Effect of Gonadotropin and Adrenocorticotropic Hormone Secretion on Invasiveness of Clinically Nonfunctioning Pituitary Adenomas: A Cell Culture Study

Objective The aim of this study was to clarify the correlation between clinical features (especially cyst formation and cavernous sinus invasion) and minor secretion of anterior pituitary hormones, especially adrenocorticotropic hormone (ACTH) and gonadotropin, by clinically nonfunctioning pituitary adenomas (CNFPAs) in cell culture. Methods We examined anterior pituitary hormones secreted by samples from 63 cases of CNFPAs grown in cell culture. Magnetic resonance imaging, including determination of the Knosp grade, cystic changes, and intraoperative cavernous sinus invasion, was performed. Results Detection of minor hormone secretion using cell culture showed that 61.9% (39/63) of CNFPAs secreted luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone, 44.4% (28/63) secreted ACTH, 57.1% (36/63) secreted prolactin, and 28.6% (18/63) secreted growth hormone; only 1 case of the null-cell adenoma was observed (1.6%). Cystic changes, Knosp grade 4 status, and cavernous sinus invasion were predominantly observed in cases of ACTH-secreting adenomas. Gonadotropin-secreting adenomas showed opposite characteristics to ACTH-secreting adenomas. Conclusions Minor secretion of ACTH and gonadotropin may be related to clinical features, especially cystic changes and invasiveness of CNFPAs, suggesting that our cell culture method could be helpful for elucidating the mechanisms of pituitary cyst formation and the invasiveness of CNFPAs.