1.2.2 Hyponatremia

Suggested citation: The Endocrine Society. Endocrine Facts and Figures: Hypothalamic-Pituitary. First Edition. 2016.

Hyponatremia is an electrolyte disorder. Serum sodium concentrations < 125 mmol/L are considered an indication of severe hyponatremia, and serum levels < 115 mmol/L are associated with substantial morbidity and increased mortality.59,60

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatremia.61 It’s caused by excess of renal water reabsorption due to inappropriate antidiuretic hormone (vasopressin) secretion.62 Sherlock et al. reported that 62% of cases of hyponatremia resulted from SIADH.63 Prevalence and Incidence

Hyponatremia is the most common electrolyte disorder encountered in hospital inpatients and clinical practice.61,64 Data from NHANES 1999-2004 (n=14,697) showed that the prevalence of US adults (age ≥ 18 years) with hyponatremia (serum sodium < 133-145 mmol/L for years 1999-2002, and <136-144 mmol/L for years 2003-2004) was 1.72%.  Table 10 lists the prevalence of hyponatremia by cause.

Table 10. Hyponatremia by cause
Ireland (n=1,698) patients with hyponatremia Retrospective analysis of hospital data Pituitary disorders  6.25
Traumatic brain injury 9.6
Intracranial neoplasm 15.8
Subarachnoid hemorrhage 19.6
Spinal disorders 0.81

Source: Sherlock et al. 200963 Demographic Differences

Data from NHANES indicated hyponatremia was more common in females as opposed to males (2.1% vs. 1.3%), and patients with hyponatremia were significantly older (52.8 vs. 45 years). Overall, hyponatremia was more common in subjects with comorbidities than those with none (2.3% vs. 1.04%); specifically, hyponatremia was significantly higher among patients with hypertension, diabetes, coronary artery disease, cancer, stroke, chronic obstructive pulmonary disease, and psychiatric disorders.65 Life Expectancy and Mortality

Hyponatremia is associated with greatly increased morbidity and mortality,61 and if not treated appropriately may lead to death.64 Untreated acute hyponatremia can cause substantial morbidity and mortality as a result of osmotically induced cerebral edema, and excessively rapid correction of chronic hyponatremia can cause severe neurologic impairment and death as a result of osmotic demyelination, particularly of the pons.66

Hyponatremia, which can be profoundly symptomatic, has also been linked to longer hospital stays, admission to the ICU, and costly readmissions.63,67-70 A recent analysis of NHANES data reported the overall mortality rate over the period 1999-2006 at 11% for hyponatremic subjects versus 4% for their normal counterparts. In addition, among subjects with hyponatremia, mortality rates were not affected by sex or race/ethnicity.65 Table 11 presents data on factors that have been shown to significantly increase mortality rate among hyponatremic patients.

Table 11. All-cause mortality among hyponatremic patients.
NHANES 1999-2004 (followed-up 2006) US (n=14,679) Sex Males 13
Females 9.8
Race/ethnicity Non-Hispanic whites 12
Non-Hispanic blacks 8.6
Hispanic 6.7
Other 11
Body mass index * Normal weight 17
Obese 0.2
Poverty income ratio * 0-0.99 19
≥ 5 1.6
Comorbidities * No comorbidities 2.5
Coronary artery disease 30
Congestive heart failure 38
Liver disease 37
Kidney disease 32
Cancer 25
Abbreviations: US, United States.
Note: *, factors showing a statistically significant increase in mortality rate (p<0.001).

