A reappraisal of the ovine corticotropin-releasing hormone stimulation test in the differential diagnosis of Cushing's syndrome: a comparison with the standard high-dose dexamethasone suppression test.

Abstract

Background: We evaluated the diagnostic efficacy of the ovine corticotropin-releasing hormone (oCRH) stimulation test in the differential diagnosis of Cushing's syndrome and compared it with the standard high-dose dexamethasone suppression test.

Methods: Twelve healthy volunteers and 30 with Cushing's syndrome (12 Cushing's disease and 18 adrenal Cushing's syndrome) were enrolled. Plasma ACTH and cortisol levels were measured before and after an intravenous bolus of 100 microg oCRH. Plasma and urinary free cortisol were determined after standard 2-day high-dose dexamethasone suppression.

Results: Basal cortisol in 12 patients with Cushing's disease and 18 with adrenal Cushing's syndrome were higher than the control group (21.4 +/- 0.1 microg/dl vs. 22.3 +/- 0.5 microg/dl vs. 9.1 +/- 1.5 microg/dl; p < 0.01). In Cushing's disease, basal plasma ACTH value was significantly higher than those with adrenal disease (61.1 +/- 1.4 pg/ml vs. 6.2 +/- 4.5 pg/ml; p < 0.01). After oCRH, plasma ACTH and cortisol significantly increased, with a mean of 2.0 +/- 0.2-fold (range 1.0-2.4) and 1.6 +/- 0.1-fold (range 1.1-2.1), respectively over the basal values in patients with Cushing's disease, and 11 (90%) attained a significant ACTH (1.5-fold) or cortisol (1.2-fold) response. All except 2 (89%) with adrenal Cushing's showed no apparent change in response to oCRH. Dexamethsone suppressed urinary free cortisol by 90% in 8 (67%) with Cushing's disease, but all (100%) with adrenal Cushing's syndrome were resistant. No patient with Cushing's disease was refractory to oCRH and dexamethasone, while none with adrenal Cushing's syndrome was responsive to both. Combination of both tests could achieved a specificity of 100% for Cushing's disease and adrenal Cushing's, when these 2 tests gave concomitant positive or negative results, respectively.

Conclusions: The oCRH test is a reliable examination in the differential diagnosis of Cushing's syndrome and is comparable to the high-dose dexamethasone test. A highest discrimination could be achieved when both are used.