Navegando por Palavras-chave "Cushing's syndrome"
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- ItemAcesso aberto (Open Access)Adipose tissue expression of 11beta-Hydroxysteroid dehydrogenase type 1 in cushing's syndrome and in obesity(Sociedade Brasileira de Endocrinologia e Metabologia, 2007-11-01) Espíndola-Antunes, Daniela [UNIFESP]; Kater, Claudio Elias [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Glucocorticoids have a major role in determining adipose tissue metabolism and distribution. 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) is a NADPH-dependent enzyme highly expressed in the liver and adipose tissue. In most intact cells and tissues it functions as a reductase (to convert inactive cortisone to active cortisol). It has been hypothesized that tissue-specific deregulation of cortisol metabolism may be involved in the complex pathophysiology of the metabolic syndrome (MS) and obesity. Transgenic mice overexpressing 11betaHSD1 in adipose tissue develop obesity with all features of the MS, whereas 11betaHSD1-knockout mice are protected from both. The bulk of evidences points to an overexpression and increased activity of 11betaHSD1 also in human adipose tissue. However, 11betaHSD1 seems to adjust local cortisol concentrations independently of its plasma levels. In Cushing's syndrome, 11betaHSD1 is downregulated and may not be responsible for the abdominal fat depots; it also undergoes downregulation in response to weight loss in human obesity. The nonselective 11betaHSD1 inhibitor carbenoxolone improves insulin sensitivity in humans, and selective inhibitors enhance insulin action in diabetic mice liver, thereby lowering blood glucose. Thus, 11betaHSD1 is now emerging as a modulator of energy partitioning and a promising pharmacological target to treat the MS and diabetes.
- ItemSomente MetadadadosAdrenocorticotropin-producing pituitary carcinoma with expression of c-erbB-2 and high PCNA index: A comparative study with pituitary adenomas and normal pituitary tissues(Humana Press Inc, 1998-03-01) Nose-Alberti, V; Mesquita, MIS; Martin, L. C.; Kayath, M. J.; Universidade Federal de São Paulo (UNIFESP)Pituitary carcinomas are very rare neoplasms with a poor prognosis. We report a case of Cushing's disease resulting from a pituitary carcinoma in a ZZ-yr-old female, who died of massive hepatic failure. At autopsy, there was invasion of the parasellar structures and vasculature by the tumor, which stained positively only for ACTH. There were two metastatic nodules in the liver, which also stained positively for ACTH. When compared to other cases of Cushing's disease (n = 52), other pituitary adenomas (n = 292), and normal pituitary tissues (n = 21), the pituitary carcinoma was the only one with c-erbB-2 membrane staining in both the sellar-located tissue and liver metastasis. C-erbB-2 staining was present in the cytoplasm of a variable number of cells in 40% of the invasive adenomas (n = 103), while only 1.2% of the noninvasive tumors (n = 241) expressed this protein (p < 0.001). No particular immunohistological type preferentially expressed this protein. in normal pituitary tissues, 10% of the cells expressed cytoplasmic c-erbB-2. A higher index of proliferating cell nuclear antigen (PCNA) in the primary tumor and liver metastasis (10%) was also found compared to other ACTH-secreting adenomas (invasive, 3.4 +/- 1.9% vs 1.7 +/- 1.5% in noninvasive) and other pituitary tumors (invasive, 2.9 +/- 1.5% vs 1.5 +/- 1.3% in noninvasive). the PCNA index was significantly higher in invasive tumors than in noninvasive adenomas (p = 0.004). PCNA staining was negative in normal pituitary tissues. Staining for p53, pRB and p(21ras) was negative in the carcinoma and liver metastasis. We suggest that the c-erbB-2 membrane pattern and a higher PCNA index may indicate a worse prognosis in adenohypophyseal neoplasia.
