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Sample records for adrenocortical disease ppnad

  1. Primary pigmented nodular adrenocortical disease

    Marie T Manipadam

    2011-01-01

    Full Text Available Primary pigmented nodular adrenocortical disease (PPNAD is a rare cause of ACTH-independent Cushing′s syndrome and has characteristic gross and microscopic pathologic findings. We report a case of PPNAD in a 15-year-old boy, which was not associated with Carney′s complex. Bilateral adrenalectomy is the treatment of choice.

  2. Familial isolated primary pigmented nodular adrenocortical disease associated with a novel low penetrance PRKAR1A gene splice site mutation

    Storr, Helen L; Metherell, Louise A; Dias, Renuka

    2010-01-01

    Primary pigmented nodular adrenocortical disease (PPNAD) is associated with inactivating germline protein kinase A regulatory subunit type 1-alpha (PRKAR1A) mutations and loss of heterozygosity at the 17q22-24 locus in approximately 50% patients. PRKAR1A mutations are observed in both isolated PP...... PPNAD (iPPNAD) and Carney complex (CNC). Most mutations result in a functionally null-allele and exhibit high penetrance. We genotyped members of an extended family for a novel PRKAR1A mutation and undertook detailed phenotyping for CNC in the affected individuals....

  3. Association of the M1V PRKAR1A mutation with primary pigmented nodular adrenocortical disease in two large families

    Pereira, Alberto M.; Hes, Frederik J.; Horvath, Anelia; Woortman, Sanne; Greene, Elizabeth; Bimpaki, Eirini; Alatsatianos, Anton; Boikos, Sosipatros; Smit, Johannes W.; Romijn, Johannes A.; Nesterova, Maria; Stratakis, Constantine A.

    2010-01-01

    Carney complex (CNC) is a familial multiple neoplasia syndrome frequently associated with primary pigmented nodular adrenocortical disease (PPNAD), a bilateral form of micronodular adrenal hyperplasia that leads to Cushing's syndrome (CS). Germline PRKAR1A mutations cause CNC and only rarely

  4. A Novel PRKAR1A Mutation Identified in a Patient with Isolated Primary Pigmented Nodular Adrenocortical Disease

    Sira Korpaisarn

    2017-08-01

    Full Text Available Primary pigmented nodular adrenocortical disease (PPNAD is a rare cause of Cushing syndrome, especially the isolated form without Carney complex, associated with germline mutations in PRKAR1A, the protein kinase A regulatory subunit type 1 alpha gene. We report a 31-year-old female who presented with secondary amenorrhea, cushingoid appearance, and hypertension without Carney complex. Biochemical laboratory examinations confirmed the ACTH-independent adrenal Cushing syndrome with negative Liddle test. A small right adrenal adenoma of 0.8 cm was shown on computed tomography while magnetic resonance imaging revealed nodularity of both adrenal glands. The histological report confirmed PPNAD using laparoscopic right adrenalectomy, and subsequent left adrenalectomy was performed 6 months later. She had inherited heterozygosity of a novel germline mutation of the PRKAR1A gene (g.114213T>G or c.709-5T>G. This splice site mutation results in exon 8 skipping. Her father carrying the same mutation had no clinical features of either PPNAD or Carney complex. This novel PRKAR1A gene mutation, c.709-5T>G, is reported here for the first time manifesting as an incomplete clinical expression of the isolated form of PPNAD and being inherited with low penetrance unlike other inherited mutations of the Carney complex which have a penetrance of almost 100%.

  5. Efficacy of dexamethasone suppression test during the diagnosis of primary pigmented nodular adrenocortical disease in Chinese adrenocorticotropic hormone-independent Cushing syndrome.

    Chen, Shi; Li, Ran; Lu, Lin; Duan, Lian; Zhang, Xuebin; Tong, Anli; Pan, Hui; Zhu, Huijuan; Lu, Zhaolin

    2018-01-01

    To evaluate the cut-off value of the ratio of 24 h urinary free cortisol (24 h UFC) levels post-dexamethasone to prior-dexamethasone in dexamethasone suppression test (DST) during the diagnosis of primary pigmented nodular adrenocortical disease in Chinese adrenocorticotropic hormone-independent Cushing syndrome. Retrospective study. The patients diagnosed with primary pigmented nodular adrenocortical disease (PPNAD, n = 25), bilateral macronodular adrenal hyperplasia (BMAH, n = 27), and adrenocortical adenoma (ADA, n = 84) were admitted to the Peking Union Medical College Hospital from 2001 to 2016. Serum cortisol, adrenocorticotropic hormone (ACTH), and 24 h UFC were measured before and after low-dose dexamethasone suppression test (LDDST) and high-dose dexamethasone suppression test (HDDST). After LDDST and HDDST, 24 h UFC elevated in patients with PPNAD (paired t-test, P = 0.007 and P = 0.001), while it remained unchanged in the BMAH group (paired t-test, P = 0.471 and P = 0.414) and decreased in the ADA group (paired t-test, P = 0.002 and P = 0.004). The 24 h UFC level after LDDST was higher in PPNAD and BMAH as compared to ADA (P < 0.017), while no significant difference was observed between PPNAD and BMAH. After HDDST, 24 h UFC was higher in patients with PPNAD as compared to that of ADA and BMAH (P < 0.017). The cut-off value of 24 h UFC (Post-L-Dex)/(Pre-L-Dex) was 1.16 with 64.0% sensitivity and 77.9% specificity, and the cut-off value of 24 h UFC (Post-H-Dex)/(Pre-H-Dex) was 1.08 with 84.0% sensitivity and 75.6% specificity. The ratio of post-dexamethasone to prior-dexamethasone had a unique advantage in distinguishing PPNAD from BMAH and ADA.

  6. PRKACA: the catalytic subunit of protein kinase A and adrenocortical tumors

    Annabel Sophie Berthon

    2015-05-01

    Full Text Available Cyclic-AMP (cAMP-dependent protein kinase (PKA is the main effector of cAMP signaling in all tissues. Inactivating mutations of the PRKAR1A gene, coding for the type 1A regulatory subunit of PKA, are responsible for Carney complex and primary pigmented nodular adrenocortical disease (PPNAD. PRKAR1A inactivation and PKA dysregulation have been implicated in various types of adrenocortical pathologies associated with ACTH-independent Cushing syndrome (AICS from PPNAD to adrenocortical adenomas and cancer, and other forms of bilateral adrenocortical hyperplasias (BAH. More recently, mutations of PRKACA, the gene coding for the catalytic subunit C alpha (Cα, were also identified in the pathogenesis of adrenocortical tumors. PRKACA copy number gain was found in the germline of several patients with cortisol-producing BAH, whereas the somatic Leu206Arg (c.617A>C recurrent PRKACA mutation was found in as many as half of all adrenocortical adenomas associated with AICS. In vitro analysis demonstrated that this mutation led to constitutive Cα activity, unregulated by its main partners, the PKA regulatory subunits. In this review, we summarize the current understanding of the involvement of PRKACA in adrenocortical tumorigenesis, and our understanding of PKA’s role in adrenocortical lesions. We also discuss potential therapeutic advances that can be made through targeting of PRKACA and the PKA pathway.

  7. Primary pigmented nodular adrenocortical disease presenting with a unilateral adrenocortical nodule treated with bilateral laparoscopic adrenalectomy: a case report

    Kaltsas Gregory

    2010-07-01

    Full Text Available Abstract Introduction Primary pigmented nodular adrenocortical disease is a rare cause of adrenocorticotropic hormone-independent Cushing's syndrome. We report an uncommon primary pigmented nodular adrenocortical disease case presenting with a unilateral adrenocortical nodule and provide a brief overview of the existing literature. Case presentation A 27-year-old Caucasian woman was admitted to our Department with adrenocorticotropic hormone-independent Cushing's syndrome. Its cause was initially considered a left adrenocortical adenoma based on computer tomography imaging. The patient underwent left laparoscopic adrenalectomy and histological examination revealed pigmented micronodular adrenal hyperplasia. Evaluation for the presence of Carney complex was negative. Six months later recurrence of hypercortisolism was documented and a right laparoscopic adrenalectomy was performed further establishing the diagnosis of primary pigmented nodular adrenocortical disease. After a nine-year follow-up there is no evidence of residual disease. Conclusions Even though primary pigmented nodular adrenocortical disease is a rare cause of Cushing's syndrome, it should be included in the differential diagnosis of adrenocorticotropic hormone-independent Cushing's syndrome, especially because adrenal imaging can be misleading mimicking other adrenocortical diseases. Bilateral laparoscopic adrenalectomy is the preferred treatment in these subjects.

  8. Primary pigmented nodular adrenocortical disease associated with Carney complex: case report and literature review

    Fabrícia Torres Gonçalves

    Full Text Available CONTEXT: Carney complex (CNC, a familial multiple neoplasm syndrome with dominant autosomal transmission, is characterized by tumors of the heart, skin, endocrine and peripheral nervous system, and also cutaneous lentiginosis. This is a rare syndrome and its main endocrine manifestation, primary pigmented nodular adrenal disease (PPNAD, is an uncommon cause of adrenocorticotropic hormone-independent Cushing's syndrome. CASE REPORT: We report the case of a 20-year-old patient with a history of weight gain, hirsutism, acne, secondary amenorrhea and facial lentiginosis. Following the diagnosing of CNC and PPNAD, the patient underwent laparoscopic bilateral adrenalectomy, and she evolved with decreasing hypercortisolism. Screening was also performed for other tumors related to this syndrome. The diagnostic criteria, screening and follow-up for patients and affected family members are discussed.

  9. Does somatostatin have a role in the regulation of cortisol secretion in primary pigmented nodular adrenocortical disease (PPNAD)? A clinical and in vitro investigation

    Z. Bram (Zakariae); P. Xekouki (Paraskevi); E. Louiset (Estelle); M. Keil (Mark); D. Avgeropoulos (Dimitrios); C. Giatzakis (Christoforos); M. Nesterova (Maria); N. Sinaii (Ninet); L.J. Hofland (Leo); R. Cherqaoui (Rabia); H. Lefebvre (Hervé); C.A. Stratakis (Constantine)

    2014-01-01

    textabstractContext: Somatostatin (SST) receptors (SSTRs) are expressed in a number of tissues, including the adrenal cortex, but their role in cortisol secretion has not been well characterized. Objectives: The objective of the study was to investigate the expression of SSTRs in the adrenal cortex

  10. Adrenocortical cancer

    Payabyab, Eden C.; Balasubramaniam, Sanjeeve; Edgerly, Maureen

    2016-01-01

    The development of new therapies has lagged behind for rare cancers without defined therapeutic targets. Adrenocortical cancer is no exception. Mitotane, an older agent considered "adrenolytic," is used both to control symptoms in advanced disease and as adjuvant therapy after surgical resection....... Molecular characterization of adrenocortical cancer has deepened our understanding of this genetically complex disease while identifying subgroups whose importance remains to be determined. Unfortunately, such studies have yet to demonstrate a therapeutic target for drug development, and to date......, no targeted therapy has achieved meaningful outcomes. Consequently, first-line therapy for metastatic disease remains a combination regimen of etoposide, doxorubicin, and cisplatinum established in a randomized clinical trial. In addition to evaluating recent studies in adrenocortical cancer, we raise one...

  11. Increased adrenocortical response to adrenocorticotropic hormone (ACTH) in sport horses with equine glandular gastric disease (EGGD).

    Scheidegger, M D; Gerber, V; Bruckmaier, R M; van der Kolk, J H; Burger, D; Ramseyer, A

    2017-10-01

    This study tested the hypothesis that adrenocortical function would be altered in horses with equine gastric ulcer syndrome (EGUS). Twenty-six sport horses competing at national or international levels in eventing (n=15) or endurance (n=11) were subjected to a gastroscopic examination and an adrenocorticotropic hormone (ACTH) stimulation test. Salivary cortisol concentrations were measured before (baseline) and after (30, 60, 90, 120 and 150min) IV ACTH injection (1μg/kg bodyweight). Within EGUS, two distinct diseases, equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD), can be distinguished. ESGD was diagnosed in 8/11 (73%; 95% confidence intervals [95%CI], 43-92%) endurance horses and 5/15 (33%; 95% CI, 14-58%) eventing horses. EGGD was observed in 9/11 (82%; 95% CI, 53-96%) endurance horses and 9/15 (60%; 95% CI, 35-81%) eventing horses. The presence or severity of ESGD was unrelated to the presence or severity of EGGD. ACTH stimulation induced a larger increase in cortisol concentration in horses with moderate EGGD than in horses with mild EGGD. Cortisol concentration during the entire sampling period (total increase in cortisol concentration during the entire sampling period [dAUC], 31.1±6.4ng/mL) and the highest measured concentration at a single time point (maximal increase in cortisol concentration [dMAX], 10.3±2.3ng/mL) were increased (P=0.005 and P=0.038, respectively), indicating that horses with glandular gastric disease exhibited increased adrenocortical responses to ACTH stimulation. These results suggest that EGGD might be associated with an enhanced adrenocortical sensitivity. Further investigations are warranted to confirm the association between adrenocortical sensitivity and EGGD and to elucidate the pathophysiological mechanisms involved. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Detection of adrenocortical autoantibodies in Addison's disease with a peroxidase-labelled protein A technique

    R.C. Silva

    1998-09-01

    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.

  13. The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease.

    Hellesen, A; Edvardsen, K; Breivik, L; Husebye, E S; Bratland, E

    2014-06-01

    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.

  14. Advanced diagnostic approaches and current medical management of insulinomas and adrenocortical disease in ferrets (Mustela putorius furo).

    Chen, Sue

    2010-09-01

    Endocrine neoplasia is the most common tumor type in domestic ferrets, especially in middle-aged to older ferrets. Islet cell tumors and adrenocortical tumors constitute the major types of endocrine neoplasms. Insulinoma is a tumor that produces and releases excessive amounts of insulin. Evaluation of fasted blood glucose levels provides a quick diagnostic assessment for the detection of insulinomas. Use of glucocorticoids, diazoxide, and diet modification are some of the medical treatment options for insulinomas. Adrenocortical neoplasia in ferrets usually overproduces one or more sex hormones. Sex hormones which can result in progressive alopecia, vulvar swelling in females, and prostagomegaly in males. Abdominal ultrasonography and sex hormone assays can be used to diagnose adrenocortical neoplasms. Drugs such as leuprolide acetate, deslorelin acetate, and the hormone melatonin can be used to treat adrenocortical neoplasms in ferrets when surgery is not an option. Copyright 2010 Elsevier Inc. All rights reserved.

  15. Diagnosis of bilateral adrenocortical hemorrhage by computed tomography

    Liu, L.; Haskin, M.E.; Rose, L.I.; Bemis, C.E.

    1982-01-01

    Adrenocortical hemorrhage has been diagnosed on the basis of the clinical presentation and response to steroids or autopsy findings. Prompt recognition of the disease has been difficult because of its similarity to other disorders. We report the diagnosis of a bilateral adrenocortical hemorrhage by computed tomography (CT), followed by biochemical confirmation of the diagnosis

  16. Rapid appearance of transient secondary adrenocortical insufficiency after alpha-particle radiation therapy for Cushing's disease

    Cook, D.M.; Jordan, R.M.; Kendall, J.W.; Linfoot, J.A.

    1976-01-01

    A 17-year-old woman received 12,000 rads of alpha-particle radiation for the treatment of Cushing's disease. One day after the completion of therapy, the patient developed nausea, vomiting, headache, and postural hypotension. Laboratory evaluation demonstrated a marked fall of the previously elevated urinary 17-hydroxycorticosteroids (17-OHCS) and undetectable plasma cortisols. The urinary 17-OHCS transiently returned to supranormal levels but over a 2 1 / 2 -week period decreased and then remained low. The patient also demonstrated a subnormal urinary aldosterone excretion in relation to plasma renin activity (PRA) during 10 mEq/24 h sodium restriction. The remainder of the endocrine evaluation was normal, suggesting that pituitary function otherwise remained intact. One and one-half years after alpha-particle therapy, the patient's urinary 17-OHCS were normal and responded normally to metyrapone. The relationship between urinary aldosterone excretion and PRA also was normal. It is postulated that there was an infarction of an ACTH secreting pituitary tumor leaving the remainder of the pituitary intact. A chronically elevated circulating level of ACTH with sudden loss of ACTH secretion appeared to have been responsible for the initial low urinary aldosterone as well as the low urinary 17-OHCS. This is the first reported case of a presumed pituitary tumor infarction in association with alpha-particle pituitary radiation

  17. Adrenocortical tumors in children

    R.C. Ribeiro

    2000-10-01

    Full Text Available Childhood adrenocortical tumors (ACT are rare. In the USA, only about 25 new cases occur each year. In Southern Brazil, however, approximately 10 times that many cases are diagnosed each year. Most cases occur in the contiguous states of São Paulo and Paraná. The cause of this higher rate has not been identified. Familial genetic predisposition to cancer (p53 mutations and selected genetic syndromes (Beckwith-Wiedemann syndrome have been associated with childhood ACT in general but not with the Brazilian counterpart. Most of the affected children are young girls with classic endocrine syndromes (virilizing and/or Cushing. Levels of urinary 17-ketosteroids and plasma dehydroepiandrosterone sulfate (DHEA-S, which are abnormal in approximately 90% of the cases, provide the pivotal clue to a diagnosis of ACT. Typical imaging findings of pediatric ACT consist of a large, well-defined suprarenal tumor containing calcifications with a thin capsule and central necrosis or hemorrhage. The pathologic classification of pediatric ACT is troublesome. Even an experienced pathologist can find it difficult to differentiate carcinoma from adenoma. Surgery is the single most important procedure in the successful treatment of ACT. The role of chemotherapy in the management of childhood ACT has not been established although occasional tumors are responsive to mitotane or cisplatin-containing regimens. Because of the heterogeneity and rarity of the disease, prognostic factors have been difficult to establish in pediatric ACT. Patients with incomplete tumor resection or with metastatic disease at diagnosis have a dismal prognosis. In patients with localized and completely resected tumors, the size of the tumor has predictive value. Patients with large tumors have a much higher relapse rate than those with small tumors.

  18. Feminizing adrenocortical carcinoma with distant metastases: can surgery be considered?

    Alessandro Fancellu

    2014-07-01

    Full Text Available Functioning adrenocortical carcinomas are rare diseases with dismal prognosis. A 41-year-old man presenting with gynecomastia had a giant feminizing adrenocortical carcinoma at stage IV. Although surgical resection was controversial, we removed the primary tumor to reduce the mass effects. He lived for 12 months with an acceptable quality of life. Gynecomastia may be the first sign of feminizing adrenal malignancies. Surgery may ameliorate the quality of life in selected patients with metastatic disease.

  19. Adrenocortical Carcinoma—Health Professional Version

    Adrenocortical carcinoma is also called cancer of the adrenal cortex. A tumor of the adrenal cortex may be functioning or nonfunctioning. Most adrenocortical tumors are functioning. Find evidence-based information on adrenocortical carcinoma including treatment and research.

  20. Adjuvant and Definitive Radiotherapy for Adrenocortical Carcinoma

    Sabolch, Aaron; Feng, Mary; Griffith, Kent; Hammer, Gary; Doherty, Gerard; Ben-Josef, Edgar

    2011-01-01

    Purpose: To evaluate the impact of both adjuvant and definitive radiotherapy on local control of adrenocortical carcinoma. Methods and Materials: Outcomes were analyzed from 58 patients with 64 instances of treatment for adrenocortical carcinoma at the University of Michigan's Multidisciplinary Adrenal Cancer Clinic. Thirty-seven of these instances were for primary disease, whereas the remaining 27 were for recurrent disease. Thirty-eight of the treatment regimens involved surgery alone, 10 surgery plus adjuvant radiotherapy, and 16 definitive radiotherapy for unresectable disease. The effects of patient, tumor, and treatment factors were modeled simultaneously using multiple variable Cox proportional hazards regression for associations with local recurrence, distant recurrence, and overall survival. Results: Local failure occurred in 16 of the 38 instances that involved surgery alone, in 2 of the 10 that consisted of surgery plus adjuvant radiotherapy, and in 1 instance of definitive radiotherapy. Lack of radiotherapy use was associated with 4.7 times the risk of local failure compared with treatment regimens that involved radiotherapy (95% confidence interval, 1.2-19.0; p = 0.030). Conclusions: Radiotherapy seems to significantly lower the risk of local recurrence/progression in patients with adrenocortical carcinoma. Adjuvant radiotherapy should be strongly considered after surgical resection.

  1. Analysis of adrenocortical hyperplasia by computed tomography in patients with Cushing's disease, idiopathic hyperaldosteronism and adrenogenital syndrome

    Komiya, Ichiro; Ohara, Noriko; Nagasawa, Yoshitaka; Asawa, Takayuki; Hashizume, Kiyoshi; Takasu, Nobuyuki; Yamada, Takashi.

    1994-01-01

    We assessed the usefulness and reliability of computed tomography (CT scan) in evaluating adrenal hyperplasia in 38 patients, including 14 with Cushing's disease, 17 with idiopathic hyperaldosteronism (IHA), and 7 with the adrenogenital syndrome (AGS). Eighty-two normal subjects were also examined. We analyzed the shape of the adrenal gland and quantitated its thickness, width and length. Visual inspection revealed V-shaped right adrenal glands in 100% of patients with Cushing's disease, 94% of patients with IHA, 100% of patients with AGS and in 41% of the normal subjects. Triangular left adrenal glands were observed in 100% of patients with Cushing's disease, 82% of patients with IHA, 67% of patients with AGS and in 12% of the normal subjects. Quantitative analysis showed that the right adrenal gland was significantly thicker and longer in patients with Cushing's disease, IHA and in those with AGS than in normal subjects. The right adrenal gland was significantly wider in the patients with Cushing's disease and AGS than in control subjects. The left adrenal gland was significantly wider and longer in patients with Cushing's disease and AGS than in the normal controls. Analysis of individual data indicated that the upper limit of normal for thickness of the right adrenal was 7 mm. Therefore, adrenal hyperplasia was strongly suggested when the right adrenal gland was more than 7 mm thick. Our findings suggest that the CT scan is useful and reliable in diagnosing adrenal hyperplasia. (author)

  2. PRKAR1A mutation causing pituitary-dependent Cushing disease in a patient with Carney complex.

    Kiefer, Florian W; Winhofer, Yvonne; Iacovazzo, Donato; Korbonits, Márta; Wolfsberger, Stefan; Knosp, Engelbert; Trautinger, Franz; Höftberger, Romana; Krebs, Michael; Luger, Anton; Gessl, Alois

    2017-08-01

    Carney complex (CNC) is an autosomal dominant condition caused, in most cases, by an inactivating mutation of the PRKAR1A gene, which encodes for the type 1 alpha regulatory subunit of protein kinase A. CNC is characterized by the occurrence of endocrine overactivity, myxomas and typical skin manifestations. Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine disease observed in CNC. Here, we describe the first case of a patient with CNC and adrenocorticotropic hormone (ACTH)-dependent Cushing disease due to a pituitary corticotroph adenoma. Loss-of-heterozygosity analysis of the pituitary tumour revealed loss of the wild-type copy of PRKAR1A , suggesting a role of this gene in the pituitary adenoma development. PRKAR1A loss-of-function mutations can rarely lead to ACTH-secreting pituitary adenomas in CNC patients. Pituitary-dependent disease should be considered in the differential diagnosis of Cushing syndrome in CNC patients. © 2017 European Society of Endocrinology.

  3. Childhood Adrenocortical Tumours: a Review

    Marques-Pereira Rosana

    2006-05-01

    Full Text Available Abstract Childhood adrenocortical tumour (ACT is not a common disease, but in southern Brazil the prevalence is 15 times higher than in other parts of the world. One hundred and thirty-seven patients have been identified and followed by our group over the past four decades. Affected children are predominantly girls, with a female-to-male ratio of 3.5:1 in patients below 4 years of age. Virilization alone (51.6% or mixed with Cushing's syndrome (42.0% was the predominant clinical picture observed in these patients. Tumours are unilateral, affecting both glands equally. TP53 R337H germline mutations underlie most childhood ACTs in southern Brazil. Epidemiological data from our casuistic studies revealed that this mutation has ~10% penetrance for ACT. Surgery is the definitive treatment, and a complete resection should always be attempted. Although adjuvant chemotherapy has shown some encouraging results, its influence on overall outcome is small. The survival rate is directly correlated to tumour size; patients with small, completely excised tumours have survival rates close to 90%, whereas in those patients with inoperable tumours and/or metastatic disease it is less than 10%. In the group of patients with large, excisable tumours, half of them have an intermediate outcome. Recent molecular biology techniques and genomic approaches may help us to better understand the pathogenesis of ACT, the risk of developing a tumour when TP53 R337H is present, and to predict its outcome. An ongoing pilot study consisting of close monitoring of healthy carriers of the TP53 R337H mutation - siblings and first-degree relatives of known affected cases - aims at the early detection of ACTs and an improvement of the cure rate.

  4. Mouse Models Recapitulating Human Adrenocortical Tumors: What is lacking?

    Felicia Leccia

    2016-07-01

    Full Text Available Adrenal cortex tumors are divided into benign forms such as primary hyperplasias and adrenocortical adenomas (ACAs, and malignant forms or adrenocortical carcinomas (ACCs. Primary hyperplasias are rare causes of ACTH-independent hypercortisolism. ACAs are the most common type of adrenal gland tumors and they are rarely functional, i.e producing steroids. When functional, adenomas result in endocrine disorders such as Cushing’s syndrome (hypercortisolism or Conn’s syndrome (hyperaldosteronism. In contrast, ACCs are extremely rare but highly aggressive tumors that may also lead to hypersecreting syndromes. Genetic analyses of patients with sporadic or familial forms of adrenocortical tumors led to the identification of potentially causative genes, most of them being involved in PKA, Wnt/β-catenin and P53 signaling pathways. Development of mouse models is a crucial step to firmly establish the functional significance of candidate genes, to dissect mechanisms leading to tumors and endocrine disorders and in fine to provide in vivo tools for therapeutic screens. In this article we will provide an overview on the existing mouse models (xenografted and genetically engineered of adrenocortical tumors by focusing on the role of PKA and Wnt/β-catenin pathways in this context. We will discuss the advantages and limitations of models that have been developed heretofore and we will point out necessary improvements in the development of next generation mouse models of adrenal diseases.

  5. Isolation of rat adrenocortical mitochondria

    Solinas, Paola [Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Fujioka, Hisashi [Electron Microscopy Facility, Department of Pharmacology, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Tandler, Bernard [Department of Biological Sciences, School of Dental Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Hoppel, Charles L., E-mail: charles.hoppel@case.edu [Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Medicine, Center for Mitochondrial Disease, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer A method for isolation of adrenocortical mitochondria from the adrenal gland of rats is described. Black-Right-Pointing-Pointer The purified isolated mitochondria show excellent morphological integrity. Black-Right-Pointing-Pointer The properties of oxidative phosphorylation are excellent. Black-Right-Pointing-Pointer The method increases the opportunity of direct analysis of adrenal mitochondria from small animals. -- Abstract: This report describes a relatively simple and reliable method for isolating adrenocortical mitochondria from rats in good, reasonably pure yield. These organelles, which heretofore have been unobtainable in isolated form from small laboratory animals, are now readily accessible. A high degree of mitochondrial purity is shown by the electron micrographs, as well as the structural integrity of each mitochondrion. That these organelles have retained their functional integrity is shown by their high respiratory control ratios. In general, the biochemical performance of these adrenal cortical mitochondria closely mirrors that of typical hepatic or cardiac mitochondria.

  6. Adrenocortical carcinoma with extension to the inferior vena cava and right atrium: 20-month-old girl with TP53 mutation

    Terry L. Levin, MD

    2015-01-01

    Full Text Available A 20-month-old female presented with respiratory distress and a right adrenal mass extending into the inferior vena cava and right atrium. The mass was initially thought to be neuroblastoma. Pathology later revealed adrenocortical carcinoma. Inferior vena cava extension is far more common in adrenocortical carcinoma than neuroblastoma, and its presence should prompt clinical and laboratory evaluation for an adrenocortical tumor. The genetic findings in TP53 associated with this disease are discussed.

  7. MicroRNAs as potential biomarkers in adrenocortical cancer: progress and challenges

    Nadia eCHERRADI

    2016-01-01

    Full Text Available Adrenocortical carcinoma is a rare malignancy with poor prognosis and limited therapeutic options. Over the last decade, pan-genomic analyses of genetic and epigenetic alterations and genome-wide expression profile studies allowed major advances in the understanding of the molecular genetics of adrenocortical carcinoma. Besides the well-known dysfunctional molecular pathways in adrenocortical tumors such as the IGF2 pathway, the Wnt pathway and TP53, high-throughput technologies enabled a more comprehensive genomic characterization of adrenocortical cancer. Integration of expression profile data with exome sequencing, SNP array analysis, methylation and microRNA profiling led to the identification of subgroups of malignant tumors with distinct molecular alterations and clinical outcomes. MicroRNAs post-transcriptionally silence their target gene expression either by degrading mRNA or by inhibiting translation. Although our knowledge of the contribution of deregulated microRNAs to the pathogenesis of adrenocortical carcinoma is still in its infancy, recent studies support their relevance in gene expression alterations in these tumors. Some microRNAs have been shown to carry potential diagnostic and prognostic values while others may be good candidates for therapeutic interventions. With the emergence of disease-specific blood-borne microRNAs signatures, analyses of small cohorts of patients with adrenocortical carcinoma suggest that circulating microRNAs represent promising non-invasive biomarkers of malignancy or recurrence. However, some technical challenges still remain, and most of the microRNAs reported in the literature have not yet been validated in sufficiently powered and longitudinal studies. In this review, we discuss the current knowledge regarding the deregulation of tumor-associated and circulating microRNAs in adrenocortical carcinoma patients, while emphasizing their potential significance in adrenocortical carcinoma pathogenic

  8. Feminizing Adrenocortical Carcinoma Without Gynecomastia

    Farida Chentli1*,

    2017-07-01

    Full Text Available Malignant feminizing adrenocortical tumors are exceedingly rare. Their main presentation is gynecomastia. In these estrogen secreting tumors (with or without other adrenocortical hormones lack of gynecomastia is exceptional as in our case. A 44-year-old man presented with abdominal pain. Radiological assessment revealed a tumor measuring 120 × 95 mm in the retroperitoneal area with numerous metastases. Pathological examination pleaded for an adrenal origin with a Weiss’s score of 5. Six months later, the tumor relapsed, and he had a second surgery and was sent for hormone assessment. Clinical examination showed a skinny man with severe fatigue. He had no Cushingoid features. Gynecomastia and galactorrhea were absent. Penile length, testicular volume, and body hair growth were normal. Several cutaneous nodules were present. Biological assessment showed high morning plasma cortisol, which failed to be suppressed by treatment with 2 mg dexamethasone. Plasma estradiol and 17OH progesterone levels were high, but his testosterone levels were low. Radiological exploration showed numerous metastases: pleural, pulmonary, retroperitoneal, and abdominal. He was treated with classical chemotherapy, but he died four months after diagnosis.

  9. Adrenocortical zonation, renewal, and remodeling

    Marjut ePihlajoki

    2015-03-01

    Full Text Available The adrenal cortex is divided into concentric zones. In humans the major cortical zones are the zona glomerulosa, zona fasciculata, and zona reticularis. The adrenal cortex is a dynamic organ in which senescent cells are replaced by newly differentiated ones. This constant renewal facilitates organ remodeling in response to physiological demand for steroids. Cortical zones can reversibly expand, contract, or alter their biochemical profiles to accommodate needs. Pools of stem/progenitor cells in the adrenal capsule, subcapsular region, and juxtamedullary region can differentiate to repopulate or expand zones. Some of these pools appear to be activated only during specific developmental windows or in response to extreme physiological demand. Senescent cells can also be replenished through direct lineage conversion; for example, cells in the zona glomerulosa can transform into cells of the zona fasciculata. Adrenocortical cell differentiation, renewal, and function are regulated by a variety of endocrine/paracrine factors including adrenocorticotropin, angiotensin II, insulin-related growth hormones, luteinizing hormone, activin, and inhibin. Additionally, zonation and regeneration of the adrenal cortex are controlled by developmental signaling pathways, such as the sonic hedgehog, delta-like homologue 1, fibroblast growth factor, and WNT/β-catenin pathways. The mechanisms involved in adrenocortical remodeling are complex and redundant so as to fulfill the offsetting goals of organ homeostasis and stress adaptation.

  10. Pediatric adrenocortical neoplasms: can imaging reliably discriminate adenomas from carcinomas?

    Flynt, Kelsey A.; Dillman, Jonathan R.; Smith, Ethan A.; Strouse, Peter J.; Davenport, Matthew S.; Caoili, Elaine M.; Else, Tobias

    2015-01-01

    There is a paucity of literature describing and comparing the imaging features of adrenocortical adenomas and carcinomas in children and adolescents. To document the CT and MRI features of adrenocortical neoplasms in a pediatric population and to determine whether imaging findings (other than metastatic disease) can distinguish adenomas from carcinomas. We searched institutional medical records to identify pediatric patients with adrenocortical neoplasms. Pre-treatment CT and MRI examinations were reviewed by two radiologists in consensus, and pertinent imaging findings were documented. We also recorded relevant histopathological, demographic, clinical follow-up and survival data. We used the Student's t-test and Wilcoxon rank sum test to compare parametric and nonparametric continuous data, and the Fisher exact test to compare proportions. We used receiver operating characteristic (ROC) curve analyses to evaluate the diagnostic performances of tumor diameter and volume for discriminating carcinoma from adenoma. A P-value ≤0.05 was considered statistically significant. Among the adrenocortical lesions, 9 were adenomas, 15 were carcinomas, and 1 was of uncertain malignant potential. There were no differences in mean age, gender or sidedness between adenomas and carcinomas. Carcinomas were significantly larger than adenomas based on mean estimated volume (581 ml, range 16-2,101 vs. 54 ml, range 3-197 ml; P-value = 0.003; ROC area under the curve = 0.92) and mean maximum transverse plane diameter (9.9 cm, range 3.0-14.9 vs. 4.4 cm, range 1.9-8.2 cm; P-value = 0.0001; ROC area under the curve = 0.92). Carcinomas also were more heterogeneous than adenomas on post-contrast imaging (13/14 vs. 2/9; odds ratio [OR] = 45.5; P-value = 0.001). Six of 13 carcinomas and 1 of 8 adenomas contained calcification at CT (OR = 6.0; P-value = 0.17). Seven of 15 children with carcinomas exhibited metastatic disease at diagnosis, and three had inferior vena cava invasion. Median

  11. Pediatric adrenocortical neoplasms: can imaging reliably discriminate adenomas from carcinomas?

    Flynt, Kelsey A.; Dillman, Jonathan R.; Smith, Ethan A.; Strouse, Peter J. [University of Michigan Health System, Section of Pediatric Radiology, C. S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); Davenport, Matthew S.; Caoili, Elaine M. [University of Michigan Health System, Division of Abdominal Imaging, Department of Radiology, Ann Arbor, MI (United States); Else, Tobias [University of Michigan Health System, Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, Ann Arbor, MI (United States)

    2015-08-15

    There is a paucity of literature describing and comparing the imaging features of adrenocortical adenomas and carcinomas in children and adolescents. To document the CT and MRI features of adrenocortical neoplasms in a pediatric population and to determine whether imaging findings (other than metastatic disease) can distinguish adenomas from carcinomas. We searched institutional medical records to identify pediatric patients with adrenocortical neoplasms. Pre-treatment CT and MRI examinations were reviewed by two radiologists in consensus, and pertinent imaging findings were documented. We also recorded relevant histopathological, demographic, clinical follow-up and survival data. We used the Student's t-test and Wilcoxon rank sum test to compare parametric and nonparametric continuous data, and the Fisher exact test to compare proportions. We used receiver operating characteristic (ROC) curve analyses to evaluate the diagnostic performances of tumor diameter and volume for discriminating carcinoma from adenoma. A P-value ≤0.05 was considered statistically significant. Among the adrenocortical lesions, 9 were adenomas, 15 were carcinomas, and 1 was of uncertain malignant potential. There were no differences in mean age, gender or sidedness between adenomas and carcinomas. Carcinomas were significantly larger than adenomas based on mean estimated volume (581 ml, range 16-2,101 vs. 54 ml, range 3-197 ml; P-value = 0.003; ROC area under the curve = 0.92) and mean maximum transverse plane diameter (9.9 cm, range 3.0-14.9 vs. 4.4 cm, range 1.9-8.2 cm; P-value = 0.0001; ROC area under the curve = 0.92). Carcinomas also were more heterogeneous than adenomas on post-contrast imaging (13/14 vs. 2/9; odds ratio [OR] = 45.5; P-value = 0.001). Six of 13 carcinomas and 1 of 8 adenomas contained calcification at CT (OR = 6.0; P-value = 0.17). Seven of 15 children with carcinomas exhibited metastatic disease at diagnosis, and three had inferior vena cava invasion. Median

  12. Treatment with docetaxel and cisplatin in advanced adrenocortical carcinoma, a phase II study

    Urup, Thomas; Pawlak, W Z; Petersen, P M

    2013-01-01

    Adrenocortical carcinoma (ACC) is a rare disease with a poor response to chemotherapy. Cisplatin is the most widely investigated drug in the treatment of ACC and in vitro studies have indicated activity of taxanes. The objectives of this study were to evaluate the efficacy and toxicity of cisplatin...... combined with docetaxel as first-line treatment of advanced ACC....

  13. Adrenocortical function in hospitalised patients with active ...

    2006-05-17

    May 17, 2006 ... Tuberculosis (TB) is a major cause of morbidity and mortality in sub-Sah aran Africa, ... To assess whether adrenocortical function was compromised in patients with active tuberculosis. (TB) during the first 5 days of ..... Hernandez-Pando R, de la Luz Streber M, Orozco H, et al. Emergent immunoregulatory.

  14. A case of Carney complex misdiagnosed as neurofibromatosis type 1 – Diagnostic difficulty in a rare disease

    Yoshitane Tsukamoto, MD, PhD

    2017-11-01

    Full Text Available We experienced a diagnostically challenging case of Carney complex (CNC. A 24-year-old woman had a past history of surgical removal of multiple cutaneous tumors in the childhood. She was followed as a patient of neurofibromatosis type 1 (NF1 and referred to our hospital for further treatment after she grew up to adulthood. At our hospital, several cutaneous tumors were excised, and the pathological diagnosis was myxoma arising from not deep soft tissue but cutis (so-called cutaneous myxoma. Despite previous clinical diagnosis of NF1, because of the probability of CNC, detailed systemic examination was undertaken including radiological and endocrinological tests. Imaging techniques showed multiple lumps in both breasts, a mass in left atrium and nodular lesions in adrenal glands. Serum ACTH level was markedly suppressed. Surgically resected specimens revealed breast myxomas, cardiac myxoma and primary pigmented nodular adrenocortical disease (PPNAD. These findings met the diagnostic criteria for CNC. Genetic analysis revealed known non-sense mutation of PRKAR1A c.124C>T (p.R42X (ClinVar ID 41382. Her 50-year-old mother was also shown to have cardiac myxomas, radiological finding of breast myxomatosis and the same PRKAR1A mutation as her daughter. In the present case, the accurate diagnosis of CNC was difficult not only because CNC is a rare disease but also because skin pigmentation was not obvious. Since cardiac myxoma might result in poor or fatal outcome, early and accurate diagnosis of CNC and subsequent systemic investigation including heart are important. Although pediatric cutaneous myxomas are rare, multiple cutaneous myxomas might suggest the possibility of CNC. In such cases, systemic investigation should be done for the accurate diagnosis.

  15. Surgical resection of synchronously metastatic adrenocortical cancer.

    Dy, Benzon M; Strajina, Veljko; Cayo, Ashley K; Richards, Melanie L; Farley, David R; Grant, Clive S; Harmsen, William S; Evans, Doug B; Grubbs, Elizabeth G; Bible, Keith C; Young, William F; Perrier, Nancy D; Que, Florencia G; Nagorney, David M; Lee, Jeffrey E; Thompson, Geoffrey B

    2015-01-01

    Metastatic adrenocortical carcinoma (ACC) is rapidly fatal, with few options for treatment. Patients with metachronous recurrence may benefit from surgical resection. The survival benefit in patients with hematogenous metastasis at initial presentation is unknown. A review of all patients undergoing surgery (European Network for the Study of Adrenal Tumors) stage IV ACC between January 2000 and December 2012 from two referral centers was performed. Kaplan-Meier estimates were analyzed for disease-free and overall survival (OS). We identified 27 patients undergoing surgery for stage IV ACC. Metastases were present in the lung (19), liver (11), and brain (1). A complete resection (R0) was achieved in 11 patients. The median OS was improved in patients undergoing R0 versus R2 resection (860 vs. 390 days; p = 0.02). The 1- and 2-year OS was also improved in patients undergoing R0 versus R2 resection (69.9 %, 46.9 % vs. 53.0 %, 22.1 %; p = 0.02). Patients undergoing neoadjuvant therapy (eight patients) had a trend towards improved survival at 1, 2, and 5 years versus no neoadjuvant therapy (18 patients) [83.3 %, 62.5 %, 41.7 % vs. 56.8 %, 26.6 %, 8.9 %; p = 0.1]. Adjuvant therapy was associated with improved recurrence-free survival at 6 months and 1 year (67 %, 33 % vs. 40 %, 20 %; p = 0.04) but not improved OS (p = 0.63). Sex (p = 0.13), age (p = 0.95), and location of metastasis (lung, p = 0.51; liver, p = 0.67) did not correlate with OS after operative intervention. Symptoms of hormonal excess improved in 86 % of patients. Operative intervention, especially when an R0 resection can be achieved, following systemic therapy may improve outcomes, including OS, in select patients with stage IV ACC. Response to neoadjuvant chemotherapy may be of use in defining which patients may benefit from surgical intervention. Adjuvant therapy was associated with decreased recurrence but did not improve OS.

