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

From the Guidelines

The diagnostic workup for Syndrome of Inappropriate Antidiuretic Hormone (SIADH) involves assessing for euvolemic hypoosmolar hyponatremia characterized by low serum osmolality and inappropriately high urine osmolality.

Diagnostic Criteria

• Hyponatremia (serum sodium < 134 mEq/L)
• Hypoosmolality (plasma osmolality < 275 mosm/kg)
• Inappropriately high urine osmolality (> 500 mosm/kg)
• Inappropriately high urinary sodium concentration (> 20 mEq/L)
• Absence of hypothyroidism, adrenal insufficiency, or volume depletion 1

Laboratory Findings

• Urine osmolality of > 300 mosm/kg
• Urinary sodium level of > 40 mEq/L
• Serum osmolality of < 275 mosm/kg
• Serum uric acid concentration of < 4 mg/dL

Clinical Assessment

• Assessment of intravascular volume status
• Biochemical measurements in blood and urine
• Evaluation of effective arterial blood volume with the fractional excretion of urate to improve diagnostic accuracy to 95% 1

Differential Diagnosis

• Paraneoplastic hyponatremia secondary to elevated atrial natriuretic peptide
• Other non-ADH-mediated causes of hyponatremia, such as sodium wasting due to drug nephrotoxicity or iatrogenic IV infusion of hypotonic fluid 1

From the Research

Diagnostic Workup for SIADH

The diagnostic workup for Syndrome of Inappropriate Antidiuretic Hormone (SIADH) involves a precise evaluation of volemia and the elimination of differential diagnoses 2. The diagnosis of SIADH should be considered if the five cardinal criteria are fulfilled:

• Hypotonic hyponatraemia
• Natriuresis
• Urine osmolality in excess of plasma osmolality
• Absence of oedema and volume depletion
• Normal renal and adrenal function 3

Key Investigations

Key investigations in the diagnostic workup for SIADH include:

• Chest radiograph or chest CT-scan 2
• Urine sodium concentration: a value of 50 mEq/L is the most accurate in separating SIADH from hypovolemic hyponatremia, with a sensitivity of 0.89, specificity of 0.69, and accuracy of 0.82 4
• Urine osmolality and plasma osmolality: to demonstrate a high urine osmolality with a low plasma osmolality, in the absence of diuretic use 5

Classification of Etiologies

The etiologies of SIADH are classified into four main groups:

• Tumors
• Drugs
• Diseases of the central nervous system
• Lung diseases 2, 3, 6

Additional Considerations

Additional considerations in the diagnostic workup for SIADH include:

• Evaluation of the clinical context to guide investigations 2
• Assessment of the response to hypertonic saline infusion to divide SIADH into different types 6
• Consideration of the urine sodium-to-BUN ratio, which may improve separation between SIADH and hypovolemia 4