The corticotropin-releasing hormone test in the diagnosis of ACTH-dependent Cushing's syndrome: A reappraisal

OBJECTIVE Stimulation with corticotropin-releasing hormone (CRH) is one of principal tools for the differential diagnosis of ACTH-dependent Cushing's syndrome. However, different dosages and species of CRH may be employed; fu rther, ACTH levels can be measured by radioimmunoassay (RIA) or immunoradio metric assay (IRMA). The aims of the present study were to perform a reappr aisal of the diagnostic accuracy of the CRH test taking these different tes ting modalities into consideration and to study the correlation between bas al ACTH and cortisol levels and their responses to CRH in patients with Cus hing's disease. PATIENTS: The study population comprised 148 patients with Cushing's diseas e and 12 patients with ectopic ACTH secretion collected through an Italian multicentre study. DESIGN Patients were submitted to stimulation with 100 mug human or ovine C RH (36% and 64% of subjects, respectively) and ACTH measured either by RIA or IRMA (28% and 72%, respectively). A 50% increase in ACTH and cortisol le vels was considered indicative of Cushing's disease. RESULTS Mean peak ACTH levels measured by RIA and IRMA were comparable, as was the diagnostic accuracy of the test with the two assays (87% for IRMA a nd 84% for RIA, ns). In patients with Cushing's disease, stimulation with o vine CRH induced greater hormonal responses compared to testing with human CRH although only the cortisol response reached statistical significance (A CTH: 247.5 +/- 28.0% vs. 168.5 +/- 21.3% over baseline, P = 0.06; cortisol: 89.3 +/- 8.5% vs. 60.8 +/- 9.6% over baseline, P < 0.05 for ovine and huma n CRH, respectively). No appreciable rise in ACTH and cortisol levels was r egistered among patients with ectopic ACTH secretion. Diagnostic accuracy o f the cortisol response was significantly greater with the ovine than with human peptide (71% vs. 49%, P < 0.05, for ovine and human CRH, respectively ) while the ACTH response yielded equal diagnostic accuracy (86% vs. 87%, n s, for the ovine and human peptide, respectively). Interestingly, the corre lation between ACTH and cortisol peak responses in patients with Cushing's disease was significantly greater for human than for ovine CRH (r = 0.68 vs . r = 0.41, P < 0.01, respectively). In addition, baseline cortisol levels exhibited a significant negative correlation with both the ACTH and cortiso l response to CRH suggesting the persistence of the negative cortisol feedb ack in patients with Cushing's disease. CONCLUSIONS (A) Both RIA and IRMA can be used indifferently for the assessm ent of the ACTH response to CRH. (B) Human and ovine CRH provide the same d iagnostic accuracy as regards the ACTH response which, incidentally, repres ents the most accurate criterion for the evaluation of the CRH test; ovine CRH is superior to the human peptide in the evaluation of the cortisol resp onse. (C) In patients with Cushing's disease, endogenous cortisol maintains the ability to negatively modulate CRH-stimulated corticotropin secretion.