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Stereotactic radiosurgery before bilateral adrenalectomy is associated with lowered risk of Nelson’s syndrome in refractory Cushing’s disease patients

  • Original Article - Brain Tumors
  • Published:
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Abstract

Background

Nelson’s syndrome is a rare but challenging sequelae of Cushing’s disease (CD) after bilateral adrenalectomy (BLA). We sought to determine if stereotactic radiosurgery (SRS) of residual pituitary adenoma performed before BLA can decrease the risk of Nelson’s syndrome.

Methods

Consecutive patients with CD who underwent BLA after non-curative resection of ACTH secreting pituitary adenoma and had at least one follow-up visit after BLA were studied. Nelson’s syndrome was diagnosed based on the combination of rising ACTH levels, increasing volume of the pituitary adenoma and/or hyperpigmentation.

Results

Fifty patients underwent BLA for refractory CD, and 43 patients (7 men and 36 women) had at least one follow-up visit after BAL. Median endocrine, imaging, and clinical follow-up were 66 months, 69 months, and 80 months, respectively. Nine patients (22%) were diagnosed with the Nelson’s syndrome at median time after BLA at 24 months (range: 0.6–119.4 months). SRS before BLA was associated with reduced risk of the Nelson’s syndrome (HR = 0.126; 95%CI [0.022–0.714], p=0.019), while elevated ACTH level within 6 months after BLA was associated with increased risk for the Nelson’s syndrome (HR = 9.053; 95%CI [2.076–39.472], p=0.003).

Conclusions

SRS before BLA can reduce the risk for the Nelson’s syndrome in refractory CD patients requiring BLA and should be considered before proceeding to BLA. Elevated ACTH concentration within 6 months after BLA is associated with greater risk of the Nelsons’ syndrome. When no prior SRS is administered, those with a high ACTH level shortly after BLA may benefit from early SRS.

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References

  1. Assié G, Bahurel H, Bertherat J, Kujas M, Legmann P, Bertagna X (2004) The Nelson’s syndrome... revisited. Pituitary 7(4):209–215

    Article  Google Scholar 

  2. Assié G, Bahurel H, Coste J et al (2007) Corticotroph tumor progression after adrenalectomy in Cushing’s Disease: a reappraisal of Nelson’s Syndrome. J Clin Endocrinol Metab 92(1):172–179

    Article  Google Scholar 

  3. Barnett AH, Livesey JH, Friday K, Donald RA, Espiner EA (1983) Comparison of preoperative and postoperative ACTH concentrations after bilateral adrenalectomy in Cushing’s disease. Clin Endocrinol (Oxf) 18(3):301–305

    Article  CAS  Google Scholar 

  4. Bunevicius A, Kano H, Lee C-C, et al (2020) Early versus late Gamma Knife radiosurgery for Cushing’s disease after prior resection: results of an international, multicenter study. J Neurosurg 1–9

  5. Bunevicius A, Laws ER, Vance ML, Iuliano S, Sheehan J (2019) Surgical and radiosurgical treatment strategies for Cushing’s disease. J Neurooncol 145(3):403–413

    Article  Google Scholar 

  6. Bunevicius A, Sheehan D, Lee Vance M, Schlesinger D, Sheehan JP (2020) Outcomes of Cushing’s disease following Gamma Knife radiosurgery: effect of a center’s growing experience and era of treatment. J Neurosurg 1–8

  7. Clayton RN, Jones PW, Reulen RC et al (2016) Mortality in patients with Cushing’s disease more than 10 years after remission: a multicentre, multinational, retrospective cohort study. Lancet Diab Endocrinol 4(7):569–576

    Article  Google Scholar 

  8. Cordeiro D, Xu Z, Li CE, et al (2019) Gamma Knife radiosurgery for the treatment of Nelson’s syndrome: a multicenter, international study. J Neurosurg 1–6

