GHRP2 Test Provides Safer Alternative for Evaluating Stress Hormone System

The Hypothalamic-Pituitary-Adrenal (HPA) axis is a vital neuroendocrine system regulating the body's response to stress, metabolism, and immunity. Dysfunction of this axis can lead to serious endocrine disorders such as adrenal insufficiency or Cushing's syndrome. The Insulin Tolerance Test (ITT) is currently considered the gold standard for assessing HPA axis integrity, but it carries significant risks due to the intentional induction of severe hypoglycemia. This study aimed to determine if the GHRP2 test could serve as a safer, yet equally effective, diagnostic tool for evaluating HPA axis function, offering a less hazardous alternative to the ITT.

The study revealed that the GHRP2 test consistently induced a robust increase in both ACTH and cortisol levels, mirroring the physiological stress response. Peak cortisol concentrations following GHRP2 administration reached an average of 20.5 µg/dL, which was statistically indistinguishable from the ITT's average peak of 21.1 µg/dL (p=0.45). Crucially, the GHRP2 test demonstrated a strong positive correlation (r = 0.87, p<0.001) with the ITT for peak cortisol responses, confirming its diagnostic agreement. Furthermore, the GHRP2 test exhibited a significantly superior safety profile, with 0% of participants experiencing severe hypoglycemia or requiring glucose infusion, compared to 100% of participants experiencing induced hypoglycemia during the ITT. The GHRP2 test also showed a high sensitivity of 92% and specificity of 88% for detecting HPA axis insufficiency, making it a highly reliable diagnostic tool without the associated risks of the ITT. The mean time to peak cortisol was also similar between tests, at 60 minutes for GHRP2 versus 75 minutes for ITT (p=0.12).