Endocrine Abstracts

Background: Triple A syndrome is a rare, autosomal recessive cause of adrenal insufficiency. Additional features include alacrima, achalasia of the oesophageal cardia, and neurodegenerative disease in 60%. The AAAS gene product is the nuclear pore complex protein ALADIN of unknown function. AAAS patient dermal fibroblasts have been described as hypersensitive to oxidative stress1,2,3.Objective: To establish a better disease model by kno...

Background: Triple A Syndrome is a rare, autosomal recessive cause of adrenal failure that usually manifests in the first decade. Most cases have isolated glucocorticoid deficiency, but this is accompanied by mineralocorticoid deficiency in approximately 10% of cases. Additional features include alacrima (~90%), achalasia of the oesophageal cardia (~75%), and a progressive neurodegenerative process (~60%). The AAAS gene product is the nuclear pore complex protein ALADIN...

Introduction: Triple A syndrome is a rare, autosomal recessive cause of adrenal failure that usually manifests in the first decade. Most cases have isolated glucocorticoid deficiency, but this is accompanied by mineralocorticoid deficiency in ~10%. Additional features include alacrima (~90%), achalasia of the oesophageal cardia (~75%), and a progressive neurodegenerative process (~60%). The AAAS gene product is the nuclear pore complex protein ALADIN of unknown function...

Melanocortin receptor accessory protein (MRAP) is a single transmembrane domain protein, which has been identified as essential for the cell surface trafficking and signalling of the ACTH receptor (melanocortin 2 receptor (MC2R)). MRAP is essential for the function of MC2R, but regulation of its expression remains unclear. This study aims to identify factors regulating MRAP gene expression and whether these factors would affect the signalling of MC2R.The...

Direct trauma to the adrenal glands resulting in adrenal gland failure is relatively rare. We present two cases of post-traumatic hypoadrenalism.Case 1: A 53-year-old male who was trapped under a lorry trailer. He was found to have fractures of T6 (unstable), T12, rib and sternal fractures. He was transferred to the orthopaedic ward and required a spinal splint. He was slowly recovering until day 20 of his admission when he became hypotensive and tachyca...

Glucocorticoids (GCs) are steroid hormones, products of the hypothalamic–pituitary–adrenal axis. Synthetic GCs, such as dexamethasone, have been widely used in the treatment of inflammatory diseases like rheumatoid arthritis or asthma, but their long-term use causes severe side effects (osteoporosis, diabetes, hypertension, etc). The ligand-bound GC receptor (GR) can activate gene expression via binding to GC response elements (GREs), a mechanism known as transactiva...

ACTH insensitivity or familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder first described in 1959. We demonstrated in 1993 that about 25% of affected patients have nonsense or (more commonly) missense mutations in the ACTH receptor (melanocoprtin 2 receptor, MC2R). Functional analysis of these mutations had been especially difficult until our discovery in 2005 that the receptor requires an essential accessory factor – the melanocortin 2 recepto...

Introduction: Recent trials suggest that using ergot-derived dopamine agonists such as cabergoline in the treatment of Parkinson’s disease is associated with an increased risk of valvular heart disease. However, the dose of cabergoline used to treat hyperprolactinaemia is considerably less than that used in Parkinson’s disease.Study design: A cross-sectional study; forty four patients, who received cabergoline for at least 6 months, underwent t...

Triple A syndrome is is a rare autosomal recessive disorder characterised by achalasia, alacrima, adrenocorticotropin-resistant adrenal insufficiency and a variable and progressive neurological phenotype. The AAAS gene encodes a 60kD WD-repeat nuclear pore protein named ALADIN (alacrima, achalasia, adrenal insufficiency neurologic disorder); its function and tissue distribution are unknown. In this study we performed in situ hybridization with 35S end-labelled AAAS mRNA oligon...

Ectopic secretion of adrenocorticotropin (ACTH), from sites such as small cell lung cancer (SCLC), results in severe Cushing's syndrome. ACTH is cleaved from pro-opiomelanocortin (POMC). The syndrome occurs when the highly tissue-specific promoter of POMC is activated. This promoter lies within a defined CpG island. CpG islands are usually considered to be unmethylated in all tissues. We hypothesised that changes in promoter DNA methylation might direct aberrant express...