What lab work is indicated for a patient with suspected Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), particularly one with a history of hypertension treated with Hydrochlorothiazide (HCTZ)?

Laboratory Workup for Suspected SIADH

For a patient with suspected SIADH, particularly one on hydrochlorothiazide (HCTZ), obtain serum and urine osmolality, urine sodium, serum electrolytes (including calcium and magnesium), serum creatinine with eGFR, thyroid-stimulating hormone (TSH), serum uric acid, and assess extracellular fluid volume status through physical examination. 1, 2

Essential Laboratory Tests

Core Diagnostic Panel

• Serum sodium and osmolality: Confirm hypotonic hyponatremia (serum Na <135 mEq/L, plasma osmolality <275 mOsm/kg) 1, 2
• Urine osmolality: Should be inappropriately high (>300-500 mOsm/kg) relative to low serum osmolality 1, 2
• Urine sodium concentration: Typically >40 mEq/L in SIADH, indicating natriuresis despite hyponatremia 1, 2
• Serum uric acid: Level <4 mg/dL has 73-100% positive predictive value for SIADH 1, 2

Additional Required Tests

• Serum creatinine with eGFR: Rule out renal insufficiency, which excludes SIADH diagnosis 1, 2
• Serum electrolytes: Include potassium, calcium, and magnesium to assess for other causes and guide treatment 1, 2
• Thyroid-stimulating hormone (TSH): Exclude hypothyroidism as a cause of hyponatremia 1, 2
• Blood urea nitrogen (BUN): Helps differentiate volume status 1, 2
• Complete blood count: Part of comprehensive initial workup 1, 2
• Liver function tests: Exclude hepatic causes of hyponatremia 1

Volume Status Assessment

Physical examination findings are critical but have limited accuracy (sensitivity 41.1%, specificity 80%) for determining volume status. 1, 2

Euvolemic Signs (Consistent with SIADH)

• Absence of orthostatic hypotension 1, 2
• Normal skin turgor and moist mucous membranes 1, 2
• No peripheral edema, ascites, or jugular venous distention 1, 2

Distinguishing Features from Other Causes

• Hypovolemic hyponatremia: Urine sodium <30 mmol/L suggests extrarenal losses; orthostatic hypotension and dry mucous membranes present 1, 2
• Hypervolemic hyponatremia: Peripheral edema, ascites, or jugular venous distention indicate heart failure or cirrhosis 1, 2

Tests NOT Recommended

Obtaining ADH and natriuretic peptide levels is not supported by evidence and should not delay treatment. 1, 2 ADH levels have limited diagnostic value, as SIADH has been documented in patients with undetectable ADH, and the "appropriateness" of ADH levels has not been clearly defined 1

Special Considerations for HCTZ-Induced Hyponatremia

Thiazide diuretics like HCTZ are a common cause of hyponatremia and can mimic SIADH. 1, 2 Key distinguishing features:

• Timing: Diuretic-induced hyponatremia typically develops within weeks of starting therapy 2
• Urine sodium: May be elevated (>20 mEq/L) due to diuretic effect, similar to SIADH 2
• Volume status: Often shows subtle hypovolemia rather than true euvolemia 2
• Response to discontinuation: Sodium typically improves within 24-72 hours after stopping HCTZ 2

Diagnostic Criteria for SIADH

SIADH diagnosis requires meeting all five cardinal criteria: 1, 2, 3

1. Hypotonic hyponatremia (serum Na <135 mEq/L, plasma osmolality <275 mOsm/kg)
2. Inappropriately concentrated urine (urine osmolality >300 mOsm/kg)
3. Elevated urine sodium (>40 mEq/L) with normal salt intake
4. Clinical euvolemia (absence of edema and volume depletion)
5. Normal renal, adrenal, and thyroid function

Common Pitfalls

• Failing to assess volume status accurately: Physical examination alone is insufficient; integrate clinical findings with laboratory data 1, 2
• Not excluding hypothyroidism and adrenal insufficiency: These must be ruled out before diagnosing SIADH 1, 2
• Ignoring medication history: HCTZ and other drugs are common reversible causes that should be identified early 1, 2
• Obtaining unnecessary tests: ADH levels do not aid diagnosis and delay appropriate treatment 1, 2