Acylated ghrelin as provocative test for the diagnosis of ACTH deficiency in patients with hypothalamus–pituitary disease

The insulin tolerance test (ITT) is the gold standard to evaluate adrenocorticotropic hormone (ACTH) insufficiency. However, alternative tests have been proposed such as metyrapone, glucagon, and ACTH stimulation test. We determined the diagnostic reliability of testing with ghrelin, the natural GH secretagogue that is a potent stimulus exploring the integrity of hypothalamic–pituitary–adrenal axis. We studied the ACTH and cortisol response to acylated ghrelin in 49 patients with history of pituitary disease. The best cortisol and ACTH cut offs to ghrelin test, defined as those with the best sensitivity (SE) and specificity (SP), were identified using the ROC analysis. We also compared accuracy of ghrelin test with that of a simple and cheap test like basal cortisol and ACTH levels. The best cortisol and ACTH cut offs to ghrelin test were ≤11.6 µg/dl (SE 86.4 %, SP 77.8 %) and ≤32.5 pg/ml (SE 72.7 %, SP 51.9 %), respectively; the best basal cortisol and ACTH cut offs were ≤10.7 µg/dl (SE 90.9 %, SP 70.4 %) and ≤25.0 pg/ml (SE 85 %, SP 37 %), respectively. The diagnostic accuracy was 81.6, 60.9, 79.6, and 57.4 %, respectively. A comparison between ROC AUC showed a great diagnostic power for cortisol, both stimulated and basal, versus ACTH, both stimulated and basal, but no difference between stimulated and basal cortisol evaluation. Our data show that testing with acylated ghrelin is not a useful diagnostic tool for the diagnosis of central hypocortisolism; particularly ghrelin test adds no more information that basal cortisol evaluation in the diagnosis of ACTH deficiency in patients with hypothalamus–pituitary disease.