- ItemSomente MetadadadosChildren with Cushing's syndrome: primary pigmented nodular adrenocortical disease should always be suspected(Springer, 2011-03-01) Goncalves da Silva, Renata Marques [UNIFESP]; Pinto, Emilia; Goldman, Suzan M. [UNIFESP]; Andreoni, Cassio [UNIFESP]; Vieira, Teresa C. [UNIFESP]; Abucham, Julio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP)Primary Pigmented Nodular Adrenocortical Disease (PPNAD) is a rare form of bilateral adrenocortical hyperplasia that is inherited in an autosomal dominant manner and leads to ACTH-independent Cushing's syndrome (CS). PPNAD may be isolated or associated with Carney Complex (CNC). for the diagnosis of PPNAD and CNC, in addition to the hormonal and imaging tests, searching for PRKAR1A mutations may be recommended. the aims of the present study are to discuss the clinical and molecular findings of two Brazilian patients with ACTH-independent CS due to PPNAD and to show the diagnostic challenge CS represents in childhood. Description of two patients with CS and the many sequential steps for the diagnosis of PPNAD is provided. Sequencing analysis of all coding exons of PRKAR1A in the blood, frozen adrenal nodules (patients 1 and 2) and testicular tumor (patient 1) is performed. After several clinical and laboratory drawbacks that misled the diagnostic investigation in both patients, the diagnosis of PPNAD was finally established and confirmed through pathology and molecular studies. in patient 1, sequencing of PRKAR1A gene revealed a novel heterozygous 10-bp deletion in exon 3, present in his blood, adrenal gland and testicular tumor. the etiologic diagnosis of endogenous CS in children is a challenge that requires expertise and a multidisciplinary collaboration for its prompt and correct management. Although rare, PPNAD should always be considered among the possible etiologies of CS, due to the high prevalence of this disease in this age group.
- ItemAcesso aberto (Open Access)Cushing's syndrome in pregnancy: an overview(Sociedade Brasileira de Endocrinologia e Metabologia, 2007-11-01) Vilar, Lucio; Freitas, Maria da Conceição; Lima, Lúcia Helena C.; Lyra, Ruy; Kater, Claudio Elias [UNIFESP]; Federal University of Pernambuco Hospital das Clínicas Division of Endocrinology and Metabolism; Hospital Getúlio Vargas Pernambuco University Medical School Division of Endocrinology and Metabolism; Universidade Federal de São Paulo (UNIFESP)Cushing's syndrome (CS) during pregnancy is a rare condition with fewer than 150 cases reported in the literature. Adrenal adenomas were found to be the commonest cause, followed by Cushing's disease. The gestation dramatically affects the maternal hypothalamic-pituitary-adrenal axis, resulting in increased hepatic production of corticosteroid-binding globulin (CBG), increased levels of serum, salivary and urinary free cortisol, lack of suppression of cortisol levels after dexamethasone administration and placental production of CRH and ACTH. Moreover, a blunted response of ACTH and cortisol to exogenous CRH may also occur. Therefore, the diagnosis of CS during pregnancy is much more difficult. Misdiagnosis of CS is also common, as the syndrome may be easily confused with preeclampsia or gestational diabetes. Because CS during pregnancy is usually associated with severe maternal and fetal complications, its early diagnosis and treatment are critical. Surgery is the treatment of choice for CS in pregnancy, except perhaps in the late third trimester, with medical therapy being a second choice. There does not seem to be a rationale for supportive treatment alone.
