History and exam

Key diagnostic factors

common

presence of risk factors

Key risk factors include older age; hospitalisation; underlying medical conditions (e.g., congestive heart failure, cirrhosis, nephrotic syndrome, acute kidney injury/chronic kidney disease, hypothyroidism, adrenal insufficiency, malignancies), use of certain medications (e.g., selective serotonin-reuptake inhibitors, thiazide diuretics, desmopressin, oxytocin, carbamazepine or its analogs, vincristine, nicotine, opioids, antipsychotics, chlorpropamide, cyclophosphamide, non-steroidal anti-inflammatory drugs), and ecstasy (methylenedioxy-methamfetamine or MDMA) use.

high fluid intake

Hyponatraemia can occur in the setting of intense exercise (e.g., marathon running, military training, wilderness exploration) due to excessive fluid intake.[3][16]​​[40]​ The presentation is usually acute, symptomatic hyponatraemia with acute cerebral and/or pulmonary oedema.

Primary polydipsia or potomania can cause euvolaemic hyponatraemia.

Potomania is caused by high fluid intake in the setting of very low solute intake. Maximal urinary dilution may be impaired by very low protein intake, and it also reduces with advancing age. It can occur in association with heavy beer drinking, very low-calorie diets with high fluid intake (e.g., the ‘tea and toast’ diet), and crash diets.

High fluid intake can also be iatrogenic (e.g., hospitalised patients receiving intravenous fluids, particularly fluids that are hypotonic to plasma).

fluid losses

Renal water losses can occur with use of diuretics (especially thiazides), salt-wasting nephropathy, cerebral salt-wasting syndrome (a rare cause of hyponatraemia resulting from urinary salt wasting; elevated brain natriuretic peptide has been implicated), and mineralocorticoid deficiency.[3]

Non-renal water losses can occur with gastrointestinal losses (e.g., severe diarrhoea or vomiting) or transdermal losses (e.g., excess sweating).

Third spacing of fluids can also occur in conditions such as pancreatitis and severe hypoalbuminaemia.

history of diabetes mellitus

May be associated with pseudohyponatraemia or true hyponatraemia, due to hyperglycaemia raising serum osmolality causing a dilutional hyponatraemia, and/or in the hypovolaemic hyponatraemia and osmotic diuresis seen in diabetic ketoacidosis.[45]

history of cirrhosis, nephrosis, congestive heart failure

Causes of hypervolaemic hyponatraemia.[3]

nausea/vomiting

Can be symptoms of cerebral oedema, which occurs more frequently in acute hyponatraemia (i.e., onset <48 hours).[3]

mild cognitive symptoms

Include confusion, headache, and balance difficulties.[3]​ Usually symptoms of chronic hyponatraemia (i.e., onset ≥48 hours), but can also occur with acute hyponatraemia (i.e., onset <48 hours).

altered mental status, seizures, coma

Signs of cerebral oedema, which occurs more frequently in acute hyponatraemia (i.e., onset <48 hours).

Patients require prompt management with hypertonic 3% saline.[5]

If patient presents with acute hyponatraemia and a history of altered mental status (e.g., schizophrenia or psychotic depression) with seizures associated with markedly increased water intake over a short period of time, a diagnosis of primary polydipsia should be considered.

low urine output

Can be a sign of volume depletion or may indicate acute kidney injury/chronic kidney disease. However, it also occurs in hypervolaemic hyponatraemia (e.g., heart failure, cirrhosis, nephrotic syndrome).

weight changes

Weight loss is a sign of volume depletion, while significant weight gain is a sign of volume overload.

orthostatic hypotension

Sign of volume depletion.

abnormal jugular venous pressure

Decreased jugular venous pressure is a sign of volume depletion, while increased jugular venous pressure is a sign of volume overload.

poor skin turgor

Sign of volume depletion.

dry mucous membranes

Sign of volume depletion.

absence of axillary sweat

Sign of volume depletion.

oedema

Sign of volume overload.

rales or crackles on lung auscultation

Sign of volume overload.

uncommon

polyuria

Most common in primary polydipsia.

