How do you diagnose and manage Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

Diagnosis of Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

SIADH is diagnosed through a set of specific laboratory criteria including hyponatremia, hypoosmolality, inappropriately high urine osmolality, high urinary sodium, and the absence of volume depletion, while excluding other causes of hyponatremia.

Diagnostic Criteria

The diagnosis of SIADH requires all of the following criteria 1:

1. Hyponatremia: Serum sodium < 134 mEq/L
2. Hypoosmolality: Plasma osmolality < 275 mOsm/kg
3. Inappropriately high urine osmolality: > 500 mOsm/kg (or at minimum > 300 mOsm/kg)
4. Inappropriately high urinary sodium concentration: > 20 mEq/L (often > 40 mEq/L)
5. Euvolemic state: Clinical assessment showing absence of edema, dehydration, or volume depletion
6. Exclusion of other causes: Normal adrenal and thyroid function, absence of diuretic use

Clinical Assessment

When evaluating a patient with suspected SIADH:

• Volume status assessment: The patient should appear clinically euvolemic - no edema, no signs of dehydration 2
• Symptom evaluation: Symptoms depend on severity and acuity of hyponatremia 1:
  • Mild (Na 125-130 mEq/L): General weakness, confusion, headache, nausea
  • Severe (Na < 120 mEq/L): Seizures, coma, potentially life-threatening manifestations

Laboratory Evaluation

A comprehensive laboratory workup should include:

• Serum studies:

  • Sodium, potassium, chloride, bicarbonate
  • BUN and creatinine (to assess renal function)
  • Glucose (to rule out hyperglycemia-induced hyponatremia)
  • Serum osmolality
  • Serum uric acid (typically < 4 mg/dL in SIADH) 2, 3
  • Thyroid function tests (TSH, free T4)
  • Morning cortisol or ACTH stimulation test (to exclude adrenal insufficiency)

• Urine studies:

  • Urine sodium (typically > 20-40 mEq/L in SIADH)
  • Urine osmolality (typically > 300 mOsm/kg, often > 500 mOsm/kg)
  • Fractional excretion of sodium (typically > 0.5% in 70% of SIADH cases) 3

Differential Diagnosis

Rule out other causes of hyponatremia:

• Hypovolemic hyponatremia:

  • Clinical signs of dehydration
  • Low urine sodium (< 20 mEq/L) unless renal salt wasting

• Hypervolemic hyponatremia:

  • Heart failure
  • Cirrhosis
  • Nephrotic syndrome
  • Clinical evidence of edema

• Medication-induced SIADH 1:

  • Antidepressants (SSRIs, SNRIs, MAOIs)
  • Antipsychotics (olanzapine, clozapine)
  • Anticonvulsants (carbamazepine, valproate)
  • Diuretics (thiazides)
  • NSAIDs
  • Opioids
  • Chemotherapeutic agents

• Endocrine disorders:

  • Hypothyroidism
  • Adrenal insufficiency

Diagnostic Algorithm

1. Identify hyponatremia: Serum sodium < 134 mEq/L
2. Confirm hypoosmolality: Plasma osmolality < 275 mOsm/kg
3. Assess volume status: Patient should be clinically euvolemic
4. Check urine studies: Urine osmolality > 300 mOsm/kg and urine sodium > 20 mEq/L
5. Rule out other causes: Normal thyroid and adrenal function
6. Consider fractional excretion of urate: Accuracy of diagnostic algorithm for SIADH can approach 95% 2

Common Etiologies to Investigate

Once SIADH is confirmed, investigate underlying causes:

• Malignancy: Especially small cell lung cancer (10-45% produce ADH) 2
• CNS disorders: Stroke, hemorrhage, trauma, infection
• Pulmonary diseases: Pneumonia, tuberculosis, asthma, COPD
• Medications: Review all medications for potential causative agents
• Post-surgical state: Common cause of transient SIADH

Common Pitfalls and Caveats

• Avoid rapid correction: Too rapid correction of hyponatremia (> 8-10 mmol/L/day) can cause osmotic demyelination syndrome 4
• Don't miss adrenal insufficiency: Can mimic SIADH but requires different treatment
• Consider reset osmostat: A variant of SIADH where the body maintains sodium at a lower setpoint
• Medication review is crucial: Many commonly prescribed medications can cause SIADH 1
• Beware of pseudohyponatremia: Caused by hyperlipidemia or hyperproteinemia
• Multiple factors: In hospitalized patients, hyponatremia is often multifactorial 5

By following this systematic approach to diagnosis, SIADH can be accurately identified and distinguished from other causes of hyponatremia, allowing for appropriate management and treatment.