Endocrine Abstracts

Endometriosis is a common gynaecological disease associated with severe pelvic pain and sub-fertility. We conducted a genome-wide association (GWA) study in 3,194 surgically confirmed endometriosis cases and 7060 controls of European ancestry from Australia and the UK using 540,000 genetic markers (SNPs). Polygenic predictive modelling showed significantly increased genetic loading among the 1364 (43%) cases with moderate-severe (rAFS III/IV) endometriosis. The strongest assoc...

The locus comprising the genes that catalyse the final steps of cortisol and aldosterone synthesis (CYP11B1 and CYP11B2 respectively) is a plausible candidate risk region for hypertension and other cardiovascular diseases. Nevertheless, there remains uncertainty as to the strength of the relationship between polymorphisms at this locus and increased blood pressure. In this study, association with hypertension at the CYP11B1/CYP11B2 locus in a Caucasian cas...

Background: Primary aldosteronism (PA) is the most common potentially curable cause of secondary hypertension and is a risk factor for cardiovascular morbidity and mortality. For patients with unilateral disease adrenalectomy can be curative. However, PA remains substantially underdiagnosed due the complex diagnostic pathway required to identify patients with unilateral disease, and the difficulties in accurate lateralization of the affected adrenal gland. Spe...

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...

Background: Primary aldosteronism (PA) is the leading, potentially reversible, cause of secondary hypertension. For most patients in whom surgery is being considered, adrenal vein sampling (AVS) is recommended to distinguish unilateral and bilateral causes. However, AVS remains technically challenging, and a significant proportion of patients are unable to progress to surgery because AVS is unavailable or unsuccessful. We have explored whether [11C]Metomidate PET/CT...

Introduction: Our MATCH study demonstrated 11-C ligand MTO was non-inferior to adrenal vein sampling in predicting surgical outcomes of adrenalectomy in patients with PA. The 20-min half-life of 11-C imposes logistic constraints. We investigated an 18-F ligand, CETO; its 2h half-life permits use in any facility with fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan capability.Objective: To compare the detection of aldosterone-producing ade...

Primary aldosteronism (PA) is considered the sole, often curable, cause of hypertension in 5–10% of patients. Yet there has been only one RCT, and practice has changed little since the advent of CT scanning. Adrenal vein sampling (AVS) and adrenalectomy remain the standard, invasive interventions, leading to a 50% reduction in pill count as the average clinical improvement.Study DesignIn MATCH (Is Metomidate PET-CT superior t...

NCKX3 (Sodium/potassium/calcium exchanger 3), a novel member of the family of K+-dependent Na+/Ca2+ exchangers, is an important component of intracellular Ca2+ homeostasis. Ca2+ homeostasis has been extensively studied in various cell systems. Dysregulation of Ca2+ homeostasis can induce the excitotoxic and neurodegeneration in central nervous system. NCKX3 gene is highly expressed in thalamic nuclei, in hippoca...

Follistatin is a hepatokine found to be elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. We report that elevated baseline circulating follistatin levels predict future T2D incidence in longitudinal cohorts including up to 5274 individuals. Individuals with elevated circulating follistatin had higher risk of developing type 2 diabetes during follow-up of 4 years (IMI-DIRECT-METSIM, n = 1079, Finland), 5 and 19 years (MDC-CC, n...

Pituitary adenomas and phaeochromocytoma/paragangliomas (PHAEO/PGL) can very rarely occur in the same patient or in the same family. Together, they are not known to be part of any classical endocrine neoplasia syndromes. In some caes the pathogenetic mechanism may be secondary to a PHAEO secreting GHRH leading to somatotroph hyperplasia and clinical acromegaly. However, we suggest several other mechanisms which could lead to the development of pituitary and PHAEO/PGL together:...