What is the workup for Syndrome of Inappropriate Antidiuretic Hormone (SIADH)?

Workup for Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

The diagnostic workup for SIADH requires confirming euvolemic hyponatremia, measuring serum and urine osmolality, and ruling out other causes of hyponatremia through laboratory testing and clinical assessment. 1

Diagnostic Criteria

The diagnosis of SIADH is established when all of the following criteria are met:

• Hyponatremia (serum sodium <134 mEq/L)
• Plasma hypoosmolality (<275 mOsm/kg)
• Inappropriately high urine osmolality (>500 mOsm/kg) relative to serum osmolality
• Elevated urinary sodium concentration (>20 mEq/L)
• Clinical euvolemia (no edema, no signs of dehydration)
• Normal thyroid and adrenal function 1

Laboratory Workup

Essential Laboratory Tests

1. Serum studies:

   • Sodium, potassium, chloride, bicarbonate
   • BUN and creatinine
   • Glucose
   • Serum osmolality
   • Liver function tests
   • Calcium 2, 1

2. Urine studies:

   • Urine sodium
   • Urine osmolality
   • Fractional excretion of sodium 1

3. Endocrine evaluation:

   • Thyroid function tests (TSH, free T4)
   • Morning cortisol or ACTH stimulation test to rule out adrenal insufficiency 1

Etiologic Workup

After confirming SIADH diagnosis, investigations should be directed toward identifying the underlying cause:

1. Malignancy Evaluation

• Chest imaging (CT scan) - especially important to rule out small cell lung cancer, which accounts for 10-45% of SIADH cases 2, 1
• Age-appropriate cancer screening

2. Pulmonary Disease Evaluation

• Chest X-ray or CT scan to assess for pneumonia, tuberculosis, asthma, or COPD 1

3. CNS Disorder Evaluation

• Brain imaging (CT or MRI) if neurological symptoms are present or to rule out stroke, hemorrhage, trauma, or infection 1

4. Medication Review

• Comprehensive review of all medications, focusing on:
  • Antidepressants (especially SSRIs, SNRIs, MAOIs)
  • Antipsychotics
  • Anticonvulsants (particularly valproate)
  • Diuretics (especially thiazides)
  • NSAIDs
  • Opioids
  • Chemotherapeutic agents 1

Clinical Assessment

• Careful volume status assessment to confirm euvolemia
• Neurological examination to detect symptoms related to hyponatremia severity
• Assessment for symptoms based on severity:
  • Mild symptoms: weakness, confusion, headache, nausea
  • Severe symptoms: seizures, decreased level of consciousness, coma 1

Pitfalls to Avoid

1. Failure to establish euvolemia: SIADH is a diagnosis of euvolemic hyponatremia. Careful clinical assessment of volume status is essential to differentiate from hypovolemic or hypervolemic hyponatremia.

2. Overlooking medication causes: Many medications can cause SIADH. A thorough medication review is essential, as discontinuation of the offending agent may resolve the condition 1.

3. Missing underlying malignancy: Small cell lung cancer is a common cause of SIADH. Appropriate imaging should be performed, particularly in patients with risk factors for lung cancer 2, 1.

4. Incomplete laboratory evaluation: Failure to measure both serum and urine osmolality can lead to missed diagnosis.

5. Not ruling out adrenal insufficiency and hypothyroidism: These conditions can mimic SIADH and must be excluded before confirming diagnosis 1.

6. Correcting sodium too rapidly: During treatment, correction of serum sodium should not exceed 8-10 mmol/L per day to avoid osmotic demyelination syndrome 1, 3.

By following this systematic approach to SIADH workup, clinicians can accurately diagnose the condition and identify the underlying cause, leading to appropriate management strategies.