Patients with chronic hypercortisolemia due to Cushing's syndrome (CS) exhibit cognitive
dysfunction. Because glucocorticoid excess is associated with hippocampal damage in
animals, and the hippocampus participates in learning and memory, we explored the
relationships between hippocampal formation (HF) volume, memory dysfunction, and cortisol
levels in 12 patients with CS. After magnetic resonance imaging, HF volume was determined
using digital sum of track ball traces of dentate gyrus, hippocampus proper and subiculum,
correcting for total intracranial volume. For 27% of the patients, HF volume fell
outside the 95% confidence intervals for normal subject volume given in the literature.
In addition, there were significant and specific correlations between HF volume and
scores for verbal paired associate learning, verbal recall, and verbal recall corrected
for full-scale IQ (r = 0.57 to 0.70, p < 0.05). HF volume was negatively correlated
with plasma cortisol levels (r = -0.73, p < 0.05). These studies suggest an association
between reduced HF volume, memory dysfunction, and elevated cortisol in patients with
CS.