Skip to main content

Advertisement

Log in

Diagnosis and management of hyponatremia in cancer patients

  • Review Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Background

Hyponatremia is among the metabolic disturbances encountered in oncology. Risk factors for hyponatremia include chemotherapy, treatment-induced nausea and vomiting, hydration, pain, narcotic drugs, and physical and emotional stress. A common cause of hyponatremia in patients with cancer is the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), which may result from ectopic production of arginine vasopressin (AVP) by the tumor tissue.

Treatment

The AVP-receptor antagonists, a new class of agents, correct hyponatremia by directly blocking the binding of AVP with its receptors. In clinical trials, conivaptan, lixivaptan, tolvaptan, and satavaptan have increased serum osmolality and normalized the serum [Na+] in hyponatremia associated with SIADH, cirrhosis, or congestive heart failure. These drugs may have a potential in cancer-related hyponatremia as well.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Adrogué HJ, Madias NE (2000) Hyponatremia. N Engl J Med 342:1581–1589

    Article  PubMed  Google Scholar 

  2. Anderson RJ, Chung H-M, Kluge R, Schrier RW (1985) Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann Intern Med 102:164–168

    PubMed  CAS  Google Scholar 

  3. Bartter FC, Schwartz WB (1967) The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 42:790–806

    Article  PubMed  CAS  Google Scholar 

  4. Baylis PH (1989) Regulation of vasopressin secretion. Baillieres Clin Endocrinol Metab 3:313–330

    Article  PubMed  CAS  Google Scholar 

  5. Baylis PH (2003) The syndrome of inappropriate antidiuretic hormone secretion. Int J Biochem Cell Biol 35:1495–1499

    Article  PubMed  CAS  Google Scholar 

  6. Berghmans T (1996) Hyponatremia related to medical anticancer treatment. Support Care Cancer 4:341–350

    Article  PubMed  CAS  Google Scholar 

  7. Berghmans T, Paesmans M, Body JJ (1999) A prospective study on hyponatraemia in medical cancer patients: epidemiology, aetiology and differential diagnosis. Support Care Cancer 8:192–197

    Article  Google Scholar 

  8. Berry PL, Belsha CW (1990) Hyponatremia. Pediatr Clin North Am 37:351–363

    PubMed  CAS  Google Scholar 

  9. Bissett D, Cornford EJ, Sokal M (1989) Hyponatraemia following cisplatin chemotherapy. Acta Oncol 28:823

    PubMed  CAS  Google Scholar 

  10. Bliss DP Jr, Battey JF, Linnoila RI, Birrer MJ, Gazdar AF, Johnson BE (1990) Expression of the atrial natriuretic factor gene in small cell lung cancer tumors and tumor cell lines. J Natl Cancer Inst 82:305–310

    Article  PubMed  CAS  Google Scholar 

  11. Boku N, Ohtsu A, Nagashima F, Muto M, Shinkai T, Yoshida A (2001) Retrospective study of hyponatremia in gastric cancer patients treated with a combination chemotherapy of 5-fluorouracil and cisplatin: a possible warning sign of severe hematological toxicities? Jpn J Clin Oncol 31:382–387

    Article  PubMed  CAS  Google Scholar 

  12. Campling BG, Sarda IR, Baer KA, Pang SC, Baker HM, Lofters WS, Flynn TG (1995) Secretion of atrial natriuretic peptide and vasopressin by small cell lung cancer. Cancer 75:2442–2451

    Article  PubMed  CAS  Google Scholar 

  13. Cancer Therapy Evaluation Program (2006) Common terminology criteria for adverse events, version 3.0. DCTD, NCI, NIH, DHHS; March 31, 2003. Available at: http://ctep.cancer.gov. Publish date: August 9, 2006. Accessed on November 15, 2006

  14. Cao L, Joshi P, Sumoza D (2002) Renal salt-wasting syndrome in a patient with cisplatin-induced hyponatremia: case report. Am J Clin Oncol 25:344–346

    Article  PubMed  Google Scholar 

  15. Comis RL, Miller M, Ginsberg SJ (1980) Abnormalities in water homeostasis in small cell anaplastic lung cancer. Cancer 45:2414–2421

