Endocrine Abstracts

Most tests of the hypothalamo-pituitary-adrenal axis (HPA) use total cortisol measurements, although only free cortisol is biologically active. Total cortisol is 90% bound to cortisol binding globulin (CBG). CBG varies between individuals, is elevated by oestrogens and reduced by acute illness or surgery. Low CBG levels may result in individuals apparently failing such tests, and receiving inappropriate steroid replacement. We hypothesised that correcting total cortisol for CB...

Objective: Three nonsynonomous SNPs, Arg16Gly, Gln27Glu and Thr164Ile, in the coding region of the ADRB2 gene affect either receptor affinity or trafficking. Their distribution has been shown to differ significantly in hypertension. We investigated the association of these loci with hypertension in the Silesian Hypertension Study.Methods: Following local ethics approval, 274 unrelated Polish subjects consisting of 146 hypertensives and 128 normotensives ...

The pathogenesis of pheochromocytomas (pheo) is poorly understood and malignant pheo need new treatment options. mTOR inhibitors, as sirolimus (S) and everolimus (E), are new promising antineoplastic drugs.Aim: To evaluate whether the IGF/mTOR pathways have a role in the pathogenesis and whether S and E may have antiproliferative effects in pheo.In 24 human pheo and two normal adrenal medulla (NM), we evaluated the mRNA expression ...

Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and scant treatment options. Mitotane alone, or in combination with cytotoxic chemotherapy, represents the referral current treatment for patients with unresectable ACC. Recent studies have shown that mTOR inhibitors suppress growth of ACC cells. This study aimed at evaluating the effects of mitotane in combination with mTOR inhibitors. In H295 and SW13 cells we tested the effects of a 6 day treatment with increa...

Background: Childhood obesity is an increasing health problem, affecting over 40 million children aged 0–5 years worldwide. It is associated with premature onset of diabetes and cardiovascular disease in adulthood. Pathologically elevated cortisol is known to induce obesity and cardio-metabolic complications, suggesting cortisol is implicated in the onset of obesity. Indeed, recent pilot-studies showed an increase in hair cortisol concentrations in obese adults and adoles...

Introduction: ACTH stimulates adrenocortical steroid production through the melanocortin 2 receptor (MC2R). MC2R trafficking and signaling depend on the melanocortin 2 receptor accessory protein (MRAP). The MRAP-homolog MRAP2 also transports the MC2R but prevents effective activation. We investigated expression of these components of the MC2R complex in human adrenal tissues in order to uncover novel regulatory mechanisms and their contribution to ACTH responsiveness.<p cl...

Introduction: Neuroendocrine tumors (NET) are rare tumors originating from various types of neuroendocrine cells. The somatostatin receptor type 2 (sst2) is expressed in NET cells and is a target for therapy with somatostatin analogues.Epigenetic changes including methylation of DNA at CpG dinucleotides, and particularly in the promoter region of genes can inhibit transcription. Methylation can be inhibited by cytidine analogues such as 5-aza-...

Introduction: Elevated levels of cortisol are known to induce a wide range of pathology, e.g. abdominal obesity, type 2 diabetes and cardiovascular disease. Measuring serum and saliva cortisol is limited to one time point. Measurement of cortisol in scalp hair is a recently developed method to measure long term cortisol levels and might reflect cortisol exposure in patients with hyper- or hypo-cortisolism and in healthy persons. Our aims were to explore this measurement of cor...

Introduction: Medullary and papillary thyroid carcinoma (MTC and PTC) are two types of thyroid cancer that can originate from activating mutations or rearrangements in the RET gene. Therapeutic options are limited in recurrent disease but since RET is a tyrosine kinase (TK) receptor involved in cellular growth and proliferation, treatment with a TK-inhibitor might be promising. Several TK-inhibitors have been tested in clinical trials, but it is unknown which inhibitor is most...

Background: Adrenocortical carcinoma (ACC) is an uncommon malignancy with a still scantily understood pathogenesis and generally poor prognosis. Surgery, performed at early stages, offers the best chance for cure, but unfortunately, it is often noncurative. Medical treatment produced disappointing responses. mTOR inhibitors, such as sirolimus (S) and temsirolimus (T), are promising antineoplastic drugs in several types of carcinomas.Methods: To evaluate ...