Dissociation between plasma bioactive and immunoactive ACTH concentrations in depressed patients

Previous studies have reported dissociations between plasma cortisol and immunoactive adrenocorticotropic hormone (ACTH) concentrations in both normal controls and in patients with major depression. In order to investigate this issue further, placebo and dexamethasone (DEX) were administered to normal controls and depressed patients at 11 PM, and plasma cortisol and ACTH were measured the following morning at 7 AM. Plasma ACTH concentrations were quantitated by both immunoassay (I-ACTH) and by bioassay (B-ACTH). In 10 normal controls, DEX (0.25, 0.5, and 1.0 mg, PO, elixir) produced a dose-related suppression of cortisol, I-ACTH and B-ACTH, with all three hormones significantly suppressed by DEX (0.5 and 1.0 mg) (p < or = 0.01). In 20 depressed patients, 7 AM plasma ACTH and cortisol concentrations were assessed following a single dose of DEX (0.5 mg). Fifteen patients were classified as suppressors and five as escapers, as reflected by mean (+/- SEM) cortisol concentration of 19.9 +/- 3.0 ng/ml and 81.2 +/- 7.0 ng/ml, respectively. Mean I-ACTH concentrations were comparable in both the escapers (8.6 +/- 1.6 pg/ml) and in the suppressors (7.0 +/- 1.0 pg/ml). In contrast, the mean B-ACTH concentration was more than two-fold higher in the escapers (4.5 +/- 0.5 pg/ml) than in the suppressors (2.2 +/- 0.3 pg/ml) (p < or = 0.001). Eleven of the 20 patients received both placebo and DEX (0.5 mg) on two separate occasions. Although DEX significantly suppressed both cortisol (p < or = 0.0001) and B-ACTH (p < or = 0.01) concentrations, I-ACTH was not significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)