Evaluation of Hypothalamic–Pituitary–Adrenal Axis by the GHRP2 Test: Comparison With the Insulin Tolerance Test

Abstract

ContextGH-releasing peptide 2 (GHRP2) stimulates the hypothalamic–pituitary–adrenal axis (HPA) through the GH secretagogue receptor (GHSR) in the hypothalamus, in which ghrelin is a natural ligand. Therefore, the GHRP2 test (GHRP2T) could be used instead of the insulin tolerance test (ITT).ObjectiveCan the GHRP2T replace the ITT for evaluation of HPA?DesignThe present retrospective study analyzed the clinical features and laboratory data from 254 patients admitted for evaluation of hypopituitarism who underwent both GHRP2T and ITT. We analyzed the association between the maximum cortisol level (Fmax) during both tests. Adrenocortical insufficiency was diagnosed by ITT. The suitability of GHRP2T was examined using the receiver operating characteristic curve.ResultsA strong correlation was found between Fmax measured using both tests (r = 0.777, P < 0.0001). However, the sensitivity (64%) and specificity (79%) showed that the GHRP2T was not suitable for clinical use. Various factors influenced the correlation, probably through their effects on ghrelin and/or GHSR, including functional adenoma (P < 0.05) and sex (P < 0.05). No substantial correlation was found between Fmax measured using both tests in patients with prolactinoma (n = 30). The exclusion of patients with functional adenoma revealed no factors that affected the association in male patients; however, age and menstruation significantly influenced it in female patients (P < 0.05). Analysis of the data from male subjects without functional adenoma (n = 104) showed high sensitivity (95%) and specificity (85%) for the GHRP2T.ConclusionITT can be substituted with GHRP2T for assessment of HPA in male patients free of functional adenoma.

Opioid-induced adrenal insufficiency in transdermal fentanyl treatment: a revisited diagnosis in clinical setting

“…In the present case, the clinical diagnosis of OIAI was established based on the laboratory findings suggesting secondary adrenal insufficiency including CRH stimulation test, clinical history of long-term fentanyl use and exclusion of other hypothalamic-pituitary diseases such as tumors. The over-action of ACTH in CRH or growth hormonereleasing peptide 2 stimulation test suggested hypothalamic dysfunction, which is compatible with the pathophysiology of OIAI, although confirmatory evaluations including insulin tolerance test were not performed [28]. In addition, suppressed reaction of cortisol in ACTH stimulation test suggested sustained adrenal insufficiency, which was compatible with the patient's persistent symptoms including abdominal pain and constipation; the repeating ACTH stimulation test was not feasible.…”

Isolated Adrenocorticotropic Hormone Deficiency Associated with Atezolizumab and Bevacizumab Administration for Treating Hepatocellular Carcinoma: A Case Series

“…The growth hormone-releasing peptide-2 test showed no cortisol response and a poor ACTH response ( Fig. 4 ), with no indication of GH deficiency ( 4 , 5 ). Based on these findings, we diagnosed the patient with isolated ACTH deficiency related to atezolizumab.…”

Diagnosis, genetics, and therapy of short stature in children: A growth hormone research society international perspective

“…GHRH is not appropriate for use as a stimulant in children as theoretically it will not diagnose GHD of hypothalamic or pituitary stalk origin. Stimulation tests in current use include the insulin tolerance test, and tests using glucagon, arginine, clonidine, L-dopa, and GH-releasing peptide-2 (GHRP2) [42]. Failure to respond to 2 provocative stimuli is needed to diagnose GHD, which limits false-positive results while not eliminating these completely.…”

“…GHRP2 is an intravenous GH secretagogue used in Japan with the advantage of stimulating ACTH release and the potential ability to assess the hypothalamic-pituitaryadrenal and GH axes simultaneously [42,91,92].…”