Gamma Knife radiosurgery for the treatment of Nelson’s syndrome: a multicenter, international study

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  • 1 Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia;
  • 2 Department of Surgery, Division of Neurosurgery, Université de Sherbrooke, Centre de Recherche du CHUS, Sherbrooke, Quebec, Canada;
  • 3 Department of Neurological Surgery, University of Pittsburgh, Pennsylvania;
  • 4 Neurosurgery and Gamma Knife Radiosurgery, Humanitas Research Hospital, Rozzano, Milano, Italy;
  • 5 Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan, People’s Republic of China; and
  • 6 Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Prague, Czech Republic
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OBJECTIVE

Nelson’s syndrome is a rare and challenging neuroendocrine disorder, and it is associated with elevated adrenocorticotrophic hormone (ACTH) level, skin hyperpigmentation, and pituitary adenoma growth. Management options including resection and medical therapy are traditional approaches. Ionizing radiation in the form of Gamma Knife radiosurgery (GKRS) is also being utilized to treat Nelson’s syndrome. In the current study the authors sought to better define the therapeutic role of stereotactic radiosurgery (SRS) in Nelson’s syndrome.

METHODS

Study patients with Nelson’s syndrome were treated with single-fraction GKRS (median margin dose of 25 Gy) at 6 different centers as part of an International Radiosurgery Research Foundation (IRRF) investigation. Data including neurological function, endocrine response, and radiological tumor response were collected and sent to the study-coordinating center for review. Fifty-one patients with median endocrine and radiological follow-ups of 91 and 80.5 months from GKRS, respectively, were analyzed for endocrine remission, tumor control, and neurological outcome. Statistical methods were used to identify prognostic factors for these endpoints.

RESULTS

At last follow-up, radiological tumor control was achieved in 92.15% of patients. Endocrine remission off medical management and reduction in pre-SRS ACTH level were achieved in 29.4% and 62.7% of patients, respectively. Improved remission rates were associated with a shorter time interval between resection and GKRS (p = 0.039). Hypopituitarism was seen in 21.6% and new visual deficits were demonstrated in 15.7% of patients.

CONCLUSIONS

GKRS affords a high rate of pituitary adenoma control and improvement in ACTH level for the majority of Nelson’s syndrome patients. Hypopituitarism is the most common adverse effect from GKRS in Nelson’s syndrome patients and warrants longitudinal follow-up for detection and endocrine replacement.

ABBREVIATIONS ACTH = adrenocorticotrophic hormone; BA = bilateral adrenalectomy; CD = Cushing’s disease; CN = cranial nerve; CS = cavernous sinus; DI = diabetes insipidus; FSH = follicle-stimulating hormone; GH = growth hormone; GKRS = Gamma Knife radiosurgery; IGF-1 = insulin-like growth factor–1; IRRF = International Radiosurgery Research Foundation; NS = Nelson’s syndrome; OC = optic chiasm; ON = optic nerve; OT = optic tract; RT = radiation therapy; SRS = stereotactic radiosurgery; T4 = free thyroxin; TSH = thyroid-stimulating hormone; TSR = transsphenoidal resection.

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Contributor Notes

Correspondence Jason Sheehan: University of Virginia Health System, Charlottesville, VA. jps2f@hscmail.mcc.virginia.edu.

INCLUDE WHEN CITING Published online July 12, 2019; DOI: 10.3171/2019.4.JNS19273.

Disclosures Dr. Lunsford is a stockholder in Elekta AB. Dr. Kano received an Elekta research grant not related to this study. Dr. Liscak is a consultant for Elekta AB.

  • 1

    Assié G, Bahurel H, Bertherat J, Kujas M, Legmann P, Bertagna X: The Nelson’s syndrome... revisited. Pituitary 7:209215, 2004

  • 2

    Azad TD, Veeravagu A, Kumar S, Katznelson L: Nelson syndrome: update on therapeutic approaches. World Neurosurg 83:11351140, 2015

  • 3

    Barber TM, Adams E, Ansorge O, Byrne JV, Karavitaki N, Wass JA: Nelson’s syndrome. Eur J Endocrinol 163:495507, 2010

  • 4

    Biller BM, Grossman AB, Stewart PM, Melmed S, Bertagna X, Bertherat J, : Treatment of adrenocorticotropin-dependent Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 93:24542462, 2008

    • Search Google Scholar
    • Export Citation
  • 5

    Caruso JP, Patibandla MR, Xu Z, Vance ML, Sheehan JP: A long-term study of the treatment of Nelson’s syndrome with Gamma Knife radiosurgery. Neurosurgery 83:430436, 2018

