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

Biol Psychiatry. 1999 Dec 15;46(12):1595-602. doi: 10.1016/s0006-3223(99)00203-6.


Background: Decreased hippocampal volume is observed in patients with Cushing'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 reversibility of human hippocampal atrophy.

Methods: The study included 22 patients with Cushing's disease. Magnetic resonance brain imaging was performed prior to transsphenoidal microadenomectomy 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 greater (p < .04) than that of the comparison structure, caudate head volume (1.5 +/- 3.4). Increase in HFV was significantly associated with magnitude of decrease in urinary free cortisol (r = -.61, p < .01). This relationship strengthened after adjustments for age, duration of disease, and months elapsed since surgery (r = -.70, p < .001). There was no significant correlation between caudate head volume change and magnitude of cortisol decrease.

Conclusions: Changes in human HFV associated with sustained hypercortisolemia are reversible, at least in part, once cortisol levels decrease. While many brain regions are likely affected by hypercortisolemia, the human hippocampus exhibits increased sensitivity to cortisol, affecting both volume loss and recovery.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age Factors
  • Atrophy
  • Caudate Nucleus / pathology
  • Cushing Syndrome / blood*
  • Cushing Syndrome / etiology
  • Cushing Syndrome / surgery
  • Cushing Syndrome / urine
  • Female
  • Hippocampus / pathology*
  • Humans
  • Hydrocortisone / blood*
  • Hydrocortisone / urine
  • Hypophysectomy*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Time Factors


  • Hydrocortisone