Endocrine Abstracts

The most robust biochemical marker for the diagnosis of PCOS is hyperandrogenism (androstenedione, testosterone), thought to originate from the ovaries and/or adrenals. However the change in circulating androgen/LH ratios with increasing body mass in women with PCOS suggests the autocrine generation of androgens within adipose tissue itself. The enzyme 17beta hydroxysteroid dehydrogenase (17betaHSD) which has seven human isoforms is an important regulator of sex steroid metabo...

The number of patients treated for malignant disease in childhood surviving into adulthood is increasing, but success is tempered by long-term side-effects of chemotherapy and radiotherapy; 40% develop one or more endocrinopathy. ALL is a common childhood malignancy treated with chemotherapy and cranial irradiation. The latter causes anterior pituitary hormone deficiencies, most frequently GH deficiency.We have determined GH status in 13 patients treate...

11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) is responsible for the conversion of hormonally active cortisol (F) to inactive cortisone (E), and is expressed in mineralocorticoid target tissues (kidney, colon). However, the most abundant source of this enzyme is human placenta, notably placental trophoblast where it is thought to protect the fetus from maternal hypercortisolaemia and play a role in fetal growth and development. During gestation placental trophobla...

Our recent studies have localised 11 beta hydroxysteroid dehydrogenase type 1 (11 beta HSD1), which activates cortisol from cortisone, to the human ocular non-pigmented ciliary epithelium, and in an open blinded study conducted on healthy male volunteers, systemic inhibition of this isozyme with oral carbenoxolone (CBX) resulted in a 17% reduction of intraocular pressure (IOP). The aim of this study was to evaluate whether CBX reduced IOP in patients with ocular hypertension (...

Central obesity is associated with increased morbidity and mortality. Pre-adipocyte proliferation and differentiation contribute to increases in adipose tissue mass, yet the mechanisms that underpin these processes remain unclear. Patients with glucocorticoid excess develop central obesity, but circulating cortisol levels in idiopathic obesity are normal. The enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inactive cortisone (E) to active cortisol (F)...

The key enzymes in the terminal stages of human adrenal gland corticosteroid biosynthesis are aldosterone synthase (AS) and 11beta-hydroxylase (11beta-OHase). Their amino acid sequences differ by only 7% but they exhibit markedly different enzymatic activities. AS is expressed solely in the zona glomerulosa and converts 11-deoxycorticosterone (DOC) to aldosterone whereas 11beta-OHase is expressed mainly in the zona fasciculata and produces cortisol from 11-deoxycortisol. The 3...

Marshall-Smith syndrome (MSS) is a congenital disorder affecting skeletal and neural development, due to mutations in the nuclear factor I/X (NFIX) gene. NFIX encodes a ubiquitously expressed transcription factor that regulates the expression of viral and cellular genes. To identify novel genes that are misregulated by NFIX mutations, RNA sequencing and proteomics analyses were performed on mouse embryonic fibroblast (MEF) cells derived from a repres...

Introduction: Patients with adrenal insufficiency (AI), continue to face many challenges including: dealing with symptoms and associated disorders; managing medication regimens; prevention and management of complications, and effective engagement and interactions with healthcare providers. In patients with AI, adrenal crisis (AC) continues to lead to unnecessary deaths. We illustrate how University Hospitals Birmingham NHS Foundation Trust used the 4E framework (En...

Introduction: Skeletal muscle cells enable investigation of myogenesis and metabolic function in vitro. Exposure to human serum can provide insight into the impact of endocrine factors upon differentiation and mitochondrial function of skeletal muscle. The aim of these experiments was to optimise the culture conditions using human serum, which it was hypothesised would enhance myogenesis and mitochondrial function of LHCN-M2 human skeletal muscle cells.<p class="a...

Background: Adrenal incidentalomas are common and require investigation to exclude malignancy and evidence of hormone overproduction. Clinical guidelines recommend overnight dexamethasone suppression tests (ONDST) to assess for cortisol hypersecretion with cortisol levels of 50-138 nmol/l termed “mild autonomous cortisol secretion” (MACS). MACS may be associated with both cardiovascular and metabolic morbidity. We assessed cardiovascular risk in patients with MACS us...