Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

Key Features

Essentials of Diagnosis

• Euvolemic hypotonic hyponatremia, particularly among hospitalized patients

• Serum sodium concentration < 135 mEq/L (< 135 mmol/L)

• Plasma osmolality < 280 mOsm/kg and U_Na > 20 mEq/L

• Risk of osmotic demyelination syndrome from overly rapid correction of serum sodium

General Considerations

• ADH is secreted in the absence of an appropriate physiologic stimuli (eg. hypovolemia or hyperosmolality)

• There is failure to suppress ADH action; water is inappropriately retained leading to relatively concentrated urine

• SIADH is a diagnosis of exclusion; must rule out other causes of hyponatremia (eg, hypovolemia, decreased solute intake, cortisol deficiency, and severe hypothyroidism)

• Major causes of SIADH are disorders affecting the CNS, lungs (eg. cancer or infection) and medications (Table 21–2)

Clinical Findings

Symptoms and Signs

• Frequently asymptomatic; symptoms depend on severity and acuity of the hyponatremia

• Acute hyponatremia (present for < 48 hours)

  • Symptoms mainly relate to brain cell swelling and rise in intracranial pressure: headache, inattentiveness, lethargy, disorientation, and nausea

  • Most serious symptoms: marked confusion, decreased level of consciousness, vomiting, seizures, coma, brainstem herniation, death

• Chronic hyponatremia (present for > 48 hours)

  • Often asymptomatic

  • Subtle abnormalities, (eg. mild concentration and cognitive deficits) and gait disturbances that can lead to falls, may be present

Differential Diagnosis

• Severe hypothyroidism and glucocorticoid insufficiency can cause hyponatremia that cannot be differentiated from SIADH by urine or serum electrolytes alone

• Hypovolemic or hypervolemic hyponatremia

Diagnosis

• SIADH is a clinical diagnosis in a euvolemic patient

• Characterized by

  • Hypotonic hyponatremia (Figure 21–1)

  • Decreased plasma osmolality (< 280 mOsm/kg)

  • U_Na > 20 mEq/L, urine osm > 100 mOsm/kg

  • Absence of heart, kidney, or liver disease

  • Normal thyroid and adrenal function

• In clinical practice, ADH levels are not measured; urine osmolality is a surrogate for ADH activity

• Low blood urea nitrogen (BUN) (< 5–10 mg/dL) and hypouricemia (< 4 mg/dL)

  • Not only dilutional

  • Increased urea and uric acid clearances in response to volume-expanded state