What are the classic signs and symptoms of Syndrome of Inappropriate Antidiuretic Hormone (SIADH)?

Classic Signs and Symptoms of SIADH

The classic signs and symptoms of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) include hyponatremia, hypoosmolality, inappropriately concentrated urine, natriuresis, and clinical euvolemia, with neurologic manifestations ranging from subtle cognitive changes to seizures and coma depending on the severity and rate of sodium decline. 1

Diagnostic Criteria

SIADH is diagnosed based on established criteria:

• Hyponatremia (serum sodium <134 mEq/L)
• Plasma hypoosmolality (<275 mOsm/kg)
• Inappropriately high urine osmolality (>500 mOsm/kg)
• Inappropriately high urinary sodium concentration (>20 mEq/L)
• Clinical euvolemia (absence of edema and volume depletion)
• Normal renal, adrenal, and thyroid function 1, 2

Clinical Manifestations

The severity of symptoms correlates with both the absolute serum sodium concentration and its rate of decline:

Mild Hyponatremia (126-135 mEq/L)

• Often asymptomatic or subtle symptoms
• Mild cognitive impairment
• Attention deficits
• Gait instability 1

Moderate Hyponatremia (120-125 mEq/L)

• Nausea
• Headache
• Muscle cramps
• Weakness
• Dizziness
• Lethargy 3, 1

Severe Hyponatremia (<120 mEq/L)

• Confusion
• Seizures
• Coma
• Death (in extreme cases) 1, 4

Neurologic Manifestations

Neurologic symptoms are particularly prominent in SIADH due to cerebral edema from water movement into brain cells:

• Altered mental status ranging from subtle confusion to delirium
• Decreased level of consciousness (from drowsiness to coma)
• Affective changes (apathy, anxiety, agitation)
• Focal neurologic deficits
• Seizures 3

Common Associations and Causes

SIADH is commonly associated with:

1. Malignancies - especially small cell lung cancer (SCLC) 3
2. CNS disorders - meningitis, encephalitis, stroke, trauma
3. Pulmonary diseases - pneumonia, tuberculosis, COPD
4. Medications - carbamazepine, SSRIs, antineoplastic agents
5. Post-surgical states 1

Key Clinical Pearls

• Symptoms are more related to the rate of sodium decline than the absolute level
• Rapid drops in sodium (>0.5 mmol/L/hour) are more likely to cause severe symptoms 2
• SIADH should be distinguished from other causes of hyponatremia, particularly hypovolemic states
• Unlike edematous disorders (heart failure, cirrhosis), patients with SIADH have normal blood pressure and no edema 5
• Laboratory values typically show lower plasma concentrations of urate, creatinine, and urea compared to hyponatremia from other causes 5

Common Pitfalls in Diagnosis

• Failing to recognize that SIADH is a diagnosis of exclusion
• Not distinguishing between SIADH and cerebral salt wasting syndrome
• Overlooking medication causes of SIADH
• Missing underlying malignancy, particularly small cell lung cancer
• Confusing SIADH with hypovolemic hyponatremia or pseudohyponatremia 1

In summary, SIADH presents with a constellation of laboratory findings (hyponatremia, concentrated urine despite hypo-osmolar plasma) and clinical features that primarily reflect neurologic dysfunction due to cerebral edema, with severity proportional to the degree and rapidity of sodium decline.