    Article  PubMed  CAS  Google Scholar 

  16. Decaux G, Soupart A (2003) Treatment of symptomatic hyponatremia. Am J Med Sci 326:25–30

    Article  PubMed  Google Scholar 

  17. Dhaliwal HS, Rohatiner AZS, Gregory W, Richards MA, Johnson PWM, Whelan JS, Gallagher CJ, Matthews J, Ganesan TS, Barnett MJ, Waxman JH, Stansfeld AG, Wrigley PFM, Slevin ML, Malpas JS, Lister TA (1993) Combination chemotherapy for intermediate and high grade non-Hodgkin’s lymphoma. Br J Cancer 68:767–774

    PubMed  CAS  Google Scholar 

  18. el Weshi A, Thieblemont C, Cottin V, Barbet N, Catimel G (1995) Cisplatin-induced hyponatremia and renal sodium wasting. Acta Oncol 34:264–265

    PubMed  Google Scholar 

  19. Elisaf MS, Konstantinides A, Siamopoulos KC (1996) Chronic hyponatremia due to reset osmostat in a patient with colon cancer. Am J Nephrol 16:349–351

    PubMed  CAS  Google Scholar 

  20. Ellis SJ (1995) Severe hyponatraemia: complications and treatment. QJM 88:905–909

    PubMed  CAS  Google Scholar 

  21. Fried LF, Palevsky PM (1997) Hyponatremia and hypernatremia. Med Clin North Am 81:585–609

    Article  PubMed  CAS  Google Scholar 

  22. Gerbes AL, Gulberg V, Gines P, Decaux G, Gross P, Gandjini H, Djian J (2003) Therapy of hyponatremia in cirrhosis with a vasopressin receptor antagonist: a randomized double-blind multicenter trial. Gastroenterology 124:933–939

    Article  PubMed  CAS  Google Scholar 

  23. Ghali JK, Koren MJ, Taylor JR, Brooks-Asplund E, Fan K, Long WA, Smith N (2006) Efficacy and safety of oral conivaptan: a vasopressin receptor V1A/V2 antagonist, assessed in a randomized, placebo-controlled trial in patients with euvolemic or hypervolemic hyponatremia. J Clin Endocrinol Metab 91:2145–2152

    Article  PubMed  CAS  Google Scholar 

  24. Gheorghiade M, Niazi I, Ouyang J, Czerwiec F, Kambayashi J, Zampino M, Orlandi C (2003) Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. Circulation 107:2690–2696

    Article  PubMed  CAS  Google Scholar 

  25. Gheorghiade M, Gattis WA, O’Connor CM, Adams KF Jr, Elkayam U, Barbagelata A, Ghali JK, Benza RL, McGrew FA, Klapholz M, Ouyang J, Orlandi C (2004) Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA 291:1963–1971

    Article  PubMed  CAS  Google Scholar 

  26. Glover DJ, Glick JH (1987) Metabolic oncologic emergencies. CA Cancer J Clin 37:302–320

    Article  PubMed  CAS  Google Scholar 

  27. Goh KP (2004) Management of hyponatremia. Am Fam Phys 69:2387–2394

    Google Scholar 

  28. Gross AJ, Steinberg SM, Reilly JG, Bliss DP Jr, Brennan J, Le PT, Simmons A, Phelps R, Mulshine JL, Ihde DC, Johnson BE (1993) Atrial natriuretic factor and arginine vasopressin production in tumor cell lines from patients with lung cancer and their relationship to serum sodium. Cancer Res 53:67–74

    PubMed  CAS  Google Scholar 

  29. Gross P, Reimann D, Henschkowski J, Damian M (2001) Treatment of severe hyponatremia: conventional and novel aspects. J Am Soc Nephrol 12:S10–S14

    PubMed  CAS  Google Scholar 

  30. Gross P, Bisaha JG, Smith N (2004) Conivaptan, a novel V1A and V2 antagonist, increased serum sodium and effective water clearance in patients with euvolemic or hypervolemic hyponatremia [abstract]. J Am Soc Nephrol 15:355A, Abstract SA-P0243

    Article  CAS  Google Scholar 

  31. Gullans SR, Verbalis JG (1993) Control of brain volume during hyperosmolar and hypoosmolar conditions. Annu Rev Med 44:289–301

    Article  PubMed  CAS  Google Scholar 

  32. Iyer AV, Krasnow SH, Dufour R, Arcenas AS (2003) Sodium-wasting nephropathy caused by cisplatin in a patient with small-cell lung cancer. Clin Lung Cancer 5:187–189

