Cushing Syndrome

Background The enzyme 11-β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes intracellular glucocorticoid reactivation by conversion of cortisone to cortisol in different tissues and have been implicated in several metabolic disorders associated with obesity. The aim of this study was to evaluate the 11β-HSD1 expression in liver, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) in morbidly obese patients undergoing bariatric surgery and its correlations with clinical, anthropometric, and biochemical variables. Methods A prospective study was conducted over a 27-month period. Hepatic, VAT, and SAT samples were obtained at the time of surgery. 11β-HSD1 and 18S gene expression was measured using real-time quantitative reverse transcriptase-polymerase chain reaction. Results Forty nine patients met the inclusion criteria [mean age: 42.2 ± 10 years, body mass index (BMI): 42 ± 6 kg/m2, 71% women and 63% with metabolic syndrome (MS)]. 11β-HSD1 mRNA levels were higher in liver than fat tissue (p < 0.001), being higher in SAT than in VAT (p < 0.001) without gender-specific differences. Hepatic expression of 11β-HSD1 correlated positively with SAT and VAT, alanine aminotransferase (ALT), and serum glucose and was inversely associated with BMI. 11β-HSD1 mRNA in VAT correlated positively with insulinemia, ALT, and LDL cholesterol. There were no associations between 11β-HSD1 mRNA in SAT and the variables analyzed. Conclusions 11β-HSD1 expression is higher in liver in comparison to adipose tissue in obese patients. The observed correlations between hepatic and VAT 11β-HSD1 expression with dyslipidemia and insulin resistance suggest that this enzyme might have a pathogenic role in obesity and related metabolic disorders.

Cortisol inhibition of phytohemagglutinin (PHA)-induced lymphocyte activation was studied in vitro in peripheral blood mononuclear cells (PBMC) of patients with pathologies of the hypothalamic-pituitary-adrenocortical (HPA) system (n = 18) as well as in students under and out of academic stress. In patients with HPA pathologies, cortisol-induced inhibition of lymphocyte interleukin-2 (IL-2) secretion in vitro positively correlated (p &lt; .005) with IL-2 synthesis, such that lymphocytes secreting less IL-2 were less cortisol sensitive. Similarly, in stressed students there was a positive correlation (p &lt; .02) between lymphocyte DNA synthesis and cortisol inhibition in vitro. Academic stress also resulted in a decrease (p &lt; .01) of lymphocyte cortisol sensitivity. The same tendency was observed in patients with Cushing&#39;s syndrome when compared with hypocortisolemic patients. Normal controls whose lymphocytes were glucocorticoid resistant showed higher lymphocyte activation ...

membahas tentang sistem Endokrin yaitu anatomi, histologi, fisiologi kelenjar adrenal, penyakit akibat kelainan kelenjar adrenal seperti cushing sindrome, addison's disease, testicular feminization syndrome, hiperaldosteronism, farmakologi obat corticosteroid serta kedokteran komunitasnya.

Adrenalectomy continues to play an important role in the management of Cushing’s syndrome (CS). Untreated CS causes considerable physical and mental morbidity and mortality. However, little information is available on the effect of adrenalectomy in ameliorating functional disabilities in CS patients. Our study assesses the long-term outcome of adrenalectomy in patients with CS. This is a retrospective analysis of CS patients managed during 1990–2005 at a tertiary care center. We analyzed the clinical presentation, endocrine evaluation, and surgical management preoperatively and following adrenalectomy. The subjects were 37 patients with CS (age 24.5 ± 15 years, range 1–60 years; male:female 1.0:1.2). There were various etiologies—unilateral adrenocortical adenoma (n = 11), adrenocortical carcinoma (n = 13), pituitary ACTH-secreting adenoma with failed transsphenoidal surgery (n = 4), ectopic unidentified ACTH source (n = 7), bilateral adrenal macronodular hyperplasia (n = 1), primary pigmented nodular adrenal hyperplasia (n = 1) —for which the patients underwent adrenalectomy: unilateral (n = 22), bilateral (n = 13), or adrenonephrectomy (n = 2). Two patients died during the perioperative period owing to chest infection and sepsis. At the median follow-up of 60 months (range 6–144 months), the patients exhibit significant persistence of obesity (41%), proximal muscle weakness (44%), menstrual irregularity (8%), hypertension (31%), and insulin-dependent diabetes (29%). Hirsutism and psychological abnormalities persisted to a lesser extent. All patients had biochemical cure of CS following surgery evidenced by the 8 a.m. basal cortisol ≤ 5 μg/dl. The hypothalamic-pituitary-adrenal axis recovered as shown by normalization of the short synacthen-stimulated cortisol level (peak level ≥ 20 μg/dl) after a median follow-up of 9 months (range 6–18 months). Incomplete clinical recovery following adrenalectomy emphasizes the need of early recognition and prompt treatment of CS. Surgery for adrenocortical adenoma is safe and effective; however, survival of patients with CS due to adrenocortical carcinoma remains poor. Bilateral adrenalectomy provides early control of hypercortisolism in selected cases of unlocalized ectopic ACTH syndrome or failed transsphenoidal surgery. Even though functional recovery is incomplete after adrenalectomy, quality of life improves considerably.

Adrenal cortical carcinoma is a rare diagnosis and may present with hormone secretion. A histological differentiation between an adrenal cortical adenoma and carcinoma can be very difficult. However, a fast diagnosis including staging and complete surgical resection is pivotal for the prognosis of an adrenal cortical carcinoma. Metastasing adrenal cortical carcinoma should be treated with a mitotane based chemotherapy, and inclusion in the &quot;firm-act study&quot; is highly recommended. The present case report demonstrates the diagnostic pitfalls in a female patients with Cushing&#39;s syndrome who suffered from metastasing adrenal cortical carcinoma.