Comparison of pituitary–adrenal responsiveness between insulin tolerance test and growth hormone-releasing peptide-2 test: A pilot study

Insulin tolerance test (ITT) is the gold standard for assessing the hypothalamic–pituitary–adrenal (HPA) function. GH-releasing peptide (GHRP)-2, which has a strong GH-stimulating activity, is useful for diagnosing GH deficiency as well as ITT. Additionally, GHRP-2 is also known to activate HPA axis. There have been no comparative studies of pituitary–adrenal responsiveness between GHRP-2 test and ITT in patients with hypothalamic/pituitary disease. To assess whether GHRP-2 test could be an alternative to ITT for diagnosing HPA axis failure, both ITT and GHRP-2 test were performed in 15 patients suspected of hypopituitarism. A 100 μg dose of GHRP-2 was administered intravenously and plasma ACTH and serum cortisol concentrations were measured. In ITT, a peak cortisol value over 18 μg/dl is considered normal. Nine patients were diagnosed as HPA axis failure by ITT. Their median peak cortisol in GHRP-2 test was 11.4 μg/ml. In 6 patients diagnosed as normal HPA axis status by ITT, their median peak cortisol in response to GHRP-2 test was 21.4 μg/dl, significantly higher (p = 0.0032) than seen in patients diagnosed as HPA axis failure. There was a strong correlation between the peak cortisol in GHRP-2 test and ITT (r = 0.817; p < 0.0001). When the cut-off value for the peak cortisol in GHRP-2 test was set to 13–14 μg/dl for diagnosing HPA axis failure, the specificity and sensitivity were 100% and 88.9%, respectively. Although further studies that include normal subjects are needed, these preliminary results suggest the possibility that GHRP-2 test may be an alternative to ITT for assessing HPA axis function.