Hyponatremia differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Iqra Qamar M.D.[2], Saeedeh Kowsarnia M.D.[3]

Overview

Different disorders which cause hyponatremia are differentiated based on volume status, clinical presentation, serum and urine osmolality.

Differentiating etiologies of Hyponatremia

Disease Clinical manifestations Paraclinical Findings
Symptoms and Signs Lab Findings
Muscle weakness/ Cramps Oliguria Vomiting/ Diarrhea Volume status JVP Edema Crackles Ascites Tachycardia Hypotension Dry mucous membranes Urine Analysis Serum Osmolality ADH levels
Urine Na Urine Osm FeNa
Renal failure [1] +/- +/- - Hypervolemic + + + + +/- - - >20 - >1% ↓ Normal or ↑
Congestive heart failure [2] +/- - - Hypervolemic + + + + +/- - - <10 - <1% ↓ ↑
Cirrhosis [2] +/- - - Hypervolemic + + + + +/- +/- - <10 - <1% ↓ ↑
SIAD or SIADH [3][4] +/- - - Euvolemic - - - - - - - - >100 - ↓ ↑
Hypothyroidism[5][6][7][8][9] +/- - - Euvolemic - - - - - - - - >100 - ↓ ↑
Adrenal insufficiency[10][11] +/- - - Euvolemic - - - - - + + - >100 - ↓ ↑
Psychogenic polydipsia[12][13][14][15][16][17] +/- - - Euvolemic - - - - - - - - <100 - ↓ ↑
Beer drinker's potomania[18][19][20] +/- - - Euvolemic - - - - - - - - <100 - ↓ ↓
Pregnancy[21] +/- - - Euvolemic - - - - - - - - Variable - ↓ ↓
Anorexia (Chronic malnutrition)[19][18][19][20] +/- - - Euvolemic - - - - +/- +/- +/- - Variable - ↓ -
Diuretic induced hyponatremia[22] +/- + - Hypovolemic - - - - + + + >20 - >1% ↓ -
Non-oliguric ATN[23] +/- - - Hypovolemic - - - - + + + >20 - >1% ↓ -
Diseases causing 3rd spacing (Pancreatitis, SBO)[2] +/- + +/- Hypovolemic - - - - + + + <10 - <1% ↓ -
Gastroenteritis +/- + + Hypovolemic - - - - + + + <10 - <1% ↓ -
Sweating +/- + - Hypovolemic - - - - - +/- +/- <10 - <1% ↓ -
Cerebral salt-losing syndrome[24][25] +/- - +/- Euvolemic - - - - - +/- - >20 >100 > 1% ↓ -

Differentiation between SIADH and Cerebral-salt wasting syndrome:

Condition Urine sodium Urine volume Blood pressure Serum uric acid Serum urea concentration Clinical features
SIADH[3][4] > 30 ↔ , ↓ ↔ ↓ ↔ , ↓ No sign of hypovolemia, Normal or positive fluid balance with absence of weight loss, CVP > 6 cm of water
Cerebral-salt-wasting syndrome >> 30 ↑ ↔ , orthostatic hypotension ↓ ↔ , ↑ Clinical signs of hypovolemia, such as hypotension, dry mucous membranes, tachycardia, or postural hypotension, Negative fluid balance or weight loss, CVP < 6 cm of water

Approach to differential diagnosis

Biochemical evaluation for finding the etiologies of hyponatremia [26][27][28]:

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2

 
 
 
 
 
 
 
 
Serum Na ≤ 135 meq/L
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check for:
• Serum osmolality
• Urine osmolality
• Urea
• Glucose
• Urine chloride
• Urine Na
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normotonicity
275–295 mOsm/kg
•Hyperlipidemia
•Hyperproteinemia
•Glycine
 
 
 
 
Hypertonicity
> 295 mOsm/kg
• Glucose
• Mannitol
• Glycine
• Severe azotemia
 
 
 
 
Hypotonicity
<275 mOsm/kg
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
UOsm < 100mOsm/kg
 
UOsm > 200mOsm/kg
 
 
UOsm 100–200mOsm/kg
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Conditions
•Polydipsia
•↓ solute excertion
(Beer potomania
,Tea & toast diet)
 
 
 
 
 
 
 
Conditions
•Polydipsia
•↓ solute excertion
(Beer potomania
,Tea & toast diet)
•Rule out SIAD
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hypovolemia
Based on history & physical exam
 
 
 
 
 
 
 
Hypervolemia
 
 
 
 
 
 
 
 
 
 
Euvolemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
UNa < 30 mEq/L
 
Variable UNa
 
UNa > 30 mEq/L
 
UNa < 30 mEq/L
 
UNa > 30 mEq/L
 
Variable UNa
 
UNa < 20 mEq/L
 
> 20 UNa < 40 mEq/L
 
UNa > 40 mEq/L
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Extrarenal losses
•Vomiting (Ucl ↓)
•Diarrhea
•Pancreatitis
•Sweating
•Small bowel obstruction
 
