Endocrine Abstracts

The ERCUSYN (European Registry on Cushing’s syndrome (CS)) study is a project funded by the European Commission Public Health Program (PHP 800200), of which the ESE is one of the 41 Partners from 25 countries. The aims include obtaining prospective and follow-up data at EU level on epidemiology, mortality, outcome of therapies, co-morbidities, assessment of diagnostic and therapeutic strategies, quality of life evaluation using a disease-generated questionnaire (CushingQo...

Introduction: Adrenocortical carcinoma (ACC) is a rare, but highly malignant endocrine tumor. Surgery is the primary choice of treatment. In case of inoperable disease or tumor recurrence, therapy with the adrenolytic drug mitotane is usually applied. Plasma mitotane concentrations of >14 mg/l (50 μM) seem required for an effect on tumor mass. Despite its clinical use, the effects of mitotane on cell proliferation and hormone production have been poorly investigated <...

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: Novel treatment options are required for patients with adrenocortical carcinomas (ACCs). mTOR-inhibitors are anti-neoplastic drugs that target the mTOR-pathway.Aim: To describe the expression of the mTOR-pathway in normal and pathological adrenocortical tissues.Methods: We evaluated mRNA expression levels of mTOR, S6K and 4EBP1 in 10 normal adrenals (NA), 11 adrenal hyperplasias (AH), 19 adrenal adenomas (ACA) and 26 AC...

Introduction: The diagnosis of Cushing’s Syndrome (CS) and in particular cyclic CS can be complicated. Standard screening tests for CS are the measurement of cortisol in 24-hours urine collections and in midnight saliva. In case of cyclic CS, results of these tests can be normal in between periods of hypercortisolism. The development of a method to measure cortisol in scalp hair provides the opportunity to investigate historical cortisol levels of months to years ago, wit...

Introduction: Corticotroph pituitary adenomas that cause Cushing’s disease (CD) predominantly express the dopamine 2 receptor (D2) and somatostatin receptor subtype (sst) 5. The expression of sst2 is relatively low because of downregulating effects of high endogenous cortisol levels. This may explain why the sst2-preferring somatostatin analog octreotide is not effective in CD. To assess whether normalization of urinary free cortisol (UFC) excretion modulates the sst expr...

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-...

Background: The mechanism underlying the spontaneous improvement of rheumatoid arthritis (RA) during pregnancy and the subsequent post-partum flare is incompletely understood. The glucocorticoid receptor (GR) polymorphisms Bcl1 and 9β are associated with an increased and decreased glucocorticoid sensitivity respectively. We examined the relation between carriership of these functional GR polymorphisms and disease course during pregnancy and post-partum in RA...

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...

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 ...