Isolated glucocorticoid deficiency and ACTH receptor mutations

Familial isolated glucocorticoid deficiency is a form of potentially lethal hereditary unresponsiveness to ACTH that manifests as primary adrenal insu fficiency, usually without mineralocorticoid deficiency. Affected children commonly present with hyperpigmentation, recurrent hypoglycemia, chronic as thenia and failure to thrive within the first 2 years of life. Typically, t hey have deficient production of cortisol and adrenal androgens in the pres ence of markedly elevated ACTH levels, while renin and aldosterone levels a re usually normal and responsive to activation of the renin-angiotensin axi s. Clinical awareness of these syndromes is of considerable prognostic and therapeutic importance. The etiological involvement of the ACTH receptor ge ne in isolated glucocorticoid deficiency has been recently established in m any, but not all, affected families. Several naturally occurring mutations of the ACTH receptor gene have been identified to date and have helped illu minate the mechanisms of ligand binding and signal transduction by this rec eptor. Discovery of the molecular defect(s) responsible for isolated glucoc orticoid deficiency in cases with a normal ACTH receptor gene coding region and for the triple A syndrome (adrenal insufficiency, alacrima, achalasia) will hopefully provide further insight into the mechanisms of adrenocortic al function and will increase the prospect of new therapeutic approaches. ( C) 2000 IMSS. Published by Elsevier Science Inc.