Source: Mohan et al. 2013 65 Key Trends and Health Outcomes

According to recently published expert panel recommendations on the diagnosis, evaluation, and treatment of hyponatremia, in cases where there is a remote possibility that the primary diagnosis is SIADH and either significant central nervous system symptoms from hyponatremia are present or the starting serum [Na] is 120 mmol/L, hypertonic saline (e.g., 3% NaCl) should be used for the initial diagnostic volume challenge to avoid any risk of lowering the serum [Na] further.71

Initial treatment consists of withholding all diuretics and cautiously repleting the patient with isotonic fluid if central nervous system abnormalities are mild. Clinicians should use hypertonic saline to raise the serum [Na] by 4-8 mmol/L acutely when seizures or a significantly altered level of consciousness are present. However, they should not use furosemide with the hypertonic saline because of the risk of precipitating hypotension, and clinicians should administer a minimum of hypertonic fluid in anticipation of the water diuresis that will ensue.71

The Food and Drug Administration has approved vasopressin receptor antagonists for the management of hyponatremic disorders. However, proper and effective use of these and other therapies requires careful thought and guidance.71


  1. Chung T, Monson J. Hypopituitarism [Updated 6 Feb 2015]. In: De Groot L, Beck-Peccoz P, Chrousos G, eds. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-
  2. Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML, Endocrine S. Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96(6):1587-1609.
  3. Corenblum B. Hypopituitarism. 2011; http://emedicine.medscape.com/article/122287-overview – a0101. Accessed June 3 2015.
  4. Thomson Reuters, IPD Data Analytics. National Center for Health Statistics. National Hospital Discharge Survey. 2010. Accessed June 3, 2015.
  5. Regal M, Paramo C, Sierra SM, Garcia-Mayor RV. Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol (Oxf). 2001;55(6):735-740.
  6. Fernandez-Rodriguez E, Lopez-Raton M, Andujar P, et al. Epidemiology, mortality rate and survival in a homogeneous population of hypopituitary patients. Clin Endocrinol (Oxf). 2013;78(2):278-284.
  7. Castinetti F, Reynaud R, Saveanu A, et al. [Clinical and genetic aspects of combined pituitary hormone deficiencies]. Ann Endocrinol (Paris). 2008;69(1):7-17.
  8. Castinetti F, Reynaud R, Saveanu A, Barlier A, Brue T. Genetic causes of combined pituitary hormone deficiencies in humans. Ann Endocrinol (Paris). 2012;73(2):53-55.
  9. Kelberman D, Rizzoti K, Lovell-Badge R, Robinson IC, Dattani MT. Genetic regulation of pituitary gland development in human and mouse. Endocr Rev. 2009;30(7):790-829.
  10. Takagi M, Ishii T, Inokuchi M, et al. Gradual loss of ACTH due to a novel mutation in LHX4: comprehensive mutation screening in Japanese patients with congenital hypopituitarism. PLoS One. 2012;7(9):e46008.
  11. de Graaff LC, Argente J, Veenma DC, Drent ML, Uitterlinden AG, Hokken-Koelega AC. PROP1, HESX1, POU1F1, LHX3 and LHX4 mutation and deletion screening and GH1 P89L and IVS3+1/+2 mutation screening in a Dutch nationwide cohort of patients with combined pituitary hormone deficiency. Horm Res Paediatr. 2010;73(5):363-371.
  12. Dateki S, Fukami M, Uematsu A, et al. Mutation and gene copy number analyses of six pituitary transcription factor genes in 71 patients with combined pituitary hormone deficiency: identification of a single patient with LHX4 deletion. J Clin Endocrinol Metab. 2010;95(8):4043-4047.
