Endocrine Abstracts

Continuation of GH at final height in hypopituitary adolescents with severe GH-deficiency results in accrual of bone mass over 12 months. We report body composition and BMD in 7 of these patients who discontinued GH but continued to have observations over 24 months. Five males and 2 females were included (17.4plus/minus0.3, years, meanplus/minusSE), in this Ethics Commitee approved study. All had severe GH-deficiency with multiple pituitary hormone deficits on appropriate repl...

Cortisol metabolism is modulated by inhibition of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta HSD1) during GH replacement (Weaver et al, Clin Endocrinol, 1994, 41, 639; Gelding et al, Clin Endocrinol, 1998, 48, 153) and in active acromegaly (Moore et al, J Clin Endocrinol Metab, 1999, 84, 4172). 11 beta HSD1 activity is also influenced by both fat mass and insulin. To determine the relative contribution of GH/IGF-I to alteration in cortisol metabolism we have examined...

A 23-year-old woman presented in May 2018 with acute left-sided hemiparesis following increasingly frequent episodes of morning drowsiness with associated weight loss. She had no significant past medical history or family history. Brain imaging excluded intracranial pathology. Blood tests during a spontaneous hypoglycaemic episode (1.5 mmol/l) identified significant hyperinsulinaemic hypoglycaemia [insulin 392 pmol/l (18–173) and C-peptide 3913 pmol/l (370–1470)]. MR...

Background: Phaeochromocytoma and paraganglioma (PPGL) are highly heritable, with 30-40% due to a germline pathogenic variant. An additional 40% of tumours will harbour a somatic variant. Understanding the variant status of a tumour enables molecular classification. Liquid biopsy offers a novel approach to non-invasive diagnostics by harnessing the ability to detect small amounts of circulating-free DNA (cfDNA) and performing genomic sequencing. There are few ...

Background: It is generally accepted that a post-operative cortisol of <50 nmol/l is a good predictor of long-term remission following trans-sphenoidal surgery (TSS).Aim: We wished to determine the rate of late recurrence and need for consequent intervention in patients who had initial biochemical remission after TSS for pituitary dependent Cushing’s.Methods: We performed a retrospective analysis of our patients who underw...

Introduction: Mutations in the succinate dehydrogenase gene (SDH) predispose to the development of paraganglioma (PGL) which arise from parasympathetic and extra-adrenal sympathetic-associated chromaffin tissues. Identification of an index case results in family ‘cascade’ screening, often of asymptomatic individuals.Aims: To identify prevalence of PGL tumours and elevated plasma metanephrines at first scre...

Introduction: Mutations in the succinate dehydrogenase gene (SDH) predispose to the development of paraganglioma (PGL) which arise from parasympathetic and extra-adrenal sympathetic-associated chromaffin tissues. Identification of an index case results in family ‘cascade’ screening, often of asymptomatic individuals.Aims: To identify prevalence of PGL tumours and elevated plasma metanephrines at first scre...

Adrenocortical carcinoma (ACC) is a rare malignancy associated with a poor prognosis (1). Current treatments are limited with surgical resection the only option for a complete cure (2). The development of translational therapies is limited by pre-clinical disease models. Three-dimensional (3D) cell culture models can accurately reflect the tumour micro-environment but are lacking in ACC (3). In the current study, we developed and characterised novel 3D models of MUC-1, HAC15 a...

Background: Pathogenic variants in genes encoding Succinate Dehydrogenase subunits B and D (SDHB/SDHD) predispose to Phaeochromocytoma and Paraganglioma (PPGL). Cascade genetic screening identifies relatives at risk and allows surveillance screening to enable early detection of PPGLs.Methods: Retrospective analysis of genetic databases and hospital records between January 2000 and December 2018 identified relatives carrying SDHB and <em...

Glucuronidation is an enzymatic process that terminally inactivates steroid hormones, including estrogens and androgens, thereby influencing carcinogenesis in hormone-dependent cancers. While estrogens drive breast carcinogenesis via the estrogen receptor alpha (ERα), androgens play a critical role as prohormones for estrogen biosynthesis and ligands for the androgen receptor (AR). Herein, the expression and regulation of two androgen inactivating UDP-glucuronosyltransfer...