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

Overview

Best diagnostic test to measure hyponatremia, serum sodium < 135 mEq/L, is direct ion-specific electrode potentiometry. Other tests are associated with false results in certain conditions.

Different etiologies of hyponatremia are differentiated based on serum osmolality, urine osmolality, and urine sodium.

To see the different caused of hyponatremia, click here.

Study of choice

Previously, there were two methods to determine serum sodium [1]   :

  • Flame emission spectrophotometry
  • Ion-specific electrode (ISE) potentiometry

ISE potentiometry has two different subtypes: Direct (undiluted) and indirect (diluted).

Direct ISE measures plasma sodium directly from a whole-blood sample and it's not associated with either pseudohyponatremia or pseudonormonatremia.

FES or indirect ISE requires sample dilution before assay [2] and both are associated with pseudohyponatremia.

Sequence of Diagnostic Studies

The most diagnostic studies which can help to diagnose and differentiate between different causes of hyponatremia are: Serum osmolality, urine osmolality, urine sodium.


Biochemical evaluation for finding the etiologies of hyponatremia :

  • Serum sodium
  • Serum osmolality
  • Serum potassium
  • Serum chloride
  • Serum creatinine
  • Serum other solutes
  • Serum urea
  • Blood Glucose
  • Total protein and albumin
  • Serum lipids
  • Total bilirubin and direct bilirubin
  • Red and white cell blood count
  • Serum cortisol
  • Adrenocorticotropine hormone
  • ADH level
  • TSH
  • Urine sodium
  • Urine chloride
  • Urine osmolality
  • Urine for other solutes
  • Fraction excretion of sodium
  • Calculated GFR


For differential diagnosis click here.

Diagnostic Approach to Hyponatremia [3] [4] [5]

 
 
 
 
 
 
 
Serum sodium < 135 mEq/L
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Psuedohyponatremia
• Check for hyperglycemia
• Check for hyperproteinemia
• Check for hyperlipidemia
• Check for other solutes in serum
• Check for sign of Jaundice
• Check for history of operation
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Measure serum Osmolality
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low < 280 momol/kg
 
 
 
 
 
 
 
Normal or High
> 280 momol/kg
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hypotonic Hyponatremia
 
 
 
 
 
 
 
Isoosmolar or Hyperosmolar hyponatremia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
• Low GFR
• History of Thiazide use
 
 
 
 
 
 
 
 
• Post TURP or hysteroscopy (Glycine, Sorbitol)
• Check direct sodium by direct potentiometry if normal measure total protein and lipid
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
Yes
 
Renal failure
Thiazide induce hyponatremia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patients with edema
(pulmonary, peripheral),ascites
 
 
 
Signs and Symptoms of hypovolemia
(↓ BP, Orthostatic hypotension)
 
 
 
 
 
 
 
Heart failure
Cirrhosis
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Less < 25 mEq/L
Hypovolemic Hyponatremia
• Extra renal loss
Gastrointestinal losses, Diuretics, Third space losses
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Measure urine sodium and serum osmolality
 
 
 
 
Measure urine sodium
 
 
25 to 40 mEq/L
• Infuse Isotonic saline 1 liter over 1 hour
• Remeasure urine sodium
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Osm < 100
 
 
 
 
 
 
 
 
 
 
Hight > 40 mEq/L
Hypovolemic Hyponatremia
• Renal loss
 
 
 
 
 
 
 
 
 
 
 
Yes
 
 
 
 
 
 
 
 
 
 
No
 
Urine osmolality measured After therapy initiated
 
Yes
 
 
 
Use of diuretics
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Recovery from one of the followings:
• Mild hypovolemia(Patients given isotonic fluids
Hypopituitarism
(Patients given glucocorticoids))
 
 
 
Low cortisol,
Positive ACTH stimulation

Primary adrenal insufficiency
 
 
 
Urine Na > 40 mEq/L
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Head injury/surgery
Cerebral-salt wasting
 
 
 
 
 
 
 
No
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient with rapid water consumption
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ensure that sodium intake > 150 mEq/L over next 24 hours (infuse 1 liter of isotonic fluid over one or more hour)
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Remeasure urine osmolality and sodium
 
 
 
 
 
 
 
No
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
High-fluid
low-protein diet including:
Beer potomania
• Tea and toast diet
 
Water intoxication:
Psychosis
• Endurance activity (Marathone)
Ecstasy use
 
 
 
 
 
Urine Na >40 or
Urine Osm > 100
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Na < 40 or
Urine Osm < 100
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hypovolemic Hyponatremia
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check for:
• Glucocorticoid deficiency with
Cortisol level and ACTH stimulationand
Hypothyroidism with TSH
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
check morning cortisol and
ACTH stimulation test
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Yes
 
No
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Glucocorticoid deficiency
 
Elevated TSH
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
No
 
 
Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SIAD
Nephrogenic SIAD
Reset Osmostat
 
 
Severe Hypothyroidism
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Evaluate underlying etiology
 
 
 
 
 
 
 
 
 

References

  1. F. S. Apple, D. D. Koch, S. Graves & J. H. Ladenson (1982). "Relationship between the direct-potentiometric and flame-photometric measurement of sodium in the blood". Clinical chemistry. 28 (9): 1931–1935. PMID 7127808. Unknown parameter |month= ignored (help)
  2. Hussain, Iram; Ahmad, Zahid; Garg, Abhimanyu (2015). "Extreme hypercholesterolemia presenting with pseudohyponatremia - a case report and review of the literature". Journal of Clinical Lipidology. 9 (2): 260–264. doi:10.1016/j.jacl.2014.11.007. ISSN 1933-2874.
  3. Adrogué, Horacio J.; Madias, Nicolaos E. (2014). "Diagnosis and Treatment of Hyponatremia". American Journal of Kidney Diseases. 64 (5): 681–684. doi:10.1053/j.ajkd.2014.06.001. ISSN 0272-6386.
  4. Sahay, Manisha; Sahay, Rakesh (2014). "Hyponatremia: A practical approach". Indian Journal of Endocrinology and Metabolism. 18 (6): 760. doi:10.4103/2230-8210.141320. ISSN 2230-8210.
  5. 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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