Endocrine disorders after primary gamma knife radiosurgery for pituitary adenomas: A systematic review and meta-analysis

Purpose: Gamma Knife radiosurgery (GKRS) is feasible for pituitary adenomas, but post-surgery GKRS may cause severe hormone deficits. We reviewed the literature on primary GKRS for pituitary adenoma focusing on radiation-induced hormone deficiencies. Methods: PubMed, Web-of-Science, Scopus, and Cochrane were searched upon the PRISMA guidelines to include studies describing primary GKRS for pituitary adenomas. Pooled-rates of GKRS-induced hormone deficiencies and clinical-radiological responses were analyzed with a random-effect model meta-analysis. Results: We included 24 studies comprising 1381 patients. Prolactinomas were the most common (34.2%), and 289 patients had non-functioning adenomas (20.9%). Median tumor volume was 1.6cm3 (range, 0.01–31.3), with suprasellar extension and cavernous sinus invasion detected in 26% and 31.1% cases. GKRS was delivered with median marginal dose 22.6 Gy (range, 6–49), maximum dose 50 Gy (range, 25–90), and isodose line 50% (range, 9–100%). Median maximum point doses were 9 Gy (range, 0.5–25) to the pituitary stalk, 7 Gy (range, 1–38) to the optic apparatus, and 5 Gy (range, 0.4–12.3) to the optic chiasm. Pooled 5 year rates of endocrine normalization and local tumor control were 48% (95%CI 45–51%) and 97% (95%CI 95–98%). 158 patients (11.4%) experienced endocrinopathies at a median of 45 months (range, 4–187.3) after GKRS, with pooled 5-year rates of 8% (95%CI 6–9%). GKRS-induced hormone deficiencies comprised secondary hypothyroidism (42.4%) and hypogonadotropic hypogonadism (33.5%), with panhypopituitarism reported in 31 cases (19.6%). Conclusion: Primary GKRS for pituitary adenoma may correlate with lower rates of radiation-induced hypopituitarism (11.4%) than post-surgery GKRS (18–32%). Minimal doses to normal pituitary structures and long-term endocrine follow-up are of primary importance.