Endocrine Abstracts

The adrenocorticotrophin hormone (ACTH) receptor, also known as the melanocortin-2-receptor (MC2R), is a key mediator of cortisol synthesis in the adrenal gland. Over 40 loss-of-function MC2R mutations have been described to give rise to familial glucocorticoid deficiency type-1 (FGD1). In contrast, to date only one naturally occurring gain-of-function mutation, F278C, has been identified in a patient with ACTH-independent Cushing’s syndrome. Previous work has demonstrate...

Introduction: Heterozygous inactivating mutations in the maternal allele of the GNAS gene typically result in pseudohypoparathyroidism (PHP). GNAS variants were recently described in 1% of patients, not known to have PHP, in the UK Genetics of Obesity cohort, resulting in reduced MC4R signalling and variable effects on PTH-R and GHRH-R signalling.Methods: NGS (Cambridge Obesity Gene Panel) and in vitro functiona...

Background: The hypothalamus-pituitary-adrenal axis (HPA) controls the neuroendocrine response to psychological and physiological stress. The balance of the hormones synthesised and secreted by these organs is tightly regulated. However, there are intrinsic differences in the relative expression of these hormones depending on sex, which can influence the magnitude of the endocrine response to stressors or the response to pharmacological treatments. Herein, we ...

Clinical vignette: We investigated a 33-year-old woman diagnosed during pregnancy with a 7cm unilateral adrenal mass associated with severe ACTH-independent glucocorticoid and androgen excess, a steroid phenotype usually indicative of adrenocortical carcinoma. Pregnancy had been achieved with in-vitro fertilisation on the assumption of underlying PCOS. Neonatal death occurred soon after emergency delivery due to foetal growth arrest at 26 weeks gestation. Hist...

Background: Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing’s syndrome. Primary unilateral macronodular adrenal hyperplasia with concomitant glucocorticoid and androgen excess has never been studied before.Methods: We investigated a woman with a large, heterogeneous 7 cm adrenal mass (with a radiologically normal contralateral adrenal) and adrenocorticotropic hormone (ACTH)-independent glucocorticoid and androge...