  9. Das L, Bhansali A, Pivonello R et al (2020) ACTH increment post total bilateral adrenalectomy for Cushing’s disease: a consistent biosignature for predicting Nelson’s syndrome. Pituitary. https://doi.org/10.1007/s11102-020-01047-x

  10. Fountas A, Lim ES, Drake WM et al (2020) Outcomes of patients with Nelson’s syndrome after primary treatment: a multicenter study from 13 UK pituitary centers. J Clin Endocrinol Metab. https://doi.org/10.1210/clinem/dgz200

  11. Gil-Cárdenas A, Herrera MF, Díaz-Polanco A, Rios JM, Pantoja JP (2007) Nelson’s syndrome after bilateral adrenalectomy for Cushing’s disease. Surgery 141(2):147–151 discussion 151-152

    Article  Google Scholar 

  12. Hughes JD, Young WF, Chang AY, Link MJ, Garces YI, Laack NN, Thompson GB, Pollock BE (2019) Radiosurgical management of patients with persistent or recurrent cushing disease after prior transsphenoidal surgery: a management algorithm based on a 25-year experience. Neurosurgery. https://doi.org/10.1093/neuros/nyz159

  13. Jenkins PJ, Trainer PJ, Plowman PN, Shand WS, Grossman AB, Wass JA, Besser GM (1995) The long-term outcome after adrenalectomy and prophylactic pituitary radiotherapy in adrenocorticotropin-dependent Cushing’s syndrome. J Clin Endocrinol Metab 80(1):165–171

    CAS  PubMed  Google Scholar 

  14. Katznelson L (2015) Bilateral adrenalectomy for Cushing’s disease. Pituitary 18(2):269–273

    Article  CAS  Google Scholar 

  15. Kelly PA, Samandouras G, Grossman AB, Afshar F, Besser GM, Jenkins PJ (2002) Neurosurgical treatment of Nelson’s syndrome. J Clin Endocrinol Metab 87(12):5465–5469

    Article  CAS  Google Scholar 

  16. Kurowska M, Nowakowski A, Zieliński G, Malicka J, Tarach JS, Maksymowicz M, Denew P (2015) Temozolomide-induced shrinkage of invasive pituitary adenoma in patient with Nelson’s syndrome: a case report and review of the literature. Case Rep Endocrinol. https://doi.org/10.1155/2015/623092

  17. Lacroix A, Feelders RA, Stratakis CA, Nieman LK (2015) Cushing’s syndrome. The Lancet 386(9996):913–927

    Article  CAS  Google Scholar 

  18. Lindholm J, Juul S, Jørgensen JO et al (2001) Incidence and late prognosis of cushing’s syndrome: a population-based study. J Clin Endocrinol Metab 86(1):117–123

    CAS  PubMed  Google Scholar 

  19. Lüdecke DK, Breustedt HJ, Brämswig J, Köbberling J, Saeger W (1982) Evaluation of surgically treated Nelson’s syndrome. Acta Neurochir (Wien) 65(1–2):3–13

    Article  Google Scholar 

  20. Mehta GU, Ding D, Patibandla MR et al (2017) Stereotactic radiosurgery for Cushing disease: results of an international, multicenter study. J Clin Endocrinol Metab 102(11):4284–4291

    Article  Google Scholar 

  21. Mehta GU, Sheehan JP, Vance ML (2013) Effect of stereotactic radiosurgery before bilateral adrenalectomy for Cushing’s disease on the incidence of Nelson’s syndrome. J Neurosurg 119(6):1493–1497

    Article  Google Scholar 

  22. Moore TJ, Dluhy RG, Williams GH, Cain JP (1976) Nelson’s syndrome: frequency, prognosis, and effect of prior pituitary irradiation. Ann Intern Med 85(6):731–734

    Article  CAS  Google Scholar 

  23. Moyes VJ, Alusi G, Sabin HI, Evanson J, Berney DM, Kovacs K, Monson JP, Plowman PN, Drake WM (2009) Treatment of Nelson’s syndrome with temozolomide. Eur J Endocrinol 160(1):115–119

