History and exam

Key diagnostic factors

common

high fluid intake

Hyponatremia 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 hyponatremia with acute cerebral and/or pulmonary edema.

Primary polydipsia or potomania can cause euvolemic hyponatremia.

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., hospitalized 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 hyponatremia resulting from urinary salt wasting; elevated brain natriuretic peptide has been implicated), and mineralocorticoid deficiency.[3]

Nonrenal water losses can occur with gastrointestinal losses (e.g., severe diarrhea or vomiting) or transdermal losses (e.g., excess sweating).

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

history of diabetes mellitus

May be associated with pseudohyponatremia or true hyponatremia, due to hyperglycemia raising serum osmolality causing a dilutional hyponatremia, and/or in the hypovolemic hyponatremia and osmotic diuresis seen in diabetic ketoacidosis.[45]

history of cirrhosis, nephrosis, congestive heart failure

Causes of hypervolemic hyponatremia.[3]

nausea/vomiting

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

mild cognitive symptoms

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

altered mental status, seizures, coma

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

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

If patient presents with acute hyponatremia 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 hypervolemic hyponatremia (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 mucus membranes

Sign of volume depletion.

absence of axillary sweat

Sign of volume depletion.

edema

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 hyperlipidemia or paraproteinemia

May be associated with pseudohyponatremia 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 pseudohyponatremia.

Risk factors

strong

older age

Hyponatremia is common in elderly people, especially those who are hospitalized or living in nursing homes.[11][23]​​​ Around 20% of people ages over 65 years have hyponatremia, rising to 35% of hospitalized patients.[3] Syndrome of inappropriate antidiuretic hormone (SIADH) is the most common cause of hyponatremia 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. 

hospitalization

Hyponatremia 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 postoperative 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 hyponatremia during admission.[3][7]​​

selective serotonin-reuptake inhibitor (SSRI) use

Hyponatremia 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 hyponatremia.[23]​ Hyponatremia generally resolves following discontinuation of the SSRI.

thiazide diuretic use

One of the most common causes of hyponatremia.[3]​​​[12][15][20][23]​​​ Hyponatremia 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 hypervolemic hyponatremia.[3]​ Hyponatremia 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 hyponatremia.[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 hyponatremia.[30]

adrenal insufficiency

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

malignancy

Hyponatremia 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]​ Hyponatremia can also occur with multiple other solid tumors and hematological malignancies.[3][33][34]​​

use of other medications

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

MDMA (ecstasy) use

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

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