Hyponatremia

Risk factors

• Diuretic use, especially thiazides (HCTZ, chlorthalidone)
• SIADH triggers: malignancy (small cell lung), CNS disease (stroke, hemorrhage, infection), pulmonary disease (pneumonia, TB), drugs (SSRIs, carbamazepine, MDMA, antipsychotics)
• Heart failure, cirrhosis, nephrotic syndrome (effective arterial underfilling)
• Adrenal insufficiency, hypothyroidism
• Polydipsia (psychogenic, beer potomania, tea-and-toast)
• Postoperative, hypotonic IV fluid administration
• Exercise-associated hyponatremia (marathon runners over-hydrating with hypotonic fluids)
• Desmopressin (DDAVP) for DI, nocturnal enuresis, or bleeding disorders, especially with high fluid intake (e.g., continued into the antidiuretic phase after pituitary surgery)

Pathophysiology

True hypotonic hyponatremia results from excess water relative to sodium. ADH-driven water retention exceeds urinary water excretion capacity. Causes are categorized by volume status: hypovolemic (volume loss replaced with hypotonic fluid), euvolemic (SIADH, hypothyroid, adrenal insufficiency), hypervolemic (HF, cirrhosis, CKD/nephrotic — total body Na increased but water more so). Pseudohyponatremia: severe hyperlipidemia or hyperproteinemia causes lab artifact with normal plasma water Na.

Clinical presentation

Differential diagnosis

• Hypovolemic hyponatremia — Volume depletion + low urine Na (<20) + high urine osm; GI losses, diuretics (high urine Na if active), bleeding
• SIADH (euvolemic) — Normal volume, low serum osm, INAPPROPRIATELY concentrated urine (osm >100), urine Na >40, normal thyroid/adrenal function
• Hypothyroidism / adrenal insufficiency — Test TSH, cortisol; mimic SIADH labs; correct hormone deficit
• Polydipsia / low solute intake — Dilute urine (<100 mOsm/kg), high water intake (psychogenic) or low solute (beer potomania)
• Hypervolemic hyponatremia — Edema, ascites; HF, cirrhosis, nephrotic syndrome; urine Na <20 (except CKD)
• Pseudohyponatremia — Severe hyperlipidemia, hyperproteinemia (multiple myeloma); normal measured osmolality
• Translocational hyponatremia — Hyperglycemia, mannitol; correct Na = measured Na + 1.6 × ((glucose - 100)/100)
• Cerebral salt wasting — After SAH, neurosurgery, or other acute CNS injury; high urine Na and concentrated urine like SIADH, but truly hypovolemic (orthostasis, negative fluid balance); treat with isotonic or hypertonic saline, not fluid restriction

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Serum Na <135] --> B[Serum osmolality]
  B -->|Normal/High| C[Pseudohyponatremia<br/>or hyperglycemia/mannitol]
  B -->|Low <275| D[True hypotonic<br/>hyponatremia]
  D --> E[Assess volume status]
  E -->|Hypovolemic| F[Urine Na]
  F -->|<20| G[Extrarenal loss<br/>GI, skin, blood]
  F -->|>40| H[Renal loss<br/>diuretic, adrenal insuff]
  E -->|Euvolemic| I[Urine osm]
  I -->|<100| J[Primary polydipsia<br/>low solute]
  I -->|>100| K[SIADH, hypothyroid,<br/>adrenal insuff]
  E -->|Hypervolemic| L[HF, cirrhosis,<br/>nephrotic, CKD]

Treatment

Complications

• Osmotic demyelination syndrome (formerly central pontine myelinolysis) — from overly rapid correction; presents days later with dysarthria, dysphagia, paraparesis, locked-in syndrome; irreversible
• Cerebral edema and herniation from severe acute hyponatremia
• Seizures
• Falls and fractures (chronic mild hyponatremia)
• Increased mortality in hospitalized patients

PANCE pearls

• First step in hyponatremia evaluation: check serum osmolality. Low (<275) = true hypotonic; normal = pseudohyponatremia; high = translocational (hyperglycemia, mannitol).
• SIADH diagnostic criteria: hypotonic hyponatremia + euvolemia + urine osm >100 + urine Na >40 + normal thyroid and adrenal function + no diuretics.
• Correct chronic hyponatremia SLOWLY: max 8-10 mEq/L per 24 hours to avoid osmotic demyelination syndrome. Higher-risk patients (alcoholics, malnourished, hypokalemic): even more cautious.
• Acute symptomatic hyponatremia (<48 h): 3% hypertonic saline is appropriate emergency treatment regardless of chronicity concerns.
• Pseudohyponatremia clue: normal serum osmolality despite low measured Na (lab artifact from hypertriglyceridemia, hyperproteinemia).
• Hyperglycemia correction formula: corrected Na = measured Na + 1.6 × ((glucose − 100)/100). Each 100 mg/dL glucose rise lowers Na ~1.6 mEq/L.
• Isotonic (0.9%) saline can lower the sodium further in SIADH, especially when urine osmolality is high (above roughly 500 mOsm/kg), because the salt is excreted in a small volume of concentrated urine and the water is retained; use fluid restriction, or 3% saline for moderately severe or severe symptoms such as confusion or seizures.

References

• European Society 2014 — Clinical practice guideline on diagnosis and treatment of hyponatraemia (Spasovski et al., Eur J Endocrinol 2014)
• Expert Panel 2013 — Diagnosis, Evaluation, and Treatment of Hyponatremia: Expert Panel Recommendations (Verbalis et al., Am J Med 2013)