GHRP-2 test results predict pituitary function severity and postoperative GH recovery in adenoma patients

Non-functioning pituitary adenomas (NFPA) are a frequent cause of adult growth hormone deficiency (AGHD). In Japan, a challenge test using the peptide GHRP-2 is standard practice to evaluate GH secretion. The established diagnostic cut-off for severe AGHD is a peak GH response of ≤9 ng/mL. However, within this 'severe' category, there's a wide spectrum of responses, from nearly zero to the 9 ng/mL threshold. It's unclear if the degree of blunting in the GHRP-2 test—for example, a peak of 1 ng/mL versus 8 ng/mL—correlates with the overall severity of pituitary dysfunction or predicts a patient's chances of recovering GH secretion after tumor removal surgery. This study investigated whether these finer gradations in GH response to GHRP-2 could provide more granular prognostic information.

This retrospective study analyzed data from 76 patients with NFPA. Among these, 36 patients (mean age 61 years; 23 male, 13 female) were diagnosed with severe AGHD based on a preoperative GHRP-2 test (peak GH ≤9 ng/mL). These 36 patients were then divided into two groups based on the median peak GH concentration of 2.83 ng/mL: a low-response group (Group L, n=18) with peak GH <2.83 ng/mL, and a moderate-response group (Group M, n=18) with peak GH ≥2.83 ng/mL. Researchers compared clinical characteristics, BMI, tumor metrics (size, volume, extension), and the number of other anterior pituitary hormone deficiencies between the two groups.

The preoperative peak GH concentration during the GHRP-2 test was directly linked to the severity of overall pituitary damage. Patients in the low-response group (Group L) were significantly older and had a higher prevalence of gonadotropin and ACTH deficiencies compared to the moderate-response group (Group M). Across all 76 patients, a lower peak GH response was associated with a higher number of deficient anterior pituitary hormone axes, confirming a dose-response relationship between the GHRP-2 stimulus and pituitary health. Most critically, the test predicted surgical outcomes.

Postoperatively, 7 patients in Group M recovered sufficient GH secretion and were no longer classified as having severe AGHD, whereas zero patients in Group L showed any recovery. This indicates that a more robust, albeit still severely blunted, preoperative response to GHRP-2 is a strong positive prognostic indicator for the recovery of somatotropic function after surgical decompression of the pituitary.