Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2015) 37 EP1218 | DOI: 10.1530/endoabs.37.EP1218

1University of Medicine and Pharmacy ‘Gr.T.Popa’, Iasi, Romania; 2Universitary Hospital St Spiridon, Iasi, Romania.


Introduction: ACTH resistance syndromes are rare, autosomal and genetically heterogeneous diseases that include familial glucocorticoid deficiency and triple A syndrome. These are characterised by early onset of primary adrenocortical insufficiency associated with hypoglycaemia, convulsions and skin pigmentation.

Case report: We present the case of primary adrenal failure in a boy diagnosed at the age of four, during a decompensation episode with hypoglycaemia and hyponatremic convulsive episode. Adrenal functional evaluation revealed: low cortisol with suboptimal ACTH response-Synacthen (cortisol T60=17.6 ng/dl) and very high ACTH >1500 pg/ml. Glucocorticoid and mineralocorticoid treatment improved the clinical and biologic status (normal natremia and glycaemia). The aetiological evaluation for this adrenal insufficiency included: negative anti-adrenal antibodies, normal long chain fatty acids, negative tuberculosis testing, normal 17-OH progesterone and normal pituitary (MRI) and normal adrenal aspect (CT). This profile suggests a possible diagnosis of ACTH resistance syndrome. Molecular analysis for the ACTH receptor gene (MC2R) and its associated protein (MRAP) is needed for confirming this diagnosis. Clinical aspect is particular: no skin hyperpigmentation (high ACTH>1500)-suggesting a possible melanocyte receptor deficiency (MC1-R). This ACTH resistance diagnosis seems to be associated with alacrima (Shirmer test confirmed low lacrimal secretion) but no achalasia symptoms were objectified.

Discussion: Several mutations have been found to affect the ACTH-R gene and results in different effects on receptor function. Given the ACTH resistance on multiple receptor locations: MC1-R, MC2-R (adrenal insufficiency, absence of hyper pigmentation) we suspect a co-factor mutation. Molecular analysis of DNA for MC2R, MRAP, and AAAS genes in literature shows that about 50% of FGD has unknown genetic cause. Recently, it was shown that MC2R interacts with Nup50, a nuclear pore complex protein, suggesting that this interaction could be a novel mechanism of action of ACTH receptor.

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