Endocrine Abstracts

Mitochondrial steroidogenic cytochrome P450 (CYP) enzymes, such as P450 side-chain cleavage, rely on electron transfer from the redox partner ferredoxin (FDX1) for catalytic activity. Previous in vitro data suggest these cofactors are key regulators of CYP enzyme activity. This study aims to establish the role of redox regulation on steroidogenesis using zebrafish as a vertebrate in vivo model.In contrast to humans, zebrafish have two F...

Background: Cytochrome P450 side-chain cleavage enzyme (CYP11A1) catalyses the first and rate-limiting step of steroidogenesis. CYP11A1 firstly converts cholesterol into 22R-hydroxycholesterol, which relies on mitochondrial steroidogenic acute regulatory protein (StAR)-mediated cholesterol import. Two further StAR-independent CYP11A1 reactions facilitate pregnenolone biosynthesis. CYP11A1 deficiency is rare and manifests with adrenal insufficiency (AI), and, in 46,XY individua...

In this study we explore and integrate a pathway for loss of functional beta cell mass in diabetes. Inflammatory cytokines induce human islet dysfunction, elevate expression of 12-lipoxygenase, increase cellular reactive species and induce NADPH oxidase. These pathways are elevated in islets from diabetic donors.NADPH oxidase-1 (NOX-1) is significantly induced in either human donor islets, primary mouse islets or homogeneous beta cell lines following sti...

A breakdown in stromal-epithelial interactions mediated by androgens is emerging as a key factor in prostate cancer (PCa) aetiology and progression. Currently however, we have limited knowledge of the mechanics of androgen and androgen receptor (AR) action in prostate stroma, or how dysfunction in that compartment contributes to the disease process.In this study, immunohistochemical analysis of 64 PCa samples revealed an inverse relationship between stro...

Background: Serum thyroglobulin (Tg) measurements are one of the main pillars of thyroid cancer follow-up, because of the high organ and disease specificity of Tg in athyrotic patients. However, 20–25% of patients have detectable serum anti-Tg auto-antibodies (TgAB), which might cause false low Tg measurements in immunometric assays (IMA). This can lead to significant challenges in patient management. Measurement of Tg by liquid chromatography-tandem mass spectrometry (LC...

Background: 5α-Reductase type 2 deficiency (5ARD) is caused by mutations in the SRD5A2 gene. Inadequate masculinisation in XY individuals results from failure to convert testosterone (T) to dihydrotestosterone (DHT), a potent androgen. A decreased serum T:DHT ratio is frequently taken to identify 5ARD, but requires hCG stimulation for prepubertal patients; findings are not always supported by genotyping. Urine steroid profiling (USP) by GC-MS is established as showing sig...

Background: SDH mutations cause about 80% of familial pheochromocytomas / paragangliomas (1). Although mutations in each subunit are associated with a particular clinical spectrum of disease, there is no clear genotype-phenotype correlation of a specific mutation, nor with penetrance of disease. We report characteristics of patients with SDH mutations seen in a single dedicated tertiary referral clinic.Methods: A retrospective observational study of pati...

Objective: Mitotane (o,p’DDD) is an effective adrenolytic agent for treatment of advanced adrenocortical carcinoma (ACC). Suppression of cortisol biosynthesis, including inhibition of 11β-hydroxylation, has been described. Decreased cortisol bioavailability is indicated by increased dose requirement for hydrocortisone replacement during mitotane treatment. Urinary excretion of common cortisol metabolites (CM) has been reported to be normal but with increase of 6&#946...

Introduction: Neonatal diabetes mellitus is a rare condition with an estimated incidence of 1 in 400 000 live births in the UK population. Half of these cases will have permanent neonatal diabetes mellitus (PNDM). We report a homozygous missense mutation (R397L) in the glucokinase (GCK) gene which is associated with PNDM, in an infant from a consanguineous Asian family.Case report: The baby was born with a birth weight of 1.68 kg at 38 weeks gesta...

Objective: Hypothyroidism is common and predominantly managed in primary care. Symptoms are non-specific, with thyroid function tests (TFT) required for diagnosis. We sought to investigate current practice in levothyroxine prescribing in primary care.Methods: We studied the initiation of levothyroxine using the General Practice Research Database (GPRD), the world’s largest database of anonymised medical records. Individuals with i) thyroid cancer ii...