CLINICAL ARTICLE J Neurosurg 131:532–538, 2019 E xcEssivE secretion of pituitary hormones, such as adrenocorticotropic hormone (ACTH) in Cushing’s disease (CD) and growth hormone (GH) causing ac- romegaly, may lead to serious endocrine complications if left untreated. Both are associated with signifcant systemic sequelae and an increased susceptibility to other medical conditions. These sequelae include increased mortality from cardiovascular and cerebrovascular disease, as well as increased morbidity from diabetes mellitus, hyperten- sion, and psychological disturbances. 2,9,13,30,40 Moreover, if ABBREVIATIONS ACTH = adrenocorticotropic hormone; CD = Cushing’s disease; CN = cranial nerve; CS = cavernous sinus; GH = growth hormone; GKS = Gamma Knife radiosurgery; IGF-I = insulin-like growth factor–I; SRS = stereotactic radiosurgery; UFC = urinary free cortisol. SUBMITTED January 12, 2018. ACCEPTED March 21, 2018. INCLUDE WHEN CITING Published online August 17, 2018; DOI: 10.3171/2018.3.JNS18110. Upfront Gamma Knife radiosurgery for Cushing’s disease and acromegaly: a multicenter, international study Amitabh Gupta, MS, MCh, 1 Zhiyuan Xu, MD, 1 Hideyuki Kano, MD, PhD, 2 Nathaniel Sisterson, BA, 2 Yan-Hua Su, MD, 3 Michal Krsek, MD, 4 Ahmed M. Nabeel, MD, PhD, 5 Amr El-Shehaby, MD, PhD, 6 Khaled A. Karim, MD, 7 Nuria Martínez-Moreno, MD, PhD, 8 David Mathieu, MD, 9 Brendan J. McShane, BA, 10 Roberto Martínez-Álvarez, MD, PhD, 8 Wael A. Reda, MD, PhD, 6 Roman Liscak, MD, 10 Cheng-Chia Lee, MD, PhD, 3 L. Dade Lunsford, MD, PhD, 2 and Jason P. Sheehan, MD, PhD 1 1 Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia; 2 Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; 3 Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China; 4 Second Department of Medicine, Third Faculty of Medicine of the Charles University, Faculty Hospital Kralovske Vinohrady, Prague, Czech Republic; 5 Gamma Knife Center Cairo-Nasser Institute, Neurosurgery Department, Benha University, Benha, Egypt; 6 Gamma Knife Center Cairo-Nasser Institute, Neurosurgery Department, Ain Shams University, Cairo, Egypt; 7 Gamma Knife Center Cairo-Nasser Institute, Clinical Oncology Department, Ain Shams University, Cairo, Egypt; 8 Department of Functional Neurosurgery and Radiosurgery, Ruber International Hospital, Madrid, Spain; 9 Division of Neurosurgery, Université de Sherbrooke, Centre de Recherche du CHUS, Sherbrooke, Québec, Canada; and 10 Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Prague, Czech Republic OBJECTIVE Gamma Knife radiosurgery (GKS) is typically used after failed resection in patients with Cushing’s disease (CD) and acromegaly. Little is known about the upfront role of GKS for patients with CD and acromegaly. In this study, the authors examine the outcome of upfront GKS for patients with these functioning adenomas. METHODS An international group of 7 Gamma Knife centers sent pooled data from 46 patients (21 with CD and 25 with acromegaly) undergoing upfront GKS to the coordinating center of the study for analysis. Diagnosis was established on the basis of clinical, endocrine, and radiological studies. All patients were treated on a common radiosurgical platform and longitudinally followed for tumor control, endocrine remission, and hypopituitarism. Patients received a tumor me- dian margin dose of 25 Gy (range 12–40.0 Gy) at a median isodose of 50%. RESULTS The median endocrine follow-up was 69.5 months (range 9–246 months). Endocrine remission was achieved in 51% of the entire cohort, with 28% remission in acromegaly and 81% remission for those with CD at the 5-year interval. Patients with CD achieved remission earlier as compared to those with acromegaly (p = 0.0005). In patients post-GKS, the pituitary adenoma remained stable (39%) or reduced (61%) in size. Hypopituitarism occurred in 9 patients (19.6%), and 1 (2.2%) developed third cranial nerve (CN III) palsy. Eight patients needed further intervention, including repeat GKS in 6 and transsphenoidal surgery in 2. CONCLUSIONS Upfront GKS resulted in good tumor control as well as a low rate of adverse radiation effects in the whole group. Patients with CD achieved a faster and far better remission rate after upfront GKS in comparison to pa- tients with acromegaly. GKS can be considered as an upfront treatment in carefully selected patients with CD who are unwilling or unable to undergo resection, but it has a more limited role in acromegaly. https://thejns.org/doi/abs/10.3171/2018.3.JNS18110 KEYWORDS Cushing’s disease; acromegaly; Gamma Knife radiosurgery; stereotactic radiosurgery J Neurosurg Volume 131 • August 2019 532 ©AANS 2019, except where prohibited by US copyright law Unauthenticated | Downloaded 11/28/22 01:48 PM UTC