SIBLINGS WITH ACTH INSENSITIVITY DUE TO LACK OF ACTH BINDING TO THE RECEPTOR

We report two siblings, a 9-year-old boy and 4-year-old girl, with ACT H insensitivity. They were referred to our hospital because of pigment ation of the skin. They had normal plasma cortisol and urinary 17-OHCS levels despite markedly high plasma ACTH, and these did not respond t o consecutive S-day ACTH-Z administration, but plasma aldosterone resp onded normally to increased plasma renin activity after a low sodium d iet. We examined the characteristics of ACTH receptors in peripheral b lood mononuclear leukocytes (MNLs) obtained from the patients and thei r family. Adenylate cyclase generation caused by an addition of ACTH d id 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 patient s. These results suggest that the patients have a defect in ACTH bindi ng to the receptors, resulting in ACTH insensitivity. The reason for t his defect in ACTH binding remains unclear because no significant muta tion in the ACTH receptor DNA sequence was detected in the MNLs of the se patients.