Endocrine Abstracts

5α reductases 1 and 2 (SRD5A1 and SRD5A2) metabolise cortisol into inactive 5α-dihydrocortisol contributing to the regulation of cortisol availability in addition to their established role in the generation of dihydrotestosterone from testosterone. Dutasteride and finasteride are commonly prescribed to patients with benign prostatic hyperplasia but their potential metabolic effects have only recently been identified. Dutasteride inhibits both SRD5A1and SRD5A2 whilst ...

Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the commonest cause of liver cirrhosis and leading indication for liver transplant worldwide. It is tightly associated with obesity and type 2 diabetes, yet the precise mechanisms that drive its aetiology are not fully defined. Dysregulation of both glucocorticoid and androgen metabolism has been implicated in its pathogenesis. The availability of these hormones to bind and activate their receptors is mainly regulat...

Recently, liquid chromatography–tandem mass spectrometry (LC–MS/MS) was stated to be the method of choice to measure sex steroids.1 Information on the mutual agreement of LC–MS/MS methods, however, is scarce. Therefore, we compared seven published LC–MS/MS methods for the simultaneous measurement of testosterone, androstenedione, and DHEA. Fifty-five random serum samples obtained from volunteers were analysed in duplicate by seven published LC&#1...

Patients with adrenal insufficiency (AI) require adjustment of hydrocortisone (HC) dose to avoid life-threatening adrenal crisis during illness, surgery and trauma. However, current dose recommendations are based on empirical grounds only and choice of dose and administration modes vary considerably. We designed the PACS study to compare cortisol levels achieved by currently recommended HC stress doses to those in i) healthy controls (n=85, 21–70 years), ii) mili...

Background: The treatment of metastatic castration-resistant prostate cancer (CRPC) remains dependent on Androgen Receptor (AR) mediated signalling, thus understanding all components involved in testosterone signalling in these men is of utmost importance. Recent studies have identified 11-ketotestosterone (11 KT) as a potent androgen receptor (AR) agonist present in humans. However, it is unknown if 11 KT is present at physiologically relevant concentrations in CRPC patients....

Hyperandrogenaemia and polycystic ovary syndrome (PCOS) are common in women with Type 1 diabetes, but it is not known if they contribute to increased cardiovascular risk. We aimed to compare associations between androgen levels, lipid variables and early atherosclerosis in reproductive-age women with and without T1DM. 87 (16 with PCOS) women with T1DM (mean±SD; age 28.7±6.1yrs, BMI 25.4±4.4kg/m2), and 87 (16 PCOS) nondiabetic women (mean±SD; age ...

BackgroundPolycystic Ovary Syndrome (PCOS) is the most prevalent endocrine disorder in women of reproductive age. The main components are hyperandrogenemia and oligo-/amenorrhea. The pathophysiology of PCOS is not fully understood which is why no causal treatment options are available. A multitude of observational studies demonstrated elevated C-reactive protein (CRP) levels in patients with PCOS compared with weight-matched controls. CRP is a sensitive ...

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women. Androgen excess is a cardinal biochemical feature of PCOS and correlates closely with markers of insulin resistance. 11-oxygenated androgens are the predominant androgens in PCOS, however their relationship with metabolic dysfunction is unclear. The aims of this study were (i) to evaluate the downstream impact on androgen metabolism of oral classic and 11-oxygenated precursor administration and (i...

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 ...

Chronic wounds (e.g. diabetic foot ulcers) have a major impact on quality of life, yet treatments remain limited. Glucocorticoids impair wound healing; preclinical research suggests that blocking glucocorticoid activation by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) improves wound repair. This investigator-initiated double-blind, randomised, placebo-controlled parallel-group phase 2b pilot trial investigated efficacy, safety and feasibility of 11&...