Background <p>Functional pituitary adenomas often require multimodal therapy when surgery and medical treatment do not achieve durable endocrine remission. Stereotactic radiosurgery (SRS) is commonly used for residual or recurrent hormone-secreting tumors, achieving high tumor control rates but variable rates of biochemical remission.</p> Objective <p>To evaluate endocrine response, tumor control, and treatment-related toxicity after linear accelerator (LINAC)-based SRS for functional pituitary adenomas.</p> Methods <p>We retrospectively reviewed 24 patients treated with single-fraction LINAC SRS between 1995 and 2012 for adrenocorticotropic hormone (ACTH)-secreting (<i>n</i> = 6), growth hormone (GH)-secreting (<i>n</i> = 10), or prolactin (PRL)-secreting (<i>n</i> = 8) pituitary adenomas. All patients had prior transsphenoidal resection; most had failed or intolerant medical therapy. Two patients underwent repeat SRS for persistent disease, yielding 26 total SRS sessions. Endocrine outcomes were categorized as complete biochemical remission off medication, biochemical control while still requiring suppressive medical therapy, partial biochemical improvement without normalization, or persistent hypersecretion. Radiographic tumor control and late complications were assessed on long-term follow-up.</p> Results <p>After initial SRS, complete biochemical remission off medication was achieved in 3 of 6 patients with ACTH-secreting adenomas (50%; mean latency 24 months). In the GH-secreting group, 2 of 10 patients (20%) achieved remission off therapy, whereas an additional 3 of 10 (30%) achieved biochemical control only while continuing suppressive medical therapy; 2 of 10 patients (20%) demonstrated partial biochemical improvement without normalization. In the prolactinoma group, 3 of 8 patients (37.5%) achieved prolactin normalization off dopamine agonist therapy, whereas an additional 2 of 8 (25%) achieved biochemical control while maintained on dopamine agonist treatment; 1 of 8 patients (12.5%) showed partial biochemical improvement without normalization. Tumor growth control was attained in 6 of 6 ACTH (100%), 9 of 10 GH (90%), and 7 of 8 PRL adenomas (87.5%). One patient with persistent Cushing’s disease underwent bilateral adrenalectomy after SRS, and one dopamine-resistant prolactinoma patient required repeat resection; no other cases of disease progression occurred. Two patients (8.3%) experienced significant radiation-related complications, including one case of unilateral blindness with temporal lobe radionecrosis and one case of cognitive decline from temporal lobe injury. One patient (4.2%) developed a new pituitary hormone deficiency after SRS.</p> Conclusions <p>LINAC-based SRS provided durable tumor control for most functional pituitary adenomas in this cohort and was associated with complete endocrine remission in a subset of patients, while others achieved biochemical control with continued medical therapy or partial hormonal improvement, with expected latency of up to several years. While uncommon, delayed toxicity (including visual loss or hypopituitarism) can occur and underscores the need for meticulous treatment planning with strict optic pathway and hypothalamic-pituitary axis dose constraints, as well as long-term endocrine follow-up.</p>