Medical Oncology

, Volume 29, Issue 1, pp 374–377 | Cite as

Hyponatremia associated with Ipilimumab-induced hypophysitis

  • Zachary R. Barnard
  • Brian P. WalcottEmail author
  • Kristopher T. Kahle
  • Brian V. Nahed
  • Jean Valery Coumans
Original Paper


A 75-year-old woman with a history of stage IV metastatic melanoma underwent treatment with the CTLA-4 blocking agent Ipilimumab. She presented 2 months after initiating treatment with a severe headache. Laboratories were consistent with severe hyponatremia. MRI of the brain revealed enlargement of the pituitary gland, enhancement of the infundibulum, and an enhancing, centrally necrotic foci in the anterior pituitary. Based on the clinical and radiographic findings, she was diagnosed with treatment-related syndrome of inappropriate antidiuretic hormone secretion (SIADH). Effective treatment consisted of fluid restriction, hyperosmolar therapy, and steroids.


Pituitary gland Melanoma Antibodies Monoclonal Inappropriate ADH syndrome 


  1. 1.
    Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. Immunity. 1995;3(5):541–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Carthon BC, Wolchok JD, Yuan J, Kamat A, Ng Tang DS, Sun J, et al. Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial. Clin Cancer Res. 2010;16(10):2861–71.PubMedCrossRefGoogle Scholar
  3. 3.
    Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–23.PubMedCrossRefGoogle Scholar
  4. 4.
    Dillard T, Yedinak CG, Alumkal J, Fleseriu M. Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: serious immune related adverse events across a spectrum of cancer subtypes. Pituitary. 2010;13(1):29–38.PubMedCrossRefGoogle Scholar
  5. 5.
    Yang JC, Hughes M, Kammula U, Royal R, Sherry RM, Topalian SL, et al. Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. J Immunother. 2007;30(8):825–30.PubMedCrossRefGoogle Scholar
  6. 6.
    Downey SG, Klapper JA, Smith FO, Yang JC, Sherry RM, Royal RE, et al. Prognostic factors related to clinical response in patients with metastatic melanoma treated by CTL-associated antigen-4 blockade. Clin Cancer Res. 2007;13(22 Pt 1):6681–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Maker AV, Phan GQ, Attia P, Yang JC, Sherry RM, Topalian SL, et al. Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: a phase I/II study. Ann Surg Oncol. 2005;12(12):1005–16.PubMedCrossRefGoogle Scholar
  8. 8.
    Attia P, Phan GQ, Maker AV, Robinson MR, Quezado MM, Yang JC, et al. Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol. 2005;23(25):6043–53.PubMedCrossRefGoogle Scholar
  9. 9.
    Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007;356(20):2064–72.PubMedCrossRefGoogle Scholar
  10. 10.
    Berghmans T, Paesmans M, Body JJ. A prospective study on hyponatraemia in medical cancer patients: epidemiology, aetiology and differential diagnosis. Support Care Cancer. 2000;8(3):192–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med. 2000;342(21):1581–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Upadhyay A, Jaber BL, Madias NE. Incidence and prevalence of hyponatremia. Am J Med. 2006;119(7 Suppl 1):S30–5.PubMedCrossRefGoogle Scholar
  13. 13.
    Sherlock M, Thompson CJ. The syndrome of inappropriate antidiuretic hormone: current and future management options. Eur J Endocrinol. 2010;162(Suppl 1):S13–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Hoorn EJ, Lindemans J, Zietse R. Development of severe hyponatraemia in hospitalized patients: treatment-related risk factors and inadequate management. Nephrol Dial Transpl. 2006;21(1):70–6.CrossRefGoogle Scholar
  15. 15.
    Gill G, Huda B, Boyd A, Skagen K, Wile D, Watson I, et al. Characteristics and mortality of severe hyponatraemia–a hospital-based study. Clin Endocrinol (Oxf). 2006;65(2):246–9.CrossRefGoogle Scholar
  16. 16.
    Arieff AI, Llach F, Massry SG. Neurological manifestations and morbidity of hyponatremia: correlation with brain water and electrolytes. Medicine (Baltimore). 1976;55(2):121–9.CrossRefGoogle Scholar
  17. 17.
    Diederich S, Franzen N, Bähr V, Oelkers W. Severe hyponatremia due to hypopituitarism with adrenal insufficiency: report on 28 cases. Eur J Endocrinol. 2003;148(6):609–17.PubMedCrossRefGoogle Scholar
  18. 18.
    Rivera J. Lymphocytic hypophysitis: disease spectrum and approach to diagnosis and therapy. Pituitary. 2006;9(1):35–45.PubMedCrossRefGoogle Scholar
  19. 19.
    Abe T. Lymphocytic infundibulo-neurohypophysitis and infundibulo-panhypophysitis regarded as lymphocytic hypophysitis variant. Brain Tumor Pathol. 2008;25(2):59–66.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Zachary R. Barnard
    • 1
  • Brian P. Walcott
    • 1
    Email author
  • Kristopher T. Kahle
    • 1
  • Brian V. Nahed
    • 1
  • Jean Valery Coumans
    • 1
  1. 1.Department of NeurosurgeryMassachusetts General Hospital and Harvard Medical SchoolBostonUSA

Personalised recommendations