Endocrine Abstracts

Congenital adrenal hyperplasia (CAH) caused by mutations in the electron donor enzyme P450 oxidoreductase (POR) is unique amongst all CAH variants in that it can be associated with ambiguous genitalia (disordered sex differentiation, DSD) both in 46,XX and 46,XY individuals. POR has a pivotal role in facilitating electron transfer from NADPH to microsomal P450 enzymes, including CYP17, which catalyses a key step in human androgen synthesis, the conversion of 17-hydroxypregneno...

P450 oxidoreductase (POR) has a pivotal role as electron donor to all cytochrome P450 enzymes that are microsomally located, i.e. CYP type II enzymes. Importantly, those include key enzymes involved in glucocorticoid and sex steroid biosynthesis such as CYP17 and CYP21. In addition, the activity of hepatic CYP enzymes involved in drug metabolism and detoxification also crucially depend on the transfer of electrons from NADPH via POR. Recently, mutations in P450 oxidoreductase ...

Introduction: Overfeeding adolescent ewes with singleton pregnancies results in reduced placental size and low lamb birth weight at term. We have investigated if reduced placental size is associated with altered placental cell proliferation and apoptosis at day 80 of pregnancy (peak placental growth period). Methods: Singleton pregnancies to a single sire were established by embryo transfer to adolescent recipient dams. Pregnant ewes were offered high (H, n = 14) or moderate (...

The diagnosis of Cushing’s Syndrome (CS) requires demonstration of excess circulating cortisol. Measurement of late night salivary cortisol (LNSF) has been advocated as a simple, non-invasive and reliable outpatient diagnostic tool for patients with suspected CS but the usefulness of its metabolite cortisone (LNSE) remains unclear. LNSE levels are approximately six times higher than LNSF in saliva due to the rapid action of 11β-hydroxysteroid dehydrogenase type 2 (11...

Introduction: Chordomas are rare slowly growing locally aggressive neoplasms of the bone arising from embryonic remnants of notochord. These tumours typically occur in the axial skeleton and have a proclivity for the spheno-occipital region of the skull base. Parasellar/clivus chordomas account for one third of all chordomas.Methods: We conducted a retrospective chart review of 4 patients with chordomas of the clivus treated in Beaumont Hospital between ...

Background: Fluticasone is an inhaled steroid commonly used for asthma with low systemic bioavailability (~9%). We present a case of significant Iatrogenic Cushing’s syndrome when fluticasone was used simultaneously with antiretroviral therapy.Case: 27-year-old man was diagnosed with HIV in 2021. His antiretroviral therapy was simplified to GENVOYA (elvitegravir/cobicistat/tenofovir/alafenamide/emtricitabine) at the...

Introduction: FKBP prolyl isomerase 4, encoded by the gene FKBP4, is a member of the FK506-binding protein family and is presumed to be a regulator of the androgen receptor (AR) pathway. Mutations in FKBP4 have been proposed to cause Androgen Insensitivity Syndrome (AIS), with only one case reported in the literature so far.Aim: To report the clinical, biochemical and genetic findings in an infant with 46, XY DSD a homoz...

Introduction: A proportion of severe obesity is due to monogenic inheritance, however access to genetic testing is often limited which may underestimate prevalence. We report our data obtained via the Rare Obesity Advanced Diagnosis™ genetic testing program established to diagnose rare genetic causes of obesity.Methods: 49 patients (22 male) under the care of a tier 3 paediatric weight management service with early-...

G-protein subunit α-11 (Gα11), which is encoded by GNA11, plays a major role in calcium homeostasis by regulating parathyroid hormone (PTH) secretion, and germline loss-of-function mutations cause familial hypocalciuric hypercalcaemia type 2 (FHH2). Since Gα11 is ubiquitously expressed, we investigated whether FHH2 is associated with additional non-calcitropic phenotypes by analysing mice harbouring a homozygous germline deletion o...

The onset of human lactation is characterised by increased breast fullness and the start of copious milk secretion. The process, which typically occurs 1-4 days postpartum, is triggered by a decrease in serum progesterone and high prolactin concentrations, although the exact levels are ill-defined. We aim to establish reference intervals for hormones triggering the onset of sustained lactation and understand how breastfeeding influences hormone secretion, so as to improve the ...