  16. Cushing's syndrome and fetal features resurgence in adrenal cortex-specific Prkar1a knockout mice.

    Isabelle Sahut-Barnola

    2010-06-01

    Full Text Available Carney complex (CNC is an inherited neoplasia syndrome with endocrine overactivity. Its most frequent endocrine manifestation is primary pigmented nodular adrenocortical disease (PPNAD, a bilateral adrenocortical hyperplasia causing pituitary-independent Cushing's syndrome. Inactivating mutations in PRKAR1A, a gene encoding the type 1 alpha-regulatory subunit (R1alpha of the cAMP-dependent protein kinase (PKA have been found in 80% of CNC patients with Cushing's syndrome. To demonstrate the implication of R1alpha loss in the initiation and development of PPNAD, we generated mice lacking Prkar1a specifically in the adrenal cortex (AdKO. AdKO mice develop pituitary-independent Cushing's syndrome with increased PKA activity. This leads to autonomous steroidogenic genes expression and deregulated adreno-cortical cells differentiation, increased proliferation and resistance to apoptosis. Unexpectedly, R1alpha loss results in improper maintenance and centrifugal expansion of cortisol-producing fetal adrenocortical cells with concomitant regression of adult cortex. Our data provide the first in vivo evidence that loss of R1alpha is sufficient to induce autonomous adrenal hyper-activity and bilateral hyperplasia, both observed in human PPNAD. Furthermore, this model demonstrates that deregulated PKA activity favors the emergence of a new cell population potentially arising from the fetal adrenal, giving new insight into the mechanisms leading to PPNAD.

  17. If It Goes up, Must It Come Down? Chronic Stress and the Hypothalamic-Pituitary Adrenocortical Axis in Humans

    Miller, Gregory E.; Chen, Edith; Zhou, Eric S.

    2007-01-01

    The notion that chronic stress fosters disease by activating the hypothalamic-pituitary adrenocortical (HPA) axis is featured prominently in many theories. The research linking chronic stress and HPA function is contradictory, however, with some studies reporting increased activation, and others reporting the opposite. This meta-analysis showed…

  18. Blood Transfusion and Survival for Resected Adrenocortical Carcinoma: A Study from the United States Adrenocortical Carcinoma Group.

    Poorman, Caroline E; Postlewait, Lauren M; Ethun, Cecilia G; Tran, Thuy B; Prescott, Jason D; Pawlik, Timothy M; Wang, Tracy S; Glenn, Jason; Hatzaras, Ioannis; Shenoy, Rivfka; Phay, John E; Keplinger, Kara; Fields, Ryan C; Jin, Linda X; Weber, Sharon M; Salem, Ahmed; Sicklick, Jason K; Gad, Shady; Yopp, Adam C; Mansour, John C; Duh, Quan-Yang; Seiser, Natalie; Solorzano, Carmen C; Kiernan, Colleen M; Votanopoulos, Konstantinos I; Levine, Edward A; Staley, Charles A; Poultsides, George A; Maithel, Shishir K

    2017-07-01

    Perioperative blood transfusion is associated with decreased survival in pancreatic, gastric, and liver cancer. The effect of transfusion in adrenocortical carcinoma (ACC) has not been studied. Patients with available transfusion data undergoing curative-intent resection of ACC from 1993 to 2014 at 13 institutions comprising the United States Adrenocortical Carcinoma Group were included. Factors associated with blood transfusion were determined. Primary and secondary end points were recurrence-free survival (RFS) and overall survival (OS), respectively. Out of 265 patients, 149 were included for analysis. Out of these, 57 patients (38.3%) received perioperative transfusions. Compared to nontransfused patients, transfused patients more commonly had stage 4 disease (46% vs 24%, P = 0.01), larger tumors (15.8 vs 10.2 cm, P Transfusion was associated with decreased RFS (8.9 vs 24.7 months, P = 0.006) and OS (22.8 vs 91.0 months, P transfusion, stage IV, hormonal hypersecretion, and adjuvant therapy were associated with decreased RFS. On multivariable analysis, only transfusion [hazard ratio (HR) = 1.7, 95% confidence interval (CI) =1.0-2.9, P = 0.04], stage IV (HR = 3.2, 95% CI = 1.7-5.9, P transfusion HR = 2.0, 95% CI = 1.1-3.8, P = 0.02; stage 4 HR = 6.2, 95% CI = 3.1-12.4, P 2 units of packed red blood cells in median RFS (8.9 vs 8.4 months, P = 0.95) or OS (26.5 vs 18.6 months, P = 0.63). Perioperative transfusion is associated with earlier recurrence and decreased survival after curative-intent resection of ACC. Strategies and protocols to minimize blood transfusion should be developed and followed.

  19. Visualization of adrenocortical carcinoma with 131I-Adosterol

    Maruoka, Shin; Nakamura, Mamoru

    1987-01-01

    There are very few literatures on successful visualization of adrenocortical carcinoma by means of 131 I-iodocholesterol scintigraphy, although many reports have referred to utility of 131 I-iodocholesterol scintigraphy for adrenal disorders. Since 1976, we have experienced 4 cases of adrenocortical carcinoma which were delineated by 131 I-6β-iodomethyl-19-norcholesterol ( 131 I-Adosterol). Three of 4 cases were adrenocortical carcinoma with Cushing's syndrome, and one was adrenocortical carcinoma with adrenogenital syndrome. In 3 cases of cortisol secreting adrenocortical carcinoma, uptake in the tumor and lack of uptake in the contralateral adrenal gland were seen. Faint to moderate uptakes were observed in the 2 cases, but another one showed as high uptake as seen in adenoma. Patient with androgen secreting adrenocortical carcinoma had increased uptake in the tumor and showed faint uptake in the contralateral adrenal gland. Intensity of 131 I-Adosterol uptake in adrenocortical carcinoma seems to depend on the extent of tumor necrosis, cell differentiation and function. (author)

  20. Visualization of adrenocortical carcinoma with /sup 131/I-Adosterol

    Maruoka, Shin; Nakamura, Mamoru

    1987-01-01

    There are very few literatures on successful visualization of adrenocortical carcinoma by means of /sup 131/I-iodocholesterol scintigraphy, although many reports have referred to utility of /sup 131/I-iodocholesterol scintigraphy for adrenal disorders. Since 1976, we have experienced 4 cases of adrenocortical carcinoma which were delineated by /sup 131/I-6US -iodomethyl-19-norcholesterol (/sup 131/I-Adosterol). Three of 4 cases were adrenocortical carcinoma with Cushing's syndrome, and one was adrenocortical carcinoma with adrenogenital syndrome. In 3 cases of cortisol secreting adrenocortical carcinoma, uptake in the tumor and lack of uptake in the contralateral adrenal gland were seen. Faint to moderate uptakes were observed in the 2 cases, but another one showed as high uptake as seen in adenoma. Patient with androgen secreting adrenocortical carcinoma had increased uptake in the tumor and showed faint uptake in the contralateral adrenal gland. Intensity of /sup 131/I-Adosterol uptake in adrenocortical carcinoma seems to depend on the extent of tumor necrosis, cell differentiation and function.

  1. Percutaneous laser ablation of unresectable primary and metastatic adrenocortical carcinoma

    Pacella, Claudio M. [Regina Apostolorum Hospital, Department of Diagnostic Imaging and Interventional Radiology, Via San Francesco 50, Albano Laziale, Rome 00041 (Italy)], E-mail: claudiomaurizio.pacella@fastwebnet.it; Stasi, Roberto; Bizzarri, Giancarlo; Pacella, Sara; Graziano, Filomena Maria; Guglielmi, Rinaldo; Papini, Enrico [Regina Apostolorum Hospital, Department of Diagnostic Imaging and Interventional Radiology, Via San Francesco 50, Albano Laziale, Rome 00041 (Italy)

    2008-04-15

    Purpose: To evaluate the feasibility, safety, and clinical benefits of percutaneous laser ablation (PLA) in patients with unresectable primary and metastatic adrenocortical carcinoma (ACC). Patients and methods: Four patients with hepatic metastases from ACC and a Cushing's syndrome underwent ultrasound-guided PLA. In one case the procedure was performed also on the primary tumor. Results: After three sessions of PLA, the primary tumor of 15 cm was ablated by 75%. After 1-4 (median 1) sessions of PLA, five liver metastases ranging from 2 to 5 cm were completely ablated, while the sixth tumor of 12 cm was ablated by 75%. There were no major complications. Treatment resulted in an improvement of performance status and a reduction of the daily dosage of mitotane in all patients. The three patients with liver metastases presented a marked decrease of 24-h urine cortisol levels, an improved control of hypertension and a mean weight loss of 2.8 kg. After a median follow-up after PLA of 27.0 months (range, 9-48 months), two patients have died of tumor progression, while two other patients remain alive and free of disease. Conclusions: Percutaneous laser ablation is a feasible, safe and well tolerated procedure for the palliative treatment of unresectable primary and metastatic ACC. Further study is required to evaluate the impact of PLA on survival.

  2. Percutaneous laser ablation of unresectable primary and metastatic adrenocortical carcinoma

    Pacella, Claudio M.; Stasi, Roberto; Bizzarri, Giancarlo; Pacella, Sara; Graziano, Filomena Maria; Guglielmi, Rinaldo; Papini, Enrico

    2008-01-01

    Purpose: To evaluate the feasibility, safety, and clinical benefits of percutaneous laser ablation (PLA) in patients with unresectable primary and metastatic adrenocortical carcinoma (ACC). Patients and methods: Four patients with hepatic metastases from ACC and a Cushing's syndrome underwent ultrasound-guided PLA. In one case the procedure was performed also on the primary tumor. Results: After three sessions of PLA, the primary tumor of 15 cm was ablated by 75%. After 1-4 (median 1) sessions of PLA, five liver metastases ranging from 2 to 5 cm were completely ablated, while the sixth tumor of 12 cm was ablated by 75%. There were no major complications. Treatment resulted in an improvement of performance status and a reduction of the daily dosage of mitotane in all patients. The three patients with liver metastases presented a marked decrease of 24-h urine cortisol levels, an improved control of hypertension and a mean weight loss of 2.8 kg. After a median follow-up after PLA of 27.0 months (range, 9-48 months), two patients have died of tumor progression, while two other patients remain alive and free of disease. Conclusions: Percutaneous laser ablation is a feasible, safe and well tolerated procedure for the palliative treatment of unresectable primary and metastatic ACC. Further study is required to evaluate the impact of PLA on survival

  3. Adrenocortical scintigraphy with {sup 131}I-6-beta-iodomethyl-norcholesterol (NP 59) in bilateral adrenocortical carcinoma

    Ruiz Hernandez, G.; Pallares, F.J.C.; Avila y Avalos, C.R. de [Hospital Clinic Universitari de Valencia (Spain). Servei de Medicina Nuclear; Bartual, A.R.; Rodrigo, S.T.; Ampudia-Blasco, F.J. [Hospital Clinic Universitari de Valencia (Spain). Servei d`Endocrinologia

    1998-06-01

    A case of a 49-year-old man suffering from bilateral adrenocortical carcinoma with local and secondary rapid progression is reported. The results of adrenocortical scintigraphy (NP 59) and histological findings allowed the diagnosis. This case report and a literature review showed the importance of using adrenocortical scintigraphy as a complementary imaging procedure of CT or MR images. (orig.) [Deutsch] Es wird ueber einen 49jaehrigen Mann berichtet, der an einem beidseitigen Nebennierenrinden-Karzinom mit schneller lokaler und sekundaerer Progression leidet. Die Ergebnisse der Nebennierenrinden-Szintigraphie (NP 59) und Histologie ermoeglichten die Diagnose: Dieser Fallbericht und ein Literaturueberblick zeigen die Bedeutung der Nebennierenrinden-Szintigraphie als ein zusaetzliches bildgebendes Verfahren neben CT und NMR. (orig.)

  4. Frequent phosphodiesterase 11A gene (PDE11A) defects in patients with Carney complex (CNC) caused by PRKAR1A mutations: PDE11A may contribute to adrenal and testicular tumors in CNC as a modifier of the phenotype.

    Libé, Rossella; Horvath, Anelia; Vezzosi, Delphine; Fratticci, Amato; Coste, Joel; Perlemoine, Karine; Ragazzon, Bruno; Guillaud-Bataille, Marine; Groussin, Lionel; Clauser, Eric; Raffin-Sanson, Marie-Laure; Siegel, Jennifer; Moran, Jason; Drori-Herishanu, Limor; Faucz, Fabio Rueda; Lodish, Maya; Nesterova, Maria; Bertagna, Xavier; Bertherat, Jerome; Stratakis, Constantine A

    2011-01-01

    Carney complex (CNC) is an autosomal dominant multiple neoplasia, caused mostly by inactivating mutations of the regulatory subunit 1A of the protein kinase A (PRKAR1A). Primary pigmented nodular adrenocortical disease (PPNAD) is the most frequent endocrine manifestation of CNC with a great inter-individual variability. Germline, protein-truncating mutations of phosphodiesterase type 11A (PDE11A) have been described to predispose to a variety of endocrine tumors, including adrenal and testicular tumors. Our objective was to investigate the role of PDE11A as a possible gene modifier of the phenotype in a series of 150 patients with CNC. A higher frequency of PDE11A variants in patients with CNC compared with healthy controls was found (25.3 vs. 6.8%, P CNC patients, those with PPNAD were significantly more frequently carriers of PDE11A variants compared with patients without PPNAD (30.8 vs. 13%, P = 0.025). Furthermore, men with PPNAD were significantly more frequently carriers of PDE11A sequence variants (40.7%) than women with PPNAD (27.3%) (P CNC patients, a high frequency of PDE11A variants, suggesting that PDE11A is a genetic modifying factor for the development of testicular and adrenal tumors in patients with germline PRKAR1A mutation.

  5. Non-invasive measurement of adrenocortical activity in a ...

    Measuring physiological stress reactions through the quantification of plasma cortisol often involves physical restraint, which acts as a stressor itself. Here, we present the validation of a non-invasive method for assessing adrenocortical activity as an indicator of stress in the bat-eared fox (Otocyon megalotis). By conducting ...

  6. Pathogenesis of canine cortisol-secreting adrenocortical tumors

    Kool, Miriam

    2015-01-01

    In dogs, hypercortisolism is one of the most frequently observed endocrine disorders, with an estimated incidence of about 1-2 cases per 1000 dogs per year. Approximately 15% of these cases is due to a cortisol-secreting adrenocortical tumor (AT). Cortisol-secreting ATs are characterized by

  7. Environmental enrichment affects adrenocortical stress responses in the endangered black-footed ferret

    Poessel, S.A.; Biggins, D.E.; Santymire, R.M.; Livieri, T.M.; Crooks, K.R.; Angeloni, L.

    2011-01-01

    Potential stressors of wildlife living in captivity, such as artificial living conditions and frequent human contact, may lead to a higher occurrence of disease and reduced reproductive function. One successful method used by wildlife managers to improve general well-being is the provision of environmental enrichment, which is the practice of providing animals under managed care with environmental stimuli. The black-footed ferret (Mustela nigripes) is a highly-endangered carnivore species that was rescued from extinction by removal of the last remaining individuals from the wild to begin an ex situ breeding program. Our goal was to examine the effect of environmental enrichment on adrenocortical activity in ferrets by monitoring fecal glucocorticoid metabolites (FGM). Results demonstrated that enrichment lowered FGM in juvenile male ferrets, while increasing it in adult females; enrichment had no effect on FGM in juvenile females and adult males. These results correspond with our findings that juvenile males interacted more with the enrichment items than did adult females. However, we did not detect an impact of FGM on the incidence of disease or on the ability of ferrets to become reproductive during the following breeding season. We conclude that an environmental enrichment program could benefit captive juvenile male ferrets by reducing adrenocortical activity. ?? 2011 Elsevier Inc.

  8. Adrenocortical carcinoma, an unusual cause of secondary hypertension.

    Veron Esquivel, Daniel; Batiz, Fernando; Farias Vega, Alfonso; Carrillo Gonzalez, Perla A

    2016-12-07

    We present the case of a female patient aged 39 years who was admitted to our hospital due to hypertension, severe hypokalaemia and metabolic alkalosis; physical examination was remarkable for plethoric moon face, centripetal obesity and bilateral lower extremity oedema. She was admitted for intravenous potassium replacement and further assessment of hypertension and associated clinical findings. Laboratory testing showed increased levels of aldosterone, renin, cortisol, testosterone and androstenedione. An abdominal CT revealed a large mass in the right adrenal gland with hepatic involvement. The patient was started on antihypertensive medications and underwent laparoscopic surgery for mass and liver biopsy. The pathological diagnosis was adrenocortical carcinoma with liver metastasis. Hyperaldosteronism is a cause of secondary hypertension and its diagnosis is usually benign. Adrenocortical carcinoma is a rare condition and aldosterone secreting tumours are even rarer; associated hypertension usually improves after tumour resection, but with the presence of metastasis, blood pressure control is difficult. 2016 BMJ Publishing Group Ltd.

  9. Adrenocortical oncocytic neoplasm presenting with Cushing's syndrome: a case report

    Kabayegit Ozlem

    2008-07-01

    Full Text Available Abstract Introduction Oncocytic neoplasms occur in several organs and are most commonly found in the thyroid, kidneys and salivary glands. Oncocytic neoplasms of the adrenal cortex are extremely rare and are usually non-functioning. Case presentation We report the case of an adrenocortical oncocytic neoplasm with uncertain malignant potential in a 31-year-old man with Cushing's syndrome. The patient had been operated on following diagnosis of a 7 cm adrenal mass. Following surgery, the Cushing's syndrome resolved. The patient is still alive with no metastases one year after the surgery. Conclusion Adrenocortical oncocytic neoplasms must be considered in the differential diagnosis of both functioning and non-functioning adrenal masses.

  10. Marital Conflict Predicts Mother-to-Infant Adrenocortical Transmission.

    Hibel, Leah C; Mercado, Evelyn

    2017-12-21

    Employing an experimental design, mother-to-infant transmission of stress was examined. Mothers (N = 117) were randomized to either have a positive or conflictual discussion with their marital partners, after which infants (age = 6 months) participated in a fear and frustration task. Saliva samples were collected to assess maternal cortisol responses to the discussion and infant cortisol responses to the challenge task. Results indicate maternal cortisol reactivity and recovery to the conflict (but not positive) discussion predicted infant cortisol reactivity to the infant challenge. Mothers' positive affect during the discussion buffered, and intrusion during the free-play potentiated, mother-to-infant adrenocortical transmission. These findings advance our understanding of the social and contextual regulation of adrenocortical activity in early childhood. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

  11. Virilizing Adrenocortical Carcinoma Advancing to Central Precocious Puberty after Surgery

    Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han; Lee, Dae-Yeol

    2015-01-01

    Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was...

  12. Clinical results of the use of mitotane for adrenocortical carcinoma

    Kasperlik-Zaluska A.A.

    2000-01-01

    Full Text Available Mitotane (o,p'-DDD acts mainly as an inhibitor of intramitochondrial pregnenolone and cortisol synthesis. Its adrenolytic effect depends on metabolic activation due to conversion to o,p'-DDA and o,p'-DDE. The drug has been used for 40 years in the treatment of adrenocortical carcinoma, mainly its regional and metastatic stage, as an adjuvant to surgical resection of the tumor. In the medical literature there are controversial opinions about its efficacy for the treatment of adrenocortical carcinoma. In our experience, mitotane administered immediately after surgery appeared to be much more efficient than when administered later. We have administered this drug in all cases of microscopically confirmed adrenocortical carcinoma, irrespectively of stage at the time of surgery, for fear of a false too optimistic classification. In our series of 82 patients with adrenocortical carcinoma, 59 patients have been treated with mitotane, 32 of them immediately after surgery, and 27 with a delay of 2 to 24 months. Today there are 18 survivors in the group of patients treated with mitotane soon after the operation and only 6 survivors in the group receiving mitotane with a delay. All patients were simultaneously given replacement therapy. Undesired effects of mitotane administration included increased aminotransferase and alkaline phosphatase activity, decreased white cell, platelet or red cell number, and myasthenia. Furthermore, we used mitotane with good results in Cushing's syndrome of non-malignant origin as pre-treatment before surgery or in long-term treatment for patients with poor tolerance of other adrenal inhibitors.

  13. Plurihormonal Cosecretion by a Case of Adrenocortical Oncocytic Neoplasm

    J. J. Corrales

    2016-01-01

    Full Text Available Adrenocortical oncocytic neoplasms (oncocytomas are extremely rare; only approximately 159 cases have been described so far. The majority are nonfunctional and benign. We describe an unusual case of a functional oncocytoma secreting an excess of glucocorticoids (cortisol and androgens (androstenedione and DHEAS, a pattern of plurihormonal cosecretion previously not reported in men, presenting with endocrine manifestations of Cushing’s syndrome. The neoplasm was considered to be of uncertain malignant potential (borderline according to the Lin-Weiss-Bisceglia criteria.

  14. Effects of centrifugation on gonadal and adrenocortical steroids in rats

    Kakihana, R.; Butte, J. C.

    1980-01-01

    Many endocrine systems are sensitive to external changes in the environment. Both the pituitary adrenal and pituitary gonadal systems are affected by stress including centrifugation stress. The effect of centrifugation on the pituitary gonadal and pituitary adrenocortical systems was examined by measuring the gonadal and adrenal steroids in the plasma and brain following different duration and intensity of centrifugation stress in rats. Two studies were completed and the results are presented. The second study was carried out to describe the developmental changes of brain, plasma and testicular testosterone and dihydrotestosterone in Sprague Dawley rats so that the effect of centrifugation stress on the pituitary gonadal syatem could be better evaluated in future studies.

  15. Transcription factor GATA-4 is a marker of anaplasia in adrenocortical neoplasms of the domestic ferret (Mustela putorius furo).

    Peterson, R A; Kiupel, M; Bielinska, M; Kiiveri, S; Heikinheimo, M; Capen, C C; Wilson, D B

    2004-07-01

    Adrenocortical neoplasms are a common cause of morbidity in neutered ferrets. Recently we showed that gonadectomized DBA/2J mice develop adrenocortical tumors that express transcription factor GATA-4. Therefore, we screened archival specimens of adrenocortical neoplasms from neutered ferrets to determine whether GATA-4 could be used as a tumor marker in this species. Nuclear immunoreactivity for GATA-4 was evident in 19/22 (86%) of ferret adrenocortical carcinomas and was prominent in areas exhibiting myxoid differentiation. Normal adrenocortical cells lacked GATA-4 expression. Two other markers of adrenocortical tumors in gonadectomized mice, inhibin-alpha and luteinizing hormone receptor, were coexpressed with GATA-4 in some of the ferret tumors. No GATA-4 expression was observed in three cases of nodular hyperplasia, but patches of anaplastic cells expressing GATA-4 were evident in 7/14 (50%) of tumors classified as adenomas. We conclude that GATA-4 can function as a marker of anaplasia in ferret adrenocortical tumors.

  16. A Case of Cushing's Syndrome with Multiple Adrenocortical Adenomas Composed of Compact Cells and Clear Cells.

    Asakawa, Masahiro; Yoshimoto, Takanobu; Ota, Mitsutane; Numasawa, Mitsuyuki; Sasahara, Yuriko; Takeuchi, Takato; Nakano, Yujiro; Oohara, Norihiko; Murakami, Masanori; Bouchi, Ryotaro; Minami, Isao; Tsuchiya, Kyoichiro; Hashimoto, Koshi; Izumiyama, Hajime; Kawamura, Naoko; Kihara, Kazunori; Negi, Mariko; Akashi, Takumi; Eishi, Yoshinobu; Sasano, Hironobu; Ogawa, Yoshihiro

    2016-06-01

    A 58-year-old woman was referred to our hospital for Cushingoid features and diagnosed as adrenal Cushing's syndrome due to a right adrenocortical mass (60 × 55 mm). The mass was composed of three different tumors; the first one was homogeneously lipid-poor neoplasm measuring 20 × 13 mm located at the most dorsal region, the second one was heterogeneous and lipid-rich tumor containing multiple foci of calcification measuring 50 × 32 mm located at the central region, and the last one was heterogeneous harboring dilated and tortuous vessels and lipid-poor one measuring 35 × 18 mm at the most ventral region of the adrenal gland. A right adrenalectomy was subsequently performed by open surgery. Macroscopic and microscopic analyses revealed that all three tumors were adrenocortical adenomas; the first one represents a pigmented adrenocortical adenoma, the second one adrenocortical adenoma associated with degeneration, and the third one adrenocortical adenoma harboring extensive degeneration. Immunohistochemical analysis of the steroidogenic enzymes also revealed that all of the tumors had the capacity of synthesizing cortisol. This is a very rare case of Cushing's syndrome caused by multiple adrenocortical adenomas including a pigmented adenoma. Immunohistochemical analysis of steroidogenic enzymes contributed to understanding of steroidogenesis in each of these three different adrenocortical adenomas in this case.

  17. Global gene expression response to telomerase in bovine adrenocortical cells

    Perrault, Steven D.; Hornsby, Peter J.; Betts, Dean H.

    2005-01-01

    The infinite proliferative capability of most immortalized cells is dependent upon the presence of the enzyme telomerase and its ability to maintain telomere length and structure. However, telomerase may be involved in a greater system than telomere length regulation, as recent evidence has shown it capable of increasing wound healing in vivo, and improving cellular proliferation rate and survival from apoptosis in vitro. Here, we describe the global gene expression response to ectopic telomerase expression in an in vitro bovine adrenocortical cell model. Telomerase-immortalized cells showed an increased ability for proliferation and survival in minimal essential medium above cells transgenic for GFP. cDNA microarray analyses revealed an altered cell state indicative of increased adrenocortical cell proliferation regulated by the IGF2 pathway and alterations in members of the TGF-B family. As well, we identified alterations in genes associated with development and wound healing that support a model that high telomerase expression induces a highly adaptable, progenitor-like state

  18. Immunoglobulins of patients with Cushing's syndrome due to pigmented adrenocortical micronodular dysplasia stimulate in vitro steroidogenesis

    Wulffraat, N. M.; Drexhage, H. A.; Wiersinga, W. M.; van der Gaag, R. D.; Jeucken, P.; Mol, J. A.

    1988-01-01

    The putative stimulation of adrenal steroid production by immunoglobulins (Igs) of five patients with pigmented adrenocortical micronodular dysplasia and clinical Cushing's syndrome was investigated. Ascorbate depletion, a process linked to steroid production, was measured by a cyto-chemical

  19. Effect of acupuncture on adrenocortical hormone production in rabbits with a central lesion

    Liao, Y.Y.; Seto, K.; Saitoh, H.; Kawakami, M.

    A study was made of adrenocortical hormone production under electroacupuncture stimulation of the Tsu-San-Li locus in rabbits with a lesion in the fornix, stria terminalis, ventromedial nucleus or arcuate nucleus. In rabbits with a lesion in the stria terminalis or ventromedial nucleus, electroacupuncture stimulation of Tsu-San-Li resulted in no increase in phase 1 but an increase in phase 2 of adrenocortical hormone production. In rabbits with a lesion in the fornix or arcuate nucleus electroacupuncture stimulation of Tsu-San-Li was followed by increased adrenocortical hormone production in the both phases. These results show that the stria terminalis and the ventromedial nucleus play a major role in the augmentation of adrenocortical hormone production by electroacupuncture stimulation of Tsu-San-Li.

  20. Rapid and Complete Remission of Metastatic Adrenocortical Carcinoma Persisting 10 Years After Treatment With Mitotane Monotherapy

    Ghorayeb, Nada El; Rondeau, Geneviève; Latour, Mathieu; Cohade, Christian; Olney, Harold; Lacroix, André; Perrotte, Paul; Sabourin, Alexis; Mazzuco, Tania L; Bourdeau, Isabelle

    2016-01-01

    Abstract Mitotane has been used for more than 5 decades as therapy for adrenocortical carcinoma (ACC). However its mechanism of action and the extent of tumor response remain incompletely understood. To date no cases of rapid and complete remission of metastatic ACC with mitotane monotherapy has been reported. A 52-year-old French Canadian man presented with metastatic disease 2 years following a right adrenalectomy for stage III nonsecreting ACC. He was started on mitotane which was well tolerated despite rapid escalation of the dose. The patient course was exceptional as he responded to mitotane monotherapy after only few months of treatment. Initiation of chemotherapy was not needed and he remained disease-free with good quality of life on low maintenance dose of mitotane during the following 10 years. A germline heterozygous TP53 exon 4 polymorphism c.215C>G (p. Pro72Arg) was found. Immunohistochemical stainings for IGF-2 and cytoplasmic β-catenin were positive. Advanced ACC is an aggressive disease with poor prognosis and the current therapeutic options remain limited. These findings suggest that mitotane is a good option for the treatment of metastatic ACC and might result in rapid complete remission in selected patients. PMID:27043680

  1. Virilizing adrenocortical carcinoma advancing to central precocious puberty after surgery.

    Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han; Lee, Dae-Yeol

    2015-05-01

    Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was ACC. Two months after surgical removal of the mass, he subsequently developed central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist to delay further pubertal progression. In patients with functioning ACC and surgical removal, clinical follow-up and hormonal marker examination for the secondary effects of excessive hormone secretion may be a useful option at least every 2 or 3 months after surgery.

  2. Virilization in a Girl with Adrenocortical Adenoma: A Case Report

    Tahniyah Haq

    2012-07-01

    Full Text Available We present a case of Cushing’s syndrome and virilization in a 15 year old girl which was suspected to be due to an adrenal carcinoma. She presented with features of virilization in addition to those of hypercortisilism. Her high androgen levels especially dehydroepiandrosterone sulfate (DHEAS were also in favor of an adrenal carcinoma. An unenhanced computerized tomography (CT scan showed a mass (size: 5.3 cm in the right adrenal gland with a soft tissue intensity of more than 10 HU which was suggestive of adrenal carcinoma. But, histopathology of the resected mass revealed a benign adrenocortical adenoma. Ibrahim Med. Coll. J. 2012; 6(2: 70-72

  3. A black adrenocortical adenoma causing Cushing's syndrome not imaged by radiocholesterol scintigraphy

    Reschini, E.; Baldini, M.; Cantalamessa, L.

    1990-01-01

    In a 33-year-old female patient with left adrenal tumour and Cushing's syndrome, adrenocortical scintigraphy with radiocholesterol did not image the tumour nor the suppressed contralateral gland. Histology showed a black adrenocortical adenoma composed only of compact cells; there was no evidence of malignancy. This demonstrates that non-visualization of the adrenal glands in a patient with Cushing's syndrome is not invariably due to adrenal carcinoma. The literature on black adrenal adenomas causing Cushing's syndrome is reviewed. (orig.)

  4. Analysis of adrenocortical tumours morphology as regards their structure and potential malignancy

    Kajor, M.; Ciupinska-Kajor, M.; Dobrosz, Z.; Ziaja, J.; Krol, R.; Heitzman, M.; Cierpka, L.

    2006-01-01

    Introduction: A consequence of diagnosis of adrenocortical carcinoma (ACC) is introduction of pharmacological therapy, precise monitoring of the patients and in some cases re-operation. The aim of the study is to analyse morphology of adrenocortical tumours as regards their malignancy by use of criteria proposed by Weiss. Material and methods: 110 adrenocortical tumours in 107 patients were analysed (M 27.1%, F 72.9%; age 32 to 77 years, mean 55.2 ± 9.7). Conn syndrome was diagnosed in 16 patients (14.9%), Cushing syndrome in 12 (11.2%), and virilisation in 3 (2.8%). In 76 patients (71.0%) biochemical tests did not reveal hormonal hyperactivity of the tumour. Results: In routine histopathological examination ACC was diagnosed in 6 tumours (5.4%), adrenocortical adenoma (ACA) in 92 (83.6%) and adrenocortical hyperplasia in 12 (10.9%). Nuclear grade III or IV was observed in 8 tumours (7.3%), mitotic rate > 5/50 high power fields in 6 (5.4%), atypical mitoses in 5 (4.5%), clear cells constituting < 25% of the tumour in 10 (9.1%), diffuse architecture in 8 (7.3%), necrosis in 16 (14.5%), veins infiltration in 4 (3.6%), sinusoids infiltration in 7 (6.3%), and tumour capsule infiltration in 5 (4.5%). Among ACC tumours 4 - 9 features of malignancy were present, among ACA - 0 - 3 features. Statistical analysis revealed correlation between number of criteria proposed by Weiss and maximal tumour size (p < 0.05). Conclusion: The structure and cell arrangement in adrenocortical adenoma are heterogeneous. Application of criteria proposed by Weiss in histopathological examination of adrenocortical tumours can be useful in differentiating adrenocortical adenoma from carcinoma. (author)

  5. Canine hyperadrenocorticism due to adrenocortical neoplasia: pretreatment evaluation of 41 dogs

    Reusch, C.E.; Feldman, E.C.

    1991-01-01

    This retrospective study identifies parameters that might separate dogs with hyperadrenocorticism caused by adrenocortical tumors from dogs with pituitary-dependent hyperadrenocorticism. Further, an attempt was made to identify factors that could separate dogs with adrenocortical adenomas from dogs with carcinomas. The records of 41 dogs with hyperadrenocorticism caused by adrenocortical neoplasia were reviewed. The history, physical examination, urinalysis, hemogram (CBC), chemistry profile adrenocorticotrophic hormone (ACTH) stimulation and low dose dexamethasone test results were typical of the nonspecific diagnosis of hyperadrenocorticism. The preceding information on the 41 dogs with adrenocortical tumors was compared with that from 44 previously diagnosed pituitary-dependent hyperadrenocorticoid dogs. There was no parameter which aided in separating these two groups of dogs. Thirty dogs with adrenocortical tumors were tested with a high-dose dexamethasone test and none had suppressed plasma cortisol concentrations 8 hours after IV administration of 0.1 mg/kg of dexamethasone. In 29 of the 41 adrenal tumor dogs, plasma endogenous ACTH was not detectable on at least one measurement (less than 20 pg/ml). The remaining 12 dogs from this group had nondiagnostic concentrations (20-45 pg/ml). Thirteen of 22 dogs (59%) with adrenocortical carcinomas had adrenal masses identified on abdominal radiographs and seven of 13 dogs (54%) with adrenocortical adenomas had radiographically visible adrenal masses. Thirteen of 17 adrenocortical carcinomas (76%) and five of eight adenomas (62%) were identified with ultrasonography. Radiographs of the thorax and ultrasonography of the abdomen identified most of the dogs (8 of 11) with metastatic lesions

  6. Noninvasive monitoring of adrenocortical function in captive jaguars (Panthera onca).

    Conforti, Valéria A; Morato, Ronaldo G; Augusto, Anderson M; de Oliveira e Sousa, Lúcio; de Avila, David M; Brown, Janine L; Reeves, Jerry J

    2012-01-01

    Jaguars are threatened with extinction throughout their range. A sustainable captive population can serve as a hedge against extinction, but only if they are healthy and reproduce. Understanding how jaguars respond to stressors may help improve the captive environment and enhance their wellbeing. Thus, our objectives were to: (1) conduct an adrenocorticotrophic hormone (ACTH) challenge to validate a cortisol radioimmunoassay (RIA) for noninvasive monitoring of adrenocortical function in jaguars; (2) investigate the relationship between fecal corticoid (FCM) and androgen metabolite (FAM) concentrations in males during the ACTH challenge; and (3) establish a range of physiological concentrations of FCMs for the proposed protocol. Seven jaguars (3 M, 4 F) received 500 IU/animal of ACTH. Pre- and post-ACTH fecal samples were assayed for corticoid (M and F) and androgen metabolites (M) by RIA. Concentrations of FCMs increased (P80.01) after ACTH injection (pre-ACTH: 0.90 ± 0.12 µg/g dry feces; post-ACTH: 2.55 ± 0.25 µg/g). Considering pre- and post-ACTH samples, FCM concentrations were higher (P80.01) in males (2.15 ± 0.20 µg/g) than in females (1.30 ± 0.20 µg/g), but the magnitude of the response to ACTH was comparable (P>0.05) between genders. After ACTH injection, FAMs increased in two (of 3) males; in one male, FCMs and FAMs were positively correlated (0.60; P80.01). Excretion of FCMs was assessed in 16 jaguars (7 M, 9 F) and found to be highly variable (range, 80.11-1.56 µg/g). In conclusion, this study presents a cortisol RIA for monitoring adrenocortical function in jaguars noninvasively. © 2011 Wiley Periodicals, Inc.

  7. Characterization of differential gene expression in adrenocortical tumors harboring beta-catenin (CTNNB1) mutations.

    Durand, Julien; Lampron, Antoine; Mazzuco, Tania L; Chapman, Audrey; Bourdeau, Isabelle

    2011-07-01

    Mutations of β-catenin gene (CTNNB1) are frequent in adrenocortical adenomas (AA) and adrenocortical carcinomas (ACC). However, the target genes of β-catenin have not yet been identified in adrenocortical tumors. Our objective was to identify genes deregulated in adrenocortical tumors harboring CTNNB1 genetic alterations and nuclear accumulation of β-catenin. Microarray analysis identified a dataset of genes that were differently expressed between AA with CTNNB1 mutations and wild-type (WT) tumors. Within this dataset, the expression profiles of five genes were validated by real time-PCR (RT-PCR) in a cohort of 34 adrenocortical tissues (six AA and one ACC with CTNNB1 mutations, 13 AA and four ACC with WT CTNNB1, and 10 normal adrenal glands) and two human ACC cell lines. We then studied the effects of suppressing β-catenin transcriptional activity with the T-cell factor/β-catenin inhibitors PKF115-584 and PNU74654 on gene expression in H295R and SW13 cells. RT-PCR analysis confirmed the overexpression of ISM1, RALBP1, and PDE2A and the down-regulation of PHYHIP in five of six AA harboring CTNNB1 mutations compared with WT AA (n = 13) and normal adrenal glands (n = 10). RALBP1 and PDE2A overexpression was also confirmed at the protein level by Western blotting analysis in mutated tumors. ENC1 was specifically overexpressed in three of three AA harboring CTNNB1 point mutations. mRNA expression and protein levels of RALBP1, PDE2A, and ENC1 were decreased in a dose-dependent manner in H295R cells after treatment with PKF115-584 or PNU74654. This study identified candidate genes deregulated in CTNNB1-mutated adrenocortical tumors that may lead to a better understanding of the role of the Wnt-β-catenin pathway in adrenocortical tumorigenesis.

  8. Germline PRKACA amplification leads to Cushing syndrome caused by 3 adrenocortical pathologic phenotypes.

    Carney, J Aidan; Lyssikatos, Charalampos; Lodish, Maya B; Stratakis, Constantine A

    2015-01-01

    We describe the pathology of 5 patients with germline PRKACA copy number gain and Cushing syndrome: 4 males and 1 female, aged 2 to 43 years, including a mother and son. Imaging showed normal or slightly enlarged adrenal glands in 4 patients and a unilateral mass in the fifth. Biochemically, the patients had corticotropin-independent hypercortisolism. Four underwent bilateral adrenalectomy; unilateral adrenalectomy was performed in the patient with the adrenal mass. Pathologically, 3 patients, including the 1 with the tumor (adenoma), had primary pigmented nodular adrenocortical disease with extranodular cortical atrophy and mild intracapsular and extracapsular extension of cortical cells. The other 2 patients had cortical hyperplasia and prominent capsular and extracapsular micronodular cortical hyperplasia. Immunoperoxidase staining revealed differences for synaptophysin, inhibin-A, and Ki-67 (nuclei) in the atrophic cortices (patients 1, 2, and 3) and hyperplastic cortices (patients 4 and 5) and for Ki-67 (nuclei) and vimentin in the extracortical nodules in the 2 groups of patients. β-Catenin stained the cell membrane, cytoplasm, and nuclei of the adenoma. The patients were well at follow-up (1-23 years); 24-hour urinary cortisol excretion was elevated in the patient who had unilateral adrenalectomy. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity.

    Mete, Ozgur; Duan, Kai

    2018-01-01

    Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype-phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations ( KCNJ5, ATP1A1, ATP2B3 , and CACNA1D ) involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5 -mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3 , and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations ( PRKACA, PRKAR1A, GNAS, PDE11A , and PDE8B ) involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH) have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

  10. The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity

    Ozgur Mete

    2018-03-01

    Full Text Available Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype–phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations (KCNJ5, ATP1A1, ATP2B3, and CACNA1D involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5-mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3, and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations (PRKACA, PRKAR1A, GNAS, PDE11A, and PDE8B involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

  11. Primary aldosteronism and hypercortisolism due to bilateral functioning adrenocortical adenomas.

    Oki, Kenji; Yamane, Kiminori; Sakashita, Yu; Kamei, Nozomu; Watanabe, Hiroshi; Toyota, Naoyuki; Shigeta, Masanobu; Sasano, Hironobu; Kohno, Nobuoki

    2008-10-01

    A 50-year-old male patient with a 15-year history of hypertension was referred to our hospital for evaluation of bilateral adrenal tumors. No Cushingoid features were observed. Computed tomographic scan showed 10-mm masses in each adrenal gland. Preoperative endocrinological examinations revealed autonomous cortisol and aldosterone secretion in this patient. The results of a subsequent adrenal venous catheterization study were consistent with the presence of a left cortisol-producing tumor and a right aldosterone-producing tumor. A left partial adrenalectomy was performed initially, but cortisol and aldosterone over-secretion persisted. Accordingly, the patient underwent a right adrenalectomy. Pathological examination of the resected specimens, including immunohistochemical analysis, demonstrated that both adenomas possibly produced cortisol and aldosterone. This is an extremely rare case of bilateral adrenal tumors, in which the left adrenocortical tumor produced and secreted cortisol or both cortisol and aldosterone and the right one produced and secreted both aldosterone and cortisol, as confirmed by clinical findings and pathological studies using immunohistochemical analysis.

