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, greater than 6.0 micrograms/100 ml). According to this criterion, 9 patients with Cushing's disease showed a paradoxical responsiveness to one or both releasing hormones (3 to both TRH and LRH, 3 to TRH alone, and 3 to LRH alone; group I). In all patients tested, paradoxical responses of cortisol were preceded by paradoxical increments in ACTH. The remaining 15 patients showed no paradoxical increments in ACTH or cortisol after TRH or LRH (group II). ACTH levels in group I (89 +/- 28 pg/ml) were significantly lower than those in group II (185 +/- 164 pg/ml; P less than 0.02). Nevertheless, in both groups, a similar plasma cortisol level was found, suggesting a relatively higher bioactivity of ACTH in group I. A second difference between both groups was a lower amplitude of cortisol variability during the day in group I. The 2 groups did not differ in clinical data, such as age, sex distribution, sellar volume, and duration of disease, or dexamethasone suppressibility, bromocriptine sensitivity, and basal PRL levels. These latter findings do not favor an intermediate lobe origin of Cushing's disease in patients with paradoxical responses to TRH/LRH. To conclude, TRH/LRH responsiveness of ACTH/cortisol discloses two subsets of patients with Cushing's disease.

Cushing's disease: a comparison of pituitary corticotroph microadenomas and macroadenomas

“…The disease is of clonal origin in the majority of cases, and subtypes could result from the heterogeneity of normal corticotroph cells (2,3). Classifications have been proposed on the basis of histological (4), radiological (5), biochemical (6) or functional criteria (7,8), but none has so far been widely accepted.…”

Stress Reactions in Response to the Procedure of LHRH Tests as Measured by Salivary and Serum Cortisol and Psychological Variables

“…In addition to serum LH and FSH, serum and salivary cortisol was determined. Since LHRH has no pharmacological effect on cortisol [9][10][11] and ACTH [12] secretion in healthy men, an increase of cortisol is considered to be a stress reaction to this med ical procedure. LHRH tests were administered individually, i.e.…”

“…Venipuncture may be accompanied by a release of cortisol [3][4][5], cate cholamines [6,7] and GH [3,5,8], The procedure of the LHRH test, a challenge test frequently used in endocri nology and reproductive medicine, offers a good oppor tunity for studying such stress effects during venipunc ture, since LHRH has no pharmacological effect on cor tisol [9][10][11] or ACTH [12] secretion in healthy men.…”

Ectopic Adrenocorticotropin Syndrome Exhibiting Paradoxical Adrenocorticotropin Responsiveness to Gonadotropin-Releasing Hormone.

“…Reaction control samples of sections were prepared Clinical, biochemical, radiographic, and morphologic features of ectopic corticotropin (ACTH)-dependent Cushing's syndrome are often indistinguishable from those of Cushing's disease (pituitary-dependent Cushing's syndrome) [4,5] . However, it is critically important to make an accurate diagnosis since clinical and biochemical remission of Cushing's disease may be achieved in the majority of cases following transsphenoidal surgery [6]. A number of dynamic tests, imaging studies and IPS and CS ACTH sampling were used in the patient presented in this report.…”