    Article  CAS  Google Scholar 

  24. Nagesser SK, van Seters AP, Kievit J, Hermans J, Krans HM, van de Velde CJ (2000) Long-term results of total adrenalectomy for Cushing’s disease. World J Surg 24(1):108–113

    Article  CAS  Google Scholar 

  25. Nieman LK, Biller BMK, Findling JW, Murad MH, Newell-Price J, Savage MO, Tabarin A (2015) Treatment of Cushing’s syndrome: an endocrine society clinical practice guideline summary of recommendations. J Clin Endocrinol Metab 100:2807–2831

    Article  CAS  Google Scholar 

  26. Oßwald A, Plomer E, Dimopoulou C et al (2014) Favorable long-term outcomes of bilateral adrenalectomy in Cushing’s disease. Eur J Endocrinol 171(2):209–215

    Article  Google Scholar 

  27. Palermo NE, Ananthakrishnan S (2015) Re-examining Nelson’s syndrome. Curr Opin Endocrinol Diabetes Obes 22(4):313–318

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  29. Pendharkar AV, Sussman ES, Ho AL, Hayden Gephart MG, Katznelson L (2015) Cushing’s disease: predicting long-term remission after surgical treatment. Neurosurg Focus 38(2):E13

    Article  Google Scholar 

  30. Pereira MA, Halpern A, Salgado LR, Mendonça BB, Nery M, Liberman B, Streeten DH, Wajchenberg BL (1998) A study of patients with Nelson’s syndrome. Clin Endocrinol (Oxf) 49(4):533–539

    Article  CAS  Google Scholar 

  31. Petersenn S, Beckers A, Ferone D et al (2015) Therapy of endocrine disease: outcomes in patients with Cushing’s disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recurrence. Eur J Endocrinol 172(6):R227–R239

    Article  CAS  Google Scholar 

  32. Ragnarsson O, Olsson DS, Chantzichristos D et al (2019) The incidence of Cushing’s disease: a nationwide Swedish study. Pituitary 22(2):179–186

    Article  Google Scholar 

  33. Ritzel K, Beuschlein F, Mickisch A, Osswald A, Schneider HJ, Schopohl J, Reincke M (2013) Clinical review: outcome of bilateral adrenalectomy in Cushing’s syndrome: a systematic review. J Clin Endocrinol Metab 98(10):3939–3948

    Article  CAS  Google Scholar 

  34. Smith PW, Turza KC, Carter CO, Vance ML, Laws ER, Hanks JB (2009) Bilateral adrenalectomy for refractory Cushing disease: a safe and definitive therapy. J Am Coll Surg 208(6):1059–1064

    Article  Google Scholar 

  35. Sonino N, Zielezny M, Fava GA, Fallo F, Boscaro M (1996) Risk factors and long-term outcome in pituitary-dependent Cushing’s disease. J Clin Endocrinol Metab 81(7):2647–2652

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosurgery, University of Virginia, Charlottesville, VA, 22908, USA

    Adomas Bunevicius, Karen Lavezzo & Jason Sheehan

  2. Department of Surgery, University of Virginia, Charlottesville, VA, USA

    Philip W. Smith

  3. Department of Medicine, University of Virginia Health System, Charlottesville, VA, USA

    Mary Lee Vance

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  1. Adomas Bunevicius
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  2. Karen Lavezzo
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Correspondence to Jason Sheehan.

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Bunevicius, A., Lavezzo, K., Smith, P.W. et al. Stereotactic radiosurgery before bilateral adrenalectomy is associated with lowered risk of Nelson’s syndrome in refractory Cushing’s disease patients. Acta Neurochir 163, 1949–1956 (2021). https://doi.org/10.1007/s00701-021-04823-1

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  • DOI: https://doi.org/10.1007/s00701-021-04823-1

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