  12. Surgical management and clinical prognosis of adrenocortical carcinoma.

    Dong, Dexin; Li, Hanzhong; Yan, Weigang; Ji, Zhigang; Mao, Quanzong

    2012-01-01

    To study the relationship between surgical management and prognosis of adrenocortical carcinoma (ACC) in order to guide the surgical management of ACC. Clinical data of 45 cases of ACC treated in our hospital were retrospectively analyzed. The 45 cases included 3 cases in stage I, 12 cases in stage II, 7 cases in stage III, and 23 cases in stage IV. 17 cases underwent complete excision, 14 cases underwent palliative excision, 8 cases had non-operative treatment and 6 cases gave up treatment. All patients were followed up from 2 to 141 months. The average survival time of 31 patients with surgery was 32.46 months, and the average survival time of 14 patients without surgery was 4.75 months. There were statistically significant differences between the two groups (p 0.05). Surgery is considered to be the only method to cure ACC. For ACC in stage I and II, tumor resection is the most effective treatment, and second surgical operation is recommended for local recurrence. For ACC in stage III, extensive surgical operation is recommended, and for ACC in stage IV, surgical operation has no effect on the prognosis. Copyright © 2012 S. Karger AG, Basel.

  13. Biology is Destiny: A Case of Adrenocortical Carcinoma Diagnosed and Resected at Inception in a Patient Under Close Surveillance for Lung Cancer.

    Miron, Benjamin; Ristau, Benjamin T; Tomaszewski, Jeffrey J; Jones, Josh; Milestone, Bart; Wong, Yu-Ning; Uzzo, Robert G; Edmondson, Donna; Scott, Walter; Kutikov, Alexander

    2016-11-01

    Adrenocortical carcinoma (ACC) is a rare malignancy that is generally associated with a poor prognosis whose existence dictates the management of incidental renal masses. We report a case of ACC diagnosed and treated at its apparent inception in a patient undergoing close surveillance imaging of a prior malignancy. Despite timely detection and resection of a localized ACC this patient rapidly progressed to systemic disease. This case highlights the rapid growth kinetics of ACC and puts into perspective the challenges associated with the established treatment paradigm for patients diagnosed with an adrenal mass.

  14. Biology is Destiny: A Case of Adrenocortical Carcinoma Diagnosed and Resected at Inception in a Patient Under Close Surveillance for Lung Cancer

    Benjamin Miron

    2016-11-01

    Full Text Available Adrenocortical carcinoma (ACC is a rare malignancy that is generally associated with a poor prognosis whose existence dictates the management of incidental renal masses. We report a case of ACC diagnosed and treated at its apparent inception in a patient undergoing close surveillance imaging of a prior malignancy. Despite timely detection and resection of a localized ACC this patient rapidly progressed to systemic disease. This case highlights the rapid growth kinetics of ACC and puts into perspective the challenges associated with the established treatment paradigm for patients diagnosed with an adrenal mass.

  15. Cushing Syndrome in a 6-Month-Old Infant due to Adrenocortical Tumor

    Volmar KeithE

    2009-09-01

    Full Text Available Cushing syndrome is rare in infancy and usually due to an adrenocortical tumor (ACT. We report an infant with Cushing syndrome due to adrenocortical carcinoma. The patient presented at six months of age with a three-month history of growth failure, rapid weight gain, acne, and irritability. Physical examination showed obesity, hypertension, and Cushingoid features. Biochemical evaluation showed very high serum cortisol, mildly elevated testosterone, and suppressed ACTH. Abdominal MRI revealed a heterogeneous right adrenal mass extending into the inferior vena cava. Evaluation for metastases was negative. The tumor was removed surgically en bloc. Pathologic examination demonstrated low mitotic rate, but capsular and vascular invasion. She received no adjuvant therapy. Her linear growth has improved and Cushingoid features resolved. Hormonal markers and quarterly PET scans have been negative for recurrence 24 months postoperatively. In conclusion, adrenocortical neoplasms in children are rare, but should be considered in the differential diagnosis of Cushing syndrome.

  16. 18F-Labelled metomidate analogues as adrenocortical imaging agents

    Erlandsson, Maria; Karimi, Farhad; Lindhe, Orjan; Langstroem, Bengt

    2009-01-01

    Introduction: Two- and one-step syntheses of 18 F-labelled analogues of metomidate, such as 2-[ 18 F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[ 18 F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[ 18 F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[ 18 F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[ 18 F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented. Methods: Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[ 18 F]fluoroethyl 4-methylbenzenesulfonate or 3-[ 18 F]fluoropropyl 4-methylbenzenesulfonate. These were used as 18 F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3. Results: The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46±3% and 79±30%, respectively. Conclusion: Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.

  17. Hair cortisol measurement in mitotane-treated adrenocortical cancer patients.

    Manenschijn, L; Quinkler, M; van Rossum, E F C

    2014-04-01

    The only approved drug for the treatment of adrenocortical cancer (ACC) is mitotane. Mitotane is adrenolytic and therefore, hydrocortisone replacement therapy is necessary. Since mitotane increases cortisol binding globulin (CBG) and induces CYP3A4 activity, high doses of hydrocortisone are thought to be required. Evaluation of hydrocortisone therapy in mitotane-treated patients has been difficult since there is no good marker to evaluate hydrocortisone therapy. Measurement of cortisol in scalp hair is a novel method that offers the opportunity to measure long-term cortisol levels. Our aim was to evaluate whether hair cortisol measurements could be useful in evaluating recent hydrocortisone treatment in mitotane-treated ACC patients. Hair cortisol levels were measured in 15 mitotane-treated ACC patients on hydrocortisone substitution and 96 healthy individuals. Cortisol levels were measured in 3 cm hair segments, corresponding to a period of 3 months. Hair cortisol levels were higher in ACC patients compared to healthy individuals (pcortisol levels above the reference range. None of the patients had hair cortisol levels below normal. In contrast to hydrocortisone doses (β=0.03, p=0.93), hair cortisol levels were associated with BMI (β=0.53, p=0.042). There was no correlation between hair cortisol levels and hydrocortisone doses (β=0.41, p=0.13). Almost half of the ACC patients had high hair cortisol levels, suggesting long-term over-substitution of hydrocortisone in some of the patients, whereas none of the patients was under-substituted. Hair cortisol measurements might be useful in long-term monitoring hydrocortisone treatment in mitotane-treated ACC patients. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Myopathy in Addison's disease.

    Mor, F; Green, P; Wysenbeek, A J

    1987-01-01

    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...

  19. DNA methylation is an independent prognostic marker of survival in adrenocortical cancer

    Jouinot, Anne; Assie, Guillaume; Libe, Rossella; Fassnacht, Martin; Papathomas, Thomas; Barreau, Olivia; De La Villeon, Bruno; Faillot, Simon; Hamzaoui, Nadim; Neou, Mario; Perlemoine, Karine; Rene-Corail, Fernande; Rodriguez, Stephanie; Sibony, Mathilde; Tissier, Frederique; Dousset, Bertrand; Sbiera, Silviu; Ronchi, Cristina; Kroiss, Matthias; Korpershoek, Esther; De Krijger, Ronald; Waldmann, Jens; Bartsch, Detlef K.; Quinkler, Marcus; Haissaguerre, Magalie; Tabarin, Antoine; Chabre, Olivier; Sturm, Nathalie; Luconi, Michaela; Mantero, Franco; Mannelli, Massimo; Cohen, Regis; Kerlan, Veronique; Touraine, Philippe; Barrande, Gaelle; Groussin, Lionel; Bertagna, Xavier; Baudin, Eric; Amar, Laurence; Beuschlein, Felix; Clauser, Eric; Coste, Joel; Bertherat, Jerome

    2017-01-01

    Context: Adrenocortical cancer (ACC) is an aggressive tumor with a heterogeneous outcome. Prognostic stratification is difficult even based on tumor stage and Ki67. Recently integrated genomics studies have demonstrated that CpG islands hypermethylation is correlated with poor survival. Objective:

  20. Adrenocortical neoplasia: Evolving concepts in tumorigenesis with an emphasis on adrenal cortical carcinoma variants

    R.R. de Krijger (Ronald); T.G. Papathomas (Thomas)

    2012-01-01

    textabstractAdrenocortical carcinoma (ACC) is a rare, heterogeneous malignancy with a poor prognosis. According to WHO classification 2004, ACC variants include oncocytic ACCs, myxoid ACCs and ACCs with sarcomatous areas. Herein, we provide a comprehensive review of these rare subtypes of

  1. Emotional and Adrenocortical Regulation in Early Adolescence: Prediction by Attachment Security and Disorganization in Infancy

    Spangler, Gottfried; Zimmermann, Peter

    2014-01-01

    The aim of the present study was to examine differences in emotion expression and emotion regulation in emotion-eliciting situations in early adolescence from a bio-psycho-social perspective, specifically investigating the influence of early mother-infant attachment and attachment disorganization on behavioural and adrenocortical responses. The…

  2. Maternal-child adrenocortical attunement in early childhood: continuity and change.

    Hibel, Leah C; Granger, Douglas A; Blair, Clancy; Finegood, Eric D

    2015-01-01

    This study evaluated continuity and change in maternal-child hypothalamic-pituitary-adrenal axis attunement in early childhood. Participants were drawn from a prospective study of 1,292 mother-child dyads, which were racially diverse, predominantly low-income, and non-urban. Child focused stress tasks designed to elicit anger, fear, and frustration were administered during early infancy, later infancy, and toddlerhood. Mothers' and children's saliva samples (later assayed for cortisol) were collected before and after the tasks. The strength of mother-child adrenocortical attunement was conserved across infancy and toddlerhood. The magnitude of maternal-child adrenocortical attunement decreased in response to the child-focused stress tasks. Maternal sensitivity and the child's task-related emotional reactivity moderated adrenocortical attunement across the task, with greater maternal sensitivity during a free-play, and lower levels of child emotional reactivity during the stress tasks, stabilizing attunement from pre- to post-task levels. The findings advance our understanding of individual differences in the social regulation of adrenocortical activity in early childhood. © 2014 Wiley Periodicals, Inc.

  3. The Relations between Bullying Exposures in Middle Childhood, Anxiety, and Adrenocortical Activity

    Carney, JoLynn V.; Hazler, Richard J.; Oh, Insoo; Hibel, Leah C.; Granger, Douglas A.

    2010-01-01

    This exploratory study investigated how exposure to bullying at school in middle childhood is associated with student anxiety levels and adrenocortical activity at a time preceding lunch when anxiety about potential bullying would potentially be higher. Ninety-one sixth-grade students (55 female and 36 male) reported being exposed one or more…

  4. A Late Onset of Adrenocortical Cancer Assosiated with Beckwith-Wiedemann Syndrome

    N S Kuznetsov

    2014-06-01

    Full Text Available Beckwith-Wiedemann syndrome (BWS is a genetic overgrowth disorder involving a predisposition to tumor development. The common features of Beckwith-Wiedemann syndrome include omphalocele, macroglos- sia and macrosomia. The increased risk for neoplasia is concentrated in the first eight years of life. However, this case presents a late onset of adrenocortical cancer assosiated with Beckwith-Wiedemann syndrome.

  5. Effect of KCNJ5 Mutations on Gene Expression in Aldosterone-Producing Adenomas and Adrenocortical Cells

    Monticone, Silvia; Hattangady, Namita G.; Nishimoto, Koshiro; Mantero, Franco; Rubin, Beatrice; Cicala, Maria Verena; Pezzani, Raffaele; Auchus, Richard J.; Ghayee, Hans K.; Shibata, Hirotaka; Kurihara, Isao; Williams, Tracy A.; Giri, Judith G.; Bollag, Roni J.; Edwards, Michael A.; Isales, Carlos M.

    2012-01-01

    Context: Primary aldosteronism is a heterogeneous disease that includes both sporadic and familial forms. A point mutation in the KCNJ5 gene is responsible for familial hyperaldosteronism type III. Somatic mutations in KCNJ5 also occur in sporadic aldosterone producing adenomas (APA). Objective: The objective of the study was to define the effect of the KCNJ5 mutations on gene expression and aldosterone production using APA tissue and human adrenocortical cells. Methods: A microarray analysis was used to compare the transcriptome profiles of female-derived APA samples with and without KCNJ5 mutations and HAC15 adrenal cells overexpressing either mutated or wild-type KCNJ5. Real-time PCR validated a set of differentially expressed genes. Immunohistochemical staining localized the KCNJ5 expression in normal adrenals and APA. Results: We report a 38% (18 of 47) prevalence of KCNJ5 mutations in APA. KCNJ5 immunostaining was highest in the zona glomerulosa of NA and heterogeneous in APA tissue, and KCNJ5 mRNA was 4-fold higher in APA compared with normal adrenals (P APA with and without KCNJ5 mutations displayed slightly different gene expression patterns, notably the aldosterone synthase gene (CYP11B2) was more highly expressed in APA with KCNJ5 mutations. Overexpression of KCNJ5 mutations in HAC15 increased aldosterone production and altered expression of 36 genes by greater than 2.5-fold (P APA, and our data suggest that these mutations increase expression of CYP11B2 and NR4A2, thus increasing aldosterone production. PMID:22628608

  6. Vincristine, cisplatin, teniposide, and cyclophosphamide combination in the treatment of recurrent or metastatic adrenocortical cancer.

    Khan, Tanweera S; Sundin, Anders; Juhlin, Claes; Wilander, Erik; Oberg, Kjell; Eriksson, Barbro

    2004-01-01

    The efficacy and tolerability of a combination of vincristine, cisplatin, teniposide, and cyclophosphamide (OPEC) in 11 patients (median age, 45 yr) with recurrent and/or metastatic adrenocortical cancer (ACC) (seven functional and four nonfunctional) were evaluated. All patients received this regimen after the failure of streptozocin and o,p'-DDD (SO) combination therapy. The regimen comprised cyclophosphamide, 600 mg/m2, and vincristine, 1.5 mg/m2, maximum dose 2.0 mg (d 1); cisplatin, 100 mg/m2 (d 2) and teniposide, 150 mg/m2 (d 4). Cycles were repeated every 4 wk. One to eight cycles (median, six cycles) of OPEC were administered to each patient. The median duration of treatment was 6 mo. The overall 2-yr survival rate was 82% and the median survival since diagnosis was 44 mo while it was 21 mo since start of OPEC therapy. Responses were obtained in nine patients: partial response in two patients, and stable disease in seven patients. The median duration of response was 6.75 mo. A total of 60 cycles of chemotherapy were given to all patients; grade 1-2 toxicity occurred in 57 cycles, while grade 3 toxicity was observed only in two cycles, according to NCI's Common Toxicity Criteria. We conclude that the OPEC regimen may be considered in recurrent or metastatic ACC as a second-line medical treatment. However, the combination is accompanied by considerable side effects and dose modifications are necessary in order to be able to recommend the treatment. This regimen needs further evaluation compared with SO therapy preferably in a randomized multicenter trial.

  7. Gemcitabine-Based Chemotherapy in Adrenocortical Carcinoma: A Multicenter Study of Efficacy and Predictive Factors.

    Henning, Judith E K; Deutschbein, Timo; Altieri, Barbara; Steinhauer, Sonja; Kircher, Stefan; Sbiera, Silviu; Wild, Vanessa; Schlötelburg, Wiebke; Kroiss, Matthias; Perotti, Paola; Rosenwald, Andreas; Berruti, Alfredo; Fassnacht, Martin; Ronchi, Cristina L

    2017-11-01

    Adrenocortical carcinoma (ACC) is rare and confers an unfavorable prognosis in advanced stages. Other than combination chemotherapy with cisplatin, etoposide, doxorubicin, and mitotane, the second- and third-line regimens are not well-established. Gemcitabine (GEM)-based chemotherapy was suggested in a phase 2 clinical trial with 28 patients. In other solid tumors, human equilibrative nucleoside transporter type 1 (hENT1) and/or ribonucleotide reductase catalytic subunit M1 (RRM1) expression have been associated with resistance to GEM. To assess the efficacy of GEM-based chemotherapy in ACC in a real-world setting and the predictive role of molecular parameters. Retrospective multicenter study. Referral centers of university hospitals. A total of 145 patients with advanced ACC were treated with GEM-based chemotherapy (132 with concomitant capecitabine). Formalin-fixed paraffin-embedded tumor material was available for 70 patients for immunohistochemistry. The main outcome measures were progression-free survival (PFS) and an objective response to GEM-based chemotherapy. The secondary objective was the predictive role of hENT1 and RRM1. The median PFS for the patient population was 12 weeks (range, 1 to 94). A partial response or stable disease was achieved in 4.9% and 25.0% of cases, with a median duration of 26.8 weeks. Treatment was generally well tolerated, with adverse events of grade 3 or 4 occurring in 11.0% of cases. No substantial effect of hENT1 and/or RRM1 expression was observed in response to GEM-based chemotherapy. GEM-based chemotherapy is a well-tolerated, but modestly active, regimen against advanced ACC. No reliable molecular predictive factors could be identified. Owing to the scarce alternative therapeutic options, GEM-based chemotherapy remains an important option for salvage treatment for advanced ACC. Copyright © 2017 Endocrine Society

  8. Mitotane treatment in patients with adrenocortical cancer causes central hypothyroidism.

    Russo, Marco; Scollo, Claudia; Pellegriti, Gabriella; Cotta, Oana Ruxandra; Squatrito, Sebastiano; Frasca, Francesco; Cannavò, Salvatore; Gullo, Damiano

    2016-04-01

    Mitotane, a steroidogenesis inhibitor with adrenolytic properties used to treat adrenocortical cancer (ACC), can affect thyroid function. A reduction of FT4 levels with normal FT3 and TSH has been described in these patients. Using an in vitro murine model, the secretory capacity of thyrotrophic cells has been shown to be inhibited by mitotane. To investigate the pathogenesis of thyroid abnormalities in mitotane-treated patients with ACC. In five female patients with ACC (median age 47; range 31-65) treated with mitotane (dosage 1·5 g/day; 1·0-3·0), we analysed the pattern of TSH and thyroid function index (FT4, FT3 and FT3/FT4 ratio) compared to an age- and gender-matched control group. The in vivo secretory activity of the thyrotrophic cells was evaluated using a standard TRH test (200 μg), and the response was compared to both a group of age-matched female controls (n = 10) and central hypothyroid patients (n = 10). Basal TSH (median 1·54 mU/l; range 1·20-2·17) was normal and scattered around our median reference value, FT3 levels (median 3·80 pmol/l; 3·30-4·29) were normal but below the median reference value of 4·37 pmol/l and FT4 levels were below the normal range in all patients (median 8·40 pmol/l; 7·6-9·9). FT3/FT4 ratio was in the upper range in 4 patients and higher than normal in one patient. A blunted TSH response to TRH was observed in mitotane-treated patients. ΔTSH (absolute TSH response, peak TSH minus basal TSH) was 3·65 (range 3·53-5·26), 12·37 (range 7·55-19·97) and 1·32 mU/l (range 0·52-4·66) in mitotane-treated patients, controls and central hypothyroid patients, respectively. PRL secretion was normal. Mitotane-treated patients with ACC showed low FT4, normal FT3 and TSH and impaired TSH response to TRH, characteristic of central hypothyroidism. Furthermore, the elevated FT3/FT4 ratio of these subjects reflects an enhanced T4 to T3 conversion rate, a compensatory mechanism characteristic of thyroid function changes

  9. Sarcoidosis Presenting Addison's Disease.

    Takahashi, Kentaro; Kagami, Shin-Ichiro; Kawashima, Hirotoshi; Kashiwakuma, Daisuke; Suzuki, Yoshio; Iwamoto, Itsuo

    2016-01-01

    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.

  10. A case of low renin hyperaldosteronism considered to be aldosterone-producing adrenocortical adenoma by CT image of adrenal gland

    Hayashi, Kozo; Tsuchihashi, Yoshihiro; Ito, Kazuro; Ozono, Noboru

    1983-01-01

    A case was reported in which hypertension, hypopotassemia, low plasma renin activity and hyperaldosteronemia were observed. Imaging suggested adrenocortical adenoma, leading to the diagnosis of low renin hyperaldosteronism. (Chiba, N.)

  11. Imaging Findings of Pelvic Tumor Thrombosis Extending from Sacral Bone Metastasis of Adrenocortical Carcinoma

    Kenichiro Ishida

    2012-01-01

    Full Text Available We report the imaging findings of a patient with adrenocortical carcinoma who showed pelvic tumor thrombosis extending from sacral bone metastasis. Contrast-enhanced computed tomography demonstrated extensive intraluminal filling defects in the pelvic veins. A lytic lesion in the sacrum was also noted and continuity between the sacral lesion and the filling defect in the branch of pelvic veins was indicated. The filling defects showed increased uptake on positron emission tomography with 18F-fluorodeoxyglucose and single-photon emission computed tomography with 131I-iodomethylnorcholesterol, and fusion images with computed tomography aided the localization of the increased uptake areas. Multimodality imaging may be beneficial for the characterization and localization of lesions in patients suspected of having metastatic adrenocortical carcinoma.

  12. Adrenocortical function and reserve in children treated for acute lymphoblastic leukemia

    Pawlaczyk, B.; Malecka, E.H.; Krause, W.

    1993-01-01

    Serum cortisol and 17 OHS, 17 KS and DHA levels in 24-hour urine were determined in 30 children (22 girls and boys) 0.5 to 4 years after completion of therapy (radio- and chemotherapy) for acute lymphoblastic leukemia (ALL). Serum cortisol after Syncthen (adrenocortical reserve) was determined in 15 girls and 4 boys. The results show that therapy for ALL depresses glucocorticosteroid synthesis; however, it does not disturb the adrenal reserve or androgenesis. (author)

  13. Morphological changes in the pituitary-adrenocortical axis in natives of La Paz

    Gosney, John; Heath, Donald; Williams, David; Rios-Dalenz, Jaime

    1991-03-01

    Increased activity of the hypothalamic-pituitary-adrenocortical axis is part of the response to the stress of initial exposure to hypoxia, but there is evidence to suggest that it persists after homeostatic stability has been regained and acclimatization achieved. The adrenal glands of five lifelong residents of La Paz, Bolivia, who had lived at altitudes in the range 3600 3800 m, were significantly larger than those in age-matched controls from sea level (15.3g vs 10.4g; Ppituitary glands of the highlanders were not significantly different in size from those of the controls (0.67 g vs 0.51 g), but contained larger populations of corticotrophs expressed in terms of the total cell population of their anterior lobes (25.6% vs 19.4%; P<0.001). In conjunction with other studies of this endocrine axis in man and animals exposed to a hypoxic environment, these data suggest that greater amounts of adrenocorticotrophic hormone (ACTH) are required to maintain normal adrenocortical function under such circumstances, probably as a result of hypoxic inhibition of adrenocortical sensitivity to stimulation. Physiological hyperplasia of the adrenal cortex may be common in people living at high altitude.

  14. High-density lipoprotein is a potential growth factor for adrenocortical cells

    Murao, Koji; Imachi, Hitomi; Cao, Wenming; Yu, Xiao; Li, Junhua; Yoshida, Kazuya; Ahmed, Rania A.M.; Matsumoto, Kensuke; Nishiuchi, Takamasa; Wong, Norman C.W.; Ishida, Toshihiko

    2006-01-01

    The entry of cholesterol contained within high-density lipoprotein (HDL) into adrenocortical cells is mediated by a human homologue of SR-BI, CD36, and LIMPII Analogous-1 (CLA-1) and thus augmenting their growth. To address the role of CLA-1, we created a mutant mCLA that lacked the C-terminal tail. HDL CE selective uptake by cells carrying the mCLA-1 receptor was fully active and equivalent to those transfected with full-length CLA-1 (fCLA-1). Expression of mCLA inhibited the proliferation of an adrenocortical cell line and the incorporation of [ 3 H]thymidine into the cells. This effect was sensitive to wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K). Our transcriptional studies revealed that the inhibitory action of mCLA required the transcriptional factor AP-1 and the effect of HDL on AP-1 activation was also abrogated by wortmannin. These findings raise the possibility that the inhibitors of the effects of HDL may be of therapeutic value for adrenocortical tumor

  15. Nationwide analysis of adrenocortical carcinoma reveals higher perioperative morbidity in functional tumors.

    Parikh, Punam P; Rubio, Gustavo A; Farra, Josefina C; Lew, John I

    2017-08-25

    Current adrenalectomy outcomes for functional adrenocortical carcinoma (ACC) remain unclear. This study examines nationwide in-hospital post-adrenalectomy outcomes for ACC. A retrospective analysis of the Nationwide Inpatient Sample database (2006-2011) to identify unilateral adrenalectomy patients for functional or nonfunctional ACC was performed. Patient demographics, comorbidities and postoperative outcomes were evaluated by t-test, Chi-square and multivariate regression. Of 2199 patients who underwent adrenalectomy, 87% had nonfunctional and 13% had functional ACC (86% hypercortisolism, 16% hyperaldosteronism, 4% hyperandrogenism). Functional ACC patients had significantly more comorbidities, and experienced certain postoperative complications more frequently including wound issues, adrenocortical insufficiency and acute kidney injury with longer hospital stay compared to nonfunctional ACC (P analysis, functional ACC was an independent prognosticator for wound complications (28.1, 95%CI 4.59-176.6). Patients with functional ACC manifest significant comorbidities with certain in-hospital complications. Such high-risk patients require appropriate preoperative medical optimization prior to adrenalectomy. Patients with functional adrenocortical carcinoma (ACC) have significant preoperative comorbidities and experience higher rates of certain postoperative complications including wound complications, hematoma formation, adrenal insufficiency, pulmonary embolism and acute kidney injury. Functional ACC patients also necessitate longer hospitalizations. These patients should undergo appropriate preoperative counseling in preparation for adrenalectomy. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Role of Endocrine Gland-Derived Vascular Endothelial Growth Factor (EG-VEGF) and Its Receptors in Adrenocortical Tumors.

    Heck, Dorothee; Wortmann, Sebastian; Kraus, Luitgard; Ronchi, Cristina L; Sinnott, Richard O; Fassnacht, Martin; Sbiera, Silviu

    2015-12-01

    Angiogenesis is essential for tumor growth and metastasis. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor predominantly expressed in steroidogenic organs like the adrenal gland, ovary, testes, and placenta. EG-VEGF has antiapoptotic, mitogenic, and chemoattractive properties mediated via the two G protein-coupled receptors prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2). We investigated the expression of EG-VEGF and its receptors in a large number of normal adrenal glands (NAG), adrenocortical adenomas (ACA), and carcinomas (ACC) using real-time PCR (NAG, n = 12; ACA, n = 24; and ACC, n = 30) and immunohistochemistry (NAG, n = 9; ACA, n = 23; and ACC, n = 163) and evaluated its impact on patients' survival. EG-VEGF, PKR1, and PKR2 mRNA and protein are expressed in NAG and the vast majority of ACA and ACC samples. The mean EG-VEGF mRNA expression was significantly lower in ACC (606.5 ± 77.1 copies) compared to NAG (4,043 ± 1,111) and cortisol-producing adenomas (CPA) (4,433 ± 2,378) (p < 0.01 and p < 0.05, respectively). However, cytoplasmic and nuclear EG-VEGF protein expression was either significantly higher or similar in ACC (H score 2.4 ± 0.05, p < 0.05 and 1.7 ± 0.08, n.s., respectively) compared to NAG (1.8 ± 0.14 and 1.7 ± 0.2). Nuclear protein expression of either EG-VEGF or PKR1 or both is predictive for a higher mortality compared to patients without nuclear expression (hazard ratio (HR) = 5.15; 95% confidence interval (CI) = 1.24-21.36, n = 100, p = 0.02 independent of age, sex, and tumor stage). These findings suggest that EG-VEGF and its receptor PKR1 might play a role in the pathogenesis of adrenocortical tumors and could serve as prognostic markers for this rare malignant disease.

  17. Not all glucocorticoid-induced obesity is the same: differences in adiposity among various diagnostic groups of Cushing syndrome.

    London, E; Lodish, M; Keil, M; Lyssikatos, C; de la Luz Sierra, M; Nesterova, M; Stratakis, C A

    2014-11-01

    The cAMP signaling pathway is implicated in bilateral adrenocortical hyperplasias (BAHs), which are often associated with ACTH-independent Cushing syndrome (CS). Although CS is invariably associated with obesity and is frequently associated with PKA signaling defects, we recently reported that its different forms appear to also present with variable weight gain and adiposity. The present study was aimed at characterizing further the phenotypic and molecular differences in periadrenal adipose tissue (PAT) among patients with subtypes of CS, by anthropometric/biochemical analyses and quantification of PKA expression and activity in BAHs in comparison to a non-CS group with aldosterone producing adenomas (APAs). Glucocorticoid levels, serum parameters, and BMI were analyzed among a larger patient cohort including those with different forms of CS, APAs, and Cushing disease. Abdominal CT scans were available for a small subset of patients examined for fat distribution. PAT collected during adrenalectomy was assayed for PKA activity, cAMP, and PKA expression. BMI and BMI z-score were lower in adults with PPNAD with PRKAR1A mutations and in pediatric patients with PPNAD with and without PRKAR1A mutations, respectively. Patients with PPNAD had higher cAMP levels in PAT and different fat distribution. Thus, PKA activity in PAT differed between CS diagnostic groups. Increased cAMP and PKA activity may have contributed to phenotypic differences among subtypes of CS. In agreement with the known roles of cAMP signaling in the regulation of adiposity, patients with PPNAD were less obese than other patients with CS. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Bilateral primary adrenocortical carcinoma complicated by Addisonian crisis: case report

    Foster, M.; Nolan, R.L.; Hong, H.H.

    2001-01-01

    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)

  19. PCP4: a regulator of aldosterone synthesis in human adrenocortical tissues

    Felizola, Saulo J. A.; Nakamura, Yasuhiro; Ono, Yoshikiyo; Kitamura, Kanako; Kikuchi, Kumi; Onodera, Yoshiaki; Ise, Kazue; Takase, Kei; Sugawara, Akira; Hattangady, Namita; Rainey, William E.; Satoh, Fumitoshi; Sasano, Hironobu

    2014-01-01

    Purkinje cell protein 4 (PCP4) is a calmodulin (CaM) binding protein that accelerates calcium association and dissociation with CaM. It has been previously detected in aldosterone-producing adenomas (APA) but details on its expression and function in adrenocortical tissues have remained unknown. Therefore, we performed the immunohistochemical analysis of PCP4 in the following tissues: normal adrenal (NA; n=15), APA (n=15), cortisol producing adenomas (CPA; n=15) and idiopathic hyperaldosteronism cases (IHA; n=5). APA samples (n=45) were also submitted to quantitative RT-PCR (qPCR) of PCP4, CYP11B1, and CYP11B2, as well as DNA sequencing for KCNJ5 mutations. Transient transfection analysis using PCP4 siRNA was also performed in H295R adrenocortical carcinoma cells, following ELISA analysis, and CYP11B2 luciferase assays were also performed after PCP4 vector transfection in order to study the regulation of PCP4 protein expression. In our findings, PCP4 immunoreactivity was predominantly detected in APA and in the zona glomerulosa (ZG) of NA and IHA. In APA, the mRNA levels of PCP4 were significantly correlated with those of CYP11B2 (P<0.0001) and were significantly higher in cases with KCNJ5 mutation than wild-type (P=0.005). Following PCP4 vector transfection, CYP11B2 luciferase reporter activity was significantly higher than controls in the presence of angiotensin-II. Knockdown of PCP4 resulted in a significant decrease in CYP11B2 mRNA levels (P=0.012) and aldosterone production (P=0.011). Our results indicate that PCP4 is a regulator of aldosterone production in normal, hyperplastic and neoplastic human adrenocortical cells. PMID:24403568

  20. Cell cycle dependent RRM2 may serve as proliferation marker and pharmaceutical target in adrenocortical cancer.

    Grolmusz, Vince Kornél; Karászi, Katalin; Micsik, Tamás; Tóth, Eszter Angéla; Mészáros, Katalin; Karvaly, Gellért; Barna, Gábor; Szabó, Péter Márton; Baghy, Kornélia; Matkó, János; Kovalszky, Ilona; Tóth, Miklós; Rácz, Károly; Igaz, Péter; Patócs, Attila

    2016-01-01

    Adrenocortical cancer (ACC) is a rare, but agressive malignancy with poor prognosis. Histopathological diagnosis is challenging and pharmacological options for treatment are limited. By the comparative reanalysis of the transcriptional malignancy signature with the cell cycle dependent transcriptional program of ACC, we aimed to identify novel biomarkers which may be used in the histopathological diagnosis and for the prediction of therapeutical response of ACC. Comparative reanalysis of publicly available microarray datasets included three earlier studies comparing transcriptional differences between ACC and benign adrenocortical adenoma (ACA) and one study presenting the cell cycle dependent gene expressional program of human ACC cell line NCI-H295R. Immunohistochemical analysis was performed on ACC samples. In vitro effects of antineoplastic drugs including gemcitabine, mitotane and 9-cis-retinoic acid alone and in combination were tested in the NCI-H295R adrenocortical cell line. Upon the comparative reanalysis, ribonucleotide reductase subunit 2 (RRM2), responsible for the ribonucleotide dezoxyribonucleotide conversion during the S phase of the cell cycle has been validated as cell cycle dependently expressed. Moreover, its expression was associated with the malignancy signature, as well. Immunohistochemical analysis of RRM2 revealed a strong correlation with Ki67 index in ACC. Among the antiproliferative effects of the investigated compounds, gemcitabine showed a strong inhibition of proliferation and an increase of apoptotic events. Additionally, RRM2 has been upregulated upon gemcitabine treatment. Upon our results, RRM2 might be used as a proliferation marker in ACC. RRM2 upregulation upon gemcitabine treatment might contribute to an emerging chemoresistance against gemcitabine, which is in line with its limited therapeutical efficacy in ACC, and which should be overcome for successful clinical applications.

  1. Magnetic resonance imaging of adrenocortical adenomas in childhood: correlation with computed tomography and ultrasound

    Hanson, J.A.; Weber, A.; Reznek, R.H.; Cotterill, A.M.; Ross, R.J.M.; Harris, R.J.; Armstrong, P.; Savage, M.O.

    1996-01-01

    There are few descriptions of the magnetic resonance (MR) appearance of hyperfunctioning adrenocortical tumours, particularly those occurring in childhood. We studied five patients, two girls and three boys, aged 6-14.3 years, presenting with clinical syndromes of adrenocortical hyperfunction. The diagnoses were Cushing's syndrome (n = 2), virilisation (n = 2), and Conn's syndrome (n = 1). Biochemical features suggested an adrenal lesion in each case. MR and ultrasound were performed in all five cases, with CT in four. Each patient had a functional adrenal tumour secreting either cortisol, androgens or aldosterone alone, or a combination of cortisol, androgens and oestradiol. The histological diagnosis was adenoma in four cases and tumour of indeterminate nature in one case. MR clearly showed the tumours (diameter 1.0-7.5 cm), all the lesions being of high signal intensity relative to liver on T2-weighted sequences. CT revealed an adrenal mass in each of the four patients scanned, three of which enhanced after intravenous contrast medium injection. The multiplanar imaging of MR allowed better distinction from adjacent structures and also demonstrated an unenlarged contralateral adrenal gland. In the patient with a 1-cm Conn's adenoma the lesion was more easily seen on MR than CT. Ultrasound showed the four larger tumours but was unable to visualise the contralateral adrenal or the Conn's adenoma. In conclusion, the MR appearances of four adrenocortical adenomas and one indeterminate tumour in children are described. MR has been found to be at least equal to CT in the detection of these tumours, with some possible advantages. Both techniques are superior to ultrasound. (orig.). With 4 figs

  2. Extension of adrenocortical carcinoma into the right atrium – echocardiographic diagnosis: A case report

    Rozenman Yoseph

    2003-05-01

    Full Text Available Abstract Background Adrenocortical carcinoma is a rare, highly malignant tumor. Cardiac involvement of the tumor is very rare. Echocardiography facilitates the evaluation of the cardiac involvement of the tumor. Case Presentation We describe a patient with an adrenal tumor. Transthoracic echo showed its extension into the right atrium. Accordingly, a combined abdominal and cardiac operation was performed, monitored by transesophageal echocardiography. Conclusion This case highlights the importance of echocardiography in revealing the cardiac involvement by this tumor and in planning the operative procedure.

  3. Adrenocortical Regulation, Eating in the Absence of Hunger and BMI in Young Children

    Francis, L. A.; Granger, D. A.; Susman, E. J.

    2012-01-01

    The purpose of this study was to examine relations among adrenocortical regulation, eating in the absence of hunger, and body mass index (BMI) in children ages 5 to 9 years (N = 43). Saliva was collected before and after the Trier Social Stress Test for children (TSST-C), and was later assayed for cortisol. Area under the curve with respect to increase (AUCi) was used as a measure of changes in cortisol release from baseline to 60 minutes post-TSST-C. Age- and sex-specific BMI scores were cal...

  4. Adjuvant Radiation Therapy Improves Local Control After Surgical Resection in Patients With Localized Adrenocortical Carcinoma

    Sabolch, Aaron; Else, Tobias; Griffith, Kent A.; Ben-Josef, Edgar; Williams, Andrew; Miller, Barbra S.; Worden, Francis; Hammer, Gary D.; Jolly, Shruti

    2015-01-01

    Purpose: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. Methods and Materials: We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. Results: From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. Conclusions: Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed

  5. Adjuvant Radiation Therapy Improves Local Control After Surgical Resection in Patients With Localized Adrenocortical Carcinoma

    Sabolch, Aaron [Department of Radiation Oncology, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Else, Tobias [Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Griffith, Kent A. [Center for Cancer Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Mchigan (United States); Ben-Josef, Edgar [Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Williams, Andrew [University of Michigan Medical School, Ann Arbor, Mchigan (United States); Miller, Barbra S. [Division of Endocrine Surgery, Department of General Surgery, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Worden, Francis [Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Hammer, Gary D. [Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States); Jolly, Shruti, E-mail: shrutij@med.umich.edu [Department of Radiation Oncology, University of Michigan Hospital and Health Systems, Ann Arbor, Mchigan (United States)

    2015-06-01

    Purpose: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of local recurrence, though the benefit of postoperative radiation therapy (RT) has not been established. In this study of grossly resected ACC, we compare local control of patients treated with surgery followed by adjuvant RT to a matched cohort treated with surgery alone. Methods and Materials: We retrospectively identified patients with localized disease who underwent R0 or R1 resection followed by adjuvant RT. Only patients treated with RT at our institution were included. Matching to surgical controls was on the basis of stage, surgical margin status, tumor grade, and adjuvant mitotane. Results: From 1991 to 2011, 360 ACC patients were evaluated for ACC at the University of Michigan (Ann Arbor, MI). Twenty patients with localized disease received postoperative adjuvant RT. These were matched to 20 controls. There were no statistically significant differences between the groups with regard to stage, margins, grade, or mitotane. Median RT dose was 55 Gy (range, 45-60 Gy). Median follow-up was 34 months. Local recurrence occurred in 1 patient treated with RT, compared with 12 patients not treated with RT (P=.0005; hazard ratio [HR] 12.59; 95% confidence interval [CI] 1.62-97.88). However, recurrence-free survival was no different between the groups (P=.17; HR 1.52; 95% CI 0.67-3.45). Overall survival was also not significantly different (P=.13; HR 1.97; 95% CI 0.57-6.77), with 4 deaths in the RT group compared with 9 in the control group. Conclusions: Postoperative RT significantly improved local control compared with the use of surgery alone in this case-matched cohort analysis of grossly resected ACC patients. Although this retrospective series represents the largest study to date on adjuvant RT for ACC, its findings need to be prospectively confirmed.

  6. Adrenocortical Carcinoma: False Positive in an I-123 Metaiodobenzylguanidine Scan

    Rey, Cristina Rodriguez; Candil, Aida Ortega; Galvan, Eliseo Vano; Martin, Maria Nieves Cabrera; Delgado, Jose Luis Carreras [Clinico San Carlos Hospital, Madrid (Spain)

    2016-06-15

    A 55-year-old man with a personal his history of left pheochromocytoma 2 years previously presented with an abdominal ultrasound showed a large left upper quadrant solid mass (calipers), with heterogeneous echogenicity and central cystic degeneration areas or necrosis. F-18 Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT was performed as ACC was suspected. ACC is an uncommon malignant neoplasm of unknown cause; however, smoking and oral contraceptives may be risk factors. Patients usually present with advanced-stage disease and have poor prognosis, with a 2-year recurrence rate that ranges form 73 to 86 %. An MIBG scan was performed after injection of 185 MBq of I-123 MIBG intravenously. Single photon emission tomography (SPECT)/CT scan showed abnormal isotope accumulation in the tumor region. The patient underwent total resection of the tumor. The histology was of ACC, with areas of necrosis and cystic areas, so the result of the MIBG scan was a false positive. Authors divided false-positive MIBG studies into three categories. The first category is neuroendocrine lesions other than pheochromocytomas (tumors of the APUD series). the second category consists in adrenal lesions other than pheochromocytomas (adenomas, ACC) the reasons for this abnormal uptake are unclear. The third category consists of tracer uptake adjacent to the adrenal due to abnormalities in the route of excretion.

