What are the causes of euvolemic hyponatremia?

Causes of Euvolemic Hyponatremia

The most common cause of euvolemic hyponatremia is Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), followed by hypothyroidism and adrenal insufficiency. 1, 2, 3

Diagnostic Criteria for Euvolemic Hyponatremia

Euvolemic hyponatremia is characterized by:

• Hyponatremia (serum sodium < 134 mEq/L)
• Normal volume status (no edema or signs of dehydration)
• Hypoosmolality (plasma osmolality < 275 mosm/kg)
• Inappropriately high urine osmolality (> 500 mosm/kg)
• Inappropriately high urinary sodium concentration (> 20-40 mEq/L)
• Absence of hypothyroidism, adrenal insufficiency, volume depletion, heart failure, or cirrhosis 1

Major Causes of Euvolemic Hyponatremia

1. Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

SIADH is the most common cause of euvolemic hyponatremia 3. It can be caused by:

• Malignancies:

  • Small cell lung cancer (most common)
  • Other lung cancers (squamous cell carcinoma, adenocarcinoma)
  • Other malignancies 1

• Medications:

  • Chemotherapeutic agents (platinum-based chemotherapy, vinca alkaloids)
  • Antidepressants
  • Anticonvulsants
  • Opioids
  • NSAIDs
  • Antipsychotics 1, 4

• Pulmonary disorders:

  • Pneumonia
  • Tuberculosis
  • Lung abscess 1

• Central nervous system disorders:

  • Stroke
  • Hemorrhage
  • Trauma
  • Infections 4

• Other causes:

  • Novel cancer immunotherapies 1
  • Post-operative state with hypotonic fluid administration 5

2. Endocrine Disorders

• Hypothyroidism: Decreased cardiac output and glomerular filtration rate lead to increased ADH release 2, 4
• Adrenal insufficiency: Cortisol deficiency results in increased ADH secretion 2, 4

3. Reset Osmostat Syndrome

• A variant of SIADH where the threshold for ADH release is reset to a lower serum osmolality 5, 4

4. Psychogenic Polydipsia

• Excessive water intake overwhelms the kidney's ability to excrete free water 4

5. Exercise-Associated Hyponatremia

• Occurs in endurance athletes due to excessive water intake and inappropriate ADH secretion 4

Laboratory Findings in Euvolemic Hyponatremia

Parameter	Finding
Serum sodium	< 134 mEq/L
Serum osmolality	< 275 mosm/kg
Urine osmolality	> 500 mosm/kg (inappropriately high)
Urine sodium	> 20-40 mEq/L
Serum uric acid	< 4 mg/dL (in SIADH)
Volume status	Clinically euvolemic

Clinical Pitfalls and Caveats

1. Diagnostic challenges: Distinguishing between hypovolemic and euvolemic hyponatremia can be difficult clinically. Careful assessment of volume status is crucial 4, 6.

2. Endocrinopathy workup: Although the yield of testing for hypothyroidism and adrenal insufficiency in euvolemic hyponatremia may be low (1.6% in one study), these conditions are easily treatable and potentially life-threatening, so evaluation is still recommended 2.

3. Medication review: Always conduct a thorough medication review, as many drugs can cause SIADH, especially in cancer patients receiving chemotherapy or immunotherapy 1.

4. Paraneoplastic phenomenon: In cancer patients, SIADH may be the first manifestation of malignancy, particularly small cell lung cancer 1.

5. Clinical consequences: Even mild chronic hyponatremia can lead to cognitive impairment, gait disturbances, increased falls, and fractures 6.

6. Diagnostic exclusion: The diagnosis of SIADH requires the exclusion of other causes of euvolemic hyponatremia, particularly hypothyroidism and adrenal insufficiency 5, 2.

By understanding the various causes of euvolemic hyponatremia and their diagnostic criteria, clinicians can implement appropriate treatment strategies to address the underlying etiology and prevent complications associated with this common electrolyte disorder.