What is the appropriate workup for a patient suspected of having syndrome of inappropriate antidiuretic hormone secretion (SIADH)?

SIADH Workup

Essential Diagnostic Criteria

The diagnosis of SIADH requires five cardinal features: hypotonic hyponatremia (serum sodium <134 mEq/L), plasma osmolality <275 mosm/kg, inappropriately concentrated urine (osmolality >100 mosm/kg, typically >500 mosm/kg), elevated urinary sodium (>20 mEq/L, often >40 mEq/L), and euvolemic status with normal thyroid, adrenal, and renal function. 1, 2

Initial Laboratory Assessment

Serum Studies

• Serum sodium and osmolality to confirm hyponatremia and hypoosmolality 1
• Serum glucose to exclude hyperglycemia-induced pseudohyponatremia (adjust sodium by 1.6 mEq/L for each 100 mg/dL glucose >100 mg/dL) 3
• Serum creatinine and BUN to assess renal function 1, 3
• Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH 1, 3
• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism 1, 3
• Morning cortisol and ACTH to rule out adrenal insufficiency 1, 3

Urine Studies

• Urine osmolality >100 mosm/kg (typically >500 mosm/kg in SIADH) despite low serum osmolality 1, 2
• Urine sodium >20 mEq/L (often >40 mEq/L) indicating inappropriate natriuresis 1, 2, 4
• Spot urine sodium/potassium ratio >1 correlates with 24-hour sodium excretion >78 mmol/day with ~90% accuracy 3

Critical Volume Status Assessment

Euvolemia is the defining feature that distinguishes SIADH from other causes of hyponatremia. 1, 2

Clinical Examination for Euvolemia

• No orthostatic hypotension, normal skin turgor, moist mucous membranes (excludes hypovolemia) 1, 5
• No peripheral edema, ascites, or jugular venous distention (excludes hypervolemia) 1, 3
• Physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%), so integrate all clinical data 3

Distinguishing SIADH from Cerebral Salt Wasting (CSW)

This distinction is critical in neurosurgical patients because treatments are opposite:

• SIADH: Euvolemic, CVP 6-10 cm H₂O, treat with fluid restriction 1, 5
• CSW: Hypovolemic, CVP <6 cm H₂O, unquenchable thirst, treat with volume/sodium replacement 1, 5
• Both have urine sodium >20 mEq/L, but CSW shows clinical volume depletion 1, 5

Identifying the Underlying Cause

Malignancy Screening

• Small cell lung cancer causes SIADH in 15% of cases 6
• Non-small cell lung cancer in 0.7% of cases 6
• Head and neck cancers in 3% of cases 6
• Chest X-ray or CT chest to evaluate for pulmonary malignancy 3

Medication Review

Discontinue or identify offending medications:

• Chemotherapy agents: cisplatin, vincristine, vinblastine, cyclophosphamide 1, 6, 2
• Antidepressants: SSRIs, SNRIs 1
• Antiepileptics: carbamazepine, oxcarbazepine 1, 2
• NSAIDs, opioids, tramadol 1

CNS and Pulmonary Disorders

• CNS disorders: meningitis, encephalitis, head trauma, subarachnoid hemorrhage 2, 7
• Pulmonary diseases: pneumonia, tuberculosis, positive pressure ventilation 6, 2

Diagnostic Algorithm

1. Confirm hyponatremia (serum sodium <135 mmol/L) with plasma osmolality <275 mosm/kg 1, 2
2. Measure urine osmolality: if >100 mosm/kg (especially >500 mosm/kg), proceed 1, 2
3. Check urine sodium: if >20 mEq/L (ideally >40 mEq/L), continue evaluation 1, 4
4. Assess volume status clinically: confirm euvolemia (no edema, no dehydration) 1, 2
5. Exclude hypothyroidism (TSH) and adrenal insufficiency (morning cortisol) 1, 3
6. Confirm normal renal function (creatinine, BUN) 1, 2
7. Identify underlying cause: review medications, obtain chest imaging, consider CNS evaluation 1, 6, 2

Common Diagnostic Pitfalls

• Misdiagnosing CSW as SIADH in neurosurgical patients leads to harmful fluid restriction instead of needed volume replacement 1, 5
• Failing to exclude hypothyroidism and adrenal insufficiency before confirming SIADH 1, 3
• Ignoring medication causes, particularly in elderly patients on multiple drugs 1
• Measuring plasma ADH levels is not required for diagnosis and should not delay treatment 1, 3
• Relying solely on physical examination for volume assessment without integrating laboratory and clinical context 3

Special Considerations

• In patients with subarachnoid hemorrhage, hyponatremia is more commonly due to CSW than SIADH, requiring aggressive volume replacement rather than restriction 1, 5
• Chronic idiopathic SIADH may occur in elderly patients when no cause is identified despite thorough evaluation 8
• Reset osmostat is a variant where AVP secretion is regulated but at a lower osmotic threshold; these patients maintain stable sodium at lower levels 2