme (ACE) inhibitor is the treatment of choice, and the fludrocortisone dose should remain unchanged. Dihydropyridine calcium channel blockers are clinically useful as second line agents, but diuretics should be avoided. In the setting of heart failure, there is an increase in total body sodium and water; therefore, it is appropriate to reduce and rarely consider ceasing the fludrocortisone. Loop diuretics may be used, but not aldosterone antagonists such as spironolactone or eplerenone. Standard treatment with ACE inhibitors, or as an alternative, AII receptor antagonists, are appropriate. Measurements of renin are no longer helpful in heart failure to determine the volume status but plasma levels of brain natriuretic peptide (BNP/proBNP) may help guide therapy. © 2014 John Wiley & Sons Ltd.
Smans, L C C J; Zelissen, P M J
To our knowledge, no case of remission in autoimmune Addison's disease has previously been reported. We describe a patient with primary adrenal insufficiency caused by autoimmune adrenalitis in whom partial remission was observed after 7 yr. A 39-yr-old male was referred because of extreme fatigue, weight loss, anorexia, nausea, and bouts of fever. During physical examination hyperpigmentation was seen. Laboratory tests showed a plasma cortisol of 0.02 micromol/l (08:30 h). Cortisol failed to increase during the ACTH stimulation test (0.02 to 0.03 micromol/l) and ACTH was markedly elevated (920 pmol/l). Adrenal auto-antibodies were weakly positive. A CT-scan showed no evidence of calcifications or other abnormalities of the adrenal glands. The diagnosis of autoimmune Addison's disease was made and replacement therapy with hydrocortisone and fludrocortisone was started. During the following years the dose of hydrocortisone was gradually decreased. Eventually, the patient decided to stop his medication completely. A repeated ACTH-stimulation test revealed a basal cortisol of 0.25 micromol/l and a peak cortisol of 0.30 micromol/l with a basal ACTH of 178 pmol/l. The patient did not have any complaints. Recovery of adrenal insufficiency, due to causes other than autoimmune adrenalitis, has been reported in the past. If our case of partial recovery of autoimmune adrenalitis is not unique this could have profound effects on treatment and follow-up of Addison's disease.
Full Text Available Abstract Introduction Idiopathic intracranial hypertension can rarely be associated with an underlying endocrine disorder such as Cushing's syndrome, hyperthyroidism, or with administration of thyroxine or growth hormone. Though cases of idiopathic intracranial hypertension associated with Addison's disease in children have been reported, there is only one documented case report of this association in adults. We describe a case of an acute adrenal insufficiency precipitated by idiopathic intracranial hypertension in a Caucasian female. Case presentation A 24-year-old Caucasian woman was acutely unwell with a background of several months of generalised fatigue and intermittent headaches. She had unremarkable neurological and systemic examination with a normal computerised tomography and magnetic resonance imaging of the brain. Normal cerebrospinal fluid but increased opening pressure at lumbar puncture suggested intracranial hypertension. A flat short synacthen test and raised level of adrenocorticotrophic hormone were consistent with primary adrenal failure. Conclusion Addison's disease can remain unrecognised until precipitated by acute stress. This case suggests that idiopathic intracranial hypertension can rarely be associated with Addison's disease and present as an acute illness. Idiopathic intracranial hypertension is possibly related to an increase in the levels of arginine vasopressin peptide in serum and cerebrospinal fluid secondary to a glucocorticoid deficient state.
Paulo S.M. Esperon
Full Text Available OBJETIVO: alertar sobre a importância de distúrbio hidroeletrolítico grave devido a doença crônica não previamente diagnosticada. MÉTODO: relato de um caso de coma hiponatrêmico devido a crise adrenal em criança portadora de doença de Addison não diagnosticada previamente, apesar de história clínica sugestiva desta doença há cerca de quatro anos. RESULTADO: Após atendimento inicial à emergência, com correção da hiponatremia grave com hipovolemia discreta, hipernatriúria e hiperpotassemia, o diagnóstico diferencial deste distúrbio hidroeletrolítico revelou tratar-se de uma crise adrenal secundária a uma insuficiência adrenal primária crônica. O tratamento com hidrocortisona oral possibilitou alta hospitalar com correção total dos distúrbios metabólicos. CONCLUSÃO: é importante manter um alto grau de suspeita de doença de Addison para evitar as graves conseqüências de seu diagnóstico tardio, como distúrbios hidroeletrolíticos graves, além de atraso de crescimento e desenvolvimento.OBJECTIVE: To show the importance of severe hydroelectrolytic disorder as a consequence of previously undiagnosed chronic disease. DESCRIPTION: Case report of hyponatremic coma caused by adrenal crisis in a child with previously undiagnosed Addison's disease despite suggestive clinical findings of this disease in the last four years. After correction of severe hyponatremia, mild hypovolemia, hypernatriuria and hyperkalemia, the differential diagnosis of this hydroelectrolytic disorder revealed an adrenal crisis resulting from a primary chronic adrenal insufficiency. Oral treatment with hydrocortisone was efficient in correcting the metabolic disorder and the patient was then discharged. COMMENTS: It is very important to highly suspect of Addison's disease in order to avoid the dangerous consequences of late diagnosis such as severe hydroelectrolytic disorders and retarded growth and development.
Berardelli, R; Karamouzis, I; D'Angelo, V; Fussotto, B; Minetto, M A; Ghigo, E; Giordano, R; Arvat, E
Mineralocorticoid receptors (MR) in the hippocampus display an important role in the control of hypothalamic-pituitary-adrenal (HPA) axis, mediating the ''proactive'' feedback of glucocorticoids (GC). Fludrocortisone (FC), a potent MR agonist, has been shown to decrease HPA activity through a hippocampal mechanism. Since it has been demonstrated that FC shows a significant inhibition of the HPA axis response to hCRH stimulus in normal subjects, also at doses usually administered as replacement therapy in patients with Addison's disease, an FC effect at MRs in human pituitary or a GR-pituitary agonism stronger than believed until now has been postulated. Ten patients affected by autoimmune Addison's disease received: (1) placebo p.o. + placebo i.v., (2) hydrocortisone (H) 10 mg p.o. + placebo i.v., (3) FC 0.1 mg p.o. + placebo i.v., (4) FC 0.1 mg and H 10 mg p.o. + placebo i.v. to verify a possible GR FC-mediated effect that might display a repercussion on the GC-replacement therapy. H reduced ACTH (p < 0.01) and increased cortisol levels (p < 0.01) with respect to the placebo session, while FC did not affect either ACTH or cortisol levels compared to placebo, and higher ACTH and lower cortisol levels (p < 0.03 and p < 0.01) were observed compared with the H session; furthermore the co-administration of FC + H showed ACTH and cortisol profiles similar to that observed during H alone. Our study showed a lack of FC effect on corticotrope secretion in Addison's disease, thus making unlikely the hypothesis of its GR pituitary agonism and the risk of glucocorticoid excess in primary adrenal insufficiency.
Full Text Available Adrenocortical autoantibodies (ACA, present in 60-80% of patients with idiopathic Addison's disease, are conventionally detected by indirect immunofluorescence (IIF on frozen sections of adrenal glands. The large-scale use of IIF is limited in part by the need for a fluorescence microscope and the fact that histological sections cannot be stored for long periods of time. To circumvent these restrictions we developed a novel peroxidase-labelled protein A (PLPA technique for the detection of ACA in patients with Addison's disease and compared the results with those obtained with the classical IIF assay. We studied serum samples from 90 healthy control subjects and 22 patients with Addison's disease, who had been clinically classified into two groups: idiopathic (N = 13 and granulomatous (N = 9. ACA-PLPA were detected in 10/22 (45% patients: 9/13 (69% with the idiopathic form and 1/9 (11% with the granulomatous form, whereas ACA-IIF were detected in 11/22 patients (50%: 10/13 (77% with the idiopathic form and 1/9 (11% with the granulomatous form. Twelve of the 13 idiopathic addisonians (92% were positive for either ACA-PLPA or ACA-IIF, but only 7 were positive by both methods. In contrast, none of 90 healthy subjects was found to be positive for ACA. Thus, our study shows that the PLPA-based technique is useful, has technical advantages over the IIF method (by not requiring the use of a fluorescence microscope and by permitting section storage for long periods of time. However, since it is only 60% concordant with the ACA-IIF method, it should be considered complementary instead of an alternative method to IIF for the detection of ACA in human sera.
Lee, Li-Chik; Fujita, Naohisa; Ohba, Yachiyo
A 62-year-old woman was admitted to our hospital with complaints of general malaise and hyperpigmentation. We diagnosed her case as primary adrenocortical insufficiency (Addison's disease) by endocrinological studies. CT demonstrated dense calcification in both adrenal beds without evidence of normal glandular remnants. Calcified adrenal is not specific to tuberculosis, but some points of CT findings are useful for pathogenetic approach. Recently, there have been several reports that ACTH producing pituitary tumors develop in patients treated with conventional corticosteroid replacement. Corticosteroid should be administered by monitoring of plasma cortisol and ACTH concentrations. (author)
Mudawi, Hatim M.; Baraka, Omer Z.; El-Hassan, Ahmed M.; El-Amin, Elwaleed M.
Histoplasmosis is a fungal infection caused by Histoplasma capsulatum. In the normal individual, both disseminated histoplasmosis and symptomatic adrenal histoplasmosis are rare. Herein, we describe the case of a 50-year-old gentleman residing in western Sudan who presented with 7-month history of generalized body weakness, easy fatigue and frequent attacks of vomiting and diarrhea. Physical examination and laboratory investigations confirmed the diagnosis of Addison's disease due to histoplasma capsulatum var duboisii infection of the adrenal glands. He was treated with intravenous hydrocortisone, followed by oral prednisolone and itraconazole. (author)
Hangaard, J; Andersen, M; Grodum, E
The physiological and pathophysiological role of cortisol in pulsatile LH release was investigated in 14 patients (5 men, 6 premenopausal women, and 3 postmenopausal women) with Addison's disease. The explicit effect of cortisol in relation to the effect of corticotropin-releasing factor (CRF......), ACTH, and opioids was ensured by hypo-, normo-, and hypercortisolism. Hypocortisolism was obtained by 24-h discontinuation of hydrocortisone (HC) followed by 23-h saline infusion. Eucortisolism was secured by infusion of HC (0.5 mg/kg) over 23 h. Stress-appropriate hypercortisolism was obtained...
Miconi, Francesco; Savarese, Emanuela; Miconi, Giovanni; Cabiati, Gabriele; Rapaccini, Valentina; Principi, Nicola; Esposito, Susanna
Celiac disease (CD) is an autoimmune disorder deriving from an aberrant adaptive immune response against gluten-containing grains in genetically predisposed subjects. In a number of patients, CD is associated with one or more other autoimmune diseases. Primary Addison's disease (AD) and CD may co-exist, although this association is relatively uncommon in children. In addition, it is not precisely defined whether a gluten-free diet influences the course of AD. A case of CD in a 12-year-old boy presenting as acute adrenal insufficiency is described here. A gluten-free diet had a significant therapeutic role in this case, wherein most of the clinical signs and symptoms of AD disappeared in a few days. In addition, the dosage of cortisol acetate, initially administered to treat the AD, was able to be rapidly reduced. This case highlights that CD can be associated with AD in children, and a gluten-free diet seems to positively influence the course of AD.
Guo Yingkun; Yang Zhigang; Li Yuan; Ma Ensen; Deng Yuping; Min Pengqiu; Yin Longlin; Hu Jian; Zhang Xiaochun; Chen Tianwu
Purpose: To describe CT morphology of untreated adrenal tuberculosis during the different stages of the natural history of the disease and to evaluate the diagnostic implications of CT features. Materials and methods: We retrospectively evaluated CT features in 42 patients with documented adrenal tuberculosis for the location, size, morphology, and enhancement patterns shown on CT images. The clinical duration were correlated with the CT features. Results: Of the 42 patients with untreated adrenal tuberculosis, bilaterally enlarged adrenal glands were revealed in 38 cases (91%), unilaterally enlarged in 3 cases (7%), and normal size in 1 case (2%). Of the 41 cases (98%) with enlargement, mass-like enlargement was seen in 20 cases (49%) and enlargement with preserved contours in 21 cases (51%). Peripheral rim enhancement presented in 22 cases (52%) on contrast-enhanced CT. Non-enhanced CT scan revealed calcification in 21 cases (50%). As the duration of Addison's disease increased, the presence of calcification and contour preservation increased concomitantly (p < 0.001), whereas peripheral rim enhancement and mass-like enlargement decreased concomitantly on CT images (p < 0.001). Conclusion: CT may be helpful in diagnosing adrenal tuberculosis when clinically suspected, and CT features are correlated to the clinical duration of Addison's disease
Ozturk, Hakan; Karaaslan, Serap
Metachronous adrenal metastasis from contralateral renal cell carcinoma (RCC) surgery is an extremely rare condition. Iatrogenic Addison's disease occurring after metastasectomy (adrenalectomy) is an even rarer clinical entity. We present a case of a 68-year-old male with hematuria and left flank pain 9 years prior. The patient underwent left transperitoneal radical nephrectomy involving the ipsilateral adrenal glands due to a centrally-located, 75-mm in diameter solid mass lesion in the upper pole of the left kidney. The tumour lesion was confined within the renal capsule, and the histo-pathological examination revealed a Fuhrman nuclear grade II clear cell carcinoma. The patient underwent transperitoneal right adrenalectomy. The histopathological examination revealed metastasis of clear cell carcinoma. The patient was diagnosed with iatrogenic Addison's disease based on the measurement of serum cortisol levels and the adrenocorticotropic hormone (ACTH) stimulation test, after which glucocorticoid and mineralocorticoid replacement was initiated. The patient did not have local recurrence or new metastasis in the first year of the follow-up. The decision to perform ipsilateral adrenalectomy during radical nephrectomy constitutes a challenge, and the operating surgeon must consider all these rare factors.
Wagner, H.; Degenhardt, G.; Wenning, N.
The findings obtained before suggest that plasma ACTH determination is another valuable parameter supplementing the determination of plasma corticoids in the diagnosis of Addison's disease. In the assessment of the success of the treatment, plasma ACTH measurement is superior to the determination of plasma corticoids. (orig./AK) [de
Full Text Available This report describes a case of West Nile virus (WNV meningoencephalitis in a child who presented with fever, headache, seizures, and altered mental status, as well as hyponatremia and bronzing of the skin. Findings that led to the diagnosis of WNV included plasma-cell pleocytosis of the cerebrospinal fluid (CSF and linear chorioretinitis on ophthalmologic exam. The diagnosis was confirmed by a positive serum and CSF WNV IgM. The acute WNV infection triggered an adrenal crisis which uncovered a new diagnosis of underlying Addison's disease. This is the first case report of severe neuroinvasive WNV disease in a pediatric patient with primary adrenal insufficiency. Neuroinvasive WNV disease is uncommon in children, but may have a more severe presentation in those with certain underlying medical conditions.
Zurawek, Magdalena; Fichna, Marta; Kazimierska, Marta; Fichna, Piotr; Dzikiewicz-Krawczyk, Agnieszka; Przybylski, Grzegorz; Ruchala, Marek; Nowak, Jerzy
Mitochondrial antiviral signaling (MAVS) protein is an intracellular adaptor molecule, downstream of viral sensors, retinoid acid-inducible gene I (RIG-I)-like receptors (RLRs). Impaired antiviral cell signaling might contribute to autoimmunity. Studies have recently shown variations in genes encoding RLRs as risk factors for autoimmune diseases. We investigated whether MAVS coding polymorphisms are associated with Addison's disease (AD) and type 1 diabetes (T1D) in Polish population. We genotyped 140 AD, 532 T1D patients and 600 healthy controls for MAVS rs17857295, rs7262903, rs45437096 and rs7269320. Genotyping was performed by TaqMan assays. Distribution of the MAVS genotypes and alleles did not reveal significant differences between patients and controls (p > 0.05). This analysis did not indicate the association of the MAVS locus with susceptibility to AD and T1D.
Bjanesoy, Trine E; Andreassen, Bettina Kulle; Bratland, Eirik; Reiner, Andrew; Islam, Shahinul; Husebye, Eystein S; Bakke, Marit
Autoimmune Addison's Disease (AAD) is an endocrine and immunological disease of uncertain pathogenesis resulting from the immune system's destruction of the hormone producing cells of the adrenal cortex. The underlying molecular mechanisms are largely unknown, but it is commonly accepted that a combination of genetic susceptibility and environmental impact is critical. In the present study, we identified multiple hypomethylated gene promoter regions in patients with isolated AAD using DNA isolated from CD4+ T cells. The identified differentially methylated regions were distributed evenly across the 10.5-kb-promoter regions covered by the array, and a substantial number localized to promoters of genes involved in immune regulation and autoimmunity. This study reveals a hypomethylated status in CD4+ T cells from AAD patients and indicates differential methylation of promoters of key genes involved in immune responses. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Ross, I L; Levitt, N S; Van der Walt, J S; Schatz, D A; Johannsson, G; Haarburger, D H; Pillay, T S
Using salivary cortisol (SC) measurements, cortisol exposure in Addison's disease patients on hydrocortisone replacement was determined and compared with healthy controls. Cortisol pharmacokinetics was assessed in 31 patients with Addison's disease on replacement hydrocortisone doses (median daily dose 20 mg; range 5-50 mg) and 30 healthy control subjects. Saliva samples (n=16) were collected between 08:00 and 00:00 h in 1 day, using a passive drool technique. Cortisol exposure was evaluated by noncompartmental approach. In the patients, cortisol exposure was significantly higher than in controls: median inter-quartile range (IQR) peak cortisol (C(max)) 174.5 (59.3-837.0) vs. 6.50 (4.7-19.3) nmol/l, p=0.0001; area under the curve (AUC) 390.1 (177.1-928.9) vs. 21.4 (14.6-28.4) minutes*nmol/l, p=0.0001, trough cortisol level (C(min)) 0.49 (0.49-0.96) vs. 0.49 (0.49-0.49) nmol/l, p=0.02, occurring at 480.0 (0.1-660.0) vs. 405.0 (180.0-570.0) min, p=0.56. First peak cortisol was 174.5 (53.0-754.7) vs. 6.27 (3.90-8.47) nmol/l, p=0.0001 and second peak cortisol 18.90 (5.22-76.9) vs. 3.12 (1.76-4.79) nmol/l, p=0.0001. The time to first peak cortisol differed between the 2 groups, 30 (30-75) vs. 0.1 (0.1-30) minutes; p=0.0001. At doses studied, hydrocortisone replacement therapy results in cortisol pharmacokinetics being markedly different from endogenous cortisol profiles in healthy control subjects. Addison's disease patients had significantly higher SC levels compared to healthy control subjects. © Georg Thieme Verlag KG Stuttgart · New York.
Lewandowski, Krzysztof C; Malicka, Katarzyna; Dąbrowska, Katarzyna; Lewiński, Andrzej
A 36-year-old woman was found to have a low morning ACTH concentration despite a history of Addison's disease. Past medical history: At the age of 23 years the subject developed Graves's disease, which was treated with radioiodine. At about the same time, she claimed to have two episodes of pancreatitis treated with cholecystectomy. About seven months later she was euthyroid on L-thyroxine (TSH 1.51 mIU/mL) but was admitted with hypotension, hyponatraemia (sodium 109 mmol/L), and low morning cortisol (119 nmol/L). Further investigations confirmed primary adrenal failure with ACTH concentration of 779 pg/mL (ref. range 0-60) prior to the dose of hydrocortisone. About nine years later she complained about tiredness. Clinically she was normotensive and not pigmented. BMI 22.3 kg/m². Periods were regular. ACTH concentration was surprisingly low (ACTH 8.53 pg/mL, ref. range 0-46), despite very low cortisol (3.37 nmol/L). She was admitted for further assessment. Pituitary MRI scan was unremarkable. An insulin tolerance test was performed and showed a clear increase of ACTH (from 15.2 to 165 pg/mL). There was, however, hardly any increase of ACTH after CRH stimulation (from 6.05 pg/mL to 10.2 pg/mL), thus demonstrating central CRH resistance. In summary, this patient developed secondary adrenal failure in the setting of previous Addison's disease. Interestingly, hypoglycaemia (but not CRH) provided a stimulus for ACTH release, thus demonstrating CRH resistance. The case confirms that besides CRH, other factors are responsible for stimulation of the ACTH-cortisol axis during insulin tolerance test.
Vrkljan, Ana Marija; Pašalić, Ante; Strinović, Mateja; Perić, Božidar; Kruljac, Ivan; Miroševć, Gorana
A case of autoimmune polyglandular syndrome (APS) is presented. A 45-year-old man was admitted due to fatigue, malaise and inappetence. He had a history of primary hypothyroidism and was on levothyroxine substitution therapy. One year before, he was diagnosed with normocytic anemia and vitamin B12 deficiency, which was treated with vitamin B12 substitution therapy. Physical examination revealed hypotension and marked hyperpigmentation. Laboratory testing showed hyponatremia, hyperkaliemia and severe normocytic anemia. Endocrinological evaluation disclosed low morning cortisol and increased adrenocorticotropic hormone levels. Hence, the diagnosis of Addison's disease was established. Additional laboratory workup showed positive parietal cell antibodies. However, his vitamin B12 levels were increased due to vitamin B12 supplementation therapy, which was initiated earlier. Gastroscopy and histopathology of gastric mucosa confirmed atrophic gastritis. Based on prior low serum vitamin B12 levels, positive parietal cell antibodies and atrophic gastritis, the patient was diagnosed with pernicious anemia. Hydrocortisone supplementation therapy was administered and titrated according to urinary-free cortisol levels. Electrolyte disbalance and red blood cell count were normalized. This case report demonstrates rather unique features of pernicious anemia in a patient with Addison's disease. It also highlights the link between type II and type III APS. Not only do they share the same etiological factors, but also overlap in pathophysiological and clinical characteristics. This case report favors older classification of APS, which consolidates all endocrine and other organ-specific autoimmune diseases into one category. This is important since it might help avoid pitfalls in the diagnosis and treatment of patients with APS.
Colucci, Randall; Jimenez, Rafael E; Farrar, William; Malgor, Ramiro; Kohn, Leonard; Schwartz, Frank L
A 56-year-old woman presented with an incidental adrenal adenoma and physical examination findings that included moderate obesity, a slight cervicothoracic fat pad ("buffalo hump"), increased supraclavicular fat pads, and white abdominal striae. Biochemical workup revealed elevated levels of 24-hour urinary free cortisol but normal serum morning cortisol and suppressed levels of corticotropin, suggestive of adrenal-dependent Cushing syndrome. The resected adrenal gland revealed macronodular cortical hyperplasia with a dominant nodule. Other findings included an absent cortisol response to corticotropin stimulation, presence of serum anti-21-hydroxylase antibodies, and mononuclear cell infiltration--consistent with adrenalitis. The findings represent, to the authors' knowledge, the first known case of a patient with coexistent functional cortisol-secreting macronodular adrenal tumor resulting in Cushing syndrome and immune-mediated adrenalitis resulting in Addison disease.
Baker, Peter R.; Nanduri, Priyaanka; Gottlieb, Peter A.; Yu, Liping; Klingensmith, Georgeanna J.; Eisenbarth, George S.; Barker, Jennifer M.
Summary Context Autoantibodies to 21-hydroxylase (21OH-AA) precede onset of autoimmune Addison's disease (AD). Progression to AD can take months to years, and early detection of metabolic decompensation may prevent morbidity and mortality. Objective To define optimal methods of predicting progression to overt AD (defined by subnormal peak cortisol response to Cosyntropin) in 21OH-AA+ individuals. Design, Setting and Participants Individuals were screened for 21OH-AA at the Barbara Davis Center from 1993 to 2011. Subjects positive for 21OH-AA (n = 87) were tested, and the majority prospectively followed for the development of Addison's disease, including seven diagnosed with AD upon 21OH-AA discovery (discovered), seven who progressed to AD (progressors) and 73 nonprogressors. Main Outcome Measured Plasma renin activity (PRA), ACTH, baseline cortisol, peak cortisol and 21OH-AA were measured at various time points relative to diagnosis of AD or last AD-free follow-up. Results Compared with nonprogressors, in the time period 2 months–2 years prior to the onset of AD, progressors were significantly more likely to have elevated ACTH (11–22 pm, P < 1E-4), with no significant differences in mean PRA (P = 0·07) or baseline cortisol (P = 0·08), and significant but less distinct differences seen with 21OH-AA levels (P < 1E-4) and poststimulation cortisol levels (P = 6E-3). Conclusion Moderately elevated ACTH is a more useful early indicator of impending AD than 21OH-AA, PRA or peak cortisol, in the 2 months–2 years preceding the onset of AD. PMID:22066755
A 30-year-old female with a history of anxiety, cannabis use, and Avoidant/Restrictive Food Intake Disorder presented for residential treatment of a Cannabis Use Disorder. Upon arrival, she had not eaten for two days and was found to be hypotensive with electrolyte disturbances. She was admitted to a nearby hospital, where the Internist diagnosed her with Addison's disease. She was treated with corticosteroid therapy, with rapid normalization of her electrolytes, eating, and anxiety. This is the first published case of undiagnosed Addison's disease presenting as an eating disorder, with cannabis use likely contributing to symptoms. This case elucidates the importance of ruling out other biologic and psychologic causes of clinical presentations before an eating disorder diagnosis can be made.
Dawoodji, Amina; Chen, Ji-Li; Shepherd, Dawn; Dalin, Frida; Tarlton, Andrea; Alimohammadi, Mohammad; Penna-Martinez, Marissa; Meyer, Gesine; Mitchell, Anna L; Gan, Earn H; Bratland, Eirik; Bensing, Sophie; Husebye, Eystein S; Pearce, Simon H; Badenhoop, Klaus; Kämpe, Olle; Cerundolo, Vincenzo
The mechanisms behind destruction of the adrenal glands in autoimmune Addison's disease remain unclear. Autoantibodies against steroid 21-hydroxylase, an intracellular key enzyme of the adrenal cortex, are found in >90% of patients, but these autoantibodies are not thought to mediate the disease. In this article, we demonstrate highly frequent 21-hydroxylase-specific T cells detectable in 20 patients with Addison's disease. Using overlapping 18-aa peptides spanning the full length of 21-hydroxylase, we identified immunodominant CD8(+) and CD4(+) T cell responses in a large proportion of Addison's patients both ex vivo and after in vitro culture of PBLs ≤20 y after diagnosis. In a large proportion of patients, CD8(+) and CD4(+) 21-hydroxylase-specific T cells were very abundant and detectable in ex vivo assays. HLA class I tetramer-guided isolation of 21-hydroxylase-specific CD8(+) T cells showed their ability to lyse 21-hydroxylase-positive target cells, consistent with a potential mechanism for disease pathogenesis. These data indicate that strong CTL responses to 21-hydroxylase often occur in vivo, and that reactive CTLs have substantial proliferative and cytolytic potential. These results have implications for earlier diagnosis of adrenal failure and ultimately a potential target for therapeutic intervention and induction of immunity against adrenal cortex cancer. Copyright © 2014 by The American Association of Immunologists, Inc.
Winqvist, O; Gustafsson, J; Rorsman, F; Karlsson, F A; Kämpe, O
Autoimmune polyendocrine syndrome type I (APS I) and idiopathic Addison's disease are both disorders with adrenal insufficiency but with differences in genetic background, clinical presentation, and extent of extraadrenal manifestations. In this study the major adrenal autoantigen identified with sera from patients with APS I was characterized by analyses using indirect immunofluorescence, Western blots of adrenal subcellular fractions and of recombinant proteins, immunoprecipitations of [35S...
Meyer, Gesine; Hackemann, Annika; Reusch, Juergen; Badenhoop, Klaus
Hypoglycemia can be a symptom in patients with Addison's disease. The common regimen of replacement therapy with oral glucocorticoids results in unphysiological low cortisol levels in the early morning, the time of highest insulin sensitivity. Therefore patients with Addison's disease are at risk for unrecognized and potentially severe nocturnal hypoglycemia also because of a disturbed counterregulatory function. Use of a continuous glucose monitoring system (CGMS) could help to adjust hydrocortisone treatment and to avoid nocturnal hypoglycemia in these patients. Thirteen patients with Addison's disease were screened for hypoglycemia wearing a CGMS for 3-5 days. In one patient we identified a hypoglycemic episode at 3:45 a.m. with a blood glucose level of 46 mg/dL, clearly beneath the 95% tolerance interval of minimal glucose levels between 2 and 4 a.m. (53.84 mg/dL). After the hydrocortisone replacement scheme was changed, the minimum blood glucose level between 2 and 4 a.m. normalized to 87 mg/dL. Continuous glucose monitoring can detect nocturnal hypoglycemia in patients with primary adrenal insufficiency and hence prevent in these patients an impaired quality of life and even serious adverse effects.