Variable UNa
•Diuretic use
Discontinue diuretics if UNa is still abnormal
 
Renal losses
•Osmotic diuresis (glucose, urea,bicarbonaturia)
•Salt-Iosing nephropathy
•Addison disease
•CSW
 
Conditions
•Heart failure
•Liver disease
•Nephrotic syndrome
 
Conditions
•Chronic kidney disease
•Diuretic use in:
Heart failure
Liver disease
Nephrotic syndrome
 
Discontinue diuretics if PNa normalize it's not SIAD if it's not normalized
 
Probable hypovolemia
 
Hypovolemia or euvolemia
 
•Probable euvolemia
•SIAD
•Cortisol deficiency
•Hypothyroidism
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer 0.9% saline
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Normalize PNa
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administer 1–2 L 0.9% saline
 
 
 
 
 
 
 
 
 
 
 
 
Failure to normalize PNa
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hypovolemia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PNa decreases or no change
 
 
 
 
 
 
 
 
 
 
 
 
PNa increases
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Decreasing UOsm
 
No change in UOsm but UNa increases
 
 
 
 
 
 
 
 
 
 
SIAD
 
 
 
 
 
 
No change in UOsm but UNa increases
 
 
Decreased UNa
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hypovolemia
 
Salt-depleted SIAD
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hypovolemia
 
 
Decreasing Uosm
 
 
Administer additional saline
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No change in UOsm
but UNa increases
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Salt-depleted SIAD

