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
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
adrenal insufficiency
malignancy
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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