Campean, Radu; Hasun, Matthias; Stöllberger, Claudia; Bucher, Johannes; Finsterer, Josef; Schnack, Christoph; Weidinger, Franz
Reversible left ventricular dysfunction, also termed Takotsubo cardiomyopathy, is rarely reported in Addison's disease after initiation of hormone replacement therapy. The pathogenesis of this cardiomyopathy is unknown. A 41-year-old white woman with a history of autoimmune Hashimoto thyroiditis diagnosed 3 years earlier and acute adrenal insufficiency diagnosed 3 weeks earlier presented with new onset of heart failure New York Heart Association class IV, which had started shortly after initiation of hormone replacement therapy with hydrocortisone 20 mg/day and fludrocortisone 0.3 mg/day. Nine days before admission she had collapsed because of dizziness and had a cerebral concussion and open fracture of her nasal bone, however, no further investigations were carried out at that time. A physical examination revealed leg edema, tachycardia, tachypnea, bilateral basal crepitations, and blood pressure 110/70 mmHg. An electrocardiogram showed sinus tachycardia, low voltage, negative T-waves in V 5 and V 6 and a corrected QT interval of 590 ms. Echocardiography revealed a reduced left ventricular systolic function with an ejection fraction of 30 %, and septal, apical, and anterior wall akinesia. Cardiac magnetic resonance imaging showed relative enhancement of gadolinium, indicating hyperemia and capillary leakage, and no myocardial scars. Because of the improvement in her cardiac function, lack of cardiovascular risk factors, and lack of signs for ischemia on magnetic resonance imaging, no coronary angiography was carried out. The results of sellar and renal magnetic resonance imaging were normal. Her troponin T was slightly elevated. Bisoprolol and ramipril were started. Her fludrocortisone dose was reduced to 0.05 mg/day. Her electrocardiogram and systolic function, documented by echocardiography and magnetic resonance imaging, normalized within 6 months. Although we could not exclude coronary artery disease by coronary angiography, her clinical course and
Kraus, A U; Penna-Martinez, M; Meyer, G; Badenhoop, K
Addison's disease is a rare autoimmune disorder leading to adrenal insufficiency and life-long glucocorticoid dependency. Vitamin D receptor (VDR) polymorphisms and vitamin D deficiency predispose to Addison's disease. Aim of the current study was, to investigate potential anti-inflammatory vitamin D effects on monocytes in Addison's disease, focusing on inflammatory CCL-2 and IL6, as well on monocyte CD14 markers. Addison's disease is genetically linked to distinct HLA susceptibility alleles. Therefore we analyzed, whether HLA genotypes differed for vitamin D effects on monocyte markers. CD14 + monocytes were isolated from Addison's disease patients (AD, n=13) and healthy controls (HC, n=15) and stimulated with 1,25-dihydroxyvitamin D 3 and IL1β as an inflammatory stimulant. Cells were processed for mRNA expression of CCL-2, IL6 and CD14 and DNA samples were genotyped for major histocompatibility class (MHC) class II-encoded HLA- DQA1-DQB1 haplotypes. We found a downregulation of CCL-2 after vitamin D treatment in IL1β-stimulated monocytes both from AD patients and HC (AD p<0.001; HC p<0.0001). CD14 expression however, was upregulated in both HC and AD patients after vitamin D treatment (p<0.001, respectively). HC showed higher CD14 transcription level than AD patients after vitamin D treatment (p=0.04). Compared to IL1β-induced inflammation, HC have increased CD14 levels after vitamin D treatment (p<0.001), whereas the IL1β-induced CD14 expression of AD patients' monocytes did not change after vitamin D treatment (p=0.8). AD patients carrying HLA high-risk haplotypes showed an increased CCL-2 expression after IL1β-induced inflammation compared to intermediate-risk HLA carriers (p=0.05). Also HC monocytes' CD14 transcription after IL1β and vitamin D co-stimulation differed according to HLA risk profile. We show that vitamin D can exert anti-inflammatory effects on AD patients' monocytes which may be modulated by HLA risk genotypes. Copyright © 2017 Elsevier
Camozzi, Valentina; Betterle, Corrado; Frigo, Anna Chiara; Zaccariotto, Veronica; Zaninotto, Martina; De Caneva, Erica; Lucato, Paola; Gomiero, Walter; Garelli, Silvia; Sabbadin, Chiara; Salvà, Monica; Costa, Miriam Dalla; Boscaro, Marco; Luisetto, Giovanni
to assess bone damage and metabolic abnormalities in patients with Addison's disease given replacement doses of glucocorticoids and mineralocorticoids. A total of 87 patients and 81 age-matched and sex-matched healthy controls were studied. The following parameters were measured: urinary cortisol, serum calcium, phosphorus, creatinine, 24-h urinary calcium excretion, bone alkaline phosphatase, parathyroid hormone, serum CrossLaps, 25 hydroxyvitamin D, and 1,25 dihydroxyvitamin D. Clear vertebral images were obtained with dual-energy X-ray absorptiometry in 61 Addison's disease patients and 47 controls and assessed using Genant's classification. Nineteen Addison's disease patients (31.1%) had at least one morphometric vertebral fracture, as opposed to six controls (12.8%, odds ratio 3.09, 95% confidence interval 1.12-8.52). There were no significant differences in bone mineral density parameters at any site between patients and controls. In Addison's disease patients, there was a positive correlation between urinary cortisol and urinary calcium excretion. Patients with fractures had a longer history of disease than those without fractures. Patients taking fludrocortisone had a higher bone mineral density than untreated patients at all sites except the lumbar spine. Addison's disease patients have more fragile bones irrespective of any decrease in bone mineral density. Supra-physiological doses of glucocorticoids and longer-standing disease (with a consequently higher glucocorticoid intake) might be the main causes behind patients' increased bone fragility. Associated mineralocorticoid treatment seems to have a protective effect on bone mineral density.
Full Text Available Abstract Background Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from β-cell autoimmunity. Methods We investigated the role of the -2221Msp(C/T and -23HphI(A/T polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317, Addison's disease (AD, n = 107 or Hashimoto's thyroiditis (HT, n = 61], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62 as well as in healthy controls (HC, n = 275. Results T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T and "AA" -23HphI(A/T polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively. The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion We demonstrate that the allele "C" of the -2221Msp(C/T and "A" -23HphI(A/T insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II.
Ammini, A.C.; Gupta, R.; Mukopadhyay, C.; Shah, P.; Sandhu, M.S.; Vijayaraghavan, M.; Berry, M.
To study the morphology of the adrenal glands of patients with Addison's disease an ultrasound and a computed tomographic scan of the adrenal glands were performed in 28 patients. Thirteen patients had bilateral, asymmetric adrenal enlargement. In six of these patients, areas of necrosis and calcification were also seen. Six patients had atrophic glands with calcification and nine patients had normal/atrophic glands without calcification. After instituting appropriate treatment, computed tomography (CT) was repeated between 6 months and 3 years later in 10 of the 13 patients with adrenal enlargement. A reduction in gland size was noted in all patients and one had functional recovery. It is concluded that the appearance of the adrenal glands on CT depends not only on the nature of the underlying disease but also on the duration of the illness and the type of treatment. The results highlighted the importance of studying adrenal morphology during the initial evaluation of patients with adrenal insufficiency. 11 refs., 4 tabs., 4 figs
Gagliardi, Lucia; Nenke, Marni A; Thynne, Tilenka R J; von der Borch, Jenny; Rankin, Wayne A; Henley, David E; Sorbello, Jane; Inder, Warrick J; Torpy, David J
Patients with Addison's disease (AD) report impaired subjective health status (SHS). Since cortisol exhibits a robust circadian cycle that entrains other biological clocks, impaired SHS may be due to the noncircadian cortisol profile achieved with conventional glucocorticoid replacement. Continuous subcutaneous hydrocortisone infusion (CSHI) reproduces a circadian cortisol profile, but its effects on SHS have not been objectively evaluated. The aim of this study was to determine the effect of CSHI on SHS in AD. This was a multicentre, double-blind, placebo-controlled trial of CSHI vs oral glucocorticoid therapy. Participants received in random order 4 weeks of: CSHI and oral placebo, and subcutaneous placebo and oral hydrocortisone, separated by a 2-week washout period. SHS was assessed using the Short-Form 36 (SF-36), General Health Questionnaire (GHQ-28), Fatigue Scale (FS), Gastrointestinal Symptom Rating Scale (GSRS); and Addison's Quality of Life Questionnaire (AddiQoL). Participants were asked their (blinded) treatment preference. Twenty-four hour urine free cortisol (UFC) and diurnal salivary cortisol collections compared cortisol exposure during each treatment. Ten participants completed the study. Baseline SHS scores (mean ± SE) were consistent with mild impairment: SF-36 physical component summary 48.4 (± 2.4), mental component summary 53.3 (± 3.0); GHQ-28 18.1 (± 3.3); GSRS 3.7 (± 1.6), and AddiQoL 94.7 (± 3.7). FS was similar to other AD cohorts 13.5 (± 1.0) (P = 0.82). UFC between treatments was not different (P = 0.87). The salivary cortisol at 0800 h was higher during CSHI (P = 0.03), but not at any other time points measured. There was no difference between the treatments in the SHS assessments. Five participants preferred CSHI, four oral hydrocortisone, and one was uncertain. Biochemical measurements indicate similar cortisol exposure during each treatment period, although a more circadian pattern was evident during CSHI. CSHI does not
Petersen, Kristina S; Rushworth, R Louise; Clifton, Peter M; Torpy, David J
Addison's disease, or primary adrenal insufficiency, is often associated with reduced well-being and fatigue despite use of currently recommended adrenal hormone replacement. Hypoglycaemia is a known manifestation of glucocorticoid deficiency, but is generally considered rare in adults and not relevant to troubling ongoing symptoms in patients with Addison's disease. A 43 year old woman with a three year history of Addison's disease complained of severe morning fatigue and headaches, despite standard glucocorticoid replacement therapy in the form of thrice daily hydrocortisone and mineralocorticoid replacement with fludrocortisone. Alternative glucocorticoid replacement regimens and the addition of dehydroepiandrosterone replacement therapy had no effect. Nocturnal hypoglycaemia was suspected and a 4-day continuous glucose monitor system (CGMS) revealed hypoglycaemia (interstitial glucose < 2.2 mmol/L) between 0200-0400 h on 3 of 4 days. The patient was counselled to take an evening snack designed to ensure slow absorption of ingested carbohydrates. Nocturnal hypoglycaemia was then absent on follow up CGMS assessment. The patient noted a marked symptomatic improvement in morning symptoms, but with persistent fatigue during the day. Currently, the best strategy for control of non-specific symptoms in treated Addison's disease is unknown, but it may be that investigation for hypoglycaemia and treatment, where necessary, could assist some sufferers to achieve improved wellbeing. A systematic study of this phenomenon in Addison's disease is required.
Full Text Available Abstract Background Addison's disease (AD is caused by an autoimmune destruction of the adrenal cortex. The pathogenesis is multi-factorial, involving genetic components and hitherto unknown environmental factors. The aim of the present study was to investigate if gene dosage in the form of copy number variation (CNV could add to the repertoire of genetic susceptibility to autoimmune AD. Methods A genome-wide study using the Affymetrix GeneChip® Genome-Wide Human SNP Array 6.0 was conducted in 26 patients with AD. CNVs in selected genes were further investigated in a larger material of patients with autoimmune AD (n = 352 and healthy controls (n = 353 by duplex Taqman real-time polymerase chain reaction assays. Results We found that low copy number of UGT2B28 was significantly more frequent in AD patients compared to controls; conversely high copy number of ADAM3A was associated with AD. Conclusions We have identified two novel CNV associations to ADAM3A and UGT2B28 in AD. The mechanism by which this susceptibility is conferred is at present unclear, but may involve steroid inactivation (UGT2B28 and T cell maturation (ADAM3A. Characterization of these proteins may unravel novel information on the pathogenesis of autoimmunity.
Background Addison's disease (AD) is caused by an autoimmune destruction of the adrenal cortex. The pathogenesis is multi-factorial, involving genetic components and hitherto unknown environmental factors. The aim of the present study was to investigate if gene dosage in the form of copy number variation (CNV) could add to the repertoire of genetic susceptibility to autoimmune AD. Methods A genome-wide study using the Affymetrix GeneChip® Genome-Wide Human SNP Array 6.0 was conducted in 26 patients with AD. CNVs in selected genes were further investigated in a larger material of patients with autoimmune AD (n = 352) and healthy controls (n = 353) by duplex Taqman real-time polymerase chain reaction assays. Results We found that low copy number of UGT2B28 was significantly more frequent in AD patients compared to controls; conversely high copy number of ADAM3A was associated with AD. Conclusions We have identified two novel CNV associations to ADAM3A and UGT2B28 in AD. The mechanism by which this susceptibility is conferred is at present unclear, but may involve steroid inactivation (UGT2B28) and T cell maturation (ADAM3A). Characterization of these proteins may unravel novel information on the pathogenesis of autoimmunity. PMID:21851588
Napier, C; Mitchell, A L; Gan, E; Wilson, I; Pearce, S H S
Autoimmune endocrinopathies demonstrate a profound gender bias, but the reasons for this remain obscure. The 1000 genes on the X chromosome are likely to be implicated in this inherent susceptibility; various theories, including skewed X chromosome inactivation and fetal microchimerism, have been proposed. GPR174 is an Xq21 putative purinergic receptor that is widely expressed in lymphoid tissues. A single-nucleotide polymorphism, rs3827440, encoding Ser162Pro, has recently been associated with Graves' disease in Chinese and Polish populations, suggesting a role of this X chromosome gene in autoimmune disease. We investigated the role of rs3827440 in a UK cohort of patients with autoimmune Addison's disease (AAD). Samples from 286 AAD cases and 288 healthy controls were genotyped using TaqMan single-nucleotide polymorphism genotyping assays (C_25954273_10) on the Applied Biosystems 7900HT Fast real-time PCR system. Using a dominant (present/absent) model, the serine-encoding T allele of rs3827440 was present in 189 of 286 AAD patients (66%) compared with 132 of 288 unaffected controls (46%) [P = .010, odds ratio 1.80 (5%-95% confidence interval 1.22-2.67)]. An allele dosage model found a significant excess of the T allele in AAD patients compared with controls [P = .03, odds ratio 1.34 (5%-95% confidence interval 1.07-1.67)]. We have demonstrated a significant association of this X chromosome-encoded immunoreceptor with AAD for the first time. This X-linked gene could have a more generalized role in autoimmunity pathogenesis: G protein-coupled receptors are promising drugable targets, and further work to elucidate the functional role of GPR174 is now warranted.
Chantzichristos, Dimitrios; Persson, Anders; Eliasson, Björn; Miftaraj, Mervete; Franzén, Stefan; Bergthorsdottir, Ragnhildur; Gudbjörnsdottir, Soffia; Svensson, Ann-Marie; Johannsson, Gudmundur
Our hypothesis was that patients with diabetes mellitus obtain an additional risk of death if they develop Addison's disease (AD). Nationwide, matched, observational cohort study cross-referencing the Swedish National Diabetes Register with Inpatient, Cancer and Cause of Death Registers in patients with diabetes (type 1 and 2) and AD and matched controls with diabetes. Clinical characteristics at baseline, overall, and cause-specific mortality were assessed. The relative risk of death was assessed using a Cox proportional hazards regression model. Between January 1996 and December 2012, 226 patients with diabetes and AD were identified and matched with 1129 controls with diabetes. Median (interquartile range) follow-up was 5.9 (2.7-8.6) years. When patients with diabetes were diagnosed with AD, they had an increased frequency of diabetes complications, but both medical history of cancer and coronary heart disease did not differ compared with controls. Sixty-four of the 226 patients with diabetes and AD (28%) died, while 112 of the 1129 controls (10%) died. The estimated relative risk increase (hazard ratio) in overall mortality in the diabetes and AD group was 3.89 (95% confidence interval 2.84-5.32) compared with controls with diabetes. The most common cause of death was cardiovascular in both groups, but patients with diabetes and AD showed an increased death rate from diabetes complications, infectious diseases and unknown causes. Patients with the rare combination of diabetes and AD showed a markedly increased mortality and died more frequently from infections and unknown causes than patients with diabetes alone. Improved strategy for the management of this combination of metabolic disorders is needed. © 2017 European Society of Endocrinology.
Anna L Mitchell
Full Text Available Autoimmune Addison's disease (AAD is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered.DNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18, on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls. The data were analysed using a meta-analysis approach.In a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7. A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene.This linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis.
Meyer, Gesine; Koch, Maike; Herrmann, Eva; Bojunga, Jörg; Badenhoop, Klaus
Several studies have shown a reduced quality of life (QoL) in patients with Addison's disease (AD), but investigations of QoL over a long-term course are lacking. Adrenal crises (AC) are life-threatening complications in AD. The purpose of this prospective study was to test whether the repeated use of QoL-questionnaires can detect prodromal periods of an AC. 110 patients with AD were asked to complete the disease specific-QoL questionnaire AddiQoL and a short questionnaire about adverse events once monthly over a period of ten months. AC was defined if at least two of the following symptoms were reported: (a) hypotension, (b) nausea or vomiting, (c) severe fatigue, (d) documented hyponatremia, hyperkalemia, or hypoglycemia, and subsequent parenteral glucocorticoid administration was carried out. Prevalence of AC was 10.9/100 patient years. AddiQoL scores in patients with AC showed a trend (p = 0,08) to a wider fluctuation over time. Subjective precrises not meeting the criteria for AC were reported by 31 patients who had significantly lower AddiQoL scores (p = 0,018). These are the first data showing the course of QoL during a period of ten months in patients with AD. Incidence of AC exceeds previous data. Our data show, that subjective precrises in AD associate with lower QoL. AC, as well as precrises affect intraindividual AddiQol-scores over time with a trend to a stronger fluctuation. Longitudinal AddiQol scores and self-reporting of precrises via patient diaries are additional clinical tools to identify higher risk for critical events.
Pazderska, Agnieszka; Fichna, Marta; Mitchell, Anna L; Napier, Catherine M; Gan, Earn; Ruchała, Marek; Santibanez-Koref, Mauro; Pearce, Simon H
The pathogenesis of autoimmune Addison's disease (AAD) is thought to be due to interplay of genetic, immune, and environmental factors. A month-of-birth effect, with increased risk for those born in autumn/winter months, has been described in autoimmune conditions such as type 1 diabetes and autoimmune thyroid disease. Month-of-birth effect was investigated in 2 independent cohorts of AAD subjects. The monthly distribution of birth in AAD patients was compared with that of the general population using the cosinor test. A total of 415 AAD subjects from the United Kingdom cohort were compared with 8 180 180 United Kingdom births, and 231 AAD subjects from the Polish cohort were compared with 2 421 384 Polish births. Association between month of birth and the susceptibility to AAD. In the entire cohort of AAD subjects, month-of-birth distribution analysis showed significant periodicity with peak of births in December and trough in May (P = .028). Analysis of the odds ratio distribution based on month of birth in 2 cohorts of patients with AAD versus the general population revealed a December peak and May trough, and January peak and July trough, in the United Kingdom and Polish cohorts, respectively. For the first time, we demonstrate that month of birth exerts an effect on the risk of developing AAD, with excess risk in individuals born in winter months and a protective effect when born in the summer. Exposure to seasonal viral infections in the perinatal period, coupled with vitamin D deficiency, could lead to dysregulation of innate immunity affecting the risk of developing AAD.
Mitchell, Anna L; Bøe Wolff, Anette; MacArthur, Katie; Weaver, Jolanta U; Vaidya, Bijay; Erichsen, Martina M; Darlay, Rebecca; Husebye, Eystein S; Cordell, Heather J; Pearce, Simon H S
Autoimmune Addison's disease (AAD) is a rare, highly heritable autoimmune endocrinopathy. It is possible that there may be some highly penetrant variants which confer disease susceptibility that have yet to be discovered. DNA samples from 23 multiplex AAD pedigrees from the UK and Norway (50 cases, 67 controls) were genotyped on the Affymetrix SNP 6.0 array. Linkage analysis was performed using Merlin. EMMAX was used to carry out a genome-wide association analysis comparing the familial AAD cases to 2706 UK WTCCC controls. To explore some of the linkage findings further, a replication study was performed by genotyping 64 SNPs in two of the four linked regions (chromosomes 7 and 18), on the Sequenom iPlex platform in three European AAD case-control cohorts (1097 cases, 1117 controls). The data were analysed using a meta-analysis approach. In a parametric analysis, applying a rare dominant model, loci on chromosomes 7, 9 and 18 had LOD scores >2.8. In a non-parametric analysis, a locus corresponding to the HLA region on chromosome 6, known to be associated with AAD, had a LOD score >3.0. In the genome-wide association analysis, a SNP cluster on chromosome 2 and a pair of SNPs on chromosome 6 were associated with AAD (P <5x10-7). A meta-analysis of the replication study data demonstrated that three chromosome 18 SNPs were associated with AAD, including a non-synonymous variant in the NFATC1 gene. This linkage study has implicated a number of novel chromosomal regions in the pathogenesis of AAD in multiplex AAD families and adds further support to the role of HLA in AAD. The genome-wide association analysis has also identified a region of interest on chromosome 2. A replication study has demonstrated that the NFATC1 gene is worthy of future investigation, however each of the regions identified require further, systematic analysis.
Edvardsen, Kine; Hellesen, Alexander; Husebye, Eystein S; Bratland, Eirik
Autoimmune Addison's disease (AAD) is caused by multiple genetic and environmental factors. Variants of genes encoding immunologically important proteins such as the HLA molecules are strongly associated with AAD, but any environmental risk factors have yet to be defined. We hypothesized that primary or reactivating infections with cytomegalovirus (CMV) could represent an environmental risk factor in AAD, and that CMV specific CD8(+) T cell responses may be dysregulated, possibly leading to a suboptimal control of CMV. In particular, the objective was to assess the HLA-B8 restricted CD8(+) T cell response to CMV since this HLA class I variant is a genetic risk factor for AAD. To examine the CD8(+) T cell response in detail, we analyzed the HLA-A2 and HLA-B8 restricted responses in AAD patients and healthy controls seropositive for CMV antibodies using HLA multimer technology, IFN-γ ELISpot and a CD107a based degranulation assay. No differences between patients and controls were found in functions or frequencies of CMV-specific T cells, regardless if the analyses were performed ex vivo or after in vitro stimulation and expansion. However, individual patients showed signs of reactivating CMV infection correlating with poor CD8(+) T cell responses to the virus, and a concomitant upregulation of interferon regulated genes in peripheral blood cells. Several recently diagnosed AAD patients also showed serological signs of ongoing primary CMV infection. CMV infection does not appear to be a major environmental risk factor in AAD, but may represent a precipitating factor in individual patients.
Brozzetti, Annalisa; Alimohammadi, Mohammad; Morelli, Silvia; Minarelli, Viviana; Hallgren, Åsa; Giordano, Roberta; De Bellis, Annamaria; Perniola, Roberto; Kämpe, Olle; Falorni, Alberto
NACHT leucine-rich-repeat protein 5 (NALP5)/maternal antigen that embryo requires (MATER) is an autoantigen in hypoparathyroidism associated with autoimmune polyendocrine syndrome type 1 (APS1) but is also expressed in the ovary. Mater is an autoantigen in experimental autoimmune oophoritis. The objectives of the study were to determine the frequency of NALP5/MATER autoantibodies (NALP5/MATER-Ab) in women with premature ovarian insufficiency (POI) and in patients with autoimmune Addison's disease (AAD) and to evaluate whether inhibin chains are a target for autoantibodies in POI. Autoantibodies against NALP5/MATER and inhibin chains-α and -βA were determined by radiobinding assays in 172 patients with AAD without clinical signs of gonadal insufficiency, 41 women with both AAD and autoimmune POI [steroidogenic cell autoimmune POI (SCA-POI)], 119 women with idiopathic POI, 19 patients with APS1, and 211 healthy control subjects. NALP5/MATER-Ab were detected in 11 of 19 (58%) sera from APS1 patients, 12 of 172 (7%) AAD sera, 5 of 41 (12%) SCA-POI sera, 0 of 119 idiopathic POI sera and 1 of 211 healthy control sera (P < .001). None of 160 POI sera, including 41 sera from women with SCA-POI and 119 women with idiopathic POI, and none of 211 healthy control sera were positive for inhibin chain-α/βA autoantibodies. NALP5/MATER-Ab are associated with hypoparathyroidism in APS1 but are present also in patients with AAD and in women with SCA-POI without hypoparathyroidism. Inhibin chains do not appear to be likely candidate targets of autoantibodies in human POI.
Saevik, Å B; Åkerman, A-K; Grønning, K; Nermoen, I; Valland, S F; Finnes, T E; Isaksson, M; Dahlqvist, P; Bergthorsdottir, R; Ekwall, O; Skov, J; Nedrebø, B G; Hulting, A-L; Wahlberg, J; Svartberg, J; Höybye, C; Bleskestad, I H; Jørgensen, A P; Kämpe, O; Øksnes, M; Bensing, S; Husebye, E S
Early detection of autoimmune Addison's disease (AAD) is important as delay in diagnosis may result in a life-threatening adrenal crisis and death. The classical clinical picture of untreated AAD is well-described, but methodical investigations are scarce. Perform a retrospective audit of patient records with the aim of identifying biochemical markers for early diagnosis of AAD. A multicentre retrospective study including 272 patients diagnosed with AAD at hospitals in Norway and Sweden during 1978-2016. Scrutiny of medical records provided patient data and laboratory values. Low sodium occurred in 207 of 247 (84%), but only one-third had elevated potassium. Other common nonendocrine tests were largely normal. TSH was elevated in 79 of 153 patients, and hypoglycaemia was found in 10%. Thirty-three per cent were diagnosed subsequent to adrenal crisis, in whom electrolyte disturbances were significantly more pronounced (P < 0.001). Serum cortisol was consistently decreased (median 62 nmol L -1 [1-668]) and significantly lower in individuals with adrenal crisis (38 nmol L -1 [2-442]) than in those without (81 nmol L -1 [1-668], P < 0.001). The most consistent biochemical finding of untreated AAD was low sodium independent of the degree of glucocorticoid deficiency. Half of the patients had elevated TSH levels. Only a minority presented with marked hyperkalaemia or other nonhormonal abnormalities. Thus, unexplained low sodium and/or elevated TSH should prompt consideration of an undiagnosed AAD, and on clinical suspicion bring about assay of cortisol and ACTH. Presence of 21-hydroxylase autoantibodies confirms autoimmune aetiology. Anticipating additional abnormalities in routine blood tests may delay diagnosis. © 2017 The Association for the Publication of the Journal of Internal Medicine.
Henry, Michelle; Ross, Ian Louis; Wolf, Pedro Sofio Abril; Thomas, Kevin Garth Flusk
Standard replacement therapy for Addison's disease (AD) does not restore a normal circadian rhythm. Periods of sub- and supra- physiological cortisol levels experienced by patients with AD likely induce disrupted sleep. Given that healthy sleep plays an important role in memory consolidation, the novelty of the current study was to characterise, using objective measures, the relationship between sleep and memory in patients with AD, and to examine the hypothesis that poor sleep is a biological mechanism underlying memory impairment in those patients. We used a within-subjects design. Ten patients with AD and 10 matched healthy controls completed standardised neuropsychological tests assessing declarative memory (Rey Auditory Verbal Learning Test) and procedural memory (Finger Tapping Task) before and after a period of actigraphy-measured sleep, and before and after a period of waking. Relative to healthy controls, patients with AD experienced disrupted sleep characterised by poorer sleep efficiency and more time spent awake. Patients also showed impaired verbal learning and memory relative to healthy controls (p=0.007). Furthermore, whereas healthy controls' declarative memory performance benefited from a period of sleep compared to waking (p=0.032), patients with AD derived no such benefit from sleep (p=0.448). Regarding the procedural memory task, analyses detected no significant between-group differences (all p's<0.065), and neither group showed significant sleep-enhanced performance. We demonstrated, using actigraphy and standardized measures of memory performance, an association between sleep disturbances and cognitive deficits in patients with AD. These results suggest that, in patients with AD, the source of memory deficits is, at least to some extent, disrupted sleep patterns that interfere with optimal consolidation of previously-learned declarative information. Hence, treating the sleep disturbances that are frequently experienced by patients with AD may
Gan, Earn H; MacArthur, Katie; Mitchell, Anna L; Pearce, Simon H S
Background Autoimmune Addison's disease (AAD) is a rare condition with a complex genetic basis. A panel of rare and functionally defective genetic variants in the sialic acid acetylesterase (SIAE) gene has recently been implicated in several common autoimmune conditions. We performed a case–control study to determine whether these rare variants are associated with a rarer condition, AAD. Method We analysed nine SIAE gene variants (W48X, M89V, C196F, C226G, R230W, T312M, Y349C, F404S and R479C) in a United Kingdom cohort of 378 AAD subjects and 387 healthy controls. All samples were genotyped using Sequenom iPlex chemistry to characterise primer extension products. Results A heterozygous rare allele at codon 312 (312*M) was found in one AAD patient (0.13%) but was not detected in the healthy controls. The commoner, functionally recessive variant at codon 89 (89*V) was found to be homozygous in two AAD patients but was only found in the heterozygous state in controls. Taking into account all nine alleles examined, 4/378 (1.06%) AAD patients and 1/387 (0.25%) healthy controls carried the defective SIAE alleles, with a calculated odds ratio of 4.13 (95% CI 0.44–97.45, two-tailed P value 0.212, NS). Conclusion We demonstrated the presence of 89*V homozygotes and the 312*M rare allele in the AAD cohort, but overall, our analysis does not support a role for rare variants in SIAE in the pathogenesis of AAD. However, the relatively small collection of AAD patients limits the power to exclude a small effect. PMID:23011869
Dalla Costa, M; Bonanni, G; Masiero, S; Faggian, D; Chen, S; Furmaniak, J; Rees Smith, B; Perniola, R; Radetti, G; Garelli, S; Chiarelli, S; Albergoni, M P; Plebani, M; Betterle, C
Steroidogenic enzyme autoantibodies (SEAbs) are frequently present and are markers of autoimmune premature ovarian failure (POF) in females with autoimmune Addison's disease (AAD). The prevalence and significance of SEAbs in males with AAD have not yet been defined. We studied the prevalence of SEAbs in a large cohort of males with AAD and assessed the relationship between SEAbs positivity and testicular function. A total of 154 males with AAD (mean age 34 years) were studied. SEAbs included autoantibodies to steroid-producing cells (StCA), detected by immunofluorescence, and steroid 17α-hydroxylase (17α-OHAbs) and side chain cleavage enzyme (SCCAbs) measured by immunoprecipitation assays. Gonadal function was evaluated by measuring follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), sex hormone-binding globulin (SHGB), anti-müllerian hormone (AMH) and inhibin-B (I-B). Twenty-six males, 10 SEAbs((+)) and 16 SEAbs((-)), were followed-up for a mean period of 7·6 years to assess the behaviour of SEAbs and testicular function. SEAbs were found in 24·7% of males with AAD, with the highest frequency in patients with autoimmune polyendocrine syndrome type 1 (APS-1). The levels of reproductive hormones in 30 SEAbs((+)) males were in the normal range according to age and were not significantly different compared to 55 SEAbs((-)) males (P > 0·05). During follow-up, both SEAbs((+)) and SEAbs((-)) patients maintained normal testicular function. SEAbs were found with high frequency in males with AAD; however, they were not associated with testicular failure. This study suggests that the diagnostic value of SEAbs in males with AAD differs compared to females, and this may be related to the immunoprivileged status of the testis. © 2014 British Society for Immunology.
