Adrenocorticotropin Insensitivity Syndromes

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I. Introduction

ACTH INSENSITIVITY syndromes comprise an uncommon group of disorders that, current evidence suggests, have at least three different molecular etiologies. The aim of this review is to examine the various forms of clinical presentation in conjunction with the current knowledge of the molecular and genetic background of these diseases, which as will be seen, reveals some interesting and unexpected physiological and anatomical relationships.

The principal pathways by which ACTH stimulates adrenal steroidogenesis are summarized in Fig. 1. The syndrome of ACTH insensitivity was originally described by Shepard et al. (1) in 1959 in a paper entitled “Familial Addison’s Disease,” which reported the case of two sisters who had what has subsequently become known most frequently as familial glucocorticoid deficiency, isolated glucocorticoid deficiency, adrenal unresponsiveness to ACTH, or hereditary unresponsiveness to ACTH. For uniformity, and since it was the first of these terms to be coined and has been most frequently used in the literature, we continue to refer to this disorder as familial glucocorticoid deficiency (FGD), although the other terms are equally descriptive (MIM^*202200).