Hypopituitarism after Gamma Knife surgery for postoperative nonfunctioning pituitary adenoma

OBJECTIVE This study investigated long-term follow-up data on the combined pituitary function test (CPFT) in patients who had undergone transsphenoidal surgery (TSS) for nonfunctioning pituitary adenoma (NFPA) to determine the clinical parameters indicative of hypopituitarism following postoperative Gamma Knife surgery (GKS). METHODS Between 2001 and 2015, a total of 971 NFPA patients underwent TSS, and 76 of them (7.8%) underwent postoperative GKS. All 76 patients were evaluated with a CPFT before and after GKS. The hormonal states were analyzed based on the following parameters: relevant factors before GKS (age, sex, extent of resection, pre-GKS hormonal states, time interval between TSS and GKS), GKS-related factors (tumor volume; radiation dose to tumor, pituitary stalk, and normal gland; distance between tumor and stalk), and clinical outcomes (tumor control rate, changes in hormonal states, need for hormone-related medication due to hormonal changes). RESULTS Of the 971 NFPA patients, 797 had gross-total resection (GTR) and 174 had subtotal resection (STR). Twenty-five GTR patients (3.1%) and 51 STR patients (29.3%) underwent GKS. The average follow-up period after GKS was 53.5 ± 35.5 months, and the tumor control rate was 96%. Of the 76 patients who underwent GKS, 23 were excluded due to pre-GKS panhypopituitarism (22) or loss to follow-up (1). Hypopituitarism developed in 13 (24.5%) of the remaining 53 patients after GKS. A higher incidence of post-GKS hypopituitarism occurred in the patients with normal pre-GKS hormonal states (41.7%, 10/24) than in the patients with abnormal pre-GKS hormonal states (10.3%, 3/29; p = 0.024). Target tumor volume (4.7 ± 3.9 cm³), distance between tumor and pituitary stalk (2.0 ± 2.2 mm), stalk dose (cutoffs: mean dose 7.56 Gy, maximal dose 12.3 Gy), and normal gland dose (cutoffs: maximal dose 13.9 Gy, minimal dose 5.25 Gy) were factors predictive of post-GKS hypopituitarism (p < 0.05). CONCLUSIONS This study analyzed the long-term follow-up CPFT data on hormonal changes in NFPA patients who underwent GKS after TSS. The authors propose a cutoff value for the radiation dose to the pituitary stalk and normal gland for the prevention of post-GKS hypopituitarism.