Full Text Available Abstract Background Three genes have been confirmed as major joint susceptibility genes for endocrine autoimmune disease:human leukocyte antigen class II, cytotoxic T-lymphocyte antigen 4 and protein tyrosine phosphatase non-receptor type 22. Recent studies showed that a genetic variation within the interferon induced helicase domain 1 (IFIH1 locus (rs1990760 polymorphism is an additional risk factor in type 1 diabetes and Graves' disease (GD. Methods The aim of the present study was to investigate the role of the rs1990760 polymorphism within the IFIH1 gene in German patients with GD (n = 258, Hashimoto's thyroiditis (HT, n = 106, Addison's disease (AD, n = 195 and healthy controls (HC, n = 227 as well as in 55 GD families (165 individuals, German and 100 HT families (300 individuals, Italian. Furthermore, the interaction between rs1990760 polymorphism with human leukocyte antigen (HLA risk haplotype DQ2(DQA*0501-DQB*0201, the risk haplotypes DQ2/DQ8 (DQA*0301-DQB*0302 and the status of thyroglobulin antibody (TgAb, thyroid peroxidase antibody (TPOAb and TSH receptor antibody (TRAb in patients and families were analysed. Results No significant differences were found between the allele and genotype frequencies for rs1990760 IFIH1 polymorphism in patients with GD, HT, AD and HC. Also no differences were observed when stratifying the IFIH1 rs1990760 polymorphism for gender, presence or absence of thyroid antibodies (GD:TRAb and HT:TPOAb/TgAb and HLA risk haplotypes (DQ2:for GD and HT, DQ2/DQ8:for AD. Furthermore the transmission analysis in GD and HT families revealed no differences in alleles transmission for rs1990760 IFIH1 from parents with or without HLA risk haplotype DQ2 to the affected offspring. In contrast, by dividing the HT parents according to the presence or absence of thyroid Ab titers, mothers and fathers both positive for TPOAb/TgAb overtransmitted the allele A of IFIH1 rs1990760 to their HT affected offspring (61.8% vs 38.2%;p = 0
Anna L Mitchell
Full Text Available Gene variants known to contribute to Autoimmune Addison's disease (AAD susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for.To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts.A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls. In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls. In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity.We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P = 0.00016; rs10931481: P = 0.0007. In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-κB1 and IL23A genes in the UK and Italian cohorts respectively.Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.
Bergthorsdottir, Ragnhildur; Ragnarsson, Oskar; Skrtic, Stanko; Glad, Camilla A M; Nilsson, Staffan; Ross, Ian Louis; Leonsson-Zachrisson, Maria; Johannsson, Gudmundur
Patients with Addison's disease (AD) have increased cardiovascular mortality. To study visceral fat and conventional and exploratory cardiovascular risk factors in patients with AD. A cross-sectional, single-center, case-control study. Patients (n = 76; n = 51 women) with AD and 76 healthy control subjects were matched for sex, age, body mass index (BMI), and smoking habits. The primary outcome variable was visceral abdominal adipose tissue (VAT) measured using computed tomography. Secondary outcome variables were prevalence of metabolic syndrome (MetS) and 92 biomarkers of cardiovascular disease. The mean ± standard deviation age of all subjects was 53 ± 14 years; mean BMI, 25 ± 4 kg/m2; and mean duration of AD, 17 ± 12 years. The median (range) daily hydrocortisone dose was 30 mg (10 to 50 mg). Median (interquartile range) 24-hour urinary free cortisol excretion was increased in patients vs controls [359 nmol (193 to 601 nmol) vs 175 nmol (140 to 244 nmol); P 1] and vasodilatory protective marker was decreased (FC, <1). Twenty-six patients (34%) vs 12 control subjects (16%) fulfilled the criteria for MetS (P = 0.01). Despite higher cortisol exposure, VAT was not increased in patients with AD. The prevalence of MetS was increased and several biomarkers of cardiovascular disease were adversely affected in patients with AD. Copyright © 2017 Endocrine Society
Methlie, Paal; Hustad, Steinar; Kellman, Ralf; Almås, Bjørg; Erichsen, Martina M; Husebye, Eystein S; Løvås, Kristian
Objective Liquid chromatography–tandem mass spectrometry (LC–MS/MS) offers superior analytical specificity compared with immunoassays, but it is not available in many regions and hospitals due to expensive instrumentation and tedious sample preparation. Thus, we developed an automated, high-throughput LC–MS/MS assay for simultaneous quantification of ten endogenous and synthetic steroids targeting diseases of the hypothalamic–pituitary–adrenal axis and gonads. Methods Deuterated internal standards were added to 85 μl serum and processed by liquid–liquid extraction. Cortisol, cortisone, prednisolone, prednisone, 11-deoxycortisol, dexamethasone, testosterone, androstenedione and progesterone were resolved by ultra-high-pressure chromatography on a reversed-phase column in 6.1 min and detected by triple-quadrupole mass spectrometry. The method was used to assess steroid profiles in women with Addison's disease (AD, n=156) and blood donors (BDs, n=102). Results Precisions ranged from 4.5 to 10.1% relative standard deviations (RSD), accuracies from 95 to 108% and extraction recoveries from 60 to 84%. The method was practically free of matrix effects and robust to individual differences in serum composition. Most postmenopausal AD women had extremely low androstenedione concentrations, below 0.14 nmol/l, and median testosterone concentrations of 0.15 nmol/l (interquartile range 0.00–0.41), considerably lower than those of postmenopausal BDs (1.28 nmol/l (0.96–1.64) and 0.65 nmol/l (0.56–1.10) respectively). AD women in fertile years had androstenedione concentrations of 1.18 nmol/l (0.71–1.76) and testosterone concentrations of 0.44 nmol/l (0.22–0.63), approximately half of those found in BDs of corresponding age. Conclusion This LC–MS/MS assay provides highly sensitive and specific assessments of glucocorticoids and androgens with low sample volumes and is suitable for endocrine laboratories and research. Its utility has been
White, Katherine; Arlt, Wiebke
Adrenal crisis is a life-threatening event that occurs regularly in Addison's patients receiving standard replacement therapy. Patient reports suggest that it is an underestimated and under-managed event. To assess the frequency of adrenal crisis in diagnosed patients and to understand the factors contributing to the risks of adrenal crisis. We conducted a postal survey of Addison's patients in four countries, UK (n=485), Canada (n=148), Australia (n=123) and New Zealand (n=85) in 2003, asking about patients' experiences of adrenal crisis and their demographic characteristics. In 2006, a shorter follow-up survey was conducted in the UK (n=261). The frequency and causes of adrenal crisis were compared across both surveys. Demographic data from the 2003 survey were analysed to establish the main variables associated with an elevated risk of crisis. Around 8% of diagnosed cases can be expected to need hospital treatment for adrenal crisis annually. Exposure to gastric infection is the single most important factor predicting the likelihood of adrenal crisis. Concomitant diabetes and/or asthma increase the frequency of adrenal crises reported by patients. The endocrinologist has a responsibility to ensure that Addison's patients have adequate access to life-saving emergency injection materials and repeated, practical training sessions in how to use them, while the general practitioner plays a vital role as in arranging prompt emergency admissions.
De Bellis, Annamaria; Bellastella, Giuseppe; Falorni, Alberto; Aitella, Ernesto; Barrasso, Mariluce; Maiorino, Maria Ida; Bizzarro, Elio; Bellastella, Antonio; Giugliano, Dario; Esposito, Katherine
Women with autoimmune Addison's disease with normal ovulatory cycles but positive for steroid cell antibodies (StCA) have been considered at risk of premature ovarian insufficiency (POI). Thirty-three women younger than 40 years, with subclinical-clinical autoimmune Addison's disease but with normally ovulatory menses, were followed up for 10 years to evaluate the long-term time-related variations of StCA, ovarian function and follicular reserve. All patients and 27 control women were investigated at the start and every year for the presence and titre of StCA (by indirect immunofluorescence), serum concentrations of anti-Mullerian hormone (AMH) and ovarian function at four consecutive menses every year. At the start of the study StCA were present in 16 women (group 1), at low/middle titres (≤1:32) in seven of them (43.8%, group 1A), at high titres (>1:32) in the remaining nine patients (group 1B, 56.2%), while they were absent from 17 patients (group 2). During the follow-up period, all women in group 1A remained StCA-positive at low/middle titres with normal ovulatory menses and normal gonadotrophin and AMH levels, while all patients in group 1B showed a further increase of StCA titres (1:128-1:256) and progressed through three stages of ovarian function. None of the patients in group 2 and controls showed the appearance of StCA or ovarian dysfunction during the follow-up. The presence of StCA at high titres can be considered a good predictive marker of subsequent development of autoimmune POI. To single out the stages of autoimmune POI may allow a timely therapeutic choice in the subclinical and early clinical stages. © 2017 European Society of Endocrinology.
Heald, Adrian H; Walther, Andreas; Davis, Julian R E; Moreno, Gabriela Y C; Kane, John; Livingston, Mark; Fowler, Helen L
Patients with Addison's disease have relatively high rates of depression and anxiety symptoms compared with population-based reference samples. Addison's disease results in deficiency of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S). There is considerable debate about the specific effects of DHEA deficiency on energy level and mood. We measured emotional well-being in 16 patients with Addison's disease and a group of 16 hospital attendees with type 2 diabetes. Participants completed the General Health Questionnaire-28 (GHQ-28), the Hospital Anxiety and Depression Scale (HADS), the World Health Organization's quality of life assessment (WHOQOL-BREF) and the Holmes-Rahe life event scale. DHEA-S was low in Addison's patients (Addison's men: 0.5 ± 0.1 μmol/l [normal range: 2.1-10.8] compared with diabetes men: 3.2 ± 1.2 μmol/l; Addison's women: 0.4 ± 0.01 μmol/l [normal range: 1.0-11.5] compared with diabetes women: 2.2 ± 0.71 μmol/l). Testosterone levels were similar in both groups studied. There were no differences in emotional well-being and quality of life (QOL) between patients with Addison's disease and Type 2 Diabetes Mellitus as measured by GHQ-28 (Addison's: 22.4 ± 2.6, Diabetes: 19.6 ± 2.7), HADS Depression (Addison's: 5.4 ± 0.9, Diabetes: 4.5 ± 1.4), HADS Anxiety and WHOQOL-BREF. There were no gender differences in affective symptomatology within the Addison's group. Life event scores were above average in both groups (Addison's: 195 ± 39.6, Diabetes: 131 ± 43.8), but not significant for difference between groups as was GHQ-28 total score. Both groups scored highly on the GHQ-28 and the life event scale, indicative of poorer health perceptions than the general population. This could be due to the chronicity of both disorders. We have not identified any specific effects of DHEA-S deficiency on mood or QOL.
Giordano, Roberta; Marzotti, Stefania; Berardelli, Rita; Karamouzis, Ioannis; Brozzetti, Annalisa; D'Angelo, Valentina; Mengozzi, Giulio; Mandrile, Giorgia; Giachino, Daniela; Migliaretti, Giuseppe; Bini, Vittorio; Falorni, Alberto; Ghigo, Ezio; Arvat, Emanuela
Although glucocorticoids are essential for health, several studies have shown that glucocorticoids replacement in Addison's disease might be involved in anthropometric and metabolic impairment, with increased cardiovascular risk, namely if conventional doses are used. As the effects of glucocorticoids are mediated by the glucocorticoid receptor, encoded by NR3C1 gene, different polymorphisms in the NR3C1 gene have been linked to altered glucocorticoid sensitivity in general population as well as in patients with obesity or metabolic syndrome. We investigated the impact of glucocorticoid receptor gene polymorphisms, including the BclI, N363S and ER22/23EK variants, on anthropometric parameters (BMI and waist circumference), metabolic profile (HOMA, OGTT and serum lipids) and ACTH levels in 50 patients with Addison's disease (34 women and 16 men, age 20-82 year) under glucocorticoids replacement. Neither N363S nor ER22/23EK variants were significantly associated with anthropometric, metabolic or hormonal parameters, while patients carrying the homozygous BclI polymorphism GG (n = 4) showed higher (P Addison's disease and may contribute, along with other factors, to the increase in central adiposity, impaired glucose metabolism and dyslipidaemia. © 2012 Blackwell Publishing Ltd.
De Nardo Pasquale
Full Text Available Abstract Introduction Prosthetic joint infection due to Mycobacterium tuberculosis is occasionally encountered in clinical practice. To the best of our knowledge, this is the first report of a prosthetic joint infection due to Mycobacterium tuberculosis complicated by psoas abscesses and secondary Addison disease. Case presentation A 67-year-old immunocompetent Caucasian woman underwent total left hip arthroplasty because of osteoarthritis. After 18 months, she underwent arthroplasty revision for a possible prosthetic infection. Periprosthetic tissue specimens for bacteria were negative, and empirical antibiotic therapy was unsuccessful. She was then admitted to our department because of complications arising 22 months after arthroplasty. A physical examination revealed a sinus tract overlying her left hip and skin and mucosal pigmentation. Her levels of C-reactive protein, basal cortisol, adrenocorticotropic hormone, and sodium were out of normal range. Results of the tuberculin skin test and QuantiFERON-TB Gold test were positive. Computed tomography revealed a periprosthetic abscess and the inclusion of the left psoas muscle. Results of microbiological tests were negative, but polymerase chain reaction of a specimen taken from the hip fistula was positive for Mycobacterium tuberculosis. Our patient's condition was diagnosed as prosthetic joint infection and muscle psoas abscess due to Mycobacterium tuberculosis and secondary Addison disease. She underwent standard treatment with rifampicin, ethambutol, isoniazid, and pyrazinamide associated with hydrocortisone and fludrocortisone. At 15 months from the beginning of therapy, she was in good clinical condition and free of symptoms. Conclusions Prosthetic joint infection with Mycobacterium tuberculosis is uncommon. A differential diagnosis of tuberculosis should be considered when dealing with prosthetic joint infection, especially when repeated smears and histology examination from infected
Henry, Michelle; Wolf, Pedro S A; Ross, Ian L; Thomas, Kevin G F
Standard replacement therapy for Addison's disease (AD) does not restore a normal circadian rhythm. In fact, hydrocortisone replacement in AD patients likely induces disrupted sleep. Given that healthy sleep plays an important role in improving quality of life, optimizing cognition, and ensuring affect regulation, the aim of this study was to investigate whether poor quality of life, mood alterations, and memory complaints reported by AD patients are associated with their disrupted sleep patterns. Sixty patients with AD and 60 matched healthy controls completed a battery of self-report questionnaires assessing perceived physical and mental health (Short-Form 36), mood (Beck Depression Inventory-II), sleep quality (Pittsburgh Sleep Quality Index), and cognition (Cognitive Failures Questionnaire). A latent variable model revealed that although AD had a significant direct effect on quality of life, the indirect effect of sleep was significantly greater. Furthermore, although AD had no direct effect on cognitive functioning, the indirect effect of sleep was significant. The overall model showed a good fit (comparative fit index = 0.91, root mean square of approximation = 0.09, and standardized root mean square residual = 0.05). Our findings suggest that disrupted sleep, and not the disease per se, may induce poor quality of life, memory impairment, and affect dysregulation in patients with AD. We think that improving sleep architecture may improve cognitive, affective, and physical functioning. Copyright © 2015 Elsevier Inc. All rights reserved.
Manso, Jacopo; Pezzani, Raffaele; Scarpa, Riccardo; Gallo, Nicoletta; Betterle, Corrado
Autoimmune Addison's disease (AAD) is the most frequent cause of adrenocortical insufficiency. The natural history of AAD usually comprises five consecutive stages with the first stage characterized by the increase of plasma renin consistent with the impairment of pars glomerulosa, which is usually the first affected layer of the adrenal cortex. We describe a 19-year-old female with Hashimoto's thyroiditis (HT) who underwent an autoantibody screening due to having the personal and family history of other autoimmune diseases in the absence of relevant clinical manifestations. She was positive for adrenal cortex autoantibodies (ACA) and steroid 21-hydroxylase autoantibodies (21-OH Ab) at high titers. She had increased basal levels of ACTH with normal basal cortisol not responding to ACTH stimulation, reduced levels of dehydroepiandrosterone-sulfate but normal levels of orthostatic renin and aldosterone. This scenario was consistent with a subclinical AAD presenting with first impairments in pars fasciculata and reticularis and conserved pars glomerulosa function. Only subsequently, progressive deficiency in pars glomerulosa function has become evident. Review of the literature showed that there was only one case, reported to date, with a similar atypical natural history of AAD. The strategies for screening for ACA/21-OH Ab in patients with HT are discussed.
Volpato, M; Prentice, L; Chen, S; Betterle, C; Rees Smith, B; Furmaniak, J
Steroid 21-hydroxylase (21-OH) autoantibodies are found in patients with autoimmune Addison's disease (AAD), either isolated or associated with autoimmune polyglandular syndrome (APS) type I and II and in adrenal-cortex autoantibody (ACA)-positive patients without AAD. In order to assess any differences in the 21-OH autoantibodies in these different patient groups, we have studied their reactivity with different epitopes on 21-OH using full length and modified 35S-labelled 21-OH proteins produced in an in vitro transcription/translation system. There were no major differences in the pattern of autoantibody reactivity with the different modified 21-OH proteins in patients with isolated AAD or with APS types I and II, and in 21-OH autoantibody-positive patients with clinical AAD, subclinical AAD and those maintaining a normal adrenal function. Our studies also indicate that the main epitopes for 21-OH autoantibodies in patients with different forms of autoimmune adrenal disease are located in the C-terminal end and in a central region of 21-OH. PMID:9486414
Hellesen, A; Edvardsen, K; Breivik, L; Husebye, E S; Bratland, E
Autoimmune Addison's disease (AAD) is caused by selective destruction of the hormone-producing cells of the adrenal cortex. As yet, little is known about the potential role played by environmental factors in this process. Type I and/or type III interferons (IFNs) are signature responses to virus infections, and have also been implicated in the pathogenesis of autoimmune endocrine disorders such as type 1 diabetes and autoimmune thyroiditis. Transient development of AAD and exacerbation of established or subclinical disease, as well as the induction of autoantibodies associated with AAD, have been reported following therapeutic administration of type I IFNs. We therefore hypothesize that exposure to such IFNs could render the adrenal cortex susceptible to autoimmune attack in genetically predisposed individuals. In this study, we investigated possible immunopathological effects of type I and type III IFNs on adrenocortical cells in relation to AAD. Both types I and III IFNs exerted significant cytotoxicity on NCI-H295R adrenocortical carcinoma cells and potentiated IFN-γ- and polyinosine-polycytidylic acid [poly (I : C)]-induced chemokine secretion. Furthermore, we observed increased expression of human leucocyte antigen (HLA) class I molecules and up-regulation of 21-hydroxylase, the primary antigenic target in AAD. We propose that these combined effects could serve to initiate or aggravate an ongoing autoimmune response against the adrenal cortex in AAD. © 2014 British Society for Immunology.
Ross, I L; Lacerda, M; Pillay, T S; Blom, D J; Johannsson, G; Dave, J A; Levitt, N S; Haarburger, D; van der Walt, J-S
Salivary cortisol has been used to monitor hydrocortisone replacement in patients with Addison's disease (AD). Since salivary cortisol is metabolised to salivary cortisone, it may be an adjunctive analyte to assess adequacy of hydrocortisone replacement in patients with AD. We aimed to characterise the exposure of salivary cortisol and cortisone in patients and healthy controls. We measured salivary cortisol and cortisone by liquid chromatography-tandem mass spectrometry and constructed a day curve (08:00 until 24:00 h) with 16 time points in 25 AD patients taking their usual hydrocortisone dose and in 26 healthy controls. The median (interquartile range) area under the curve (AUC) for cortisol was not different for patients, compared with controls [55.63 (32.91-151.07) nmol*min*l -1 vs. 37.49 (27.41-52.00) nmol*min*l -1 ; p=0.098, respectively], whereas the peak cortisol C max was higher in patients [32.61 (5.75-146.19) nmol/l vs. 8.96 (6.96-12.23) nmol/l; p=0.013], compared with controls. The AUC for cortisone [23.65 (6.10-54.76) nmol*min*l -1 vs. 227.73 (200.10-280.52) nmol*min*l -1 ; p≤ 0.001, respectively], and peak cortisone C max was lower in patients than in controls [11.11 (2.91-35.85) nmol/l vs. 33.12 (25.97-39.95) nmol/l; p=0.002]. The AUC for salivary cortisol and salivary cortisone were not correlated with any measures of hydrocortisone dose. The time-course and AUC of salivary cortisol were similar between Addison's patients and healthy controls. Patients had substantially lower salivary cortisone AUC, compared to healthy controls. Salivary cortisol AUC and pharmacokinetics were not related to hydrocortisone dose and thus are not likely useful markers for the adequacy of hydrocortisone replacement. © Georg Thieme Verlag KG Stuttgart · New York.
Ross, Ian; Boulle, Andrew; Soule, Steven; Levitt, Naomi; Pirie, Fraser; Karlsson, Anders; Mienie, Japie; Yang, Ping; Wang, Hongjie; She, Jin-Xiong; Winter, William; Schatz, Desmond
We sought to determine whether autoimmunity is the predominant cause of Addison's disease in South Africa and whether human leucocyte antigen (HLA) DQ association exists. We compiled a national registry of patients from primary care, referral centres and private practices. A total of 144 patients, 94 of European descent, 34 Mixed Ancestry, 5 Asian and 11 Black Africans (mean age 45.9 years, range 2.7-88 years; mean duration of disease 13.1 years, range 0-50 years) and controls were matched for gender and ethnicity. All potential causes were investigated. Fifty one per cent of cases (74 patients) were autoimmune in aetiology. Either 21-hydroxylase autoantibodies (72 patients, 50% of entire patient group) or adrenocortical autoantibodies (35 patients, 24%) were present, while 23% of patients had both. None of the Asian (n = 5) or Black (n = 11) patients had evidence of autoimmune disease. Overall 8% of patients had tuberculosis, 4% adrenoleucodystrophy, 1% adrenocorticotrophic hormone resistance syndrome and 6% X-linked adrenal hypoplasia. In those with autoimmune disease primary hypothyroidism (47%), premature ovarian failure (8%) and type 1 diabetes (7%) were the most prevalent accompanying autoimmune conditions. HLA DQB1*0201 alleles predominated in the autoimmune group (DQB1*0201: 65%vs 43% of controls P = 0.017) with the *0201/*0302 heterozygous genotype being the most prevalent (28%vs 8%P = 0.02). While autoimmunity accounts for at least half of patients with Addison's disease in South Africa and is associated with HLA DQB1*0201, none of the Black Africans or Asians in this cohort had adrenal autoantibodies. Moreover, 21-hydroxylase autoantibodies were detectable in a higher proportion than adrenocortical autoantibodies, especially in those patients with a long history after disease onset.
Daniels, Jo; Sheils, Elizabeth
Addison's disease (AD) is a rare chronic illness caused by adrenocortical insufficiency. Due to the pivotal role of the regulating hormone cortisol in AD, there is a common symptom overlap between the presentation of anxiety and adrenal crisis. Previous literature has identified the prevalence of anxiety in endocrinological disorders, however there is a paucity of research examining the complex interplay between AD and anxiety. This paper describes a single case study of a patient with severe health anxiety and co-morbid AD. The aims of the study were to establish if standard cognitive behavioural therapy for health anxiety in AD can lead to a reduction in psychological distress, and whether this approach is an effective intervention for the reduction of Emergency Department admissions. A single case design was used, with pre- and post-measures of health anxiety, general anxiety and depression. Data on Emergency Department admissions prior to and following treatment were used to assess change in this domain. Reliable and clinically significant reductions were seen across all measures, from severe to sub-clinical levels. There was a complete amelioration of Emergency Department admissions in the 12 months following completion of treatment. This preliminary study provides a sound rationale for further research into AD complicated by anxiety. Findings support the clinical utility of the cognitive behavioural therapy model for complex presentations of AD, offering a potential treatment option where anxiety is elevated and interfering with self-management and leading to high levels of health service use.
Bøe Wolff, A S; Oftedal, B; Johansson, S; Bruland, O; Løvås, K; Meager, A; Pedersen, C; Husebye, E S; Knappskog, P M
Autoimmune Addison's disease (AAD) is often associated with other components in autoimmune polyendocrine syndromes (APS). Whereas APS I is caused by mutations in the AIRE gene, the susceptibility genes for AAD and APS II are unclear. In the present study, we investigated whether polymorphisms or copy number variations in the AIRE gene were associated with AAD and APS II. First, nine SNPs in the AIRE gene were analyzed in 311 patients with AAD and APS II and 521 healthy controls, identifying no associated risk. Second, in a subgroup of 25 of these patients, AIRE sequencing revealed three novel polymorphisms. Finally, the AIRE copy number was determined by duplex quantitative PCR in 14 patients with APS I, 161 patients with AAD and APS II and in 39 healthy subjects. In two Scandinavian APS I patients previously reported to be homozygous for common AIRE mutations, we identified large deletions of the AIRE gene covering at least exon 2 to exon 8. We conclude that polymorphisms in the AIRE gene are not associated with AAD and APS II. We further suggest that DNA analysis of the parents of patients found to be homozygous for mutations in AIRE, always should be performed.
Skov, Jakob; Höijer, Jonas; Magnusson, Patrik K E; Ludvigsson, Jonas F; Kämpe, Olle; Bensing, Sophie
The pathophysiology behind autoimmune Addison's disease (AAD) is poorly understood, and the relative influence of genetic and environmental factors remains unclear. In this study, we examined the heritability of AAD and explored disease-associated autoimmune comorbidity among Swedish twins. A population-based longitudinal cohort of 112,100 Swedish twins was used to calculate the heritability of AAD, and to explore co-occurrence of 10 organ-specific autoimmune disorders in twin pairs with AAD. Diagnoses were collected 1964-2012 through linkage to the Swedish National Patient Register. The Swedish Prescribed Drug Register was used for additional diagnostic precision. When available, biobank serum samples were used to ascertain the AAD diagnosis through identification of 21-hydroxylase autoantibodies. We identified 29 twins with AAD. Five out of nine (5/9) monozygotic pairs and zero out of fifteen (0/15) dizygotic pairs were concordant for AAD. The probandwise concordance for monozygotic twins was 0.71 (95% CI 0.40-0.90) and the heritability 0.97 (95% CI 0.88-99). Autoimmune disease patterns of monozygotic twin pairs affected by AAD displayed a higher degree of similarity than those of dizygotic twins, with an incidence rate ratio of 15 (95% CI 1.8-116) on the number of shared autoimmune diagnoses within pairs. The heritability of AAD appears to be very high, emphasizing the need for further research on the genetic etiology of the disease. Monozygotic twin concordance for multiple autoimmune manifestations suggests strong genetic influence on disease specificity in organ-specific autoimmunity.
Ian Louis Ross
Full Text Available BACKGROUND: Addison's disease (AD has been associated with an increased risk of cardiovascular disease. Glucocorticoid receptor polymorphisms that alter glucocorticoid sensitivity may influence metabolic and cardiovascular risk factors in patients with AD. The 9β polymorphism of the glucocorticoid receptor gene is associated with relative glucocorticoid resistance and has been reported to increase the risk of myocardial infarction in the elderly. We explored the impact of this polymorphism in patients with AD. MATERIALS AND METHODS: 147 patients with AD and 147 age, gender and ethnicity matched healthy controls were recruited. Blood was taken in a non-fasted state for plasma lipid determination, measurement of cardiovascular risk factors and DNA extraction. RESULTS: Genotype data for the 9β polymorphism was available for 139 patients and 146 controls. AD patients had a more atherogenic lipid profile characterized by an increase in the prevalence of small dense LDL (p = 0.003, increased triglycerides (p = 0.002, reduced HDLC (p<0.001 an elevated highly sensitive C-reactive protein (p = 0.01, compared with controls. The 9β polymorphism (at least one G allele was found in 28% of patients and controls respectively. After adjusting for age, gender, ethnicity, BMI and hydrocortisone dose per metre square of body surface area in patients, there were no significant metabolic associations with this polymorphism and hydrocortisone doses were not higher in patients with the polymorphism. CONCLUSIONS: This study did not identify any associations between the 9β polymorphism and cardiovascular risk factors or hydrocortisone dose and determination of this polymorphism is therefore unlikely to be of clinical benefit in the management of patients with AD.