  13. Reynaud R, Gueydan M, Saveanu A, et al. Genetic screening of combined pituitary hormone deficiency: experience in 195 patients. J Clin Endocrinol Metab. 2006;91(9):3329-3336.
  14. Appelman-Dijkstra NM, Kokshoorn NE, Dekkers OM, et al. Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96(8):2330-2340.
  15. Ammirati M, Wei L, Ciric I. Short-term outcome of endoscopic versus microscopic pituitary adenoma surgery: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2013;84(8):843-849.
  16. Schneider HJ, Kreitschmann-Andermahr I, Ghigo E, Stalla GK, Agha A. Hypothalamopituitary dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage: a systematic review. JAMA. 2007;298(12):1429-1438.
  17. Fernandez A, Brada M, Zabuliene L, Karavitaki N, Wass JA. Radiation-induced hypopituitarism. Endocr Relat Cancer. 2009;16(3):733-772.
  18. Abu Dabrh AM, Asi N, Farah WH, et al. Radiotherapy Versus Radiosurgery in Treating Patients with Acromegaly: A Systematic Review and Meta-Analysis. Endocr Pract. 2015;21(8):943-956.
  19. Bostrom JP, Meyer A, Pintea B, et al. Risk-adapted single or fractionated stereotactic high-precision radiotherapy in a pooled series of nonfunctioning pituitary adenomas: high local control and low toxicity. Strahlenther Onkol. 2014;190(12):1095-1103.
  20. Roland Linder DKaFV. Surgery of Pituitary Tumors in Germany: Hypopituitarism, Mortality, Costs and the Effect of Surgeon. The Endocrine Society’s 94th Annual Meeting and Expo, June 23–26, 2012 – Houston, TX 2012; http://press.endocrine.org/doi/abs/10.1210/endo-meetings.2012.NP.16.MON-718. Accessed March 15, 2016.
  21. Bates AS, Van’t Hoff W, Jones PJ, Clayton RN. The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab. 1996;81(3):1169-1172.
  22. Bulow B, Hagmar L, Mikoczy Z, Nordstrom CH, Erfurth EM. Increased cerebrovascular mortality in patients with hypopituitarism. Clin Endocrinol (Oxf). 1997;46(1):75-81.
  23. Tomlinson JW, Holden N, Hills RK, et al. Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet. 2001;357(9254):425-431.
  24. Svensson J, Bengtsson BA, Rosen T, Oden A, Johannsson G. Malignant disease and cardiovascular morbidity in hypopituitary adults with or without growth hormone replacement therapy. J Clin Endocrinol Metab. 2004;89(7):3306-3312.
  25. van Bunderen CC, van Nieuwpoort IC, Arwert LI, et al. Does growth hormone replacement therapy reduce mortality in adults with growth hormone deficiency? Data from the Dutch National Registry of Growth Hormone Treatment in adults. J Clin Endocrinol Metab. 2011;96(10):3151-3159.
  26. Gaillard RC, Mattsson AF, Akerblad AC, et al. Overall and cause-specific mortality in GH-deficient adults on GH replacement. Eur J Endocrinol. 2012;166(6):1069-1077.
  27. Pappachan JM, Raskauskiene D, Kutty VR, Clayton RN. Excess mortality associated with hypopituitarism in adults: a meta-analysis of observational studies. J Clin Endocrinol Metab. 2015;100(4):1405-1411.
  28. Burman P, Mattsson AF, Johannsson G, et al. Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality. Journal of Clinical Endocrinology & Metabolism. 2013;98(4):1466-1475.
  29. Sherlock M, Ayuk J, Tomlinson JW, et al. Mortality in patients with pituitary disease. Endocr Rev. 2010;31(3):301-342.
  30. Nielsen EH, Lindholm J, Laurberg P. Excess mortality in women with pituitary disease: a meta-analysis. Clin Endocrinol (Oxf). 2007;67(5):693-697.
  31. Rosen T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet. 1990;336(8710):285-288.
