Abstract
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.
Similar content being viewed by others
References
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.
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.
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.
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.
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.
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.
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.
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.
Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007;356(20):2064–72.
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.
Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med. 2000;342(21):1581–9.
Upadhyay A, Jaber BL, Madias NE. Incidence and prevalence of hyponatremia. Am J Med. 2006;119(7 Suppl 1):S30–5.
Sherlock M, Thompson CJ. The syndrome of inappropriate antidiuretic hormone: current and future management options. Eur J Endocrinol. 2010;162(Suppl 1):S13–8.
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.
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.
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.
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.
Rivera J. Lymphocytic hypophysitis: disease spectrum and approach to diagnosis and therapy. Pituitary. 2006;9(1):35–45.
Abe T. Lymphocytic infundibulo-neurohypophysitis and infundibulo-panhypophysitis regarded as lymphocytic hypophysitis variant. Brain Tumor Pathol. 2008;25(2):59–66.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Barnard, Z.R., Walcott, B.P., Kahle, K.T. et al. Hyponatremia associated with Ipilimumab-induced hypophysitis. Med Oncol 29, 374–377 (2012). https://doi.org/10.1007/s12032-010-9794-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12032-010-9794-7