Investigations
1st investigations to order
serum sodium concentration
serum electrolytes, urea, creatinine, and glucose
Test
Should be ordered in all patients with suspected hyponatraemia.
May reveal other electrolyte abnormalities or renal impairment.
Serum glucose (random or fasting) should be checked to exclude hyperglycaemia-associated hyponatraemia. If the patient is hyperglycaemic, a sodium correction formula should be used. If the glucose level is >5.5 mmol/L (100 mg/dL), the most accurate correction formula is: corrected sodium (mmol/L) = measured sodium (mmol/L) + 0.024 {(glucose [mmol/L] x 18)-100}. This formula should be used to determine if true hyponatraemia is present.[42]
Result
variable
serum osmolality
Test
Serum osmolality can be used to differentiate between hypotonic and hypertonic hyponatraemia.[2][3] [ Osmolality Estimator (serum) Opens in new window ]
Serum osmolality <275 mmol/kg: indicates hypotonic hyponatraemia.
Serum osmolality >295 mmol/kg: indicates hypertonic hyponatraemia.
Serum osmolality normal: indicates isotonic hyponatraemia (pseudohyponatraemia).
Result
variable
urine sodium concentration
Test
Ordered to confirm the presence of hypovolaemia or euvolaemia.
A spot urine test allows urinary sodium concentration to be measured quickly and conveniently.
Urine sodium concentration, in combination with the volume status of the patient from examination, can provide further clues to the classification and aetiology.
In hypovolaemic hyponatraemia, urine sodium concentration >20 mmol/L indicates renal sodium loss (e.g., diuretics), and ≤20 mmol/L indicates non-renal sodium loss (e.g., gastrointestinal losses).
In hypervolaemic hyponatraemia, urine sodium concentration >20 mmol/L indicates acute kidney injury/chronic kidney disease or diuretic use, and ≤20 mmol/L indicates congestive heart failure, cirrhosis, or nephrotic syndrome.
In euvolaemic hyponatraemia, urine sodium concentration is >20 mmol/L in most patients; however, patients with a concomitant low sodium intake may have a low urinary sodium.
Result
variable
urine osmolality
Test
Used to further evaluate the cause of euvolaemic hyponatraemia.
High (≥300 mmol/kg): indicates syndrome of inappropriate antidiuretic hormone (SIADH) due to the inappropriate dilution of plasma as a result of pathological vasopressin release, or may also be due to medication-related effects.[2][5]
Intermediate (150-300 mmol/kg): indicates potomania or a partial effect of medications or mild SIADH in conjunction with high fluid intake.[5]
Low (<100-150 mmol/kg): indicates primary polydipsia.[5]
Note: in hyponatraemia due to prolonged physical exercise with high fluid intake urine osmolality is high initially reflecting vasopressin release. This is followed by low urine osmolality as self-correction and aquaresis (loss of water) occur.
Result
variable
urine electrolytes
Test
Should be ordered in all patients with hyponatraemia to determine electrolyte-free water excretion.
Result
variable
urine flow rate
Test
Volume of urine excreted in a specific time period.
Should be ordered in all patients with hyponatraemia to determine electrolyte-free water excretion.
Result
variable
electrolyte-free water excretion
Test
Should be calculated in patients with hyponatraemia using the following formula: electrolyte-free water excretion = V x [1 - (UNa + UK)/(PNa)], where V is the urine flow rate, UNa is the urine concentration of sodium (mmol/L), UK is the urine concentration of potassium (mmol/L), and PNa is the plasma concentration of sodium (mmol/L).
Resulting value indicates how much electrolyte-free water is being lost through the urine at any given time (per day). Can be used to help determine if water is being retained (negative value) as in syndrome of inappropriate antidiuretic hormone secretion (SIADH), or excreted (positive value) as in polydipsia or potomania.[43][44]
Helps to determine the treatment plan by determining ongoing water gains or losses.
Result
negative (e.g., SIADH); positive (e.g., polydipsia, potomania)
fractional excretion of sodium
Test
Although a spot urine sodium test can be helpful if the result is very low, the fractional excretion of sodium provides a more accurate assessment of volume status as it corrects for the effect of variations in urine volume on the urine sodium. [ Fractional Excretion of Sodium (SI units) Opens in new window ]
Calculated using the following formula: [(urinary sodium concentration x plasma creatinine concentration)/(plasma sodium concentration × urinary creatinine concentration)] x 100%.
A value of <1% usually indicates pre-renal causes of hyponatraemia.
Result
variable
thyroid-stimulating hormone
Test
Order in patients with euvolaemic hyponatraemia. Other thyroid function tests may also be needed to determine whether primary or secondary hypothyroidism is present.
Hypothyroidism must be excluded for a diagnosis of syndrome of inappropriate antidiuretic hormone to be made.
Result
may exclude thyroid dysfunction
serum cortisol level and/or adrenocorticotrophic hormone test
Test
Order in patients with euvolaemic hyponatraemia.
Adrenal insufficiency must be excluded for a diagnosis of syndrome of inappropriate antidiuretic hormone to be made.
Result
may exclude adrenal insufficiency
serum lipids and serum protein electrophoresis
Test
Normal in true hyponatraemia. Elevated lipids or proteins can cause pseudohyponatraemia.
Most common cause of high serum proteins is multiple myeloma.
Result
may exclude pseudohyponatraemia
Investigations to consider
CT brain, chest, abdomen/pelvis
Test
Ordered to identify potential causes of syndrome of inappropriate antidiuretic hormone (SIADH; e.g., malignancy such as small cell lung cancer, gastrointestinal tract cancers; central nervous system disorders such as subarachnoid haemorrhage; or other pulmonary disease such as pneumonia) and should be guided by history and physical examination.[4][31]
At times, SIADH may be the presenting finding of a malignancy, or it may precede the malignancy diagnosis.
Result
may reveal possible causes of SIADH
other tests targeted at evaluating the underlying cause
Test
Other tests may be required, as determined by the history and examination, to evaluate the underlying cause, including FBC, LFTs, abdominal ultrasound, chest x-ray, ECG, echocardiogram, renal/liver biopsy, serum albumin, urinalysis, and GFR.
Result
variable (depending on cause)
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