Whole-Sellar Stereotactic Radiosurgery for Functioning Pituitary Adenomas BACKGROUND: Functioning pituitary adenomas (FPAs) can be difficult to delineate on postoperative magnetic resonance imaging, making them difficult targets for stereo- tactic radiosurgery (SRS). In such cases, radiation delivery to the entire sella has been utilized as a radiosurgical equivalent of a total hypophysectomy. OBJECTIVE: To evaluate the outcomes of a cohort of patients with FPA who underwent SRS to the whole-sellar region. METHODS: This is a retrospective review of patients who underwent whole-sellar SRS for FPA between 1989 and 2012. Sixty-four patients met the inclusion criteria: they were treated with whole-sellar SRS following surgical resection for persistently elevated hormone levels, and (1) no visible lesions on imaging studies and/or (2) tumor infil- tration of dura or adjacent venous sinuses observed at the time of a prior resection. The median radiosurgical volume covering sellar structures was 3.2 mL, with a median margin dose of 25 Gy. RESULTS: The median endocrine follow-up was 41 months; 22 (68.8%) patients with acromegaly, 20 (71.4%) patients with Cushing disease, and 2 (50.0%) patients with prolactinoma achieved endocrine remission. The 2-, 4-, and 6-year actuarial remission rates were 54%, 78%, and 87%, respectively. New-onset neurological deficit was found in 4 (6.3%) patients following treatment. New-onset hypopituitarism was observed in 27 (43.5%) patients, with panhypopituitarism in 2 (3.2%). Higher margin/maximum dose were significantly associated with a higher remission rate and development of post-SRS hypopituitarism. CONCLUSION: Whole-sellar SRS for invasive or imaging-negative FPA following failed resection can offer reasonable rates of endocrine remission. Hypopituitarism following whole-sellar SRS is the most common complication. KEY WORDS: Acromegaly, Cushing disease, Functioning pituitary adenoma, Gamma-knife, Prolactinoma, Stereotactic radiosurgery, Whole-sellar radiation Neurosurgery 75:227–237, 2014 DOI: 10.1227/NEU.0000000000000425 www.neurosurgery-online.com F unctioning pituitary adenomas (FPAs) are associated with significant morbidity and even mortality secondary to their hormonal hypersecretion. Removal of the offending adeno- mas is typically the treatment of choice for those with Cushing disease, acromegaly, and medically refractory prolactinomas. Hormone remission rates from modern surgical series range from 63% to 95% for microadenomas, and from 47% to 77% for macroadenomas. 1-7 Reoperations for such patients prove less successful, particularly because the adenomas are often ill-defined on neuroimaging studies and intraoperative inspec- tion. 8-10 For such patients, partial or even total hypophysectomies have been advocated to ach- ieve endocrine remission, but these approaches convey greater risks of hypopituitarism. 9,11,12 Since the 1960s, stereotactic radiosurgery (SRS) has been increasingly utilized as a generally safe and effective treatment for FPAs, especially for those patients in whom transsphenoidal Cheng-Chia Lee, MD*‡§ Ching-Jen Chen, BA* Chun-Po Yen, MD* Zhiyuan Xu, MD* David Schlesinger, PhD*k Francis Fezeu, MD* Jason P. Sheehan, MD, PhD*k *Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia; ‡Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan; §School of Medicine, National Yang-Ming University, Taipei, Taiwan; kDepartment of Radiation Oncology, University of Virginia Health System, Charlottesville, Virginia Correspondence: Jason P. Sheehan, MD, PhD, Department of Neurological Surgery, University of Virginia Health System, Charlottesville, VA 22908. E-mail: jsheehan@virginia.edu Received, October 24, 2013. Accepted, April 22, 2014. Published Online, May 23, 2014. Copyright © 2014 by the Congress of Neurological Surgeons. ABBREVIATIONS: ACTH, adrenocorticotropic hor- mone; FPA, functioning pituitary adenoma; CD, Cushing disease; FSR, fractionated stereotactic radiotherapy; GH, growth hormone; GKS, Gamma- knife radiosurgery; Gy, gray; IGF-1, insulin-like growth factor-1; SRS, stereotactic radiosurgery; TSH, thyroid-stimulating hormone; UFC, urine free cortisol RESEARCH—HUMAN—CLINICAL STUDIES RESEARCH—HUMAN—CLINICAL STUDIES NEUROSURGERY VOLUME 75 | NUMBER 3 | SEPTEMBER 2014 | 227 Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited.