What are the causes of mild hyponatremia with a serum sodium level of 135 mmol/L and normal other electrolytes?

Causes of Mild Hyponatremia (Serum Sodium 135 mmol/L)

A serum sodium of 135 mmol/L represents the threshold definition of hyponatremia and warrants evaluation to identify the underlying cause, even though it is classified as mild and often asymptomatic. 1

Clinical Significance

While 135 mmol/L is at the borderline of normal (hyponatremia is defined as <135 mmol/L), even mild hyponatremia in this range is associated with:

• Increased fall risk - 21% of hyponatremic patients present with falls compared to 5% of normonatremic patients 1
• Cognitive impairment and gait disturbances 2
• Increased mortality risk - hyponatremic patients are 7 times more likely to die in hospital 1
• Higher fracture rates over long-term follow-up 2

Primary Causes by Volume Status

Hypervolemic Hyponatremia (Most Common in Clinical Practice)

Cirrhosis with ascites is a leading cause, occurring in approximately 60% of cirrhotic patients due to:

• Non-osmotic hypersecretion of vasopressin 3
• Enhanced proximal nephron sodium reabsorption 3
• Impaired free water clearance 1
• Systemic vasodilation from portal hypertension 3

Heart failure causes hypervolemic hyponatremia through:

• Increased ADH release despite volume overload 3
• Decreased effective arterial blood volume 3

Euvolemic Hyponatremia

Syndrome of Inappropriate Antidiuretic Hormone (SIADH) is characterized by:

• Inappropriate urinary concentration (urine osmolality >300 mOsm/kg) 3
• Urine sodium >20-40 mmol/L 3
• Normal thyroid, adrenal, and renal function 3

Common SIADH causes include:

• Malignancy (especially small cell lung cancer affecting 1-5% of patients) 3
• CNS disorders 4
• Pulmonary disease 4
• Medications (see below) 5

Hypovolemic Hyponatremia

Diuretic-induced hyponatremia occurs in 8-30% of patients on diuretics:

• Loop diuretics cause hypokalaemia and impaired free water excretion 1
• Thiazide diuretics are particularly implicated 5

Gastrointestinal losses from:

• Diarrhea, vomiting, or other GI fluid losses 4, 6

Medication-Induced Causes

Commonly implicated drugs include:

• Diuretics (thiazides and loop diuretics) - most common drug cause 1, 5
• Antidepressants (SSRIs, SNRIs) 5
• Antiepileptics (carbamazepine, oxcarbazepine) 5
• Antihypertensives (ACE inhibitors, ARBs) 5
• Proton pump inhibitors 5
• Antibiotics 5

Other Important Causes

Excessive free water intake:

• Exercise-associated hyponatremia from excessive water consumption 7
• Psychogenic polydipsia 7

Beer potomania:

• Very low-salt diet combined with excessive beer consumption 3
• Low solute intake impairing free water excretion 3

Hypothyroidism and adrenal insufficiency:

• Must be excluded in euvolemic hyponatremia 3

Diagnostic Approach for Sodium 135 mmol/L

Initial workup should include:

• Serum and urine osmolality 3
• Urine sodium concentration 3
• Assessment of extracellular fluid volume status (orthostatic vitals, skin turgor, edema, ascites) 3
• Thyroid-stimulating hormone 3
• Serum creatinine and BUN 3
• Medication review 5

Key diagnostic parameters:

• Urine sodium <30 mmol/L suggests hypovolemic hyponatremia (71-100% positive predictive value for saline responsiveness) 3
• Urine sodium >20 mmol/L with high urine osmolality (>500 mOsm/kg) suggests SIADH 3
• Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH 3

Critical Pitfalls to Avoid

Do not dismiss mild hyponatremia as clinically insignificant - even at 135 mmol/L, it warrants investigation and may indicate worsening hemodynamic status, particularly in liver disease 3

In neurosurgical patients, even mild hyponatremia requires closer monitoring as it may indicate cerebral salt wasting or SIADH 3

Distinguish between SIADH and cerebral salt wasting in neurological patients, as treatment approaches differ fundamentally (fluid restriction vs. volume replacement) 1, 3