- ItemAcesso aberto (Open Access)Desenvolvimento de um radioimunoensaio de dexametasona no soro como subsídio para o diagnóstico da síndrome de Cushing(Sociedade Brasileira de Patologia ClínicaSociedade Brasileira de PatologiaSociedade Brasileira de Citopatologia, 2011-10-01) Hayashi, Lilian Fukusima [UNIFESP]; Noguti, Keiko O; Nakamura, Odete H; Kater, Claudio Elias [UNIFESP]; Vieira, José Gilberto Henriques [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)INTRODUCTION: The 1 mg dexamethasone suppression test (DxST) is widely used to screen Cushing's syndrome (CS) due to its high diagnostic accuracy. CS is an endocrine-metabolic disorder caused by hypercorticism, which is characterized by the absence of cortisol suppression in DxST. OBJECTIVE: To develop a radioimmunoassay (RIA) for the measurement of serum dexamethasone (Dx) to complement DxST. METHODS: Three rabbits were inoculated with dexamethasone-21-hemisuccinate-BSA in order to choose the best antibody. Serum Dx RIA was performed according to RE 899/2003 (Agência Nacional de Vigilância Sanitária [ANVISA]) regulations. Serum samples from 96 volunteers from Universidade Federal de São Paulo (UNIFESP) and Santa Casa de Misericórdia de São Paulo were analyzed, 67 of which were submitted to DxST and 29 were not. There were 12 patients with CS. RESULTS: The Dx antibody chosen showed good specificity. Intra- and interassay CV were < 20% with 93.8% accuracy and the lowest detection limit was 19.5 ng/dl. Serum Dx concentration was similar among both volunteers and CS patients (absence of cortisol suppression): 205 to 703 ng/dl and 174 to 661 ng/dl (95% CI), respectively. Values were undetectable among those that were not submitted to the test. Discussion: The anti-Dx antibody shows high specificity and reliability to quantify serum Dx in DxST. The Dx RIA presented reproducibility and reliability in the determination of serum Dx levels during DxST. CONCLUSION: The current RIA for serum Dx is accurate and reliable, which permits to establish a reference value range to substantiate DxST interpretation.
- ItemSomente MetadadadosGrowth hormone axis in Cushing's syndrome(Karger, 1996-01-01) Wajchenberg, B. L.; Liberman, B.; Neto, D. G.; Morozimato, M. Y.; Semer, M.; Bracco, L. O.; Salgado, L. R.; Knoepfelmacher, M.; Borges, MHS; Pinto, ACAR; Kater, C. E.; Lengyel, AMJ; Universidade Federal de São Paulo (UNIFESP)All levels of the growth hormone (GH), GH binding protein (GHBP), insulin-like growth factor (IGF) and IGF binding protein (IGFBP) axis are influenced by chronic hypercortisolism. Thus, there is a blunted response to GHRH alone or together with other stimuli associated with a marked suppression of endogenous GH secretion but accompanied by normal GHBP, normal to low IGF-1 and GHBPs 1 and 3 with the correspondent 41.5 and 38.5-kD molecular forms of the latter presenting values similar to normal. These findings may suggest enhanced GH sensitivity with normal or increased IGF-1 bioavailability to the correspondent tissue receptors. In conclusion, the glucocorticoid (GC)-induced target tissue resistance can neither be attributed to the suppression of the GH axis nor to changes in circulating GHBPs 1 and 3. However, it may be related either to the described 12- to-20-kD inhibitor(s) which antagonizes postbinding IGF-1 bioactivity (gene expression) and/or by the downmodulation of activator protein-1 (Fos/Jun) activity by the GC-GC receptor complex.
- ItemAcesso aberto (Open Access)Síndrome de Cushing subclínica em populações de risco(Sociedade Brasileira de Endocrinologia e Metabologia, 2007-11-01) Caetano, Maria Silvia S. [UNIFESP]; Vilar, Lucio; Kater, Claudio Elias [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Federal de Pernambuco Hospital das Clínicas Divisão de EndocrinologiaBased on autopsy studies, adrenal masses are among the most common tumors in humans. Endogenous Cushing's syndrome (CS) is unusual and adrenal adenomas account for 10% of all cases of CS. Patients with subclinical CS (SCS) present abnormal cortisol dynamics without obvious manifestations. The prevalence of hypercortisolism in clinically inapparent adrenal masses has been reported as 9%. Data from several small series of patients indicate that fewer than 20% develop hormone overproduction when followed for up to 10 years. Follow-up of patients with subclinical CS suggests that rarely masses increase in size or progress to overt CS. Adrenal incidentalomas and subclinical CS are related to metabolic disorders, in special to type-2 diabetes. The scarce available data suggest that treatment of hypercortisolism correct the metabolic abnormalities and blood pressure. Some studies evaluating the prevalence of subclinical CS in overweight type-2 diabetes patients suggest that it is considerably higher in populations at risk than in the general population.