Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Causes of hyponatremia in adults

Richard H Sterns, MD
Section Editor
Michael Emmett, MD
Deputy Editor
John P Forman, MD, MSc


Hyponatremia is commonly defined as a serum sodium concentration below 135 meq/L but can vary to a small degree in different clinical laboratories [1,2]. The dilutional fall in serum sodium is in most patients associated with a proportional reduction in the serum osmolality (ie, to a level below 275 mosmol/kg), but there are some exceptions. (See 'Hyponatremia with a high or normal serum osmolality' below.)

In virtually all patients, hyponatremia results from the intake (either oral or intravenous) and subsequent retention of water [3-6]. A water load will, in normal individuals, be rapidly excreted as the dilutional fall in serum osmolality suppresses the release of antidiuretic hormone (ADH, also called vasopressin) (figure 1), thereby allowing excretion of the excess water in a dilute urine. The maximum attainable urine volume in normal individuals on a regular diet is over 10 L/day. This provides an enormous range of protection against the development of hyponatremia since the daily fluid intake in most healthy individuals is less than 2 to 2.5 L/day.

In contrast to the response in normal individuals, patients who develop hyponatremia typically have an impairment in renal water excretion, most often due to an inability to suppress ADH secretion. An uncommon exception occurs in patients with primary polydipsia who can become hyponatremic because they rapidly drink such large quantities of fluid that they overwhelm the excretory capacity of the kidney even though ADH release is appropriately suppressed.

An overview of the causes of hyponatremia will be presented here (table 1). Most of the individual causes of hyponatremia are discussed in detail separately, as are issues related to the diagnosis and treatment of hyponatremia [3,7]. (See "Diagnostic evaluation of adults with hyponatremia" and "Overview of the treatment of hyponatremia in adults".)


Understanding the factors that determine the serum sodium concentration is required to appreciate the factors that promote the development of hyponatremia and what the composition of intravenous fluids must be to correct the hyponatremia.