  7. Clinical and prognostic aspects of adrenocortical neoplasms in childhood.

    Teinturier, C; Pauchard, M S; Brugières, L; Landais, P; Chaussain, J L; Bougnères, P F

    1999-02-01

    A retrospective study of 54 children was undertaken to define the clinical presentation and secretory patterns of adrenal tumors and to evaluate the outcome of surgical resection and medical therapy. Different factors were studied in univariate and multivariate analysis by using the Cox proportional hazard model. Median age at diagnosis was 4 years. Boys and girls were affected equally. The disease was revealed by virilization (61%) or by a palpable mass (39%) with a 0.1-5.5 year delay from initial symptoms. At initial examination, we found that 76% of children were virilized. Ninety-four percent of the tested tumors secreted androgens, which were associated with glucocorticoids in 36%. Adrenal tumors in children were smaller than in adults. Half of them measured less than 10 cm. There were recurrences in 40% of children. The survival rate at 5 years was 49%, 70% if resection was microscopically complete and 7% if not (P < 0.001). In children, rare adrenal tumors have different diagnostic and prognostic characteristics than in adults; however, recurrences remain frequent. The efficacy of chemotherapy, mainly o,p'-DDD (Mitotane), remains to be evaluated in comparative trials.

  8. Evaluation of adrenocortical function in Florida manatees (Trichechus manatus latirostris)

    Tripp, K.M.; Verstegen, J.P.; Deutsch, C.; Bonde, Robert K.; de Wit, M.; Manire, Charles A.; Gaspard, J.; Harr, K.E.

    2011-01-01

    The study objectives were to determine the predominant manatee glucocorticoid; validate assays to measure this glucocorticoid and adrenocorticotropic hormone (ACTH); determine diagnostic thresholds to distinguish physiological vs. pathological concentrations; identify differences associated with sex, age class, female reproductive status, capture time, and lactate; and determine the best methods for manatee biologists and clinicians to diagnose stress. Cortisol is the predominant manatee glucocorticoid. IMMULITE 1000 assays for cortisol and ACTH were validated. Precision yielded intra- and inter-assay coefficients of variation for serum cortisol: ≤23.5 and ≤16.7%; and ACTH: ≤6.9 and ≤8.5%. Accuracy resulted in a mean adjusted R(2)≥0.87 for serum cortisol and ≥0.96 for ACTH. Assay analytical sensitivities for cortisol (0.1 µg/dl) and ACTH (10.0 pg/ml) were verified. Methods were highly correlated with another IMMULITE 1000 for serum cortisol (r=0.97) and ACTH (r=0.98). There was no significant variation in cortisol or ACTH with sex or age class and no correlation with female progesterone concentrations. Cortisol concentrations were highest in unhealthy manatees, chronically stressed by disease or injury. ACTH was greatest in healthy free-ranging or short-term rehabilitating individuals, peracutely stressed by capture and handling. Cortisol concentrations ≥1.0 µg/dl were diagnostic of chronic stress; ACTH concentrations ≥87.5 pg/ml were diagnostic of peracute stress. In healthy long-term captive manatees, cortisol (0.4±0.2 µg/dl) and ACTH (47.7±15.9 pg/ml) concentrations were lower than healthy free-ranging, short-term rehabilitated or unhealthy manatees. Capture time was not significantly correlated with cortisol; ACTH correlation was borderline significant. Cortisol and ACTH were positively correlated with lactate.

  9. Cushing's Syndrome caused by pigmented adrenocortical micro nodular dysplasia - A familial case

    Gomez-Segovia, I; Gallowitsch, H J; Kresnik, E; Kumnig, G; Mikosch, P; Lind, P [Dept.of Nuclear Medicine and Endocrinology, LKH Klagenfurt (Austria)

    2002-09-01

    Introduction: We present a Case of Cushing's syndrome (CS) in a 16 year old male adolescent. Adrenocortical micro nodular dysplasia is a rare cause of CS. It mostly develops in the first two decades of life. In pathogenesis a stimulatory effect of circulating Immunoglobulins on adrenal steroidogenesis has been postulated. Familial cases have been reported in relation to Carney's Syndrome. We report the clinical case at first diagnosis and preoperative follow up of 1 year prior to treatment. The leading symptoms were severe bilateral (fibrotic) gynaecomastia, weight gain and growth retardation, without hypertension,but osteoporosis, secondary hypogonadism and glucose intolerance. Laboratory findings and the results of functional tests were diagnostic for CS. In addition LDH (I-131 Isotopes), CK, Lipoproteins, GPT, Androstendion, Prolactin were elevated. MRI abdomen revealed a slight enlargement of the adrenals, and suspected a bilateral micro nodular dysplasia. Iodo-cholesterol-scan under dexamethason suppression showed a diffuse bilateral Iodo-cholesterol uptake confirming the autonomous production of cortisol bilateral in the adrenals.Whole body bone scan showed a diffuse reduced diphosphonate uptake in the skeleton and the growth plates. The bone mineral density was significantly reduced.Radiologically osteoporosis was overt. The rapid increase of free urinary cortisol excretion/24h within one year of observation led to a total bilateral adrenalectomy. Postoperative 5 year follow up examinations. Documentation of the outcome and recovery of clinical signs,symptoms and laboratory findings, discussion about the most appropriate long-term substitution therapy. Familial anamnesis:affected family member was the father (micro nodular bilateral adrenocortical dysplasia), the aunt (pararenal incidentaloma, histologically lipoma) and a cousin (micro nodular adrenocortical dysplasia). Sequential analysis of the menin gene from the patient was negative.The detection of

  10. Cushing's Syndrome caused by pigmented adrenocortical micro nodular dysplasia - A familial case

    Gomez-Segovia, I.; Gallowitsch, H.J.; Kresnik, E.; Kumnig, G.; Mikosch, P.; Lind, P.

    2002-01-01

    Introduction: We present a Case of Cushing's syndrome (CS) in a 16 year old male adolescent. Adrenocortical micro nodular dysplasia is a rare cause of CS. It mostly develops in the first two decades of life. In pathogenesis a stimulatory effect of circulating Immunoglobulins on adrenal steroidogenesis has been postulated. Familial cases have been reported in relation to Carney's Syndrome. We report the clinical case at first diagnosis and preoperative follow up of 1 year prior to treatment. The leading symptoms were severe bilateral (fibrotic) gynaecomastia, weight gain and growth retardation, without hypertension,but osteoporosis, secondary hypogonadism and glucose intolerance. Laboratory findings and the results of functional tests were diagnostic for CS. In addition LDH (I-131 Isotopes), CK, Lipoproteins, GPT, Androstendion, Prolactin were elevated. MRI abdomen revealed a slight enlargement of the adrenals, and suspected a bilateral micro nodular dysplasia. Iodo-cholesterol-scan under dexamethason suppression showed a diffuse bilateral Iodo-cholesterol uptake confirming the autonomous production of cortisol bilateral in the adrenals.Whole body bone scan showed a diffuse reduced diphosphonate uptake in the skeleton and the growth plates. The bone mineral density was significantly reduced.Radiologically osteoporosis was overt. The rapid increase of free urinary cortisol excretion/24h within one year of observation led to a total bilateral adrenalectomy. Postoperative 5 year follow up examinations. Documentation of the outcome and recovery of clinical signs,symptoms and laboratory findings, discussion about the most appropriate long-term substitution therapy. Familial anamnesis:affected family member was the father (micro nodular bilateral adrenocortical dysplasia), the aunt (pararenal incidentaloma, histologically lipoma) and a cousin (micro nodular adrenocortical dysplasia). Sequential analysis of the menin gene from the patient was negative.The detection of

  11. Resveratrol inhibits steroidogenesis in human fetal adrenocortical cells at the end of first trimester

    Savchuk, Iuliia; Morvan, Marie-Line; Søeborg, Tue

    2017-01-01

    SCOPE: Resveratrol has a diverse array of healthful effects on metabolic parameters in different experimental paradigms but has also potential to inhibit steroidogenesis in rodent adrenals. The aim of the present study was to characterize the effects of resveratrol on human fetal adrenal...... steroidogenesis at gestational weeks (GW) 9-12. METHODS AND RESULTS: Adrenals from aborted fetuses (GW10-12) were used to prepare primary cultures of human fetal adrenocortical cells (HFAC). HFAC were treated in the presence or absence of ACTH (10 ng/ml) with or without resveratrol (10 μM) for 24 hours....... The production of steroids by HFAC was analyzed by gas and liquid chromatography coupled to tandem/mass spectrometry. The expression of steroidogenic enzymes at GW 9-12 was quantified by automated Western blotting. We observed that resveratrol significantly suppressed synthesis of dehydroepiandrosterone (DHEA...

  12. Differentiating pheochromocytoma from lipid-poor adrenocortical adenoma by CT texture analysis: feasibility study.

    Zhang, Gu-Mu-Yang; Shi, Bing; Sun, Hao; Jin, Zheng-Yu; Xue, Hua-Dan

    2017-09-01

    To investigate the feasibility of using CT texture analysis (CTTA) to differentiate pheochromocytoma from lipid-poor adrenocortical adenoma (lp-ACA). Ninety-eight pheochromocytomas and 66 lp-ACAs were included in this retrospective study. CTTA was performed on unenhanced and enhanced images. Receiver operating characteristic (ROC) analysis was performed, and the area under the ROC curve (AUC) was calculated for texture parameters that were significantly different for the objective. Diagnostic accuracies were evaluated using the cutoff values of texture parameters with the highest AUCs. Compared to lp-ACAs, pheochromocytomas had significantly higher mean gray-level intensity (Mean), entropy, and mean of positive pixels (MPP), but lower skewness and kurtosis on unenhanced images (P feasible to use CTTA to differentiate pheochromocytoma from lp-ACA.

  13. Adrenocortical Secreting Mass in a Patient with Gardner's Syndrome: A Case Report

    Nabila Mejdoub Rekik

    2010-01-01

    Full Text Available Gardner's syndrome (GS is a dysplasia characterized by neoformations of the intestine, soft tissue, and osseous tissue. Endocrine neoplasms have occasionally been reported in association with GS. Adrenal masses in GS are rare, and few have displayed clinical manifestations. In the current paper, The authors report a 37-year-old male patient with GS including familial adenomatous polyposis (FAP and mandible osteoma who presented with an incidental adrenal mass. Computerized tomography adrenal scan identified bilateral masses. Functional analyses showed a hormonal secretion pattern consistent with pre-Cushing's syndrome. Other extraintestinal manifestations were hypertrophy of the pigmented layer of the retina and histiocytofibroma in the right leg. This paper describes a rare association of adrenocortical secreting mass in an old male patient with Gardner syndrome.

  14. Adrenocortical carcinoma presenting as varicocele and renal vein thrombosis: a case report

    Horne John M

    2011-08-01

    Full Text Available Abstract Introduction Adrenocortical carcinomas are rare aggressive tumors. Their annual incidence is approximately one to two per million among the population of the United States of America. Patients with active endocrine tumors often present with Cushing's syndrome accompanied by virilizing features. Conversely, patients with non-functioning tumors may present with symptoms related to a mass-occupying lesion, such as abdominal pain and flank pain. Although varicoceles and acute kidney injuries are common problems in medicine, they are uncommon presentations of these rare tumors and easy to miss. We report a case of a large adrenocortical carcinoma that presented as testicular pain, varicocele, and acute kidney injury secondary to renal vein thrombosis. Case presentation A 54-year-old Caucasian man with a left-sided varicocele presented to our emergency department with lower abdominal pain and a decrease in urination. Four months previously, he had noticed pain and swelling in his left groin and had been diagnosed with left-sided varicocele. For one week, he began developing left-sided abdominal pain and decreased urination frequency, so he came to our emergency department for evaluation. His physical examination revealed a hard mass occupying the entire left side of his abdomen, crossing the midline, and extending to the pelvic brim. His blood tests showed acute kidney injury and mild anemia. Computed tomography of his abdomen showed a large retroperitoneal mass on the left side, displacing the left kidney inferiorly and the spleen superiorly with thoracic epidural compression. Thrombus was also identified in his left renal vein and inferior vena cava. Computed tomography of his chest showed bilateral pulmonary nodules. A computed tomography-guided abdominal mass biopsy was performed, and the diagnosis of adrenocortical carcinoma was made on the basis of pathology and immunohistochemistry. His hormonal evaluations were normal. His kidney

  15. A mathematical model of the hypothalamo-pituitary-adrenocortical system and its stability analysis

    Savic, Danka; Jelic, Smiljana

    2005-01-01

    It is commonly assumed that the hypothalamo-pituitary-adrenocortical (HPA) axis generates oscillations, because a regular daily rhythm of its component hormones is observed. We offer another plausible explanation of the origin of its circadian oscillations: HPA just responds to an independent external pacemaker (from the suprachiazmatic nucleus, SCN). Five versions (with and without time delay) of a qualitative non-phenomenological mathematical model of the HPA axis as a feedback mechanism are constructed wherein all the terms in the equations are introduced according to the rules of chemical kinetics, i.e. are physicochemically interpretable. The dynamics of the HPA axis model was examined using linear stability analysis. The results show stability of this system, meaning that it does not generate diurnal oscillations. Computer simulation based on this model shows oscillations that are system's response to an external pulsing activator (SCN) implying that the observed time-periodic pattern does not have to be an intrinsic property of the HPA axis

  16. Biosynthesis of Various Steroids in vitro by Isolated Adrenal Cells in Primary Aldosteronism, Cushing's Syndrome, and Adrenogenital Syndrome due to Adrenocortical Adenoma

    MIZUNO, SHIGERU; FUNAHASHI, HIROOMI

    1981-01-01

    To a further understanding of the role of steroid hormones in adrenal disorders, we have prepared free cell system of adrenal cells, using adrenal tissues that had been removed by operation from (i) cases of Cushing's syndrome due to adrenocortical adenoma or adrenocortical hyperplasia, (ii) a case of primary aldosteronism, and (iii) a patient with virilizing adrenal tumor. Twelve important steroid hormones were measured, such as pregnenolone, cortisol and aldosterone, which were produced by ...

  17. Adrenal incidentalomas showing unilateral concordant visualization by adrenocortical scintigraphy. Comparison with adenomas in Cushing's syndrome

    Tani, Atsushi; Nakajo, Masayuki; Tsuchimochi, Shinsaku; Nakabeppu, Yoshiaki; Umanodan, Tomokazu

    2000-01-01

    An adrenocortical adenoma causing Cushing's syndrome (Cushing's adenoma) produces a unilateral concordant visualization (UCV) imaging pattern in which the adenoma is only visualized on radioiodocholesterol adrenocortical scintigraphy. But because this imaging pattern is also noted in some patients with adrenal incidentalomas, we examined whether the UCV-incidentaloma was essentially identical with Cushing's adenoma and would develop Cushing's syndrome. The subjects were 9 patients with UCV-incidentalomas (mean size, 30 mm; range, 20-45 mm) and 6 patients with Cushing's adenomas (mean size, 28 mm; range, 25-35 mm). Endocrinological evaluations showed several abnormalities including blunted diurnal rhythm of plasma cortisol within the normal range, low plasma ACTH and/or high 24-hr urinary 17-OHCS levels in 8 of 9 patients with UCV-incidentalomas, but these abnormalities did not meet the diagnostic criteria of Cushing's syndrome. Adrenal uptake of the tracer in the patients with UCV-incidentalomas was not statistically different from that in the patients with Cushing's adenomas and had no relationship with hormonal values in either patient group. Tumor size on CT correlated with the levels of 24-hr urinary 17-OHCS (r=0.75, p=0.02) and plasma cortisol at 7:00 (r=0.82, p=0.007) in the patients with UCV-incidentalomas, but not in the patients with Cushing's adenomas. Although 3 UCV-incidentalomas increased slightly in size, none of 9 patients with UCV-incidentalomas has developed Cushing's syndrome for 4 to 52 months. These results suggest that the UCV-incidentaloma may be essentially different from the Cushing's adenoma and unlikely to develop Cushing's syndrome. (author)

  18. Naturally Occurring Adrenocortical Insufficiency--An Epidemiological Study Based on a Swedish-Insured Dog Population of 525,028 Dogs.

    Hanson, J M; Tengvall, K; Bonnett, B N; Hedhammar, Å

    2016-01-01

    Naturally occurring adrenocortical insufficiency (NOAI) in dogs is considered an uncommon disease with good prognosis with hormonal replacement treatment. However, there are no epidemiological studies with estimates for the general dog population. To investigate the epidemiological characteristics of NOAI in a large population of insured dogs. Data were derived from 525,028 client-owned dogs insured by a Swedish insurance company representing 2,364,652 dog-years at risk (DYAR) during the period between 1995-2006. Retrospective cohort study. Incidence rates, prevalences, and relative risks for dogs with NOAI (AI with no previous claim for hypercortisolism), were calculated for the whole dog population, and for subgroups divided by breed and sex. Mortality rates were calculated and compared in dogs with NOAI and the remaining dogs overall. In total 534 dogs were identified with NOAI. The overall incidence was 2.3 cases per 10,000 DYAR. The relative risk of disease was significantly higher in the Portuguese Water Dog, Standard Poodle, Bearded Collie, Cairn Terrier, and Cocker Spaniel compared with other breeds combined. Female dogs overall were at higher risk of developing AI than male dogs (RR 1.85; 95% CI, 1.55-2.22; P dogs with NOAI than in dogs overall. The data supports the existence of breed-specific differences in incidence rates of NOAI in dogs. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  19. Carney complex (CNC

    Bertherat Jérôme

    2006-06-01

    Full Text Available Abstract The Carney complex (CNC is a dominantly inherited syndrome characterized by spotty skin pigmentation, endocrine overactivity and myxomas. Skin pigmentation anomalies include lentigines and blue naevi. The most common endocrine gland manifestations are acromegaly, thyroid and testicular tumors, and adrenocorticotropic hormone (ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD. PPNAD, a rare cause of Cushing's syndrome, is due to primary bilateral adrenal defect that can be also observed in some patients without other CNC manifestations or familial history of the disease. Myxomas can be observed in the heart, skin and breast. Cardiac myxomas can develop in any cardiac chamber and may be multiple. One of the putative CNC genes located on 17q22-24, (PRKAR1A, has been identified to encode the regulatory subunit (R1A of protein kinase A. Heterozygous inactivating mutations of PRKAR1A were reported initially in 45 to 65 % of CNC index cases, and may be present in about 80 % of the CNC families presenting mainly with Cushing's syndrome. PRKAR1A is a key component of the cAMP signaling pathway that has been implicated in endocrine tumorigenesis and could, at least partly, function as a tumor suppressor gene. Genetic analysis should be proposed to all CNC index cases. Patients with CNC or with a genetic predisposition to CNC should have regular screening for manifestations of the disease. Clinical work-up for all the manifestations of CNC should be performed at least once a year in all patients and should start in infancy. Cardiac myxomas require surgical removal. Treatment of the other manifestations of CNC should be discussed and may include follow-up, surgery, or medical treatment depending on the location of the tumor, its size, the existence of clinical signs of tumor mass or hormonal excess, and the suspicion of malignancy. Bilateral adrenalectomy is the most common treatment for Cushing

  20. Carney complex (CNC).

    Bertherat, Jérôme

    2006-06-06

    The Carney complex (CNC) is a dominantly inherited syndrome characterized by spotty skin pigmentation, endocrine overactivity and myxomas. Skin pigmentation anomalies include lentigines and blue naevi. The most common endocrine gland manifestations are acromegaly, thyroid and testicular tumors, and adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). PPNAD, a rare cause of Cushing's syndrome, is due to primary bilateral adrenal defect that can be also observed in some patients without other CNC manifestations or familial history of the disease. Myxomas can be observed in the heart, skin and breast. Cardiac myxomas can develop in any cardiac chamber and may be multiple. One of the putative CNC genes located on 17q22-24, (PRKAR1A), has been identified to encode the regulatory subunit (R1A) of protein kinase A. Heterozygous inactivating mutations of PRKAR1A were reported initially in 45 to 65% of CNC index cases, and may be present in about 80% of the CNC families presenting mainly with Cushing's syndrome. PRKAR1A is a key component of the cAMP signaling pathway that has been implicated in endocrine tumorigenesis and could, at least partly, function as a tumor suppressor gene. Genetic analysis should be proposed to all CNC index cases. Patients with CNC or with a genetic predisposition to CNC should have regular screening for manifestations of the disease. Clinical work-up for all the manifestations of CNC should be performed at least once a year in all patients and should start in infancy. Cardiac myxomas require surgical removal. Treatment of the other manifestations of CNC should be discussed and may include follow-up, surgery, or medical treatment depending on the location of the tumor, its size, the existence of clinical signs of tumor mass or hormonal excess, and the suspicion of malignancy. Bilateral adrenalectomy is the most common treatment for Cushing's syndrome due to PPNAD.

  1. Failure to Thrive in the Context of Carney Complex.

    Tirosh, Amit; Auerbach, Adi; Bonella, Belen; Zavras, Phaedon D; Belyavskaya, Elena; Lyssikatos, Charalampos; Meir, Karen; Weiss, Ram; Daum, Hagit; Lodish, Maya B; Gillis, David; Stratakis, Constantine A

    2018-01-01

    Carney complex (CNC) is a rare syndrome associated with multiple tumors and several other unique manifestations. We describe the clinical, genetic, and laboratory findings in a cohort of patients with CNC and failure to thrive (FTT). A retrospective case series of pediatric patients with CNC presenting with FTT. We describe a patient with infantile Cushing syndrome (CS) who presented with severe FTT and liver disease; the patient was subsequently diagnosed with CNC. This led to the realization that at least 10 other patients with CNC and FTT have been investigated in the last 22 years at the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Four of those had primary pigmented nodular adrenocortical disease (PPNAD), 2 had cardiac myxomas, and 3 had liver disease. Pediatric patients with CNC may present with FTT whose primary cause is variable and includes CS due to PPNAD, hepatic involvement, and other manifestations of CNC. FTT due to liver disease and/or other causes is a unique new presentation of this rare syndrome with which clinicians need to be familiar. © 2017 S. Karger AG, Basel.

  2. Rosiglitazone induces autophagy in H295R and cell cycle deregulation in SW13 adrenocortical cancer cells

    Cerquetti, Lidia; Sampaoli, Camilla; Amendola, Donatella; Bucci, Barbara; Masuelli, Laura; Marchese, Rodolfo; Misiti, Silvia; De Venanzi, Agostino; Poggi, Maurizio; Toscano, Vincenzo; Stigliano, Antonio

    2011-01-01

    Thiazolidinediones, specific peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands, used in type-2 diabetes therapy, show favourable effects in several cancer cells. In this study we demonstrate that the growth of H295R and SW13 adrenocortical cancer cells is inhibited by rosiglitazone, a thiazolidinediones member, even though the mechanisms underlying this effect appeared to be cell-specific. Treatment with GW9662, a selective PPAR-γ-inhibitor, showed that rosiglitazone acts through both PPAR-γ-dependent and -independent mechanisms in H295R, while in SW13 cells the effect seems to be independent of PPAR-γ. H295R cells treated with rosiglitazone undergo an autophagic process, leading to morphological changes detectable by electron microscopy and an increased expression of specific proteins such as AMPKα and beclin-1. The autophagy seems to be independent of PPAR-γ activation and could be related to an increase in oxidative stress mediated by reactive oxygen species production with the disruption of the mitochondrial membrane potential, triggered by rosiglitazone. In SW13 cells, flow cytometry analysis showed an arrest in the G0/G1 phase of the cell cycle with a decrease of cyclin E and cdk2 activity, following the administration of rosiglitazone. Our data show the potential role of rosiglitazone in the therapeutic approach to adrenocortical carcinoma and indicate the molecular mechanisms at the base of its antiproliferative effects, which appear to be manifold and cell-specific in adrenocortical cancer lines.

  3. Rosiglitazone induces autophagy in H295R and cell cycle deregulation in SW13 adrenocortical cancer cells

    Cerquetti, Lidia; Sampaoli, Camilla [Endocrinology, Department of Clinical and Molecular Medicine, Sant' Andrea Hospital, Faculty of Medicine and Psychology ' Sapienza' University of Rome, Via di Grottarossa, 1035-00189 Rome (Italy); Research Center S. Pietro Hospital, Via Cassia, 600-00189 Rome (Italy); Amendola, Donatella; Bucci, Barbara [Research Center S. Pietro Hospital, Via Cassia, 600-00189 Rome (Italy); Masuelli, Laura [Department of Experimental Medicine, ' Sapienza' University of Rome, Rome (Italy); Marchese, Rodolfo [Research Center S. Pietro Hospital, Via Cassia, 600-00189 Rome (Italy); Misiti, Silvia [Endocrinology, Department of Clinical and Molecular Medicine, Sant' Andrea Hospital, Faculty of Medicine and Psychology ' Sapienza' University of Rome, Via di Grottarossa, 1035-00189 Rome (Italy); Research Center S. Pietro Hospital, Via Cassia, 600-00189 Rome (Italy); De Venanzi, Agostino; Poggi, Maurizio; Toscano, Vincenzo [Endocrinology, Department of Clinical and Molecular Medicine, Sant' Andrea Hospital, Faculty of Medicine and Psychology ' Sapienza' University of Rome, Via di Grottarossa, 1035-00189 Rome (Italy); Stigliano, Antonio, E-mail: antonio.stigliano@uniroma1.it [Endocrinology, Department of Clinical and Molecular Medicine, Sant' Andrea Hospital, Faculty of Medicine and Psychology ' Sapienza' University of Rome, Via di Grottarossa, 1035-00189 Rome (Italy); Research Center S. Pietro Hospital, Via Cassia, 600-00189 Rome (Italy)

    2011-06-10

    Thiazolidinediones, specific peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}) ligands, used in type-2 diabetes therapy, show favourable effects in several cancer cells. In this study we demonstrate that the growth of H295R and SW13 adrenocortical cancer cells is inhibited by rosiglitazone, a thiazolidinediones member, even though the mechanisms underlying this effect appeared to be cell-specific. Treatment with GW9662, a selective PPAR-{gamma}-inhibitor, showed that rosiglitazone acts through both PPAR-{gamma}-dependent and -independent mechanisms in H295R, while in SW13 cells the effect seems to be independent of PPAR-{gamma}. H295R cells treated with rosiglitazone undergo an autophagic process, leading to morphological changes detectable by electron microscopy and an increased expression of specific proteins such as AMPK{alpha} and beclin-1. The autophagy seems to be independent of PPAR-{gamma} activation and could be related to an increase in oxidative stress mediated by reactive oxygen species production with the disruption of the mitochondrial membrane potential, triggered by rosiglitazone. In SW13 cells, flow cytometry analysis showed an arrest in the G0/G1 phase of the cell cycle with a decrease of cyclin E and cdk2 activity, following the administration of rosiglitazone. Our data show the potential role of rosiglitazone in the therapeutic approach to adrenocortical carcinoma and indicate the molecular mechanisms at the base of its antiproliferative effects, which appear to be manifold and cell-specific in adrenocortical cancer lines.

  4. Impact of {sup 18}F-FDG PET/CT on the management of adrenocortical carcinoma: analysis of 106 patients

    Takeuchi, Satoshi; Macapinlac, Homer A.; Chuang, Hubert H. [The University of Texas MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States); Balachandran, Aparna [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Houston, TX (United States); Habra, Mouhammed Amir [The University of Texas MD Anderson Cancer Center, Department of Endocrine Neoplasia and Hormonal Disorders, Houston, TX (United States); Phan, Alexandria T. [The University of Texas MD Anderson Cancer Center, Department of Gastrointestinal Medical Oncology, Houston, TX (United States); Bassett, Roland L. [The University of Texas MD Anderson Cancer Center, Department of Biostatistics, Houston, TX (United States)

    2014-11-15

    Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. Limited data are available about on value of {sup 18}F-FDG PET/CT in ACC. We evaluated the impact of PET/CT on the management of ACC. We performed a retrospective review in patients with ACC who had undergone PET/CT. The impact of PET/CT on the management plan was evaluated by comparing the findings on PET/CT to the findings on contrast-enhanced CT. The sensitivity, specificity, and accuracy of each form of imaging were calculated. The correlations between PET/CT parameters, including maximum standardized uptake value (SUV{sub max}), total lesion glycolysis, and decline in SUV{sub max} after chemotherapy, and clinical outcome were evaluated. Included in the analysis were 106 patients with 180 PET/CT scans. Of the 106 patients, 7 underwent PET/CT only for initial staging, 84 underwent PET/CT only for restaging, and 15 underwent PET/CT for both initial staging and restaging. PET/CT changed the management plan in 1 of 22 patients (5 %) at initial staging and 9 of 99 patients (9 %) at restaging. In 5 of the patients in whom PET/CT changed the management plan, PET/CT showed response to chemotherapy but contrast-enhanced CT showed stable disease. Sensitivity, specificity, and accuracy were 100 %, 100 %, and 100 % for PET/CT at initial staging; 92.6 %, 100 %, and 96.4 % for CT at initial staging; 98.4 %, 100 %, and 99.5 % for PET/CT at restaging; and 96.8 %, 98.6 %, and 98.0 % for CT at restaging, respectively. No PET/CT parameters were associated with survival at either initial diagnosis or recurrence. PET/CT findings could substantially change the management plan in a small proportion of patients with ACC. Although lesion detection was similar between PET/CT and CT, PET/CT may be preferred for chemotherapeutic response assessment because it may predict response before anatomic changes are detected on CT. (orig.)

  5. Surgical management of Cushing Syndrome secondary to micronodular adrenal hyperplasia

    Powell, Anathea C.; Stratakis, Constantine A.; Patronas, Nicholas J.; Steinberg, Seth M.; Batista, Dalia; Alexander, H. Richard; Pingpank, James F.; Keil, Meg; Bartlett, David L.; Libutti, Steven K.

    2008-01-01

    Background We reviewed our experience with micronodular adrenal hyperplasia (MAH), its pigmented variant primary pigmented nodular adrenocortical disease (PPNAD), and the association with Carney’s Complex (CNC) in order to better characterize the disorders. Methods This study is a retrospective analysis of clinical data and operative reports of 34 patients identified with MAH and/or PPNAD who underwent resection between 1969 and 2006 at the Clinical Research Center, an inpatient research hospital, at the National Institutes of Health. Symptoms and anthropometric and biochemical data were used to evaluate effect of resection. Results Fifteen patients (44%) presented as adults and 19 (56%) as children. Twenty five patients (74%) presented with non-cyclic Cushing syndrome and nine patients (26%) presented with cyclic Cushing Syndrome. Thirty one patients underwent bilateral resection; this was curative biochemically in 30 patients. Fourteen operations were performed laparoscopically (41%), and 20 were perfomed as open resections (59%). There was one post-operative complication in the laparoscopic group (7%) and 6 complications in the open group (30%) (p=0.20). Follow-up was available for 25 patients (74%). Statistically significant improvements in anthropometrics were observed for both adults and children. The most frequent manifestation of CNC requiring additional operation was cardiac myxoma which was associated strongly with an atypical (cyclic) presentation of Cushing Syndrome (p=0.009). Conclusion Cushing Syndrome due to MAH and PPNAD may be cured by bilateral adrenal resection. All patients should be screened for manifestations of CNC at the time of adrenal diagnosis with particular attention to cardiac disease. PMID:18549891

  6. Chloroquine enhances the efficacy of cisplatin by suppressing autophagy in human adrenocortical carcinoma treatment

    Qin L

    2016-03-01

    Full Text Available Liang Qin,1,* Tianyuan Xu,1,* Leilei Xia,1 Xianjin Wang,1 Xiang Zhang,1 Xiaohua Zhang,1 Zhaowei Zhu,1 Shan Zhong,1 Chuandong Wang,2 Zhoujun Shen1 1Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 2Key Laboratory of Stem Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: It has been demonstrated that chloroquine (CQ enhances the efficacy of chemotherapy. However, little is known about whether CQ could enhance the efficacy of cisplatin (DDP in the treatment of adrenocortical carcinoma (ACC. In this study, we explore the efficacy and mechanism by which CQ affects DDP sensitivity in human ACC in vitro and in vivo.Methods: The autophagic gene Beclin-1 expression was detected by immunohistochemistry, and the protein levels were analyzed using immunoblotting assays of ACC tissues and normal adrenal cortex tissues. The ACC SW13 cells were treated with DDP and/or CQ. The cell viability assay was performed using the MTT method. Qualitative autophagy detection was performed by monodansylcadaverine staining of autophagic vacuoles. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to count cell apoptosis by flow cytometry. The autophagy-related protein (Beclin-1, LC3, and p62 and apoptosis relative protein (Bax and Bcl-2 levels were evaluated with Western blot analysis. Furthermore, a murine model of nude BALB/c mice bearing SW13 cell xenografts was established to evaluate the efficacy of concomitant therapy.Results: The expression of the autophagic gene Beclin-1 was significantly downregulated in ACC tissues compared to normal adrenal cortex tissues. The Beclin-1 protein level in ACC tissues was lower than that in normal adrenal cortex tissues (P<0.05. In vitro concomitant therapy (DDP and CQ was more

  7. The involvement of the hypothalamopituitary-adrenocortical axis in stress physiology and its significance in the assessment of animal welfare in cattle

    Emma J. Brown

    2017-04-01

    Full Text Available The intensification of cattle production has raised concern for animal welfare due to the stress that is associated with farming practices. The welfare of an animal is determined by the animal’s ability to cope with or adapt to its continuously changing environment and the biological cost that is associated with this adaptation and maintenance. Stressors arise from various psychological, physiological and physical aspects of farming practices due to management and human–cattle interactions. Measuring the activity of the hypothalamopituitary-adrenocortical (HPA axis with plasma cortisol levels is a useful method for determining the effects of stress on animals as it is stimulated at the onset of a perceived stress. The activation of the HPA axis affects various target tissues or systems and can result in suppression of the immune system, increased susceptibility to disease and adverse effects on reproductive success in prenatal and neonatal calves. Although some levels of stress associated with farming practices are unavoidable, improvements in farming methods need to be implemented in order to maintain or increase the efficiency of cattle production in a way that does not compromise the welfare of the animal.

  8. A mathematical model of the hypothalamo-pituitary-adrenocortical system and its stability analysis

    Savic, Danka [Vinca Institute of Nuclear Sciences, Laboratory for Theoretical and Condensed Matter Physics, P.O. Box 522, Belgrade 11001 (Serbia and Montenegro)] e-mail: dankasav@eunet.yu; Jelic, Smiljana [Vinca Institute of Nuclear Sciences, Laboratory for Theoretical and Condensed Matter Physics, P.O. Box 522, Belgrade 11001 (Serbia and Montenegro)

    2005-10-01

    It is commonly assumed that the hypothalamo-pituitary-adrenocortical (HPA) axis generates oscillations, because a regular daily rhythm of its component hormones is observed. We offer another plausible explanation of the origin of its circadian oscillations: HPA just responds to an independent external pacemaker (from the suprachiazmatic nucleus, SCN). Five versions (with and without time delay) of a qualitative non-phenomenological mathematical model of the HPA axis as a feedback mechanism are constructed wherein all the terms in the equations are introduced according to the rules of chemical kinetics, i.e. are physicochemically interpretable. The dynamics of the HPA axis model was examined using linear stability analysis. The results show stability of this system, meaning that it does not generate diurnal oscillations. Computer simulation based on this model shows oscillations that are system's response to an external pulsing activator (SCN) implying that the observed time-periodic pattern does not have to be an intrinsic property of the HPA axis.

  9. Polychlorinated biphenyl 126 stimulates basal and inducible aldosterone biosynthesis of human adrenocortical H295R cells

    Li, L.-A.; Wang, P.-W.; Chang, Louis W.

    2004-01-01

    To understand the effects of polychlorinated biphenyls (PCBs) on adrenal aldosterone biosynthesis, we have performed a systematical study to characterize the corresponding steroidogenic response of human adrenocortical cell line H295R to PCB126 exposure. We found that PCB126 at high concentrations stimulated basal and inducible aldosterone production. The aldosterone induction occurred concomitantly with activation of the CYP11B2 gene. Despite the fact that PCB126 acted in synergy with both potassium and angiotensin II (Ang II) in activation of aldosterone synthesis, PCB126 only modestly increased CYP11B2 mRNA expression in the presence of Ang II contrary to the synergistic transcriptional induction elicited by PCB126 and potassium. This implicated that PCB126 had differential interactions with the potassium and Ang II signaling systems in the regulation of aldosterone biosynthesis. In addition, high concentrations of PCB126 elevated transcriptional expression of the type I Ang II receptor (AT 1 ) and might thus sensitize the cellular Ang II responsiveness in both basal and inducible aldosterone biosynthesis. SF-1 was not involved in the PCB126-induced transcriptional regulation despite its importance in steroidogenic gene activation

  10. Cytodiagnosis of myxoid adrenocortical carcinoma and role of immunocytochemistry to differentiate it from renal cell carcinoma

    Santosh Kumar Mondal

    2014-01-01

    Full Text Available Adrenocortical carcinoma (ACC is a rare malignancy and cytodiagnosis of this tumor is not routinely encountered by a cytopathologist. Here, we report a case of ACC initially diagnosed by computed tomography (CT-guided fine needle aspiration cytology (FNAC with the help of immunocytochemistry. A 48-year-old lady presented with flank pain and abdominal mass for the last 6 months. A CT scan of her abdomen revealed a large mass arising from the upper part of the left kidney. CT-guided FNAC was performed. Cytologic smears showed pleomorphic large cells arranged discretely and in small aggregates against a myxoid background. The cells had a high nucleocytoplasmic ratio, anisonucleosis and conspicuous nucleoli. Based on cytomorphology, differential diagnoses of ACC and renal cell carcinoma (RCC were made. On immunocytochemistry, the tumor cells were synaptophysin, inhibin, vimentin and Melan-A positive but cytokeratin and epithelial membrane antigen negative. Thus, a cytodiagnosis of myxoid ACC was made and histopathologic examination was suggested. Subsequent histologic examination and immunohistochemistry proved the case to be myxoid ACC.

  11. Human Adrenocortical Remodeling Leading to Aldosterone-Producing Cell Cluster Generation

    Koshiro Nishimoto

    2016-01-01

    Full Text Available Background. The immunohistochemical detection of aldosterone synthase (CYP11B2 and steroid 11β-hydroxylase (CYP11B1 has enabled the identification of aldosterone-producing cell clusters (APCCs in the subcapsular portion of the human adult adrenal cortex. We hypothesized that adrenals have layered zonation in early postnatal stages and are remodeled to possess APCCs over time. Purposes. To investigate changes in human adrenocortical zonation with age. Methods. We retrospectively analyzed adrenal tissues prepared from 33 autopsied patients aged between 0 and 50 years. They were immunostained for CYP11B2 and CYP11B1. The percentage of APCC areas over the whole adrenal area (AA/WAA, % and the number of APCCs (NOA, APCCs/mm2 were calculated by four examiners. Average values were used in statistical analyses. Results. Adrenals under 11 years old had layered zona glomerulosa (ZG and zona fasciculata (ZF without apparent APCCs. Some adrenals had an unstained (CYP11B2/CYP11B1-negative layer between ZG and ZF, resembling the rat undifferentiated cell zone. Average AA/WAA and NOA correlated with age, suggesting that APCC development is associated with aging. Possible APCC-to-APA transitional lesions were incidentally identified in two adult adrenals. Conclusions. The adrenal cortex with layered zonation remodels to possess APCCs over time. APCC generation may be associated with hypertension in adults.

  12. Adrenocortical regulation, eating in the absence of hunger and BMI in young children.

    Francis, L A; Granger, D A; Susman, E J

    2013-05-01

    The purpose of this study was to examine relations among adrenocortical regulation, eating in the absence of hunger, and body mass index (BMI) in children ages 5-9years (N=43). Saliva was collected before and after the Trier Social Stress Test for Children (TSST-C), and was later assayed for cortisol. Area under the curve with respect to increase (AUCi) was used as a measure of changes in cortisol release from baseline to 60min post-TSST-C. Age- and sex-specific BMI scores were calculated from measured height and weight, and eating in the absence of hunger was assessed using weighed food intake during a behavioral procedure. We also included a measure of parents' report of child impulsivity, as well as family demographic information. Participants were stratified by age into younger (5-7years) and older (8-9years) groups. In younger children, parents' reports of child impulsivity were significantly and positively associated with BMI; cortisol AUCi was not associated with BMI or eating in the absence of hunger. In older children, however, greater stress-related cortisol AUCi was related to higher BMI scores and greater energy intake in the absence of hunger. The results suggest that cortisol AUCi in response to psychosocial stress may be linked to problems with energy balance in children, with some variation by age. Published by Elsevier Ltd.

  13. Adrenocortical responses to offspring-directed threats in two open-nesting birds.

    Butler, Luke K; Bisson, Isabelle-Anne; Hayden, Timothy J; Wikelski, Martin; Romero, L Michael

    2009-07-01

    Dependent young are often easy targets for predators, so for many parent vertebrates, responding to offspring-directed threats is a fundamental part of reproduction. We tested the parental adrenocortical response of the endangered black-capped vireo (Vireo atricapilla) and the common white-eyed vireo (V. griseus) to acute and chronic threats to their offspring. Like many open-nesting birds, our study species experience high offspring mortality. Parents responded behaviorally to a predator decoy or human 1-2m from their nests, but, in contrast to similar studies of cavity-nesting birds, neither these acute threats nor chronic offspring-directed threats altered plasma corticosterone concentrations of parents. Although parents in this study showed no corticosterone response to offspring-directed threats, they always increased corticosterone concentrations in response to capture. To explain these results, we propose that parents perceive their risk of nest-associated death differently depending on nest type, with cavity-nesting adults perceiving greater risk to themselves than open-nesters that can readily detect and escape from offspring-directed threats. Our results agree with previous studies suggesting that the hypothalamic-pituitary-adrenal axis, a major physiological mechanism for coping with threats to survival, probably plays no role in coping with threats to offspring when risks to parents and offspring are not correlated. We extend that paradigm by demonstrating that nest style may influence how adults perceive the correlation between offspring-directed and self-directed threats.

