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Clark AJL et al. - Patients present in early life with low or undetectable cortisol and – because of the failure of the negative feedback loop to the pituitary and hypothalamus – grossly elevated ACTH levels. About half of all cases result from mutations in the ACTH receptor (melanocortin 2 receptor) or from mutations in the melanocortin 2 receptor accessory protein (MRAP), but other genetic causes of this potentially lethal disorder remain to be discovered.

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