Endocrine Abstracts

Synthetic glucocorticoids are administered to pregnant women at risk of pre-term delivery to mature organs and improve neonatal survival. We have shown that glucocorticoid action is essential to mature the fetal heart. Here, we tested the hypotheses that antenatal glucocorticoid exposure, prior to the normal increase in glucocorticoid levels, will advance fetal heart maturation and this will depend on cardiovascular glucocorticoid receptor (GR).Male SMGR...

Nicotinamide adenine dinucleotide (NAD+) levels increase during metabolic stress, which acts as a consumed substrate by, amongst other proteins, the sirtuins, which adapt transcriptional programmes to increase energy availability and regulate insulin sensitivity. Thus, maintaining appropriate skeletal muscle NAD+ availability is critical for regulating systemic energy homeostasis. In order to gain better insight into ageing muscle NAD+ dynamics we used ta...

ACTH independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing’s syndrome. Both Phosphodiesterase 11A4 (PDE11A4) mutations and inactivating mutations of armadillo repeat containing 5(ARMC5) have been associated with familial AIMAH. A family with autosomal dominant AIMAH was studied trying to elucidate the involved genetic basis.Methods and results: Adrenal hypercortisolism with giant bilateral AH was diagnosed in three adult me...

Introduction: Thyroxine plays a key role in the development of the structures of the ear, the auditory pathway and in myelination of the central nervous system. The association between congenital hypothyroidism (CH) and neurodevelopmental outcome is clearly established. However, there is a lack of data about the prevalence and severity of hearing loss in the CH population.Methods: Between 1/1/12 and 31/12/13, 187 children were diagnosed with CH and treat...

Background: Reduced bone mineral density (BMD) z-scores from Dual energy X-Ray absorptiometry (DEXA) have been reported in childhood HSCT survivors. However, BMD z-scores are unreliable in patients with short stature.Objective: To investigate the influence of HSCT/TBI on size-corrected BMD in childhood leukaemia survivors.Method: Post-pubertal leukaemia survivors (16–26 years) treated with HSCT/TBI (10–1...

Glucocorticoids are routinely administered to pregnant women at risk of pre-term delivery to mature foetal organs and improve neonatal survival. Previous work in glucocorticoid receptor (GR)-deficient mice showed that GR activation is essential for maturation of the foetal heart. Here, we tested the hypotheses that i) antenatal glucocorticoid exposure, prior to the normal increase in glucocorticoid levels, will advance foetal heart maturation and ii) this would depend on mater...

Introduction: Humans with glucocorticoid receptor (GR) deficiency and global heterozygous GR knockout (GR+/−) show compensatory activation of the hypothalamic-pituitary-adrenal axis, resulting in salt-sensitive hypertension due to increased mineralocorticoid activity. Previous studies suggest renal mechanisms, including changes in cell proliferation, gene expression and electrolyte transport, may contribute to this phenotype but underlying adaptive adrenal responses have...

NAD+, an essential coenzyme in energy production, has recently risen to prominence as a signalling molecule central in mediating cellular metabolism and mitochondrial function. NAD+ dependent protein deacetylase sirtuin (SIRT) proteins regulate key metabolic transcription factors, including FOXOs and PGC-1α in muscle, in response to cellular energy demands and metabolic stress. Declining NAD+, metabolic and mitochondrial function are hallm...

Background: Adult survivors of childhood leukaemia treated with bone marrow transplantation and total body irradiation (BMT/TBI) have an increased risk of diabetes mellitus (DM) disproportionate to their level of adiposity or other recognised risk factors. Post prandial hyperglycaemia due to reduced β-cell reserve after irradiation will be missed by fasting glucose (FG) levels. However, the UK National Institute of Clinical Excellence (NICE) screening guidelines recommend...

Introduction: Cerebral oedema has rarely been reported in adrenal insufficiency. We report a case of decompensated cerebral oedema due to autoimmune adrenalitis.Case report: A 12-year-old boy presented to hospital with a 1 day history of headache, fever up to 39.9 °C, confusion, diarrhoea, and vomiting. He had a left-sided ptosis, reduced conscious level (Glasgow coma scale 8/15) and was hypertensive (blood pressure 134/90 mmHg). He required intubat...