Endocrine Abstracts

Oestrogen quantification in serum is challenging as concentrations are low, especially in men and post-menopausal women. Additionally, oestrogens do not ionise readily and structure similarities can lead to cross-reactivity and reduced specificity, especially with immunoassay. Full characterisation of oestrogen metabolism and its role in disease progression has therefore not been fully investigated. We aimed to develop and validate a liquid chromatography mass spectrometry met...

Gas chromatography–mass spectrometry (GC–MS) has been used for urinary steroid analysis for over 50 years. The process of hydrolysis to release steroids from their conjugates is routinely performed using commercially available snail Helix-Pomatia sulfatase (HP). However, as this is a naturally occurring enzyme its production process results in batch variation and so each batch requires experimental validation to adjust for the difference in efficiency of the enzymati...

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...

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...

Objective: Quantify classic and 11-oxygenated androgens in serum and saliva and determine variations across age, sex, body mass index (BMI), menstruation and hormonal contraception use.Methods: Morning serum samples were collected from 292 healthy volunteers (125 men, 22-95 years; 167 women, 21-91 years). Morning saliva was collected from 83 healthy volunteers (51 women, 32 men). 25 individuals (12 women, 13 men) also collected a 7-timepoint diurnal sali...

Background: Advancements in medical care have significantly improved survival after major traumatic injury and the main risks are now sepsis and multi-organ failure. An understanding of the hormonal, inflammatory and metabolic changes that occur following trauma is still evolving but it is clear that they impact significantly upon patient prognosis. To date, studies that have examined trauma-induced changes in steroid metabolism have analysed samples taken from patients post-h...

Background: The gonads are the major source of classic androgens during reproductive years. Additionally, the adrenal gland produces precursors for both classic and 11-oxygenated androgen biosynthesis, with androgen activation predominantly occurring in peripheral target tissues of androgen action. We used liquid chromatography-tandem mass spectrometry to profile classic and 11-oxygenated androgens in serum and saliva across the adult age range and assessed diurnal as well as ...

Introduction: Gas chromatography mass spectrometry (GC-MS) is the gold standard method for urinary steroid profiling. However, GC-MS requires chemical derivatisation, long run times, is labour intensive, expensive, and unsuitable for rapid multi-sample analysis, limiting its use in routine clinical practice. GC-MS urinary steroid metabolomics, the combination of steroid profiling and machine learning (Generalized Matrix Learning Vector Quantization) was shown to have superior ...

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...