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Jan 2016. | This topic last updated: Jan 11, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med 2000; 342:1581.
  2. Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant 2014; 29 Suppl 2:i1.
  3. Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders, 5th ed, McGraw-Hill, New York 2001. p.699.
  4. Danziger J, Zeidel ML. Osmotic homeostasis. Clin J Am Soc Nephrol 2015; 10:852.
  5. Sterns RH. Disorders of plasma sodium--causes, consequences, and correction. N Engl J Med 2015; 372:55.
  6. Fenske WK, Christ-Crain M, Hörning A, et al. A copeptin-based classification of the osmoregulatory defects in the syndrome of inappropriate antidiuresis. J Am Soc Nephrol 2014; 25:2376.
  7. Clayton JA, Le Jeune IR, Hall IP. Severe hyponatraemia in medical in-patients: aetiology, assessment and outcome. QJM 2006; 99:505.
  8. EDELMAN IS, LEIBMAN J, O'MEARA MP, BIRKENFELD LW. Interrelations between serum sodium concentration, serum osmolarity and total exchangeable sodium, total exchangeable potassium and total body water. J Clin Invest 1958; 37:1236.
  9. Anderson RJ, Chung HM, Kluge R, Schrier RW. Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann Intern Med 1985; 102:164.
  10. Chung HM, Kluge R, Schrier RW, Anderson RJ. Clinical assessment of extracellular fluid volume in hyponatremia. Am J Med 1987; 83:905.
  11. Pham PC, Pham PM, Pham PT. Vasopressin excess and hyponatremia. Am J Kidney Dis 2006; 47:727.
  12. Alam NH, Majumder RN, Fuchs GJ. Efficacy and safety of oral rehydration solution with reduced osmolarity in adults with cholera: a randomised double-blind clinical trial. CHOICE study group. Lancet 1999; 354:296.
  13. Ashraf N, Locksley R, Arieff AI. Thiazide-induced hyponatremia associated with death or neurologic damage in outpatients. Am J Med 1981; 70:1163.
  14. Schrier RW. An odyssey into the milieu intérieur: pondering the enigmas. J Am Soc Nephrol 1992; 2:1549.
  15. Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med 2007; 356:2064.
  16. SCHWARTZ WB, BENNETT W, CURELOP S, BARTTER FC. A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. Am J Med 1957; 23:529.
  17. Schrier RW. Body water homeostasis: clinical disorders of urinary dilution and concentration. J Am Soc Nephrol 2006; 17:1820.
  18. Derubertis FR Jr, Michelis MF, Bloom ME, et al. Impaired water excretion in myxedema. Am J Med 1971; 51:41.
  19. Hanna FW, Scanlon MF. Hyponatraemia, hypothyroidism, and role of arginine-vasopressin. Lancet 1997; 350:755.
  20. Schrier RW, Bichet DG. Osmotic and nonosmotic control of vasopressin release and the pathogenesis of impaired water excretion in adrenal, thyroid, and edematous disorders. J Lab Clin Med 1981; 98:1.
  21. Skowsky WR, Kikuchi TA. The role of vasopressin in the impaired water excretion of myxedema. Am J Med 1978; 64:613.
  22. Kreisman SH, Hennessey JV. Consistent reversible elevations of serum creatinine levels in severe hypothyroidism. Arch Intern Med 1999; 159:79.
  23. Archambeaud-Mouveroux F, Dejax C, Jadaud JM, et al. [Myxedema coma with hypervasopressinism. 2 cases]. Ann Med Interne (Paris) 1987; 138:114.
  24. Iwasaki Y, Oiso Y, Yamauchi K, et al. Osmoregulation of plasma vasopressin in myxedema. J Clin Endocrinol Metab 1990; 70:534.
  25. Schmitz PH, de Meijer PH, Meinders AE. Hyponatremia due to hypothyroidism: a pure renal mechanism. Neth J Med 2001; 58:143.
  26. Kilpatrick ES. Disorders of sodium balance: hypothyroidism and hyponatraemia: an old wives' tale? BMJ 2006; 332:854.
  27. Warner MH, Holding S, Kilpatrick ES. The effect of newly diagnosed hypothyroidism on serum sodium concentrations: a retrospective study. Clin Endocrinol (Oxf) 2006; 64:598.
