Endocrine Abstracts

Medical treatment of adrenocortical carcinoma (ACC) is limited to common cytotoxic agents, which are usually given in combination with mitotane. Recently we have developed a novel therapeutic approach by coupling a monoclonal IGF1 receptor blocking antibody (1H7) to sterically stabilized liposomal doxorubicin (SSLD). 1H7 coupled liposomes showed in vitro high and significant cellular association and furthermore internalization in various human tumor cell lines as well a...

Objective: It is still unknown how pituitary adenomas grow over years and whether growth kinetics follow a distinct growth model. Definition of adenoma growth kinetics would substantially enhance knowledge of biological behaviour. The objective of this study was to define a growth model for non-functioning pituitary adenomas.Methods: Fifteen patients who had five or more serial high-quality examinations with magnetic resonance images or computerized tomo...

Aldosterone is synthesized acutely upon stimulation of the renin-angiotensin-aldosterone system from the cells of the zona glomerulosa. Several enzymes are involved in this steroidogenic process including the steroidogenic acute regulatory protein (StAR), P450 side chain cleavage enzyme (Cyp11a1) and aldosterone synthase, the product of the gene Cyp11b2.We investigated the short time transcriptional regulation of these genes in wild type mi...

Objective: To evaluate reduced fertility rates and their possible causes in a cohort of well controlled male adult patients with congenital adrenal hyperplasia.Methods: We clinically assessed 22 male patients with congenital adrenal hyperplasia (15 salt wasting form, 7 simple virilising, age 18–49) according to their hormonal control. Further, we performed testicular ultrasound, MRI of the testis and a sperm count of each. As laboratory markers 17-O...

Recent molecular studies suggest a role of ectopic G protein coupled receptors in primary aldosteronism (PA). The clinical relevance of these findings is not known. We therefore combined expression profiling and a clinical testing of hormone responsiveness in patients with primary aldosteronism. Sixteen tissues from aldosterone producing adenomas and 6 normal adrenal glands were subjected to a quantitative PCR for determination of mRNA expression levels of AT2R, GIPR, MC2R, Gn...

BackgroundUnilateral forms of primary aldosteronism (PA) are usually surgically treated to remove the source of aldosterone excess. After adrenalectomy, aldosteronism persists in a subset of patients indicating abnormal aldosterone production from the unresected gland.ObjectiveTo retrospectively analyze histopathology and post-surgical outcomes in a 3-year prospective cohort of patients diagnosed with unilate...

Context: Transcriptomic based characterization of signaling pathways in the adrenals of different subtypes of Cushing’s syndrome.Patients: For preliminary NGS analyses, a total of 27 adrenal samples were used. The cohort consisted of the following patient groups: Cortisol producing adenoma (CPA, n=9), primary bilateral macronodular adrenal hyperplasia (PBMAH, n=10). The adjacent normal adrenal tissue from pheochromocytoma patients ...

Background: The role of ferroptosis – a regulated form of cell death – in the pathophysiology of aldosterone-producing adenomas (APA) is unclear.Objective: To identify mechanisms of ferroptosis in human adrenal cells and translate these findings to APA pathophysiology.Methods: Cell death detection, lipid ROS generation and mRNA sequencing were performed on HAC15 cells treated with the specific ferroptosis inducer RSL3 (1,...

Cushing’s disease tumours bear activating mutations in the ubiquitin-specific-protease 8 gene (USP8) gene in 40-60% of cases. We have previously observed that patients with USP8 mutant tumours have smaller tumour size and show a better response to high dose (8mg) dexamethasone stimulation test compared to those with wild type USP8 (1). The aim of this study was to define the role of USP8 on glucocorticoid receptor (GR) in corticotroph tumour cells. We did experim...

Introduction: Transsphenoidal surgery is the gold standard in Cushing’s disease and recurrence is a major risk. We wondered which impact remission and recurrence might have on control rates of hypercortisolism and conducted a systematic analysis of our cohort of patients with Cushing’s syndrome after undergoing surgical therapy.Methods: We analysed the course of the disease in 74 patients with ACTH-dependent Cushing’s syndrome (63 Cushing&...