  14. Adrenocortical carcinoma: the dawn of a new era of genomic and molecular biology analysis.

    Armignacco, R; Cantini, G; Canu, L; Poli, G; Ercolino, T; Mannelli, M; Luconi, M

    2018-05-01

    Over the last decade, the development of novel and high penetrance genomic approaches to analyze biological samples has provided very new insights in the comprehension of the molecular biology and genetics of tumors. The use of these techniques, consisting of exome sequencing, transcriptome, miRNome, chromosome alteration, genome, and epigenome analysis, has also been successfully applied to adrenocortical carcinoma (ACC). In fact, the analysis of large cohorts of patients allowed the stratification of ACC with different patterns of molecular alterations, associated with different outcomes, thus providing a novel molecular classification of the malignancy to be associated with the classical pathological analysis. Improving our knowledge about ACC molecular features will result not only in a better diagnostic and prognostic accuracy, but also in the identification of more specific therapeutic targets for the development of more effective pharmacological anti-cancer approaches. In particular, the specific molecular alteration profiles identified in ACC may represent targetable events by the use of already developed or newly designed drugs enabling a better and more efficacious management of the ACC patient in the context of new frontiers of personalized precision medicine.

  15. Kindergarten stressors and cumulative adrenocortical activation: the "first straws" of allostatic load?

    Bush, Nicole R; Obradović, Jelena; Adler, Nancy; Boyce, W Thomas

    2011-11-01

    Using an ethnically diverse longitudinal sample of 338 kindergarten children, this study examined the effects of cumulative contextual stressors on children's developing hypothalamic-pituitary-adrenocortical (HPA) axis regulation as an early life indicator of allostatic load. Chronic HPA axis regulation was assessed using cumulative, multiday measures of cortisol in both the fall and spring seasons of the kindergarten year. Hierarchical linear regression analyses revealed that contextual stressors related to ethnic minority status, socioeconomic status, and family adversity each uniquely predicted children's daily HPA activity and that some of those associations were curvilinear in conformation. Results showed that the quadratic, U-shaped influences of family socioeconomic status and family adversity operate in different directions to predict children's HPA axis regulation. Results further suggested that these associations differ for White and ethnic minority children. In total, this study revealed that early childhood experiences contribute to shifts in one of the principal neurobiological systems thought to generate allostatic load, confirming the importance of early prevention and intervention efforts. Moreover, findings suggested that analyses of allostatic load and developmental theories accounting for its accrual would benefit from an inclusion of curvilinear associations in tested predictive models.

  16. Agonist-induced desensitization of adenylyl cyclase in Y1 adrenocortical tumor cells

    Olson, M.F.; Tsao, J.; Pon, D.J.; Schimmer, B.P.

    1991-01-01

    Y1 adrenocortical tumor cells (Y1DS) and Y1 mutants resistant to ACTH-induced desensitization of adenylyl cyclase (Y1DR) were transfected with a gene encoding the mouse beta 2-adrenergic receptor (beta 2-AR). Transfectants expressed beta 2-ARs that were able to stimulate adenylyl cyclase activity and steroid biosynthesis. These transfectants were used to explore the basis for the DR mutation in Y1 cells. The authors demonstrate that beta-adrenergic agonists desensitize the adenylyl cyclase system in transfected Y1DS cells whereas transfected Y1DR cells are resistant to desensitization by beta-adrenergic agonists. The fate of the beta 2-ARs during desensitization was evaluated by photoaffinity labelling with [125I]iodocyanopindolol diazerine. Desensitization of Y1DS transfectants was accompanied by a modest loss in receptor density that was insufficient to account for the complete loss of responsiveness to beta-adrenergic agonists. The extent of receptor loss induced by beta-adrenergic agonists in Y1DR transfectants exceeded that in the Y1DS transfectants indicating that the mutation which protects Y1DR cells from agonist-induced desensitization is prior to receptor down-regulation in the desensitization pathway. From these results we infer that ACTH and isoproterenol desensitize adenylyl cyclase by a common pathway and that receptor loss is not a major component of the desensitization process in these cells

  17. Adrenocortical carcinoma, an unusual extracolonic tumor associated with Lynch II syndrome.

    Medina-Arana, V; Delgado, L; González, L; Bravo, A; Díaz, H; Salido, E; Riverol, D; González-Aguilera, J J; Fernández-Peralta, A M

    2011-06-01

    Lynch syndrome (LS) is an autosomal dominant condition that predisposes to colorectal cancer and specific other tumors. Extracolonic tumors occur mainly in the endometrium, stomach, ovary, small intestine and urinary tract. The presence of rare tumors in patients belonging to families who have Lynch syndrome is always interesting, because the question arises whether these tumors should be considered as a coincidence or are related with the syndrome. In this last case, they are also the result of the defect in the mismatch repair system, opening the possibility of extending the tumor spectrum associated with the syndrome. Here we describe a patient from a Lynch syndrome family with a germline mutation c.2063T>G (p.M688R) in the MSH2 gene, who developed an adrenal cortical carcinoma, a tumor not usually associated with LS. We analyzed the adrenocortical tumour for microsatellite instability (MSI), LOH and the presence of the germline c.2063T>G (M688R) mutation. The adrenal cortical carcinoma showed the MSH2 mutation, loss of heterozygosity of the normal allele in the MSH2 gene and loss of immunohistochemical expression for MSH2 protein, but no microsatellite instability. Additionally, the adrenal cortical carcinoma did not harbour a TP53 mutation. The molecular study indicates that this adrenal cortical cancer is probably due to the mismatch repair defect.

  18. StAR Protein Stability in Y1 and Kin-8 Mouse Adrenocortical Cells.

    Clark, Barbara J; Hudson, Elizabeth A

    2015-03-04

    The steroidogenic acute regulatory protein (STAR) protein expression is required for cholesterol transport into mitochondria to initiate steroidogenesis in the adrenal and gonads. STAR is synthesized as a 37 kDa precursor protein which is targeted to the mitochondria and imported and processed to an intra-mitochondrial 30 kDa protein. Tropic hormone stimulation of the cAMP-dependent protein kinase A (PKA) signaling pathway is the major contributor to the transcriptional and post-transcriptional regulation of STAR synthesis. Many studies have focused on the mechanisms of cAMP-PKA mediated control of STAR synthesis while there are few reports on STAR degradation pathways. The objective of this study was to determine the effect of cAMP-PKA-dependent signaling on STAR protein stability. We have used the cAMP-PKA responsive Y1 mouse adrenocortical cells and the PKA-deficient Kin-8 cells to measure STAR phosphorylation and protein half-life. Western blot analysis and standard radiolabeled pulse-chase experiments were used to determine STAR phosphorylation status and protein half-life, respectively. Our data demonstrate that PKA-dependent STAR phosphorylation does not contribute to 30 kDa STAR protein stability in the mitochondria. We further show that inhibition of the 26S proteasome does not block precursor STAR phosphorylation or steroid production in Y1 cells. These data suggest STAR can maintain function and promote steroidogenesis under conditions of proteasome inhibition.

  19. Rosiglitazone Inhibits Adrenocortical Cancer Cell Proliferation by Interfering with the IGF-IR Intracellular Signaling

    Luconi Michaela

    2008-07-01

    Full Text Available Rosiglitazone (RGZ, a thiazolidinedione ligand of the peroxisome proliferator-activated receptor (PPAR-γ, has been recently described as possessing antitumoral properties. We investigated RGZ effect on cell proliferation in two cell line models (SW13 and H295R of human adrenocortical carcinoma (ACC and its interaction with the signaling pathways of the activated IGF-I receptor (IGF-IR. We demonstrate a high expression of IGF-IR in the two cell lines and in ACC. Cell proliferation is stimulated by IGF-I in a dose- and time-dependent manner and is inhibited by RGZ. The analysis of the main intracellular signaling pathways downstream of the activated IGF-IR, phosphatidyl inositol 3-kinase (PI3K-Akt, and extracellular signal-regulated kinase (ERK1/2 cascades reveals that RGZ rapidly interferes with the Akt and ERK1/2 phosphorylation/activation which mediates IGF-I stimulated proliferation. In conclusion, our results suggest that RGZ exerts an inhibitory effect on human ACC cell proliferation by interfering with the PI3K/Akt and ERK1/2 signaling pathways downstream of the activated IGF-IR.

  20. Determination by R/A of plasma cortisol levels as a parameter of adrenocortical function before and after radiotherapy of gynaecological genital carcinoma

    Freischem, C.W.

    1980-01-01

    rn 20 female patients with carcinoma of the genitals, day profiles of cortisol were established and ACTH stimulation tests carried out directly after radiotherapy and 6 months later. Plasma concentrations of cortisol were determined in a RIA as parameters of the adrenocortical function. The assumption of a change in adrenocortical activity after radiotherapy of gynaecological genital carcinoma could not be validated. Instead, there was a typical diurnal rhythm of plasma cortisol, with a peak in the early morning hours and a decrease until midnight. The same applies to the ACTH stimulation tests: In all cases, plasma cortisol levels were elevated after intravenous application of ACTH. This means that the 1976 findings of Samundzham and Butsan could not be proved. Since adrenal functions were absolutely normal in the observed cases, the adynamic clinical picture of patients after radiotherapy, which is rather infrequent, cannot be explained as being due to an impaired adrenocortical function. (orig./MG) [de

  1. Differential expression of microRNA-675, microRNA-139-3p and microRNA-335 in benign and malignant adrenocortical tumours

    Helwig, J; Bertram, S; Sheu, S Y; Suttorp, A C; Seggewiß, J; Willscher, E; Walz, M K; Worm, K; Schmid, K W

    2011-01-01

    Background For the clinical management of adrenocortical neoplasms it is crucial to correctly distinguish between benign and malignant tumours. Even histomorphologically based scoring systems do not allow precise separation in single lesions, thus novel parameters are desired which offer a more accurate differentiation. The tremendous potential of microRNAs (miRNAs) as diagnostic biomarkers in surgical pathology has recently been shown in a broad variety of tumours. Methods In order to elucidate the diagnostic impact of miRNA expression in adrenocortical neoplasms, a cohort of 20 adrenocortical specimens including normal adrenal tissue (n=4), adrenocortical adenomas (ACAs) (n=9), adrenocortical carcinomas (ACCs) (n=4) and metastases (n=3) was analysed using TaqMan low density arrays to identify specific miRNA profiles in order to distinguish between benign and malignant adrenocortical lesions. Results were validated in a validation cohort (n=16). Results Concerning the differential diagnosis of ACAs and ACCs, 159 out of 667 miRNAs were up- and 89 were down-regulated in ACAs. Using real-time PCR analysis of three of the most significantly expressed single key miRNAs allowed separation of ACAs from ACCs. ACCs exhibited significantly lower levels of miR-139-3p (up to 8.49-fold, p<0.001), miR-675 (up to 23.25-fold, p<0.001) and miR-335 (up to 5.25-fold, p<0.001). A validation cohort of 16 specimen with known Weiss score showed up-regulation of miR-335 and miR-675 in the majority of cases with probable malignant course, although overlapping values exist. Conclusion miRNA profiling of miR-675 and miR-335 helps in discriminating ACCs from ACAs. miRNA analysis may indicate malignant behaviour in cases with indeterminate malignant potential. PMID:21471143

  2. Assessment of survey radiography and comparison with x-ray computed tomography for detection of hyperfunctioning adrenocortical tumors in dogs

    Voorhout, G.; Stolp, R.; Rijnberk, A.; Waes, P.F.G.M. van

    1990-01-01

    Results of abdominal survey radiography and x-ray computed tomography (CT) were compared in 13 dogs with hyperadrenocorticism histologically attributed to adrenocortical tumors. X-ray computed tomography enabled accurate localization of the tumor in all 13 dogs. Apart from 2 poorly demarcated irregular-shaped and mineralized carcinomas, there were no differences between adenoma (n = 3) and carcinoma (n = 10) on CT images. In 1 dog, invasion of the caudal vena cava by the tumor was suggested on CT images and was confirmed during surgery. Suspicion of adhesions between tumors of the right adrenal gland and the caudal vena cava on the basis of CT images was confirmed during surgery in only 2 of 6 dogs. Survey radiography allowed accurate localization of the tumor in 7 dogs (4 on the right side and 3 on the left). In 6 of these dogs, the tumor was visible as a well-demarcated soft tissue mass and, in the other dog, as a poorly demarcated mineralized mass. The smallest tumor visualized on survey radiographs had a diameter of 20 mm on CT images. Six tumors with diameter less than or equal to 20 mm were not visualized on survey radiographs. In 1 of these dogs, a mineralized nodule was found in the left adrenal region, without evidence of a mass. In a considerable number of cases, survey radiography can provide presurgical localization of adrenocortical tumors in dogs with hyperadrenocorticism; CT is redundant in these instances. In the absence of positive radiographic findings, CT is valuable for localization of adrenocortical tumors

  3. The N-terminal neurotensin fragment, NT1-11, inhibits cortisol secretion by human adrenocortical cells.

    Sicard, Flavie; Contesse, Vincent; Lefebvre, Hervé; Ait-Ali, Djida; Gras, Marjorie; Cartier, Dorthe; Decker, Annick; Chartrel, Nicolas; Anouar, Youssef; Vaudry, Hubert; Delarue, Catherine

    2006-08-01

    Neurotensin (NT) modulates corticosteroid secretion from the mammalian adrenal gland. The objective of this study was to investigate the possible involvement of NT in the control of cortisol secretion in the human adrenal gland. In vitro studies were conducted on cultured human adrenocortical cells. This study was conducted in a university research laboratory. Adrenal explants from patients undergoing expanded nephrectomy for kidney cancer were studied. Cortisol secretion from cultured adrenocortical cells was measured. NT1-11, the N-terminal fragment of NT, dose-dependently inhibited basal and ACTH-stimulated cortisol production by human adrenocortical cells in primary culture. In contrast, NT had no influence on cortisol output at concentrations up to 10(-6) m. HPLC and RT-PCR analyses failed to detect any significant amounts of NT and NT mRNA, respectively, in adrenal extracts. Molecular and pharmacological studies were performed to determine the type of NT receptor involved in the corticostatic effect of NT1-11. RT-PCR analysis revealed the expression of NT receptor type (NTR) 3 mRNA but not NTR1 and NTR2 mRNAs in the human adrenal tissue. However, the pharmacological profile of the adrenal NT1-11 receptor was different from that of NTR3, indicating that this receptor type is not involved in the action of NT1-11 on corticosteroidogenesis. Our results indicate that NT1-11 may act as an endocrine factor to inhibit cortisol secretion through activation of a receptor distinct from the classical NTR1, NTR2, and NTR3.

  4. The Contingency of Cocaine Administration Accounts for Structural and Functional Medial Prefrontal Deficits and Increased Adrenocortical Activation

    Anderson, Rachel M.; Cosme, Caitlin V.; Glanz, Ryan M.; Miller, Mary C.; Romig-Martin, Sara A.; LaLumiere, Ryan T.

    2015-01-01

    The prelimbic region (PL) of the medial prefrontal cortex (mPFC) is implicated in the relapse of drug-seeking behavior. Optimal mPFC functioning relies on synaptic connections involving dendritic spines in pyramidal neurons, whereas prefrontal dysfunction resulting from elevated glucocorticoids, stress, aging, and mental illness are each linked to decreased apical dendritic branching and spine density in pyramidal neurons in these cortical fields. The fact that cocaine use induces activation of the stress-responsive hypothalamo-pituitary-adrenal axis raises the possibility that cocaine-related impairments in mPFC functioning may be manifested by similar changes in neuronal architecture in mPFC. Nevertheless, previous studies have generally identified increases, rather than decreases, in structural plasticity in mPFC after cocaine self-administration. Here, we use 3D imaging and analysis of dendritic spine morphometry to show that chronic cocaine self-administration leads to mild decreases of apical dendritic branching, prominent dendritic spine attrition in PL pyramidal neurons, and working memory deficits. Importantly, these impairments were largely accounted for in groups of rats that self-administered cocaine compared with yoked-cocaine- and saline-matched counterparts. Follow-up experiments failed to demonstrate any effects of either experimenter-administered cocaine or food self-administration on structural alterations in PL neurons. Finally, we verified that the cocaine self-administration group was distinguished by more protracted increases in adrenocortical activity compared with yoked-cocaine- and saline-matched controls. These studies suggest a mechanism whereby increased adrenocortical activity resulting from chronic cocaine self-administration may contribute to regressive prefrontal structural and functional plasticity. SIGNIFICANCE STATEMENT Stress, aging, and mental illness are each linked to decreased prefrontal plasticity. Here, we show that chronic

  5. Synthetic high-density lipoprotein nanodisks for targeted withalongolide delivery to adrenocortical carcinoma

    Kuai R

    2017-09-01

    Full Text Available Rui Kuai,1,2,* Chitra Subramanian,3,* Peter T White,3,* Barbara N Timmermann,4 James J Moon,1,2,5 Mark S Cohen,3,6 Anna Schwendeman1,2 1Department of Pharmaceutical Sciences, College of Pharmacy, 2Biointerfaces Institute, University of Michigan, 3Department of Surgery, University of Michigan, Ann Arbor, MI, 4Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, 5Department of Biomedical Engineering, 6Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA *These authors contributed equally to this work Abstract: Adrenocortical carcinoma (ACC is a rare endocrine malignancy and has a 5-year survival rate of <35%. ACC cells require cholesterol for steroid hormone production, and this requirement is met via expression on the cell surface of a high level of SRB1, responsible for the uptake of high-density lipoproteins (HDLs, which carry and transport cholesterol in vivo. Here, we describe how this natural lipid carrier function of SRB1 can be utilized to improve the tumor-targeted delivery of a novel natural product derivative – withalongolide A 4,19,27-triacetate (WGA-TA – which has shown potent antitumor efficacy, but poor aqueous solubility. Our strategy was to use synthetic HDL (sHDL nanodisks, which are effective in tumor-targeted delivery due to their smallness, long circulation half-life, documented safety, and ability to bind to SRB1. In this study, we prepared sHDL nanodisks using an optimized phospholipid composition combined with ApoA1 mimetic peptide (22A, which has previously been tested in clinical trials, to load WGA-TA. Following optimization, WGA-TA nanodisks showed drug encapsulation efficiency of 78%, a narrow particle size distribution (9.81±0.41 nm, discoid shape, and sustained drug release in phosphate buffered saline. WGA-TA-sHDL nanodisks exhibited higher cytotoxicity in the ACC cell line H295R half maximal inhibitory concentration ([IC50] 0.26±0.045 µM than free WGA-TA (IC50 0.492±0

  6. Molecular Profiling of Refractory Adrenocortical Cancers and Predictive Biomarkers to Therapy

    Sherri Z. Millis

    2015-01-01

    Full Text Available Purpose Current first-line chemotherapy for patients with metastatic adrenocortical cancer (ACC includes doxorubicin, etoposide, cisplatin, and mitotane with a reported response rate of only 23.2%. New therapeutic leads for patients with refractory tumors are needed; there is no standard second-line treatment. Methods Samples from 135 ACC tumors were analyzed by immunohistochemistry, in situ hybridization (FISH or CISH, and/or gene sequencing at a single commercial reference laboratory (Caris Life Sciences to identify markers associated with drug sensitivity and resistance. Results Overexpression of proteins related to demonstrated chemotherapy sensitivity or resistance included topoisomerase 1, progesterone receptor, and topoisomerase 2-alpha in 46%, 63%, and 42% of cases, respectively. Loss of excision repair cross-complementary group 1 (ERCC1, phosophatase and tensin homolog, O(6-methylguanine-methyltransferase, and ribonucleotide reductase M1 (RRM1 was identified in 56%, 59%, 71%, and 58% of cases, respectively. Other aberrations included overexpression of programmed death-ligand 1 or programmed cell death protein 1 tumor-infiltrating lymphocytes in >40% of cases. In all, 35% of cases had a mutation in the canonical Wnt signaling pathway (either CTNNB1 or APC and 48% had a mutation in TP53. No other genomic alterations were identified. Conclusion Biomarker alterations in ACC may be used to direct therapies, including recommendations for and potential resistance of some patients to traditional chemotherapies, which may explain the low response rate in the unselected population. Limited outcomes data support the use of mitotane and platinum therapies for patients with low levels of the proteins RRM1 and ERCC1.

  7. Effects of Insufficient Sleep on Pituitary-Adrenocortical Response to CRH Stimulation in Healthy Men.

    Guyon, Aurore; Morselli, Lisa L; Balbo, Marcella L; Tasali, Esra; Leproult, Rachel; L'Hermite-Balériaux, Mireille; Van Cauter, Eve; Spiegel, Karine

    2017-06-01

    Severe sleep restriction results in elevated evening cortisol levels. We examined whether this relative hypercortisolism is associated with alterations in the pituitary-adrenocortical response to evening corticotropin-releasing hormone (CRH) stimulation. Eleven subjects participated in 2 sessions (2 nights of 10 hours vs. 4 hours in bed) in randomized order. Sleep was polygraphically recorded. After the second night of each session, blood was sampled at 20-minute intervals from 09:00 to 24:00 for adrenocorticotropic hormone (ACTH) and cortisol measurements, and perceived stress was assessed hourly. Ovine CRH was injected at 18:00 (1 µg/kg body weight). Prior to CRH injection, baseline ACTH, but not cortisol, levels were elevated after sleep restriction. Relative to the well-rested condition, sleep restriction resulted in a 27% decrease in overall ACTH response to CRH (estimated by the incremental area under the curve from 18:00 to 24:00; p = .002) while the cortisol response was decreased by 21% (p = .083). Further, the magnitude of these decreases was correlated with the individual amount of sleep loss (ACTH: rSp = -0.65, p = .032; cortisol: rSp = -0.71, p = .015). The acute post-CRH increment of cortisol was reduced (p = .002) without changes in ACTH reactivity, suggesting decreased adrenal sensitivity. The rate of decline from peak post-injection levels was reduced for cortisol (p = .032), but not for ACTH. Scores of perceived stress were unaffected by CRH injection and were low and similar under both sleep conditions. Sleep restriction is associated with a reduction of the overall ACTH and cortisol responses to evening CRH stimulation, and a reduced reactivity and slower recovery of the cortisol response. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  8. Novelty-induced emotional arousal modulates cannabinoid effects on recognition memory and adrenocortical activity.

    Campolongo, Patrizia; Morena, Maria; Scaccianoce, Sergio; Trezza, Viviana; Chiarotti, Flavia; Schelling, Gustav; Cuomo, Vincenzo; Roozendaal, Benno

    2013-06-01

    Although it is well established that cannabinoid drugs can influence cognitive performance, the findings-describing both enhancing and impairing effects-have been ambiguous. Here, we investigated the effects of posttraining systemic administration of the synthetic cannabinoid agonist WIN55,212-2 (0.1, 0.3, or 1.0 mg/kg) on short- and long-term retention of object recognition memory under two conditions that differed in their training-associated arousal level. In male Sprague-Dawley rats that were not previously habituated to the experimental context, WIN55,212-2 administered immediately after a 3-min training trial, biphasically impaired retention performance at a 1-h interval. In contrast, WIN55,212-2 enhanced 1-h retention of rats that had received extensive prior habituation to the experimental context. Interestingly, immediate posttraining administration of WIN55,212-2 to non-habituated rats, in doses that impaired 1-h retention, enhanced object recognition performance at a 24-h interval. Posttraining WIN55,212-2 administration to habituated rats did not significantly affect 24-h retention. In light of intimate interactions between cannabinoids and the hypothalamic-pituitary-adrenal axis, we further investigated whether cannabinoid administration might differently influence training-induced glucocorticoid activity in rats in these two habituation conditions. WIN55,212-2 administered after object recognition training elevated plasma corticosterone levels in non-habituated rats whereas it decreased corticosterone levels in habituated rats. Most importantly, following pretreatment with the corticosterone-synthesis inhibitor metyrapone, WIN55,212-2 effects on 1- and 24-h retention of non-habituated rats became similar to those seen in the low-aroused habituated animals, indicating that cannabinoid-induced regulation of adrenocortical activity contributes to the environmentally sensitive effects of systemically administered cannabinoids on short- and long

  9. Salivary cortisol as an indicator of adrenocortical function in healthy infants, using massage therapy

    Monalisa de Cássia Fogaça

    Full Text Available CONTEXT AND OBJECTIVE: The evaluation of adrenocortical function with the use of therapeutic massage has been little studied in Brazil. The purpose of this study was to evaluate the salivary cortisol levels before and after Shantala massage therapy on healthy infants. DESIGN AND SETTING: Prospective case series, in a public nursery, in São Paulo. METHODS: Saliva was obtained from 11 infants at the times of 8:00-9:00 a.m. and 4:00-5:00 p.m. in a nursery and 9:00-10:00 p.m. at home. They received a 15-minute therapeutic massage on two consecutive days, and saliva was collected before and after the massage. The procedure was repeated after a one-week interval. Cortisol values (intra-assay < 5%; inter-assay < 10% at different times of the day were compared by ANOVA. RESULTS: The mean cortisol values (nmol/l ± SD on the first day were: morning (M = 14.1 ± 5.7, afternoon (A = 8.3 ± 2.7, night (N = 3.3 ± 1.1; after two consecutive days of therapeutic massage: M = 22.3 ± 13.5, A = 13.4 ± 6.0, N = 5.8 ± 3.5; after a one-week interval: M = 15.8 ± 7.7, A = 14.3 ± 7.7, N = 3.4 ± 2.0. CONCLUSION: There was a modification in the salivary cortisol values following massage, thus reflecting possible adaptation of the hypothalamic-pituitary-adrenal axis.

  10. Adrenocortical and adrenomedullary homologs in eight species of adult and developing teleosts: morphology, histology, and immunohistochemistry.

    Grassi Milano, E; Basari, F; Chimenti, C

    1997-12-01

    Morphology, histology, and immunohistochemistry of the adrenocortical and adrenomedullary homologs (adrenal glands) of the following developing and adult teleosts were examined: Salmoniformes-Oncorhynchus mykiss (rainbow trout), Salmo trutta fario (brown trout), Coregonus lavaretus (white fish); Cyprinodontiformes-Gambusia affinis (mosquito fish). Perciformes-Dicentrarchus labrax (sea bass), Sparus aurata (sea bream), Diplodus sargus (white bream), Oblada melanura (saddled bream). The anatomical relationships of the gland with the renal system and venous vessels were also noted. In adults of all species steroidogenic and catecholaminergic chromaffin cells were found in the head kidney, which is pronephric in origin and subsequently transformed into a hematopoietic lymphatic organ. In Perciformes, chromaffin cells are distributed around the anterior and posterior cardinal veins and ducts of Cuvier; in Salmoniformes, around the posterior cardinal veins and in the hematopoietic tissue; and in G. affinis, around the ducts of Cuvier and posterior cardinal veins, while a few are visible also around the sinus venosus. In Perciformes and Salmoniformes, numerous chromaffin cells are also present in the posterior kidney, derived from the opisthonephros, in contact with the caudal vein. Steroidogenic cells are always confined to the head kidney. During development chromaffin and steroidogenic cells appear early after hatching in the pronephric kidney, at the level of the ducts of Cuvier and of the cephalic part of the posterior cardinal veins. Later, chromaffin cells in Perciformes reach the anterior cardinal veins, and subsequently, in both Perciformes and Salmoniformes, they reach the developing posterior kidney. Their localization along the posterior kidney is still in progress about 4 months after hatching and is completed about a year after hatching. These findings support the concept that the structure of the adrenal gland in teleosts is intermediate between that of the

  11. Role of changes in functional status of hypothalamic-pituitary-adrenocortical axis in immunoenhancement after low dose radiation

    Liu Shuzheng; Zhao Yong; Han Zhenbo

    1994-01-01

    Whole-body irradiation (WBI) of mice with 75 mGy X-rays caused increase in 5-hydroxytryptamine (5HT) content of hypothalamus and decrease in serum adrenocorticotropic hormone (ACTH) and corticosterone (CS) level, accompanied with potentiation of immune functions, expressed as increased spontaneous incorporation of 3 H-TdR into thymocytes, augmented proliferative reaction of the splenocytes to Con A and increased production of interleukin-2 by the splenocytes. After intra hypothalamic injection of 5HT there occurred a lowering of serum ACTH level and enhancement of immune reactivity of the splenic and thymic lymphocytes. It is assumed that low dose radiation could influence the central 5-hydroxytryptaminergic neurons causing increase in hypothalamic 5HT content and this, in turn, decreases pituitary secretion of ACTH with a down-regulation of the adrenocortical function. This would partially release the tonic suppression normally exerted on the immune organs by the hypothalamic-pituitary-adrenocortical axis, thus leading to potentiation of immune functions. These neuroendocrine changes should be considered as an important factor in the analysis of the mechanism of immunoenhancement after WBI with low doses

  12. The effect of a maternal history of childhood abuse on adrenocortical attunement in mothers and their toddlers.

    Fuchs, Anna; Moehler, Eva; Resch, Franz; Kaess, Michael

    2017-07-01

    We investigated circadian mother-child adrenocortical attunement in the context of a maternal history of childhood abuse (HoA). Mothers were screened after birth using the Childhood Trauma Questionnaire. Women reporting moderate or severe abuse formed the HoA group (n = 37; HoAG) and were compared with a non-maltreated comparison group (n = 45; CG). Three years later, cortisol awakening response (CAR) and diurnal slope (DSL) were assessed. Mother-child interaction was coded using the Emotional Availability Scales at 12 months of age. For the CAR, we found adrenocortical attunement only in the HoAG (2-way interaction: p = .004), particularly if mothers scored low on structuring (3-way interaction: p = .042) and children scored low on responsiveness (3-way interaction: p = .044). DSL-attunement was dependent on maternal sensitivity (3-way interaction: p = .012) and child involvement (3-way interaction: p = .012). In the context of a maternal HoA, it seems possible for mother-child-dyads to show less optimal interactional quality but be stronger attuned to each other biologically. © 2017 Wiley Periodicals, Inc.

  13. Oncocytic adrenocortical neoplasms--a clinicopathologic study of 13 new cases emphasizing the importance of their recognition.

    Wong, Daniel D; Spagnolo, Dominic V; Bisceglia, Michele; Havlat, Marek; McCallum, Dugald; Platten, Michael A

    2011-04-01

    Oncocytic adrenocortical neoplasms (OANs) are a rare but important subtype of adrenal tumors with unique clinical and morphological features. We present 13 previously unpublished cases, of which 3 were classified as benign, 2 as having borderline malignant potential, and 8 as malignant according to the Lin-Weiss-Bisceglia criteria. Seven tumors (54%) showed evidence of endocrine activity. All were composed of more than 90% oncocytes confirmed immunohistochemically using the antimitochondrial antibody mES-13 and ultrastructurally in 4 cases. Small oncocytes were a frequent finding that challenges the conventional notion of oncocytes as necessarily having abundant cytoplasm. Most cases were immunoreactive for vimentin, synaptophysin, inhibin-α, melan A, and calretinin, the latter being a novel finding in this group of neoplasms. Cytokeratin positivity with AE1/AE3 and CAM5.2 was variable. The literature was comprehensively reviewed to identify all cases of OANs reported to date. Hormone production is not as uncommon as previously believed, occurring in 30%. The Lin-Weiss-Bisceglia criteria were retrospectively applied to all published cases with sufficient information and were shown to effectively separate tumors according to their future risk of recurrence and survival using Kaplan-Meier survival curves (log-rank test, P interval = 27.5-88.5 months), providing the first preliminary evidence that the prognosis of malignant OANs is likely to be more favorable than conventional adrenocortical carcinomas, in which the reported median survival is between 14 and 32 months. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic-Pituitary-Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo

    Kertes, Darlene A.; Kamin, Hayley S.; Hughes, David A.; Rodney, Nicole C.; Bhatt, Samarth; Mulligan, Connie J.

    2016-01-01

    Exposure to stress early in life permanently shapes activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight (BW), and HPA axis functioning. Little is known about the biological mechanisms by which…

  15. The Role of the Pituitary-Adrenocortical Axis System in the Regulation of Secretion of Digestive Glands of Wrestlers during Sports and Postsports Ontogenesis

    Panov, Sergei F.; Panova, Irina P.; Volunskaya, Elena V.; Chebotarev, Andrei V.

    2016-01-01

    According to many researchers its necessary to research a hormonal profile in order to determine mechanisms of regulation of functions of the digestive conveyor during sports activities. In the paper the results of the carried out research on studying of a role of pituitary-adrenocortical axis system of adaptive reactions in activities of the…

  16. {sup 18}F-Labelled metomidate analogues as adrenocortical imaging agents

    Erlandsson, Maria; Karimi, Farhad [Department of Biochemistry and Organic Chemistry, Uppsala University, Box 576, S-751 23 Uppsala (Sweden); Lindhe, Orjan [Uppsala Imanet, GE Healthcare, Box 967, S-751 09 Uppsala (Sweden); Langstroem, Bengt [Department of Biochemistry and Organic Chemistry, Uppsala University, Box 576, S-751 23 Uppsala (Sweden)], E-mail: bengt.langstrom@biorg.uu.se

    2009-05-15

    Introduction: Two- and one-step syntheses of {sup 18}F-labelled analogues of metomidate, such as 2-[{sup 18}F]fluoroethyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (1), 2-[{sup 18}F]fluoroethyl 1-[(1R)-1-(4-chlorophenyl)ethyl]-1H-imidazole-5-carboxylate (2), 2-[{sup 18}F]fluoroethyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (3), 3-[{sup 18}F]fluoropropyl 1-[(1R)-1-(4-bromophenyl)ethyl]-1H-imidazole-5-carboxylate (4) and 3-[{sup 18}F]fluoropropyl 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylate (5) are presented. Methods: Analogues 1-5 were prepared by a two-step reaction sequence that started with the synthesis of either 2-[{sup 18}F]fluoroethyl 4-methylbenzenesulfonate or 3-[{sup 18}F]fluoropropyl 4-methylbenzenesulfonate. These were used as {sup 18}F-alkylating agents in the second step, in which they reacted with the ammonium salt of a 1-[(1R)-1-phenylethyl]-1H-imidazole-5-carboxylic acid. One-step-labelling syntheses of 1, 2 and 5 were also explored. Analogues 1-4 were biologically validated by frozen-section autoradiography and organ distribution. Metabolite analysis was performed for 2 and 3. Results: The radiochemical yield of the two-step synthesis was in the range of 10-29% and that of the one-step synthesis was 25-37%. Using microwave irradiation in the one-step synthesis of 1 and 2 increased the radiochemical yield to 46{+-}3% and 79{+-}30%, respectively. Conclusion: Both the frozen-section autoradiography and organ distribution results indicated that analogue 2 has a potential as an adrenocortical imaging agent, having the highest degree of specific adrenal binding and best ratio of adrenal to organ uptake among the compounds studied.

  17. Association of mitotane with chylomicrons and serum lipoproteins: practical implications for treatment of adrenocortical carcinoma.

    Kroiss, Matthias; Plonné, Dietmar; Kendl, Sabine; Schirmer, Diana; Ronchi, Cristina L; Schirbel, Andreas; Zink, Martina; Lapa, Constantin; Klinker, Hartwig; Fassnacht, Martin; Heinz, Werner; Sbiera, Silviu

    2016-03-01

    Oral mitotane (o,p'-DDD) is a cornerstone of medical treatment for adrenocortical carcinoma (ACC). Serum mitotane concentrations >14  mg/l are targeted for improved efficacy but not achieved in about half of patients. Here we aimed at a better understanding of intestinal absorption and lipoprotein association of mitotane and metabolites o,p'-dichlorodiphenylacetic acid (o,p'-DDA) and o,p'-dichlorodiphenyldichloroethane (o,p'-DDE). Lipoproteins were isolated by ultracentrifugation from the chyle of a 29-year-old patient and serum from additional 14 ACC patients treated with mitotane. HPLC was applied for quantification of mitotane and metabolites. We assessed NCI-H295 cell viability, cortisol production, and expression of endoplasmic reticulum (ER) stress marker genes to study the functional consequences of mitotane binding to lipoproteins. Chyle of the index patient contained 197  mg/ml mitotane, 53  mg/ml o,p'-DDA, and 51  mg/l o,p'-DDE. Of the total mitotane in serum, lipoprotein fractions contained 21.7±21.4% (VLDL), 1.9±0.8% (IDL), 8.9±5.5% (LDL1), 18.9±9.6% (LDL2), 10.1±4.0% (LDL3), and 26.3±13.0% (HDL2). Only 12.3±5.5% were in the lipoprotein-depleted fraction. Mitotane content of lipoproteins directly correlated with their triglyceride and cholesterol content. O,p'-DDE was similarly distributed, but 87.9±4.2% of o,p'-DDA found in the HDL2 and lipoprotein-depleted fractions. Binding of mitotane to human lipoproteins blunted its anti-proliferative and anti-hormonal effects on NCI-H295 cells and reduced ER stress marker gene expression. Mitotane absorption involves chylomicron binding. High concentrations of o,p'-DDA and o,p'-DDE in chyle suggest intestinal mitotane metabolism. In serum, the majority of mitotane is bound to lipoproteins. In vitro, lipoprotein binding inhibits activity of mitotane suggesting that lipoprotein-free mitotane is the therapeutically active fraction. © 2016 European Society of Endocrinology.

  18. Cyclic estrous-like behavior in a spayed cat associated with excessive sex-hormone production by an adrenocortical carcinoma.

    Meler, Erika N; Scott-Moncrieff, J Catharine; Peter, Augustine T; Bennett, Sara; Ramos-Vara, Jose; Salisbury, S Kathleen; Naughton, James F

    2011-06-01

    A 15-year-old, spayed female domestic shorthair cat was evaluated for 1-year duration of cyclic intermittent estrous behavior. Diagnostic testing performed before referral, including baseline progesterone concentration, human chorionic gonadotropin (hCG) hormone stimulation test and surgical exploratory laparotomy, had remained inconclusive for a remnant ovary. Evaluation of sex hormones before and after adrenocorticotropic hormone (ACTH) administration revealed increased basal concentrations of androstenedione, estradiol, progesterone, and 17α-hydroxyprogesterone and normal ACTH-stimulated hormone concentrations. Enlargement of the right adrenal gland was identified by abdominal ultrasound. The cat underwent an adrenalectomy and histopathology of the excised adrenal gland was consistent with an adrenocortical carcinoma. Clinical signs resolved immediately following surgery, and most hormone concentrations declined to within or below the reference interval (RI) by 2 months after surgery. Copyright © 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

  19. Adrenal incidentalomas showing unilateral concordant visualization by adrenocortical scintigraphy. Comparison with adenomas in Cushing's syndrome

    Tani, Atsushi; Nakajo, Masayuki; Tsuchimochi, Shinsaku; Nakabeppu, Yoshiaki; Umanodan, Tomokazu [Kagoshima Univ. (Japan). Faculty of Medicine

    2000-06-01

    An adrenocortical adenoma causing Cushing's syndrome (Cushing's adenoma) produces a unilateral concordant visualization (UCV) imaging pattern in which the adenoma is only visualized on radioiodocholesterol adrenocortical scintigraphy. But because this imaging pattern is also noted in some patients with adrenal incidentalomas, we examined whether the UCV-incidentaloma was essentially identical with Cushing's adenoma and would develop Cushing's syndrome. The subjects were 9 patients with UCV-incidentalomas (mean size, 30 mm; range, 20-45 mm) and 6 patients with Cushing's adenomas (mean size, 28 mm; range, 25-35 mm). Endocrinological evaluations showed several abnormalities including blunted diurnal rhythm of plasma cortisol within the normal range, low plasma ACTH and/or high 24-hr urinary 17-OHCS levels in 8 of 9 patients with UCV-incidentalomas, but these abnormalities did not meet the diagnostic criteria of Cushing's syndrome. Adrenal uptake of the tracer in the patients with UCV-incidentalomas was not statistically different from that in the patients with Cushing's adenomas and had no relationship with hormonal values in either patient group. Tumor size on CT correlated with the levels of 24-hr urinary 17-OHCS (r=0.75, p=0.02) and plasma cortisol at 7:00 (r=0.82, p=0.007) in the patients with UCV-incidentalomas, but not in the patients with Cushing's adenomas. Although 3 UCV-incidentalomas increased slightly in size, none of 9 patients with UCV-incidentalomas has developed Cushing's syndrome for 4 to 52 months. These results suggest that the UCV-incidentaloma may be essentially different from the Cushing's adenoma and unlikely to develop Cushing's syndrome. (author)

  20. Autoimmune Addison's disease - An update on pathogenesis.

    Hellesen, Alexander; Bratland, Eirik; Husebye, Eystein S

    2018-06-01

    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.

  1. CYP2W1 is highly expressed in adrenal glands and is positively associated with the response to mitotane in adrenocortical carcinoma.

    Cristina L Ronchi

    Full Text Available Adrenocortical tumors comprise frequent adenomas (ACA and rare carcinomas (ACC. Human cytochrome P450 2W1 (CYP2W1 is highly expressed in some cancers holding the potential to activate certain drugs into tumor cytotoxins.To investigate the CYP2W1 expression in adrenal samples and its relationship with clinical outcome in ACC.CYP2W1 expression was investigated by qRT-PCR in 13 normal adrenal glands, 32 ACA, 25 ACC, and 9 different non-adrenal normal tissue samples and by immunohistochemistry in 352 specimens (23 normal adrenal glands, 33 ACA, 239 ACC, 67 non-adrenal normal or neoplastic samples.CYP2W1 mRNA expression was absent/low in normal non-adrenal tissues, but high in normal and neoplastic adrenal glands (all P<0.01 vs non-adrenal normal tissues. Accordingly, CYP2W1 immunoreactivity was absent/low (H-score 0-1 in 72% of non-adrenal normal tissues, but high (H-score 2-3 in 44% of non-adrenal cancers, in 65% of normal adrenal glands, in 62% of ACAs and in 50% of ACCs (all P<0.001 vs non-adrenal normal tissues, being significantly increased in steroid-secreting compared to non-secreting tumors. In ACC patients treated with mitotane only, high CYP2W1 immunoreactivity adjusted for ENSAT stage was associated with longer overall survival and time to progression (P<0.05 and P<0.01, respectively, and with a better response to therapy both as palliative (response/stable disease in 42% vs 6%, P<0.01 or adjuvant option (absence of disease recurrence in 69% vs 45%, P<0.01.CYP2W1 is highly expressed in both normal and neoplastic adrenal glands making it a promising tool for targeted therapy in ACC. Furthermore, CYP2W1 may represent a new predictive marker for the response to mitotane treatment.