References

  1. ↑ Tannen RL, Regal EM, Dunn MJ, Schrier RW (May 1969). "Vasopressin-resistant hyposthenuria in advanced chronic renal disease". N. Engl. J. Med. 280 (21): 1135–41. doi:10.1056/NEJM196905222802101. PMID 5782121.
  2. ↑ 2.0 2.1 2.2 Schrier RW (May 1992). "An odyssey into the milieu intérieur: pondering the enigmas". J. Am. Soc. Nephrol. 2 (11): 1549–59. PMID 1610976.
  3. ↑ 3.0 3.1 Tian W, Fu Y, Garcia-Elias A, Fernández-Fernández JM, Vicente R, Kramer PL, Klein RF, Hitzemann R, Orwoll ES, Wilmot B, McWeeney S, Valverde MA, Cohen DM (August 2009). "A loss-of-function nonsynonymous polymorphism in the osmoregulatory TRPV4 gene is associated with human hyponatremia". Proc. Natl. Acad. Sci. U.S.A. 106 (33): 14034–9. doi:10.1073/pnas.0904084106. PMC 2729015. PMID 19666518.
  4. ↑ 4.0 4.1 Gitelman SE, Feldman BJ, Rosenthal SM (July 2006). "Nephrogenic syndrome of inappropriate antidiuresis: a novel disorder in water balance in pediatric patients". Am. J. Med. 119 (7 Suppl 1): S54–8. doi:10.1016/j.amjmed.2006.05.008. PMID 16843086.
  5. ↑ Ellison DH, Berl T (May 2007). "Clinical practice. The syndrome of inappropriate antidiuresis". N. Engl. J. Med. 356 (20): 2064–72. doi:10.1056/NEJMcp066837. PMID 17507705.
  6. ↑ SCHWARTZ WB, BENNETT W, CURELOP S, BARTTER FC (October 1957). "A syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone". Am. J. Med. 23 (4): 529–42. PMID 13469824.
  7. ↑ Schrier RW (July 2006). "Body water homeostasis: clinical disorders of urinary dilution and concentration". J. Am. Soc. Nephrol. 17 (7): 1820–32. doi:10.1681/ASN.2006030240. PMID 16738014.
  8. ↑ Derubertis FR, Michelis MF, Bloom ME, Mintz DH, Field JB, Davis BB (July 1971). "Impaired water excretion in myxedema". Am. J. Med. 51 (1): 41–53. PMID 5570319.
  9. ↑ Schrier RW, Bichet DG (July 1981). "Osmotic and nonosmotic control of vasopressin release and the pathogenesis of impaired water excretion in adrenal, thyroid, and edematous disorders". J. Lab. Clin. Med. 98 (1): 1–15. PMID 7019365.
  10. ↑ Warner MH, Holding S, Kilpatrick ES (May 2006). "The effect of newly diagnosed hypothyroidism on serum sodium concentrations: a retrospective study". Clin. Endocrinol. (Oxf). 64 (5): 598–9. doi:10.1111/j.1365-2265.2006.02489.x. PMID 16649984.
  11. ↑ Shakir MK, Krook LS, Schraml FV, Hays JH, Clyde PW (July 2008). "Symptomatic hyponatremia in association with a low-iodine diet and levothyroxine withdrawal prior to I131 in patients with metastatic thyroid carcinoma". Thyroid. 18 (7): 787–92. doi:10.1089/thy.2008.0050. PMID 18631009.
  12. ↑ Hariprasad MK, Eisinger RP, Nadler IM, Padmanabhan CS, Nidus BD (December 1980). "Hyponatremia in psychogenic polydipsia". Arch. Intern. Med. 140 (12): 1639–42. PMID 7458496.
  13. ↑ BARLOW ED, DE WARDENER HE (April 1959). "Compulsive water drinking". Q. J. Med. 28 (110): 235–58. PMID 13658352.
  14. ↑ Rao KJ, Miller M, Moses A (January 1975). "Water intoxication and thioridazine (Mellaril)". Ann. Intern. Med. 82 (1): 61. PMID 1235764.
  15. ↑ Illowsky BP, Kirch DG (June 1988). "Polydipsia and hyponatremia in psychiatric patients". Am J Psychiatry. 145 (6): 675–83. doi:10.1176/ajp.145.6.675. PMID 3285701.
  16. ↑ de Leon J (February 2003). "Polydipsia--a study in a long-term psychiatric unit". Eur Arch Psychiatry Clin Neurosci. 253 (1): 37–9. doi:10.1007/s00406-003-0403-z. PMID 12664312.
  17. ↑ Kawai N, Baba A, Suzuki T, Shiraishi H (February 2001). "Roles of arginine vasopressin and atrial natriuretic peptide in polydipsia-hyponatremia of schizophrenic patients". Psychiatry Res. 101 (1): 39–45. PMID 11223118.
  18. ↑ 18.0 18.1 Hilden T, Svendsen TL (August 1975). "Electrolyte disturbances in beer drinkers. A specific "hypo-osmolality syndrome"". Lancet. 2 (7928): 245–6. PMID 49796.
  19. ↑ 19.0 19.1 19.2 Thaler SM, Teitelbaum I, Berl T (June 1998). ""Beer potomania" in non-beer drinkers: effect of low dietary solute intake". Am. J. Kidney Dis. 31 (6): 1028–31. PMID 9631849.
  20. ↑ 20.0 20.1 Fox BD (March 2002). "Crash diet potomania". Lancet. 359 (9310): 942. PMID 11918914.
  21. ↑ Davison JM, Shiells EA, Philips PR, Lindheimer MD (April 1990). "Influence of humoral and volume factors on altered osmoregulation of normal human pregnancy". Am. J. Physiol. 258 (4 Pt 2): F900–7. doi:10.1152/ajprenal.1990.258.4.F900. PMID 2330984.
  22. ↑ Ashraf N, Locksley R, Arieff AI (June 1981). "Thiazide-induced hyponatremia associated with death or neurologic damage in outpatients". Am. J. Med. 70 (6): 1163–8. PMID 7234886.
  23. ↑ KLEEMAN CR, ADAMS DA, MAXWELL MH (August 1961). "An evaluation of maximal water diuresis in chronic renal disease. I. Normal solute intake". J. Lab. Clin. Med. 58: 169–84. PMID 13756614.
  24. ↑ Singh S, Bohn D, Carlotti AP, Cusimano M, Rutka JT, Halperin ML (November 2002). "Cerebral salt wasting: truths, fallacies, theories, and challenges". Crit. Care Med. 30 (11): 2575–9. doi:10.1097/01.CCM.0000034676.11528.E4. PMID 12441772.
  25. ↑ Taplin CE, Cowell CT, Silink M, Ambler GR (December 2006). "Fludrocortisone therapy in cerebral salt wasting". Pediatrics. 118 (6): e1904–8. doi:10.1542/peds.2006-0702. PMID 17101713.
  26. ↑ Spasovski, Goce; Vanholder, Raymond; Allolio, Bruno; Annane, Djillali; Ball, Steve; Bichet, Daniel; Decaux, Guy; Fenske, Wiebke; Hoorn, Ewout J.; Ichai, Carole; Joannidis, Michael; Soupart, Alain; Zietse, Robert; Haller, Maria; van der Veer, Sabine; Van Biesen, Wim; Nagler, Evi (2014). "Clinical practice guideline on diagnosis and treatment of hyponatraemia". Nephrology Dialysis Transplantation. 29 (suppl_2): i1–i39. doi:10.1093/ndt/gfu040. ISSN 1460-2385.
  27. ↑ Wiebke Fenske, Sebastian K. G. Maier, Anne Blechschmidt, Bruno Allolio & Stefan Stork (2010). "Utility and limitations of the traditional diagnostic approach to hyponatremia: a diagnostic study". The American journal of medicine. 123 (7): 652–657. doi:10.1016/j.amjmed.2010.01.013. PMID 20609688. Unknown parameter |month= ignored (help)
  28. ↑ E. J. Hoorn, M. L. Halperin & R. Zietse (2005). "Diagnostic approach to a patient with hyponatraemia: traditional versus physiology-based options". QJM : monthly journal of the Association of Physicians. 98 (7): 529–540. doi:10.1093/qjmed/hci081. PMID 15955797. Unknown parameter |month= ignored (help)

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