Endocrine Abstracts

Anaplastic thyroid cancer (ATC) is the most aggressive thyroid cancer with a median survival of about 6 months. So far, no therapies offering a survival benefit are established. Thus, new therapeutic approaches are urgently needed. In general, genetic alterations leading to ATC increase PI3K and MAPK/ERK signaling and include mutations in receptor tyrosine kinases and tumor suppressor genes. They often occur together with the loss of P53, the most prevalent mutation in human A...

As thyroid hormones (TH) are essential for the normal heart function, a low TH state in ischemic cardiovascular events is often correlated to a poor prognosis. While clinical and experimental data suggests that TH intervention in acute myocardial infarction might be beneficial, a detailed insight in the mechanisms on TH action in IR injury or post infarct recovery of the heart is still lacking. In this study, we examined the effect of thyroid hormone pre- and postconditioning ...

Background: Thyroid hormone (TH) action is mediated by TH receptors (TRs) α&β. Both regulate gene expression by binding TREs on the DNA (canonical signaling) or activate cellular signaling pathways (noncanonical signaling). Bone is a major TH target and noncanonical TR α & β effects on bone metabolism were suggested. We studied mouse model bones to distinguish between signaling types.Methods: Growth of WT mice and mice with ei...

Autosomal dominant hypocalcemia type 1 (ADH1), caused by pathogenic gain-of-function calcium-sensing receptor gene (CASR ) variants, is characterized by low parathyroid hormone (PTH) levels, hypocalcemia, hypercalciuria, hyperphosphatemia and hypomagnesemia. Current standard-of-care (SoC) (calcium and active vitamin D) can exacerbate hypercalciuria, which may result in renal complications. Encaleret is an investigational oral calcilytic, functioning as a negative allo...

Background: Prior small studies have suggested increased risk of cardiovascular (CV) conditions in patients with hypoparathyroidism (HypoPT). We evaluated whether chronic HypoPT is associated with increased risk of select CV hard endpoints (i.e., myocardial infarction (MI), stroke, and a composite CV endpoint) in a large contemporary cohort.Methods: A retrospective cohort study, based on a US commercial claims database (Q1 2007 - Q2 2017), was conducted ...

Primary aldosteronism (PA) describes the most frequent cause of secondary arterial hypertension. Aldosterone itself represents a BP-independent cardiovascular risk factor associated with increased rates of morbidity and mortality. Recently a worsening of lipid metabolism after treatment has been described.Objective: Our aim was to analyse changes in lipid parameters according to treatment outcome in PA patients. Data of 215 consecutive PA patients with u...

Hypoparathyroidism, a rare disorder characterized by absent or low levels of parathyroid hormone (PTH), often results from thyroid surgery. However, nonsurgical etiologies are present in >10% of patients. Data about this group of patients are limited.In this post hoc REPLACE (NCT00732615, EudraCT2008-005063-34) analysis, baseline characteristics and response to 50–100 μg/day rhPTH(1-84) in patients with postsurgical or nonsurgical ...

The melanocortin 4 receptor (MC4R) represents the major hypothalamic G-protein coupled receptor (GPCR) controlling feeding behavior and therefore body weight regulation. MC4R is highly expressed in the paraventricular nucleus (PVN) where hormonal and neuroendocrine signals from periphery and arcuate nucleus (ARC) are allocated. MC4R knockout in mice or natural occurring loss-of function variants result in hyperphagia and early-onset obesity. MC4R mutations represent the most f...

Glucocorticoids act via the glucocorticoid receptor (GR). Upon ligand binding, GR translocates to the nucleus and binds directly to glucocorticoid responsive elements (GREs) to regulate transcriptional output. Glucocorticoid secretion increases in response to stress to affect transcriptional output within specific areas of the brain including the hippocampus (HC). Therefore, here we assess changes in genome-wide GR chromatin binding profiles in the rat HC in response to a gluc...

Background: Hypothalamic damage caused by craniopharyngioma (CP) is related to memory deficits, disturbed attention, and impaired processing speed. This is the first study that aims to establish a structure to function relationship by assessing cognitive function in adult patients with childhood-onset (CO) CP along with volumetric analysis of the hypothalamus.Method: Forty-one (24 women) surgically treated CO-CP patients (median age at diagnosis; 11 year...