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The Dexamethasone-Suppressed Corticotropin-Releasing Hormone Stimulation Test Differentiates Mild Cushing’s Disease from Normal Physiology

Office of the Director (J.A.Y.), Warren Grant Magnuson Clinical Center and The Developmental Endocrinology Branch (J.A.Y., G.B.C, G.P.C., L.K.N.), National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892-1862

The dexamethasone-suppressed CRH test (Dex-CRH test) differentiates patients with Cushing’s syndrome (CS) from those with pseudo-Cushing states, who have decreased ACTH responses to CRH because of negative feedback exerted by chronic hypercortisolism. Normal subjects, however, have not been studied with the Dex-CRH test, raising concern that this test might not separate patients with CS from patients with normal adrenal function. To determine whether the criterion that separates CS from pseudo-Cushing states also would differentiate patients with Cushing’s disease (CD) from individuals with eucortisolism, we studied 20 healthy volunteers during low-dose (2 mg/day) dexamethasone suppression, and then during the Dex-CRH test (CRH stimulation test performed 2 h after completion of low-dose dexamethasone suppression), and contrasted their results with those of 20 patients with surgically proven mild CD [urine free cortisol (UFC) <1000 nmol/day).

Basal UFC was significantly greater in patients with CD (P < 0.001) but within the normal range (55–250 nmol/day) in 4 patients. During low-dose dexamethasone suppression, a UFC less than 100 nmol/day (36 µg/day) was found in all but 1 volunteer subject, and a urine 17-hydroxycorticosteroid excretion less than 14.6 µmol/day (5.3 mg/day) was found in all but 2 subjects. During the Dex-CRH test, plasma cortisol less than 38 nmol/L was found in all 20 normal volunteers until 30 min after CRH administration. By contrast, the 15-min CRH-stimulated plasma cortisol exceeded 38 nmol/L in all patients with CD (P < 0.001). Plasma dexamethasone measured just before CRH administration was similar in normal volunteers (13.0 ± 6.1 µmol/L) and patients with CD (16.4 ± 6.4 µmol/L). We conclude that cortisol measurements obtained during the Dex-CRH test are suppressed in normal volunteers below those found in mild CD. These results suggest that the Dex-CRH test may be useful in the evaluation of CS in patients without significant hypercortisoluria. However, its value in patients with episodic hormonogenesis has not been tested.

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