Endocrine Abstracts

Objectives: Antagonism of the IGF-1 receptor (IGF-1R) has been shown to reduce TED-related inflammation and proptosis. VRDN-001, a high-affinity antagonist antibody to IGF-1R, has distinct pharmacological properties that may enable differentiated dosing and better efficacy than observed with other antibodies. We assessed VRDN-001 in vitro pharmacology compared with teprotumumab and clinical proof of concept in a phase 1/2 randomized controlled trial (NCT05176639)....

Over 40 years ago, the first enkephalin analogs that stimulated growth hormone (GH) release were synthesized in 1984, leading to the development of GHRP-6. In 1995, Merck developed a potent non-peptide orally active long-acting growth hormone GHS, ibutamoren, and cloned the GHS receptor in 1996, which led to ghrelin being identified as its natural ligand in 1999. These discoveries uncovered a new physiological pathway for GH regulation linking the GI tract and the hypothalamic...

Objective: Arthropathy is the commonest morbidity in acromegaly and the main determinant of quality of life in these patients. Most of current knowledge is derived from studies using conventional x-rays. This study aims to characterise acromegalic arthropathy using modern imaging techniques.Methods: Case control study comprising of 60 acromegaly patients (29 males, mean age 54.8± 12.9yrs) and 300 age/gender-matched controls from the publicly availab...

Introduction: The androgen receptor (AR) mediates the peripheral effects of testosterone. The main mechanism of action for the AR is direct regulation of gene transcription. Available evidence suggests that the number of CAG repeats in exon-1 of the AR gene is negatively correlated with transcriptional activity of the AR and that CAG repeat number links to mortality rate in T2DM men. The aim of this analysis was to determine the association between CAG repeat number and all ca...

We describe a 68 year lady who was found to have bilateral adrenal masses (7 cm on the right side and 1.3 cm on the left) during investigations for gastrointestinal symptoms, in early 2016. Biochemistry revealed high urinary normetanephrines of 41.7pmol/24h (ref 0–3) and metanephrines of 40pmol/24h (ref 0–1.8). A PET and MIBG scan revealed uptake in both adrenals and therefore a diagnosis of bilateral phaeochromocytoma was made. The patient had complained of occasion...

Global knockout models of the androgen receptor (ARKO) illustrates the many roles androgens and their receptor have in the development of male reproductive organs and the gender differences in many features like the musculoskeletal system. However, neither the global ARKO nor orchidectomy models discriminate between direct and indirect effects of androgens. To determine direct and indirect effects of androgens on muscle, we developed a muscle-specific ARKO (called satARKO for ...

Objectives: Abnormal pubertal timing affects >4% of adolescents and is associated with adverse health outcomes. Up to 80% of variation in the timing of pubertal onset is genetically determined. Self-limited delayed puberty (DP) segregates in an autosomal dominant pattern, but in the majority the neuroendocrine pathophysiology and genetic regulation remain unclear. Mis-regulation of the embryonic migration of GnRH neurons has been implicated in the pathogenesis of DP (Howar...

Introduction: Hypercalcaemia in Williams-Beuren syndrome (WBS) is usually mild and transient, but may be severe in about 5% of new presentations. Often some children will not respond well to traditional therapies.Case report: We describe three cases of acute hypercalcaemia and their management in a regional Paediatric unit. Case 1: A 16-month-old known WBS girl, presented with irritability, reduced feeding. Corrected serum calcium was 4.51 mmol/l. She wa...

Medical treatment of acromegaly is based on either suppressing pituitary GH secretion or inhibiting GH action by preventing interaction with its receptor in order to suppress the elevated levels of IGF1. AZP-3813 is a 16-amino acid, bicyclic peptide antagonist of the GH receptor (GHR) derived from peptide sequences discovered using a unique, cell-free in vitro transcription-translation system screened against the human GHR, and that was optimized by rational design to increase...

Background: September is celebrated as PCOS awareness month worldwide and is aimed at improving the lives of those with PCOS, promoting research, and strengthening advocacy efforts. While significant financial and human resources are invested in promotions during this month, to the best of our knowledge, there is no evidence to show the impact of this initiative. In our study, we evaluated the global digital impact of PCOS Awareness Month, tracking commonly used hashtags as su...