    • Search Google Scholar
    • Export Citation
  • 6

    Castinetti F, Régis J, Dufour H, Brue T: Role of stereotactic radiosurgery in the management of pituitary adenomas. Nat Rev Endocrinol 6:214223, 2010

    • Search Google Scholar
    • Export Citation
  • 7

    Dickerman RD, Oldfield EH: Basis of persistent and recurrent Cushing disease: an analysis of findings at repeated pituitary surgery. J Neurosurg 97:13431349, 2002

    • Search Google Scholar
    • Export Citation
  • 8

    Ghostine S, Ghostine MS, Johnson WD: Radiation therapy in the treatment of pituitary tumors. Neurosurg Focus 24(5):E8, 2008

  • 9

    Hammer GD, Tyrrell JB, Lamborn KR, Applebury CB, Hannegan ET, Bell S, : Transsphenoidal microsurgery for Cushing’s disease: initial outcome and long-term results. J Clin Endocrinol Metab 89:63486357, 2004

    • Search Google Scholar
    • Export Citation
  • 10

    Heaney AP, Fernando M, Yong WH, Melmed S: Functional PPAR-gamma receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas. Nat Med 8:12811287, 2002

    • Search Google Scholar
    • Export Citation
  • 11

    Howlett TA, Plowman PN, Wass JA, Rees LH, Jones AE, Besser GM: Megavoltage pituitary irradiation in the management of Cushing’s disease and Nelson’s syndrome: long-term follow-up. Clin Endocrinol (Oxf) 31:309323, 1989

    • Search Google Scholar
    • Export Citation
  • 12

    Jane JA Jr, Vance ML, Woodburn CJ, Laws ER Jr: Stereotactic radiosurgery for hypersecreting pituitary tumors: part of a multimodality approach. Neurosurg Focus 14(5):e12, 2003

    • Search Google Scholar
    • Export Citation
  • 13

    Jenkins PJ, Trainer PJ, Plowman PN, Shand WS, Grossman AB, Wass JA, : The long-term outcome after adrenalectomy and prophylactic pituitary radiotherapy in adrenocorticotropin-dependent Cushing’s syndrome. J Clin Endocrinol Metab 80:165171, 1995

    • Search Google Scholar
    • Export Citation
  • 14

    Katznelson L: Bilateral adrenalectomy for Cushing’s disease. Pituitary 18:269273, 2015

  • 15

    Kemink SA, Grotenhuis JA, De Vries J, Pieters GF, Hermus AR, Smals AG: Management of Nelson’s syndrome: observations in fifteen patients. Clin Endocrinol (Oxf) 54:4552, 2001

    • Search Google Scholar
    • Export Citation
  • 16

    Kim W, Clelland C, Yang I, Pouratian N: Comprehensive review of stereotactic radiosurgery for medically and surgically refractory pituitary adenomas. Surg Neurol Int 3 (Suppl 2):S79S89, 2012

    • Search Google Scholar
    • Export Citation
  • 17

    Lamberts SW, Uitterlinden P, Klijn JM: The effect of the long-acting somatostatin analogue SMS 201-995 on ACTH secretion in Nelson’s syndrome and Cushing’s disease. Acta Endocrinol (Copenh) 120:760766, 1989

    • Search Google Scholar
    • Export Citation
  • 18

    Liu JK, Fleseriu M, Delashaw JB Jr, Ciric IS, Couldwell WT: Treatment options for Cushing disease after unsuccessful transsphenoidal surgery. Neurosurg Focus 23(3):E8, 2007

    • Search Google Scholar
    • Export Citation
  • 19

    Loeffler JS, Shih HA: Radiation therapy in the management of pituitary adenomas. J Clin Endocrinol Metab 96:19922003, 2011

  • 20

    Lüdecke DK, Breustedt HJ, Brämswig J, Köbberling J, Saeger W: Evaluation of surgically treated Nelson’s syndrome. Acta Neurochir (Wien) 65:313, 1982

    • Search Google Scholar
    • Export Citation
  • 21

    Marek J, Ježková J, Hána V, Kršek M, Liščák R, Vladyka V, : Gamma knife radiosurgery for Cushing’s disease and Nelson’s syndrome. Pituitary 18:376384, 2015

    • Search Google Scholar
    • Export Citation
  • 22

    Mauermann WJ, Sheehan JP, Chernavvsky DR, Laws ER, Steiner L, Vance ML: Gamma Knife surgery for adrenocorticotropic hormone-producing pituitary adenomas after bilateral adrenalectomy. J Neurosurg 106:988993, 2007

