Endocrine Abstracts

Section 1: Case history: A 30 year-old female patient with a background of symptomatic primary hyperparathyroidism diagnosed in 2008 and a history of two failed neck surgeries, was reviewed in clinic complaining of persistent symptoms of hypercalcaemia. Previous pre-operative neck imaging had failed to localise a parathyroid adenoma and the patient had undergone two neck explorations by an experienced ENT surgeon; one which removed thymic tissue and the other which removed a m...

Case history: Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant disorder caused by heterozygous pathogenic variants in the FLCN gene encoding folliculin on chromosome 17p11, first described clinically in 1975. It is a ‘hamartomatous’ disorder usually manifesting with pulmonary cysts, benign cutaneous tumours and conferring a high risk of renal malignancy. A 43 year old man had a 34 x 22 mm right adrenal nodule discov...

Case history: We present a 71 year old man, with a 3 year history of problematic hypertension (BP exceeding 190/100 on treatment), incidentally found to be hypokalaemic (K 1.8 mmol/l) during investigations for leg weakness. He had no clinical features to suggest an endocrinopathy. Investigations at his local centre revealed hypokalaemia dating back over 3 years.Investigations: Biochemistry:Na 142 mmol/l (135–145 mmol/l)<p ...

Introduction: Primary aldosteronism (PA) is a common and potentially reversible cause of secondary hypertension, characterised by resistance to standard antihypertensive therapy and possible hypokalaemia. Lateralisation investigations, including adrenal vein sampling (AVS), are required to distinguish between unilateral or bilateral disease, with unilateral disease representing a potentially surgically curable form of PA. The majority of patients proceeding to adrenalectomy re...

Background: Primary aldosteronism (PA) is now recognised to account for 5–10% of all cases of hypertension (and 20–25% of refractory hypertension). For patients with a demonstrable unilateral cause, adrenalectomy offers the potential for cure of PA, although resolution of hypertension occurs in only ~50% of patients. We have examined histological appearances and radiological features in patients with APAs undergoing adrenalectomy in an attempt to further our understa...

Tumours caused by mutations in the SDH enzyme complex have a unique tumour metabolome due to a truncated citric acid cycle. The accumulation of the onco-metabolite succinate is believed to drive tumourigenesis. The aim was to investigate the role of MRI spectroscopy (H-MRS) to detect in vivo succinate elevations in suspected SDH deficient tumours including GIST, phaeochromocytoma/paraganglioma (PPGL) and pituitary adenomas (PA). Suitable patients were identified based...

Recent discoveries in mutations in TCA cycle enzymes; succinate dehydrogenase (SDH), fumarate hydratase (FH), iso-citrate dehydrogenase (IDH) and malate dehydrogenase MDH2, have reinforced the link between mitochondrial dysfunction and cancer1. Phaeochromocytoma and paraganglioma (PPGL) are now recognised to be the most heritable tumour, with 40%1 having a genetic defect. Mutations in the SDH genes are the most frequently implicated genetic abnor...

Background: Primary Aldosteronism (PA) is the commonest curable cause of hypertension. Whole exome sequencing (WES) of an aldosterone producing adenoma from a 46-year-old man with resistant hypertension revealed a novel somatic mutation (Val380Asp) of the single transmembrane domain of Cell Adhesion Molecule-1 (CADM1). A Gly379Asp mutation was identified by WES of a PA patient in Munich. Both patients were cured of hypertension by adrenalectomy.Method: A...

Background: PA is the commonest curable cause of hypertension. Whole exome sequencing (WES) in 2011 and 2013 identified common somatic mutations in genes regulating membrane polarisation in 60-80% of aldosterone-producing adenomas (APA). In search of the missing variants, we undertook further WES. One APA from a 46-year-old gentleman revealed a novel somatic mutation (Val380Asp); which introduced a charged amino-acid into the single transmembrane domain of Cell Adhesion Molecu...

Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell-clusters of normal adrenals could suggest the existence of co-driver mutations which influence the development or phenotype of APAs [1]. Gain-of-function mutations in both CTNNB1 and the G-protein coupled receptor GNA11 were found by whole exome sequencing in 3/10 APAs. Further sequencing of...