  32. Schneider HJ, Aimaretti G, Kreitschmann-Andermahr I, Stalla GK, Ghigo E. Hypopituitarism. Lancet. 2007;369(9571):1461-1470.
  33. Littley MD, Shalet SM, Beardwell CG, Ahmed SR, Applegate G, Sutton ML. Hypopituitarism following external radiotherapy for pituitary tumours in adults. Q J Med. 1989;70(262):145-160.
  34. Snyder PJ, Fowble BF, Schatz NJ, Savino PJ, Gennarelli TA. Hypopituitarism following radiation therapy of pituitary adenomas. Am J Med. 1986;81(3):457-462.
  35. Cohen-Inbar O, Ramesh A, Xu Z, Vance ML, Schlesinger D, Sheehan JP. Gamma knife radiosurgery in patients with persistent acromegaly or Cushing’s disease: long-term risk of hypopituitarism. Clin Endocrinol (Oxf). 2016;84(4):524-531.
  36. Fatemi N, Dusick JR, Mattozo C, et al. Pituitary hormonal loss and recovery after transsphenoidal adenoma removal. Neurosurgery. 2008;63(4):709-718; discussion 718-709.
  37. Webb SM, Rigla M, Wagner A, Oliver B, Bartumeus F. Recovery of hypopituitarism after neurosurgical treatment of pituitary adenomas. J Clin Endocrinol Metab. 1999;84(10):3696-3700.
  38. Arafah BM, Kailani SH, Nekl KE, Gold RS, Selman WR. Immediate recovery of pituitary function after transsphenoidal resection of pituitary macroadenomas. J Clin Endocrinol Metab. 1994;79(2):348-354.
  39. Aimaretti G, Ambrosio MR, Benvenga S, et al. Hypopituitarism and growth hormone deficiency (GHD) after traumatic brain injury (TBI). Growth Horm IGF Res. 2004;14 Suppl A:S114-117.
  40. Stochholm K, Gravholt CH, Laursen T, et al. Mortality and GH deficiency: a nationwide study. Eur J Endocrinol. 2007;157(1):9-18.
  41. Johannsson G, Nilsson AG, Bergthorsdottir R, et al. Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation. J Clin Endocrinol Metab. 2012;97(2):473-481.
  42. Attanasio AF, Bates PC, Ho KK, et al. Human growth hormone replacement in adult hypopituitary patients: long-term effects on body composition and lipid status–3-year results from the HypoCCS Database. J Clin Endocrinol Metab. 2002;87(4):1600-1606.
  43. Di Iorgi N, Napoli F, Allegri AE, et al. Diabetes insipidus–diagnosis and management. Horm Res Paediatr. 2012;77(2):69-84.
  44. Maghnie M, Cosi G, Genovese E, et al. Central Diabetes Insipidus in Children and Young Adults. New England Journal of Medicine. 2000;343(14):998-1007.
  45. Di Iorgi N, Allegri AE, Napoli F, et al. Central diabetes insipidus in children and young adults: etiological diagnosis and long-term outcome of idiopathic cases. J Clin Endocrinol Metab. 2014;99(4):1264-1272.
  46. Schreckinger M, Szerlip N, Mittal S. Diabetes insipidus following resection of pituitary tumors. Clin Neurol Neurosurg. 2013;115(2):121-126.
  47. Juul KV, Schroeder M, Rittig S, Norgaard JP. National Surveillance of Central Diabetes Insipidus (CDI) in Denmark: results from 5 years registration of 9309 prescriptions of desmopressin to 1285 CDI patients. J Clin Endocrinol Metab. 2014;99(6):2181-2187.
  48. Nemergut EC, Zuo Z, Jane JA, Jr., Laws ER, Jr. Predictors of diabetes insipidus after transsphenoidal surgery: a review of 881 patients. J Neurosurg. 2005;103(3):448-454.
  49. Kristof RA, Rother M, Neuloh G, Klingmuller D. Incidence, clinical manifestations, and course of water and electrolyte metabolism disturbances following transsphenoidal pituitary adenoma surgery: a prospective observational study. J Neurosurg. 2009;111(3):555-562.
  50. Agha A, Liew A, Finucane F, et al. Conventional glucocorticoid replacement overtreats adult hypopituitary patients with partial ACTH deficiency. Clinical endocrinology. 2004;60(6):688-693.
