Adrenocorticotropin and Cortisol Responsiveness to Thyrotropin-Releasing Hormone and Luteinizing Hormone-Releasing Hormone Discloses Two Subsets of Patients with Cushing's Disease

Abstract

In 23 consecutive patients with Cushing's disease and 52 control subjects, the responses of ACTH and cortisol to TRH and LRH were investigated. From the pattern of cortisol levels after the administration of the releasing hormone in the controls, a criterion for paradoxical responsiveness could be derived (maximum cortisol increase, >6.0/xg/100 ml). Accordingto this criterion, 9 patients with Cushing's disease showed aparadoxical responsiveness to one or both releasing hormones(3 to both TRH and LRH, 3to TRH alone, and 3 to LRH alone;group I). In all patients tested, paradoxical responses of cortisolwere preceded by paradoxical increments in ACTH. The remaining15 patients showed no paradoxical increments in ACTHor cortisol after TRH or LRH (group II). ACTH levels in groupI (89 ± 28 pg/ml) were significantly lower than those in group II(185 ± 164 pg/ml; P < 0.02). Nevertheless, in both groups, asimilar plasma cortisol level was found, suggesting a relatively higher bioactivity of ACTH in group I. A second differencebetween both groups was a lower amplitude of cortisol variabilityduring the day in group I. The 2 groups did not differ in clinicaldata, such as age, sex distribution, sellar volume, and duration ofdisease, or dexamethasone suppressibility, bromocriptine sensitivity,and basal PRL levels. These latter findings do not favoran intermediate lobe origin of Cushing's disease in patients with paradoxical responses to TR/LRH. To conclude, TRH/LRH responsiveness of ACTH/cortisoldiscloses two subsets of patients withCushing's disease. (J ClinEndocrinol Metab55: 1188, 1982)