Endocrine Abstracts

Introduction: MSC is a simple and reliable mean to diagnose hypercortisolism, yet its value to asses the outcome of treatment has rarely been addressed.Objective: Compare MSC and other classical parameters, to assess the outcome of TSS in CD.Patients and methods: Sixty-eight patients from a single Center operated for CD between 1996 and 2006. Outcome was assessed between 6–12 months post TSS. Remission was defined as: morning ...

Background: Insulin resistance and ageing are risk factors for the development of type 2 diabetes and atherosclerosis. Insulin signalling in macrophages affects their inflammatory responses and foam cell formation capacity, yet the mechanisms linking these remain unclear. Recent evidence has emerged linking macrophage lipid metabolism and inflammatory response such as an interferon-cholesterol pathway flux axis. Insulin has been shown to directly regulate chol...

The brain plays a crucial role in maintaining the body’s energy needs, a process involving the activity of a group of hypothalamic neurons that express the neuropeptidergic marker pro-opiomelanocortin (POMC). POMC neuronal dysfunction can cause obesity and its associated metabolic sequelae. However, this population of neurons is highly diverse at a molecular and functional level, and whether or not such heterogeneity is implicated in disease establishment or progression h...

Eneboparatide (AZP-3601) is a novel, synthetic, 36-amino-acid peptide agonist of the parathyroid hormone type 1 receptor (PTHR1), with potent selectivity for the R0 conformation. This results in prolonged calcemic responses, while having a short circulating half-life. Eneboparatide is being developed for the treatment of chronic hypoparathyroidism (cHP). Studies in hypoparathyroid animal models and, most recently, in hypoparathyroid patients, have demonstrated that eneboparati...

Background and aim: Loss-of-function mutations in TRMT10A, a transfer RNA (tRNA) methyltransferase, cause early onset diabetes and microcephaly. tRNAs play a crucial role in cellular homeostasis and post-transcriptional modifications modulate tRNA function and fragmentation. tRNA-derived halves (tiRNAs, 29-50 nt) and fragments (tRFs, 14-30 nt) are a new class of functional small noncoding RNAs, involved in cellular stress responses. Here we set out to investigate the ...

Objective: Treatment with metreleptin ameliorates hepatic steatosis in patients with lipodystrophy. The anti-steatotic effect of metreleptin is partially independent of its anorexic action, which suggests a direct effect of metreleptin on hepatic lipid metabolism. However, this mechanism is unknown. Based on previous findings in rodents, we hypothesized that metreleptin reduces hepatic lipid content by stimulating very-low density lipoprotein triglyceride (VLDL1-TG) secretion,...

Background: CYP11A1 encodes the P450 side chain cleavage enzyme (P450scc) responsible for initiating steroidogenesis and classically gives rise to disordered sex development plus adrenal and gonadal insufficiency. The rs6161 variant in exon 5 of CYP11A1 (c.940G>A; p.E314K) has previously been considered as ‘benign’. When next generation sequencing was performed in patients with primary adrenal insufficiency of unknown etiology the rs6161 variant was foun...

Background: CYP11A1 encodes the P450 side chain cleavage enzyme (P450scc) responsible for initiating steroidogenesis and classically gives rise to disordered sex development plus adrenal and gonadal insufficiency. The rs6161 variant in exon 5 of CYP11A1 (c.940G>A; p.E314K) has previously been considered as ‘benign’. When next generation sequencing was performed in patients with primary adrenal insufficiency of unknown etiology the rs6161 variant was foun...

Introduction: Bilateral Macronodular Adrenocortical Disease (BMAD) is a rare cause of Cushing syndrome due to bilateral adrenocortical macronodules. Germline inactivating variants of the tumor suppressor gene ARMC5 have been described by our group 10 years ago and are responsible for 20-25% of apparently sporadic BMAD cases and 80% of familial presentations. ARMC5 patients present with a more pronounced phenotype than wild-type patients, in terms of cortisol ...

Background: Individuals with hypoparathyroidism often experience a range of symptoms associated with reduced health-related quality of life (HRQoL) and work productivity. Conventional therapy aims to alleviate hypocalcemia and acute symptoms but fails to restore normal parathyroid hormone (PTH) physiology or improve HRQoL. In the PaTHway trial, 79% of participants treated with TransCon PTH vs. 5% placebo (P<0.0001) met the primary efficacy endpoint (normal serum c...