Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing's disease

Background: Decreased hippocampal volume is observed in patients with Cushi ng's syndrome and other conditions associated with elevated cortisol levels , stress, or both. Reversibility of hippocampal neuronal atrophy resulting from stress occurs in animals. Our study investigated the potential for rev ersibility of human hippocampal atrophy. Methods: The study included 22 patients with Gushing's disease. Magnetic re sonance brain imaging was performed prior to transsphenoidal microadenomect omy and again after treatment. Results: Following treatment, hippocampal formation volume (HFV) increased by up to 10%. The mean percent change (3.2 +/- 2.5) was significantly great er (p < .04) than that of the comparison structure, caudate head volume (1. 5 +/- 3.4). Increase in HFV was significantly associated with magnitude of deer-ease in urinary free cortisol (r = -.61, p < .01). This relationship s trengthened after adjustments for age, duration of disease, and months elap sed since surgery (r = -.70, p < .001). There was no significant correlatio n between caudate head volume change and magnitude of cortisol decrease. Conclusions: Changes in human HFV associated with sustained hypercortisolem ia are reversible, at least in part, once cortisol levels decrease. While m any brain regions are likely affected by hypercortisolemia, the human hippo campus exhibits increased sensitivity to cortisol, affecting both volume lo ss and recovery. Biol Psychiatry 1999;46:1595-1602 (C) 1999 Society of Biol ogical Psychiatry.