title: Isolated glucocorticoid deficiency and ACTH receptor mutations.
abstract: Familial isolated glucocorticoid deficiency is a form of potentially lethal hereditary unresponsiveness to ACTH that manifests as primary adrenal insufficiency, usually without mineralocorticoid deficiency. Affected children commonly present with hyperpigmentation, recurrent hypoglycemia, chronic asthenia and failure to thrive within the first 2 years of life. Typically, they have deficient production of cortisol and adrenal androgens in the presence of markedly elevated ACTH levels, while renin and aldosterone levels are usually normal and responsive to activation of the renin-angiotensin axis. Clinical awareness of these syndromes is of considerable prognostic and therapeutic importance. The etiological involvement of the ACTH receptor gene in isolated glucocorticoid deficiency has been recently established in many, but not all, affected families. Several naturally occurring mutations of the ACTH receptor gene have been identified to date and have helped illuminate the mechanisms of ligand binding and signal transduction by this receptor. Discovery of the molecular defect(s) responsible for isolated glucocorticoid 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 adrenocortical function and will increase the prospect of new therapeutic approaches.
authors.affiliation: Hellenic National Center for the Research, Prevention and Treatment of Diabetes Mellitus and Its Complications, Athens, Greece. ctsigos@hndc.gr
authors.forename: C
authors.initials: C
authors.lastname: Tsigos
mesh_terms: D000818:Animals; D005938:Glucocorticoids / Q000172:deficiency*; D006801:Humans; D009154:Mutation; D018043:Receptors, Corticotropin / Q000235:genetics*
chemical_list: D005938:Glucocorticoids; D018043:Receptors, Corticotropin