Endocrine Abstracts

Pituitary development, in particular the differentiation of anterior pituitary endocrine cells, remains to be fully understood, and may have implications for adult pituitary plasticity and hyperplasia. We have used prolactin-reporter transgenic rats to characterise prolactin transcription during the appearance of newly formed lactotroph cells during fetal development.Transgenic rats with the firefly luciferase reporter gene inserted into exon 1b of a 160...

Activating mutations of the calcium sensing receptor (CaSR) result in autosomal dominant hypocalcaemia with hypercalciuria (ADHH), in which patients may also suffer from polyuria, polydipsia, nephrocalcinosis, renal impairment, and ectopic calcification. A mouse model, Nuf, with an activating Leu723Gln CaSR mutation has been reported to develop the features of ADHH as well as cataracts that consist of dot nuclear opacities, which have not been described in ADHH patients...

We have created transgenic mice in which Cyp11b1, the gene encoding 11β-hydroxylase, has been knocked out. Since mice do not secrete adrenal androgens, this knockout line allows a more detailed investigation of phenotypes associated with congenital adrenal hyperplasia (CAH) without the overwhelming virilisation that characterises patients with CAH. Starting with a BAC containing the mouse Cyp11b1/b2 locus and including flanking up- and downstream sequences, a const...

Aim: To assess whether adults in Scotland currently receiving growth hormone (GH) meet the NICE criteria for starting and continuing GH replacement.Methods: We surveyed all endocrinologists in Scotland and identified the main centres using GH replacement. A cross-sectional case note review was carried out of all patients commenced on GH.Results: About 208 patients (51% women; 24% professionals, 90% Caucasian) were identified, 69 of...

Background: In most people, prolactin circulates predominantly as a 23-kDa monomer, and a high-molecular-weight form which in the vast majority of cases consists of a complex of prolactin and an anti-prolactin IgG autoantibody, commonly referred to as macroprolactin. This cross-reacts with conventional laboratory assays for prolactin.Report: In a consecutive series of 218 patients with prolactin elevated to 400 μ/l or more in men (normal range &#880...

3-iodothyronamine (T1AM) is a novel, endogenous rapid acting biogenic amine, which is a potent agonist of the G-protein coupled trace amine-associated receptor 1, TAAR1. It has been suggested that endogenous T1AM could be generated by enzymatic deiodonation and decarboxylation of T4. The presence of T1AM in rat brain and the distribution of the TAAR1 receptor in the hypothalamus suggest that T1AM may affect food intake and regulate e...

Background: Grade 3 pancreatic neuroendocrine tumor (G3-PanNET) and neuroendocrine carcinoma (PanNEC) are both defined by Ki67>20% and/or mitoses >20 per 2mm2. PanNET and PanNEC are thought to be molecularly distinct entities and progression from PanNET to PanNEC is considered rare. MEN1, ATRX, DAXX, and TSC1/2 mutations are common in PanNET, while TP53, RB1, KRAS, and SMAD4 mutations are typical of PanNEC. Immunostains for ATRX/DAXX/p53/Rb aid in the classification of...

Background: Pancreatic neuroendocrine tumors (panNETs) are heterogeneous, with grade (G) defined by Ki67 proliferation index (<3% G1, 3-20% G2, and >20% G3) or mitotic rate. Previous studies suggest that baseline Ki67 index may be confounded by biopsy site (primary or metastasis), biopsy technique and primary tumor size. Ki67 differences leading to grade discordance in PanNETs at baseline is relatively understudied. Our study aims to evaluate grade discordance in synch...

Paltusotine is an investigational oral, once-daily, non-peptide, SST2 agonist in development for the treatment of acromegaly and neuroendocrine tumors. Interim analysis results from subjects with acromegaly treated with paltusotine for up to 2 years in ACROBAT Advance (NCT04261712), an ongoing, open-label extension study are reported here. Prior to Advance, subjects previously completed one of two Phase 2 parent studies, Evolve (NCT03792555, with normal IGF-1 using injected lo...

CRN04894 is a potent, orally bioavailable nonpeptide that is a highly selective antagonist for melanocortin type 2 receptor (MC2R). This receptor is found exclusively in the adrenal cortex and is the primary mediator of adrenal activation. We report results from a randomized, double-blinded, placebo-controlled (6 active:3 placebo/cohort), multiple ascending dose (40, 60, and 80 mg) study in health volunteers evaluating safety, pharmacokinetics, and pharmacodynamics of oral, on...