  28. Shakir MK, Krook LS, Schraml FV, et al. Symptomatic hyponatremia in association with a low-iodine diet and levothyroxine withdrawal prior to I131 in patients with metastatic thyroid carcinoma. Thyroid 2008; 18:787.
  29. Davison JM, Shiells EA, Philips PR, Lindheimer MD. Influence of humoral and volume factors on altered osmoregulation of normal human pregnancy. Am J Physiol 1990; 258:F900.
  30. Johnson BE, Chute JP, Rushin J, et al. A prospective study of patients with lung cancer and hyponatremia of malignancy. Am J Respir Crit Care Med 1997; 156:1669.
  31. Chute JP, Taylor E, Williams J, et al. A metabolic study of patients with lung cancer and hyponatremia of malignancy. Clin Cancer Res 2006; 12:888.
  32. Johnson BE, Damodaran A, Rushin J, et al. Ectopic production and processing of atrial natriuretic peptide in a small cell lung carcinoma cell line and tumor from a patient with hyponatremia. Cancer 1997; 79:35.
  33. Campbell GA, Rosner MH. The agony of ecstasy: MDMA (3,4-methylenedioxymethamphetamine) and the kidney. Clin J Am Soc Nephrol 2008; 3:1852.
  34. Hartung TK, Schofield E, Short AI, et al. Hyponatraemic states following 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') ingestion. QJM 2002; 95:431.
  35. Holmes SB, Banerjee AK, Alexander WD. Hyponatraemia and seizures after ecstasy use. Postgrad Med J 1999; 75:32.
  36. Holden R, Jackson MA. Near-fatal hyponatraemic coma due to vasopressin over-secretion after "ecstasy" (3,4-MDMA). Lancet 1996; 347:1052.
  37. Cherney DZ, Davids MR, Halperin ML. Acute hyponatraemia and 'ecstasy': insights from a quantitative and integrative analysis. QJM 2002; 95:475.
  38. Henry JA, Fallon JK, Kicman AT, et al. Low-dose MDMA ("ecstasy") induces vasopressin secretion. Lancet 1998; 351:1784.
  39. Wolff K, Tsapakis EM, Winstock AR, et al. Vasopressin and oxytocin secretion in response to the consumption of ecstasy in a clubbing population. J Psychopharmacol 2006; 20:400.
  40. Rosenson J, Smollin C, Sporer KA, et al. Patterns of ecstasy-associated hyponatremia in California. Ann Emerg Med 2007; 49:164.
  41. Farah R, Farah R. Ecstasy (3,4-methylenedioxymethamphetamine)-induced inappropriate antidiuretic hormone secretion. Pediatr Emerg Care 2008; 24:615.
  42. Budisavljevic MN, Stewart L, Sahn SA, Ploth DW. Hyponatremia associated with 3,4-methylenedioxymethylamphetamine ("Ecstasy") abuse. Am J Med Sci 2003; 326:89.
  43. Rogers G, Elston J, Garside R, et al. The harmful health effects of recreational ecstasy: a systematic review of observational evidence. Health Technol Assess 2009; 13:iii.
  44. Ayus JC, Wheeler JM, Arieff AI. Postoperative hyponatremic encephalopathy in menstruant women. Ann Intern Med 1992; 117:891.
  45. van Dijken GD, Blom RE, Hené RJ, et al. High incidence of mild hyponatraemia in females using ecstasy at a rave party. Nephrol Dial Transplant 2013; 28:2277.
  46. Moritz ML, Kalantar-Zadeh K, Ayus JC. Ecstacy-associated hyponatremia: why are women at risk? Nephrol Dial Transplant 2013; 28:2206.
  47. KLEEMAN CR, ADAMS DA, MAXWELL MH. An evaluation of maximal water diuresis in chronic renal disease. I. Normal solute intake. J Lab Clin Med 1961; 58:169.
  48. Tannen RL, Regal EM, Dunn MJ, Schrier RW. Vasopressin-resistant hyposthenuria in advanced chronic renal disease. N Engl J Med 1969; 280:1135.
  49. Hariprasad MK, Eisinger RP, Nadler IM, et al. Hyponatremia in psychogenic polydipsia. Arch Intern Med 1980; 140:1639.
  50. BARLOW ED, DE WARDENER HE. Compulsive water drinking. Q J Med 1959; 28:235.
  51. Rao KJ, Miller M, Moses A. Water intoxication and thioridazine (Mellaril). Ann Intern Med 1975; 82:61.
  52. Illowsky BP, Kirch DG. Polydipsia and hyponatremia in psychiatric patients. Am J Psychiatry 1988; 145:675.
  53. de Leon J. Polydipsia--a study in a long-term psychiatric unit. Eur Arch Psychiatry Clin Neurosci 2003; 253:37.
