Endocrine Abstracts

Introduction: The ectopic ACTH syndrome (EAS) is associated with a variety of malignancies, mostly of (neuro-)endocrine origin. Several series report on the relative contribution of EAS in the spectrum of Cushing’s syndrome. However, information on the incidence/prevalence of EAS in the setting of patients diagnosed with thoracic or gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) is virtually absent.Study design: In our tertiary academic ...

Background: In case of inoperable disease or tumor recurrence, there are only a few medical treatment options for patients with adrenocortical carcinoma (ACC). The oral alkylating drug Temozolomide (TMZ) shows efficacy in a subset of patients with melanoma, glioblastoma or pancreatic neurendocrine tumours. Response to TMZ seems determined by the tumoral expression level of the DNA repair enzyme O(6)-Methylguanine-DNA methyltransferase (MGMT).Aims: To eva...

Introduction: In case of inoperable disease or tumor recurrence, therapy with mitotane (MIT), sometimes in combination with doxorubicin (DOX), etoposide (ETO), cisplatin (CIS) or streptozocin (STREP), is frequently applied in patients with adrenocortical carcinoma (ACC). The multidrug resistance pump MDR1 is responsible for resistance of tumor cells to cytostatic drugs. The activity of MDR1 is inhibited by the calcium-channel blocker verapamil. There are equivocal data in the ...

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: 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...

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...

Purpose: Hypopituitarism is frequently associated with lifelong replacement therapy. However, it has been suggested that recovery from hypopituitarism after transsphenoidal surgery (TSS) for pituitary adenomas may occur during follow up. The aim of this study was to assess the frequency of hypothalamus-pituitary-adrenal (HPA) axis recovery after TSS in patients with non-functioning pituitary adenomas and acromegaly.Methods: Over the 3-year observational ...