Other diagnostic factors

uncommon

history of hyperlipidaemia or paraproteinaemia

May be associated with pseudohyponatraemia in settings where ion-selective methods are not available for the measurement of serum sodium concentration.[3]

Multiple myeloma is the most common cause of high protein levels causing pseudohyponatraemia.

Risk factors

strong

older age

Hyponatraemia is common in elderly people, especially those who are hospitalised or living in nursing homes.[11][23]​​​ Around 20% of people aged over 65 years have hyponatraemia, rising to 35% of hospitalised patients.[3] Syndrome of inappropriate antidiuretic hormone (SIADH) is the most common cause of hyponatraemia in older people.[4]​​[23]​​​ Renal function, thirst sensation, and hormonal modulators of sodium homeostasis are often impaired; contributing factors such as medication use or an underlying chronic medical condition may be present. 

hospitalisation

Hyponatraemia can be present on admission to hospital, or it can develop (or worsen) during the hospital stay as a result of factors including organ failure, medications, or the post-operative state.[2][11][24] In a large, US-based cohort study that assessed over 50,000 hospital admissions, just under 38% of patients with a normal initial sodium level developed hyponatraemia during admission.[3][7]

selective serotonin-reuptake inhibitor (SSRI) use

Hyponatraemia has been found to occur in up to 32% of patients taking SSRIs.[3][18] It can occur in up to 12% of patients during the first two weeks of treatment and is severe in some patients.[19] Patient factors, such as older age and female gender, may increase the risk of SSRI-associated hyponatraemia.[23]​ Hyponatraemia generally resolves following discontinuation of the SSRI.

thiazide diuretic use

One of the most common causes of hyponatraemia.[3]​​​[12][15][20][23]​​​ Hyponatraemia may appear within days or even years of starting treatment, but will generally resolve once the drug has been discontinued.

underlying medical conditions

Congestive heart failure, cirrhosis, nephrotic syndrome, and acute kidney injury/chronic kidney disease are associated with hypervolaemic hyponatraemia.[3] Hyponatraemia can also occur secondary to a wide range of other underlying medical conditions including sepsis and infection,​ and following acute stroke. In these settings it can indicate a poor prognosis.[25][26]​​​

severe hypothyroidism

Severe hypothyroidism has been associated with hyponatraemia.[3][27][28]​ This is likely to be due to increased vasopressin release and/or upregulation of aquaporin-2 channels.[29]​ Milder hypothyroidism does not appear to be associated with hyponatraemia.[30]

adrenal insufficiency

Primary and secondary adrenal insufficiency has been associated with hyponatraemia due to loss of renal sodium and extracellular fluid volume contraction from reduced secretion of cortisol and aldosterone.[2][3]​​

malignancy

Hyponatraemia commonly occurs with certain malignancies, particularly small cell lung cancer (due to SIADH) where it has been reported to occur in approximately 25% of patients.[31][32]​ Hyponatraemia can also occur with multiple other solid tumours and haematological malignancies.[3][33][34]

use of other medications

Many other medications, aside from selective serotonin-reuptake inhibitors and thiazide diuretics, are associated with hyponatraemia. Desmopressin, oxytocin, carbamazepine or its analogs, vincristine, nicotine, opioids, antipsychotics, chlorpropamide, cyclophosphamide, and non-steroidal anti-inflammatory drugs are examples.[3][17]

MDMA (ecstasy) use

Acute, symptomatic hyponatraemia may occur with the use of the illegal recreational drug ecstasy (methylenedioxy-methamfetamine or MDMA).[3]​ It causes vasopressin release and in the setting of high fluid intake may result in acute cerebral oedema, acute pulmonary oedema, and death.

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