Baleva, Marta P; Mihaylova, Snejina; Yankova, Petja; Atanasova, Iliana; Nikolova-Vlahova, Milena; Naumova, Elissaveta
Selective IgA deficiency (IgAD) is the most prevalent type of primary immune deficiencies, but partial IgA deficiency is even more common. Addison's disease is a rare condition associated with primary adrenal insufficiency due to infection or autoimmune destruction of the adrenals. The association between IgA deficiency and Addison's disease is very rare. We observed a 22-year-old male patient with marked darkening of the skin, especially on the palms and areolae, jaundice on the skin and sclera, astheno-adynamia, hypotension (80/50 mm Hg), and pain in the right hypochondrium. The laboratory investigations revealed increased serum levels of total and indirect bilirubin, AST, ALT, GGT and LDH, negative HBsAg, anti-HBc IgM, anti-HCV and anti-HAV IgM, very low serum IgA levels (0.16 g/l) with normal IgG and IgM, negative ANA, ANCA, AMA, LKM-1, anti-GAD-60, anti-IA-2, anti-thyroglobulin antibodies, a mild increase in anti-TPO antibodies titer, a marked increase in IgG anti-tissue transglutaminase antibodies, with no typical changes in cellular immunity, negative T-SPOT-TB test, HLA - A*01; B*08; DRB1*03; DQB1*02, karyotype - 46, XY. We present a rare case of partial IgA deficiency with Addison's disease, hepatitis, thyroiditis and positive anti-tissue transglutaminase antibodies. IgAD and some autoimmune disorders share several predisposing HLA genes, thus explaining the increased prevalence of IgAD in certain patient groups.
Brønstad, Ingeborg; Skinningsrud, Beate; Bratland, Eirik; Løvås, Kristian; Undlien, Dag; Sverre Husebye, Eystein; Wolff, Anette Susanne Bøe
Steroid 21-hydroxylase, encoded by CYP21A2, is the major autoantigen in autoimmune Addison's disease (AAD). CYP21A2 is located in the region of the HLA complex on chromosome 6p21.3, which harbours several risk alleles for AAD. The objective was to investigate whether CYP21A2 gene variants confer risk of AAD independently of other risk alleles in the HLA loci. DNA samples from 381 Norwegian patients with AAD and 340 healthy controls (HC) previously genotyped for the HLA-A, -B, -DRB1, and -DQB1 and MICA loci were used for genotyping of CYP21A2. Genotyping of CYP21A2 was carried out by direct sequencing. Linkage of CYP21A2 to the HLA loci was assessed using UNPHASED version 3.0.10 and PHASE version 2.1. Heterozygotes of the single-nucleotide polymorphisms (SNPs) rs397515394, rs6467, rs6474, rs76565726 and rs6473 were detected significantly more frequently in AAD patients compared with HC (P<0.005), but all SNPs were in a linkage disequilibrium (LD) with high-risk HLA-DRB1 haplotypes. rs6472C protected against AAD (odds ratio=0.15, 95% CI (0.08-0.30), P=3.8×10(-10)). This SNP was not in an LD with HLA loci (P=0.02), but did not increase protection when considering the effect of HLA-DRB1 alleles. Mutations causing congenital adrenal hyperplasia were found in heterozygosity in <1.5% of the cases in both groups. Genetic variants of CYP21A2 associated to AAD are in LD with the main AAD risk locus HLA-DRB1, and CYP21A2 does not constitute an independent susceptibility locus. © 2014 European Society of Endocrinology.
Boag, Alisdair M; Christie, Michael R; McLaughlin, Kerry A; Syme, Harriet M; Graham, Peter; Catchpole, Brian
Canine hypoadrenocorticism likely arises from immune-mediated destruction of adrenocortical tissue, leading to glucocorticoid and mineralocorticoid deficiency. In humans with autoimmune Addison's disease (AAD) or autoimmune polyendocrine syndrome (APS), circulating autoantibodies have been demonstrated against enzymes associated with adrenal steroid synthesis. The current study investigates autoantibodies against steroid synthesis enzymes in dogs with spontaneous hypoadrenocorticism. Coding regions of canine CYP21A2 (21-hydroxylase; 21-OH), CYP17A1 (17-hydroxylase; 17-OH), CYP11A1 (P450 side-chain cleavage enzyme; P450scc) and HSD3B2 (3β hydroxysteroid dehydrogenase; 3βHSD) were amplified, cloned and expressed as 35S-methionine radiolabelled recombinant protein. In a pilot study, serum samples from 20 dogs with hypoadrenocorticism and four unaffected control dogs were screened by radio-immunoprecipitation assay. There was no evidence of reactivity against 21-OH, 17-OH or 3βHSD, but five dogs with hypoadrenocorticism showed immunoreactivity to P450scc compared with controls. Serum samples were subsequently obtained from 213 dogs diagnosed with hypoadrenocorticism and 110 dogs from a hospital control population. Thirty control dogs were randomly selected to establish a threshold for antibody positivity (mean + 3 × standard deviation). Dogs with hypoadrenocorticism were more likely to be P450scc autoantibody positive than hospital controls (24% vs. 1.2%, respectively; p = 0.0016). Sex was significantly associated with the presence of P450scc autoantibodies in the case population, with 30% of females testing positive compared with 17% of males (p = 0.037). Significant associations with breed (p = 0.015) and DLA-type (DQA1*006:01 allele; p = 0.017) were also found. This cross-sectional study indicates that P450scc autoantibodies are present in a proportion of dogs affected with hypoadrenocorticism.
Alisdair M Boag
Full Text Available Canine hypoadrenocorticism likely arises from immune-mediated destruction of adrenocortical tissue, leading to glucocorticoid and mineralocorticoid deficiency. In humans with autoimmune Addison's disease (AAD or autoimmune polyendocrine syndrome (APS, circulating autoantibodies have been demonstrated against enzymes associated with adrenal steroid synthesis. The current study investigates autoantibodies against steroid synthesis enzymes in dogs with spontaneous hypoadrenocorticism. Coding regions of canine CYP21A2 (21-hydroxylase; 21-OH, CYP17A1 (17-hydroxylase; 17-OH, CYP11A1 (P450 side-chain cleavage enzyme; P450scc and HSD3B2 (3β hydroxysteroid dehydrogenase; 3βHSD were amplified, cloned and expressed as 35S-methionine radiolabelled recombinant protein. In a pilot study, serum samples from 20 dogs with hypoadrenocorticism and four unaffected control dogs were screened by radio-immunoprecipitation assay. There was no evidence of reactivity against 21-OH, 17-OH or 3βHSD, but five dogs with hypoadrenocorticism showed immunoreactivity to P450scc compared with controls. Serum samples were subsequently obtained from 213 dogs diagnosed with hypoadrenocorticism and 110 dogs from a hospital control population. Thirty control dogs were randomly selected to establish a threshold for antibody positivity (mean + 3 × standard deviation. Dogs with hypoadrenocorticism were more likely to be P450scc autoantibody positive than hospital controls (24% vs. 1.2%, respectively; p = 0.0016. Sex was significantly associated with the presence of P450scc autoantibodies in the case population, with 30% of females testing positive compared with 17% of males (p = 0.037. Significant associations with breed (p = 0.015 and DLA-type (DQA1*006:01 allele; p = 0.017 were also found. This cross-sectional study indicates that P450scc autoantibodies are present in a proportion of dogs affected with hypoadrenocorticism.
Granata, Antonio; Tirabassi, Giacomo; Pugni, Valeria; Arnaldi, Giorgio; Boscaro, Marco; Carani, Cesare; Balercia, Giancarlo
There is evidence suggesting that autoimmune Addison's disease (AD) could be associated with sexual dysfunctions probably caused by gluco- and mineralocorticoid deficiency; however, no study has yet treated this subject in males. To evaluate male sexuality and psychological correlates in autoimmune AD before and after gluco- and mineralocorticoid replacement therapy. Twelve subjects with a first diagnosis of autoimmune AD were studied before (baseline) and 2 months after (recovery phase) initiating hormone replacement therapy. Erectile function (EF), orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS), overall satisfaction (OS), depression, and anxiety were studied using a number of questionnaires (International Index of Erectile Function, Beck Depression Inventory, and Spielberger State-Trait Anxiety Inventory); clinical, biochemical, and hormone data were included in the analysis. At baseline, low values were found for EF, OF, SD, IS, and OS and high values for depression and anxiety; all of these parameters improved significantly in the recovery phase compared with baseline. EF variation between the two phases correlated significantly and positively with the variation of serum cortisol, urinary free cortisol, systolic blood pressure, and diastolic blood pressure and inversely with that of upright plasma renin activity. Multiple linear regression analysis using EF variation as dependent variable confirmed the relationship of the latter with variation of serum cortisol, urinary free cortisol, and upright plasma renin activity but not with variation of systolic and diastolic blood pressure. Our study showed that onset of autoimmune AD in males is associated with a number of sexual dysfunctions, all reversible after initiating replacement hormone therapy; cortisol and aldosterone deficiency seems to play an important role in the genesis of erectile dysfunction although the mechanism of their activity is not clear. © 2012 International Society
Jane Austen is typically described as having excellent health until the age of 40 and the onset of a mysterious and fatal illness, initially identified by Sir Zachary Cope in 1964 as Addison's disease. Her biographers, deceived both by Cassandra Austen's destruction of letters containing medical detail, and the cheerful high spirits of the existing letters, have seriously underestimated the extent to which illness affected Austen's life. A medical history reveals that she was particularly susceptible to infection, and suffered unusually severe infective illnesses, as well as a chronic conjunctivitis that impeded her ability to write. There is evidence that Austen was already suffering from an immune deficiency and fatal lymphoma in January 1813, when her second and most popular novel, Pride and Prejudice, was published. Four more novels would follow, written or revised in the shadow of her increasing illness and debility. Whilst it is impossible now to conclusively establish the cause of her death, the existing medical evidence tends to exclude Addison's disease, and suggests there is a high possibility that Jane Austen's fatal illness was Hodgkin's disease, a form of lymphoma.
Fichna, Marta; Żurawek, Magdalena; Bratland, Eirik; Husebye, Eystein S; Kasperlik-Załuska, Anna; Czarnocka, Barbara; Januszkiewicz-Lewandowska, Danuta; Nowak, Jerzy
Autoimmune Addison's disease (AAD) results from T cell-mediated destruction of the adrenal cortex, commonly accompanied by autoantibodies to 21-hydroxylase (21OH). In order to gain insight into the obscure aetiology of this disease, we investigated the roles of the IL2 and IL2RA genes, encoding interleukin-2 and subunit alpha of its receptor (IL2Ra), respectively. The association of AAD with IL2 and IL2RA polymorphisms (rs6822844, rs2069762, rs3136534, rs11594656, rs3118470 and rs2104286) was tested in 223 patients and 672 healthy controls. Functional studies consisted of gene expression analysis in cultured PBMCs exposed to 21OH and evaluation of serum interleukin by ELISA assays. The frequency of the minor C allele of rs3136534 was significantly decreased in AAD subjects compared to controls (OR 0.71; 95%CI 0.561-0.887; p = 0.003). Only AAD cells responded to 21OH with an elevated IL2 and IL2RA mRNA synthesis (p = 0.004 and p = 0.009 versus controls, respectively), paralleled by increased supernatant levels of both cytokines (p = 0.031 and p = 0.001 versus controls). IL2 mRNA level in 21OH-stimulated AAD PBMCs correlated negatively with age (p = 0.036) and positively with serum antibodies to 21OH (p = 0.006). Carriers of the rs2104286 AA genotype demonstrated higher IL2RA mRNA (p = 0.022) and soluble IL2Ra secretion (p = 0.029) upon 21OH stimulation. Serum interleukin-2 in AAD subjects was significantly higher compared to controls (4.61 ± 4.3 versus 1.71 ± 3.2 pg/mL, p < 0.001), whereas sIL2Ra levels remained similar in both groups (p = 0.885). In conclusion, the study reveals an association between AAD and IL2 locus. It confirms specific 21OH-directed reactivity of the peripheral AAD lymphocytes, which display increased synthesis of interleukin-2 and sIL2Ra.
Ian Louis Ross
Full Text Available BACKGROUND: Patients with Addison's disease (AD in Scandinavia have an increased risk for premature death due to cardiovascular disease (CVD. Serum lipids are important risk factors for CVD and vascular mortality. Replacement doses of hydrocortisone have historically been higher in Sweden than South Africa. The primary aim was to study the lipid profiles in a large group of patients with AD with the hypothesis that the lipid profile in patients in Sweden would be worse than in South Africa. METHODS: In a cross-sectional study, 110 patients with AD (55 from South Africa, 55 from Sweden matched for age, gender, ethnicity and BMI were studied. Anthropometric measures, blood pressure, lipids, highly sensitive C-reactive protein (hs-CRP and adiponectin were studied. RESULTS: All patients were Caucasian and the majority were women N = 36 (65.5%. Mean (standard deviation; SD ages of the Swedish and South African patients were 52.9 (13.0 and 52.6 (14.4 years and BMI 25.3 (3.2 and 25.8 (4.1 kg/m2, respectively. The mean total daily hydrocortisone dose was greater in the Swedish patients than the South African patients, [33.0 (8.1 versus 24.3 (8.0 mg; p<0.0001]. South African patients had higher median (interquartilerange; IQR triglycerides (TG [1.59 (1.1-2.46 versus 0.96 (0.74-1.6 mmol/l; p<0.001], total cholesterol (TC [6.02(1.50 versus 5.13 (0.87 mmol/l; p<0.001], LDL-C [4.43 (1.44 versus 2.75 (0.80 mmol/l; p<0.001] and median hs-CRP [2.15 (0.93-5.45 versus 0.99 (0.57-2.10 mg/L; p<0.003] and lower HDL-C [0.80 (0.40 versus 1.86 (0.46 mmol/l; p<0.001] than the Swedish patients. Approximately 20% of the patients in both cohorts had hypertension and diabetes mellitus. CONCLUSIONS: South African patients with AD have worse lipid profiles and higher hs-CRP compared to their matched Swedish patients, despite lower doses of hydrocortisone. It is uncertain at this time whether these are due to genetic or environmental factors.
Ross, Ian Louis; Bergthorsdottir, Ragnhildur; Levitt, Naomi; Dave, Joel Alex; Schatz, Desmond; Marais, David; Johannsson, Gudmundur
Background Patients with Addison's disease (AD) in Scandinavia have an increased risk for premature death due to cardiovascular disease (CVD). Serum lipids are important risk factors for CVD and vascular mortality. Replacement doses of hydrocortisone have historically been higher in Sweden than South Africa. The primary aim was to study the lipid profiles in a large group of patients with AD with the hypothesis that the lipid profile in patients in Sweden would be worse than in South Africa. Methods In a cross-sectional study, 110 patients with AD (55 from South Africa, 55 from Sweden) matched for age, gender, ethnicity and BMI were studied. Anthropometric measures, blood pressure, lipids, highly sensitive C-reactive protein (hs-CRP) and adiponectin were studied. Results All patients were Caucasian and the majority were women N = 36 (65.5%). Mean (standard deviation; SD) ages of the Swedish and South African patients were 52.9 (13.0) and 52.6 (14.4) years and BMI 25.3 (3.2) and 25.8 (4.1) kg/m2, respectively. The mean total daily hydrocortisone dose was greater in the Swedish patients than the South African patients, [33.0 (8.1) versus 24.3 (8.0) mg; p<0.0001]. South African patients had higher median (interquartilerange; IQR) triglycerides (TG) [1.59 (1.1–2.46) versus 0.96 (0.74–1.6) mmol/l; p<0.001], total cholesterol (TC) [6.02(1.50) versus 5.13 (0.87) mmol/l; p<0.001], LDL-C [4.43 (1.44) versus 2.75 (0.80) mmol/l; p<0.001] and median hs-CRP [2.15 (0.93–5.45) versus 0.99 (0.57–2.10) mg/L; p<0.003] and lower HDL-C [0.80 (0.40) versus 1.86 (0.46) mmol/l; p<0.001] than the Swedish patients. Approximately 20% of the patients in both cohorts had hypertension and diabetes mellitus. Conclusions South African patients with AD have worse lipid profiles and higher hs-CRP compared to their matched Swedish patients, despite lower doses of hydrocortisone. It is uncertain at this time whether these are due to genetic or environmental factors. PMID:24603607
Full Text Available Addison’s disease is an endocrine disorder characterized by primary adrenal insufficiency due to various causes. Mycobacterium tuberculosis infection was a major cause in the past but is rare nowadays. We describe a patient admitted to our hospital who was diagnosed with tuberculous Addison’s disease.
Sara Ferreira; Margarida Freitas-Silva
Addison’s disease is an endocrine disorder characterized by primary adrenal insufficiency due to various causes. Mycobacterium tuberculosis infection was a major cause in the past but is rare nowadays. We describe a patient admitted to our hospital who was diagnosed with tuberculous Addison’s disease.
Pazderska, Agnieszka; Oftedal, Bergithe E; Napier, Catherine M; Ainsworth, Holly F; Husebye, Eystein S; Cordell, Heather J; Pearce, Simon H S; Mitchell, Anna L
Autoimmune Addison's disease (AAD) is a rare but highly heritable condition. The BACH2 protein plays a crucial role in T lymphocyte maturation, and allelic variation in its gene has been associated with a number of autoimmune conditions. We aimed to determine whether alleles of the rs3757247 single nucleotide polymorphism (SNP) in the BACH2 gene are associated with AAD. This case-control association study was performed in two phases using Taqman chemistry. In the first phase, the rs3757247 SNP was genotyped in 358 UK AAD subjects and 166 local control subjects. Genotype data were also available from 5154 healthy UK controls from the Wellcome Trust (WTCCC2) for comparison. In the second phase, the SNP was genotyped in a validation cohort comprising 317 Norwegian AAD subjects and 365 controls. The frequency of the minor T allele was significantly higher in subjects with AAD from the United Kingdom compared to both the local and WTCCC2 control cohorts (58% vs 45 and 48%, respectively) (local controls, P = 1.1 × 10 -4 ; odds ratio [OR], 1.68; 95% confidence interval [CI], 1.29-2.18; WTCCC2 controls, P = 1.4 × 10 -6 ; OR, 1.44; 95% CI, 1.23-1.69). This finding was replicated in the Norwegian validation cohort (P = .0015; OR, 1.41; 95% CI, 1.14-1.75). Subgroup analysis showed that this association is present in subjects with both isolated AAD (OR, 1.53; 95% CI, 1.22-1.92) and autoimmune polyglandular syndrome type 2 (OR, 1.37; 95% CI, 1.12-1.69) in the UK cohort, and with autoimmune polyglandular syndrome type 2 in the Norwegian cohort (OR, 1.58; 95% CI, 1.22-2.06). We have demonstrated, for the first time, that allelic variability at the BACH2 locus is associated with susceptibility to AAD. Given its association with multiple autoimmune conditions, BACH2 can be considered a "universal" autoimmune susceptibility locus.
Chantzichristos, Dimitrios; Persson, Anders; Eliasson, Björn; Miftaraj, Mervete; Franzén, Stefan; Svensson, Ann-Marie; Johannsson, Gudmundur
We determined the incidence and prevalence of Addison's disease (AD) among persons with or without type 1 diabetes mellitus (T1DM) in nationwide, matched cohort studies. Persons with T1DM were identified from the Swedish National Diabetes Register and each was matched for age, sex, year and county to five controls randomly selected from the general population. Persons with AD were identified from the Swedish National Inpatient Register. Baseline demographics and seasonal onset variation of AD were presented by descriptive statistics. Prevalence and incidence were estimated by proportions and incidence rates, respectively. Times to AD were analyzed using the Cox proportional hazard model. Between 1998 and 2013, 66 persons with T1DM were diagnosed with AD at a mean age (s.d.) of 36.4 (13.0) years among 36 514 persons with T1DM, while 32 were diagnosed with AD at a mean age of 42.7 (15.2) years among 182 570 controls. The difference in mean age at diagnosis of AD between the groups was 6.3 years ( P value = 0.036). The incidence of AD for a person with or without T1DM was therefore 193 and 18 per million person-years, respectively. The adjusted relative risk increase of developing AD in T1DM was 10.8 (95% CI: 7.1-16.5). The highest incidence of AD was observed during February-March and September-October. The prevalence of AD in persons with or without T1DM in December 2012 was 3410 and 208 per million, respectively. The odds ratio for AD in persons with T1DM vs controls was 16.5 (95% CI: 11.1-24.5). The risk to develop AD among persons with T1DM is more than 10 times higher than in persons without T1DM. Persons with T1DM develop AD at a younger age. The incidence of AD may have a seasonal pattern. © 2018 European Society of Endocrinology.
Penna-Martinez, Marissa; Filmann, Natalie; Bogdanou, Dimitra; Shoghi, Firouzeh; Huenecke, Sabine; Schubert, Ralf; Herrmann, Eva; Koehl, Ulrike; Husebye, Eystein S; Badenhoop, Klaus
On the basis of the immunomodulatory actions of vitamin D (VD), we investigated the effects of high-dose VD therapy over a 3 mo period on the immune response in patients with Addison's disease (AD). This randomized, controlled, crossover trial included 13 patients with AD who received either cholecalciferol (4000 IU/d) for 3 mo followed by 3 mo placebo oil or the sequential alternative placebo followed by verum. Glucocorticoid replacement doses remained stable. The primary outcome measures were changes in 25-hydroxyvitamin D3 (25(OH)D 3 ) levels and immune cells including T helper cells (Th; CD3 + CD4 + ), late-activated Th cells (CD3 + CD4 + HLA-DR + ), regulatory T cells (CD3 + CD4 + CD25 bright CD127 dim/neg ), cytotoxic T cells (Tc; CD3 + CD8 + ), late-activated Tc cells (CD3 + CD8 + HLA-DR + ), and monocytes. The explorative analysis included the correlation of changes with VD-related gene polymorphisms and 21-hydroxylase antibody titers. Ten of 13 patients (77%) were VD deficient. Median 25(OH)D 3 concentrations increased significantly to 41.5 ng/ml (median changes: 19.95 ng/ml; P = 0.0005) after 3 mo of cholecalciferol treatment. Within the T-cells, only the late-activated Th (median changes: 1.6%; P = 0.02) and late-activated Tc cells (median changes: 4.05%; P = 0.03) decreased, whereas monocytes (median changes: 1.05%; P = 0.008) increased after VD therapy. T-cell changes were associated with two polymorphisms (CYP27B1-rs108770012 and VDR-rs10735810), but no changes in the 21-hydroxylase antibody titers were observed. Three months of treatment with cholecalciferol achieved sufficient 25(OH)D 3 levels and can regulate late-activated T-cells and monocytes in patients with AD. Explorative analysis revealed potential genetic contributions. This pilot trial provides novel insights about immunomodulation in AD. Copyright © 2017 Elsevier Inc. All rights reserved.
Ross, I L; Babu, S; Armstrong, T; Zhang, L; Schatz, D; Pugliese, A; Eisenbarth, G; Baker Ii, P
Genetic similarities between patients from the United States and South African (SA) Addison's Disease (AD) strengthen evidence for genetic association. SA-AD (n = 73), SA healthy controls (N = 78), and US-AD patients (N = 83) were genotyped for DQA1, DQB1, DRB1, and HLA-B alleles. Serum was tested for the quantity of 21OH-AA and IFNα-AA at the Barbara Davis Center. Although not as profound as in US-AD, in SA-AD 21OH-AA + subjects the predominantly associated risk haplotypes were DRB1*0301-DQB1*0201 (DR3), DRB1*04xx-DQB1*0302 (DR4), and the combined DR3/4 genotype. DQB1*0302 associated DRB1*04xx haplotypes conferred higher risk than those DRB1*04xx haplotypes associated with other DQB1 alleles. We found negative association in 21OH-AA + SA-AD for DQA1*0201-DQB1*0202 and DQA1*0101-DQB1*0501 vs SA controls, and positive association for DQA1*0401-DQB1*0402 vs US-AD. Apart from the class II DR3 haplotype, HLA-B8 did not have an independent effect; however together DR3 and HLA-B8 conferred the highest risk vs 21OH-AA negative SA-AD and SA-controls. HLA-B7 (often with DR4) conferred novel risk in 21OH-AA + SA-AD vs controls. This study represents the first comparison between South African and United States AD populations utilizing genotyping and serology performed at the same center. SA-AD and US-AD 21OH-AA + patients share common HLA risk haplotypes including DR4 (with HLA-B7) and DR3 (with HLA-B8), strengthening previously described HLA associations and implicating similar genetic etiology. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Fichna, Marta; Rogowicz-Frontczak, Anita; Żurawek, Magdalena; Fichna, Piotr; Gryczyńska, Maria; Zozulińska-Ziółkiewicz, Dorota; Ruchała, Marek
Autoimmune Addison's disease (AAD) associates with exceptional susceptibility to develop other autoimmune conditions, including type 1 diabetes (T1D), marked by positive serum autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and insulinoma-associated protein 2 (IA-2A). Zinc transporter 8 (ZnT8) is a new T1D autoantigen, encoded by the SLC30A8 gene. Its polymorphic variant rs13266634C/T seems associated with the occurrence of serum ZnT8 antibodies (ZnT8A). This study was designed to determine the prevalence of serum ZnT8A and their clinical implication in 140 AAD patients. Other beta cell and thyroid-specific autoantibodies were also investigated, and ZnT8A results were confronted with the rs13266634 genotype. ZnT8A were detectable in 8.5 %, GADA in 20.7 %, IA-2A in 5.7 %, IAA in 1.6 % and various anti-thyroid antibodies in 7.1-67.8 % individuals. Type 1 diabetes was found in 10 % AAD patients. ZnT8A were positive in 57.1 % of T1D patients and 3.4 % non-diabetic AAD. Analysis of ZnT8A enabled to identify autoimmunity in two (14.3 %) T1D individuals previously classified as autoantibody-negative. ZnT8A-positive patients revealed significantly higher number of autoimmune conditions (p < 0.001), increased prevalence of T1D (p < 0.001) and other beta cell-specific autoantibodies. Carriers of the rs13266634 T-allele displayed increased frequency (p = 0.006) and higher titres of ZnT8A (p = 0.002). Our study demonstrates high incidence of ZnT8A in AAD patients. ZnT8A are associated with coexisting T1D and predictive of T1D in non-diabetic subjects. Moreover, positive ZnT8A in AAD indicate elevated risk for additional autoimmune conditions. Autoantibodies to beta cell antigens, comprising ZnT8, could be included in routine screening panels in AAD.
Tzoufi, Meropi; Makis, Alexandros; Chaliasos, Nikolaos; Nakou, Iliada; Siomou, Ekaterini; Tsatsoulis, Agathoklis; Zikou, Anastasia; Argyropoulou, Maria; Bonnefont, Jean Paul; Siamopoulou, Antigone
Kearns-Sayre syndrome (KSS) is a rare mitochondrial DNA deletion syndrome defined as the presence of ophthalmoplegia, pigmentary retinopathy, onset less than age 20 years, and one of the following: cardiac conduction defects, cerebellar syndrome, or cerebrospinal fluid protein above 100 mg/dl. KSS may affect many organ systems causing endocrinopathies, encephalomyopathy, sensorineural hearing loss, and renal tubulopathy. Clinical presentation at diagnosis is quite heterogeneous and, usually, few organs are affected with progression to generalized disease early in adulthood. We present the case of a boy with KSS presenting at the age of 5 years with myopathy, Addison's disease, primary hypoparathyroidism, and Fanconi syndrome. The proper replacement treatment along with the administration of mitochondrial metabolism-improving agents had a brief ameliorating effect, but gradual severe multisystemic deterioration was inevitable over the next 5 years. This report highlights the fact that in case of simultaneous presentation of polyendocrinopathies and renal disease early in childhood, KSS should be considered.
Schneiderman, M; Czuzoj-Shulman, N; Spence, A R; Abenhaim, H A
To assess if pregnancies among women with Addison's disease (AD) are at higher risk of adverse maternal and neonatal outcomes. Population-based retrospective cohort study. All births in the United States' Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from 2003 to 2011. Baseline characteristics were compared between women with AD and those without, and prevalence over time was measured. Logistic regression was used to estimate the effect of AD on maternal and neonatal outcomes by calculating the crude and adjusted odds ratios (OR) and corresponding 95% confidence intervals (95% CI). We calculated a prevalence of AD in pregnancy of 5.5/100 000, increasing from 5.6 to 9.6/100 000 (P = 0.0001) over the 9-year study period. Compared with women without AD, women with AD were more likely to deliver preterm (OR 1.50, 95% CI 1.16-1.95), deliver by caesarean section (OR 1.32, 95% CI 1.08-1.61), have impaired wound healing (OR 4.28, 95% CI 2.55-7.18), develop infections (OR 2.44, 95% CI 1.66-3.58) and develop thromboembolism (OR 5.21, 95% CI 2.15-12.63), require transfusions (OR 6.69, 95% CI 4.69-9.54), and have prolonged postpartum hospital admissions (OR 5.71, 95% CI 4.37-7.47). Maternal mortality was significantly higher than in the comparison group (OR 22.30, 95% CI 6.82-72.96). Congenital anomalies (OR 3.62, 95% CI 2.05-6.39) and small-for-gestational age infants (OR 1.78, 95% CI 1.15-2.75) were more likely in these pregnancies. Addison's disease significantly increases the risk of severe adverse maternal and neonatal outcomes, so pregnant women with AD are best managed in tertiary-care centres. Pregnancies complicated by Addison's disease have an increased risk of adverse maternal and neonatal outcomes. © 2016 Royal College of Obstetricians and Gynaecologists.
