Endocrine Abstracts

Background: CMA showed price paid for liothyronine tablets rose from £15.15 in 2009 to £258.19 in 2017; a £100 million fine against suppliers was made public December 2021. BTA published guidance on use of liothyronine for appropriate patients in May 2023 suggesting daily dose 5-10mg at possible split twice day. This report investigated link between amounts and costs of T3 prescribing for different dose levels over the last 6 years.<p class=...

Gas chromatography mass spectrometry (GC-MS) is the gold standard for urinary steroid profiling. Our established GC-MS method quantifies mineralocorticoids, glucocorticoids, and androgens. GC-MS assays require chemical derivatisation and long run times, rendering them unsuitable for high-throughput analysis. Our aim was to develop and validate a high-throughput urinary steroid profiling method using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-LC...

Importance: Thyroid hormone is essential for cognitive development. The Thr92Ala substitution in deiodonase-2 appears to reduce intracellular availability of active thyroid hormone. Individuals with low-normal serum thyroid hormone levels and this substitution might have insufficient intracellular thyroid hormone for optimal cognitive development.Objective: To explore whether individuals with low thyroid hormone bioavailability – free thyroxine in t...

Context: Cytochrome P450 (CYP) 17A1 is located at major branch points of steroidogenesis exerting two distinct catalytic activities: 17α-hydroxylase generates glucocorticoid precursors and 17,20-lyase generates the principal sex steroid precursor dehydroepiandrosterone (DHEA). CYP17A1 deficiency (17OHD) is a rare form of congenital adrenal hyperplasia. In severe 17OHD, affected individuals typically present with both glucocorticoid and sex steroid deficiency and mineraloc...

Steroid 17α-hydroxylase (CYP17A1) exerts two distinct activities that catalyze conversion reactions at key branch points in steroidogenesis. CYP17A1 17α-hydroxylase activity is the key step in cortisol synthesis whereas CYP17A1 17,20 lyase activity generates sex steroid precursors. Inactivating CYP17A1 mutations result in CYP17A1 deficiency (17OHD), a rare form of congenital adrenal hyperplasia that classically presents with combined glucocorticoid and sex steroid de...

Background: The Controlled Antenatal Thyroid Screening II (CATS) study, a large randomised trial of thyroxine supplementation for suboptimal gestational thyroid function (SGTF), reported a higher prevalence of elevated attention deficit hyperactivity disorder (ADHD) scores in 9 year-old children exposed to higher thyroid hormone (TH) in utero. Here we investigated if this was accompanied by altered neurodevelopment.Methods: 85 children aged 11-1...

Comprehensive multi-steroid profiling offers a powerful tool for the investigation, diagnosis and management of steroidogenic disorders by simultaneously quantifying multiple steroids from several pathways of steroid biosynthesis and metabolism. Difficulties can arise when optimising chromatography and mass spectrometry conditions for many analytes in a single method. Low concentrations of ammonium fluoride have previously been shown to enhance the sensitivity of select analyt...

Case history: Vitamin D-dependent rickets type 2 (VDDR2) is an autosomal recessive condition caused by resistance to 1,25(OH)2D3, either through vitamin D receptor (VDR) mutations (type A) or abnormal expression of interfering proteins (type B), resulting in hypocalcaemia despite elevated plasma 1,25(OH)2D3 and parathyroid hormone concentrations. We report a proband, born to Caucasian non-consanguineous parents, who presente...

Background: Development of multi-steroid profiling allows comprehensive investigation into the different branches of steroid metabolism. Immunoassays only allow analysis of a single steroid per assay and suffer from problems with specificity due to cross reactivity of similar steroids. Liquid-chromatography mass spectrometry has the specificity to analyse multiple steroids in a single experiment and the dynamic range to quantify steroids at high concentrations such as those ob...

Background: In women, androgen excess is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD). Androgen precursors are released from the adrenal gland and converted to active androgens in peripheral tissues including adipose tissue. Although the liver plays a key role in all metabolic processes in the body, its involvement in androgen metabolism is yet to be explored. Here, we describe the investigation of androgen metabolism in human liver using norm...