title: Siblings with ACTH insensitivity due to lack of ACTH binding to the receptor.
abstract: We report two siblings, a 9-year-old boy and 4-year-old girl, with ACTH insensitivity. They were referred to our hospital because of pigmentation of the skin. They had normal plasma cortisol and urinary 17-OHCS levels despite markedly high plasma ACTH, and these did not respond to consecutive 3-day ACTH-Z administration, but plasma aldosterone responded normally to increased plasma renin activity after a low sodium diet. We examined the characteristics of ACTH receptors in peripheral blood mononuclear leukocytes (MNLs) obtained from the patients and their family. Adenylate cyclase generation caused by an addition of ACTH did not occur in MNLs from the patients. In studies on ACTH binding to MNLs, a lack of high-affinity ACTH binding was observed in the patients. These results suggest that the patients have a defect in ACTH binding to the receptors, resulting in ACTH insensitivity. The reason for this defect in ACTH binding remains unclear because no significant mutation in the ACTH receptor DNA sequence was detected in the MNLs of these patients.
authors.affiliation: Department of Pediatrics, University of Occupational and Environmental Health, Kitakyushu, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Kawada
authors.forename: M
authors.initials: M
authors.lastname: Noda
authors.forename: M
authors.initials: M
authors.lastname: Yamagishi
authors.forename: O
authors.initials: O
authors.lastname: Ishida
authors.forename: T
authors.initials: T
authors.lastname: Fujihira
authors.forename: F
authors.initials: F
authors.lastname: Shirakawa
authors.forename: I
authors.initials: I
authors.lastname: Morimoto
mesh_terms: D015065:17-Hydroxycorticosteroids / Q000652:urine; D000262:Adenylyl Cyclases / Q000097:blood; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D000450:Aldosterone / Q000097:blood; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000737:chemistry; D004039:Diet, Sodium-Restricted; D004351:Drug Resistance; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D018043:Receptors, Corticotropin / Q000235:genetics / Q000378:metabolism*; D012083:Renin / Q000097:blood; D012880:Skin Pigmentation
chemical_list: D015065:17-Hydroxycorticosteroids; D018043:Receptors, Corticotropin; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D004247:DNA; D012083:Renin; D000262:Adenylyl Cyclases; D006854:Hydrocortisone