  54. Kawai N, Baba A, Suzuki T, Shiraishi H. Roles of arginine vasopressin and atrial natriuretic peptide in polydipsia-hyponatremia of schizophrenic patients. Psychiatry Res 2001; 101:39.
  55. Jose CJ, Perez-Cruet J. Incidence and morbidity of self-induced water intoxication in state mental hospital patients. Am J Psychiatry 1979; 136:221.
  56. Goldman MB, Luchins DJ, Robertson GL. Mechanisms of altered water metabolism in psychotic patients with polydipsia and hyponatremia. N Engl J Med 1988; 318:397.
  57. Thompson CJ, Edwards CR, Baylis PH. Osmotic and non-osmotic regulation of thirst and vasopressin secretion in patients with compulsive water drinking. Clin Endocrinol (Oxf) 1991; 35:221.
  58. Thompson CJ, Selby P, Baylis PH. Reproducibility of osmotic and nonosmotic tests of vasopressin secretion in men. Am J Physiol 1991; 260:R533.
  59. LANGGARD H, SMITH WO. Self-induced water intoxication without predisposing illness. N Engl J Med 1962; 266:378.
  60. Gillum DM, Linas SL. Water intoxication in a psychotic patient with normal renal water excretion. Am J Med 1984; 77:773.
  61. Klonoff DC, Jurow AH. Acute water intoxication as a complication of urine drug testing in the workplace. JAMA 1991; 265:84.
  62. Dubovsky SL, Grabon S, Berl T, Schrier RW. Syndrome of inappropriate secretion of antidiuretic hormone with exacerbated psychosis. Ann Intern Med 1973; 79:551.
  63. Goldman MB, Robertson GL, Luchins DJ, Hedeker D. The influence of polydipsia on water excretion in hyponatremic, polydipsic, schizophrenic patients. J Clin Endocrinol Metab 1996; 81:1465.
  64. Goldman MB, Robertson GL, Luchins DJ, et al. Psychotic exacerbations and enhanced vasopressin secretion in schizophrenic patients with hyponatremia and polydipsia. Arch Gen Psychiatry 1997; 54:443.
  65. Flegel KM, Cole CH. Inappropriate antidiuresis during carbamazepine treatment. Ann Intern Med 1977; 87:722.
  66. Cohen BJ, Mahelsky M, Adler L. More cases of SIADH with fluoxetine. Am J Psychiatry 1990; 147:948.
  67. Levine S, McManus BM, Blackbourne BD, Roberts WC. Fatal water intoxication, schizophrenia, and diuretic therapy for systemic hypertension. Am J Med 1987; 82:153.
  68. Stuart CA, Neelon FA, Lebovitz HE. Disordered control of thirst in hypothalamic-pituitary sarcoidosis. N Engl J Med 1980; 303:1078.
  69. Cheng JC, Zikos D, Skopicki HA, et al. Long-term neurologic outcome in psychogenic water drinkers with severe symptomatic hyponatremia: the effect of rapid correction. Am J Med 1990; 88:561.
  70. Tanneau RS, Henry A, Rouhart F, et al. High incidence of neurologic complications following rapid correction of severe hyponatremia in polydipsic patients. J Clin Psychiatry 1994; 55:349.
  71. Alexander RC, Karp BI, Thompson S, et al. A double blind, placebo-controlled trial of demeclocycline treatment of polydipsia-hyponatremia in chronically psychotic patients. Biol Psychiatry 1991; 30:417.
  72. Hilden T, Svendsen TL. Electrolyte disturbances in beer drinkers. A specific "hypo-osmolality syndrome". Lancet 1975; 2:245.
  73. Thaler SM, Teitelbaum I, Berl T. "Beer potomania" in non-beer drinkers: effect of low dietary solute intake. Am J Kidney Dis 1998; 31:1028.
  74. Fox BD. Crash diet potomania. Lancet 2002; 359:942.
  75. Purssell RA, Pudek M, Brubacher J, Abu-Laban RB. Derivation and validation of a formula to calculate the contribution of ethanol to the osmolal gap. Ann Emerg Med 2001; 38:653.
  76. Katz MA. Hyperglycemia-induced hyponatremia--calculation of expected serum sodium depression. N Engl J Med 1973; 289:843.
  77. Hillier TA, Abbott RD, Barrett EJ. Hyponatremia: evaluating the correction factor for hyperglycemia. Am J Med 1999; 106:399.
  78. Weisberg LS. Pseudohyponatremia: a reappraisal. Am J Med 1989; 86:315.
  79. Turchin A, Seifter JL, Seely EW. Clinical problem-solving. Mind the gap. N Engl J Med 2003; 349:1465.