  51. Aimaretti G, Ambrosio MR, Di Somma C, et al. Residual pituitary function after brain injury-induced hypopituitarism: a prospective 12-month study. J Clin Endocrinol Metab. 2005;90(11):6085-6092.
  52. Ananthakrishnan S. Diabetes insipidus in pregnancy: etiology, evaluation, and management. Endocr Pract. 2009;15(4):377-382.
  53. Aleksandrov N, Audibert F, Bedard MJ, Mahone M, Goffinet F, Kadoch IJ. Gestational diabetes insipidus: a review of an underdiagnosed condition. J Obstet Gynaecol Can. 2010;32(3):225-231.
  54. Saborio P, Tipton GA, Chan JC. Diabetes insipidus. Pediatr Rev. 2000;21(4):122-129; quiz 129.
  55. Hadjizacharia P, Beale EO, Inaba K, Chan LS, Demetriades D. Acute diabetes insipidus in severe head injury: a prospective study. J Am Coll Surg. 2008;207(4):477-484.
  56. Timper K, Fenske W, Kuhn F, et al. Diagnostic Accuracy of Copeptin in the Differential Diagnosis of the Polyuria-polydipsia Syndrome: A Prospective Multicenter Study. J Clin Endocrinol Metab. 2015;100(6):2268-2274.
  57. Vande Walle J, Stockner M, Raes A, Norgaard JP. Desmopressin 30 years in clinical use: a safety review. Curr Drug Saf. 2007;2(3):232-238.
  58. Arima H, Oiso Y, Juul KV, Norgaard JP. Efficacy and safety of desmopressin orally disintegrating tablet in patients with central diabetes insipidus: results of a multicenter open-label dose-titration study. Endocr J. 2013;60(9):1085-1094.
  59. Kennedy PG, Mitchell DM, Hoffbrand BI. Severe hyponatraemia in hospital inpatients. Br Med J. 1978;2(6147):1251-1253.
  60. Gross P, Reimann D, Neidel J, et al. The treatment of severe hyponatremia. Kidney Int Suppl. 1998;64:S6-11.
  61. Hannon MJ, Thompson CJ. The syndrome of inappropriate antidiuretic hormone: prevalence, causes and consequences. Eur J Endocrinol. 2010;162 Suppl 1:S5-12.
  62. Ragnarsson O, Mattsson AF, Monson JP, et al. The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients. Eur J Endocrinol. 2014;171(5):571-579.
  63. Sherlock M, O’Sullivan E, Agha A, et al. Incidence and pathophysiology of severe hyponatraemia in neurosurgical patients. Postgrad Med J. 2009;85(1002):171-175.
  64. Patterson JH. The impact of hyponatremia. Pharmacotherapy. 2011;31(5 Suppl):5S-8S.
  65. Mohan S, Gu S, Parikh A, Radhakrishnan J. Prevalence of hyponatremia and association with mortality: results from NHANES. Am J Med. 2013;126(12):1127-1137 e1121.
  66. Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013;126(10 Suppl 1):S1-42.
  67. Jahangiri A, Wagner J, Tran MT, et al. Factors predicting postoperative hyponatremia and efficacy of hyponatremia management strategies after more than 1000 pituitary operations. J Neurosurg. 2013;119(6):1478-1483.
  68. Callahan MA, Do HT, Caplan DW, Yoon-Flannery K. Economic impact of hyponatremia in hospitalized patients: a retrospective cohort study. Postgrad Med. 2009;121(2):186-191.
  69. Sherlock M, Reulen RC, Alonso AA, et al. ACTH deficiency, higher doses of hydrocortisone replacement, and radiotherapy are independent predictors of mortality in patients with acromegaly. J Clin Endocrinol Metab. 2009;94(11):4216-4223.
  70. Deitelzweig S, Amin A, Christian R, Friend K, Lin J, Lowe TJ. Health care utilization, costs, and readmission rates associated with hyponatremia. Hosp Pract (1995). 2013;41(1):89-95.
  71. Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW, Sterns RH. Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med. 2007;120(11 Suppl 1):S1-21.

Back to Top