Molnár, Ágnes; Kövesdi, Annamária; Szücs, Nikolette; Tóth, Miklós; Igaz, Péter; Rácz, Károly; Patócs, Attila
Glucocorticoid substitution is essential in patients with chronic primary adrenocortical insufficiency (Addison's disease) and both over-treatment and inadequate dosage have deleterious effects. Individual sensitivity to glucocorticoids is partly genetically determined. To test the hypothesis whether the well-characterized SNPs of the GR and HSD11B1 genes may modulate the individual sensitivity to exogenous glucocorticoids and may influence clinical and/or laboratory parameters and the glucocorticoid substitution dosage in patients with Addison's disease. 68 patients with primary adrenocortical insufficiency were involved. Clinical and laboratory data, as well as the dosage of the hormone replacement therapy were collected. Peripheral blood DNA was isolated, and the GR and HSD11B1 SNPs were examined using allele-specific PCR or Taqman assay on Real Time PCR. The allele frequency of the GR N363S polymorphism was higher in patients compared to the control group and the disease appeared significantly earlier in patients harbouring the GR A3669G compared to noncarriers. These patients had higher ACTH level measured at the time of diagnosis. Homozygous BclI carriers had higher body mass index (BMI) and lower total hydrocortisone equivalent supplementation dose needed than heterozygous or noncarriers. The BMI and weight gain during hormone replacement therapy were also higher in carriers of the HSD11B1 rs4844880 treated with glucocorticoids other than dexamethasone. The BclI polymorphism of the GR gene and the rs4844880 of the HSD11B1 gene may contribute to weight gain and may affect the individual need of glucocorticoid substitution dose in these patients. © 2016 John Wiley & Sons Ltd.
Bernecker, C; Halim, F; Haase, M; Willenberg, H S; Ehlers, M; Schott, M
Autoimmune Addison's disease (AD) is a rare but potentially life threatening disease. The exact etiology of the immune response to the adrenal gland is still unknown. MicroRNAs (miRNAs) critically control gene-expression and play an important role in regulating the immune response. The aim of this study was to determine key immunoregulatory miRNAs influencing autoimmune adrenal insufficiency. For this purpose selected miRNAs were amplified by a semiquantitative SYBR Green PCR from blood mononuclear cells and after purification from CD4+ and CD 8+ cells of 6 patients with autoimmune adrenal insufficiency and 10 healthy controls. In CD4+ T-cells miRNA 181a*_1 (18.02 in AD vs. 11.99 in CG, p=0.0047) is significantly increased whereas miRNA 200a_1 (12.48 in AD vs. 19.40 in CG, p=0.0003) and miRNA 200a_2* (8.59 in AD vs. 17.94 in CG, p=0.0160) are significantly decreased. miRNA 200a_1 (12.37 in AD group vs. 18.12 in control group, p=0.001) and miRNA 200a_2* (10.72 in AD group vs. 17.84 in control group, p=0.022) are also significantly decreased in CD8+ T-cells. This study could show for the first time a significant change of three defined miRNAs in PBMCs, CD4+, and CD8+ T-cells of autoimmune AD patients in vivo. These data may help to better understand the cause of the autoimmune processes leading to autoimmune AD. They extend our very limited knowledge concerning miRNAs in autoimmune Addison's disease. © Georg Thieme Verlag KG Stuttgart · New York.
Bush, Lisabeth A; Ruess, Lynne; Jack, Tom; Person, Donald A
A young Marshallese woman presented with the insidious development of fever, cough, fatigue, profound weakness, massive weight loss, cachexia, alopecia, amenorrhea, and periumbilical hyperpigmentation. Limited laboratory studies revealed anemia, leukocytosis, and hyponatremia. Imaging studies, as well as digital photographs, transmitted over the Internet, using the secure Pacific Island Health Care Project (PIHCP), store-and-forward telemedicine system, suggested the diagnosis of disseminated tuberculosis, and antimycobacterial antibiotics were begun. Sputum cultures eventually grew Mycobacterium tuberculosis. Based on the constellation of clinical signs and symptoms, the transmitted images, and limited laboratory data, adrenal tuberculosis (Addison's disease) with adrenal insufficiency was diagnosed and corticosteroids were initiated. The patient responded dramatically This case underscores the utility of telemedicine in the diagnosis and treatment of patients with unusual conditions, rarely seen today in the United States, from remote sites in the Developing World.
Edvardsen, Kine; Bjånesøy, Trine; Hellesen, Alexander; Breivik, Lars; Bakke, Marit; Husebye, Eystein S; Bratland, Eirik
Autoimmune Addison's disease (AAD) is a disorder caused by an immunological attack on the adrenal cortex. The interferon (IFN)-inducible chemokine CXCL10 is elevated in serum of AAD patients, suggesting a peripheral IFN signature. However, CXCL10 can also be induced in adrenocortical cells stimulated with IFNs, cytokines, or microbial components. We therefore investigated whether peripheral blood mononuclear cells (PBMCs) from AAD patients display an enhanced propensity to produce CXCL10 and the related chemokine CXCL9, after stimulation with type I or II IFNs or the IFN inducer poly (I:C). Although serum levels of CXCL10 and CXCL9 were significantly elevated in patients compared with controls, IFN stimulated patient PBMC produced significantly less CXCL10/CXCL9 than control PBMC. Low CXCL10 production was not significantly associated with medication, disease duration, or comorbidities, but the low production of poly (I:C)-induced CXCL10 among patients was associated with an AAD risk allele in the phosphatase nonreceptor type 22 (PTPN22) gene. PBMC levels of total STAT1 and -2, and IFN-induced phosphorylated STAT1 and -2, were not significantly different between patients and controls. We conclude that PBMC from patients with AAD are deficient in their response to IFNs, and that the adrenal cortex itself may be responsible for the increased serum levels of CXCL10.
Bjånesøy, Trine; Hellesen, Alexander; Breivik, Lars; Bakke, Marit; Husebye, Eystein S.; Bratland, Eirik
Autoimmune Addison's disease (AAD) is a disorder caused by an immunological attack on the adrenal cortex. The interferon (IFN)-inducible chemokine CXCL10 is elevated in serum of AAD patients, suggesting a peripheral IFN signature. However, CXCL10 can also be induced in adrenocortical cells stimulated with IFNs, cytokines, or microbial components. We therefore investigated whether peripheral blood mononuclear cells (PBMCs) from AAD patients display an enhanced propensity to produce CXCL10 and the related chemokine CXCL9, after stimulation with type I or II IFNs or the IFN inducer poly (I:C). Although serum levels of CXCL10 and CXCL9 were significantly elevated in patients compared with controls, IFN stimulated patient PBMC produced significantly less CXCL10/CXCL9 than control PBMC. Low CXCL10 production was not significantly associated with medication, disease duration, or comorbidities, but the low production of poly (I:C)-induced CXCL10 among patients was associated with an AAD risk allele in the phosphatase nonreceptor type 22 (PTPN22) gene. PBMC levels of total STAT1 and -2, and IFN-induced phosphorylated STAT1 and -2, were not significantly different between patients and controls. We conclude that PBMC from patients with AAD are deficient in their response to IFNs, and that the adrenal cortex itself may be responsible for the increased serum levels of CXCL10. PMID:25978633
Pedersen, Niels C; Brucker, Lynn; Tessier, Natalie Green; Liu, Hongwei; Penedo, Maria Cecilia T; Hughes, Shayne; Oberbauer, Anita; Sacks, Ben
Sebaceous adenitis (SA) and Addison's disease (AD) increased rapidly in incidence among Standard Poodles after the mid-twentieth century. Previous attempts to identify specific genetic causes using genome wide association studies and interrogation of the dog leukocyte antigen (DLA) region have been non-productive. However, such studies led us to hypothesize that positive selection for desired phenotypic traits that arose in the mid-twentieth century led to intense inbreeding and the inadvertent amplification of AD and SA associated traits. This hypothesis was tested with genetic studies of 761 Standard, Miniature, and Miniature/Standard Poodle crosses from the USA, Canada and Europe, coupled with extensive pedigree analysis of thousands more dogs. Genome-wide diversity across the world-wide population was measured using a panel of 33 short tandem repeat (STR) loci. Allele frequency data were also used to determine the internal relatedness of individual dogs within the population as a whole. Assays based on linkage between STR genomic loci and DLA genes were used to identify class I and II haplotypes and disease associations. Genetic diversity statistics based on genomic STR markers indicated that Standard Poodles from North America and Europe were closely related and reasonably diverse across the breed. However, genetic diversity statistics, internal relatedness, principal coordinate analysis, and DLA haplotype frequencies showed a marked imbalance with 30 % of the diversity in 70 % of the dogs. Standard Poodles with SA and AD were strongly linked to this inbred population, with dogs suffering with SA being the most inbred. No single strong association was found between STR defined DLA class I or II haplotypes and SA or AD in the breed as a whole, although certain haplotypes present in a minority of the population appeared to confer moderate degrees of risk or protection against either or both diseases. Dogs possessing minor DLA class I haplotypes were half as
Giordano, Roberta; Guaraldi, Federica; Marinazzo, Elisa; Fumarola, Federica; Rampino, Alessia; Berardelli, Rita; Karamouzis, Ioannis; Lucchiari, Manuela; Manetta, Tilde; Mengozzi, Giulio; Arvat, Emanuela; Ghigo, Ezio
In patients with Addison's disease (AD), a dual-release preparation of hydrocortisone (Plenadren, PLEN) has been demonstrated to maintain cortisol levels in a more physiological range than conventional glucocorticoid therapy, and to exert positive effects. This study aimed to assess variations of anthropometric, metabolic, and hormonal parameters in patients with AD after switching from conventional hydrocortisone (HC) treatment to PLEN. In nineteen AD patients (15 F and 4 M, age 27-65 years) treated with HC 20 mg/day thrice daily, body weight, BMI, waist circumference, fasting glucose, HbA1c, serum lipids, plasma renin activity, electrolytes, and blood pressure were evaluated at baseline, and 1, 3, 6, and 12 months after switching from HC to PLEN. At baseline, and after 1 and 12 months of PLEN, blood ACTH and cortisol (at 0800 h at fasting, and 30, 60, 90, 120, and 240 min after drug ingestion), and health-related quality of life (HRQoL), using 30-AddiQoL questionnaire, were evaluated. During PLEN, waist and serum lipid progressively decreased. After 12 months of PLEN, a significant difference was observed in waist circumference (P = 0.007), HbA1c (P = 0.002), total and LDL-cholesterol levels (P < 0.05). ACTH levels at 240 min and the area under the curve (AUC) were lower (P < 0.05) during PLEN than HC, while cortisol peaks and AUC were similar. 30-AddiQoL total score also improved (P = 0.04) during PLEN. In AD patients, PLEN reduces central adiposity, and improves glucose and metabolism parameters and HRQoL.
Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy.
Björnsdottir, Sigridur; Øksnes, Marianne; Isaksson, Magnus; Methlie, Paal; Nilsen, Roy M; Hustad, Steinar; Kämpe, Olle; Hulting, Anna-Lena; Husebye, Eystein S; Løvås, Kristian; Nyström, Thomas; Bensing, Sophie
Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI). The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD. An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden. Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp. Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment. We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms. Continuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD. © 2015 John Wiley & Sons Ltd.
Kluger, Nicolas; Matikainen, Niina; Sintonen, Harri; Ranki, Annamari; Roine, Risto P; Schalin-Jäntti, Camilla
Patients with Addison's disease (AD) on conventional replacement therapy have impaired health-related quality of life (HRQoL). It is possible that lower hydrocortisone (HC) doses recommended by current guidelines could restore HRQoL. We compared HRQoL in AD patients treated according to current HC recommendations to that of the age- and gender-standardized general population. We assessed HRQoL in a cross-sectional setting with the 15D instrument in a Finnish AD cohort (n = 107) and compared the results with those of a large sample of general population (n = 5671). We examined possible predictors of HRQoL in AD. Within the patient group, HRQoL was also assessed by SF-36. Mean HC dose was 22 mg/d, corresponding to 12 ± 4 mg/m2. HRQoL was impaired in AD compared with the general population (15D score; 0·853 vs 0·918, P < 0·001). Within single 15D dimensions, discomfort and symptoms, vitality and sexual activity were most affected. Stepwise regression analysis demonstrated that Patient's Association membership (P = 0·02), female gender (P < 0·01), presence of other autoimmune or inflammatory comorbidity (P < 0·02), lower education (P < 0·02) and longer disease duration (P < 0·05) independently predicted impaired HRQoL, whereas replacement regimens, autoimmune-related comorbidities, total number of comorbidities or level of healthcare follow-up did not. In AD, HRQoL was impaired also as assessed by SF-36. HRQoL is significantly impaired in AD compared with the general population despite use of recommended HC doses. Patient's Association membership was the most significant predictor of impaired HRQoL. This finding should be explored in more detail in the future. © 2014 John Wiley & Sons Ltd.
A 30-year-old female with a history of anxiety, cannabis use, and Avoidant/Restrictive Food Intake Disorder presented for residential treatment of a Cannabis Use Disorder. Upon arrival, she had not eaten for two days and was found to be hypotensive with electrolyte disturbances. She was admitted to a nearby hospital, where the Internist diagnosed her with Addison’s disease. She was treated with corticosteroid therapy, with rapid normalization of her electrolytes, eating, and anxiety. This is ...
Baranski Lamback, Elisa; Morandi, Grazia; Rapti, Eleni; Christov, Georgi; Brogan, Paul A; Hindmarsh, Peter
Polyglandular autoimmune syndrome (PGA) and eosinophilic granulomatosis with polyangiitis (EGPA) do not seem to represent a coincidental association. A case of a 15-year-old boy is reported who presented with severe systemic inflammation, perimyocarditis and cardiogenic shock, in whom EGPA was initially suspected and later diagnosed with autoimmune adrenalitis with PGA. The severity of the systemic inflammation and perimyocarditis suggests a more widespread autoimmune-mediated process. Autoimmune adrenal insufficiency should be considered in all cases of pericarditis and perimyocarditis, especially when the severity of clinical manifestations exceeds the expected for the severity of the cardiac findings, as timely identification and prompt treatment may be life-saving.
Wolf, Jutta Manuela
Die Psychoneuroimmunologie beschäftigt sich unter anderem mit der Frage, ob und unter welchen Bedingungen psychosozialer Stress krank macht. Humanstudien, die dieser Frage nachgehen, können dabei meist nur korrelative Zusammenhänge aufdecken. Um trotzdem Aussagen zu Mechanismen, Ursache-Wirkungsbeziehungen und klinische Relevanz treffen zu können, muss z.B. auf Befunde aus der Tierforschung oder aus in vitro-Studien zurückgegriffen werden. Ziel der vorliegenden Arbeit war es, eine Methode zu ...
... These conditions can lead to an adrenal crisis. Pregnancy Women with adrenal insufficiency who become pregnant are ... can benefit from following a diet rich in sodium. A health care provider or a dietitian can ...
A 12-year old dog with a 9-year history of primary adrenal insufficiency was referred to the service for hyporexia, muscle weakness, polyuria and polydipsia. Ultrasound examination showed an unresectable mass in the left adrenal gland, with local vascular invasion, which prompted the euthanasia of the animal. Additionally ...
Vermont Center for Geographic Information — (Link to Metadata) This metadata applies to the following collection area(s): Addison County 2012 1.6m and related SLOPE datasets. Created using ArcGIS "SLOPE"...
Vermont Center for Geographic Information — (Link to Metadata) This metadata applies to the following collection area(s): Addison County 2012 1.6m and related ASPECT datasets. This metadata complies with the...
Soumya Brata Sarkar; Subrata Sarkar; Supratim Ghosh; Subhankar Bandyopadhyay
Addison's disease is a rare endocrinal disorder, with several oral and systemic manifestations. A variety of pathological processes may cause Addison's disease. Classically, hyperpigmentation is associated with the disease, and intraoral pigmentation is perceived as the initial sign and develops earlier than the dermatological pigmentation. The symptoms of the disease usually progress slowly and an event of illness or accident can make the condition worse and may lead to a life-threatening cr...
Vermont Center for Geographic Information — (Link to Metadata) This metadata applies to the following collection area(s): Addison County 2012 1.6m and related "normalized" Digital Surface Model (nDSM). Created...
In the first part of this thesis we discuss a concise stepwise approach for the diagnostic evaluation of adrenal insufficiency (AI), taking into account the possible pitfalls associated with the different tests. The second part describes the history of replacement therapy, discusses the current
Schultebraucks, Katharina; Wingenfeld, Katja; Heimes, Jana; Quinkler, Marcus; Otte, Christian
Patients with primary adrenal insufficiency (AI) need to replace glucocorticoids and mineralocorticoids that act on glucocorticoid (GR) and mineralocorticoid receptors (MR). Both receptors are highly expressed in the hippocampus and are closely associated with cognitive function, which might be impaired by insufficient or increased GR and MR stimulation. However, little is known about cognitive function in patients with AI. It was examined whether patients with AI exhibit worse cognitive function compared to sex-, age-, and education-matched controls. Cognitive function (executive function, concentration, verbal memory, visual memory, working memory, and autobiographical memory) was assessed in 30 patients with AI (mean age 52.4 yrs. ±14.4, n=21 women, mean duration of illness 18.2 yrs. ±11.1) and 30 matched controls. We also measured depressive symptoms, body mass index (BMI), and blood pressure. Patients with AI showed more depressive symptoms, had a greater BMI and lower systolic blood pressure compared to controls. Adjusted analyses controlling for these variables revealed that patients with AI performed significantly worse in verbal learning (F=7.8, p=.007). Executive function, concentration, working memory, verbal memory, visuospatial memory, and autobiographical memory did not differ between groups. No clinically relevant cognitive impairment was found in patients with AI compared to matched controls. Even long-term glucocorticoid and mineralocorticoid substitution over almost two decades appears to have only subtle effects on cognition in patients with AI. Copyright © 2015 Elsevier Ltd. All rights reserved.
In the first part of this thesis we discuss a concise stepwise approach for the diagnostic evaluation of adrenal insufficiency (AI), taking into account the possible pitfalls associated with the different tests. The second part describes the history of replacement therapy, discusses the current imperfections and gives a perspective on future developments. Next, we discuss the results of the use of salivary cortisol day curves in the individual adjustment of therapy in AI, showing that over-re...
Bayrak, Z; Turan, V; Demirtaş, G; Erdoğan, M; Aşkar, N
Primer adrenal yetmezlik nadir görülen bir endokrinolojik hastalıktır. Çoğu idiopatiktir. Tip 1 diabetes mellitus, hipertiroidizm, hipotiroidizm, pernisiyöz anemi gibi otoimmun hastalıklarla ilişkilidir. Yirmi sekiz yaşında 18 yıldır Addison hastalığı nedeni ile tedavi gören ve gebelik istemi olan olguyu gebeliğin ilk haftalarından doğuma ve puerperal döneme kadar takip ettik. Endokrinoloji kliniği ile birlikte takip ettiğimiz hastada kortikosteroid tedavisi ile antenatal ve postnatal dönemde...
Full Text Available MeCab user dictionary for science technology term Addison-Biermer貧血 名詞 サ変接続 * * * * 悪性貧血... アクセイヒンケツ アクセイヒンケツ Thesaurus2015 200906044106165134 C LS51 UNKNOWN_2 Addison - Biermer 貧血
Zhernakova, Alexandra; Withoff, Sebo; Wijmenga, Cisca
Many endocrine diseases, including type 1 diabetes mellitus, Graves disease, Addison disease and Hashimoto disease, originate as an autoimmune reaction that affects disease-specific target organs. These autoimmune diseases are characterized by the development of specific autoantibodies and by the
What Works Clearinghouse, 2010
"Scott Foresman-Addison Wesley Elementary Mathematics" is a core curriculum for students at all ability levels in prekindergarten through grade 6. The program supports students' understanding of key math concepts and skills and covers a range of mathematical content across grades. The What Works Clearinghouse (WWC) reviewed 12 studies on…
What Works Clearinghouse, 2013
"Scott Foresman-Addison Wesley Elementary Mathematics" is a core mathematics curriculum for students in prekindergarten through grade 6. The program aims to improve students' understanding of key math concepts through problem-solving instruction, hands-on activities, and math problems that involve reading and writing. The curriculum…
Discussão: A doença de Addison é uma patologia rara em idade pediátrica e o seu diagnóstico requer um elevado grau de suspeição, dada a inespecificidade da sintomatologia inicial. Os autores pretendem alertar para a suspeição necessária perante uma clínica de hiponatrémia associada a sintomas constitucionais e gastrointestinais.
Moreira, A.C.; Foss, M.C.; Iazigi, N.
The diagnostic value of 900-1,100 am plasma ACTH radioimmunoassay were studied in 10 patients with Cushing's disease before and after treatment, three patients with Cushing's syndrome with adrenal tumours, one Nelson's syndrome patient; 13 patients with Addison's disease and 12 patients with hypo-pituitarism. Twenty-seven normal subjects were controls. The measurement of basal plasma ACTH gave good differentiation between: a. pituitary Cushing's disease from adrenal tumors; b. Addison's disease from hypo-pituitarism. However this assay has a limited value for the differentiation between Cushing's disease from normal subjects and it is often unhelpful in the differential diagnosis of hypo-pituitarism from normal subjects. (author)
Gracia-Ramos, Abraham Edgar; Cruz-Domínguez, María del Pilar; Vera-Lastra, Olga Lidia
Castleman's disease is an atypical lymphoproliferative disorder which may be compatible with paraneoplastic manifestations of POEMS syndrome. a 53 year old man with a history of type 2 diabetes, hypothyroidism and Addison's disease presented with numbness and weakness in limbs, dyspnea, skin hardening, Raynaud's phenomenon, weight loss and fatigue. A physical exam showed tachypnea, generalized cutaneous hyperpigmentation and skin hardening of extremities, muscle weakness, hypoesthesia and hyporeflexia. Laboratory showed hyperprolactinemia, low testosterone, hypothyroidism and Addison's disease. Electrophoresis of proteins showed polyclonal hypergammaglobulinemia. Somatosensory evoked potentials reported peripheral neuropathy and severe axonal polyneuropathy by electromyography. Chest X-rays showed bilateral reticular infiltrates and mediastinal widening. An echocardiogram displayed moderate pulmonary hypertension. Skin biopsy had no evidence of scleroderma. CT reported axillar, mediastinal and retroperitoneal nodes. The mediastinal lesion biopsy reported hyaline vascular Castleman's disease, multicentric variety. He was treated with rituximab. the case meet criteria for multicentric hyaline vascular Castleman's disease, POEMS variant, treated with rituximab.
Kline, Sarah; Rooker, Leah; Nobrega-Lee, Michelle; Guthrie, Amanda
A 22-yr-old, captive-born, presumed female Hoffmann's two-toed sloth (Choloepus hoffmanni) presented in respiratory distress with severe dehydration and symptoms of hypotension. During treatment, dysphagia was noted and oral examination revealed enlarged palatine tonsils and mucosal plaques. Bloodwork showed a decreased sodium:potassium ratio, a low baseline cortisol, a decreased adrenocorticotropin response test, and a blunted aldosterone stimulation test. All values were compared to a healthy male Hoffmann's two-toed sloth at the same facility. Despite aggressive medical management and treatment for hypoadrenocorticism, the sloth was found deceased. Necropsy revealed abdominal effusion, multifocal plaques throughout the upper gastrointestinal tract, and testes. Histopathology showed marked adrenal cortical atrophy and intranuclear mucosal inclusions in the gastrointestinal tract; advanced molecular techniques did not uncover any viral etiologies. This is the first reported case of hypoadrenocorticism in a sloth.
Bain, Anna; Stewart, Munro; Mwamure, Peter; Nirmalaraj, Kingsley
A 57-year-old Caucasian woman with known autoimmune hypothyroidism diagnosed in 2006 presented to hospital with flu-like symptoms and circulatory collapse. She reported weight loss and gradual increase in her skin pigmentation over a 1-year period. Aggressive fluid resuscitation was instituted. Hormonal tests showed primary adrenal insufficiency. Appropriate steroid replacement was started with rapid clinical response. Subsequent antibody tests confirmed the diagnosis of autoimmune polyglandular type 2 (Schmidt's) syndrome. The adrenal crisis had been precipitated by influenza virus type B infection. 2015 BMJ Publishing Group Ltd.
Schultebraucks, Katharina; Wingenfeld, Katja; Otte, Christian; Quinkler, Marcus
Primary adrenal insufficiency (AI) requires hormone replacement therapy with fludrocortisone and hydrocortisone stimulating glucocorticoid (GR) and mineralocorticoid receptors (MR). Evidence from animal and human studies shows that MR function is crucial for cognitive function and mood. Regarding patients with AI, very little is known about the role of MR in cognitive function and mood. A repeated-measures within-subject design was used to determine whether cognitive function and mood are related to MR occupation in patients with AI. Intraindividually, patients were examined twice, with 1 week between testing days: once with fludrocortisone (high MR occupation) and once without fludrocortisone (low MR occupation). All patients kept their stable regimen of hydrocortisone. The assessment of cognitive function included executive function, attention, and verbal, visuospatial and working memory. Additionally, mood and blood pressure were measured. Verbal memory improved significantly during high MR occupation (after fludrocortisone intake) compared to low MR occupation [without fludrocortisone, t(29) = -2.1, p = 0.046]. There were trend level differences in the Number-Combination test [t(29) = -1.9, p = 0.074] and in the Stroop interference task [t(29) = -1.9, p = 0.068]. No significant differences in visuospatial and working memory were found. Furthermore, the current mood state was better during high MR occupation compared to low MR occupation [t(29) = -2.4, p = 0.023] as was diastolic blood pressure [F(2, 29) = 3.6, p = 0.07]. Cognitive function and mood in patients with AI depend in part on MR occupation. Because the medium effect size indicates a potential clinical significance, further studies should systematically examine which dosages of fludrocortisone are associated with optimal cognitive function and mood in AI patients. © 2015 S. Karger AG, Basel.
Magitta, N. F.; Wolff, A. S. Boe; Johansson, S.; Skinningsrud, B.; Lie, B. A.; Myhr, K-M; Undlien, D. E.; Joner, G.; Njolstad, P. R.; Kvien, T. K.; Forre, O.; Knappskog, P. M.; Husebye, E. S.
Variants in the gene encoding NACHT leucine-rich-repeat protein 1 (NALP1), an important molecule in innate immunity, have recently been shown to confer risk for vitiligo and associated autoimmunity. We hypothesized that sequence variants in this gene may be involved in susceptibility to a wider
Skedros, John G.; Kiser, Casey J.; Mendenhall, Shaun D.
This report describes a patient who had a series of daily interscalene nerve blocks to treat pain following a shoulder manipulation for postsurgical stiffness. She experienced acute respiratory compromise that persisted for many weeks. All typical and unusual causes of these symptoms were ruled out. Her treating pulmonologist theorized that the ipsilateral carotid body had been injured. However, it was subsequently determined that the constellation of symptoms and their prolonged duration wer...
Hangaard, J; Andersen, M; Grodum, E
, increasing significantly (P glucocorticoids, when the pulse frequency was also significantly reduced (P ... of glucocorticoids on the TSH response to TRH, our data indicate that even physiological serum levels of cortisol have an influence on endogenous TSH secretion, probably caused by regulation of the pituitary sensitivity to TRH....
Shapiro, M. S.; Trebich, C.; Shilo, L.; Shenkman, L.
Severe generalized myalgias and muscle contractures of the lower extremities were the major initial manifestations of adrenal insufficiency in a 26 year old black male. The intensity of increased skin pigmentation was not fully appreciated until the patient's skin colour was compared to that of his brother. Replacement with physiological doses of gluco- and mineralocorticoids was associated with complete amelioration of symptomatology.
Full Text Available A female Rottweiler dog was presented with a history of intermittent vomiting and diarrhoea, dysorexia, weakness, and weight loss. Haemocytometry and biochemistry values were within normal ranges except for electrolyte analyses, that demonstrated hyponatremia and hyperkalemia with a decreased sodium/potassium ratio. A diagnosis of hypoadrenocorticism was suspected. Basal and post-ACTH stimulation cortisolemia were within the normal values. Electrocardiography was normal, and thoracic radiography showed no significant modifications. On abdominal ultrasonography, adrenal glands appeared normal, while the bowel was distended, and several thin linear hyperechoic objects floating in the lumen were observed. Two adult female whipworms (Trichuris vulpis were collected following bowel irrigation. Anthelmintic treatment against the parasite was curative.
Kauw, D.; Repping-Wuts, H.; Noordzij, A.; Stikkelbroeck, N.; Hermus, A.R.; Faber, M.J.
BACKGROUND: Addison's disease and Cushing's syndrome are rare. The Dutch Adrenal Society offers an online forum for Dutch adrenal patients to meet and communicate. However, little is known about the added value such a forum has for the delivery of patient-centered care. OBJECTIVE: Our aim was to
Jaya Prakash Sahoo
Full Text Available Background: Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab titer in Addison's disease with primary hypothyroidism. Materials and Methods: This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (22 pmol/L and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical was defined as high thyroid stimulating hormone (TSH with/without low free thyroxine (fT4. TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Results: Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. Conclusions: The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations.
Castillo, Víctor; Ortemberg, L.
La enfermedad de Addison (EA), la hiperplasia adrenal congénita (HAC) por déficit de 21 αhidroxilasa adrenal y el hipoparatiroidismo (HoPTH) son de diagnóstico poco frecuente, representando el 3% (EA) y 0,5% (tanto HAC como HoPTH) de las enfermedades endócrinas atendidas. Se describen 1 caso de EA congénito (collie de 6 meses de edad), 2 casos de HAC (una caniche toy y una labradora, ambas de 2 años) y 2 de HoPTH (cocker spaniel de 11 meses y una mestiza de 7 años). Por la signología clínica ...
