GH responsiveness to corticotropin-releasing hormone identifies corticotroph-like somatotroph adenomas in acromegaly.

PURPOSE: Corticotropin-releasing hormone (CRH) induces an increase in growth hormone (GH) secretion in a subset of patients with acromegaly; however, the characteristics of these CRH responders remain poorly defined.

METHODS

22 CRH responders were retrospectively compared with 43 nonresponders.

RESULTS

CRH responders exhibited significantly larger tumors and more frequent visual field impairment than nonresponders, despite comparable baseline GH and insulin-like growth factor 1 (IGF-1) levels, and disease duration. Tumor volume and diameter were positively correlated with the GH increase ratio in CRH test, whereas GH and IGF-1 per tumor volume or diameter were significantly lower in CRH responders, indicating reduced GH secretory capacity relative to tumor size. Immunohistochemical analyses revealed higher corticotropin-releasing hormone receptor 1 (CRHR1) and lower CRHR2 expression in CRH responders. In addition, T-box transcription factor (TPIT) and adrenocorticotropic hormone (ACTH) expression were significantly more frequent in adenomas from CRH responders, suggesting a corticotroph-like phenotype. GH responses to CRH were significantly correlated with those to luteinizing hormone-releasing hormone but not thyrotropin-releasing hormone or oral glucose tolerance testing. GH responses to CRH tended to be inversely correlated with somatostatin receptor subtype 2 expression as a predictor of first-generation somatostatin receptor ligand efficacy but not with octreotide response or MRI signal intensity.

CONCLUSIONS

These findings support that GH responsiveness to CRH identifies a biologically distinct subset of somatotroph adenomas characterized by corticotroph-like features, larger tumor size, and reduced GH secretory capacity. GH responsiveness to CRH may serve as a noninvasive indicator of intrinsic tumor biology and behavior.