    • Search Google Scholar
    • Export Citation
  • 23

    Mehta GU, Sheehan JP, Vance ML: Effect of stereotactic radiosurgery before bilateral adrenalectomy for Cushing’s disease on the incidence of Nelson’s syndrome. J Neurosurg 119:14931497, 2013

    • Search Google Scholar
    • Export Citation
  • 24

    Nelson DH, Meakin JW, Thorn GW: ACTH-producing pituitary tumors following adrenalectomy for Cushing’s syndrome. Ann Intern Med 52:560569, 1960

    • Search Google Scholar
    • Export Citation
  • 25

    Oldfield EH: Cushing disease. J Neurosurg 98:948951, 2003

  • 26

    Patel J, Eloy JA, Liu JK: Nelson’s syndrome: a review of the clinical manifestations, pathophysiology, and treatment strategies. Neurosurg Focus 38(2):E14, 2015

    • Search Google Scholar
    • Export Citation
  • 27

    Pereira MA, Halpern A, Salgado LR, Mendonça BB, Nery M, Liberman B, : A study of patients with Nelson’s syndrome. Clin Endocrinol (Oxf) 49:533539, 1998

    • Search Google Scholar
    • Export Citation
  • 28

    Pollock BE, Young WF Jr: Stereotactic radiosurgery for patients with ACTH-producing pituitary adenomas after prior adrenalectomy. Int J Radiat Oncol Biol Phys 54:839841, 2002

    • Search Google Scholar
    • Export Citation
  • 29

    Raverot G, Sturm N, de Fraipont F, Muller M, Salenave S, Caron P, : Temozolomide treatment in aggressive pituitary tumors and pituitary carcinomas: a French multicenter experience. J Clin Endocrinol Metab 95:45924599, 2010

    • Search Google Scholar
    • Export Citation
  • 30

    Ritzel K, Beuschlein F, Mickisch A, Osswald A, Schneider HJ, Schopohl J, : Clinical review: Outcome of bilateral adrenalectomy in Cushing’s syndrome: a systematic review. J Clin Endocrinol Metab 98:39393948, 2013

    • Search Google Scholar
    • Export Citation
  • 31

    Sheehan JP, Niranjan A, Sheehan JM, Jane JA Jr, Laws ER, Kondziolka D, : Stereotactic radiosurgery for pituitary adenomas: an intermediate review of its safety, efficacy, and role in the neurosurgical treatment armamentarium. J Neurosurg 102:678691, 2005

    • Search Google Scholar
    • Export Citation
  • 32

    Snell JW, Sheehan J, Stroila M, Steiner L: Assessment of imaging studies used with radiosurgery: a volumetric algorithm and an estimation of its error. Technical note. J Neurosurg 104:157162, 2006

    • Search Google Scholar
    • Export Citation
  • 33

    Sonino N, Zielezny M, Fava GA, Fallo F, Boscaro M: Risk factors and long-term outcome in pituitary-dependent Cushing’s disease. J Clin Endocrinol Metab 81:26472652, 1996

    • Search Google Scholar
    • Export Citation
  • 34

    Tishler RB, Loeffler JS, Lunsford LD, Duma C, Alexander E III, Kooy HM, : Tolerance of cranial nerves of the cavernous sinus to radiosurgery. Int J Radiat Oncol Biol Phys 27:215221, 1993

    • Search Google Scholar
    • Export Citation
  • 35

    Tritos NA, Biller BM, Swearingen B: Management of Cushing disease. Nat Rev Endocrinol 7:279289, 2011

  • 36

    Vik-Mo EO, Øksnes M, Pedersen PH, Wentzel-Larsen T, Rødahl E, Thorsen F, : Gamma knife stereotactic radiosurgery of Nelson syndrome. Eur J Endocrinol 160:143148, 2009

    • Search Google Scholar
    • Export Citation
  • 37

    Wolffenbuttel BH, Kitz K, Beuls EM: Beneficial gamma-knife radiosurgery in a patient with Nelson’s syndrome. Clin Neurol Neurosurg 100:6063, 1998

    • Search Google Scholar
    • Export Citation
  • 38

    Xu Z, Lee Vance M, Schlesinger D, Sheehan JP: Hypopituitarism after stereotactic radiosurgery for pituitary adenomas. Neurosurgery 72:630637, 2013

    • Search Google Scholar
    • Export Citation

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