Lakhotia, Manoj; Pahadia, Hans Raj; Kumar, Harish; Singh, Jagdish; Tak, Sandeep
Autoimmune Polyglandular syndrome (APS) are rare condition characterised by presence of immune dysfunction of two or more endocrine glands and other non-endocrine organs. APS is divided into 2 major subtypes based on age of presentation, pattern of disease combinations and mode of inheritance. APS 1(juvenile) usually manifest in early adolescence or in infancy. It is characterised by multiple endocrinal deficiency with mucocutaneous candidiasis and ectodermal dystrophy. Of the endocrine diseases, hypoparathyroidism form an important component followed by Addison's disease, type 1A diabetes, hypogonadism and thyroid disease. On the other hand APS II usually manifest in 3rd or 4th decade of life with female preponderance. Endocrine diseases commonly include autoimmune thyroid disease (graves or autoimmune thyroiditis), type 1A diabetes, and Addison's disease. Hypoparathyroidism is of rare occurrence and there is no mucocutaneous candidiasis. We report here a case of APS type II in a 29-year-old male who initially presented with hypothyroidism, which was soon followed by Addison's disease. The involvement of thyroid gland preceding the involvement of adrenal is of rare occurrence. The patient also had celiac disease which makes the combination further uncommon.
Full Text Available El título de este trabajo pretende, además de consignar su objetivo, señalar una insuficiencia: la de la patología psicosomática, impregnada, desde su origen, por conceptos psicoanalíticos que han dado lugar a explicaciones demasiado subjetivistas y alejadas de las ideas fisiopatológicas no superadas, al menos clínicamente, por la moderna versión norteamericana de las antiguas y equilibradas doctrinas socráticas de integración. Perseguimos en esta comunicación dos propósitos: contrastrar las concepciones psicosomáticas y fisiopatológicas del Basedow y de la insuficiencia suprarrenal, en el intento de poner de manifiesto la insuficiencia del criterio psicosomático; y, estudiar la fisiopatología de los principales síntomas del Basedow y del Addison que se expresan por la doble vertiente somatopsíquica. Estos síntomas serán, en el hipertiroidismo, la hiperemotividad y, singularmente, la prisa; y en la insuficiencia suprarrenal, la astenia.
Hill, R.C.; Buchanan, J.W.
Third degree heart block developed in an obese, 10-year-old Labrador retriever with adrenocortical failure. A permanent transthoracic pacemaker was fitted, but the pulse generator migrated 2 years later, to the ventral part of the flank, where an abscess formed. A new pacemaker was fitted, but also migrated and rotated and a syndrome analogous to Twiddler's syndrome in man developed. After a further 2 years the second pacemaker was located, encapsulated within the right pleural cavity. Culture of the brownish exudate around the pulse generator yielded Pseudomonas sp
Aldosterone - urine; Addison disease - urine aldosterone; Cirrhosis - serum aldosterone ... Laxative abuse Lower than normal levels may indicate Addison disease , a disorder in which the adrenal glands do ...
... multiple sclerosis (MS), low levels of steroid hormones (Addison's disease), depression, schizophrenia, chronic fatigue syndrome (CFS), muscle damage ... Sjögren's syndrome that causes symptoms including dry mouth. Addison's disease. Research about the effects of DHEA on Addison's ...
Rzymski, K.; Sobieszczyk, S.; Kosowicz, J.; Akademia Medyczna, Poznan
In 30 cases of chronic adrenal insufficiency (Addison's disease) CT of the adrenal glands was performed using a fourth generation scanner and a 2 mm slice thickness. Adrenal glands were visualized in all the cases. In 26 patients the adrenals were atrophied; the adrenal shape was abnormal in 21 patients. In 15 patients CT disclosed calcifications in one or both glands, which were particularly frequent in patients over the age of 50. Atrophy of adrenal glands was of high occurrence in cases of autoimmune origin. (orig.) [de
High grade primary adrenal intravascular large B-cell lymphoma manifesting as Addison disease Linfoma intravascular de alto grado de células B grandes y origen suprarrenal que se manifiesta en forma de enfermedad de Addison
J. Venizelos; D. Tamiolakis; M. Lambropoulou; G. Alexiadis; G. Petrakis; N. Papadopoulos
We report a rare case of a 68 aged male who presented with adrenal failure and was diagnosed of high grade large B-cell lymphoma primarily arising in the adrenal glands. The patient was administrated with additional chemotherapy but he passed away 7 months later due to infection in the lungs. Intravascular lymphoma should be suspected in patients with bilateral adrenal masses who present with rapidly progressive adrenal insufficiency.Publicamos el caso poco frecuente de un varón de 68 años de...
High grade primary adrenal intravascular large B-cell lymphoma manifesting as Addison disease Linfoma intravascular de alto grado de células B grandes y origen suprarrenal que se manifiesta en forma de enfermedad de Addison
Full Text Available We report a rare case of a 68 aged male who presented with adrenal failure and was diagnosed of high grade large B-cell lymphoma primarily arising in the adrenal glands. The patient was administrated with additional chemotherapy but he passed away 7 months later due to infection in the lungs. Intravascular lymphoma should be suspected in patients with bilateral adrenal masses who present with rapidly progressive adrenal insufficiency.Publicamos el caso poco frecuente de un varón de 68 años de edad que debutó con insuficiencia adrenal y fue diagnosticado de linfoma de alto grado de células B grandes ubicado principalmente en las glándulas suprarrenales. Al paciente le administraron quimioterapia adicional, pero falleció 7 meses después de infección pulmonar. El linfoma intravascular debe sospecharse en los pacientes con masas suprarrenales bilaterales que presenten insuficiencia adrenal rápidamente progresiva.
Muscogiuri, Giovanna; Mitri, Joanna; Mathieu, Chantal; Badenhoop, Klaus; Tamer, Gonca; Orio, Francesco; Mezza, Teresa; Vieth, Reinhold; Colao, Annamaria; Pittas, Anastassios
It has been suggested that vitamin D may play a role in the pathogenesis of several endocrine diseases, such as hyperparathyroidism, type 1 diabetes (T1DM), type 2 diabetes (T2DM), autoimmune thyroid diseases, Addison's disease and polycystic ovary syndrome (PCOS). In this review, we debate the role of vitamin D in the pathogenesis of endocrine diseases. Narrative overview of the literature synthesizing the current evidence retrieved from searches of computerized databases, hand searches and authoritative texts. Evidence from basic science supports a role for vitamin D in many endocrine conditions. In humans, inverse relationships have been reported not only between blood 25-hydroxyvitamin D and parathyroid hormone concentrations but also with risk of T1DM, T2DM, and PCOS. There is less evidence for an association with Addison's disease or autoimmune thyroid disease. Vitamin D supplementation may have a role for prevention of T2DM, but the available evidence is not consistent. Although observational studies support a potential role of vitamin D in endocrine disease, high quality evidence from clinical trials does not exist to establish a place for vitamin D supplementation in optimizing endocrine health. Ongoing randomized controlled trials are expected to provide insights into the efficacy and safety of vitamin D in the management of endocrine disease. © 2014 European Society of Endocrinology.
Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi
Text mining is a flexible technology that can be applied to numerous different tasks in biology and medicine. We present a system for extracting disease-gene associations from biomedical abstracts. The system consists of a highly efficient dictionary-based tagger for named entity recognition...... of human genes and diseases, which we combine with a scoring scheme that takes into account co-occurrences both within and between sentences. We show that this approach is able to extract half of all manually curated associations with a false positive rate of only 0.16%. Nonetheless, text mining should...... not stand alone, but be combined with other types of evidence. For this reason, we have developed the DISEASES resource, which integrates the results from text mining with manually curated disease-gene associations, cancer mutation data, and genome-wide association studies from existing databases...
Freeman, Hugh James
Celiac disease (CD) is an autoimmune small intestinal mucosal disorder that often presents with diarrhea, malabsorption and weight loss. Often, one or more associated endocrine disorders may be associated with CD. For this review, methods involved an extensive review of published English-language materials. In children and adolescents, prospective studies have demonstrated a significant relationship to insulin-dependent or type 1 diabetes, whereas in adults, autoimmune forms of thyroid disease, particularly hypothyroidism, may commonly co-exist. In some with CD, multiple glandular endocrinopathies may also occur and complicate the initial presentation of the intestinal disease. In others presenting with an apparent isolated endocrine disorder, serological screening for underlying subclinical CD may prove to be positive, particularly if type 1 diabetes, autoimmune thyroid or other autoimmune endocrine diseases, such as Addison's disease are first detected. A number of reports have also recorded hypoparathyroidism or hypopituitarism or ovarian failure in CD and these may be improved with a strict gluten-free diet.
... glands, such as Addison's disease, type 1 diabetes, Graves' disease, or vitiligo. Research suggests a link may exist ... disorders (such as Addison's disease, type 1 diabetes, Graves' disease, or vitiligo). Research suggests a link may exist ...
Kauw, Dirkjan; Repping-Wuts, Han; Noordzij, Alida; Stikkelbroeck, Nike; Hermus, Ad; Faber, Marjan
Addison's disease and Cushing's syndrome are rare. The Dutch Adrenal Society offers an online forum for Dutch adrenal patients to meet and communicate. However, little is known about the added value such a forum has for the delivery of patient-centered care. Our aim was to analyze the purposes of online patient-to-patient forum conversations, within the context of patient-centered care. For this study a consecutive sample of 300 questions ("threads") from the past 3.5 years was selected from the forum. The content of these patient-driven questions was analyzed based on the dimensions of patient-centeredness of the Picker Institute. This analysis was performed using ATLAS.ti. From the 390 questions analyzed, 80.8% (N=315) were intended to gain more information about the disease, the treatment, and to verify if other patients had similar complaints. To a much lesser extent (38/390, 9.7%), questions expressed a call for emotional support. Patients answered primarily by giving practical tips to fellow patients and to share their own experiences. On an online patient forum for Cushing's syndrome and Addison's disease, patients appear to primarily gain knowledge and, to a lesser extent, emotional support from their peers. This experience-based knowledge has become a very important information source. As such, patients can make a substantial contribution to the creation of patient-centered care if this knowledge is integrated into the care provided by health care professionals.
Meyer, Gesine; Badenhoop, Klaus; Linder, Roland
Adrenal crises are potentially life-threatening complications in patients with adrenal insufficiency (AI). Our objective was to investigate the frequency of adrenal crises in different forms of AI. The Statutory Health Insurance (SHI) database of the Techniker Krankenkasse - covering more than 12% of the German population - was analysed for diagnostic codes from 1 January 2010 to 31 December 2013. By analysis of routine data from a large healthcare provider. Diagnoses of AI were recorded and classified in primary AI, secondary AI and autoimmune polyglandular syndrome (APS). The ICD-code E27·2 (AC) was retrieved in all cohorts. We found a prevalence of 222/million for secondary and 126/million for primary AI. AC was documented with a frequency of 4·8/100 patient years. Crises were significantly more frequent in patients with primary (7·6/100 patient years) compared to those with secondary AI (3·2/100 patient years; P < 0·0001). Prevalence of crises was higher in individuals with APS (10·9/100 patient years) and highest in patients with primary AI and type 1 diabetes (12·5/100 patient years). Applying a SHI database comprising more than 9 million individuals, we identified robust data about the risk of AC in different groups of patients with AI. Our data confirm and extend the clinical observation that patients with APS are at highest risk for AC. Approximately 1 of 8 patients with primary AI and type 1 diabetes suffers from an AC each year. Specific targeting of efforts aiming at the prevention of AC is necessary. © 2016 John Wiley & Sons Ltd.
Kahaly, George J; Schuppan, Detlef
Celiac disease (CD) is a small-intestinal inflammatory disease that is triggered by the ingestion of the storage proteins (gluten) of wheat, barley and rye. Endocrine autoimmunity is prevalent in patients with CD and their relatives. The genes that predispose to endocrine autoimmune diseases, e.g. type 1 diabetes, autoimmune thyroid diseases, and Addison's disease, i.e. DR3-DQ2 and DR4-DQ8, are also the major genetic determinants of CD, which is the best understood HLA-linked disease. Thus, up to 30% of first-degree relatives both of patients with CD and/or endocrine autoimmunity are affected by the other disease. In CD, certain gluten proteins bind with high affinity to HLA-DQ2 or -DQ8 in the small-intestinal mucosa, to activate gluten-specific T cells which are instrumental in the destruction of the resorptive villi. Here, the autoantigen tissue transglutaminase increases the T cell response by generating deamidated gluten peptides that bind more strongly to DQ2 or DQ8. Classical symptoms such as diarrhea and consequences of malabsorption like anemia and osteoporosis are often absent in patients with (screening-detected) CD, but this absence does not significantly affect these patients' incidence of endocrine autoimmunity. Moreover, once autoimmunity is established, a gluten-free diet is not able to induce remission. However, ongoing studies attempt to address how far a gluten-free diet may prevent or retard the development of CD and endocrine autoimmunity in children at risk. The close relationship between CD and endocrine autoimmunity warrants a broader immune genetic and endocrine screening of CD patients and their relatives. © 2015 S. Karger AG, Basel.
... adrenal gland is damaged due to, for example, Addison disease or other adrenal gland disease, and surgery The ... Call your health care provider if you have Addison disease and are unable to take your glucocorticoid medicine ...
... response Different diseases, such as Cushing syndrome and Addison disease , can lead to either too much or too ... disorders A lower than normal level may indicate: Addison disease in which the adrenal glands do not produce ...
... levels, it may indicate: Diarrhea Vomiting Kidney disease Addison disease , a condition in which your body's adrenal glands ... Version [Internet]. Kenilworth (NJ): Merck & Co. Inc.; c2017. Addison Disease [cited 2017 Apr 2]; [about 2 screens]. Available ...
... bed rest. The disorder may be associated with Addison's disease, diabetes, and certain neurological disorders including Multiple System ... bed rest. The disorder may be associated with Addison's disease, diabetes, and certain neurological disorders including Multiple System ...
... until the adrenal glands start functioning normally again. Addison's Disease This rare disorder develops when the adrenal glands ... not make enough cortisol. In most cases of Addison's disease, the body also doesn't make enough of ...
... occurs when there is not enough cortisol) Addison disease (adrenal glands do not produce enough cortisol) Hypopituitarism (pituitary gland ... A.M. Editorial team. Addison Disease Read more Adrenal Gland Disorders Read more Pituitary Disorders Read more A.D. ...
Leone, James E; Gray, Kimberly A; Massie, John E; Rossi, Jennifer M
To present the case of a collegiate tennis player with celiac disease symptoms. Celiac disease is a common intestinal disorder that is often confused with other conditions. It causes severe intestinal damage manifested by several uncomfortable signs and symptoms. Failure by the sports medicine staff to recognize symptoms consistent with celiac disease and treat them appropriately can have deleterious consequences for the athlete. Irritable bowel syndrome, Crohn disease, Addison disease, lupus erythematosus, juvenile rheumatoid arthritis, lactose intolerance, herpes zoster, psychogenic disorder (depression), fibromyalgia, complex regional pain syndrome, hyperthyroidism, anemia, type I diabetes. The athlete underwent a series of blood and allergen tests to confirm or refute a diagnosis of celiac disease. When celiac disease was suspected, dietary modifications were made to eliminate all wheat-based and gluten-based products from the athlete's diet. The athlete was able to fully compete in a competitive National Collegiate Athletic Association Division I tennis program while experiencing the debilitating effects associated with celiac disease. The immediacy of symptom onset was notable because the athlete had no history of similar complaints. Celiac disease is a potentially life-threatening condition that affects more people than reported. A properly educated sports medicine staff can help to identify symptoms consistent with celiac disease early, so damage to the intestine is minimized. Prompt recognition and appropriate management allow the athlete to adjust the diet accordingly, compete at a high-caliber level, and enjoy a healthier quality of life.
Dec 2, 2009 ... Histoplasmosis, caused by two varieties of dimorphic fungi, Histoplasma ... from asymptomatic primary infection to disseminated disease in immunocompromised .... Addison's disease) tongue, gingivae, buccal mucosa,.
... standing up. Endocrine problems. Thyroid conditions, adrenal insufficiency (Addison's disease) and low blood sugar (hypoglycemia) can cause orthostatic hypotension, as can diabetes — which can damage ...
... management, and therapy of rare diseases, including the lipid storage diseases. Research on lipid storage diseases within the Network includes ... management, and therapy of rare diseases, including the lipid storage diseases. Research on lipid storage diseases within the Network includes ...
Regardless of their origin, neuroactive steroids are capable of modifying neural activities by modulating different types of membrane receptors. Neurosteroids are synthesized de novo in neurones and glia. Steroidogenic enzymes are found in the central nervous system. Classical steroid receptors are localized in the cytoplasm, they exert regulatory actions on the genome, and their activation causes medium- and long-term effects. Non-classical receptors are located within the membrane and act as mediators of short-term effects. Other important players are co-repressors and co-activators that can interfere with or enhance the activity of steroid receptors. Beyond their function in stress, corticosteroids play a very important role in fear, anxiety, and memory functions. Patients with Cushing's syndrome frequently develop mood disorder, reversible brain atrophy with transient memory loss, rarely delirium or psychosis. Well-known peripheral symptom is steroidal myopathy. In patients with Addison's disease the main signs are weakness of muscles, lack of energy, decreased mental functions and reduced quality of life. Estrogen and progesterone have their own respective hormone receptors, whereas allopregnanolone acts via the GABA receptors. These hormones have significant role in the development of brain, the architecture of neural circuits and dendrites, density of axonal connections, and the number of neurons. They influence maturation, neuroprotection, seizures, cognitive functions, mood, anxiety, pain, and restitution of peripheral nerves. Androgens also affect cognitive functions, pain, anxiety, mood, and additionally aggression.
... Syndrome (PCOS) Pregnancy and Thyroid Disease Primary Hyperparathyroidism Prolactinoma Thyroid Tests Turner Syndrome Contact Us The National ... Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información de la ...
Mukkada, Philson J; Franklin, Teenu; Rajeswaran, Rangasami; Joseph, Santhosh
Ribbing disease is a rare sclerosing dysplasia that involves long tubular bones, especially the tibia and femur. It occurs after puberty and is reported to be more common in women. In this article we describe how Ribbing disease can be differentiated from diseases like Engelmann-Camurati disease, van Buchem disease, Erdheim-Chester disease, osteoid osteoma, chronic osteomyelitis, stress fracture, etc
... Home › Aging & Health A to Z › Prostate Diseases Font size A A A Print Share Glossary Basic ... body. Approximately 3 million American men have some type of prostate disease. The most common prostate diseases ...
... But some of them can make you sick. Infectious diseases are diseases that are caused by germs. There ... many different ways that you can get an infectious disease: Through direct contact with a person who is ...
Semantic dementia; Dementia - semantic; Frontotemporal dementia; FTD; Arnold Pick disease; 3R tauopathy ... doctors tell Pick disease apart from Alzheimer disease. (Memory loss is often the main, and earliest, symptom ...
... with facebook share with twitter share with linkedin Prion Diseases Prion diseases are a related group of ... deer and elk. Why Is the Study of Prion Diseases a Priority for NIAID? Much about TSE ...
... diseases. The primary research focus was on oral bacteria. Periodontal diseases were thought to begin when chalky white ... tools to target their treatment specifically to the bacteria that trigger periodontal disease. At the same time, because biofilms form ...
to other autoimmune diseases, the etiology of T1D remains obscure but ..... T1D, type 1 diabetes; AIT, autoimmune thyroiditis; CD, celiac disease; AD, Addison's disease. Table 5. .... (GAD65Ab) in prediabetic adults developing diabetes.
... 2011 survey of clinical practice patterns in the management of Graves' disease. Journal of Clinical Endocrinology and Metabolism. 2012 Dec;97( ... 30 a.m. to 5 p.m. eastern time, M-F Follow Us NIH… Turning Discovery Into ... Disease Urologic Diseases Endocrine Diseases Diet & Nutrition ...
... you're like most people, you think that heart disease is a problem for others. But heart disease is the number one killer in the ... of disability. There are many different forms of heart disease. The most common cause of heart disease ...
Gaucher disease is a rare, inherited disorder. It is a type of lipid metabolism disorder. If you ... affected. It usually starts in childhood or adolescence. Gaucher disease has no cure. Treatment options for types ...
... spread to the nervous system, causing facial paralysis ( Bell's palsy ), or meningitis. The last stage of Lyme disease ... My Lyme Disease Risk? Bug Bites and Stings Bell's Palsy Rocky Mountain Spotted Fever Meningitis View more About ...
... Stargardt disease, lipofuscin accumulates abnormally. The Foundation Fighting Blindness supports research studying lipofuscin build up and ways to prevent it. A decrease in color perception also occurs in Stargardt disease. This is ...
... night blindness due to degeneration of the retina (retinitis pigmentosa). If the disease progresses, other symptoms may include ... night blindness due to degeneration of the retina (retinitis pigmentosa). If the disease progresses, other symptoms may include ...
... likely need to plan for their loved one's future care. The final phase of the disease may ... disease and other dementias. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine . 25th ed. Philadelphia, PA: ...
... SEARCH Definition Treatment Prognosis Clinical Trials Organizations Publications Definition Menkes disease is caused by a defective gene named ATPTA ... arteries. Weakened bones (osteoporosis) may result in fractures. × Definition Menkes disease is caused by a defective gene named ATPTA ...
... SEARCH Definition Treatment Prognosis Clinical Trials Organizations Publications Definition Fabry disease is caused by the lack of or faulty ... severe symptoms similar to males with the disorder. × Definition Fabry disease is caused by the lack of or faulty ...
Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases: Diseases caused by viruses, such as hepatitis ...
... Lactose Intolerance Liver Disease Ménétrier’s Disease Microscopic Colitis Ostomy Surgery of the Bowel Pancreatitis Peptic Ulcers (Stomach ... and outreach materials. Clinical Trials Clinical trials offer hope for many people and opportunities to help researchers ...
... Staying Safe Videos for Educators Search English Español Kidney Disease KidsHealth / For Teens / Kidney Disease What's in ... Coping With Kidney Conditions Print What Do the Kidneys Do? You might never think much about some ...
... which had been particularly high in people of Eastern European and Ashkenazi Jewish descent, but Sandhoff disease ... which had been particularly high in people of Eastern European and Ashkenazi Jewish descent, but Sandhoff disease ...
Parvovirus B19; Erythema infectiosum; Slapped cheek rash ... Fifth disease is caused by human parvovirus B19. It often affects preschoolers or school-age children during the spring. The disease spreads through the fluids in the nose and mouth ...
This paper is aimed to discuss the involvement of delayed radiation effects of A-bomb exposure in cardiovascular diseases. First, the relationship between radiation and cardiovascular diseases is reviewed in the literature. Animal experiments have confirmed the relationship between ionizing radiation and vascular lesions. There are many reports which describe ischemic heart disease, cervical and cerebrovascular diseases, and peripheral disease occurring after radiation therapy. The previous A-bomb survivor cohort studies, i.e., the RERF Life Span Study and Adult Health Study, have dealt with the mortality rate from cardiovascular diseases, the prevalence or incidence of cardiovascular diseases, pathological findings, clinical observation of arteriosclerosis, ECG abnormality, blood pressure abnormality, and cardiac function. The following findings have been suggested: (1) A-bomb exposure is likely to be involved in the mortality rate and incidence of ischemic heart disease and cerebrovascular diseases; (2) similarly, the involvement of A-bomb exposure is considered in the prevalence of the arch of aorta; (3) ECG abnormality corresponding to ischemic heart disease may reflect the involvement of A-bomb exposure. To confirm the above findings, further studies are required on the basis of more accurate information and the appropriate number of cohort samples. Little evidence has been presented for the correlation between A-bomb exposure and both rheumatic heart disease and congenital heart disease. (N.K.) 88 refs
Penaranda P, Edgar; Spinel B, Nestor; Restrepo, Jose F; Rondon H, Federico; Millan S, Alberto; Iglesias G Antonio
We present a review article on the autoinflammatory diseases, narrating its historical origin and describing the protein and molecular structure of the Inflammasome, the current classification of the autoinflammatory diseases and a description of the immuno genetics and clinical characteristics more important of every disease.
Taylor, George C.
This overview of the public health significance of Lyme disease includes the microbiological specifics of the infectious spirochete, the entomology and ecology of the ticks which are the primary disease carrier, the clinical aspects and treatment stages, the known epidemiological patterns, and strategies for disease control and for expanded public…
... excretion of large amounts of dilute urine, accompanied by extreme thirst), adrenal hypertension, Addison's disease (caused by destruction of the adrenal glands), dehydration, inappropriate antidiuretic hormone secretion, or other diseases involving electrolyte imbalance. (b) Classification. Class II. ...
... Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer Disease Anemia Angina Ankylosing Spondylitis Anthrax ... Patient Resources For Health Professionals Subscribe Search hCG Pregnancy Send Us Your Feedback Choose Topic At a ...
... Adrenal Insufficiency and Addison's Disease National Institute of Neurological Disorders and Stroke: Dysautonomia Educational Resources (5 links) Boston Children's Hospital: Achalasia Disease InfoSearch: Achalasia Addisonianism Alacrimia Syndrome ...
Rina R Rus
Full Text Available Dent disease is an x-linked disorder of proximal renal tubular dysfunction that occurs almost exclusively in males. It is characterized by significant, mostly low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and chronic kidney disease. Signs and symptoms of this condition appear in early childhood and worsen over time. There are two forms of Dent disease, which are distinguished by their genetic cause and pattern of signs and symptoms (type 1 and type 2. Dent disease 2 is characterized by the features described above and also associated with extrarenal abnormalities (they include mild intellectual disability, hypotonia, and cataract. Some researchers consider Dent disease 2 to be a mild variant of a similar disorder called Lowe syndrome.We represent a case of a 3-year old boy with significant proteinuria in the nephrotic range and hypercalciuria. We confirmed Dent disease type 1 by genetic analysis.
Ohn, Jungyoon; Park, Seon Yong; Moon, Jungyoon; Choe, Yun Seon; Kim, Kyu Han
Morgellons disease is a rare disease with unknown etiology. Herein, we report the first case of Morgellons disease in Korea. A 30-year-old woman presented with a 2-month history of pruritic erythematous patches and erosions on the arms, hands, and chin. She insisted that she had fiber-like materials under her skin, which she had observed through a magnifying device. We performed skin biopsy, and observed a fiber extruding from the dermal side of the specimen. Histopathological examination sho...
Full Text Available Abstract Celiac disease is a chronic intestinal disease caused by intolerance to gluten. It is characterized by immune-mediated enteropathy, associated with maldigestion and malabsorption of most nutrients and vitamins. In predisposed individuals, the ingestion of gluten-containing food such as wheat and rye induces a flat jejunal mucosa with infiltration of lymphocytes. The main symptoms are: stomach pain, gas, and bloating, diarrhea, weight loss, anemia, edema, bone or joint pain. Prevalence for clinically overt celiac disease varies from 1:270 in Finland to 1:5000 in North America. Since celiac disease can be asymptomatic, most subjects are not diagnosed or they can present with atypical symptoms. Furthermore, severe inflammation of the small bowel can be present without any gastrointestinal symptoms. The diagnosis should be made early since celiac disease causes growth retardation in untreated children and atypical symptoms like infertility or neurological symptoms. Diagnosis requires endoscopy with jejunal biopsy. In addition, tissue-transglutaminase antibodies are important to confirm the diagnosis since there are other diseases which can mimic celiac disease. The exact cause of celiac disease is unknown but is thought to be primarily immune mediated (tissue-transglutaminase autoantigen; often the disease is inherited. Management consists in life long withdrawal of dietary gluten, which leads to significant clinical and histological improvement. However, complete normalization of histology can take years.
Full Text Available Celiac disease is a multysystemic autoimmune disease induced by gluten in wheat, barley and rye. It is characterized by polygenic predisposition, high prevalence (1%, widely heterogeneous expression and frequent association with other autoimmune diseases, selective deficit of IgA and Down, Turner and Williams syndrome. The basis of the disease and the key finding in its diagnostics is symptomatic or asymptomatic inflammation of the small intestinal mucosa which resolves by gluten-free diet. Therefore, the basis of the treatment involves elimination diet, so that the disorder, if timely recognized and adequately treated, also characterizes excellent prognosis.
Taylor, Frederick L; Levine, Laurence A
Peyronie's disease is a psychologically and physically devastating disorder that is manifest by a fibrous inelastic scar of the tunica albuginea, resulting in palpable penile scar in the flaccid condition and causing penile deformity, including penile curvature, hinging, narrowing, shortening, and painful erections. Peyronie's disease remains a considerable therapeutic dilemma even to today's practicing physicians.
Radiological semiotics of parasitogenic diseases of the intestinal tract is presented. The problem of radiological examination in the case of the diseases consists in the determination of the large intestine state, depth and extension of lesions, and also in solution of treatment efficiency problem
... the country. NIH is the leading supporter of biomedical research in the world. Much of NINDS’ research on Batten disease and the neuronal ceroid lipofuscinoses focuses on gaining a better understanding of the disease, gene therapy, and developing novel drugs to treat the disorders. ...
... and ridding your body of toxic substances. Liver disease can be inherited (genetic) or caused by a variety of factors that damage the ... that you can't stay still. Causes Liver disease has many ... or semen, contaminated food or water, or close contact with a person who is ...
... X-linked form of Leigh’s disease, a high-fat, low-carbohydrate diet may be recommended. View Full Treatment Information Definition Leigh's disease is a rare inherited neurometabolic disorder that affects the central nervous system. This progressive disorder begins in infants between the ...
... ears and head) special tests that check your balance and how well your ears work. Can Meniere’s disease be prevented or avoided? Because ... find ways to limit the stress in your life or learn how to deal with stress ... Let your family, friends, and co-workers know about the disease. Tell ...
