Ghrelin immunoexpression in pituitary adenomas

Ghrelin, an orexigenic hormone, is normally produced mainly in stomach. In addition, it has been demonstrated in gastric carcinoid tumors and less often in other neuroendocrine tumors. We investigated ghrelin expression by immunohistochemistry (streptavidin-biotin-peroxidase complex method) in the full spectrum of resected pituitary adenoma subtypes. Quantification of staining considered both the frequency of ghrelin-reactive tumor cells as well as their staining intensity. Cytoplasmic ghrelin immunopositivity was identified in several adenoma subtypes. Cellular staining varied considerably. In addition, the intensity of cell staining differed within the same tumor and between adenoma subtypes. The highest scores were noted in GH producing adenomas exposed to long-acting somatostatin analogs. In decreasing order, lower scores were encountered in ACTH adenomas in Cushing disease, silent subtype 3 adenomas, untreated GH adenomas, silent corticotroph adenomas of subtypes 1 and 2, dopamine agonist-treated PRL adenomas, ACTH adenomas in Nelson syndrome, and gonadotroph adenomas. No significant immunoreactivity was noted in TSH, untreated PRL, and null cell adenomas. The high immunoexpression of ghrelin in GH adenomas exposed to long-acting somatostatin analogs remains unexplained, but may be due to either increased ghrelin production or to suppression of its release. Based on our findings, it appears that ghrelin immunopositivity does not serve as a biomarker of biologic behavior, prognosis and therapeutic responsiveness in pituitary adenomas.