Endocrine Abstracts

Familial glucocorticoid deficiency (FGD, OMIM#202200) is a rare autosomal recessive disorder characterised by adrenal resistance to the action of ACTH, with isolated glucocorticoid deficiency. Recently, mutations in NNT, encoding the mitochondrial anti-oxidant nicotinamide nucleotide transhydrogenase have been reported to cause FGD.Our index case, from a highly consanguineous Kashmiri family, was diagnosed with adrenal insufficiency during a sep...

Introduction: The adipokine adiponectin promotes insulin sensitivity and its circulating levels are inversely related to adiposity in adults and older children. In small for gestational age (SGA) infants adiponectin levels decline rapidly with age in early life and have been inversely associated with subsequent weight gain. There are few data in early infancy, especially in non-SGA infants.We therefore investigated the association between adiponectin lev...

Polycystic ovary syndrome (PCOS) is a triad of insulin resistance, hyperandrogenism and anovulation. PCOS is associated with increased adrenocortical drive, which may have adverse metabolic consequences. Here we analysed the relationship of urinary androgen and glucocorticoid metabolite excretion with insulin resistance in a large PCOS cohort.We compared results from 127 PCOS patients (Rotterdam criteria) with 100 BMI-matched controls. All subjects under...

Background: 5α-Reductase type 2 deficiency (5ARD) is caused by mutations in the SRD5A2 gene. Inadequate masculinisation in XY individuals results from failure to convert testosterone (T) to dihydrotestosterone (DHT), a potent androgen. A decreased serum T:DHT ratio is frequently taken to identify 5ARD, but requires hCG stimulation for prepubertal patients; findings are not always supported by genotyping. Urine steroid profiling (USP) by GC-MS is established as showing sig...

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterised by unresponsiveness to ACTH and isolated cortisol deficiency. FGD is caused by mutations in genes encoding the ACTH receptor (melanocortin 2 receptor (MC2R)), its accessory protein (MRAP) or the steroidogenic acute regulatory protein (StAR). One significant feature is generalized skin hyperpigmentation which is thought to be due to elevated ACTH acting on the melanocortin 1 receptor (...

Introduction: We describe a case of 17- beta hydroxysteroid dehyrogenase Type III (17-βHSD3) deficiency in a girl from the travelling community. This case demonstrates how the clinical picture may not correlate with the biochemical results.Case: A 4.7 year old girl presented for elective hernia repair. Intraoperatively, what was felt to be a testis was palpated. Investigations revealed a 46, XY karyotype. Pelvic ultrasound demonstrated absence of mu...

In peripheral target tissues, levels of active glucocorticoid hormones are controlled by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which catalyses the reduction of cortisone to cortisol within the endoplasmic reticulum. For functional 11-ketoreductase activity, 11β-HSD1 requires the NADPH-generating enzyme hexose-6-phosphate dehydrogenase (H6PDH). Loss of 11-ketoreductase activity results in increased cortisol clearance and activation of the HPA axis wi...

Background: The Endocrine Society clinical practice guidelines suggest use of the 1 mg overnight dexamethasone suppression test (ONDST) to screen for cortisol excess in patients with adrenal incidentalomas, followed by the 48-h, 2 mg/day, low-dose dexamethasone-suppression test (LDDST), to confirm a positive result. Visceral fat accumulates in cortisol-excess and accounts for increased cardiovascular risk. In this study, we investigate whether the LDDST offers additional infor...

GH deficiency (GHD) in adults shares several clinical features with syndromes of glucocorticoid excess. Many patients with GHD also receive glucocorticoid therapy. GH inhibits the generation of active glucocorticoid by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), but the confounding effect of ACTH deficiency/ cortisol replacement therapy has not been evaluated.Aims: To assess corticosteroid exposure and metabolism and body composition in...

Androgen excess is a key feature of polycystic ovarian syndrome (PCOS). Pre-receptor regulation contributes to this with increased activation of testosterone (T) to 5α-dihydrotesterone (DHT) by 5α-reductase type 1 (SRD5A1), as we have shown previously in PCOS (Lancet 1990,335:431; JCE&M 2003,88:2760). Peripheral blood mononuclear cells (PBMCs) are easily accessible and a useful model for studying pre-receptor regulation in the immune compartment. We have previous...