Isolated ACTH Deficiency

Abstract

The term isolated ACTH deficiency refers to the occurrence of hypo-adrenalism secondary to defective synthesis and release of ACTH, with preservation of function of all other pituitary trophic hormones. It is an example of monotropic (unitropic) pituitary hormone deficiency. Before embarking on a discussion of this entity, a few general introductory remarks are appropriate:

• 1. Isolated ACTH deficiency is rare, comprising less than 50 well-documented cases in the world literature. This contrasts with isolated growth hormone (GH) failure and isolated gonadotropin deficiency, both of which are encountered with considerably greater frequency than isolated ACTH deficiency.

• 2. The heterogeneous nature of isolated ACTH deficiency may be the reason for marked differences—both in clinical presentations as well as hormonal data—encountered in patients with this deficiency. Apparently, selective ACTH deficiency is not an all-or-none disorder.

• 3. The lack of availability of sensitive assays for ACTH in the past coupled with the dearth of diagnostic studies delineating the hypothalamic from the pituitary varieties of ACTH deficiency have hampered our understanding of the real nature of this disorder. The availability of synthetic corticotropin releasing factor (CRF) for diagnostic purposes may, at least in part, solve this problem.

• 4. Finally, the diagnosis of selective ACTH deficiency can be entirely missed owing to the nonspecific nature of the symptoms and the seemingly normal baseline studies obtained in many patients with this disorder. Selective ACTH deficiency falls in the category of diseases that are potentially fatal if missed, but completely and gratifyingly treatable if detected.