No central adrenal insufficiency found in patients with Prader-Willi syndrome with an overnight metyrapone test.

Background: Individuals with Prader-Willi syndrome (PWS) have hypothalamic dysfunction and may have central adrenal insufficiency (CAI). The prevalence of CAI in PWS remains unknown. Methods: Twenty-one subjects with PWS aged 4-53 years underwent a low dose adrenocorticotropic hormone (ACTH) stimulation test (LDAST) (1 mu g/m(2), maximum 1 mu g) followed by an overnight metyrapone test (OMT). Metyrapone (30 mg/kg, maximum 3 g) was administered at 2400 h. Cortisol, 11-deoxycortisol (11-DOC) and ACTH levels were collected the following morning at 0800 h. OMT was the standard test for comparison. Peak cortisol = 15.5 mu g/dL (427.6 nmol/L) on LDAST and 0800 h 11-DOC = 7 mu g/dL (200 nmol/L) on OMT were classified as adrenal sufficiency. Results: Twenty subjects had 0800 h 11-DOC values = 7 mu g/dL on OMT indicating adrenal sufficiency. One subject had an inconclusive OMT result. Six of the 21 (29%) subjects had peak cortisol < 15.5 mu g/dL on LDAST. Conclusions: We found no evidence of CAI based on OMT, yet 29% of our PWS population failed the LDAST. This suggests that the LDAST may have a high false positive rate in diagnosing CAI in individuals with PWS. OMT may be the preferred method of assessment for CAI in patients with PWS.