What are the investigations and management for Syndrome of Inappropriate Antidiuretic Hormone (SIADH)?

Investigations for SIADH

The diagnosis of SIADH requires demonstrating hyponatremia (serum sodium <134 mEq/L), plasma hypoosmolality (<275 mosm/kg), inappropriately high urine osmolality (>500 mosm/kg), and elevated urinary sodium (>20 mEq/L) in a euvolemic patient with normal thyroid, adrenal, and renal function. 1

Essential Laboratory Investigations

Initial Serum Studies

• Serum sodium: Threshold <135 mEq/L defines hyponatremia, but full workup warranted when <131 mmol/L 1, 2
• Serum osmolality: Must be <275 mosm/kg to confirm hypotonic hyponatremia 1
• Serum creatinine and BUN: Required to exclude renal causes and assess kidney function 2
• Thyroid-stimulating hormone (TSH): Essential to rule out hypothyroidism as an alternative diagnosis 2
• Morning cortisol: Necessary to exclude adrenal insufficiency 2
• Serum glucose: Hyperglycemia causes pseudohyponatremia (add 1.6 mEq/L to sodium for each 100 mg/dL glucose >100 mg/dL) 2
• Serum uric acid: Level <4 mg/dL has 73-100% positive predictive value for SIADH 1, 2

Urine Studies

• Urine osmolality: Must be >500 mosm/kg (inappropriately concentrated relative to low plasma osmolality) 1
• Urine sodium concentration: Should be >20 mEq/L, indicating continued natriuresis despite hyponatremia 1, 3
• Spot urine sodium/potassium ratio: Ratio >1 correlates with 24-hour sodium excretion >78 mmol/day with ~90% accuracy 2

Clinical Assessment of Volume Status

Confirming euvolemia is critical to distinguish SIADH from other causes of hyponatremia, particularly cerebral salt wasting in neurosurgical patients. 1, 2

Signs of Euvolemia (SIADH)

• No peripheral edema 1
• No orthostatic hypotension 1
• Normal skin turgor 1
• Moist mucous membranes 1
• Central venous pressure 6-10 cm H₂O (if measured) 1

Distinguishing from Cerebral Salt Wasting

Physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) for volume assessment 2. In neurosurgical patients, CVP <6 cm H₂O indicates cerebral salt wasting rather than SIADH, requiring opposite treatment (volume replacement vs. fluid restriction) 1, 2.

Investigations to Identify Underlying Cause

Malignancy Screening

• Chest imaging: Small cell lung cancer is a common cause, affecting 1-5% of lung cancer patients 2
• CT chest/abdomen/pelvis: To evaluate for occult malignancy if clinically indicated 1

Neurological Evaluation

• Brain imaging (CT or MRI): For any CNS symptoms or suspected neurological disease 1
• CNS disorders including meningitis, encephalitis, and subarachnoid hemorrhage are common causes 4, 3

Pulmonary Assessment

• Chest X-ray: Pneumonia and other lung diseases frequently cause SIADH 3

Medication Review

Identify offending drugs including:

• Antidepressants (SSRIs, trazodone) 1, 2
• Anticonvulsants (carbamazepine) 1, 5
• Chemotherapy agents (cisplatin, vincristine, cyclophosphamide) 1, 5
• NSAIDs and opioids 1

Tests NOT Recommended

Do not obtain plasma ADH or natriuretic peptide levels—these are not supported by evidence and should not delay treatment. 2

Common Diagnostic Pitfalls

• Failing to assess volume status accurately: This is essential for differentiating SIADH from cerebral salt wasting, which requires opposite management 1, 2
• Using diuretics during evaluation: Diuretics invalidate the diagnosis by causing inappropriate natriuresis 1
• Ignoring mild hyponatremia (130-135 mmol/L): Even mild hyponatremia increases fall risk (21% vs. 5%) and mortality (60-fold increase) 2
• Misdiagnosing pseudohyponatremia: Always check serum osmolality and glucose to exclude this 2

Monitoring During Treatment

• Serum sodium every 2 hours during initial correction for severe symptoms 1
• Serum sodium every 4 hours after resolution of severe symptoms 2
• Daily sodium monitoring for chronic management to ensure correction does not exceed 8 mmol/L in 24 hours 1, 6