Objective: Interleukin 6 (IL6) has the ability to influence each level of the hypothalamo-pituitaryadrenocortical (HPA) axis. The aim of the study was to test whether IL6 concentration correlates with the adrenal cortex response to ACTH in healthy humans. We postulated that higher basal IL6 concentration would be associated with the higher cortisol response to the stimulation. Design and methods: Basal IL6 concentration was measured and a low dose (1 mg) ACTH test was performed to assess cortisol response. Twenty-seven apparently healthy subjects (11 male, 16 female, mean age 31.1 years, age range 22-47 years) were included in the study. Results: Data are presented as meanGS.E.M. Basal IL6 level was 0.84G0.10 pg/ml. Basal cortisol was 351.9G18.3 nmol/l. Maximal cortisol during synacthen test was 653.0G20.6 nmol/l. Maximal cortisol increment was 301.1G20.0 nmol/l. IL6 concentration was not correlated with basal or maximal cortisol concentration, but correlated significantly with cortisol increment (rZ0.63, 95% confidence interval) 0.42-0.83). Conclusions: In our study, we found that higher basal IL6 concentration is associated with the higher cortisol response to ACTH stimulation. Based on previous research and our data, IL6, even in low concentrations and under physiologic conditions, modulates adrenal cortex responsivity to ACTH. Therefore, it seems that immune modulation of HPA axis is also present under physiologic and not only pathologic conditions. European Journal of Endocrinology 159 649-652

It is well known that glucocorticoids induce insulin resistance, but the exact time scale in humans is not well known. The aim of the study was to determine the time scale of effects of pharmacologic doses of glucocorticoids on insulin sensitivity. Subjects were treated with repeated methylprednisolone infusions and oral prednisone for Graves' orbitopathy. Insulin sensitivity was determined using euglycemic hyperinsulinemic clamp (EHGC) before, during the first glucocorticoid infusion and after 2 months of treatment. EHGC started 2 h after the start of the glucocorticoid infusion, and lasted for 2 h. In another group of patients, insulin sensitivity was determined by short insulin tolerance test (SITT) before and during the first glucocorticoid infusion. SITT started 15 min after the start of the glucocorticoid infusion and lasted for 15 min. Ten subjects were included in each protocol. All were euthyroid during the study period. Four hours after the start of the glucocorticoid infusion significant reduction of insulin sensitivity was observed, which did not change for a further 2 months of glucocorticoid treatment [before 7.82 (95% confidence interval (CI) 5.35-10.29), first infusion, 4.93 (95% CI 2.99-6.87), after 2 months 5.36 (95%CI 3.91-6.81) mg/kg/min]. No significant change in insulin sensitivity occurred during the first 30 min of glucocorticoid infusion [before 139.7 (95%CI 94.1-185.3), during 146.7 (95%CI 106.3-187.1) mumol/l/min]. In humans, glucocorticoid- induced insulin resistance develops quickly, in about 4 h, and does not change during further glucocorticoid treatment.

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Graves orbitopathy (GO) is an autoimmune disorder of the retrobulbar tissue 1 probably initiated by autoreactive T lymphocytes which trigger a cascade of events including secretion of cytokines, 2 simulating proliferation of orbital fibroblastas, expansion of adipose tissue and secretion of glycosaminoglycans by the orbital fibroblasts. Therefore, immunosuppressants and anti-inflammatory agents are the treatment of choice for moderate-to-severe-and active GO. 3,4 Although different immunosuppressants including biological agents

INTRODUCTION Endogenous Cushing's syndrome is a clinical state resulting from prolonged, inappropriate exposure to excessive endogenous secretion of Cortisol and hence excess circulating free cortisol, characterized by loss of the normal feedback mechanisms of the hypothalamo-pituitary-adrenal axis and the normal circadian rhythm of cortisol secretion [2]. The etiology of Cushing's syndrome may be excessive ACTH secretion from the pituitary gland, ectopic ACTH secretion by nonpituitary tumor, or excessive autonomous secretion of cortisol from a hyperfunctioning adrenal adenoma or carcinoma. Other than this broad ACTH-dependent and ACTH-independent categories, the syndrome may be caused by ectopic CRH secretion, PPNAD, MAH, ectopic action of GIP or catecholamines, and other adrenel-dependent processes associated with adrenocortical hyperfunction. CASE REPORT A 31 year-old men with b-month history of hyperpigmentation, weight gain and proximal myopathy was refereed to Institute of Endocrinology for evaluation of hypercortisolism. At admission, patient had classic cushingoid habit with plethoric face, dermal and muscle atrophy, abdominal strie rubrae and centripetal obesity. The standard laboratory data showed hyperglycaemia and hypokaliemia with high potassium excretion level. The circadian rhythm of cortisol secretion was blunted, with moderately elevated ACTH level, and without cortisol suppression after low-dose and high-dose dexamethason suppression test. Urinary 5HIAA was elevated. Abdominal and sellar region magnetic resonance imaging was negative. CRH stimulation resulted in ACTH increase of 87% of basal, but without significant increase of cortisol level, only 7%. Thoracal CT scan revealed 14 mm mass in right apical pulmonary segment. A wedge resection of anterior segment of right upper lobe was performed. Microscopic evaluation showed tumor tissue consisting of solid areas of uniform, oval cells with eosinophilic cytoplasm and centrally located nuclei. Stromal tissue was scanty, and mitotic figures were infrequent. Tumor cells were immunoreactive for synaptophysin, neuron-specific enolase, and ACTH. The postoperative course was uneventful and the patient was discharged on glucocorticoid supplementation. Signs of Cushing's syndrome were in regression, and patient remained normotensive and normoglycaemic without therapy. DISCUSSION A multitude of normal nonpituitary cells from different organs and tissues have been shown to express the POMC gene from which ACTH is derived. The tumors most commonly associated the ectopic ACTH syndrome arise from neuroendocrine tissues, APUD cells. POMC gene expression in non-pituitary cells differs from that in pituitary cells both qualitatively and quantitatively [8], Aggressive tumors, like small cell cancer of the lung (SCCL) preferentially release intact POMC, whereas carcinoids rather overprocess the precursor, releasing ACTH and smaller peptides like CLIP. Some tumors associated with ectopic ACTH syndrome express other markers of neuroendocrine differentiation like two ...