  2. Comparisons among serum, egg albumin and yolk concentrations of corticosterone as biomarkers of basal and stimulated adrenocortical activity of laying hens.

    Cook, N J; Renema, R; Wilkinson, C; Schaefer, A L

    2009-09-01

    1. Serial blood samples from individual birds were analysed for corticosterone concentrations under basal and stimulated conditions, and matched to eggs from the same birds for comparison to albumin and yolk concentrations of corticosterone. 2. Serum corticosterone exhibited increases in response to stimulation by ACTH and Handling stress. There were no significant increases in egg albumin or yolk concentrations of corticosterone following stimulation. 3. Several significant correlations were observed between the mean and area under the curve (AUC) measurements of serum corticosterone concentrations with albumin and yolk corticosterone concentrations in eggs laid from 1 to 2 d later. 4. The results demonstrated a relationship between endogenous concentrations of serum corticosterone that reflected daily adrenocortical output with albumin and yolk corticosterone concentrations in eggs laid the following day. 5. The results do not support the concept of albumin and yolk concentrations of corticosterone as biomarkers of acute adrenocortical responses to stimulation.

  3. Autoimmune Addison's disease.

    Napier, Catherine; Pearce, Simon H S

    2012-12-01

    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.

  4. Assessment of the role of transcript for GATA-4 as a marker of unfavorable outcome in human adrenocortical neoplasms

    Martin Regina M

    2004-07-01

    Full Text Available Abstract Background Malignant neoplasia of the adrenal cortex is usually associated with very poor prognosis. When adrenocortical neoplasms are diagnosed in the early stages, distinction between carcinoma and adenoma can be very difficult to accomplish, since there is yet no reliable marker to predict tumor recurrence or dissemination. GATA transcription factors play an essential role in the developmental control of cell fate, cell proliferation and differentiation, organ morphogenesis, and tissue-specific gene expression. Normal mouse adrenal cortex expresses GATA-6 while its malignant counterpart only expresses GATA-4. The goal of the present study was to assess whether this reciprocal change in the expression of GATA factors might be relevant for predicting the prognosis of human adrenocortical neoplasms. Since human adrenal cortices express luteinizing hormone (LH/hCG receptor and the gonadotropins are known to up-regulate GATA-4 in gonadal tumor cell lines, we also studied the expression of LH/hCG receptor. Methods We conducted a study on 13 non-metastasizing (NM and 10 metastasizing/recurrent (MR tumors obtained from a group of twenty-two adult and pediatric patients. The expression of GATA-4, GATA-6, and LH/hCG receptor (LHR in normal and tumoral human adrenal cortices was analysed using reverse transcriptase-polymerase chain reaction (RT-PCR complemented by dot blot hybridization. Results Messenger RNA for GATA-6 was detected in normal adrenal tissue, as well as in the totality of NM and MR tumors. GATA-4, by its turn, was detected in normal adrenal tissue, in 11 out of 13 NM tumors, and in 9 of the 10 MR tumors, with larger amounts of mRNA found among those presenting aggressive clinical behavior. Transcripts for LH receptor were observed both in normal tissue and neoplasms. A more intense LHR transcript accumulation was observed on those tumors with better clinical outcome. Conclusion Our data suggest that the expression of GATA-6 in

  5. Masked volume wise principal component analysis of small adrenocortical tumours in dynamic [11C]-metomidate positron emission tomography

    Razifar, Pasha; Hennings, Joakim; Monazzam, Azita; Hellman, Per; Långström, Bengt; Sundin, Anders

    2009-01-01

    In previous clinical Positron Emission Tomography (PET) studies novel approaches for application of Principal Component Analysis (PCA) on dynamic PET images such as Masked Volume Wise PCA (MVW-PCA) have been introduced. MVW-PCA was shown to be a feasible multivariate analysis technique, which, without modeling assumptions, could extract and separate organs and tissues with different kinetic behaviors into different principal components (MVW-PCs) and improve the image quality. In this study, MVW-PCA was applied to 14 dynamic 11C-metomidate-PET (MTO-PET) examinations of 7 patients with small adrenocortical tumours. MTO-PET was performed before and 3 days after starting per oral cortisone treatment. The whole dataset, reconstructed by filtered back projection (FBP) 0–45 minutes after the tracer injection, was used to study the tracer pharmacokinetics. Early, intermediate and late pharmacokinetic phases could be isolated in this manner. The MVW-PC1 images correlated well to the conventionally summed image data (15–45 minutes) but the image noise in the former was considerably lower. PET measurements performed by defining 'hot spot' regions of interest (ROIs) comprising 4 contiguous pixels with the highest radioactivity concentration showed a trend towards higher SUVs when the ROIs were outlined in the MVW-PC1 component than in the summed images. Time activity curves derived from '50% cut-off' ROIs based on an isocontour function whereby the pixels with SUVs between 50 to 100% of the highest radioactivity concentration were delineated, showed a significant decrease of the SUVs in normal adrenal glands and in adrenocortical adenomas after cortisone treatment. In addition to the clear decrease in image noise and the improved contrast between different structures with MVW-PCA, the results indicate that the definition of ROIs may be more accurate and precise in MVW-PC1 images than in conventional summed images. This might improve the precision of PET

  6. What is the optimal bone-preserving strategy for patients with Addison's disease?

    Lee, Paul; Greenfield, Jerry R

    2015-08-01

    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.

  7. Adrenocortical and Adipose Responses to High-Altitude-Induced, Long-Term Hypoxia in the Ovine Fetus

    Dean A. Myers

    2012-01-01

    Full Text Available By late gestation, the maturing hypothalamo-pituitary-adrenal (HPA axis aids the fetus in responding to stress. Hypoxia represents a significant threat to the fetus accompanying situations such as preeclampsia, smoking, high altitude, and preterm labor. We developed a model of high-altitude (3,820 m, long-term hypoxia (LTH in pregnant sheep. We describe the impact of LTH on the fetal HPA axis at the level of the hypothalamic paraventricular nucleus (PVN, anterior pituitary corticotrope, and adrenal cortex. At the PVN and anterior pituitary, the responses to LTH are consistent with hypoxia being a potent activator of the HPA axis and potentially maladaptive, while the adrenocortical response to LTH appears to be primarily adaptive. We discuss mechanisms involved in the delicate balance between these seemingly opposing responses that preserve the normal ontogenic rise in fetal plasma cortisol essential for organ maturation and in this species, birth. Further, we examine the response to, and ramifications of, an acute secondary stressor in the LTH fetus. We provide an integrative model on the potential role of adipose in modulating these responses to LTH. Integration of these adaptive responses to LTH plays a key role in promoting normal fetal growth and development under conditions of a chronic stress.

  8. Adrenocortical Production Is Associated with Higher Levels of Luteinizing Hormone in Nonobese Women with Polycystic Ovary Syndrome

    Luciana Tock

    2014-01-01

    Full Text Available Objective. Insulin resistance (IR and ovarian and adrenal hyperandrogenism are a common finding in women with polycystic ovary syndrome (PCOS. The aim of the present study was to access possible differences in insulin resistance, gonadotropins, and androgens production in obese and nonobese PCOS women. Study Design. We studied 37 PCOS women (16 nonobese and 21 obese and 18 nonobese controls. Fasting glucose, insulin, androgens, and gonadotropins levels were determined. Salivary cortisol was measured basal and in the morning after dexamethasone (DEX 0.25 mg. Results. Nonobese PCOS women showed higher basal salivary cortisol and serum dehydroepiandrosterone sulfate and luteinizing hormone (LH levels than controls and obese PCOS. These hormones levels did not differ between the obese and control groups. After DEX administration no differences were found between the three groups. In PCOS women, salivary cortisol levels showed negative correlation with BMI (r=-0.52; P=0.001 and insulin (r=-0.47; P=0.003 and positive correlation with LH (r=0.40; P=0.016. Conclusion. Our results show an increased adrenocortical production in nonobese PCOS women, not related to IR and associated with a normal hypothalamic-pituitary-adrenal suppression. Higher LH levels might be involved in this event.

  9. Amplification of 9q34 in childhood adrenocortical tumors: a specific feature unrelated to ethnic origin or living conditions

    Figueiredo B.C.

    2000-01-01

    Full Text Available Adrenocortical tumors (ACT in children under 15 years of age exhibit some clinical and biological features distinct from ACT in adults. Cell proliferation, hypertrophy and cell death in adrenal cortex during the last months of gestation and the immediate postnatal period seem to be critical for the origin of ACT in children. Studies with large numbers of patients with childhood ACT have indicated a median age at diagnosis of about 4 years. In our institution, the median age was 3 years and 5 months, while the median age for first signs and symptoms was 2 years and 5 months (N = 72. Using the comparative genomic hybridization technique, we have reported a high frequency of 9q34 amplification in adenomas and carcinomas. This finding has been confirmed more recently by investigators in England. The lower socioeconomic status, the distinctive ethnic groups and all the regional differences in Southern Brazil in relation to patients in England indicate that these differences are not important to determine 9q34 amplification. Candidate amplified genes mapped to this locus are currently being investigated and Southern blot results obtained so far have discarded amplification of the abl oncogene. Amplification of 9q34 has not been found to be related to tumor size, staging, or malignant histopathological features, nor does it seem to be responsible for the higher incidence of ACT observed in Southern Brazil, but could be related to an ACT from embryonic origin.

  10. State of the art knowledge in adrenocortical and behavioral responses to environmental challenges in a threatened South American ratite: Implications to in situ and ex-situ conservation.

    Luis, Navarro Joaquín; Lèche, Alvina; Costa, Natalia S Della; Cortez, Marilina Vera; Marin, Raúl H; Martella, Mónica B

    2018-04-12

    The Greater Rhea (Rhea americana) is an endemic ratite to South America, whose wild populations have undergone a remarkable decrease due to habitat degradation and fragmentation by the expansion of the agricultural frontier, poaching and predation by dogs. Anthropogenic perturbations in wild environments, as well as the management in captivity, can generate different stress responses in this species, thus, the monitoring of adrenocortical and behavioral activities are considered primary assessment tools with both conservation and welfare implications. In this review we analyze and integrate the different measurements of glucocorticoids (in plasma, feces, and yolk) carried out in different captive and wild populations, taking into account the diverse predictable and unpredictable conditions to which the Greater Rhea responds in each of those environments. In addition, the translocation of this bird is presented as an application of stress physiology in field ecology for conservation purposes, in which we evaluated how this species responds when it is released into a novel environment. Our results indicate that this ratite has a striking high sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis compared to that of other bird species and shows a wide variety of adrenocortical responses depending on the environment in which it lives. This suggests that its HPA axis has a phenotypic plasticity that enables the rhea to cope with the environmental challenges. In this sense, we propose that one of the routes of this plasticity could be mediated by the maternal transfer of steroid hormones to the egg. Finally, we discuss the importance of integrating the monitoring of the adrenocortical response along with the environmental variables that define the life history of the species, in management and conservation programs ex-situ and in situ. Copyright © 2018. Published by Elsevier Inc.

  11. Role of glutathione redox cycle and catalase in defense against oxidative stress induced by endosulfan in adrenocortical cells of rainbow trout (Oncorhynchus mykiss)

    Dorval, J.; Hontela, A.

    2003-01-01

    The role of antioxidants in maintaining the functional integrity of adrenocortical cells during in vitro exposure to endosulfan, an organochlorine pesticide, was investigated in rainbow trout (Oncorhynchus mykiss). Aminotriazole (ATA), an inhibitor of catalase (CAT), L-buthionine sulfoximine (L-BSO), an inhibitor of glutathione (GSH) synthesis, and N-acetyl cysteine (NAC), a glutathione precursor, were used to investigate the role of CAT and GSH redox cycle in protection against the adrenal toxicity of endosulfan, a pesticide that impairs cell viability (LC 50 366 μM) and cortisol secretion (EC 50 19 μM) in a concentration-related manner. Pretreatment with ATA and L-BSO enhanced the toxicity of endosulfan (LC 50 and EC 50 , respectively, 302 and 2.6 μM with ATA, 346 and 3.1 μM with L-BSO), while pretreatment with NAC had no significant effect on cell viability and increased the EC 50 of endosulfan to 51 μM. CAT activity was significantly reduced following exposure to endosulfan when cells were pretreated with ATA. Pretreatment with L-BSO significantly decreased glutathione peroxidase (GPx) activity and reduced glutathione (GSH) levels in a concentration-related manner following exposure to endosulfan, while GSH levels were significantly higher in NAC pretreated cells compared to untreated cells. Finally, pretreatment with ATA and L-BSO increased, while pretreatment with NAC decreased, lipid hydroperoxides (LOOH) levels. CAT, GPx, and GSH were identified as important antioxidants in maintaining the function and integrity of rainbow trout adrenocortical cells and ATA, L-BSO, and NAC were identified as effective modulators of CAT and GSH redox cycle. Moreover, this study suggests that the glutathione redox cycle may be more efficient than catalase in protecting adrenocortical cells against endosulfan-induced oxidative stress

  12. Adrenocortical changes and arterial hypertension in lipoatrophic A-ZIP/F-1 mice

    Lamounier-Zepter, V.; Bornstein, S.R.; Kuneš, Jaroslav; Zicha, Josef; Kršek, M.; Ehrhart-Bornstein, M.; Ziegler, Ch.G.; Kiessling, A.; Funk, R.H.; Haluzík, M.

    2008-01-01

    Roč. 280, 1-2 (2008), s. 39-46 ISSN 0303-7207 Grant - others:-(DE) EH161/4-1 Institutional research plan: CEZ:AV0Z50110509 Keywords : adrenal gland * adipose tissue * hypertension Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 3.611, year: 2008

  13. Methylprednisolone Pulse Treatment of Graves´Ophthalmopathy is not associated with secondary Adrenocortical insufficiency

    Nygaard, Birte; Kristensen, Lars Østergaard

    2015-01-01

    Objective: Graves' ophthalmopathy (GO) is an inflammatory disease in the orbital region. The first-line medical treatment is glucocorticoids. An important potential side effect of glucocorticoid treatment is suppression of the hypothalamic-pituitary-adrenal (HPA) axis with impairment of endogenous...

  14. Species-specific sensitivity to selenium-induced impairment of cortisol secretion in adrenocortical cells of rainbow trout (Oncorhynchus mykiss) and brook trout (Salvelinus fontinalis)

    Miller, L.L.; Hontela, A.

    2011-01-01

    Species differences in physiological and biochemical attributes exist even among closely related species and may underlie species-specific sensitivity to toxicants. Rainbow trout (RT) are more sensitive than brook trout (BT) to the teratogenic effects of selenium (Se), but it is not known whether all tissues exhibit this pattern of vulnerability. In this study, primary cultures of RT and BT adrenocortical cells were exposed to selenite (Na 2 SO 3 ) and selenomethionine (Se-Met) to compare cell viability and ACTH-stimulated cortisol secretion in the two fish species. Cortisol, the primary stress hormone in fish, facilitates maintenance of homeostasis when fish are exposed to stressors, including toxicants. Cell viability was not affected by Se, but selenite impaired cortisol secretion, while Se-Met did not (RT and BT EC 50 > 2000 mg/L). RT cells were more sensitive (EC 50 = 8.7 mg/L) to selenite than BT cells (EC 50 = 90.4 mg/L). To identify the targets where Se disrupts cortisol synthesis, selenite-impaired RT and BT cells were stimulated with ACTH, dbcAMP, OH-cholesterol, and pregnenolone. Selenite acted at different steps in the cortisol biosynthesis pathway in RT and BT cells, confirming a species-specific toxicity mechanism. To test the hypothesis that oxidative stress mediates Se-induced toxicity, selenite-impaired RT cells were exposed to NAC, BSO and antioxidants (DETCA, ATA, Vit A, and Vit E). Inhibition of SOD by DETCA enhanced selenite-induced cortisol impairment, indicating that oxidative stress plays a role in Se toxicity; however, modifying GSH content of the cells did not have an effect. The results of this study, with two closely related salmonids, provided additional evidence for species-specific differences in sensitivity to Se which should be considered when setting thresholds and water quality guidelines. - Research Highlights: → We investigated species-specific sensitivity to Se in trout adrenocortical cells. → Selenite, not Se-Met, disrupts

  15. High-Throughput Screening of Chemical Effects on Steroidogenesis Using H295R Human Adrenocortical Carcinoma Cells.

    Karmaus, Agnes L; Toole, Colleen M; Filer, Dayne L; Lewis, Kenneth C; Martin, Matthew T

    2016-04-01

    Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2060 chemical samples on steroidogenesis via high-performance liquid chromatography followed by tandem mass spectrometry quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a 3 stage screening strategy. The first stage established the maximum tolerated concentration (MTC; ≥ 70% viability) per sample. The second stage quantified changes in hormone levels at the MTC whereas the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were prestimulated with 10 µM forskolin for 48 h to induce steroidogenesis followed by chemical treatment for 48 h. Of the 2060 chemical samples evaluated, 524 samples were selected for 6-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 17β-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into 5 distinct profiles generally representing putative mechanisms of action, including CYP17A1 and HSD3B inhibition. A distinct pattern was observed between imidazole and triazole fungicides suggesting potentially distinct mechanisms of action. From a chemical testing and prioritization perspective, this assay platform provides a robust model for high-throughput screening of chemicals for effects on steroidogenesis. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

  16. The stress of being contaminated? Adrenocortical function and reproduction in relation to persistent organic pollutants in female black legged kittiwakes.

    Tartu, Sabrina; Angelier, Frédéric; Herzke, Dorte; Moe, Børge; Bech, Claus; Gabrielsen, Geir W; Bustnes, Jan Ove; Chastel, Olivier

    2014-04-01

    High levels of environmental pollutants such as persistent organic pollutants (POPs) including PCB and DDT have been found in the Arctic and many of those pollutants may impair reproduction through endocrine disruption. Nevertheless, their effects on stress hormones remain poorly understood, especially in free-ranging birds. Corticosterone, the principal glucocorticoid in birds, can indirectly impair reproduction. The aim of the present study was to examine the relationships between POPs and reproduction through their potential consequences on different reproductive traits (breeding decision, egg-laying date, breeding success) and corticosterone secretion (baseline and stress-induced levels). We addressed those questions in an Arctic population of female black-legged kittiwakes during the pre-breeding stage and measured several legacy POPs (PCBs and pesticides: HCB, p,p'-DDE, CHL) in whole blood. POP levels were not related to breeding decision neither to breeding success, whereas females with high levels of pesticides laid their eggs earlier in the season. We found a negative relationship between POP levels and body condition index in non-breeding females. Black-legged kittiwakes with higher levels of PCB showed stronger adrenocortical response when subjected to a capture-handling stress protocol. We suggest that PCBs may disrupt corticosterone secretion whereas the positive relationship between pesticides and egg-laying date could either originate from a direct effect of pesticides or may be related to other confounding factors such as age or individual's quality. Although no direct negative reproduction output of POPs was found in this study, it is possible that the most contaminated individuals would be more sensitive to environmental stress and would be less able to maintain parental investment than less polluted individuals. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Activation in the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system in women with carpal tunnel syndrome.

    Fernández-de-Las-Peñas, César; Díaz-Rodríguez, Lourdes; Salom-Moreno, Jaime; Galiano-Castillo, Noelia; Valverde-Herreros, Lis; Martínez-Martín, Javier; Pareja, Juan A

    2014-08-01

    The aim of this study is to investigate the differences in salivary cortisol (hypothalamic-pituitary-adrenocortical [HPA] axis), α-amylase activity (sympathetic nervous system [SNS]), and immunoglobulin A (IgA; immune system) concentrations between women with carpal tunnel syndrome (CTS) and healthy women. A cross-sectional study. Activation of HPA, SNS, and immune system in CTS has not been clearly determined. One hundred two women (age: 45 ± 7 years) with electrodiagnostic and clinical diagnosis of CTS and 102 matched healthy women. The intensity of the pain was assessed with a Numerical Pain Rating Scale (0-10), and disability was determined with Boston Carpal Tunnel Questionnaire. Salivary cortisol concentration, α-amylase activity, salivary flow rate, and IgA concentration were collected from nonstimulated saliva. Women with CTS exhibited lower salivary flow rate (P  0.2) were found between groups as a total. Women with severe CTS exhibited lower salivary flow rate (P < 0.001), higher α-amylase activity (P = 0.002), and higher cortisol concentration (P = 0.03) than healthy women and than those with minimal/moderate CTS (P < 0.05). Within women with CTS, significant positive associations between α-amylase activity and the intensity of pain were found: the highest the level of pain, the higher the α-amylase activity, i.e., higher SNS activation. These results suggest that women with severe CTS exhibit changes in activation in the HPA axis and SNS but not in the humoral immune system. Activation of the SNS was associated with the intensity of pain. Future studies are needed to elucidate the direction of this relationship. Wiley Periodicals, Inc.

  18. No effect of pinealectomy on the parallel shift in circadain rhythms of adrenocortical activity and food intake in blinded rats.

    Takahashi, K; Inoue, K; Takahashi, Y

    1976-10-01

    Twenty-four-hr patterns of plasma corticosterone levels were determined at 4-hr intervals every 3-4 weeks in sighted and blinded pinealectomized rats of adult age. Through the whole period of the experiment, 24-hr patterns of food intake were also measured weekly. The sighted rats manifested the same 24-hr patterns of plasma corticosterone levels and food intake for 15 weeks after pinealectomy as those observed in the intact control rats. The magnitude of peak levels of plasma corticosterone and the amount of food intake did not differ between the two groups. A phase shift in circadian rhythms of plasma corticosterone levels and food intake was observed in both groups of blinded rats, with and without pinealectomy. Between the two groups, the patterns of phase shift were essentially similar for 10 weeks examined after optic enucleation. The peak elevation of plasma levels took place at 11 p.m. at the end of the 4th week after optic enucleation. Thereafter, 4- to 8-hr delay of peak appearance was observed every 3 weeks. No significant differences were found in peak values between the two groups of blinded rats. Furthermore, the circadian rhythm of food intake shifted in parallel with that of plasma corticosterone levels. A phase reversal of these two activities was observed between the 8th and 10th week after the operation. These results indicate that the pineal gland does not play any important role either in the maintenance of normal circadian periodicities of adrenocortical activity and food intake or in the shift in circadian rhythms of the two activities in the blinded rats.

  19. The effect of oxygen on aldosterone release from bovine adrenocortical cells in vitro: PO2 versus steroidogenesis.

    Raff, H; Kohandarvish, S

    1990-08-01

    Hypoxia decreases plasma aldosterone in vivo without a decrease in PRA, angiotensin II (ANG II), ACTH, or cortisol. The present study evaluated whether this could be due to a direct, specific inhibitory effect on the zona glomerulosa related to the magnitude of the decrease in oxygen (O2). Bovine adrenocortical cells were dispersed with collagenase and studied in vitro within 48 h. Cells were stimulated for 2 h with ANG II (0.1-1000 nM) or (Bu)2cAMP (0.3-3 mM) under oxygen levels ranging from 0 to 100% O2 (PO2 from 66 +/- 4 to 561 +/- 46 torr) vs. a reference gas mixture (21% O2 PO2 approximately 140 torr). Exposure to 123 +/- 8, 110 +/- 12, 100 +/- 16, and 66 +/- 4 torr led to 27%, 30%, 40% and 70% inhibition, respectively, of 3 nM ANG II-stimulated aldosterone secretion as compared to 140 +/- 16 torr (reference). Exposure to hyperoxia (288 +/- 36 to 561 +/- 46 torr) led to a small (10%) increase in ANG II-stimulated aldosterone secretion which was not statistically significant. The P50 (half-maximal PO2) for aldosteronogenesis was approximately 95 torr. The results for other doses of ANG II and for cAMP were similar. The inhibitory effect of low O2 was reversed by returning the cells to reference conditions (140 +/- 16 torr). Cortisol secretion was not significantly affected by changes in oxygen tension. We conclude that small changes in O2 within the physiological range directly and specifically inhibit aldosteronogenesis in a dose-dependent manner with a P50 of approximately 95 torr. Inhibition of cAMP-stimulated aldosterone secretion suggests a postreceptor site of action. This direct, reversible, and specific effect on the zona glomerulosa of the adrenal cortex may account for the dissociation of renin and aldosterone during hypoxia in vivo.

  20. Tumor-specific loss of 11p15.5 alleles in del11p13 Wilms tumor and in familial adrenocortical carcinoma

    Henry, I.; Grandjouan, S.; Couillin, P.

    1989-01-01

    The authors have compared constitutional and tumor genotypes in nine cases of hereditary Wilms tumor (WT) and in three unrelated cases of familial adrenocortical carcinoma (ADCC). Since susceptibility to these tumors can be observed in malformation syndromes associated with a constitutional deletion of band 11p13 (WT) and with a constitutional duplication of band 11p15.5 (WT, ADCC), they investigated these two candidate regions by using 11p polymorphic markers. As expected, somatic chromosomal events, resulting in a loss of heterozygosity limited to region 11p15.5, were observed in the tumor of two familial cases of adrenocortical carcinoma. Surprisingly, however, analysis of the WT of two patients with a constitutional deletion of band 11p13, associated with aniridia, genitourinary abnormalities, and mental retardation (WAGR syndrome), revealed a loss of heterozygosity limited to region 11p15.5. These data therefore suggest that observation of a specific loss of heterozygosity may not necessarily point to the site of the initial germinal mutation. Together with previous similar observations of a loss of heterozygosity limited to 11p15.5 in breast cancer and in rhabdomyosarcoma, the data suggest that region 11p15.5 may carry a non-tissue-specific gene that could be involved in genetic predisposition, in tumor progression, or in both

  1. Non-invasive monitoring of adrenocortical activity in captive African Penguin (Spheniscus demersus) by measuring faecal glucocorticoid metabolites.

    Ozella, L; Anfossi, L; Di Nardo, F; Pessani, D

    2015-12-01

    Measurement of faecal glucocorticoid metabolites (FGMs) has become a useful and widely-accepted method for the non-invasive evaluation of stress in vertebrates. In this study we assessed the adrenocortical activity of five captive African Penguins (Spheniscus demersus) by means of FGM evaluation following a biological stressor, i.e. capture and immobilization. In addition, we detected individual differences in secretion of FGMs during a stage of the normal biological cycle of penguins, namely the breeding period, without any external or induced causes of stress. Our results showed that FGM concentrations peaked 5.5-8h after the induced stress in all birds, and significantly decreased within 30 h. As predictable, the highest peak of FGMs (6591 ng/g) was reached by the youngest penguin, which was at its first experience with the stressor. This peak was 1.8-2.7-fold higher compared to those of the other animals habituated to the stimulus. For the breeding period, our results revealed that the increase in FGMs compared to ordinary levels, and the peaks of FGMs, varied widely depending on the age and mainly on the reproductive state of the animal. The bird which showed the lowest peak (2518 ng/g) was an old male that was not in a reproductive state at the time of the study. Higher FGM increases and peaks were reached by the two birds which were brooding (male: 5552%, 96,631 ng/g; female: 1438%, 22,846 ng/g) and by the youngest bird (1582%, 39,700 ng/g). The impact of the reproductive state on FGM levels was unexpected compared to that produced by the induced stress. The EIA used in this study to measure FGM levels proved to be a reliable tool for assessing individual and biologically-relevant changes in FGM concentrations in African Penguin. Moreover, this method allowed detection of physiological stress during the breeding period, and identification of individual differences in relation to the reproductive status. The increase in FGM levels as a response to capture and

  2. In vivo and in vitro evaluation of [18F]FETO with respect to the adrenocortical and GABAergic system in rats

    Mitterhauser, Markus; Wadsak, Wolfgang; Wabnegger, Leila; Sieghart, Werner; Viernstein, Helmut; Kletter, Kurt; Dudczak, Robert

    2003-01-01

    11β-Hydroxylase (CYP11B1, P450 11β ) plays an important role in the biosynthesis of cortisol and aldosterone and has been shown to be a good target for the in vivo imaging of adrenocortical incidentalomas in nuclear medicine. [ 11 C]Metomidate (MTO), a potent inhibitor of this enzyme, is used for positron emission tomography (PET) imaging of adrenocortical pathology. The synthesis of (R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid 2-[ 18 F]fluoroethylester (FETO), a close analogue to MTO and etomidate (ETO), has been presented recently, and the present investigation aimed to characterise the in vivo distribution of FETO. Since ETO is a well-known anaesthetic drug acting via the GABAergic system, the interaction of FETO with GABA A receptors was also evaluated. Eighteen male Sprague-Dawley rats were injected with 1.73-3.06 MBq of FETO into a tail vein after venodilatation in a 40 C water bath. Rats were sacrificed by exsanguination from the abdominal aorta under deep ether anaesthesia after 10 (n=6), 30 (n=6) or 60 min (n=6); organs were removed, weighed and counted. For binding experiments, rat cerebellar membranes were incubated for 90 min at 4 C in TC-50 buffer, 150 mM NaCl and 2 nM of [ 3 H]flunitrazepam in the absence or presence of 10 μM diazepam or various concentrations of ETO, MTO and FETO. In vivo evaluation evinced very high uptake in the adrenal glands (7.52%±1.19% ID/g at 30 min), followed by lung (1.18%±0.19% ID/g, 10 min), liver (0.59%±0.13% ID/g, 10 min) and duodenum (0.7%±0.29% ID/g, 60 min). No defluorination nor fluoroethyl-ester cleavage was observed. When brain regions were compared with the thalamus (the reference region), highest relative uptake was seen in the cortex (2.34), followed by ''rest brain'' (2.13) and cerebellum (1.96). FETO and ETO were able to increase the binding of [ 3 H]flunitrazepam with similar potencies and to a comparable extent. It is concluded that FETO shows characteristics suitable for the imaging of

  3. In vivo and in vitro evaluation of [{sup 18}F]FETO with respect to the adrenocortical and GABAergic system in rats

    Mitterhauser, Markus [Department of Nuclear Medicine, AKH Wien, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria); Department of Pharmaceutic Technology and Biopharmaceutics, University of Vienna (Austria); Hospital Pharmacy of the General Hospital of Vienna (Austria); Wadsak, Wolfgang [Department of Nuclear Medicine, AKH Wien, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria); Department of Inorganic Chemistry, University of Vienna (Austria); Ludwig-Boltzmann-Institute for Nuclear Medicine, Vienna (Austria); Wabnegger, Leila; Sieghart, Werner [Institute for Brain Research, University of Vienna (Austria); Viernstein, Helmut [Department of Pharmaceutic Technology and Biopharmaceutics, University of Vienna (Austria); Kletter, Kurt [Department of Nuclear Medicine, AKH Wien, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria); Dudczak, Robert [Department of Nuclear Medicine, AKH Wien, University of Vienna, Waehringer Guertel 18-20, 1090, Vienna (Austria)

    2003-10-01

    11{beta}-Hydroxylase (CYP11B1, P450{sub 11{beta}}) plays an important role in the biosynthesis of cortisol and aldosterone and has been shown to be a good target for the in vivo imaging of adrenocortical incidentalomas in nuclear medicine. [{sup 11}C]Metomidate (MTO), a potent inhibitor of this enzyme, is used for positron emission tomography (PET) imaging of adrenocortical pathology. The synthesis of (R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid 2-[{sup 18}F]fluoroethylester (FETO), a close analogue to MTO and etomidate (ETO), has been presented recently, and the present investigation aimed to characterise the in vivo distribution of FETO. Since ETO is a well-known anaesthetic drug acting via the GABAergic system, the interaction of FETO with GABA{sub A} receptors was also evaluated. Eighteen male Sprague-Dawley rats were injected with 1.73-3.06 MBq of FETO into a tail vein after venodilatation in a 40 C water bath. Rats were sacrificed by exsanguination from the abdominal aorta under deep ether anaesthesia after 10 (n=6), 30 (n=6) or 60 min (n=6); organs were removed, weighed and counted. For binding experiments, rat cerebellar membranes were incubated for 90 min at 4 C in TC-50 buffer, 150 mM NaCl and 2 nM of [{sup 3}H]flunitrazepam in the absence or presence of 10 {mu}M diazepam or various concentrations of ETO, MTO and FETO. In vivo evaluation evinced very high uptake in the adrenal glands (7.52%{+-}1.19% ID/g at 30 min), followed by lung (1.18%{+-}0.19% ID/g, 10 min), liver (0.59%{+-}0.13% ID/g, 10 min) and duodenum (0.7%{+-}0.29% ID/g, 60 min). No defluorination nor fluoroethyl-ester cleavage was observed. When brain regions were compared with the thalamus (the reference region), highest relative uptake was seen in the cortex (2.34), followed by ''rest brain'' (2.13) and cerebellum (1.96). FETO and ETO were able to increase the binding of [{sup 3}H]flunitrazepam with similar potencies and to a comparable extent. It is concluded

  4. Expression of StAR and Key Genes Regulating Cortisol Biosynthesis in Near Term Ovine Fetal Adrenocortical Cells: Effects of Long-Term Hypoxia.

    Vargas, Vladimir E; Myers, Dean A; Kaushal, Kanchan M; Ducsay, Charles A

    2018-02-01

    We previously demonstrated decreased expression of key genes regulating cortisol biosynthesis in long-term hypoxic (LTH) sheep fetal adrenals compared to controls. We also showed that inhibition of the extracellular signal-regulated kinases (ERKs) with the mitogen-activated protein kinase (MEK)/ERK inhibitor UO126 limited adrenocorticotropic (ACTH)-induced cortisol production in ovine fetal adrenocortical cells (FACs), suggesting a role for ERKs in cortisol synthesis. This study was designed to determine whether the previously observed decrease in LTH cytochrome P45011A1/cytochrome P450c17 (CYP11A1/CYP17) in adrenal glands was maintained in vitro, and whether ACTH alone with or without UO126 treatment had altered the expression of CYP11A1, CYP17, and steroidogenic acute regulatory protein (StAR) in control versus LTH FACs. Ewes were maintained at high altitude (3820 m) from ∼40 days of gestation (dG). At 138 to 141 dG, fetal adrenal glands were collected from LTH (n = 5) and age-matched normoxic controls (n = 6). Fetal adrenocortical cells were challenged with ACTH (10 -8 M) with or without UO126 (10 µM) for 18 hours. Media samples were collected for cortisol analysis and messenger RNA (mRNA) for CYP11A1, CYP17, and StAR was quantified by quantitative real-time polymerase chain reaction. Cortisol was higher in the LTH versus control ( P StAR mRNA was decreased in LTH versus control ( P StAR expression.

  5. Stages of Adrenocortical Carcinoma

    ... the adrenal gland is the adrenal medulla . Enlarge Anatomy of the adrenal gland. There are two adrenal ... spleen , or liver ) or to large blood vessels ( renal vein or vena cava ) and may have spread ...

  6. Addison disease in patients treated with glucocorticoid therapy.

    Cronin, C C

    2012-02-03

    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.

  7. DISEASES

    Pletscher-Frankild, Sune; Pallejà, Albert; Tsafou, Kalliopi

    2015-01-01

    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...

  8. [Potentialities of computed tomography and ultrasound in diagnosis of hormonally active adrenal diseases: results of comparison CT and US with operative adn histological data].

    Denisova, L B; Vorontsova, S V; Emel'ianova, L N

    2000-01-01

    The data given in the paper suggest that X-ray computed tomography (CT) is highly effective in detecting all types of hormonally active adrenal abnormalities. CT used in hormonally active adrenal diseases yielded data on major quantitative and qualitative (primarily densitometric) criteria that could be used in assessing the images of the adrenal area in these patients. Ultrasound study (USS) made at the first stage of topical diagnostic searches was of informative value in detecting adrenal tumor lesions, the technique being highly sensitive in the diagnosis of adrenal pheochromocytomas and adenocarcinomas, but less informative in the detection of hormonally active adrenocortical adenomas (aldesterone-producing ones in particular) than CT. The diagnosis of various adrenocortical hyperplasies and the differentiation of hyperplastic and tumor forms of hypercorticoidism are a prerogative of CT that substantially supplements USS findings in such cases.

  9. Cellular immunity and immunopathology in autoimmune Addison's disease.

    Bratland, Eirik; Husebye, Eystein S

    2011-04-10

    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.

  10. Functional morphology of pituitary -thyroid and -adrenocortical axes in middle-aged male rats treated with Vitex agnus castus essential oil.

    Šošić-Jurjević, Branka; Ajdžanović, Vladimir; Filipović, Branko; Trifunović, Svetlana; Jarić, Ivana; Ristić, Nataša; Milošević, Verica

    2016-09-01

    We previously reported that Vitex agnus-castus L. essential oil (VACEO), when administered to middle-aged males, exerts a bone-protective effect, induces silencing of locomotor activities and decreases pituitary prolactin immunopositivity. To further assess the putative endocrine effects of VACEO, we examined the pituitary-thyroid and -adrenocortical axes in our model. Sixteen-month-old Wistar rats were subcutaneously administered 60mg/kg of VACEO dissolved in sterile olive oil, while the control group received the same amount of vehicle alone for three weeks. Pituitaries, thyroids and adrenals were analyzed by qualitative and quantitative histological approaches. Concentration of thyroid stimulating hormone (TSH), total thyroxine and triiodothyronine (TH), adrenocorticotrophic hormone (ACTH), corticosterone in serum and in adrenal tissue were measured. In VACEO-treated rats, the relative volume density of pituitary thyrotrophs increased (p<0.001), while intensity of cytoplasmic TSHβ immunostaining decreased (p<0.001), consistent with elevated TSH in serum (p<0.01). The thyroid tissue was characterized by a micro-follicular structure, increased relative volume of follicular epithelium (p<0.05), decreased volume of luminal colloid (p<0.001) and increased basolateral expression of sodium-iodide symporter-immunopositivity (p<0.05). Serum TH also increased (p<0.01). The relative volume density of pituitary corticotrophs decreased (p<0.05), compatible with decline in circulating ACTH (p<0.05). Neither tissue nor serum corticosterone levels were affected by VACEO treatment. In conclusion, the observed changes in TSH and ACTH strongly indicate central endocrine effects of prolonged VACEO treatment. In this respect, production of ACTH decreased without impact on corticosterone production. Increase in serum concentration of both TH and TSH are not compatible with a negative feedback loop and suggest a major change in set-point regulation of the hypothalamic

  11. Activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis at midgestation by estrogen-induced changes in placental corticosteroid metabolism

    Pepe, G.J.; Waddell, B.J.; Albrecht, E.D.

    1990-01-01

    We have hypothesized that the change in placental cortisol (F)-cortisone (E) metabolism induced by estrogen late in gestation is important to activation of the baboon fetal hypothalamic-pituitary-adrenocortical axis, culminating in the ontogenesis of de novo F secretion by the fetal adrenal. The present study tested this hypothesis in vivo by comparing the proportion of F in the fetus derived via maternal and fetal production on day 100 (n = 7; term = day 184) and day 165 (n = 4) in untreated baboons and on day 100 in baboons (n = 9) in which 50-mg pellets of androstenedione were implanted sc in the mother in increasing numbers (i.e. two on day 70, four on day 78, six on day 86, and eight on day 94) to increase placental estrogen production. Maternal, uterine, and umbilical venous samples were collected during constant maternal infusion (120 min) of [3H]F/[14C]E, endogenous and radiolabeled F/E content was determined, and corticosteroid dynamics were quantified. The MCR and peripheral interconversion of F and E as well as the production rate of F were unaltered in the mother. However, at midgestation, androstenedione increased (P less than 0.05) estrogen by 62% and altered transuterofeto placental F-E metabolism from preferential reduction of E to preferential oxidation of F, a pattern similar to that at term. In untreated baboons, on day 100 none of the F in the fetus was due to fetal production, whereas by day 165, 49 +/- 6% was of fetal origin. In animals treated with androstenedione at midgestation, 22 +/- 4% of fetal F was derived de novo within the fetus. Thus, production of F by the fetus was negligible on day 100, increased near term in association with an increase in transplacental oxidation of F to E, and was induced at midgestation in baboons in which placental F-E metabolism was altered by an increase in estrogen production

  12. A case of Addison's disease accompanied with bilateral adrenal calcification on CT

    Lee, Li-Chik; Fujita, Naohisa; Ohba, Yachiyo

    1985-01-01

    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)

  13. Current status of adrenalectomy for Cushing's disease

    Brunicardi, F.C.; Rosman, P.M.; Lesser, K.L.; Andersen, D.K.

    1985-01-01

    To evaluate the current use of adrenalectomy in the treatment of Cushing's disease, we reviewed seven consecutive patients who have undergone adrenalectomy for Cushing's disease at this medical center during 1983 to 1984. Seventy-one percent (5/7) had pituitary, or type I, Cushing's disease, while 29% (2/7) had adrenal, or type II, Cushing's disease from either an adenoma or an adrenocortical carcinoma. Presenting signs and symptoms, either initially or at the time of recurrence, were typical of Cushing's syndrome. Four of five patients with type I disease had recurrent disease after transphenoidal hypophysectomy, bilateral adrenalectomy, or unilateral adrenalectomy. In three of five patients, medical therapy of hypercortisolism was abandoned because of adverse side effects. Preoperative evaluation in all patients included cortisol and ACTH levels, dexamethasone suppression tests, and computerized tomography (both abdominal and head). In patients with a prior history of adrenalectomy, radiocholesterol scans were also performed and were useful. Angiographic procedures were not required in these patients. In patients with type I disease, posterior operative approaches were used. In patients with type II disease, an anterolateral approach was used. Posterolateral incisions are preferred over Hugh-Young incisions and provide better exposure with a reduced risk of poor wound healing. Morbidity and mortality included one death and three nonhealing wounds. In the six surviving patients, symptoms resolved with variable frequency. Findings suggestive of Nelson's syndrome (hyperpigmentation) have occurred in two patients; serial computerized tomographic scans fail to reveal evidence of pituitary tumors

  14. Contribution of the TP53 R337H mutation to the cancer burden in southern Brazil: Insights from the study of 55 families of children with adrenocortical tumors.

