What are the diagnostic criteria for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

Diagnostic Criteria for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

SIADH is diagnosed when a patient presents with euvolemic hypoosmolar hyponatremia characterized by low serum osmolality and inappropriately high urine osmolality in the absence of diuretic treatment, adrenal insufficiency, heart failure, cirrhosis, and hypothyroidism.

Essential Diagnostic Criteria

The diagnosis of SIADH requires all of the following criteria:

1. Hyponatremia (serum sodium < 134 mEq/L)
2. Hypoosmolality (plasma osmolality < 275 mOsm/kg)
3. Inappropriately high urine osmolality (> 500 mOsm/kg) relative to serum osmolality
4. Elevated urinary sodium concentration (> 20-30 mEq/L) with normal salt intake
5. Clinical euvolemia (absence of edema, ascites, or signs of dehydration)
6. Normal renal function
7. Absence of other causes of hyponatremia:
   • No diuretic use
   • Normal adrenal function
   • Normal thyroid function
   • No heart failure
   • No cirrhosis
   • No volume depletion

Laboratory Findings Supporting SIADH Diagnosis

Additional laboratory findings that support the diagnosis include:

• Serum uric acid < 4 mg/dL (present in ~70% of SIADH cases) 1
• Low blood urea nitrogen (BUN)
• Fractional excretion of sodium > 0.5% (in 70% of cases) 2
• Normal acid-base balance with lower anion gap 2
• Nearly normal total CO2 and serum potassium despite dilution 2

Diagnostic Algorithm

1. Confirm hyponatremia: Serum sodium < 134 mEq/L
2. Assess volume status: Patient must be clinically euvolemic (no edema, no signs of dehydration)
3. Measure serum osmolality: Must be < 275 mOsm/kg
4. Measure urine osmolality: Must be > 300 mOsm/kg (typically > 500 mOsm/kg) and inappropriately high relative to low serum osmolality
5. Measure urine sodium: Must be > 20-30 mEq/L with normal salt intake
6. Rule out other causes:
   • Check thyroid function (TSH, free T4)
   • Check adrenal function (morning cortisol or ACTH stimulation test)
   • Review medication history for drugs associated with SIADH
   • Rule out heart failure, cirrhosis, and renal disease

Common Etiologies of SIADH

SIADH can be caused by:

1. Malignancies: Small cell lung cancer (most common), head and neck cancers, pancreatic cancer
2. Pulmonary disorders: Pneumonia, tuberculosis, asthma, COPD
3. Central nervous system disorders: Stroke, hemorrhage, trauma, infection, tumors
4. Medications: SSRIs, carbamazepine, oxcarbazepine, cyclophosphamide, vincristine, NSAIDs, opioids, antipsychotics

Clinical Pearls and Pitfalls

• Pitfall: Failing to exclude pseudohyponatremia (caused by hyperlipidemia or hyperproteinemia)
• Pitfall: Confusing SIADH with cerebral salt wasting syndrome, which presents with hypovolemia rather than euvolemia
• Pitfall: Not considering reset osmostat syndrome, a variant of SIADH where the osmoregulatory system functions normally but at a lower set point
• Pearl: The fractional excretion of urate can improve diagnostic accuracy for SIADH to approximately 95% 1
• Pearl: In patients with SIADH and poor nutrition, urine sodium may be falsely low despite SIADH 2

Clinical Manifestations

Symptoms depend on the severity and rapidity of sodium decline:

• Mild (Na 125-135 mEq/L): Headache, irritability, difficulty concentrating
• Moderate (Na 115-125 mEq/L): Nausea, confusion, muscle cramps
• Severe (Na <115 mEq/L): Seizures, coma, respiratory arrest

Early detection and appropriate management of SIADH can prevent severe hyponatremia, which can lead to seizures, coma, and death 1.