The Pituitary in Isolated ACTH Deficiency: A Histologic, Immunocytochemical, and In Situ Hybridization Study

A 74-year-old man presented in a near terminal state with progressive generalized muscular weakness, gastrointestinal disturbances, and lethargy. Investigations revealed hypotension, hyponatremia, hypoglycemia, and low plasma cortisol concentration accompanied by undetectable plasma adrenocorticotropic hormone (ACTH) level. The patient died shortly after admission to hospital, with adrenocortical failure being the provisional cause of death. Autopsy disclosed profound bilateral atrophy of adrenal cortices with evidence of a mild focal inflammatory reaction. The pituitary gland appeared normal on both gross and histologic examinations. There was no histologic evidence of inflammation, fibrosis, or adenohypophysial cell hyperplasia. By immunocytochemistry, no ACTH and B-endorphin immunoreactive cells were identified in the adenohypophysis. In situ hybridization (ISH) for pro-opiomelanocortin (POMC) mRNA yielded conclusively negative results. The case presented here was regarded as isolated ACTH deficiency. Although the remaining pituitary functions were not assessed, clinical and morphologic findings strongly support the supposition that aside from ACTH deficiency, secretory function of other pituitary hormones was preserved. This is the first case in which the pituitary was studied by immunocytochemistry and ISH. The possible pathogenetic mechanisms accounting for the isolated ACTH deficiency are discussed.