    Mastellaro, Maria J; Seidinger, Ana L; Kang, Guolian; Abrahão, Renata; Miranda, Eliana C M; Pounds, Stanley B; Cardinalli, Izilda A; Aguiar, Simone S; Figueiredo, Bonald C; Rodriguez-Galindo, Carlos; Brandalise, Silvia R; Yunes, José A; Barros-Filho, Antônio de A; Ribeiro, Raul C

    2017-08-15

    The tumor protein p53 (TP53) arginine-to-histidine mutation at codon 337 (R337H) predisposes children to adrenocortical tumors (ACTs) and, rarely, to other childhood tumors, but its impact on adult cancer remains undetermined. The objective of this study was to investigate the frequency and types of cancer in relatives of children with ACT who carry the TP53 R337H mutation. TP53 R337H testing was offered to relatives of probands with ACT. The parental lineage segregating the R337H mutation was identified in all families. The frequency and distribution of cancer types were compared according to R337H status. The authors' data also were compared with those publicly available for children with TP53 mutations other than R337H. The mean and median follow-up times for the probands with ACT were 11.2 years and 9.7 years (range, 3-32 years), respectively. During this time, cancer was diagnosed in 12 of 81 first-degree relatives (14.8%) carrying the R337H mutation but in only 1 of 94 noncarriers (1.1%; P = .0022). At age 45 years, the cumulative risk of cancer was 21% (95% confidence interval, 5%-33%) in carriers and 2% (95% confidence interval, 0%-4%) in noncarriers (P = .008). The frequency of cancer was higher in the R337H segregating lineages than in the nonsegregating lineages (249 of 1410 vs 66 of 984 individuals; P cancer were the most common types. TP53 R337H carriers have a lifelong predisposition to cancer with a bimodal age distribution: 1 peak, represented by ACT, occurs in the first decade of life, and another peak of diverse cancer types occurs in the fifth decade. The current findings have implications for genetic counseling and surveillance of R337H carriers. Cancer 2017;123:3150-58. © 2017 American Cancer Society. © 2017 American Cancer Society.

  15. Screening for Addison's disease in patients with type 1 diabetes mellitus and recurrent hypoglycaemia

    Likhari, Taruna; Magzoub, Saeed; Griffiths, Melanie J; Buch, Harit N

    2007-01-01

    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

  16. Screening for Addison's disease in patients with type 1 diabetes mellitus and recurrent hypoglycaemia.

    Likhari, Taruna; Magzoub, Saeed; Griffiths, Melanie J; Buch, Harit N; Gama, R

    2007-06-01

    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.

  17. Prevalence of coeliac disease in Italian patients affected by Addison's disease.

    Biagi, Federico; Campanella, Jonia; Soriani, Alessandra; Vailati, Alberto; Corazza, Gino R

    2006-03-01

    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.

  18. Treatment Option Overview (Adrenocortical Carcinoma)

    ... affect the prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  19. General Information about Adrenocortical Carcinoma

    ... the adrenal gland is the adrenal medulla . Enlarge Anatomy of the adrenal gland. There are two adrenal ... spleen , or liver ) or to large blood vessels ( renal vein or vena cava ) and may have spread ...

  20. Autoimmunity predominates in a large South African cohort with Addison's disease of mainly European descent despite long-standing disease and is associated with HLA DQB*0201.

    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

    2010-09-01

    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.

  1. MANAGEMENT OF ENDOCRINE DISEASE: Regenerative therapies in autoimmune Addison's disease.

    Gan, Earn H; Pearce, Simon H

    2017-03-01

    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.

  2. Treatment of Addison's disease during pregnancy.

    Oliveira, Diana; Lages, Adriana; Paiva, Sandra; Carrilho, Francisco

    2018-01-01

    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.

  3. Bilateral Testicular Tumors Resulting in Recurrent Cushing Disease After Bilateral Adrenalectomy.

    Puar, Troy; Engels, Manon; van Herwaarden, Antonius E; Sweep, Fred C G J; Hulsbergen-van de Kaa, Christina; Kamphuis-van Ulzen, Karin; Chortis, Vasileios; Arlt, Wiebke; Stikkelbroeck, Nike; Claahsen-van der Grinten, Hedi L; Hermus, Ad R M M

    2017-02-01

    Recurrence of hypercortisolism in patients after bilateral adrenalectomy for Cushing disease is extremely rare. We present a 27-year-old man who previously underwent bilateral adrenalectomy for Cushing disease with complete clinical resolution. Cushingoid features recurred 12 years later, with bilateral testicular enlargement. Hormonal tests confirmed adrenocorticotropic hormone (ACTH)-dependent Cushing disease. Surgical resection of the testicular tumors led to clinical and biochemical remission. Gene expression analysis of the tumor tissue by quantitative polymerase chain reaction showed high expression of all key steroidogenic enzymes. Adrenocortical-specific genes were 5.1 × 105 (CYP11B1), 1.8 × 102 (CYP11B2), and 6.3 × 104 (MC2R) times higher than nonsteroidogenic fibroblast control. This correlated with urine steroid metabolome profiling showing 2 fivefold increases in the excretion of the metabolites of 11-deoxycortisol, 21-deoxycortisol, and total glucocorticoids. Leydig-specific genes were 4.3 × 101 (LHCGR) and 9.3 × 100 (HSD17B3) times higher than control, and urinary steroid profiling showed twofold increased excretion of the major androgen metabolites androsterone and etiocholanolone. These distinctly increased steroid metabolites were suppressed by dexamethasone but unresponsive to human chorionic gonadotropin stimulation, supporting the role of ACTH, but not luteinizing hormone, in regulating tumor-specific steroid excess. We report bilateral testicular tumors occurring in a patient with recurrent Cushing disease 12 years after bilateral adrenalectomy. Using mRNA expression analysis and steroid metabolome profiling, the tumors demonstrated both adrenocortical and gonadal steroidogenic properties, similar to testicular adrenal rest tumors found in patients with congenital adrenal hyperplasia, suggesting the presence of pluripotent cells even in patients without congenital adrenal hyperplasia. Copyright © 2017 by the Endocrine Society

  4. Assessement of computer tomography usefulness in the diagnosis of arterial hypertension in adrenal diseases

    Pacho, R.; Feltynowski, T.

    1981-01-01

    The results of computer tomoqraphy done in 105 patients with hypertension due to various adrenal diseases diagnosed clinically and after laboratory investigations were analysed. The investigation was done with a Delta-Scan Ohio-Nuclear-Siemens unit. In 35 cases the findings of computer tomography were confirmed surgically: 12 cases of adrenal adenoma the smallest one had 5 mm in diameter due to primary hyperaidosteronism, 3 cases of adenoma, 2 carcinomas and 1 case of adrenocortical hypertrophy in Cushing's sydrome as well as 15 phaeochromocytomas inclunding two situated outside the adrenals. A case of ganglioneuroma in a 3-year-old child was also diagnosed correctly. The characteristic features of pathological adrenal changes observed during computer tomography in these patients were described. The high effectiveness of the diagnoses based on the results of laboratory investigations and computer tomography is stressed. (author)

  5. Management of hypoadrenocorticism (Addison’s disease in dogs

    Lathan P

    2018-02-01

    Full Text Available Patty Lathan,1 Ann L Thompson2 1College of Veterinary Medicine, Mississippi State University, Starkville, MS, USA; 2School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia Abstract: Hypoadrenocorticism (HOAC; Addison’s disease is an endocrine condition seen in small animal practice. Dogs with this disease can present in a variety of ways from acute hypovolemic collapse to vague, chronic, waxing, and waning clinical signs. In the most common form of this disease, animals have both mineralocorticoid and glucocorticoid deficiency, resulting in hyponatremia and hyperkalemia, and signs of cortisol deficiency. The etiology may be immune-mediated destruction of the adrenal cortex, drug-induced adrenocortical necrosis (mitotane, enzyme inhibition (trilostane, or infiltrative processes such as neoplastic or fungal disease. Much less commonly, dogs have signs of cortisol deficiency, but no electrolyte changes. This is referred to as atypical HOAC. The veterinarian needs to have a clinical suspicion for HOAC to make a diagnosis in a timely manner. Treatment of dogs with an acute presentation prioritizes correcting the hypovolemia, hyperkalemia, acidosis, and hypoglycemia. Fluid therapy addresses most of these issues, but other directed therapies may be required in the most severe cases. For chronic management, all patients with Addison’s disease will require replacement of glucocorticoids (usually prednisone, and most patients require replacement of mineralocorticoids with either desoxycorticosterone pivalate or fludrocortisone. Atypical Addisonians do not require mineralocorticoid supplementation, but electrolytes should be monitored in case the need arises in the future. The prognosis for dogs treated for HOAC promptly and appropriately is excellent; most patients die from other diseases. However, if the diagnosis is missed, patients may die as a consequence of HOAC. Thus, knowledge of the hallmarks of Addison

  6. Effects of bisphenol A-related diphenylalkanes on vitellogenin production in male carp (Cyprinus carpio) hepatocytes and aromatase (CYP19) activity in human H295r adrenocortical carcinoma cells

    Letcher, Robert J.; Sanderson, J. Thomas; Bokkers, Abraham; Giesy, John P.; Berg, Martin van den

    2005-01-01

    The present study investigated the effects of the known xenoestrogen bisphenol A (BPA) relative to eight BPA-related diphenylalkanes on estrogen receptor (ER)-mediated vitellogenin (vtg) production in hepatocytes from male carp (Cyprinus carpio), and on aromatase (CYP19) activity in the human adrenocortical H295R carcinoma cell line. Of the eight diphenylalkanes, only 4,4'-(hexafluoropropylidene)diphenol (BHF) and 2,2'-bis(4-hydroxy-3-methylphenyl)propane (BPRO) induced vtg, i.e., to a maximum of 3% to 4% (at 100 μM) compared with 8% for BPA relative to the maximum induction by 17β-estradiol (E2, 1 μM). Bisphenol A diglycidyl ether (BADGE) was a potent antagonist of vtg production with an IC50 of 5.5 μM, virtually 100% inhibition of vtg at 20 μM, and an inhibitive (IC50) potency about one-tenth that of the known ER antagonist tamoxifen (IC50, 0.6 μM). 2,2'-Diallyl bisphenol A, 4,4'-(1,4-phenylene-diisopropylidene)bisphenol, BPRO, and BHF were much less inhibitory with IC50 concentrations of 20-70 μM, and relative potencies of 0.03 and 0.009 with tamoxifen. Bisphenol ethoxylate showed no anti-estrogenicity (up to 100 μM), and 4,4'-isopropylidene-diphenol diacetate was only antagonistic at 100 μM. When comparing the (anti)estrogenic potencies of these bisphenol A analogues/diphenylalkanes, anti-estrogenicity occurred at lower concentrations than estrogenicity. 4,4'-Isopropylidenebis(2,6-dimethylphenol) (IC50, 2.0 μM) reduced E2-induced (EC50, 100 nM) vtg production due to concentration-dependent cytotoxicity as indicated by a parallel decrease in MTT activity and vtg, whereas the remaining diphenylalkanes did not cause any cytotoxicity relative to controls. None of the diphenylalkanes (up to 100 μM) induced EROD activity indicating that concentration-dependent, CYP1A enzyme-mediated metabolism of E2, or any Ah-receptor-mediated interaction with the ER, was not a likely explanation for the observed anti-estrogenic effects. At concentrations as great as 100

  7. From Appearance of Adrenal Autoantibodies to Clinical Symptoms of Addison's Disease: Natural History.

    Betterle, Corrado; Garelli, Silvia; Presotto, Fabio; Furmaniak, Jadwiga

    2016-01-01

    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.

  8. Cushing syndrome: maybe not so uncommon of an endocrine disease.

    Guaraldi, Federica; Salvatori, Roberto

    2012-01-01

    Cushing syndrome (CS) is the result of extended exposure to excessive glucocorticoids from endogenous or exogenous sources. Traditionally, the most common cause of endogenous CS is a pituitary adenoma (Cushing disease). Less common causes are adrenocortical tumors and extrapituitary adrenocorticotropin-producing neoplasias. This review provides updated information regarding the potential for increased prevalence of CS in specific patient populations. Here the authors provide to family physicians clinical guidance for recognition of CS by presenting a case, discussing the advantages/disadvantages of the diagnostic tests, and discussing information about the treatment options. CS is expected to have an incidence of 10 to 15 people per million; however, studies of patients with diabetes, obesity, hypertension, and osteoporosis found a high prevalence of CS among these populations. The clinical manifestations of CS range from the distinctive clinical features (purple striae, facial plethora, proximal myopathy) to common conditions such as hypertension, obesity, and diabetes. Clinical practice guidelines recommend biochemical tests to screen patients for CS; however, the sensitivity and specificity of these tests vary, so a careful analysis must be performed to avoid misdiagnosis. CS is challenging to diagnose. Nevertheless, with a systematic approach to testing patients and an increased awareness of the high-risk patient populations, the disease can be identified in a timely manner.

  9. Polymorphisms of the GR and HSD11B1 genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison's disease.

    Molnár, Ágnes; Kövesdi, Annamária; Szücs, Nikolette; Tóth, Miklós; Igaz, Péter; Rácz, Károly; Patócs, Attila

    2016-08-01

    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.

  10. Assessment of the relationship between melatonin, hormones of the pituitary-ovarian, -thyroid and -adrenocortical axes, and osteoprotegerin and its ligand sRANKL in girls with anorexia nervosa

    Zofia Ostrowska

    2013-05-01

    Full Text Available Background: It has been suggested that disturbances in melatonin (MEL secretion might play a role in osteoporosis development in females with anorexia nervosa (AN. It might be hypothesized that changes in the levels of hormones of the pituitary-ovarian, -thyroid and -adrenocortical axes might mediate the potential relationship between MEL and bone tissue.Aim: We investigated whether a relationship existed between MEL and LH, FSH-E2, TSH-FT3, FT4 and ACTH-cortisol axes in girls with AN. We also aimed to establish whether such a relationship might adversely affect the balance of the OPG/sRANKL system.Material/Methods: Eighty-six girls with AN and 21 healthy subjects aged 12.6 to 18.2 years participated in the study. The serum levels of hormones as well as OPG and sRANKL were determined by radioimmunoassay (RIA, immunoradiometric assay (IRMA or enzyme-linked immunosorbent assay (ELISA methods.Discussion: Our study participants with AN showed a significant reduction in body mass and body mass index (BMI, a decrease in LH, E2 and FT3 concentrations, increased MEL concentration at 02.00 hours and increased amplitude between its nocturnal and morning levels (Δ MEL2.00/9.00 as well as an increase in cortisol concentration. These changes were associated with a significant increase of OPG and sRANKL levels and a decrease in the OPG/sRANKL ratio. BMI values correlated positively with LH, FSH, E2, FT3 and the OPG/sRANKL ratio while the correlation between BMI and cortisol was negative. Δ MEL2.00/9.00 correlated positively with cortisol and negatively with LH, FSH, E2, FT3 concentrations and the OPG/sRANKL ratio. A positive correlation was observed between LH, E2 and the OPG/sRANKL ratio as well as between cortisol and sRANKL while the correlation between LH and OPG as well as between cortisol and the OPG/sRANKL ratio was negative. E2 and LH were shown to be significant and independent predictors of Δ MEL2.00/9.00. LH turned out to be a

  11. Treatment Options by Stage (Adrenocortical Carcinoma)

    ... affect the prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... or in other parts of the body. Treatment Option Overview Key Points There are different types of ...

  12. Late recurrent adrenocortical carcinoma presenting radiologically as ...

    A. Beltagy

    2016-07-01

    Jul 1, 2016 ... malignancy with an estimated incidence of 1–2 per million peo- ple [2]. There are 3 .... scopic features of a tumour composed of solid sheets of eosinophilic cells with vesicular .... World J Surg 2001;25:891–7. [14] Hermsen GC ...

  13. Fluconazole inhibits human adrenocortical steroidogenesis in vitro

    R. van der Pas (Rob); L.J. Hofland (Leo); J. Hofland (Johannes); A.E. Taylor (A.); W. Arlt (Wiebke); J. Steenbergen (Jacobie); P.M. van Koetsveld (Peter); W.W. de Herder (Wouter); F.H. de Jong (Frank); R.A. Feelders (Richard)

    2012-01-01

    textabstractThe antifungal agent ketoconazole is often used to suppress cortisol production in patients with Cushing's syndrome (CS). However, ketoconazole has serious side effects and is hepatotoxic. Here, the in vitro effects of ketoconazole and fluconazole, which might be less toxic, on human

  14. Residual adrenal function in autoimmune Addison's disease: improvement after tetracosactide (ACTH1-24) treatment.

    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

    2014-01-01

    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.

  15. Farber's Disease

    ... 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 ...

  16. Genetic homogeneity of autoimmune polyglandular disease type I

    Bjoerses, P.; Aaltonen, J.; Vikman, A. [Univ. of Helsinki (Finland)] [and others

    1996-10-01

    Autoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease (MIM 240300) characterized by hypoparathyroidism, primary adrenocortical failure, and chronic mucocutaneous candidiasis. The disease is highly prevalent in two isolated populations, the Finnish population and the Iranian Jewish one. Sporadic cases have been identified in many other countries, including almost all European countries. The APECED locus has previously been assigned to chromosome 21q22.3 by linkage analyses in 14 Finnish families. Locus heterogeneity is a highly relevant question in this disease affecting multiple tissues and with great phenotypic diversity. To solve this matter, we performed linkage and haplotype analyses on APECED families rising from different populations. Six microsatellite markers on the critical chromosomal region of 2.6 cM on 21q22.3 were analyzed. Pair-wise linkage analyses revealed significant LOD scores for all these markers, maximum LOD score being 10.23. The obtained haplotype data and the geographic distribution of the great-grandparents of the Finnish APECED patients suggest the presence of one major, relatively old mutation responsible for {approximately}90% of the Finnish cases. Similar evidence for one founder mutation was also found in analyses of Iranian Jewish APECED haplotypes. These haplotypes, however, differed totally from the Finnish ones. The linkage analyses in 21 non-Finnish APECED families originating from several European countries provided independent evidence for linkage to the same chromosomal region on 21q22.3 and revealed no evidence for locus heterogeneity. The haplotype analyses of APECED chromosomes suggest that in different populations APECED is due to a spectrum of mutations in a still unknown gene on chromosome 21. 21 refs., 3 figs., 3 tabs.

  17. Endocrine Diseases

    ... 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 ...

  18. Ribbing disease

    Mukkada, Philson J; Franklin, Teenu; Rajeswaran, Rangasami; Joseph, Santhosh

    2010-01-01

    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

  19. Recurrent hypoglycaemia in type-1 diabetes mellitus may unravel the association with Addison's disease: a case report.

    Passanisi, Stefano; Timpanaro, Tiziana; Lo Presti, Donatella; Caruso-Nicoletti, Manuela

    2014-09-12

    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.

  20. Basal and Adrenocorticotropic Hormone Stimulated Plasma Cortisol Levels Among Egyptian Autistic Children: Relation to Disease Severity

    Hewedi Doaa H

    2010-10-01

    Full Text Available Abstract Background Autism is a disorder of early childhood characterized by social impairment, communication abnormalities and stereotyped behaviors. The hypothalamic-pituitary-adrenocortical (HPA axis deserves special attention, since it is the basis for emotions and social interactions that are affected in autism. Aim To assess basal and stimulated plasma cortisol, and adrenocorticotropic hormone (ACTH levels in autistic children and their relationship to disease characteristics. Methods Fifty autistic children were studied in comparison to 50 healthy age-, sex- and pubertal stage- matched children. All subjects were subjected to clinical evaluation and measurement of plasma cortisol (basal and stimulated and ACTH. In addition, electroencephalography (EEG and intelligence quotient (IQ assessment were done for all autistic children. Results Sixteen% of autistic patients had high ACTH, 10% had low basal cortisol and 10% did not show adequate cortisol response to ACTH stimulation. Autistic patients had lower basal (p = 0.032 and stimulated cortisol (p = 0.04 and higher ACTH (p = 0.01 than controls. Childhood Autism Rating Scale (CARS score correlated positively with ACTH (r = 0.71, p = 0.02 and negatively with each of basal (r = -0.64, p = 0.04 and stimulated cortisol (r = -0.88, p Conclusions The observed hormonal changes may be due to a dysfunction in the HPA axis in autistic individuals. Further studies are warranted regarding the role of HPA axis dysfunction in the pathogenesis of autism.

  1. Treatment of Cushing's disease with adrenal blocking drugs and megavoltage therapy to the pituitary

    Ross, W.M.; Evered, D.C.; Hunter, P.; Benaim, M.; Cook, D.; Hall, R.

    1979-01-01

    Eighteen patients with Cushing's disease were seen over a 40-month period and considered for treatment by pituitary irradiation and adrenal blocking drugs. Fourteen patients entered the study and each received megavoltage therapy to give a mean dose of 4600 rad to the pituitary over 31 days. Each patient was treated for one (two patients) or two (12 patients) years with one or both of the adrenocortical enzyme inhibitors, metyrapone or aminoglutethimide to suppress cortisol secretion. Doses were adjusted to maintain urinary free cortisol secretion below 300 nmol/24 h. One patient failed to complete the trial. Normal urinary free cortisol excretion and plasma cortisol concentration were maintained after treatment in eight of the remaining 13 patients after therapy. Only one patient required cortisol replacement and normal menstrual function was restored in five of the six women. The remaining five patients relapsed and four were subsequently treated by total adrenalectomy. It was noted that the patients who responded to treatment were substantially younger than the therapeutic failures. It is suggested that this treatment is most useful in the management of younger patients. (author)

  2. Prostate Diseases

    ... 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 ...

  3. Infectious 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 ...

  4. Pick disease

    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 ...

  5. Prion Diseases

    ... 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 ...

  6. Periodontal Diseases

    ... 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 ...

  7. The natural history of autoimmune Addison's disease with a non-classical presentation: a case report and review of literature.

    Manso, Jacopo; Pezzani, Raffaele; Scarpa, Riccardo; Gallo, Nicoletta; Betterle, Corrado

    2018-05-24

    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.

  8. Steroid Profiling by Gas Chromatography–Mass Spectrometry and High Performance Liquid Chromatography–Mass Spectrometry for Adrenal Diseases

    McDonald, Jeffrey G.; Matthew, Susan

    2012-01-01

    The ability to measure steroid hormone concentrations in blood and urine specimens is central to the diagnosis and proper treatment of adrenal diseases. The traditional approach has been to assay each steroid hormone, precursor, or metabolite using individual aliquots of serum, each with a separate immunoassay. For complex diseases, such as congenital adrenal hyperplasia and adrenocortical cancer, in which the assay of several steroids is essential for management, this approach is time consuming and costly, in addition to using large amounts of serum. Gas chromatography/mass spectrometry profiling of steroid metabolites in urine has been employed for many years but only in a small number of specialized laboratories and suffers from slow throughput. The advent of commercial high-performance liquid chromatography instruments coupled to tandem mass spectrometers offers the potential for medium- to high-throughput profiling of serum steroids using small quantities of sample. Here, we review the physical principles of mass spectrometry, the instrumentation used for these techniques, the terminology used in this field and applications to steroid analysis. PMID:22170384

  9. Addison's Disease

    ... 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 ...

  10. Graves' Disease

    ... 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 ...

  11. Heart Diseases

    ... 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 ...

  12. Environmental Stressors and Their Impact on Health and Disease with Focus on Oxidative Stress.

    Münzel, Thomas; Daiber, Andreas

    2018-03-20

    Epidemiological, preclinical and interventional clinical studies have demonstrated that environmental stressors are associated with health problems, namely cardiovascular diseases. According to estimations of the World Health Organization (WHO), environmental risk factors account for an appreciable part of global deaths and life years spent with disability. This Forum addresses the impact of the environmental risk factors such as traffic noise exposure, air pollution by particulate matter (PM), mental stress/loneliness, and the life style risk factor (water-pipe) smoking on health and disease with focus on the cardiovascular system. We will critically discuss the use of observatory/modifiable biomarkers of oxidative stress and inflammation in environmental research on the aforementioned risk factors highlighting the need of exposome studies. Another focus will be on the epigenetic regulation via microRNAs in environmental stress upon exposure to noise and toxins/heavy metals as well as mental stress conditions, providing mechanistic insights into the modulation of microRNA signaling by oxidative stress, and vice versa the contribution of microRNAs to oxidative stress conditions. We will also provide an in-depth overview on the mechanistic pathways that lead to health problems (e.g., cardiovascular diseases) in response to environmental psychosocial stress, air pollution exposure in the form of ambient PM and diesel exhaust, traffic noise exposure, and the life style drug (water-pipe) smoking. Almost all stressors share the activation of the hypothalamic-pituitary-adrenocortical axis and of the sympathetic nervous system with subsequent onset of inflammation and oxidative stress, defining the here proposed therapeutic (antioxidant and exercise) strategies. Antioxid. Redox Signal. 28, 735-740.

  13. Gaucher 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 ...

  14. Lyme Disease

    ... 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 ...

  15. Stargardt Disease

    ... 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 ...

  16. Refsum Disease

    ... 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 ...

  17. Addison Disease

    ... 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, ...

  18. Alzheimer disease

    ... 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: ...

  19. Menkes Disease

    ... 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 ...

  20. Fabry Disease

    ... 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 ...

  1. Liver Diseases

    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 ...

  2. Liver disease

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the ...

  3. Digestive Diseases

    ... 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 ...

  4. Kidney Disease

    ... 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 ...

  5. Sandhoff Disease

    ... 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 ...

  6. Fifth 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 ...

  7. Cardiovascular diseases

    Kodama, Kazunori

    1992-01-01

    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

  8. Autoinflammatory Diseases

    Penaranda P, Edgar; Spinel B, Nestor; Restrepo, Jose F; Rondon H, Federico; Millan S, Alberto; Iglesias G Antonio

    2010-01-01

    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.

  9. Lyme Disease.

    Taylor, George C.

    1991-01-01

    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…

  10. Gaucher disease

    ... please enable JavaScript. Gaucher disease is a rare genetic disorder in which a person lacks an enzyme called glucocerebrosidase (GBA). Causes Gaucher disease is rare in the general population. People of Eastern and Central European (Ashkenazi) Jewish heritage are more likely to have this disease. It ...

  11. A Complex Interplay: Cognitive Behavioural Therapy for Severe Health Anxiety in Addison's Disease to Reduce Emergency Department Admissions.

    Daniels, Jo; Sheils, Elizabeth

    2017-07-01

    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.

  12. Peripheral Blood Cells from Patients with Autoimmune Addison's Disease Poorly Respond to Interferons In Vitro, Despite Elevated Serum Levels of Interferon-Inducible Chemokines.

    Edvardsen, Kine; Bjånesøy, Trine; Hellesen, Alexander; Breivik, Lars; Bakke, Marit; Husebye, Eystein S; Bratland, Eirik

    2015-10-01

    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.

  13. Peripheral Blood Cells from Patients with Autoimmune Addison's Disease Poorly Respond to Interferons In Vitro, Despite Elevated Serum Levels of Interferon-Inducible Chemokines

    Bjånesøy, Trine; Hellesen, Alexander; Breivik, Lars; Bakke, Marit; Husebye, Eystein S.; Bratland, Eirik

    2015-01-01

    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

  14. Extrahepatic Manifestations of Hepatitis B Virus Infection: Addison’s Disease and Myelofibrosis in a Patient with Persistent Hepatitis B Surface Antigenemia

    François Somlo

    1993-01-01

    Full Text Available A 60-year-old white male patient was admitted to the hospital with acute abdominal pain, seemingly a self-limited ileus. He was found to be hepatitis B surface antigen (HBsAg-positive. Previous dental treatment was suspected to be the initial source of the infection with hepatitis B virus. Five months later he was re-admitted with a diagnosis of adrenal insufficiency (Addison’s disease which responded well to steroids. Four years later he developed fever and leucocytosis. A bone marrow biopsy revealed myelofibrosis. He had several episodes of pyrexia during his lifetime. After a 12-year period the patient suffered a fatal myocardial infarction. At autopsy the adrenal glands were reduced to scarred remnants and HBsAg was found to be present in the residual adrenocortical cells by immunoflouresence methods. Bone marrow at autopsy revealed myelosclerosis as well HBsAg (via immunofluoresence. Hepatitis B virus was therefore closely correlated with the development of Addison’s disease and myelofibrosis in this case.

  15. MANAGEMENT OF ENDOCRINE DISEASE: Management of Cushing's syndrome during pregnancy: solved and unsolved questions.

    Brue, Thierry; Amodru, Vincent; Castinetti, Frederic

    2018-06-01

    With fewer than 200 reported cases, Cushing's syndrome (CS) in pregnancy remains a diagnostic and therapeutic challenge. In normal pregnancies, misleading signs may be observed such as striae or hypokalemia, while plasma cortisol and urinary free cortisol may rise up to 2- to 3-fold. While the dexamethasone suppression test is difficult to use, reference values for salivary cortisol appear valid. Apart from gestational hypertension, differential diagnosis includes pheochromocytoma and primary aldosteronism. The predominant cause is adrenal adenoma (sometimes without decreased ACTH), rather than Cushing's disease. There are considerable imaging pitfalls in Cushing's disease. Aberrant receptors may, in rare cases, lead to increased cortisol production during pregnancy in response to HCG, LHRH, glucagon, vasopressin or after a meal. Adrenocortical carcinoma (ACC) is rare and has poor prognosis. Active CS during pregnancy is associated with a high rate of maternal complications: hypertension or preeclampsia, diabetes, fractures; more rarely, cardiac failure, psychiatric disorders, infection and maternal death. Increased fetal morbidity includes prematurity, intrauterine growth retardation and less prevalently stillbirth, spontaneous abortion, intrauterine death and hypoadrenalism. Therapy is also challenging. Milder cases can be managed conservatively by controlling comorbidities. Pituitary or adrenal surgery should ideally be performed during the second trimester and patients should then be treated for adrenal insufficiency. Experience with anticortisolic drugs is limited. Metyrapone was found to allow control of hypercortisolism, with a risk of worsening hypertension. Cabergoline may be an alternative option. The use of other drugs is not advised because of potential teratogenicity and/or lack of information. Non-hormonal (mechanical) contraception is recommended until sustained biological remission is obtained. © 2018 European Society of Endocrinology.

  16. Dent disease

    Rina R Rus

    2017-04-01

    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.

  17. Morgellons Disease

    Ohn, Jungyoon; Park, Seon Yong; Moon, Jungyoon; Choe, Yun Seon; Kim, Kyu Han

    2017-01-01

    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...

  18. Celiac disease

    Holtmeier Wolfgang

    2006-03-01

    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.

  19. Celiac disease

    Radlović Nedeljko

    2013-01-01

    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.

  20. Peyronie's Disease.

    Taylor, Frederick L; Levine, Laurence A

    2007-11-01

    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.

  1. Parasitogenic diseases

    Rozenshtraukh, L.S.

    1985-01-01

    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

  2. Batten Disease

    ... 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. ...

  3. Liver Disease

    ... 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 ...

  4. Leigh's Disease

    ... 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 ...

  5. Meniere's Disease

    ... 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 ...

  6. Parasitic diseases

    Rozenshtraukh, L.S.

    1983-01-01

    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

  7. Angara disease

    Jane

    2011-10-12

    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.

  8. Huntington's Disease

    ... 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 ...

  9. Coeliac disease

    2013-03-08

    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-.

  10. Celiac Disease

    Manoochehr Karjoo

    2014-08-01

    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.

  11. Refractory disease in autoimmune diseases

    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

  12. Thyroid diseases and cerebrovascular disease

    Squizzato, A.; Gerdes, V. E. A.; Brandjes, D. P. M.; Büller, H. R.; Stam, J.

    2005-01-01

    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

  13. Morgellons Disease.

    Ohn, Jungyoon; Park, Seon Yong; Moon, Jungyoon; Choe, Yun Seon; Kim, Kyu Han

    2017-04-01

    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.

  14. [Infectious diseases].

    Chapuis-Taillard, Caroline; de Vallière, Serge; Bochud, Pierre-Yves

    2009-01-07

    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.

  15. Hirschsprung disease.

    Haricharan, Ramanath N; Georgeson, Keith E

    2008-11-01

    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.

  16. Crohn's disease.

    Shanahan, Fergus

    2012-02-03

    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.

  17. Norries disease

    Saini J

    1992-01-01

    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.

  18. Blount disease

    ... 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 ...

  19. Pneumococcal Disease

    ... 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 ...

  20. Behcet's Disease

    ... 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 ...

  1. Coeliac disease

    Reilly, Norelle R; Husby, Steffen; Sanders, David S

    2018-01-01

    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...

  2. Addison disease

    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 ...

  3. Alpers' Disease

    ... 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 ...

  4. Heart Disease

    ... 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, ...

  5. Alexander Disease

    ... 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 ...

  6. Retinal Diseases

    ... 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 ...

  7. Sever's Disease

    ... 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 ...

  8. Parkinson disease

    ... 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 ...

  9. Behcet's Disease

    ... 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 ...

  10. Extrapyramidal disease

    2010-01-01

    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

  11. Menkes disease

    Tümer, Zeynep; Møller, Lisbeth B

    2010-01-01

    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....

  12. Elm diseases

    John W. Peacock

    1989-01-01

    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...

  13. Ollier disease

    Jüppner Harald

    2006-09-01

    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.

  14. Pregnancy and Rheumatic Disease

    ... 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 ...

  15. Pheochromocytoma and Adrenocortical Adenoma in the Same Gland

    Wei-Ren Hwang

    2007-07-01

    Full Text Available A right adrenal tumor was found incidentally during abdominal computed tomography exam in a 51-year-old female patient, who had had diabetes and hypertension for more than 10 years. The computed tomography scan was arranged for possible pancreatic lesion by a neurologist. Norepinephrine level was high in the plasma and urine. Vanillylmandelic acid level was elevated in the urine. Diurnal cortisol rhythm, plasma adrenocorticotropic hormone and urine free cortisol were all normal, but the plasma cortisol concentration could not be suppressed after a standard low-dose dexamethasone suppression test. Therefore, adrenal cortical adenoma with subclinical Cushing's syndrome was highly suspected; however, further imaging studies, including magnetic resonance image and 131I-6β-iodomethylnorcholesterol adrenal scintigraphy failed to discriminate an additional tumor. After right adrenalectomy, a small adrenal cortical adenoma and a large pheochromocytoma were noted. This is an extremely rare case of an adrenal incidentaloma consisting of both medullary and cortical tumors in the same gland.

  16. The adrenocortical response of tufted puffin chicks to nutritional deficits

    Kitaysky, A.S.; Romano, Marc D.; Piatt, John F.; Wingfield, J.C.; Kikuchi, M.

    2005-01-01

    In several seabirds, nutritional state of a nest-bound chick is negatively correlated with the activity of its hypothalamus-pituitary-adrenal (HPA) axis. Increased corticosterone (cort) secretion has been shown to facilitate changes in behavior that allow hungry chicks to obtain more food from parents. However, if parents are not willing/able to buffer their young from temporary food shortages, increased cort secretion could be detrimental to undernourished chicks. In a system where parents are insensitive to chick demands, low benefits and high costs of activation of the HPA-axis in hungry chicks should lead to a disassociation of the nutritional state of the young and the activity of its HPA-axis. We tested this novel hypothesis for the tufted puffin (Fratercula cirrhata), a seabird with intermittent provisioning of a nest-bound semi-precocial chick. We examined the HPA-axis activity of captive chicks exposed to the following: (1) a short-term (24 h) food deprivation; and (2) an array of prolonged (3 weeks) restrictions in feeding regimens. We found that in response to a short-term food deprivation chicks decreased baseline levels of cort and thyroid hormones. In response to prolonged restrictions, food-limited chicks exhibited signs of nutritional deficit: they had lower body mass, endogenous lipid reserves, and thyroid hormone titers compared to chicks fed ad libitum. However, baseline and maximum acute stress-induced levels of cort were also lower in food-restricted chicks compared to those of chicks fed ad libitum. These results support a major prediction of the study hypothesis that puffin chicks suppress HPA-axis activity in response to short- and long-term nutritional deficits. This physiological adaptation may allow a chick to extend its development in the nest, while eluding detrimental effects of chronic cort elevation. 

  17. Crohn's disease.

    von Roon, Alexander C; Reese, George E; Orchard, Timothy R; Tekkis, Paris P

    2007-11-07

    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.

  18. Dent's disease

    Thakker Rajesh V

    2010-10-01

    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

  19. Parkinson's disease

    Astradsson, Arnar; Aziz, Tipu Z

    2015-01-01

    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...

  20. Hashimoto's Disease

    ... 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, ...

  1. Prionic diseases

    Abelardo Q-C Araujo

    2013-09-01

    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.

  2. Parkinson's Disease

    ... 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 ...

  3. Grover's Disease

    ... 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. ...

  4. Huntington's disease

    Hjermind, Lena Elisabeth; Law, Ian; Jønch, Aia

    2011-01-01

    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...

  5. Canavan disease

    ... 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. ...

  6. DEVIC'S DISEASE

    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-.

  7. Wilson's Disease

    ... 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 ...

  8. Morgellons disease?

    Accordino, Robert E; Engler, Danielle; Ginsburg, Iona H; Koo, John

    2008-01-01

    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.

  9. Celiac disease

    Hvas, Christian Lodberg; Jensen, Michael Dam; Reimer, Maria Christina

    2015-01-01

    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...

  10. disease patient

    Setareh Mamishi

    2016-09-01

    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.

  11. [Addison's disease].

    Quinkler, M

    2012-09-01

    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.

  12. Joint diseases

    Weissman, S.D.

    1989-01-01

    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

  13. Thyroid disease

    Falk, S.

    1990-01-01

    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.

  14. Thyroid disease

    Falk, S.

    1990-01-01

    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

  15. Gaucher's disease

    Hainaux, B.; Christophe, C.; Hanquinet, S.; Perlmutter, N.

    1992-01-01

    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.)

  16. Mitochondrial Disease

    Bulent Kurt; Turgut Topal

    2013-01-01

    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 ...

  17. Cushing disease

    Torres Esteche, V.; Menafra Prieto, M.; Ormaechea Gorricho, R.; Vignolo Scalone, G.; Larre Borges, A.

    1998-01-01

    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

  18. Diabetic Eye Disease

    ... 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 ...

  19. Heavy Chain Diseases

    ... 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 ...

  20. Thyroid diseases

    Noma, Koji

    1992-01-01

    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.)

  1. Autoantibodies against Cytochrome P450 Side-Chain Cleavage Enzyme in Dogs (Canis lupus familiaris) Affected with Hypoadrenocorticism (Addison's Disease).

    Boag, Alisdair M; Christie, Michael R; McLaughlin, Kerry A; Syme, Harriet M; Graham, Peter; Catchpole, Brian

    2015-01-01

    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.

  2. Autoantibodies against Cytochrome P450 Side-Chain Cleavage Enzyme in Dogs (Canis lupus familiaris Affected with Hypoadrenocorticism (Addison's Disease.

    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.

  3. Women's Heart Disease: Heart Disease Risk Factors

    ... this page please turn JavaScript on. Feature: Women's Heart Disease Heart Disease Risk Factors Past Issues / Winter 2014 Table ... or habits may raise your risk for coronary heart disease (CHD). These conditions are known as risk ...

  4. Diseases of the skull

    Koval', G.Yu.

    1984-01-01

    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

  5. Hirayama disease

    Atul T Tayade

    2010-01-01

    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.

  6. Parkinson's Disease Dementia

    ... 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 ...

  7. HIV and Cardiovascular Disease

    ... 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 ...

  8. What Is Celiac Disease?

    ... 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 ...

  9. Celiac Disease Changes Everything

    ... 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 ...

  10. Undifferentiated Connective Tissue Disease

    ... 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 ...

  11. Associated Autoimmune Diseases

    ... 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 ...

  12. Genetics and Rheumatic Disease

    ... 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 ...

  13. Mad Cow Disease

    ... 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 ...

  14. Niemann-Pick disease

    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, ...

  15. American Lyme Disease Foundation

    ... 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 ...

  16. Heart disease and women

    ... this page: //medlineplus.gov/ency/article/007188.htm Heart disease and women To use the sharing features on ... please enable JavaScript. People often DO NOT consider heart disease a woman's disease. Yet cardiovascular disease is the ...

  17. Inflammation and Heart Disease

    ... 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 ...

  18. Men and Heart Disease

    ... 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 ...

  19. Heart disease and diet

    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 ...

  20. Heart disease - risk factors

    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. ...

  1. Coronary heart disease

    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 ...

  2. Osler's disease

    Ahlhelm, F.; Mueller, U.; Lieb, J.; Schneider, G.; Ulmer, S.

    2013-01-01

    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

  3. Renal disease in patients with celiac disease.

    Boonpheng, Boonphiphop; Cheungpasitporn, Wisit; Wijarnpreecha, Karn

    2018-04-01

    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.

  4. Hematopoietic diseases

    Dohi, Hiroo

    1992-01-01

    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.)

