Endocrine Abstracts

Background: Congenital Hyperinsulinism in Infancy (CHI) is characterised by inappropriate insulin release from islet β-cells. We currently attribute hypoglycaemia to β-cell dysfunction because of defects in the ion channel genes ABCC8 or KCNJ11. However, the CHI pancreas is also associated with the inappropriate expression of foetal-like transcription factors and enhanced cell proliferation. We hypothesised that islet cell differentiation and neogen...

Background: The mechanisms responsible for inappropriate insulin release from β-cells in Congenital Hyperinsulinism in Infancy (CHI) have largely focused upon defects in KATP channels. Little is known about insulin biogenesis, the profiles of insulin in insulin-containing secretory granules or whether the impact of KATP channel defects (due to mutations in ABCC8 or KCNJ11) is the same in diffuse- and focal disease.<p class="abst...

Introduction: In many endocrine centres the 250μg Short Synacthen (Cosyntropin) Test (SST) is the reference standard for the diagnosis of adrenal insufficiency (AI) 1, but it is time consuming, expensive, and requires hospital attendance and venepuncture. The morning physiological peak of cortisol shortly after waking is a good predictor for a negative SST; however, a morning serum cortisol requires venepuncture. Serum cortisol and salivary cortisone correlate ...

Introduction: The 250µg Short Synacthen test (SST) is the reference standard for a diagnosis of adrenal insufficiency (AI) in most endocrine centres. The test is expensive and time consuming, requiring clinic attendance. We hypothesised that a cheaper home waking salivary cortisone (WSC) is predictive of the SST 30-minute cortisol >430 nmol/l cut-off and carried out a diagnostic accuracy study to assess the predictive value of the WSC in diagnosing and excluding AI. W...

Clinical Endocrinology, 2018, 88(1): 21–29 (DOI: https://doi.org/10.1111/cen.13447)...

Background: Large populations of HIV and tuberculosis occur in South Africa and, amongst these patients, Addison’s disease is probably underdiagnosed. Preliminary data in 60 HIV-positive patients with a CD4 count less than 100 cells/mm3 showed that the overall prevalence of hypoadrenalism was 6.7%, with 1 patient having primary hypoadrenalism and 3 patients having central hypoadrenalism. This report describes the prevalence of hypoadrenalism and its association...

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: Atypical congenital hyperinsulinism in infancy (CHI-A) represent patients who generally present symptoms of hypoglycaemia later in the neonatal period, are poorly responsive to medical intervention and have no known genetic cause of disease. Our objective was to compare the expression profiles of insulin and somatostatin in islets from patients with CHI-A, diffuse CHI (CHI-D) and age-matched control tissue.Methods and materials: CHI tissues w...

Background: In diffuse CHI (CHI-D) insulin release is uncontrolled due to mutations in the ABCC8/KCNJ11 genes. Increased rates of cell proliferation have also been reported, but the mechanisms responsible for this are unknown. We hypothesized that this may arise as a consequence of failure to terminate proliferation in the neonatal period. Here, we examined the proliferative index (PI) of islet cells in CHI-D patients and compared this with focal CHI (CHI-F) ...

Background/hypothesis: Congenital hyperinsulinism in infancy (CHI) mainly arises from mutations in ATP-sensitive potassium channel genes. However, the expression pattern of defects can be markedly diverse. In diffuse CHI (CHI-D) all islet cells express gene defects, whereas patients with focal CHI (CHI-F) only express defects in a localised region of islet cells due to loss of a maternally-imprinted locus. Here, we examined the properties of a novel population of CHI islet cel...