THE inaccessibility of many tissues makes routine investigation for receptor defects impossible. ACTH insensitivity syndrome, first described by Shepard et al.1 in 1959 and now reported in more than 63 patients,12345678910111213141516171819 is an example of this problem. Defects in adrenal ACTH receptors have been postulated because of high circulating ACTH levels and the ability of the adrenal-cortex cells to achieve steroidogenesis through an elevation of cyclic AMP.12345678910111213141516171819 In the majority of cases, the clinical presentation includes hyperpigmentation, hypoglycemia, and extremely low glucocorticoid levels with normal mineralocorticoid concentrations.2345678910111213141516 Differences between cases suggest that the syndrome may have multiple causes. Adrenal cells… © 1987, Massachusetts Medical Society. All rights reserved.