Acylated ghrelin as a provocative test for the diagnosis of GH deficiency in adults

Objective: Insulin tolerance test (ITT) is the test of reference for the diagnosis of adult GH deficiency (GHD), although GHRH in combination with arginine (ARG) or GH secretagogues are considered equally reliable tests. Testing with GH secretagogue alone is, anyway, a potent stimulus exploring the integrity of hypothalamic pathways controlling somatotropic function. We therefore aimed to determine the diagnostic reliability of testing with ghrelin, the natural GH secretagogue. Methods: We studied the GH response (every 15 min from K15 to C120 min) to acylated ghrelin (1 mg/kg i.v. at 0 min) in 78 patients with a history of pituitary disease (49 male, 29 female; age (meanGS.D.): 52.1G18.7 years; BMI: 26.7G5.3 kg/m 2 ). The lack of GH response to GHRHCARG and/or ITT was considered the gold standard for the diagnosis of GHD. The best GH cut-off to ghrelin test, defined as the one with the best sensitivity (SE) and specificity (SP), was identified using the receiver-operating characteristic curve analysis. Results: The best GH cut-off to ghrelin test was 7.3 mg/l in lean subjects (SE 88.2%, SP 90.9%), 2.9 mg/l in overweight subjects (SE 92.6%, SP 100%) and 0.6 mg/l in obese subjects (SE 50%, SP 100%). The diagnostic accuracy was 89.3, 94.1 and 62.5% respectively. Conclusions: Our data show that testing with acylated ghrelin represents a reliable diagnostic tool for the diagnosis of adult GHD, in lean and overweight subjects, if appropriate cut-off limits are assumed. Obesity strongly reduces GH response to ghrelin, GH weight-related cut-off limit and diagnostic reliability of the test.