Plasma cortisol response to thyrotropin-releasing hormone and luteinizing hormone-releasing hormone in Cushing's disease.

In 3 of 6 patients with pituitary-dependent Cushing's disease, a paradoxical increase of plasma cortisol was observed both after LRH (delta max, 13.9 +/- 3.7 microgram/100 ml; 113 +/- 52%) and TRH (delta max, 8.0 +/- 2.9 microgram/100 ml; 53 +/- 18%) administration, the maximum values being achieved 30--60 min after the iv bolus injection. In the remaining 3 patients and in 15 control subjects, plasma cortisol levels did not rise in response to either LRH or TRH administration but rather showed a slight to distinct decrease during the study period. The paradoxical cortisol response in half of the patients with Cushing's disease may be the consequence of loss of specificity of the pituitary receptor or alteration in the hypothalamo-pituitary pathways.