Loss of pituitary hormone function after stereotactic radiosurgery for pituitary adenomas: mechanisms and management

BACKGROUND: Stereotactic radiosurgery (SRS) is an essential modality for treating recurrent or residual pituitary adenomas (PAs), offering high rates of tumor control and moderately effective endocrine management in both functioning (FPAs) and non-functioning pituitary adenomas (NFPAs). Endocrine remission is less consistently achieved, and in hypersecretory states such as acromegaly and Cushing's disease, hormone normalization may be delayed by years relative to surgical resection. The impact of pre-treatment hormone suppression on radiosensitivity remains controversial, with evidence suggesting it may further delay endocrine remission. METHODS: A review of the literature was conducted to evaluate the rates and predictors of hypopituitarism following SRS for pituitary adenomas, the differential radiosensitivity of pituitary axes, and strategies aimed at reducing radiation induced endocrinopathy. RESULTS: Hypopituitarism remains the most common complication of SRS, occurring in 21-50% of patients, and arises from radiation-induced damage to the hypothalamus, pituitary gland, or stalk. The radiosensitivity of pituitary axes varies across studies; while some series identify the somatotropic axis as most vulnerable followed by the gonadotropic, corticotropic, and thyrotropic axes, larger multicentric cohorts have reported thyrotropin and cortisol deficiencies as more prevalent. Hypopituitarism may develop years after treatment, underscoring the importance of long-term followup. Advances in volumetric and automated segmentation imaging have improved tumor targeting and reduced unintended radiation exposure to adjacent structures, while strategies such as pituitary transposition and optimized dose protocols have shown promise in mitigating radiation-induced endocrinopathies. CONCLUSION: Current evidence underscores the importance of individualized treatment planning, careful dose modulation, and advanced imaging techniques to minimize complications while maintaining therapeutic efficacy. Further research is needed to clarify predictors of hypopituitarism, optimize treatment protocols, and explore strategies to enhance patient outcomes following SRS for pituitary adenomas.