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Cordeiro D, Xu Z, Mehta GU, et al. Hypopituitarism after Gamma Knife radiosurgery for pituitary adenomas: a multicenter, international study. J Neurosurg. 2018;doi: 10.3171/2018.5.JNS18509.
Cordeiro, D., Xu, Z., Mehta, G. U., Ding, D., Vance, M. L., Kano, H., Sisterson, N., Yang, H. C., Kondziolka, D., Lunsford, L. D., Mathieu, D., Barnett, G. H., Chiang, V., Lee, J., Sneed, P., Su, Y. H., Lee, C. C., Krsek, M., Liscak, R., Nabeel, A. M., El-Shehaby, A., Karim, K. A., Reda, W. A., Martinez-Moreno, N., Martinez-Alvarez, R., Blas, K., Grills, I., Lee, K. C., Kosak, M., Cifarelli, C. P., Katsevman, G. A., & Sheehan, J. P. (2018). Hypopituitarism after Gamma Knife radiosurgery for pituitary adenomas: a multicenter, international study. Journal of neurosurgery, . https://doi.org/10.3171/2018.5.JNS18509
Cordeiro, Diogo, et al. "Hypopituitarism after Gamma Knife radiosurgery for pituitary adenomas: a multicenter, international study." Journal of neurosurgery vol. (2018). doi: https://doi.org/10.3171/2018.5.JNS18509
Cordeiro D, Xu Z, Mehta GU, Ding D, Vance ML, Kano H, Sisterson N, Yang HC, Kondziolka D, Lunsford LD, Mathieu D, Barnett GH, Chiang V, Lee J, Sneed P, Su YH, Lee CC, Krsek M, Liscak R, Nabeel AM, El-Shehaby A, Karim KA, Reda WA, Martinez-Moreno N, Martinez-Alvarez R, Blas K, Grills I, Lee KC, Kosak M, Cifarelli CP, Katsevman GA, Sheehan JP. Hypopituitarism after Gamma Knife radiosurgery for pituitary adenomas: a multicenter, international study. J Neurosurg. 2018 Nov 09; doi: 10.3171/2018.5.JNS18509. Epub 2018 Nov 09. PMID: 31369225.
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J Neurosurg. 2018 Nov 09; doi: 10.3171/2018.5.JNS18509. Epub 2018 Nov 09.

Hypopituitarism after Gamma Knife radiosurgery for pituitary adenomas: a multicenter, international study.

Journal of neurosurgery

Diogo Cordeiro, Zhiyuan Xu, Gautam Mehta, Dale Ding, Mary Lee Vance, Hideyuki Kano, Nathaniel Sisterson, Huai-che Yang, Douglas Kondziolka, L. Dade Lunsford, David Mathieu, Gene Barnett, Veronica Chiang, John Lee, Penny Sneed, Yan-Hua Su, Cheng-chia Lee, Michal Krsek, Roman Liscak, Ahmed Nabeel, Amr El-Shehaby, Khaled Karim, Wael Reda, Nuria Martinez-Moreno, Roberto Martinez-Alvarez, Kevin Blas, Inga Grills, Kuei Lee, Mikulas Kosak, Christopher Cifarelli, Gennadiy Katsevman, Jason Sheehan

Affiliations

  1. Department of Neurological Surgery, University of Virginia, Charlottesville, Virginia
  2. Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
  3. Department of Neurosurgery, New York University, New York, New York
  4. Department of Surgery, Division of Neurosurgery, Université de Sherbrooke, Centre de recherche du CHUS, Sherbrooke, Quebec, Canada
  5. Department of Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio
  6. Department of Neurosurgery, Yale University, New Haven, Connecticut
  7. Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania
  8. Department of Radiation Oncology, University of California, San Francisco, California
  9. Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China
  10. Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Prague, Czech Republic
  11. Department of Neurosurgery, Faculty of Medicine, Benha University, Qalubya, Egypt
  12. Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt
  13. Gamma Knife Center Cairo-Nasser Institute, Neurosurgery Department, Ain Shams University, Cairo, Egypt
  14. Department of Functional Neurosurgery and Radiosurgery, Ruber International Hospital, Madrid, Spain
  15. Radiation Oncology Department, Beaumont Health System, Royal Oak, Michigan
  16. Third Department of Medicine, Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
  17. Department of Neurosurgery, West Virginia University, Morgantown, West Virginia

PMID: 31369225 DOI: 10.3171/2018.5.JNS18509

Abstract

OBJECTIVE: Recurrent or residual adenomas are frequently treated with Gamma Knife radiosurgery (GKRS). The most common complication after GKRS for pituitary adenomas is hypopituitarism. In the current study, the authors detail the timing and types of hypopituitarism in a multicenter, international cohort of pituitary adenoma patients treated with GKRS.

METHODS: Seventeen institutions pooled clinical data obtained from pituitary adenoma patients who were treated with GKRS from 1988 to 2016. Patients who had undergone prior radiotherapy were excluded. A total of 1023 patients met the study inclusion criteria. The treated lesions included 410 nonfunctioning pituitary adenomas (NFPAs), 262 cases of Cushing’s disease (CD), and 251 cases of acromegaly. The median follow-up was 51 months (range 6–246 months). Statistical analysis was performed using a Cox proportional hazards model to evaluate factors associated with the development of new-onset hypopituitarism.

RESULTS: At last follow-up, 248 patients had developed new pituitary hormone deficiency (86 with NFPA, 66 with CD, and 96 with acromegaly). Among these patients, 150 (60.5%) had single and 98 (39.5%) had multiple hormone deficiencies. New hormonal changes included 82 cortisol (21.6%), 135 thyrotropin (35.6%), 92 gonadotropin (24.3%), 59 growth hormone (15.6%), and 11 vasopressin (2.9%) deficiencies. The actuarial 1-year, 3-year, 5-year, 7-year, and 10-year rates of hypopituitarism were 7.8%, 16.2%, 22.4%, 27.5%, and 31.3%, respectively. The median time to hypopituitarism onset was 39 months. In univariate analyses, an increased rate of new-onset hypopituitarism was significantly associated with a lower isodose line (p = 0.006, HR = 8.695), whole sellar targeting (p = 0.033, HR = 1.452), and treatment of a functional pituitary adenoma as compared with an NFPA (p = 0.008, HR = 1.510). In multivariate analyses, only a lower isodose line was found to be an independent predictor of new-onset hypopituitarism (p = 0.001, HR = 1.38).

CONCLUSIONS: Hypopituitarism remains the most common unintended effect of GKRS for a pituitary adenoma. Treating the target volume at an isodose line of 50% or greater and avoiding whole-sellar radiosurgery, unless necessary, will likely mitigate the risk of post-GKRS hypopituitarism. Follow-up of these patients is required to detect and treat latent endocrinopathies.

© AANS, except where prohibited by US copyright law.

Keywords: hypopituitarism; pituitary adenoma; Cushing’s disease; acromegaly; stereotactic radiosurgery

Conflict of interest statement

Dr. Lunsford reports being a consultant for Insightec DSMB and having direct stock ownership in Elekta. Dr. Grills reports having direct stock ownership in Greater Michigan Gamma Knife, where she is o

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