    Article  PubMed  Google Scholar 

  33. Kinzie BJ (1987) Management of the syndrome of inappropriate secretion of antidiuretic hormone. Clin Pharm 6:625–633

    PubMed  CAS  Google Scholar 

  34. Langfeldt LA, Cooley ME (2003) Syndrome of inappropriate antidiuretic hormone secretion in malignancy: review and implications for nursing management. Clin J Oncol Nurs 7:425–430

    Article  PubMed  Google Scholar 

  35. List AF, Hainsworth JD, Davis BW, Hande KR, Greco FA, Johnson DH (1986) The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in small-cell lung cancer. J Clin Oncol 4:1191–1198

    PubMed  CAS  Google Scholar 

  36. Nielsen S (2002) Renal aquaporins: an overview. BJU Int 90(Suppl 3):1–6

    Article  PubMed  CAS  Google Scholar 

  37. Østerlind K (1994) Factors confounding evaluation of treatment effect in lung cancer. Lung Cancer 10(Suppl 1):S97–S103

    Article  PubMed  Google Scholar 

  38. Palmer BF (2003) Hyponatremia in patients with central nervous system disease: SIADH versus CSW. Trends Endocrinol Metab 14:182–187

    Article  PubMed  CAS  Google Scholar 

  39. Poe CM, Taylor LM (1989) Syndrome of inappropriate antidiuretic hormone: assessment and nursing implications. Oncol Nurs Forum 16:373–381

    PubMed  CAS  Google Scholar 

  40. Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G (2006) Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med 119:71.e1–71.e8

    Article  CAS  Google Scholar 

  41. Robertson GL (2001) Antidiuretic hormone. Normal and disordered function. Endocrinol Metab Clin North Am 30:671–694

    Article  PubMed  CAS  Google Scholar 

  42. Schrier RW, Gross P, Gheorghiade M, Berl T, Verbalis JG, Czerwiec FS, Orlandi C, for the SALT Investigators (2006) Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med 355:2099–2112

    Article  PubMed  CAS  Google Scholar 

  43. Schwartz WB, Bennett W, Curelop S, Bartter FC (1957) A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. Am J Med 23:529–542

    Article  PubMed  CAS  Google Scholar 

  44. Silverman P, Distelhorst CW (1989) Metabolic emergencies in clinical oncology. Semin Oncol 16:504–515

    PubMed  CAS  Google Scholar 

  45. Sørensen JB, Andersen MK, Hansen HH (1995) Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in malignant disease. J Intern Med 238:97–110

    Article  PubMed  Google Scholar 

  46. Soupart A, Gross P, Legros JJ, Alfoldi S, Annane D, Heshmati HM, Decaux G (2006) Successful long-term treatment of hyponatremia in syndrome of inappropriate antidiuretic hormone secretion with satavaptan (SR121463B), an orally active nonpeptide vasopressin V2-receptor antagonist. Clin J Am Soc Nephrol 1:634–640

    Article  CAS  Google Scholar 

  47. Vanhees SL, Paridaens R, Vansteenkiste JF (2000) Syndrome of inappropriate antidiuretic hormone associated with chemotherapy-induced tumour lysis in small-cell lung cancer: case report and literature review. Ann Oncol 11:1061–1065

    Article  PubMed  CAS  Google Scholar 

  48. Verbalis JG (2002) Vasopressin V2 receptor antagonists. J Mol Endocrinol 29:1–9

    Article  PubMed  CAS  Google Scholar 

  49. Wong F, Blei AT, Blendis LM, Thuluvath PJ (2003) A vasopressin receptor antagonist (VPA-985) improves serum sodium concentration in patients with hyponatremia: a multicenter, randomized, placebo-controlled trial. Hepatology 37:182–191

    Article  PubMed  CAS  Google Scholar 

  50. Zeltser D, Rosansky S, van Rensburg H, Verbalis JG, Smith N (2007) Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia. Am J Nephrol 27:447–457

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Harry Raftopoulos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Raftopoulos, H. Diagnosis and management of hyponatremia in cancer patients. Support Care Cancer 15, 1341–1347 (2007). https://doi.org/10.1007/s00520-007-0309-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-007-0309-9

Keywords

Navigation