Foundations of roentgenological semiotics of parasitic diseases of lungs, w hich are of the greatest practical value, are presented. Roentgenological pictu res of the following parasitic diseases: hydatid and alveolar echinococcosis, pa ragonimiasis, toxoplasmosis, ascariasis, amebiasis, bilharziasis (Schistosomias is) of lungs, are considered
Oct 12, 2011 ... 1988). Since the disease emerged in this specific geographic area, HHS was initially referred to as “Angara. Disease”. The disease is caused by an avian adenovirus serotype-iv in Pakistan. This virus is responsible for development of intranuclear inclusion bodies in the cells of liver, pancreas and kidneys.
... monitor a disease) for HD. A large and related NINDS-supported study aims to identify additional genetic factors in people that influence the course of the disease. Other research hopes to identify variations in the genomes of individuals with HD that may point to new targets ...
Mar 8, 2013 ... Two factors are involved in the development of coeliac disease, namely the ... degradation by gastric, pancreatic and intestinal brush ... epithelial layer with chronic inflammatory cells in patients ... Coeliac disease increases the risk of malignancies, such as small bowel adenocarcinoma and enteropathy-.
Full Text Available Celiac disease also known as gluten-sensitive enteropathy is characterized by intestinal mucosal damage and malabsorption from dietary intake of wheat, rye or barley. Symptoms may appear with introduction of cereal in the first 3 years of life. A second peak in symptoms occurs in adults during the third or forth decade and even as late as eight decade of life. The prevalence of this disease is approximately 1 in 250 adults. The disease is more prevalent in Ireland as high as 1 in 120 adults. The disorder occurs in Arab, Hispanics, Israeli Jews, Iranian and European but is rare in Chinese and African American. To have celiac disease the patient should have the celiac disease genetic markers as HLA DQ 2 and HLA DQ 8. Patient with celiac disease may have 95 per cent for DQ 2 and the rest is by DQ 8. Someone may have the genetic marker and never develops the disease. In general 50 percent with markers may develop celiac disease. To develop the disease the gene needs to become activated. This may happen with a viral or bacterial infection, a surgery, delivery, accident, or psychological stress. After activation of gene cause the tight junction to opens with the release of Zonulin This results in passage of gluten through the tight junction and formation of multiple antibodies and autoimmune disease. This also allows entrance of other proteins and development of multiple food allergies. As a result is shortening, flattening of intestinal villi resulting in food, vitamins and minerals malabsorption.
Vasconcelos, Carlos; Kallenberg, Cees; Shoenfeld, Yehuda
Refractory disease (RD) definition has different meanings but it is dynamic, according to knowledge and the availability of new drugs. It should be differentiated from severe disease and damage definitions and it must take into account duration of adequate therapy and compliance of the patient. It
Squizzato, A.; Gerdes, V. E. A.; Brandjes, D. P. M.; Büller, H. R.; Stam, J.
Background and Purpose-Acute cerebral ischemia has been described in different diseases of the thyroid gland, and not only as a result of thyrotoxic atrial fibrillation and cardioembolic stroke. The purpose of this review is to summarize the studies on the relationship between thyroid diseases and
Ohn, Jungyoon; Park, Seon Yong; Moon, Jungyoon; Choe, Yun Seon; Kim, Kyu Han
Morgellons disease is a rare disease with unknown etiology. Herein, we report the first case of Morgellons disease in Korea. A 30-year-old woman presented with a 2-month history of pruritic erythematous patches and erosions on the arms, hands, and chin. She insisted that she had fiber-like materials under her skin, which she had observed through a magnifying device. We performed skin biopsy, and observed a fiber extruding from the dermal side of the specimen. Histopathological examination showed only mild lymphocytic infiltration, and failed to reveal evidence of any microorganism. The polymerase chain reaction for Borrelia burgdorferi was negative in her serum.
Chapuis-Taillard, Caroline; de Vallière, Serge; Bochud, Pierre-Yves
In 2008, several publications have highlighted the role of climate change and globalization on the epidemiology of infectious diseases. Studies have shown the extension towards Europe of diseases such as Crimea-Congo fever (Kosovo, Turkey and Bulgaria), leismaniosis (Cyprus) and chikungunya virus infection (Italy). The article also contains comments on Plasmodium knowlesi, a newly identified cause of severe malaria in humans, as well as an update on human transmission of the H5NI avian influenza virus. It also mentions new data on Bell's palsy as well as two vaccines (varicella-zoster and pneumococcus), and provides a list of recent guidelines for the treatment of common infectious diseases.
Haricharan, Ramanath N; Georgeson, Keith E
Hirschsprung disease is a relatively common condition managed by pediatric surgeons. Significant advances have been made in understanding its etiologies in the last decade, especially with the explosion of molecular genetic techniques and early diagnosis. The surgical management has progressed from a two- or three-stage procedure to a primary operation. More recently, definitive surgery for Hirschsprung disease through minimally invasive techniques has gained popularity. In neonates, the advancement of treatment strategies for Hirschsprung disease continues with reduced patient morbidity and improved outcomes.
Crohn\\'s disease is a disorder mediated by T lymphocytes which arises in genetically susceptible individuals as a result of a breakdown in the regulatory constraints on mucosal immune responses to enteric bacteria. Regulation of immune reactivity to enteric antigens has improved understanding of the pathophysiological mechanisms of Crohn\\'s disease, and has expanded therapeutic options for patients with this disorder. Disease heterogeneity is probable, with various underlying defects associated with a similar pathophysiological outcome. Although most conventional drug treatments are directed at modification of host response, therapeutic manipulation of the enteric flora is becoming a realistic option.
Full Text Available A 2-month-old male infant was found to have Norrie′s disease. The clinical presentation and detailed histological features diagnostic of the disease are discussed. This is the first authentic, histologically proven case of Norrie′s disease from India. The absence of hearing loss and mental retardation at the time of presentation at the early stage of infancy and the fact that the case was sporadic do not detract from the diagnosis. However the child at the age of one year developed hearing loss.
... Unlike bowlegs , which tend to straighten as the child develops, Blount disease slowly gets worse. It can cause severe bowing of one or both legs. This condition is more common among African American children. It is also associated with obesity ...
... pneumococcal disease kills one in every four to five people over the age of 65 who gets it. ... A second PPSV23 vaccine is recommended for these persons five years after the first PPSV23. CDC recommends only ...
... this research; and the dissemination of information on research progress in these diseases. Contact Us NIAMS Archive Viewers and Players Social Media Moderation Policy FOIA Privacy Statement Accessibility Disclaimer Digital Strategy ...
Reilly, Norelle R; Husby, Steffen; Sanders, David S
Coeliac disease is increasingly recognized as a global problem in both children and adults. Traditionally, the findings of characteristic changes of villous atrophy and increased intraepithelial lymphocytosis identified in duodenal biopsy samples taken during upper gastrointestinal endoscopy have...... been required for diagnosis. Although biopsies remain advised as necessary for the diagnosis of coeliac disease in adults, European guidelines for children provide a biopsy-sparing diagnostic pathway. This approach has been enabled by the high specificity and sensitivity of serological testing. However......, these guidelines are not universally accepted. In this Perspective, we discuss the pros and cons of a biopsy-avoiding pathway for the diagnosis of coeliac disease, especially in this current era of the call for more biopsies, even from the duodenal bulb, in the diagnosis of coeliac disease. In addition, a contrast...
... underlying liver disease, failure to thrive, infection-associated encephalopathy, spasticity, myoclonus (involuntary jerking of a muscle or group of muscles), seizures, or liver failure. An increased protein level is seen in ...
... it may be caused by diseases, such as connective tissue disorders, excessive iron buildup in your body (hemochromatosis), the buildup of abnormal proteins (amyloidosis) or by some cancer treatments. Causes of heart infection A heart infection, ...
... Administrator Channels Synapses Circuits Cluster Neurosurgery Research Fellowships Scientific Director, Division of Intramural Research ... Disease Information Page What research is being done? Recent discoveries show that most individuals (approximately 90 percent) with ...
... Linked Retinoschisis (XLRS) X-Linked Retinitis Pigmentosa (XLRP) Usher Syndrome Other Retinal Diseases Glossary News & Research News & Research ... central portion of the retina called the macula. Usher Syndrome Usher syndrome is an inherited condition characterized by ...
... boys 10 years to 12 years of age. Soccer players and gymnasts often get Sever’s disease, but ... Crisis Situations Pets and Animals myhealthfinder Food and Nutrition Healthy Food Choices Weight Loss and Diet Plans ...
... The disease leads to shaking ( tremors ) and trouble walking and moving . ... include: Difficulty starting movement, such as starting to walk or ... are not moving. This is called resting tremor. Occur when your ...
... organs and affect the central nervous system, causing memory loss and impaired speech, balance, and movement. The effects of the disease may include blindness, stroke, swelling of the spinal cord, and intestinal ...
2010380 Evaluation non-motor symptoms in Parkinson’s disease and its influence on ability of daily living. WANG Rongfei(王荣飞),et al. Dept Neurol,1st Hosp,Guangzhou Med Coll,Guangzhou 510000. Chin J Neurol 2010;43(4):273-276. Objective To evaluate the non-motor symptoms (NMS) in Parkinson’s disease (PD),and its influence on ability of daily living (ADL) in PD
Tümer, Zeynep; Møller, Lisbeth B
Menkes disease (MD) is a lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar 'kinky' hair are the main manifestations. MD is inherited as an X-linked recessive trait, and as expected the vast majority...... of surplus copper from cells. Severely affected MD patients die usually before the third year of life. A cure for the disease does not exist, but very early copper-histidine treatment may correct some of the neurological symptoms....
John W. Peacock
Dutch elm disease was found in Cleveland, Ohio, in 1930, and is now in most of the contiguous 48 states. The disease is caused by a fungus that has killed millions of wild and planted elms. Losses have been the greatest in the eastern United States. The fungus attacks all elms, but our native species, American, slippery, and rock elm have little or no resistance to the...
Full Text Available Abstract Enchondromas are common intraosseous, usually benign cartilaginous tumors, that develop in close proximity to growth plate cartilage. When multiple enchondromas are present, the condition is called enchondromatosis also known as Ollier disease (WHO terminology. The estimated prevalence of Ollier disease is 1/100,000. Clinical manifestations often appear in the first decade of life. Ollier disease is characterized by an asymmetric distribution of cartilage lesions and these can be extremely variable (in terms of size, number, location, evolution of enchondromas, age of onset and of diagnosis, requirement for surgery. Clinical problems caused by enchondromas include skeletal deformities, limb-length discrepancy, and the potential risk for malignant change to chondrosarcoma. The condition in which multiple enchondromatosis is associated with soft tissue hemangiomas is known as Maffucci syndrome. Until now both Ollier disease and Maffucci syndrome have only occurred in isolated patients and not familial. It remains uncertain whether the disorder is caused by a single gene defect or by combinations of (germ-line and/or somatic mutations. The diagnosis is based on clinical and conventional radiological evaluations. Histological analysis has a limited role and is mainly used if malignancy is suspected. There is no medical treatment for enchondromatosis. Surgery is indicated in case of complications (pathological fractures, growth defect, malignant transformation. The prognosis for Ollier disease is difficult to assess. As is generally the case, forms with an early onset appear more severe. Enchondromas in Ollier disease present a risk of malignant transformation of enchondromas into chondrosarcomas.
May 15, 2012 ... to diseases and insects and reduction in fertility of flowering plants ..... soaking duration was noticed to cause the treated seeds to give low height .... Addison-. Wesley, London. Stadler J, Phillips RL, Leonard M (1989).Mitotic ...
... Cushing's syndrome, there's too much cortisol, while with Addison's disease, there is too little. Some people are born unable to make enough cortisol. Causes of adrenal gland disorders include Genetic mutations Tumors ...
... the thyroid gland produces less hormone than normal); Addison's disease (condition in which the adrenal gland produces less hormone than normal); any condition that causes difficulty urinating such as an enlarged prostate (a ...
Sep 15, 1990 ... suggest that iron overload from any cause may predispose to infection7 and there are .... consumption and acute inflammatory diseases. However, it ..... Addison GM, Beamish MR, Hales C ',Hodgkins M, Jacobs A, Llewellin P.
Foster, M.; Nolan, R.L.; Hong, H.H.
Primary adrenal carcinoma is a rare malignancy. Primary adrenal insufficiency (i.e. Addison's disease) is a rare complication of bilateral infiltration. We report a case of primary bilateral adrenal carcinoma complicated by an episode of primary adrenal insufficiency. (author)
... of Conditions Not Listed? Not Listed? Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer ... ammonia, but both can damage the eyes, skin, respiratory tract, and, if swallowed, the mouth, throat, and ...
... of Conditions Not Listed? Not Listed? Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer ... Less Related Images View More × Diagram of the Respiratory System, including the Lungs. Image credit: National Cancer ...
... of Conditions Not Listed? Not Listed? Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer ... and can be associated with congenital heart defects, respiratory and hearing problems, leukemia , and thyroid disorders . Many ...
... of Conditions Not Listed? Not Listed? Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer ... and can be associated with congenital heart defects, respiratory and hearing problems, leukemia , and thyroid disorders . Many ...
... of Conditions Not Listed? Not Listed? Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer ... to produce sputum, a health practitioner may collect respiratory samples using a procedure called a bronchoscopy. Bronchoscopy ...
... of Conditions Not Listed? Not Listed? Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer ... surfactants, a newborn may develop life-threatening neonatal respiratory distress syndrome (RDS). Tests include: Lamellar body count ...
... of Conditions Not Listed? Not Listed? Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer ... as kidney failure, insulin shock or diabetic coma, respiratory distress, or heart rhythm changes. What does the ...
... of Conditions Not Listed? Not Listed? Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer ... tested? Pertussis, commonly called whooping cough, is a respiratory infection caused by the bacteria Bordetella pertussis . These ...
... of Conditions Not Listed? Not Listed? Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer ... deficiency. AAT levels may be decreased in neonatal respiratory distress syndrome and in conditions that cause a ...
... of Conditions Not Listed? Not Listed? Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer ... person-to-person contact or by exposure to respiratory secretions. The virus is spread when a mosquito ...
... of Conditions Not Listed? Not Listed? Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer ... rivers. Infection occurs when the parasite enters the respiratory system through the nose of a person swimming ...
... of Conditions Not Listed? Not Listed? Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer ... or "erythema infectiosum." The virus is found in respiratory droplets during an infection and is easily transmitted ...
... of Conditions Not Listed? Not Listed? Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer ... spreads from person-to-person through contact with respiratory secretions that contain the streptococcal bacteria. During influenza ...
... of Conditions Not Listed? Not Listed? Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer ... the body. For example, pericarditis may follow a respiratory infection or a chest cold. Bleeding – bleeding disorders ...
... DHEA sulfate may be due to: Adrenal gland disorders that produce lower than normal amounts of adrenal hormones, including adrenal insufficiency and Addison disease The pituitary gland not producing normal amounts of its hormones ( hypopituitarism ) ...
... Addison disease - serum aldosterone; Primary hyperaldosteronism - serum aldosterone; Bartter syndrome - serum aldosterone ... normal level of aldosterone may be due to Bartter syndrome (group of rare conditions that affect the kidneys) ...
... with Rheumatic Disease Pregnancy & Rheumatic Disease Pregnancy and Rheumatic Disease Fast Facts Diseases with the potential to affect ... control. What are the effects of pregnancy on rheumatic disease? The effects of pregnancy on rheumatic diseases vary ...
von Roon, Alexander C; Reese, George E; Orchard, Timothy R; Tekkis, Paris P
Crohn's disease is a long-term chronic condition of the gastrointestinal tract. It is characterised by transmural, granulomatous inflammation that occurs in a discontinuous pattern, with a tendency to form fistulae. The cause is unknown but may depend on interactions between genetic predisposition, environmental triggers, and mucosal immunity. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments in adults to induce remission in Crohn's disease? What are the effects of lifestyle interventions in adults with Crohn's disease to maintain remission? What are the effects of surgical interventions in adults with small-bowel Crohn's disease to induce remission? What are the effects of surgical interventions in adults with colonic Crohn's disease to induce remission? What are the effects of medical interventions to maintain remission in adults with Crohn's disease; and to maintain remission following surgery? We searched: Medline, Embase, The Cochrane Library and other important databases up to March 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 60 systematic reviews, RCTs, or observational studies that met our inclusion criteria. In this systematic review we present information relating to the effectiveness and safety of the following interventions: aminosalicylates, antibiotics, azathioprine/mercaptopurine, ciclosporin, corticosteroids (oral), enteral nutrition, fish oil, infliximab, methotrexate, probiotics, resection, segmental colectomy, smoking cessation, and strictureplasty.
Thakker Rajesh V
Full Text Available Abstract Dent's disease is a renal tubular disorder characterized by manifestations of proximal tubule dysfunction, including low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, nephrocalcinosis, and progressive renal failure. These features are generally found in males only, and may be present in early childhood, whereas female carriers may show a milder phenotype. Prevalence is unknown; the disorder has been reported in around 250 families to date. Complications such as rickets or osteomalacia may occur. The disease is caused by mutations in either the CLCN5 (Dent disease 1 or OCRL1 (Dent disease 2 genes that are located on chromosome Xp11.22 and Xq25, respectively. CLCN5 encodes the electrogenic Cl-/H+ exchanger ClC-5, which belongs to the CLC family of Cl- channels/transporters. OCRL1 encodes a phosphatidylinositol bisphosphate (PIP2 5-phosphatase and mutations are also associated with Lowe Syndrome. The phenotype of Dent's disease is explained by the predominant expression of ClC-5 in the proximal tubule segments of the kidney. No genotype-phenotype correlation has been described thus far, and there is considerable intra-familial variability in disease severity. A few patients with Dent's disease do not harbour mutations in CLCN5 and OCRL1, pointing to the involvement of other genes. Diagnosis is based on the presence of all three of the following criteria: low-molecular-weight proteinuria, hypercalciuria and at least one of the following: nephrocalcinosis, kidney stones, hematuria, hypophosphatemia or renal insufficiency. Molecular genetic testing confirms the diagnosis. The differential diagnosis includes other causes of generalized dysfunction of the proximal tubules (renal Fanconi syndrome, hereditary, acquired, or caused by exogenous substances. Antenatal diagnosis and pre-implantation genetic testing is not advised. The care of patients with Dent's disease is supportive, focusing on the treatment of hypercalciuria and
Astradsson, Arnar; Aziz, Tipu Z
INTRODUCTION: The mean age of onset of Parkinson's disease is about 65 years, with a median time of 9 years between diagnosis and death. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of fetal cell or stem cell......-derived therapy in people with Parkinson's disease? We searched: Medline, Embase, The Cochrane Library and other important databases up to September 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from...
Case study of a DOE 2015 Housing Innovation Award winning custom home in the mixed humid climate that got a HERS 41 without PV, with 2x4 16” on-center walls with 1 inch rigid foam, a sealed conditioned crawl space insulated on inside with 2 inches poly iso, a vented attic with R-38 blown fiberglass, a central heat pump with fresh air intake.
... diagnosed with hypothyroidism or had not yet started treatment for hypothyroidism. 4 Problems during pregnancy. The unborn baby's brain ... can last up to a year and requires treatment. Most often, thyroid function returns to normal as the ... from Hashimoto's disease treated during pregnancy? During pregnancy, ...
Abelardo Q-C Araujo
Full Text Available Prion diseases are neurodegenerative illnesses due to the accumulation of small infectious pathogens containing protein but apparently lacking nucleic acid, which have long incubation periods and progress inexorably once clinical symptoms appear. Prions are uniquely resistant to a number of normal decontaminating procedures. The prionopathies [Kuru, Creutzfeldt-Jakob disease (CJD and its variants, Gerstmann-Sträussler-Scheinker (GSS syndrome and fatal familial insomnia (FFI] result from accumulation of abnormal isoforms of the prion protein in the brains of normal animals on both neuronal and non-neuronal cells. The accumulation of this protein or fragments of it in neurons leads to apoptosis and cell death. There is a strong link between mutations in the gene encoding the normal prion protein in humans (PRNP - located on the short arm of chromosome 20 – and forms of prion disease with a familial predisposition (familial CJD, GSS, FFI. Clinically a prionopathy should be suspected in any case of a fast progressing dementia with ataxia, myoclonus, or in individuals with pathological insomnia associated with dysautonomia. Magnetic resonance imaging, identification of the 14-3-3 protein in the cerebrospinal fluid, tonsil biopsy and genetic studies have been used for in vivo diagnosis circumventing the need of brain biopsy. Histopathology, however, remains the only conclusive method to reach a confident diagnosis. Unfortunately, despite numerous treatment efforts, prionopathies remain short-lasting and fatal diseases.
... a long and relatively healthy life. What Causes Parkinson's Disease? In the very deep parts of the brain, there is a collection of nerve cells that help control movement, known as the basal ganglia (say: BAY-sul GAN-glee-ah). In a ...
... Information for Authors Information for Reviewers Human & Animal Rights Job Postings Sections of the ... dermatosis) is a condition that appears suddenly as itchy red spots on the trunk, most often in older men. Minor cases of Grover's disease may be rather common. ...
Hjermind, Lena Elisabeth; Law, Ian; Jønch, Aia
In this open-label pilot study, the authors evaluated the effect of memantine on the distribution of brain glucose metabolism in four Huntington's disease (HD) patients as determined by serial 18-fluoro-deoxyglucose [F(18)]FDG-PET scans over a period of 3-4 months (90-129 days, with one patient...
... affects how the body breaks down and uses aspartic acid . ... scan Head MRI scan Urine chemistry for elevated aspartic acid ... Matalon KM, Matalon RK. Aspartic acid (Canavan disease). In: ... JW III, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ed. ...
had been poor in the right eye and he had found it hard to pass urine. ... right optic:-nerve disease, and was followed in 1880 by mention pupil was large and reacted very sluggishly to light, and the left .... The enzyme theory is that an enzyme-.
... yellowing of the skin and the whites of the eye (jaundice) Golden-brown eye discoloration (Kayser-Fleischer rings) Fluid buildup ... is inherited as an autosomal recessive trait, which means that to develop the disease you must inherit one copy of the ...
Accordino, Robert E; Engler, Danielle; Ginsburg, Iona H; Koo, John
Morgellons disease, a pattern of dermatologic symptoms very similar, if not identical, to those of delusions of parasitosis, was first described many centuries ago, but has recently been given much attention on the internet and in the mass media. The present authors present a history of Morgellons disease, in addition to which they discuss the potential benefit of using this diagnostic term as a means of building trust and rapport with patients to maximize treatment benefit. The present authors also suggest "meeting the patient halfway" and creating a therapeutic alliance when providing dermatologic treatment by taking their cutaneous symptoms seriously enough to provide both topical ointments as well as antipsychotic medications, which can be therapeutic in these patients.
Hvas, Christian Lodberg; Jensen, Michael Dam; Reimer, Maria Christina
This national clinical guideline approved by the Danish Society for Gastroenterology and Hepatology describes the diagnosis and treatment of celiac disease (CD) in adults. CD is a chronic immunemediated enteropathy of the small intestine triggered by the ingestion of gluten-containing proteins......, which are found in wheat, rye, and barley. The disease prevalence is 0.5-1.0%, but CD remains under-diagnosed. The diagnosis relies on the demonstration of lymphocyte infiltration, crypt hyperplasia, and villous atrophy in duodenal biopsies. Serology, malabsorption, biochemical markers......, and identification of specific HLA haplotypes may contribute to CD diagnosis. Classical CD presents with diarrhoea and weight loss, but non-classical CD with vague or extraintestinal symptoms is common. The treatment for CD is a lifelong gluten-free diet (GFD), which, in the majority of patients, normalises...
Full Text Available Background and Purpose: Chronic granulomatous disease (CGD is an inherited disorder of the nicotinamide adenine dinucleotide phosphate (NADPH oxidase complex. This disorder results in recurrent life-threatening bacterial and fungal infections. Aspergillus species are the most common fungal infections in these patients. Case Report: Herein, we present a case of fungal infection in a girl with CGD. We confirmed aspergillosis through the positive microscopic and macroscopic examinations, as well as radiology results. Invasive aspergillosis in this patient with pneumonia, lung abscess, and osteomyelitis of the ribs was not initially treated with amphotericin B (Am B and recombinant interferon-gamma. Conclusion: Among infectious diseases, fungal infections, in particular aspergillosis, remain a serious problem in CGD patients. Considering poor clinical response and deficient immune system, rapid diagnosis of fungal infection and optimizing the treatment of these patients are recommended.
The authors discuss how x-ray examination is essential in the diagnosis and evaluation of the arthritides. Most arthritides are first suspected by the clinician, and x-ray evaluation of these entities along with laboratory testing is important for confirmation of the clinical diagnosis and in staging of the disease process. Several arthritides are often diagnosed first by the podiatrist on x-ray evaluation, including pseudogout, ankylosing spondylitis, early rheumatoid arthritis, degenerative joint disease, and tuberculosis of bone. The joint responds to insult in only a limited number of ways that become apparent on x-ray. The soft tissues surrounding the joint, the articulating bones, and alignment of the joint space may all be involved by the arthritic process. On roentgenographic examination, the soft tissues must be examined for edema, masses, calcifications, and atrophy. The articulating bones must be examined for demineralization, erosions, osteophytes, periosteal reaction, cysts and sclerosis
Presenting a multidisciplinary approach to the diagnosis and treatment of thyroid disease, this volume provides a comprehensive picture of current thyroid medicine and surgery. The book integrates the perspectives of the many disciplines that deal with the clinical manifestations of thyroid disorders. Adding to the clinical usefulness of the book is the state-of-the-art coverage of many recent developments in thyroidology, including the use of highly sensitive two-site TSH immunoradionetric measurements to diagnose thyroid activity; thyroglobulin assays in thyroid cancer and other diseases; new diagnostic applications of MRI and CT; treatment with radionuclides and chemotherapy; new developments in thyroid immunology, pathology, and management of hyperthyroidism; suppressive treatment with thyroid hormone; and management of Graves' ophthalmopathy. The book also covers all aspects of thyroid surgery, including surgical treatment of hyperthyroidism; papillary, follicular, and other carcinomas; thyroidectomy; and prevention and management of complications.
Presenting a multidisciplinary approach to the diagnosis and treatment of thyroid disease, this volume provides a comprehensive picture of current thyroid medicine and surgery. The book integrates the perspectives of the many disciplines that deal with the clinical manifestations of thyroid disorders. Adding to the clinical usefulness of the book is the state-of-the-art coverage of many recent developments in thyroidology, including the use of highly sensitive two-site TSH immunoradionetric measurements to diagnose thyroid activity; thyroglobulin assays in thyroid cancer and other diseases; new diagnostic applications of MRI and CT; treatment with radionuclides and chemotherapy; new developments in thyroid immunology, pathology, and management of hyperthyroidism; suppressive treatment with thyroid hormone; and management of Graves' ophthalmopathy. The book also covers all aspects of thyroid surgery, including surgical treatment of hyperthyroidism; papillary, follicular, and other carcinomas; thyroidectomy; and prevention and management of complications
Hainaux, B.; Christophe, C.; Hanquinet, S.; Perlmutter, N.
We report our observations made by conventional radiography, ultrasound, computerized tomography (CT), and magnetic resonance imaging (MRI) on a 3 1/2-year-old girl with Gaucher's disease. The interest of the case consists in the exceptional lungs involvement, the demonstration by MRI of the bone marrow involvement and the necrosis and fibrosis of the liver, as shown by CT. This liver complication has been previously reported only once. (orig.)
Bulent Kurt; Turgut Topal
Mitochondria are the major energy source of cells. Mitochondrial disease occurs due to a defect in mitochondrial energy production. A valuable energy production in mitochondria depend a healthy interconnection between nuclear and mitochondrial DNA. A mutation in nuclear or mitochondrial DNA may cause abnormalities in ATP production and single or multiple organ dysfunctions, secondarily. In this review, we summarize mitochondrial physiology, mitochondrial genetics, and clinical expression and ...
Torres Esteche, V.; Menafra Prieto, M.; Ormaechea Gorricho, R.; Vignolo Scalone, G.; Larre Borges, A.
A review of the Cushings disease in its various aspects. It highlights the importance of early diagnosis to avoid repercussions hypercortisolism secondary to parenchymal. We describe the findings in the Nuclear Magnetic Resonance (NMR), noting that the pituitary adenoma is often of small size and sometimes not visible on MRI. The treatment of choice remains surgical treatment other contingencies exist for particular cases (Author) [es
... Disease, & Other Dental Problems Diabetes & Sexual & Urologic Problems Diabetic Eye Disease What is diabetic eye disease? Diabetic eye disease is a group ... eye diseases that can threaten your sight are Diabetic retinopathy The retina is the inner lining at ...
... of heavy chain produced: Alpha Gamma Mu Alpha Heavy Chain Disease Alpha heavy chain disease (IgA heavy ... the disease or lead to a remission. Gamma Heavy Chain Disease Gamma heavy chain disease (IgG heavy ...
This chapter reviews the correlation between thyroid disease, other than cancer, and radiation in the literature. Radiation-induced thyroid disturbance is discussed in the context of external and internal irradiation. External irradiation of 10 to 40 Gy may lower thyroid function several months or years later. Oral administration of I-131 is widely given to patients with Basedow's disease; it may also lower thyroid function with increasing radiation doses. When giving 70 Gy or more of I-131, hypothyroidism has been reported to occur in 20-30% and at least 10%. Thyroiditis induced with internal I-131 irradiation has also been reported, but no data is available concerning external irradiation-induced thyroiditis. The incidence of nodular goiter was found to be several ten times higher with external irradiation than internal irradiation. Thyroid disturbance is correlated with A-bomb survivors. A-bomb radiation can be divided into early radiation within one minute after A-bombing and the subsequent residual radiation. Nodular goiter was significantly more frequent in the exposed group than the non-exposed group; it increased with increasing radiation doses and younger age (20 years or less) at the time of exposure. The incidence of decrease in thyroid function was higher with increasing radiation doses. However, in the case of Nagasaki, the incidence of hypothyroidism was significantly higher in the low-dose exposed group, especially A-bomb survivors aged 10-39 at the time of exposure and women. (N.K.)
