Glucocorticoid receptors in anorexia nervosa and Cushing's disease

Background: Patients with anorexia nervosa do not display cushingoid featur es in spite of elevated cortisol plasma levels. Whether a cortisol resistan ce or a reduced availability of the metabolic substrates necessary to devel op the effect of glucocorticoids is responsible for this has nor been estab lished. Methods: Twenty-two patients with severe restrictive anorexia nervosa, 10 p atients with active Cushing's disease, and 24 healthy volunteers without ps ychiatric disorders or mood alterations were investigated Glucocorticoid re ceptor characteristics were examined on mononuclear leukocytes by measuring [H-3]dexamethasone binding and the effect of dexamethasone on [H-3]thymidi ne incorporation, which represents an index of DNA synthesis. Results: The number of glucocorticoid receptors on mononuclear leukocytes ( MNL) was comparable in patients with anorexia nervosa, patients with active Cushing's disease, and normal subjects (binding capacity 3.3 +/- 0.23 vs. 3.7 +/- 0.30 and 3.5 +/- 0.20 fmol/10(6) cells). Conversely, glucocorticoid receptor affinity was significantly decreased in anorexia nervosa as well as in Gushing's patients compared to control subjects (dissociation constan t 4.0 +/- 0.31 and 4.1 +/- 0.34 vs. 2.9 +/- 0.29 nmol/L, p <.001) and inver sely correlated with the levels of urinary free cortisol in both groups of patients. Basal [H-3]thymidine incorporation in MNL was significantly reduc ed in anorexia nervosa as well as in Gushing's patients compared to control subjects (p <.001) and was diminished by dexamethasone to an extent simila r to control subjects in patients with anorexia nervosa, but significantly (p <.001) Less in those with Gushing's disease. In patients with anorexia n ervosa, the incorporation of [H-3]thymidine into the MNL was inversely corr elated with urinary free cortisol levels. Conclusions: These data indicate that the lack of cushingoid features in pa tients with anorexia nervosa is not ascribable to a reduced sensitivity to glucocorticoids but is more likely due to the paucity of metabolic substrat es. (C) 1999 Society of Biological Psychiatry.