Endocrine Abstracts

Background and aims: HNF1A-MODY causes monogenic diabetes with a lean, insulin sensitive phenotype. Altered glucocorticoid (GC) metabolism has been implicated in the pathogenesis of type 2 diabetes (T2D) and inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which regenerates active cortisol from inactive cortisone have been trialled as a therapeutic approach. 11β-HSD1 is down-regulated in hepatocytes from Hnf1a knock-out mice but the role...

Background and aims: HNF1A-MODY causes monogenic diabetes with a lean, insulin sensitive phenotype. Altered glucocorticoid (GC) metabolism has been implicated in the pathogenesis of type 2 diabetes (T2D) and inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which regenerates active cortisol from inactive cortisone have been trialled as a therapeutic approach. 11β-HSD1 is down-regulated in hepatocytes from Hnf1a knock-out mice but the role...

Introduction: The WHO classification distinguishes G3NET as a separate entity. Literature on G3NETs is limited to case-reports and small case-series. We aimed to characterise G3NETs from a large tertiary centre.Methods: Retrospective analysis from NET database: 2012–2019. All referrals are discussed at a specialist NET-MDT before entry into clinical pathway. Core NET-MDT consists of a radiologist, nuclear-medicine radiologist, histopathologist, spec...

The prevalence of metabolic syndrome and its hepatic manifestation, non-alcoholic fatty liver disease (NAFLD), continues to escalate. Glucocorticoids (GCs) and bile acids (BAs) are established regulators of metabolic phenotype. 5β-reductase (AKR1D1) is highly expressed in human and rodent liver, where it inactivates steroid hormones and catalyses a fundamental step in BA synthesis. We have previously demonstrated that AKR1D1 modulates hepatic GC availability and GC recept...

Background: Urinary steroid metabolite profiling is an accurate reflection of adrenal and gonadal steroid output and metabolism in peripheral target cells of steroid action. Measurement of steroid metabolite excretion by gas chromatography-–mass spectrometry (GC–MS) is considered reference standard for biochemical diagnosis of steroidogenic disorders. However, performance of GC–MS analysis and interpretation of the resulting data requires significant expertise a...

Introduction: Dysregulation of glucocorticoid (GC) metabolism is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). The only available treatment for NAFLD is weight loss and the gold standard diagnostic test is liver biopsy, which is invasive and resource intensive. NAFLD ranges from simple steatosis, to inflammation (steatohepatitis/NASH), fibrosis and cirrhosis. It may be regarded as the hepatic manifestation of the metabolic syndrome and is strongl...

Introduction: Dysregulated glucocorticoid (GC) metabolism has been implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). NAFLD extends from simple steatosis, to inflammation (steatohepatitis/NASH), fibrosis and consequent cirrhosis. It is often regarded as the hepatic manifestation of the metabolic syndrome and is independently associated with increased liver and cardiovascular mortality. Changes in GC metabolism have thus far been described in small num...

Context: Differentiating adrenocortical adenoma (ACA) from adrenocortical carcinoma (ACC) represents a continuous challenge in patients with (often incidentally discovered) adrenal masses, with unfavorable sensitivities and specificities provided by tumor size, imaging and even histology. We have previously developed urine steroid metabolomics as a tool for the detection of adrenal malignancy employing gas chromatography mass spectrometry (GC-MS) for the detection of 32 distin...

Suppression of excess androgen production poses a considerable clinical challenge in the management of patients with congenital adrenal hyperplasia (CAH). Whilst the major route of androgen synthesis in humans is the classic pathway via androstenedione and testosterone, the relative contribution of the alternative pathway originating from 17-hydroxyprogesterone to androgen excess in CAH has not been defined. Androgen effects of both pathways are elicited in androgen target tis...

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 ...