The GHRP-2 stimulation test showed 95% sensitivity and 85% specificity for detecting adrenal insufficiency in male patients without functional pituitary adenomas, making it a viable and safer alternative to the insulin tolerance test.
95% sensitivity, 85% specificityGHRP-2 test performance in male patients without functional adenomas compared to the insulin tolerance test gold standard
What the researchers found
A strong correlation was found between maximum cortisol levels measured by the GHRP-2 test and the insulin tolerance test (r = 0.777, P < 0.001). In male subjects without functional adenoma (n = 104), the GHRP-2 test achieved high sensitivity (95%) and specificity (85%) for diagnosing adrenocortical insufficiency.
The results support using the GHRP-2 test as a substitute for the insulin tolerance test when evaluating HPA axis function in male patients free of functional pituitary adenomas. However, the test's performance was affected by sex and the presence of functional adenomas, limiting its applicability in those subgroups.
Why it matters
The insulin tolerance test is considered the gold standard for evaluating adrenal function but requires inducing hypoglycemia, which can be dangerous — especially for patients with seizure disorders, heart disease, or severe pituitary insufficiency. The GHRP-2 test stimulates the same adrenal axis through a different, safer mechanism. Validating this peptide-based alternative gives clinicians a safer diagnostic tool for a substantial portion of their patients.
How the study worked
This was a retrospective study analyzing clinical and laboratory data from 254 patients admitted for evaluation of hypopituitarism who underwent both the GHRP-2 test and the insulin tolerance test. Researchers compared maximum cortisol responses (Fmax) between the two tests using correlation analysis. Adrenocortical insufficiency was diagnosed using ITT as the reference standard. The suitability of the GHRP-2 test was assessed using receiver operating characteristic (ROC) curve analysis.
What this study cannot tell us
This was a retrospective study, which is inherently less rigorous than a prospective design. The GHRP-2 test performed less well in female patients and those with functional pituitary adenomas, significantly limiting its universal applicability. The study used the insulin tolerance test as the reference standard, but the ITT itself has imperfect reproducibility. The specific cortisol cutoff values used were not detailed in the abstract.
How to read the evidence
This is a retrospective diagnostic accuracy study with a moderate sample size (254 patients). While the correlation and ROC analysis are well-conducted, the retrospective design and single-center nature limit the evidence strength compared to a prospective multi-center validation study.
When this study was published
Published in 2018, this study remains relevant as the GHRP-2 test continues to be used in clinical endocrinology, particularly in Japan where it is more commonly available than in some Western countries.
The bigger picture
GHRP-2 (growth hormone-releasing peptide 2) works through the ghrelin receptor (GHSR) in the hypothalamus, providing a unique window into HPA axis function. This study adds to growing evidence that synthetic peptides like GHRP-2 can serve as diagnostic tools beyond their originally studied growth hormone-stimulating effects. The trend toward safer, peptide-based diagnostic tests reflects broader advances in understanding how peptide signaling pathways can be leveraged clinically.
Questions still open
- Why does the GHRP-2 test perform differently in female patients, and could adjusting cutoff values improve its accuracy in women?
- How does the GHRP-2 test compare to other alternatives like the CRH test or the metyrapone test for HPA axis evaluation?
- Could the GHRP-2 test be validated prospectively in a larger, multi-center study to establish standardized diagnostic criteria?
Common questions
What is GHRP-2 and how does it test adrenal function?
Why is the GHRP-2 test considered safer than the insulin tolerance test?
Read the original research
Evaluation of Hypothalamic-Pituitary-Adrenal Axis by the GHRP2 Test: Comparison With the Insulin Tolerance Test.
Journal of the Endocrine Society, 2(8), 860-869
Citation
Hayakawa, Tomoaki; Kitamura, Tetsuhiro; Tamada, Daisuke; Mukai, Kosuke; Hayashi, Reiko; Takahara, Mitsuyoshi; Otsuki, Michio; Shimomura, Iichiro. (2018). Evaluation of Hypothalamic-Pituitary-Adrenal Axis by the GHRP2 Test: Comparison With the Insulin Tolerance Test.. Journal of the Endocrine Society, 2(8), 860-869. https://doi.org/10.1210/js.2018-00102