  5. Neonatal Cushing Syndrome: A Rare but Potentially Devastating Disease.

    Tatsi, Christina; Stratakis, Constantine A

    2018-03-01

    Neonatal Cushing syndrome (CS) is most commonly caused by exogenous administration of glucocorticoids and rarely by endogenous hypercortisolemia. CS owing to adrenal lesions is the most common cause of endogenous CS in neonates and infants, and adrenocortical tumors (ACTs) represent most cases. Many ACTs develop in the context of a TP53 gene mutation, which causes Li-Fraumeni syndrome. More rarely, neonatal CS presents as part of other syndromes such as McCune-Albright syndrome or Beckwith-Wiedemann syndrome. Management usually includes resection of the primary tumor with or without additional medical treatment, but manifestations may persist after resolution of hypercortisolemia. Published by Elsevier Inc.

  6. Association between periodontal diseases and systemic diseases

    Patrícia Weidlich

    2008-08-01

    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.

  7. Skin Diseases: Skin Health and Skin Diseases

    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 ...

  8. Lysosomal storage disease 2 - Pompe's disease

    van der Ploeg, Ans T.; Reuser, Arnold J. J.

    2008-01-01

    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

  9. Huntington's disease: a perplexing neurological disease ...

    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 ...

  10. Parkinson's Disease Videos

    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: ...

  11. Parkinson disease - discharge

    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 ...

  12. Parkinson's Disease Videos

    Full Text Available ... Tips for Care Partners Nurse Webinars: Nursing Solutions: Innovations in PD Nurse Education CareMAP: Managing Advanced Parkinson's ... Progression of the Disease? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis How Is Parkinson's Disease ...

  13. Understanding cardiovascular disease

    ... 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 ...

  14. Pediatric Celiac Disease

    ... 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 ...

  15. Parkinson's Disease Videos

    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: ...

  16. Degenerative Nerve Diseases

    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 ...

  17. Ebola (Ebola Virus Disease)

    ... Controls Cancel Submit Search the CDC Ebola (Ebola Virus Disease) Note: Javascript is disabled or is not ... gov . Recommend on Facebook Tweet Share Compartir Ebola Virus Disease (EVD) is a rare and deadly disease ...

  18. Mixed Connective Tissue Disease

    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 ...

  19. Cardiovascular Disease and Diabetes

    ... 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 ...

  20. Lou Gehrig's Disease (ALS)

    ... 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 ...

  1. Parkinson's Disease Videos

    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 ...

  2. Lyme Disease Data

    ... 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 ...

  3. Arthritis and Rheumatic Diseases

    ... 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 ...

  4. Parkinson's Disease Videos

    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 ...

  5. Chronic kidney disease

    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 ...

  6. Tay-Sachs Disease

    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 ...

  7. Menopause and Heart Disease

    ... 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 ...

  8. Autoimmune liver disease panel

    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 ...

  9. Lyme disease (image)

    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 ...

  10. Quiz: Alzheimer's Disease

    ... of this page please turn JavaScript on. Feature: Alzheimer's Disease Quiz: Alzheimer's Disease Past Issues / Winter 2015 Table of Contents ... How many Americans over age 65 may have Alzheimer's disease? as many as 5 million as many ...

  11. Parkinson's Disease Videos

    Full Text Available ... Parkinson's Disease: One Voice, Many Listeners Expert Briefings: Medical Therapies: What's in the Parkinson's Pipeline? Expert Briefings: Under-recognized Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping ...

  12. Heart Diseases and Disorders

    ... 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 ...

  13. Polycystic ovarian disease: endocrinological parameters with specific reference to growth hormone and somatomedin-C.

    Urdl, W

    1988-01-01

    Thirty-three women (22-38 years old) with polycystic ovarian disease (PCOD) were included in this study. The criteria for diagnosis were: an LH/FSH ratio greater than 2.0; polycystic ovaries, diagnosed by means of palpation and ultrasound; androgenism and menstrual cycle abnormalities. Using endocrine parameters, we attempted to define distinct forms of PCOD. The patients were placed in three groups according to serum levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17 alpha OHP) and the estrone/androstendione (E1/delta 4A) ratio. Patients in group I (n = 18) had an elevated T level (greater than 1.0 ng/ml) and a 17 alpha OHP level under 4.0 ng/ml. This type of POCD was called the "androgen" type. Patients in group II (n = 7) had normal T- and 17 alpha OHP levels under 4.0 ng/ml and an elevated (E1/delta 4A) ratio. This type of PCOD was called the "estrogen" type. Group III (n = 8) comprised patients with 17 alpha OHP levels over 4.0 ng/ml. This type of PCOD was called the "adrenocortical" type. In two patients of this group, a modified ACTH test revealed late-onset congenital hyperplasia. The endocrine parameters of the patients with PCOD were compared with those of 17 adult without signs of PCOD. Statistical evaluation was done by variance analysis. Women with acromegaly often show signs of androgenism as well as menstrual cycle abnormalities. This may indicate an association between the growth factors human growth hormone (HGH) and somatomedin-C (Sm-C) and the biosynthese and metabolism of steroid hormone. Recent experiments have demonstrated such associations. Our study showed an association between the HGH and Sm-C levels and abnormal steroid hormone concentrations in women with androgen type PCOD (group I). These patients had a significantly decreased HGH level, a significantly decreased HGH/Sm-C ratio, and an increased average Sm-C level. These data suggest that elevated Sm-C levels can, by a negative-feedback mechanism, inhibit pituitary HGH

  14. Parasitic diseases of lungs

    Rozenshtraukh, L.C.; Rybakova, N.I.; Vinner, M.G.

    1987-01-01

    Roentgenologic semiotics of the main parasitic diseases of lungs is described: echinococcosis, paragonimiasis, cysticercosis, toxoplasmosis, ascariasis, amebiosis and some rarely met parasitic diseases

  15. Biomarker for Glycogen Storage Diseases

    2017-07-03

    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

  16. Diabetes and Celiac Disease

    ... 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. ...

  17. Poorly Responsive Celiac Disease

    ... 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 ...

  18. The integrated disease network.

    Sun, Kai; Buchan, Natalie; Larminie, Chris; Pržulj, Nataša

    2014-11-01

    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.

  19. Epigenetics of kidney disease.

    Wanner, Nicola; Bechtel-Walz, Wibke

    2017-07-01

    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.

  20. [Periodontal disease in pediatric rheumatic diseases].

    Fabri, Gisele M C; Savioli, Cynthia; Siqueira, José T; Campos, Lucia M; Bonfá, Eloisa; Silva, Clovis A

    2014-01-01

    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.

  1. Occupational skin diseases

    Mahler, V; Aalto-Korte, K; Alfonso, J H

    2017-01-01

    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...

  2. Pregnancy and periodontal disease

    Sağlam, Ebru; Saruhan, Nesrin; Çanakçı, Cenk Fatih

    2015-01-01

    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...

  3. Neuroinflammation in Alzheimer's disease and prion disease

    Eikelenboom, P.; Bate, C.; van Gool, W. A.; Hoozemans, J. J. M.; Rozemuller, J. M.; Veerhuis, R.; Williams, A.

    2002-01-01

    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,

  4. Human Environmental Disease Network

    Taboureau, Olivier; Audouze, Karine

    2017-01-01

    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...

  5. Menopause and Rheumatic Disease.

    Talsania, Mitali; Scofield, Robert Hal

    2017-05-01

    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.

  6. Wilson’s Disease

    Figen Hanağası

    2013-12-01

    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

  7. Lysosomal storage diseases

    Ferreira, Carlos R.; Gahl, William A.

    2016-01-01

    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

  8. Nonalcoholic fatty liver disease - A multisystem disease?

    Mikolasevic, Ivana; Milic, Sandra; Turk Wensveen, Tamara; Grgic, Ivana; Jakopcic, Ivan; Stimac, Davor; Wensveen, Felix; Orlic, Lidija

    2016-01-01

    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

  9. Parkinson's Disease Videos

    Full Text Available ... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping ... Library is an extensive collection of books, fact sheets, videos, podcasts, and more. To get started, use ...

  10. Parkinson's Disease Videos

    Full Text Available ... PD Library Search library Topic Type Expert Briefings: Marijuana and PD: What Do We Really Know? Nurse ... Mind Guide to Parkinson's Disease Guide to Deep Brain Stimulation Sleep: A Mind Guide to Parkinson’s Disease ...

  11. Lyme Disease Transmission

    ... not known to transmit Lyme disease include Lone star ticks ( Amblyomma americanum ), the American dog tick ( Dermacentor ... of Vector-Borne Diseases (DVBD) Email Recommend Tweet YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs ...

  12. Parkinson's Disease Videos

    Full Text Available ... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping ... Beckham Leads Stretches Is Compulsive Behavior a Side Effect of PD Medications? What Are Some Practical Strategies ...

  13. APOE Genotyping, Cardiovascular Disease

    ... Resources For Health Professionals Subscribe Search APOE Genotyping, Cardiovascular Disease Send Us Your Feedback Choose Topic At a ... help understand the role of genetic factors in cardiovascular disease . However, the testing is sometimes used in clinical ...

  14. Parkinson's Disease Videos

    Full Text Available ... Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research ... Progression of the Disease? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis What Are Some Strategies ...

  15. Parkinson's Disease Videos

    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? Why Is It Important to Continue Self-Care ...

  16. Children and Parasitic Diseases

    ... 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 ...

  17. Parkinson's Disease Videos

    Full Text Available ... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping ... with Advanced Parkinson's How Does the DBS Device Work? What Are the Strategies for Managing Problems with ...

  18. Parkinson's Disease Videos

    Full Text Available ... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping ... 2016: Coping Strategy: Yoga & Stretching CareMAP: Medications and General Health Part 1 Expert Briefings: Depression and PD: ...

  19. Celiac Disease: Diagnosis.

    Byrne, Greg; Feighery, Conleth F

    2015-01-01

    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.

  20. Celiac Disease Tests

    ... 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 ...

  1. Addison's Disease: Treatment

    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: ...

  2. Lyme disease antibody

    ... JavaScript. The Lyme disease blood test looks for antibodies in the blood to the bacteria that causes ... needed. A laboratory specialist looks for Lyme disease antibodies in the blood sample using the ELISA test . ...

  3. Parkinson's Disease Videos

    Full Text Available ... There is a lot to know about Parkinson's disease. Learn about symptoms, how it is diagnosed and ... quality of life and live well with Parkinson's disease. Learn More Expert Care Patient Centered Care Centers ...

  4. Parkinson's Disease Videos

    Full Text Available ... PD Expert Briefings: Parkinson's Disease: Financial, Legal and Medical Planning Tips for Care Partners Nurse Webinars: Nursing ... Parkinson's Disease: One Voice, Many Listeners Expert Briefings: Medical Therapies: What's in the Parkinson's Pipeline? Expert Briefings: ...

  5. Parkinson's Disease Videos

    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? CareMAP: Cambios para Realizar en Casa, Parte 1 ...

  6. Fatty Liver Disease

    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 ...

  7. Gum Disease and Men

    ... 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 ...

  8. Parkinson's Disease Videos

    Full Text Available ... Progression of the Disease? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis What Are Some Strategies ... to Know? Why Is Comprehensive Care or Team Approach Important? 2013 PSA Featuring Katie Couric What Are ...

  9. Progression of Liver Disease

    ... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

  10. Parkinson's Disease Videos

    Full Text Available ... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping ... for Following a Medication Schedule? CareMAP: Medications and General Health Part 1 What Is Patient-Centered Care? ...

  11. Parkinson's Disease Videos

    Full Text Available ... Progression of the Disease? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis What Are Some Strategies for Problems with Urination? CareMAP: Changes Around the ...

  12. Valvular heart disease

    Gelson, E; Gatzoulis, M; Johnson, M

    2007-01-01

    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

  13. Parkinson's Disease Videos

    Full Text Available ... for Parkinson's Care Partners OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis What Is the Progression ... Disease? What Are Some Strategies to Improve the Quality of Community Care for PD Patients? Hallucinations and ...

  14. Parkinson's Disease Videos

    Full Text Available ... of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping Skills for ... the Helpline? What are some strategies to prevent falls in PD patients? How Does Speech Therapy Help ...

  15. Machado-Joseph Disease

    ... Caregiver Education » Fact Sheets Machado-Joseph Disease Fact Sheet What is Machado-Joseph disease? What are the ... the repeat is in a protein-producing or coding region of the gene. Modifications of the mutant ...

  16. Parkinson's Disease Videos

    Full Text Available ... of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping Skills for ... or Exercise Programs Are Recommended? CareMAP: Movement and Falls: Part 1 Expert Briefings: Depression and PD: Treatment ...

  17. Parkinson's Disease Videos

    Full Text Available ... Patients with Parkinson's Disease? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis CareMAP: Movimientos y Caídas, Parte 2 What Are Some Strategies for Problems with Urination? Caregiver ...

  18. Parkinson's Disease Videos

    Full Text Available ... Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research ... Is Parkinson's Disease Diagnosed? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis CareMAP: Getting Dressed What ...

  19. Parkinson's Disease Videos

    Full Text Available ... and Apathy in Parkinson's Disease Nurse Webinars: Interdisciplinary Education on Parkinson's Disease Expert Briefings: Getting Around: Transportation and Travel with PD Expert Briefings: Sleep and Parkinson's Nurse: ...

  20. Parkinson's Disease Videos

    Full Text Available ... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping ... Excessive Daytime Sleepiness? Is Compulsive Behavior a Side Effect of PD Medications? CareMAP: Putting Things in Place ...

  1. Parkinson's Disease Videos

    Full Text Available ... Bringing Care to You Expert Care Programs Professional Education Expert Care Research shows people with Parkinson’s who ... and Apathy in Parkinson's Disease Nurse Webinars: Interdisciplinary Education on Parkinson's Disease Expert Briefings: Getting Around: Transportation ...

  2. Parkinson's Disease Videos

    Full Text Available ... Expert Briefings: Parkinson's Disease: Financial, Legal and Medical Planning Tips for Care Partners Nurse Webinars: Nursing Solutions: ... and Parkinson's Disease 2010 Expert Briefings: Legal Issues: Planning Ahead When You are Living with Parkinson's Expert ...

  3. Parkinson's Disease Videos

    Full Text Available ... PD: What Do We Really Know? Nurse Webinars: Nursing Solutions: Improving Caregiver Strain through Science and Model ... Disease Psychosis: Hallucinations, Delusions and Paranoia Nurse Webinars: Nursing Solutions: Understanding Fatigue and Apathy in Parkinson's Disease ...

  4. Pregnancy and Thyroid Disease

    ... People Who Were Treated with hGH Thyroid Disease & Pregnancy Thyroid disease is a group of disorders that ... prescribes. What role do thyroid hormones play in pregnancy? Thyroid hormones are crucial for normal development of ...

  5. Parkinson's Disease Videos

    Full Text Available ... Parkinson's There is a lot to know about Parkinson's disease. Learn about symptoms, how it is diagnosed and ... your quality of life and live well with Parkinson's disease. Learn More Expert Care Patient Centered Care Centers ...

  6. Glomerular Disease in Women

    Kate Wiles

    2018-03-01

    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.

  7. Genetic Disease Foundation

    ... has used its fundraising efforts to help further research programs at Mount Sinai. Spotlight: Gaucher Gaucher Disease is the most common of the lipid storage diseases. Learn about its symptoms, how it ...

  8. Tay-Sachs Disease

    ... 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 ...

  9. Acid Lipase Disease

    ... 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 ...

  10. Maple syrup urine disease

    ... this page: //medlineplus.gov/ency/article/000373.htm Maple syrup urine disease To use the sharing features on this page, please enable JavaScript. Maple syrup urine disease (MSUD) is a disorder in ...

  11. Parkinson's Disease Videos

    Full Text Available ... Help with Cognitive Impairment? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis Parkinson’s Disease Psychosis: A Caregiver’s Story What Are Some Strategies for Problems with Urination? CareMAP: Las Actividades en ...

  12. [Emerging noninfectious diseases].

    Consiglio, Ezequiel

    2008-11-01

    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.

  13. Parkinson's Disease Videos

    Full Text Available ... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping ... What Medications Help with Cognitive Impairment? CareMAP: Balancing Life and Caregiving Help is just a click away. ...

  14. Parkinson's Disease Videos

    Full Text Available ... library Topic Type Living Alone: Home Safety and Management in PD Expert Briefings: Marijuana and PD: What ... Misconceptions About Parkinson's Disease? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis What Are Some Strategies ...

  15. Parkinson's Disease Videos

    Full Text Available ... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping ... Pensamiento y el Comportamiento, Parte 2 CareMAP: Balancing Life and Caregiving Jose Maria Lobo: Musica en vivo ...

  16. Motor Neuron Diseases

    ... 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 ...

  17. Parkinson's Disease Videos

    Full Text Available ... this disease. Learn more In your area About Shop A A ... Webinars: Nursing Solutions: Improving Caregiver Strain through Science and Model Interventions Expert Briefings: Parkinson's Disease Psychosis: ...

  18. Parkinson's Disease Videos

    Full Text Available ... library Topic Type Living Alone: Home Safety and Management in PD Expert Briefings: Marijuana and PD: What ... Overview of Parkinson's Disease OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis Is There a Cure ...

  19. Parkinson's Disease Videos

    Full Text Available ... Delusions and Paranoia Nurse Webinars: Nursing Solutions: Understanding Fatigue and Apathy in Parkinson's Disease Nurse Webinars: Interdisciplinary ... Missing? Communication and the PD Partnership Expert Briefings: Fatigue, Sleep Disorders and Parkinson's Disease Expert Briefings: What's ...

  20. Parkinson's Disease Videos

    Full Text Available ... Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research ... Help with Cognitive Impairment? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis Parkinson’s Disease Psychosis: A ...

  1. Parkinson's Disease Videos

    Full Text Available ... Learn More Research Research We Fund Parkinson's Outcomes Project Grant Opportunities Science News & Progress Patient Engagement Research ... Help with Freezing Episodes? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis Overview of Parkinson's Disease ...

  2. Parkinson's Disease Videos

    Full Text Available ... With Non-Parkinson's Disease Medications? Caregiver Summit 2016: Maintaining Dignity & Identity What to Expect Emotionally Walking for ... Around the House: Part 2 What Is the Relationship Between Depression and Parkinson's Disease? Tips for Caregivers ...

  3. Gallstone disease and mortality

    Shabanzadeh, Daniel Mønsted; Sørensen, Lars Tue; Jørgensen, Torben

    2017-01-01

    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...

  4. Childhood Interstitial Lung Disease

    ... rule out conditions such as asthma , cystic fibrosis , acid reflux, heart disease, neuromuscular disease, and immune deficiency. Various ... a lung infection. Acid-blocking medicines can prevent acid reflux, which can lead to aspiration. Lung Transplant A ...

  5. Parkinson's Disease Videos

    Full Text Available ... Fatigue, Sleep Disorders and Parkinson's Disease Expert Briefings: What's in the Parkinson's Pipeline? Expert Briefings: Nutrition and Parkinson's Disease 2010 Expert Briefings: Legal Issues: Planning Ahead When You are Living with Parkinson's Expert ...

  6. Parkinson's Disease Videos

    Full Text Available ... Otros Trastornos que Tienen Síntomas Similares? How Does Speech Therapy Help Parkinson's ... Disease? Are There Disorders That Have Similar Symptoms? How Does Parkinson's Disease ...

  7. Parkinson's Disease Videos

    Full Text Available ... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping ... and Its Treatment Affect Sexual Functioning? CareMAP: Balancing Life and Caregiving Help is just a click away. ...

  8. Takayasu's disease and pregnancy

    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.

  9. Chronic Kidney Diseases

    ... Safe Videos for Educators Search English Español Chronic Kidney Diseases KidsHealth / For Kids / Chronic Kidney Diseases What's ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...

  10. Hypertensive heart disease

    ... page: //medlineplus.gov/ency/article/000163.htm Hypertensive heart disease To use the sharing features on this page, please enable JavaScript. Hypertensive heart disease refers to heart problems that occur because of ...

  11. Heart disease and intimacy

    ... this page: //medlineplus.gov/ency/patientinstructions/000540.htm Heart disease and intimacy To use the sharing features on ... Libby P, Bonow RO, Braunwald E, eds. Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine . 10th ed. Philadelphia, ...

  12. Aspirin and heart disease

    ... medlineplus.gov/ency/patientinstructions/000092.htm Aspirin and heart disease To use the sharing features on this page, ... healthy people who are at low risk for heart disease. You provider will consider your overall medical condition ...

  13. Parkinson's Disease Videos

    Full Text Available ... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping ... About Sexual Dysfunction? Attachment: consultation.jpg CareMAP: Balancing Life and Caregiving What Medications Help with Cognitive Impairment? ...

  14. Parkinson's Disease Videos

    Full Text Available ... library Topic Type Living Alone: Home Safety and Management in PD Expert Briefings: Marijuana and PD: What ... Progression of the Disease? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis What Are Some Strategies ...

  15. Parkinson's Disease Videos

    Full Text Available ... for PD Patients? Are There Any Ways to Control the Rate of Progression of the Disease? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis What Are Some Strategies ...

  16. Parkinson's Disease Videos

    Full Text Available ... Managing Depression, Anxiety & Psychosis OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis What Is the Relationship Between Depression and Parkinson's Disease? What Are Some Strategies for Problems with Urination? Hallucinations and Delusions CareMAP: ...

  17. Parkinson's Disease Videos

    Full Text Available ... Briefings: Dealing with Dementia in PD Expert Briefings: Anxiety in Parkinson's Disease Expert Briefings: Nutrition and Parkinson's ... and Tomorrow Expert Briefings: A Closer Look at Anxiety and Depression in Parkinson's Disease Expert Briefings: Driving ...

  18. Congenital heart disease

    Congenital heart disease (CHD) is a problem with the heart's structure and function that is present at birth. ... Fraser CD, Kane LC. Congenital heart disease. In: Townsend CM Jr, ... Sabiston Textbook of Surgery: The Biological Basis of Modern ...

  19. Heart Disease Risk Factors

    ... About CDC.gov . Home About Heart Disease Coronary Artery Disease Heart Attack Heart Attack Signs and Symptoms ... Privacy FOIA No Fear Act OIG 1600 Clifton Road Atlanta , GA 30329-4027 USA 800-CDC-INFO ( ...

  20. Leprosy (Hansen's Disease)

    ... with facebook share with twitter share with linkedin Leprosy (Hansen's Disease) Credit: NIAID Some classic histopathologic changes ... as Mycobacterium leprae . Why Is the Study of Leprosy (Hansen's Disease) a Priority for NIAID? At the ...

  1. Parkinson's Disease Videos

    Full Text Available ... Sexual Dysfunction? Attachment: consultation.jpg What Is the Relationship Between Depression and Parkinson's Disease? OHSU - Therapeutic Approaches for PD: Depression, Anxiety & Psychosis Parkinson’s Disease Psychosis: A Caregiver’s Story CareMAP: ...

  2. Myonecrosis of Behcet's disease

    Stubbs, Alana Y.; Taljanovic, Mihra S.; Massey, Brandon Z.; Graham, Anna R.; Friend, Christopher J.; Walsh, Joshua A.

    2008-01-01

    Behcet's disease is an inflammatory disease of unknown cause characterized by intermittent episodes of acute inflammation manifested by oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. We report a rare case of myonecrosis associated with Behcet's disease. Myonecrosis of Behcet's disease can mimic soft tissue abscess and therefore awareness of this entity in the appropriate clinical setting is important for initiation of appropriate and timely treatment. (orig.)

  3. Addison′s disease

    Soumya Brata Sarkar; Subrata Sarkar; Supratim Ghosh; Subhankar Bandyopadhyay

    2012-01-01

    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...

  4. Parkinson's disease and anxiety

    Walsh, K; Bennett, G

    2001-01-01

    There has been a recent surge of interest in the subject of anxiety in patients with Parkinson's disease. Up to 40% of patients with Parkinson's disease experience clinically significant anxiety. This anxiety may be a psychological reaction to the stress of the illness or may be related to the neurochemical changes of the disease itself. Antiparkinsonian drugs may have a role in the pathogenesis of the anxiety. The anxiety disorders in Parkinson's disease patients appear to be clustered in th...

  5. [Tick-borne diseases].

    Tissot Dupont, H; Raoult, D

    1993-05-01

    Due to their worldwide distribution, from hottest to coldest climates, and due to their behaviour, ticks are capable of transmitting numerous human and animal bacterial viral or parasitous diseases. Depending on the disease, they play the role of biological vector or intermediate host. In France, six tick borne diseases are of epidemiologic importance. Q fever (not often tick-borne), Mediterranean Spotted Fever, Lyme disease, Turalemia (human and animal), Babesiosis and Tick-borne Viral Encephalitis.

  6. Gender and Cardiovascular Disease

    Den Ruijter, Hester M.; Pasterkamp, Gerard

    2015-01-01

    More women than men die of cardiovascular disease (CVD) each year in every major developed country and most emerging economies. Nonetheless, CVD has often been considered as men’s disease due to the higher rates of coronary artery disease (CAD) of men at younger age. This has led to the

  7. Diseases of lodgepole pine

    Frank G. Hawksworth

    1964-01-01

    Diseases are a major concern to forest managers throughout the lodgepole pine type. In many areas, diseases constitute the primary management problem. As might be expected for a tree that has a distribution from Baja California, Mexico to the Yukon and from the Pacific to the Dakotas, the diseases of chief concern vary in different parts of the tree's range. For...

  8. Parkinson's Disease Videos

    Full Text Available ... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping ... How Does Parkinson's Disease Affect Memory? CareMAP: Balancing Life and Caregiving CareMAP: La Alimentación y la Deglución, ...

  9. Parkinson's Disease Videos

    Full Text Available ... We Walk at Moving Day CareMAP: Managing Caregiver Stress Aware in Care: Real Stories CareMAP: End-of- ... Progression of the Disease? OHSU - Parkinson's Disease: Pharmacological Management of Depression, Anxiety & Psychosis Overview of Parkinson's Disease ...

  10. Symptoms of Celiac Disease

    ... tested for celiac disease and if negative the test should be repeated on a periodic basis. These conditions include insulin-dependent diabetes mellitus (requiring insulin therapy), Hashimoto’s thyroiditis, Turner’s syndrome, Williams syndrome, Graves disease and Sjogren’s disease. what turns ...

  11. Peptic Ulcer Disease

    ... Site ACG Patients Home / Digestive Health Topic / Peptic Ulcer Disease Peptic Ulcer Disease Basics Overview An “ulcer” is an open ... for pain in patients at risk for peptic ulcer disease. Peptic – caused by acid. PPIs – P roton P ump ...

  12. Armillaria Root Disease

    R.E. Williams; C.G. III Shaw; P.M. Wargo; W.H. Sites

    1986-01-01

    Armillaria root disease is found throughout temperate and tropical regions of the world. In the continental United States, the disease has been reported in nearly every State. Hosts include hundreds of species of trees, shrubs, vines, and forbs growing in forests, along roadsides, and in cultivated areas. The disease is caused by fungi, which live as parasites on...

  13. Parkinson's Disease Videos

    Full Text Available ... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping ... and Parkinson's Disease? Hallucinations and Delusions CareMAP: Balancing Life and Caregiving CareMAP: Travel and Transportation: Part 1 ...

  14. diseases free body

    thararose

    2018-01-01

    Diseases are very common now a days . It is our food habits itself that causes this diseases. Diseases can cause many health problems. goiter causes and symptoms It is very important to follow healthy food habits and to maintain good health. A healthy body is always a treasure to every person.

  15. Granulomatous diseases in otolaryngology

    Kuczkowski, J.; Barcinski, G.; Narozny, W.

    1994-01-01

    The authors describe clinical material of 49 patients treated in period 1960-1992 at the Dept. of Otolaryngology Medical Acad. of Gdansk on reason various granulomatous diseases. On the ground of retrospective analysis 44 cases with mild granulomas disease and 5 cases with malignant granulomatous disease were separated. Clinical course diagnosis, treatment and prognosis were discussed. (author)

  16. Parkinson's Disease Videos

    ... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping Skills for ... Caregivers: Caremap and Caring & Coping CareMAP: Movement and Falls: Part ... There Any Ways to Control the Rate of Progression of the Disease? CareMAP: ...

  17. Parkinson's Disease Videos

    Full Text Available ... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping Skills for ... Caregivers: Caremap and Caring & Coping CareMAP: Movement and Falls: Part ... There Any Ways to Control the Rate of Progression of the Disease? CareMAP: ...

  18. Lyme Disease (For Kids)

    ... Staying Safe Videos for Educators Search English Español Lyme Disease KidsHealth / For Kids / Lyme Disease What's in this article? Ticks Want to Suck ... and summer, you might hear about something called Lyme disease. It has nothing to do with limes, but ...

  19. Parkinson's Disease Videos

    Full Text Available ... Nonmotor Symptoms of Parkinson's Disease Expert Briefings: Gait, Balance and Falls in Parkinson's Disease Expert Briefings: Coping ... Foundation How Is Parkinson's Disease Diagnosed? CareMAP: Balancing Life and Caregiving CareMAP: Travel and Transportation: Part 1 ...

  20. Dutch elm disease

    James W. Walters

    1992-01-01

    Since its discovery in the United States in 1930, Dutch elm disease has killed thousands of native elms. The three native elms, American, slippery, and rock, have little or no resistance to Dutch elm disease, but individual trees within each species vary in susceptibility to the disease. The most important of these, American elm, is scattered in upland stands but is...

  1. Heart Disease in Women

    ... United States, 1 in 4 women dies from heart disease. The most common cause of heart disease in both men and women is narrowing ... the blood vessels that supply blood to the heart itself. This is called coronary artery disease, and ...

  2. Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease

    Hansen, Peter Riis

    2018-01-01

    Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory...... pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future...... prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations...

  3. Coronary Artery Disease - Coronary Heart Disease

    ... not as great as men's. Heredity (Including Race) Children of parents with heart disease are more likely to develop it themselves. African Americans have more severe high blood pressure than Caucasians and a higher risk of heart ...

  4. Disease-modifying drugs in Alzheimer's disease

    Ghezzi L

    2013-12-01

    Full Text Available Laura Ghezzi, Elio Scarpini, Daniela Galimberti Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, Milan, Italy Abstract: Alzheimer's disease (AD is an age-dependent neurodegenerative disorder and the most common cause of dementia. The early stages of AD are characterized by short-term memory loss. Once the disease progresses, patients experience difficulties in sense of direction, oral communication, calculation, ability to learn, and cognitive thinking. The median duration of the disease is 10 years. The pathology is characterized by deposition of amyloid beta peptide (so-called senile plaques and tau protein in the form of neurofibrillary tangles. Currently, two classes of drugs are licensed by the European Medicines Agency for the treatment of AD, ie, acetylcholinesterase inhibitors for mild to moderate AD, and memantine, an N-methyl-D-aspartate receptor antagonist, for moderate and severe AD. Treatment with acetylcholinesterase inhibitors or memantine aims at slowing progression and controlling symptoms, whereas drugs under development are intended to modify the pathologic steps leading to AD. Herein, we review the clinical features, pharmacologic properties, and cost-effectiveness of the available acetylcholinesterase inhibitors and memantine, and focus on disease-modifying drugs aiming to interfere with the amyloid beta peptide, including vaccination, passive immunization, and tau deposition. Keywords: Alzheimer's disease, acetylcholinesterase inhibitors, memantine, disease-modifying drugs, diagnosis, treatment

  5. Radiotherapy of benign diseases

    Haase, W.

    1982-01-01

    Still today radiotherapy is of decisive relevance for several benign diseases. The following ones are briefly described in this introductory article: 1. Certain inflammatory and degenerative diseases as furuncles in the face, acute thrombophlebitis, recurrent sudoriparous abscesses, degenerative skeletal diseases, cervical syndrome and others; 2. rheumatic joint diseases; 3. Bechterew's disease; 4. primary presenile osteoporosis; 5. synringomyelia; 6. endocrine ophthalmopathy; 7. hypertrophic processes of the connective tissue; 8. hemangiomas. A detailed discussion and a profit-risk analysis is provided in the individual chapters of the magazine. (MG) [de

  6. Diagnosis of Pompe disease

    Vissing, John; Lukacs, Zoltan; Straub, Volker

    2013-01-01

    The diagnosis of Pompe disease (acid maltase deficiency, glycogen storage disease type II) in children and adults can be challenging because of the heterogeneous clinical presentation and considerable overlap of signs and symptoms found in other neuromuscular diseases. This review evaluates some...... to identify late-onset Pompe disease often leads to false-negative results and subsequent delays in identification and treatment of the disorder. Serum creatine kinase level can be normal or only mildly elevated in late-onset Pompe disease and is not very helpful alone to suggest the diagnosis...

  7. Pediatric Inflammatory Bowel Diseases

    Lauritzen, Didde; Andreassen, Bente Utoft; Heegaard, Niels Henrik H

    2018-01-01

    Background: Kidney disease has been reported in adults with inflammatory bowel disease (IBD) and is regarded an extraintestinal manifestation or more rarely a side effect of the medical treatment. Methods: In this cross-sectional study we describe the extent of kidney pathology in a cohort of 56...... children with IBD. Blood and urine samples were analyzed for markers of kidney disease and ultrasonography was performed to evaluate pole-to-pole kidney length. Results: We found that 25% of the patients had either previously reported kidney disease or ultrasonographic signs of chronic kidney disease...... are at risk of chronic kidney disease, and the risk seems to be increased with the severity of the disease....

  8. Pregnancy and rheumatic diseases.

    Gayed, M; Gordon, C

    2007-11-01

    Pregnancy is an issue that should be discussed with all patients with rheumatic diseases who are in the reproductive age group. Infertility is rarely due to the disease but can be associated with cyclophosphamide therapy. Most rheumatic diseases that are well controlled prior to pregnancy do not deteriorate in pregnancy, providing that the patient continues with appropriate disease-modifying therapy. Some patients with inflammatory arthritis go in to remission during pregnancy. Patients with renal involvement may be at increased risk of disease flare. This needs to be distinguished from pre-eclampsia. Intrauterine growth restriction is more likely in patients with active systemic disease, hypertension, a history of thrombosis and renal involvement. Premature delivery may need to be planned to reduce the risks of stillbirth and can be associated with a variety of neonatal complications. Post-partum flare is common in all the rheumatic diseases.

  9. Heart Disease, Stroke, or Other Cardiovascular Disease and Adult Vaccination

    ... Adult Diseases Resources Heart Disease, Stroke, or Other Cardiovascular Disease and Adult Vaccination Language: English (US) Español (Spanish) ... important step in staying healthy. If you have cardiovascular disease, talk with your doctor about getting your vaccinations ...

  10. Coeliac disease and epilepsy.

    Cronin, C C

    2012-02-03

    Whether there is an association between coeliac disease and epilepsy is uncertain. Recently, a syndrome of coeliac disease, occipital lobe epilepsy and cerebral calcification has been described, mostly in Italy. We measured the prevalence of coeliac disease in patients attending a seizure clinic, and investigated whether cerebral calcification occurred in patients with both coeliac disease and epilepsy. Screening for coeliac disease was by IgA endomysial antibody, measured by indirect immunofluorescence using sections of human umbilical cord. Of 177 patients screened, four patients were positive. All had small-bowel histology typical of coeliac disease. The overall frequency of coeliac disease in this mixed patient sample was 1 in 44. In a control group of 488 pregnant patients, two serum samples were positive (1 in 244). Sixteen patients with both coeliac disease and epilepsy, who had previously attended this hospital, were identified. No patient had cerebral calcification on CT scanning. Coeliac disease appears to occur with increased frequency in patients with epilepsy, and a high index of suspicion should be maintained. Cerebral calcification is not a feature of our patients with epilepsy and coeliac disease, and may be an ethnically-or geographically-restricted finding.

  11. Viral Disease Networks?

    Gulbahce, Natali; Yan, Han; Vidal, Marc; Barabasi, Albert-Laszlo

    2010-03-01

    Viral infections induce multiple perturbations that spread along the links of the biological networks of the host cells. Understanding the impact of these cascading perturbations requires an exhaustive knowledge of the cellular machinery as well as a systems biology approach that reveals how individual components of the cellular system function together. Here we describe an integrative method that provides a new approach to studying virus-human interactions and its correlations with diseases. Our method involves the combined utilization of protein - protein interactions, protein -- DNA interactions, metabolomics and gene - disease associations to build a ``viraldiseasome''. By solely using high-throughput data, we map well-known viral associated diseases and predict new candidate viral diseases. We use microarray data of virus-infected tissues and patient medical history data to further test the implications of the viral diseasome. We apply this method to Epstein-Barr virus and Human Papillomavirus and shed light into molecular development of viral diseases and disease pathways.

  12. Hereditary neuromuscular diseases

    Oezsarlak, O. E-mail: ozkan.ozsarlak@uza.be; Schepens, E.; Parizel, P.M.; Goethem, J.W. van; Vanhoenacker, F.; Schepper, A.M. de; Martin, J.J

    2001-12-01

    This article presents the actual classification of neuromuscular diseases based on present expansion of our knowledge and understanding due to genetic developments. It summarizes the genetic and clinical presentations of each disorder together with CT findings, which we studied in a large group of patients with neuromuscular diseases. The muscular dystrophies as the largest and most common group of hereditary muscle diseases will be highlighted by giving detailed information about the role of CT and MRI in the differential diagnosis. The radiological features of neuromuscular diseases are atrophy, hypertrophy, pseudohypertrophy and fatty infiltration of muscles on a selective basis. Although the patterns and distribution of involvement are characteristic in some of the diseases, the definition of the type of disease based on CT scan only is not always possible.

  13. Genetics of complex diseases

    Mellerup, Erling; Møller, Gert Lykke; Koefoed, Pernille

    2012-01-01

    A complex disease with an inheritable component is polygenic, meaning that several different changes in DNA are the genetic basis for the disease. Such a disease may also be genetically heterogeneous, meaning that independent changes in DNA, i.e. various genotypes, can be the genetic basis...... for the disease. Each of these genotypes may be characterized by specific combinations of key genetic changes. It is suggested that even if all key changes are found in genes related to the biology of a certain disease, the number of combinations may be so large that the number of different genotypes may be close...... to the number of patients suffering from the disease. This hypothesis is based on a study of bipolar disorder....

  14. Castleman disease (literature review

    A. L. Melikyan

    2016-01-01

    Full Text Available Castleman disease (angiofollicular hyperplasia of lymph nodes – a rare benign lymphoproliferative disease with prolonged asymptomatic course, associated with a wide variety of autoimmune and oncological diseases and the risk of non-Hodgkin’s lymphoma. The rare occurrence of this disease and a variety of clinical course did not allow for a complete and consistent research on the etiology and pathogenesis and the standard therapies development. In recent years, the number of patients with Castleman disease in the Russian Federation has increased, which requires its recognition among non-neoplastic and neoplastic lymphadenopathy. The article provides an overview about clinical and histological variants of Castleman’s disease, its pathogenesis concepts, classification and treatment.

  15. Celiac disease in Iran

    Malekzadeh R

    2007-06-01

    Full Text Available Background: Until a few decades ago, celiac disease was considered to be essentially a disease of European people and to be very rare in Middle Eastern countries. During the last two decades, having met the criteria for the WHO general screening, the advent and application of novel serological assays used to screen for celiac disease and the use of endoscopic small bowel biopsy have led to increasing numbers of diagnoses of celiac disease in western countries. With this new data, our knowledge on both the clinical pattern and epidemiology of celiac disease has increased, and is now known to be a relatively common autoimmune disorder. Studies performed in different parts of the developing world have shown that the prevalence of celiac disease in this area is similar to or even higher than that in western countries. In fact, celiac disease is known to be the most common form of chronic diarrhea in Iran. However, contrary to common belief, celiac disease is more than a pure digestive alteration. It is a protean systemic disease, and, with a 95 percent genetic predisposition, has a myriad of symptoms including gastrointestinal, dermatological, dental, neurological and behavioral that can occur at a variety of ages. Monosymptomatic, oligosymptomatic, atypical (without gastrointestinal symptoms, silent and latent forms of celiac disease have been identified. In this study we review the epidemiology of celiac disease based on the studies performed in Iran and discuss its pathogenesis, the role of antibodies in the diagnosis of celiac disease and the importance of its diagnosis and treatment in Iran.

  16. [Male breast diseases].

    Firmin-Lefebvre, D; Misery, L

    2013-01-01

    Because andrology is relatively undeveloped in France, the dermatologist is often the doctor first consulted for diseases of the nipple in men. All dermatological diseases can in fact occur at this site. There are some specific nipple diseases such as gynaecomastia, congenital abnormalities, hyperplasia, benign tumours and breast cancer. All clinical examinations and laboratory examinations should focus on diagnosis of this type of cancer and its elimination. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  17. Diseases Transmitted by Birds.

    Levison, Matthew E

    2015-08-01

    Although many people these days actually work very hard at leisure time activities, diseases are most commonly acquired from birds during the course of work in the usual sense of the term, not leisure. However, travel for pleasure to areas where the diseases are highly endemic puts people at risk of acquiring some of these bird-related diseases (for example, histoplasmosis and arbovirus infections), as does ownership of birds as pets (psittacosis).

  18. CDC Disease Detective Camp

    2010-08-02

    The CDC Disease Detective Camp gives rising high school juniors and seniors exposure to key aspects of the CDC, including basic epidemiology, infectious and chronic disease tracking, public health law, and outbreak investigations. The camp also helps students explore careers in public health.  Created: 8/2/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 8/2/2010.

  19. At Risk for Kidney Disease?

    ... Heart Disease Mineral & Bone Disorder Causes of Chronic Kidney Disease Diabetes and high blood pressure are the most ... blood vessels in your kidneys. Other causes of kidney disease Other causes of kidney disease include a genetic ...

  20. Heart Disease in Hispanic Women

    ... Heart Disease in Women Heart Disease in Hispanic Women “I thought it couldn’t be true,” says ... disease is their No. 1 killer. Why Hispanic women? While heart disease doesn’t discriminate, you could ...