Calcitonin Gene-Related Peptide Expression in Somatotroph Adenomas: Implications for Clinical Course and Treatment Outcomes

BACKGROUND: Calcitonin gene-related peptide (CGRP) is a potent vasodilatory neuropeptide involved in inflammation, vascular regulation, and pain mechanisms with potential relevance to endocrine and neurological processes. Furthermore, it exerts specific effects on the tumor microenvironment in certain malignancies. The contribution of CGRP to pituitary adenogenesis has yet to be elucidated. This study aimed to investigate CGRP expression by immunohistochemistry in patients with acromegaly and nonfunctioning pituitary adenomas (NFPAs) and its associations with tumor features, symptoms, and treatment response. METHODS: This study included tissue samples obtained from 49 patients who were followed and underwent transsphenoidal surgery at our center: 30 with acromegaly and 19 with NFPAs. Tumor samples were evaluated for CGRP using a polyclonal anti-CGRP antibody (GeneTex, 1:200). Clinical, radiological, and surgical data were collected. Histopathology included hormone staining, estrogen receptor, granularity, transcription factors, Ki-67, and mitotic count. RESULTS: CGRP positivity was observed in 50% of acromegaly patients and in none of the NFPA group (p < 0.001). CGRP expression was not significantly associated with tumor size, invasion, need for surgery, residual tumor, treatment resistance, or granularity. In acromegaly cases with CGRP-positive adenomas, chronic headache tended to be more common (40% vs. 13%, p = 0.09), and postoperative headache resolution rate was lower (33.3% vs. 80%, p = 0.07). The postoperative remission rate tended to be lower (60% vs. 86.7%, p = 0.09). CONCLUSION: CGRP was found to be notably present in somatotropin-producing adenoma tissues, yet it was entirely absent from nonfunctioning adenoma tissues. The detection of CGRP within adenoma tissue could correlate with an increased incidence of persistent headaches and diminished postoperative remission probabilities in acromegaly.