Different forms of skull diseases viz. inflammatory diseases, skull tumors, primary and secondary bone tumors, are considered. Roentgenograms in some above-mentioned diseases are presented and analysed
Atul T Tayade
Full Text Available A 17-year-old male, who gave up his favorite sport cricket and started playing football, presented with one-year history of slowly progressive atrophic weakness of forearms and hands. Neurological examination showed weak and wasted arms, forearms and hand but no evidence of pyramidal tract, spinothalmic tract and posterior column lesions. Plain cervical spine radiographs showed no abnormal findings. Cervical magnetic resonance imaging (MRI showed asymmetric cord atrophy; images obtained with neck flexed showed the anterior shifting of the posterior wall of the lower cervical dural sac resulting in cord compression. These findings suggest Hirayama disease, a kind of cervical myelopathy related to the flexion movements of the neck.
... Find your local chapter Join our online community Parkinson's Disease Dementia Parkinson's disease dementia is an impairment ... disease. About Symptoms Diagnosis Causes & risks Treatments About Parkinson's disease dementia The brain changes caused by Parkinson's ...
... Select a Language: Fact Sheet 652 HIV and Cardiovascular Disease HIV AND CARDIOVASCULAR DISEASE WHY SHOULD PEOPLE WITH HIV CARE ABOUT CVD? ... OF CVD? WHAT ABOUT CHANGING MEDICATIONS? HIV AND CARDIOVASCULAR DISEASE Cardiovascular disease (CVD) includes a group of problems ...
... Disease" Articles Celiac Disease Changes Everything / What is Celiac Disease? / Symptoms, Diagnosis and Treatment / Four Inches and Seven Pounds… / Learning to Live Well with Celiac Disease / Living Gluten-Free Spring 2015 Issue: Volume 10 ...
... Disease" Articles Celiac Disease Changes Everything / What is Celiac Disease? / Symptoms, Diagnosis and Treatment / Four Inches and Seven Pounds… / Learning to Live Well with Celiac Disease / Living Gluten-Free Spring 2015 Issue: Volume 10 ...
... Home Conditions Undifferentiated Connective Tissue Disease (UCTD) Undifferentiated Connective Tissue Disease (UCTD) Make an Appointment Find a Doctor ... by Barbara Goldstein, MD (February 01, 2016) Undifferentiated connective tissue disease (UCTD) is a systemic autoimmune disease. This ...
... gland in the neck, thick and coarse hair. Addison’s Disease Arare disease involving the adrenal gland. The prevalence of celiac disease in people with addison’s disease is significant. Symptoms of Addison’s may include weight ...
... Well with Rheumatic Disease Genetics and Rheumatic Disease Genetics and Rheumatic Disease Fast Facts Studying twins has ... 70%, and for non-identical pairs, even lower. Genetics and ankylosing spondylitis Each rheumatic disease has its ...
... Safe Videos for Educators Search English Español Mad Cow Disease KidsHealth / For Teens / Mad Cow Disease What's ... are people to get it? What Is Mad Cow Disease? Mad cow disease is an incurable, fatal ...
NPD; Sphingomyelinase deficiency; Lipid storage disorder - Niemann-Pick disease; Lysosomal storage disease - Niemann-Pick ... lipofuscinoses or Batten disease (Wolman disease, cholesteryl ... metabolism of lipids. In: Kliegman RM, Stanton BF, St. Geme JW, ...
... Infectious Diseases, 35: 451-464, 2002) What is Lyme Disease? Lyme disease (LD) is an infection caused by ... mission with your own tax-deductible contribution. American Lyme Disease Foundation, Inc. PO Box 466 Lyme, CT 06371 ...
... Disease Venous Thromboembolism Aortic Aneurysm More Inflammation and Heart Disease Updated:Jun 13,2017 Understand the risks of ... inflammation causes cardiovascular disease, inflammation is common for heart disease and stroke patients and is thought to be ...
... Pressure Salt Cholesterol Million Hearts® WISEWOMAN Men and Heart Disease Fact Sheet Recommend on Facebook Tweet Share Compartir Source: Interactive Atlas of Heart Disease and Stroke Heart Disease Facts in Men Heart disease is the leading ...
Diet - heart disease; CAD - diet; Coronary artery disease - diet; Coronary heart disease - diet ... diet and lifestyle can reduce your risk of: Heart disease, heart attacks, and stroke Conditions that lead ...
Heart disease - prevention; CVD - risk factors; Cardiovascular disease - risk factors; Coronary artery disease - risk factors; CAD - risk ... a certain health condition. Some risk factors for heart disease you cannot change, but some you can. ...
Heart disease, Coronary heart disease, Coronary artery disease; Arteriosclerotic heart disease; CHD; CAD ... buildup of plaque in the arteries to your heart. This may also be called hardening of the ...
Ahlhelm, F.; Mueller, U.; Lieb, J.; Schneider, G.; Ulmer, S.
Osler's disease, also known as hereditary hemorrhagic telangiectasia (HHT) and Osler-Weber-Rendu syndrome, is an autosomal dominant disorder leading to abnormal blood vessel formation in the skin, mucous membranes and often in organs, such as the lungs, liver and brain (arteriovenous malformations AVM). Various types are known. Patients may present with epistaxis. Teleangiectasia can be identified by visual inspection during physical examination of the skin or oral cavity or by endoscopy. Diagnosis is made after clinical examination and genetic testing based on the Curacao criteria. Modern imaging modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI) have become more important as they can depict the AVMs. Pulmonary AVMs can be depicted in CT imaging even without the use of a contrast agent while other locations including the central nervous system (CNS) usually require administration of contrast agents. Knowledge of possible clinical manifestations in various organs, possible complications and typical radiological presentation is mandatory to enable adequate therapy of these patients. Interventional procedures are becoming increasingly more important in the treatment of HHT patients. (orig.) [de
Boonpheng, Boonphiphop; Cheungpasitporn, Wisit; Wijarnpreecha, Karn
Celiac disease, an inflammatory disease of small bowel caused by sensitivity to dietary gluten and related protein, affects approximately 0.5-1% of the population in the Western world. Extra-intestinal symptoms and associated diseases are increasingly recognized including diabetes mellitus type 1, thyroid disease, dermatitis herpetiformis and ataxia. There have also been a number of reports of various types of renal involvement in patients with celiac disease including diabetes nephropathy, IgA nephropathy, membranous nephropathy, membranoproliferative glomerulonephritis, nephrotic syndrome related to malabsorption, oxalate nephropathy, and associations of celiac disease with chronic kidney disease and end-stage kidney disease. This review aims to present the current literature on possible pathologic mechanisms underlying renal disease in patients with celiac disease.
A-bombing panicked many people with anxiety because they suffered from various symptoms after A-bombing (ie, they generally called them A-bomb disease). In this chapter, major two conditions (ie, leukopenia and anemia), which caused their symptoms, are reviewed based on the early data soon after A-bombing. According to the chronological changes in both white blood cell (WBC) and red blood cell (RBC) counts, both leukopenia and anemia are discussed. The findings can be divided into acute (one week or at least 10 days), subacute (2 weeks to one month), and delayed (thereafter) periods. During an acute period, some exposed even at ≤200 m from the hypocenter showed WBC count of 6,000/mm 3 or more one week after exposure but others exposed at 1,500-2,000 m showed WBC count of less than 3,000/mm 3 , suggesting the influence of shielding on WBC count. WBC count sometimes became the lowest during a subacute period, although it was normal during an acute period. A survey for WBC count during a delayed period (one year later) showed that WBC count of less than 4,000/mm 3 was more frequent in the exposed group (78/523 A-bomb survivors, 14.9%) than the non-exposed group (6/173 persons, 3.5%). In the exposed group, leukopenia was independent of distance and symptoms at the time of exposure. For anemia, there was no data available during an acute period. Anemia frequently occurred during a subacute period. Morphological abnormality of RBC tended to be high in death cases. A delayed survey on anemia 10 years after exposure showed that there was no statistically significant difference in any of the factors, such as hemoglobin, RBC count, hematocrit, mean corpuscular volume and mean corpuscular hemoglobin, between the exposed and non-exposed groups. (N.K.)
Full Text Available Current evidence suggests that periodontal disease may be associated with systemic diseases. This paper reviewed the published data about the relationship between periodontal disease and cardiovascular diseases, adverse pregnancy outcomes, diabetes and respiratory diseases, focusing on studies conducted in the Brazilian population. Only a few studies were found in the literature focusing on Brazilians (3 concerning cardiovascular disease, 7 about pregnancy outcomes, 9 about diabetes and one regarding pneumonia. Although the majority of them observed an association between periodontitis and systemic conditions, a causal relationship still needs to be demonstrated. Further studies, particularly interventional well-designed investigations, with larger sample sizes, need to be conducted in Brazilian populations.
Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Skin Health and Skin Diseases Past Issues / Fall 2008 Table of Contents ... acne to wrinkles Did you know that your skin is the largest organ of your body? It ...
van der Ploeg, Ans T.; Reuser, Arnold J. J.
Pompe's disease, glycogen-storage disease type II, and acid maltase deficiency are alternative names for the same metabolic disorder. It is a pan-ethnic autosomal recessive trait characterised by acid alpha-glucosidase deficiency leading to lysosomal glycogen storage. Pompe's disease is also
Huntington's disease is an inherited intricate brain illness. It is a neurodegenerative, insidious disorder; the onset of the disease is very late to diagnose. It is caused by an expanded CAG repeat in the Huntingtin gene, which encodes an abnormally long polyglutamine repeat in the Huntingtin protein. Huntington's disease ...
Full Text Available ... Expert Briefings: Anxiety in Parkinson's Disease Expert Briefings: Nutrition and Parkinson's Disease NY Nightly News with Chuck ... Briefings: What's in the Parkinson's Pipeline? Expert Briefings: Nutrition and Parkinson's Disease 2010 Expert Briefings: Legal Issues: ...
Your doctor has told you that you have Parkinson disease . This disease affects the brain and leads ... have you take different medicines to treat your Parkinson disease and many of the problems that may ...
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... page: //medlineplus.gov/ency/patientinstructions/000759.htm Understanding cardiovascular disease To use the sharing features on this page, ... lead to heart attack or stroke. Types of Cardiovascular Disease Coronary heart disease (CHD) is the most common ...
... a protein found in wheat, rye, and barley. Pediatric Celiac Disease If your child has celiac disease, ... physician. Established by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) Celiac Disease Eosinophilic ...
Full Text Available ... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping ... Conference: Lessons Learned How Does the DBS Device Work? OHSU - Parkinson's Disease: Managing Depression, Anxiety & Psychosis CareMAP: ...
Degenerative nerve diseases affect many of your body's activities, such as balance, movement, talking, breathing, and heart function. Many ... viruses. Sometimes the cause is not known. Degenerative nerve diseases include Alzheimer's disease Amyotrophic lateral sclerosis Friedreich's ...
Mixed connective tissue disease Overview Mixed connective tissue disease has signs and symptoms of a combination of disorders — primarily lupus, scleroderma and polymyositis. For this reason, mixed connective tissue disease ...
... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Cardiovascular Disease & Diabetes Updated:Jan 29,2018 The following ... clear that there is a strong correlation between cardiovascular disease (CVD) and diabetes. At least 68 percent ...
... disease. Who Gets ALS? Although this disease can strike anyone, ALS is extremely rare in kids. According ... home to provide care that the family cannot handle alone. Living With Lou Gehrig's Disease Living with ...
Full Text Available ... Does Caregiving Change from Day to Day? Unconditional Love How Does Parkinson's Disease Affect the Urinary System? ... Mind Guide to Parkinson's Disease Guide to Deep Brain Stimulation Sleep: A Mind Guide to Parkinson’s Disease ...
... materials Why is CDC concerned about Lyme disease? Data and Statistics Recommend on Facebook Tweet Share Compartir ... sixth most common Nationally Notifiable disease . Lyme Disease Data File To facilitate the public health and research ...
... Health Topics Arthritis and Rheumatic Diseases Arthritis and Rheumatic Diseases Arthritis is often used to refer to any ... primary immunodeficiency syndrome March 11, 2013 Arthritis and Rheumatic Disease News Research Brief | January 9, 2017 Tofacitinib Shows ...
Full Text Available ... Progression of the Disease? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis OHSU - Overview of Parkinson's ... Disease? What Are Some Strategies to Improve the Quality of Community Care for PD Patients? CareMAP: Dealing ...
disease, together with other related non -communicable diseases. (NCDs), poses not only a threat ... but because if we do not act against NCDs we will also be increasing individual and ... respiratory diseases and cancer. This is in recognition ...
Tay-Sachs disease is a rare, inherited disease. It is a type of lipid metabolism disorder. It causes too ... cells, causing mental and physical problems. . Infants with Tay-Sachs disease appear to develop normally for the first few ...
... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Menopause and Heart Disease Updated:Jun 23,2017 Heart ... can become more evident after the onset of menopause. Menopause does not cause cardiovascular diseases . However, certain ...
Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cholangitis (formerly called primary biliary cirrhosis). This group of tests ...
Lyme disease is an acute inflammatory disease characterized by skin changes, joint inflammation and symptoms similar to the ... that is caused by the bacterium Borrelia burgdorferi . Lyme disease is transmitted by the bite of a deer ...
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... Resources Heart Diseases & Disorders Back to Patient Resources Heart Diseases & Disorders Millions of people experience irregular or abnormal ... harmless and happen in healthy people free of heart disease. However, some abnormal heart rhythms can be serious ...
Rozenshtraukh, L.C.; Rybakova, N.I.; Vinner, M.G.
Roentgenologic semiotics of the main parasitic diseases of lungs is described: echinococcosis, paragonimiasis, cysticercosis, toxoplasmosis, ascariasis, amebiosis and some rarely met parasitic diseases
Fructose Metabolism, Inborn Errors; Glycogen Storage Disease; Glycogen Storage Disease Type I; Glycogen Storage Disease Type II; Glycogen Storage Disease Type III; Glycogen Storage Disease Type IV; Glycogen Storage Disease Type V; Glycogen Storage Disease Type VI; Glycogen Storage Disease Type VII; Glycogen Storage Disease Type VIII
... some in the family will have celiac disease. • Symptoms of celiac disease vary widely, but are often absent in persons ... Abnormal labs XX Diabetes and Celiac Disease | continued CELIAC DISEASE Classic symptoms... Gas, bloating, diarrhea, constipation, vomiting, weight loss, anemia. ...
... Close Celiac Disease Understanding Celiac Disease What is Celiac Disease? Symptoms Screening and Diagnosis Treatment and Follow-Up Dermatitis ... Schuppan D, Kelly CP. Etiologies and predictors of diagnosis in nonresponsive celiac disease. Clin Gastroenterol Hepatol 2007; 5 : 445–50. Finding ...
Sun, Kai; Buchan, Natalie; Larminie, Chris; Pržulj, Nataša
The growing body of transcriptomic, proteomic, metabolomic and genomic data generated from disease states provides a great opportunity to improve our current understanding of the molecular mechanisms driving diseases and shared between diseases. The use of both clinical and molecular phenotypes will lead to better disease understanding and classification. In this study, we set out to gain novel insights into diseases and their relationships by utilising knowledge gained from system-level molecular data. We integrated different types of biological data including genome-wide association studies data, disease-chemical associations, biological pathways and Gene Ontology annotations into an Integrated Disease Network (IDN), a heterogeneous network where nodes are bio-entities and edges between nodes represent their associations. We also introduced a novel disease similarity measure to infer disease-disease associations from the IDN. Our predicted associations were systemically evaluated against the Medical Subject Heading classification and a statistical measure of disease co-occurrence in PubMed. The strong correlation between our predictions and co-occurrence associations indicated the ability of our approach to recover known disease associations. Furthermore, we presented a case study of Crohn's disease. We demonstrated that our approach not only identified well-established connections between Crohn's disease and other diseases, but also revealed new, interesting connections consistent with emerging literature. Our approach also enabled ready access to the knowledge supporting these new connections, making this a powerful approach for exploring connections between diseases.
Wanner, Nicola; Bechtel-Walz, Wibke
DNA methylation and histone modifications determine renal programming and the development and progression of renal disease. The identification of the way in which the renal cell epigenome is altered by environmental modifiers driving the onset and progression of renal diseases has extended our understanding of the pathophysiology of kidney disease progression. In this review, we focus on current knowledge concerning the implications of epigenetic modifications during renal disease from early development to chronic kidney disease progression including renal fibrosis, diabetic nephropathy and the translational potential of identifying new biomarkers and treatments for the prevention and therapy of chronic kidney disease and end-stage kidney disease.
Fabri, Gisele M C; Savioli, Cynthia; Siqueira, José T; Campos, Lucia M; Bonfá, Eloisa; Silva, Clovis A
Gingivitis and periodontitis are immunoinflammatory periodontal diseases characterized by chronic localized infections usually associated with insidious inflammation This narrative review discusses periodontal diseases and mechanisms influencing the immune response and autoimmunity in pediatric rheumatic diseases (PRD), particularly juvenile idiopathic arthritis (JIA), childhood-onset systemic lupus erythematosus (C-SLE) and juvenile dermatomyositis (JDM). Gingivitis was more frequently observed in these diseases compared to health controls, whereas periodontitis was a rare finding. In JIA patients, gingivitis and periodontitis were related to mechanical factors, chronic arthritis with functional disability, dysregulation of the immunoinflammatory response, diet and drugs, mainly corticosteroids and cyclosporine. In C-SLE, gingivitis was associated with longer disease period, high doses of corticosteroids, B-cell hyperactivation and immunoglobulin G elevation. There are scarce data on periodontal diseases in JDM population, and a unique gingival pattern, characterized by gingival erythema, capillary dilation and bush-loop formation, was observed in active patients. In conclusion, gingivitis was the most common periodontal disease in PRD. The observed association with disease activity reinforces the need for future studies to determine if resolution of this complication will influence disease course or severity. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.
Mahler, V; Aalto-Korte, K; Alfonso, J H
BACKGROUND: Work-related skin diseases (WSD) are caused or worsened by a professional activity. Occupational skin diseases (OSD) need to fulfil additional legal criteria which differ from country to country. OSD range amongst the five most frequently notified occupational diseases (musculoskeletal...... diseases, neurologic diseases, lung diseases, diseases of the sensory organs, skin diseases) in Europe. OBJECTIVE: To retrieve information and compare the current state of national frameworks and pathways to manage patients with occupational skin disease with regard to prevention, diagnosis, treatment...... in Science and Technology (COST) Action TD 1206 (StanDerm) (www.standerm.eu). RESULTS: Besides a national health service or a statutory health insurance, most European member states implemented a second insurance scheme specifically geared at occupational diseases [insurance against occupational risks...
Castro, Margaret de.
The present study investigates the extraction and radioimmunoassay (RIA) conditions of plasma βLPH. It was extracted by the activated silicic acid method, with a mean extraction efficiency of 31.6% and a mean intra-extraction variation coefficient of 8.1%. Radioiodination was performed by the chloramine-T method and βLPH 125 I was purified by gel chromatography on Sephadex G100. Estimated specific activity ranged from 100 to 192.8 μCi/μg, with a mean incorporation percentage of 66.6%. The titer of the first antibody was 1:50.000/100 μl. The assay was performed under non-equilibrium conditions, with a pre-incubation period of 24 hours and incubation of 4 hours. Mean immunoreactivity (Bo/Total) was 21.1%, with a mean Blank/Total ratio of 2.3%. Sensitivity, expressed as the mean minimum detectable dose, was 40 pg/tube, equivalent to 56 pg/ml plasma. Intra-assay variation coefficients were 6.5%, 3.8% and 6.8%, respectively, at B/Bo levels of 0.8, 0.6 and 0.4 of the standard curve. At B/Bo equal to 0.5, the intra-assay variation coefficient was 20.9%. Replicates of 14 plasma samples showed a correlation coefficient of r 0.99, (p< 0.05). Parallelism between the curve obtained with different volumes of an extract with a high βLPH value and the standard curve was found. The method was controlled biologically by the presence of correlation between the plasma βLPH levels and determined pathological states and with clinical functional studies. Twenty seven normal individuals, 10 patients with Cushing's disease to a tumor of the hypophysis, 4 patients with Cushing syndrome due to an adrenal tumor, 10 patients Addison disease, and 8 patients with hypopituitarism were studied. (author). 119 refs., 28 figs., 2 tabs
Sağlam, Ebru; Saruhan, Nesrin; Çanakçı, Cenk Fatih
Some maternal immunological changes due to pregnancy increases susceptibility to infections. Periodontal disease, the main cause is plaque, is a common disease which is seen multifactorial and varying severity. There are many clinical criteria for diagnosis of periodontal disease. Correlation between pregnancy and periodontal inflammation is known for many years. Periodontal disease affects pregnant’s systemic condition and also has negative effects on fetus. Periodontal disease increases the...
Eikelenboom, P.; Bate, C.; van Gool, W. A.; Hoozemans, J. J. M.; Rozemuller, J. M.; Veerhuis, R.; Williams, A.
Alzheimer's disease (AD) and prion disease are characterized neuropathologically by extracellular deposits of Abeta and PrP amyloid fibrils, respectively. In both disorders, these cerebral amyloid deposits are co-localized with a broad variety of inflammation-related proteins (complement factors,
Taboureau, Olivier; Audouze, Karine
During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied...... by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information...... and their disease relationships from the reported TDDB database. The resulting human EDN takes into consideration the level of evidence of the toxicant-disease relationships allowing including some degrees of significance in the disease-disease associations. Such network can be used to identify uncharacterized...
Talsania, Mitali; Scofield, Robert Hal
Menopause occurs naturally in women at about 50 years of age. There is a wealth of data concerning the relationship of menopause to systemic lupus erythematosus, rheumatoid arthritis, and osteoarthritis; there are limited data concerning other rheumatic diseases. Age at menopause may affect the risk and course of rheumatic diseases. Osteoporosis, an integral part of inflammatory rheumatic diseases, is made worse by menopause. Hormone replacement therapy has been studied; its effects vary depending on the disease and even different manifestations within the same disease. Cyclophosphamide can induce early menopause, but there is underlying decreased ovarian reserve in rheumatic diseases. Published by Elsevier Inc.
Full Text Available Wilson’s disease is a autosomal recessive disorder of copper metabolism. Clinical phenotypes include hepatic, haemolytic, neurologic and psychiatric diseases. Wilson’s disease is caused by mutations in the ATP7B gene. ATP7B encodes a hepatic copper-transporting protein, which is important for copper excretion into bile. Neurological symptoms in Wilson’s disease include variable combinations of dysathria, ataxia, parkinsonism, dystonia and tremor. Wilson’s disease is lethal if untreated. This review discusses the epidemiology, genetics, clinical features, etiopathophysiology, diagnostic tests, and treatment of Wilson’s disease
Ferreira, Carlos R.; Gahl, William A.
Lysosomes are cytoplasmic organelles that contain a variety of different hydrolases. A genetic deficiency in the enzymatic activity of one of these hydrolases will lead to the accumulation of the material meant for lysosomal degradation. Examples include glycogen in the case of Pompe disease, glycosaminoglycans in the case of the mucopolysaccharidoses, glycoproteins in the cases of the oligosaccharidoses, and sphingolipids in the cases of Niemann-Pick disease types A and B, Gaucher disease, Tay-Sachs disease, Krabbe disease, and metachromatic leukodystrophy. Sometimes, the lysosomal storage can be caused not by the enzymatic deficiency of one of the hydrolases, but by the deficiency of an activator protein, as occurs in the AB variant of GM2 gangliosidosis. Still other times, the accumulated lysosomal material results from failed egress of a small molecule as a consequence of a deficient transporter, as in cystinosis or Salla disease. In the last couple of decades, enzyme replacement therapy has become available for a number of lysosomal storage diseases. Examples include imiglucerase, taliglucerase and velaglucerase for Gaucher disease, laronidase for Hurler disease, idursulfase for Hunter disease, elosulfase for Morquio disease, galsulfase for Maroteaux-Lamy disease, alglucosidase alfa for Pompe disease, and agalsidase alfa and beta for Fabry disease. In addition, substrate reduction therapy has been approved for certain disorders, such as eliglustat for Gaucher disease. The advent of treatment options for some of these disorders has led to newborn screening pilot studies, and ultimately to the addition of Pompe disease and Hurler disease to the Recommended Uniform Screening Panel (RUSP) in 2015 and 2016, respectively. PMID:29152458
Mikolasevic, Ivana; Milic, Sandra; Turk Wensveen, Tamara; Grgic, Ivana; Jakopcic, Ivan; Stimac, Davor; Wensveen, Felix; Orlic, Lidija
Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians. PMID:27920470
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... because they disproportionately affect impoverished people. More on: Neglected Tropical Diseases Prevention One of the most important ways to help prevent these parasitic diseases is to teach children the importance of washing hands correctly with soap ...
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Byrne, Greg; Feighery, Conleth F
Historically the diagnosis of celiac disease has relied upon clinical, serological, and histological evidence. In recent years the use of sensitive serological methods has meant an increase in the diagnosis of celiac disease. The heterogeneous nature of the disorder presents a challenge in the study and diagnosis of the disease with patients varying from subclinical or latent disease to patients with overt symptoms. Furthermore the related gluten-sensitive disease dermatitis herpetiformis, while distinct in some respects, shares clinical and serological features with celiac disease. Here we summarize current best practice for the diagnosis of celiac disease and briefly discuss newer approaches. The advent of next-generation assays for diagnosis and newer clinical protocols may result in more sensitive screening and ultimately the possible replacement of the intestinal biopsy as the gold standard for celiac disease diagnosis.
... diet When To Get Tested? When you have symptoms suggesting celiac disease, such as chronic diarrhea, abdominal pain, anemia , and ... Celiac tests are usually ordered for people with symptoms suggesting celiac disease, including anemia and abdominal pain. Sometimes celiac testing ...
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What is fatty liver disease? Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. Fatty liver disease is a condition in which fat builds ...
... Club Program Perio Store Education & Careers Careers in Periodontics Perio Exam for Dental Licensure Recommended Competencies Periodontal ... your risk of cardiovascular disease. Both diseases are chronic inflammatory conditions, and researchers believe that inflammation is ...
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Gelson, E; Gatzoulis, M; Johnson, M
Valvular disease may be unmasked in pregnancy when physiological changes increase demands on the heart. Women with valvular heart disease require close follow-up during pregnancy, delivery, and postpartum
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Full Text Available Gender differences exist in the prevalence of glomerular diseases. Data based on histological diagnosis underestimate the prevalence of preeclampsia, which is almost certainly the commonest glomerular disease in the world, and uniquely gender-specific. Glomerular disease affects fertility via disease activity, the therapeutic use of cyclophosphamide, and underlying chronic kidney disease. Techniques to preserve fertility during chemotherapy and risk minimization of artificial reproductive techniques are considered. The risks, benefits, and effectiveness of different contraceptive methods for women with glomerular disease are outlined. Glomerular disease increases the risk of adverse outcomes in pregnancy, including preeclampsia; yet, diagnosis of preeclampsia is complicated by the presence of hypertension and proteinuria that precede pregnancy. The role of renal biopsy in pregnancy is examined, in addition to the use of emerging angiogenic biomarkers. The safety of drugs prescribed for glomerular disease in relation to reproductive health is detailed. The impact of both gender and pregnancy on long-term prognosis is discussed.
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... better understanding of how neurological deficits arise in lipid storage diseases and on the development of new treatments targeting disease mechanisms. Specific research on the gangliodisoses including expanding the use of ...
... of Neurological Disorders and Stroke conducts and supports research to understand lipid storage diseases such as acid lipase deficiency and ... of Neurological Disorders and Stroke conducts and supports research to understand lipid storage diseases such as acid lipase deficiency and ...
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In recent years, emerging diseases were defined as being infectious, acquiring high incidence, often suddenly, or being a threat or an unexpected phenomenon. This study discusses the hallmarks of emerging diseases, describing the existence of noninfectious emerging diseases, and elaborating on the advantages of defining noninfectious diseases as emerging ones. From the discussion of various mental health disorders, nutritional deficiencies, external injuries and violence outcomes, work injuries and occupational health, and diseases due to environmental factors, the conclusion is drawn that a wide variety of noninfectious diseases can be defined as emergent. Noninfectious emerging diseases need to be identified in order to improve their control and management. A new definition of "emergent disease" is proposed, one that emphasizes the pathways of emergence and conceptual traits, rather than descriptive features.
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... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ... and other neurodegenerative diseases to better understand the function of neurons and other support cells and identify candidate therapeutic ...
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Shabanzadeh, Daniel Mønsted; Sørensen, Lars Tue; Jørgensen, Torben
OBJECTIVES: The objective of this cohort study was to determine whether subjects with gallstone disease identified by screening of a general population had increased overall mortality when compared to gallstone-free participants and to explore causes of death. METHODS: The study population (N...... built. RESULTS: Gallstone disease was present in 10%. Mortality was 46% during median 24.7 years of follow-up with 1% lost. Overall mortality and death from cardiovascular diseases were significantly associated to gallstone disease. Death from unknown causes was significantly associated to gallstone...... disease and death from cancer and gastrointestinal disease was not associated. No differences in mortality for ultrasound-proven gallstones or cholecystectomy were identified. CONCLUSIONS: Gallstone disease is associated with increased overall mortality and to death from cardiovascular disease. Gallstones...
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basic disease appears to be unaffected by pregnancy. S Afr Med J ... Takayasu's disease is an idiopathic chronic granulomatous .... prevalence of tuberculosis in Asia." In our 3 .... lower limbs may be significantly lower than the central blood.
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