Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by hypotonic hyponatremia and euvolemia due to the continued, unregulated release or action of antidiuretic hormone (ADH) . This leads to excessive water reabsorption , dilutional hyponatremia, and suppressed renin-aldosterone activity.
Normal Physiology of ADH
- ADH (vasopressin) is synthesized in the hypothalamus and stored in the posterior pituitary .
- It acts on V2 receptors in the renal collecting ducts , promoting free water reabsorption without sodium.
- ADH secretion is normally regulated by serum osmolality and plasma volume .
Pathophysiology of SIADH
In SIADH:
- ADH secretion is inappropriate , independent of serum osmolality or volume status.
- This causes excess water retention , dilution of serum sodium , and decreased serum osmolality .
- Suppression of renin and aldosterone leads to further natriuresis (urinary sodium loss).
- Volume receptors activate natriuretic peptides , promoting sodium excretion despite hyponatremia.
Result:
- Hypotonic hyponatremia with low plasma osmolality and high urine osmolality .
Causes of SIADH
| Category | Examples |
|---|---|
| Malignancies | Small cell lung carcinoma (most common), pancreatic, prostate, lymphoma |
| CNS Disorders | Stroke, trauma, meningitis, encephalitis, subarachnoid hemorrhage |
| Pulmonary Diseases | Pneumonia, tuberculosis, COPD, asthma |
| Drugs | SSRIs, TCAs, carbamazepine, vincristine, cyclophosphamide, opiates, NSAIDs |
| Surgery & Stress | Post-operative state, pain, nausea |
| Idiopathic | Especially in elderly |
Clinical Features
Symptoms correlate with the severity and rapidity of hyponatremia :
- Mild (<130 mEq/L) : Nausea, anorexia, fatigue, headache
- Moderate (<125 mEq/L) : Muscle cramps, irritability, confusion
- Severe (<120 mEq/L) :
- Seizures
- Altered mental status
- Cerebral edema
- Coma
- Respiratory arrest
Diagnostic Criteria (Bartter-Schwartz Criteria)
- Serum hyponatremia (<135 mEq/L) and hypo-osmolality (<275 mOsm/kg)
- Urine osmolality >100 mOsm/kg (inappropriately concentrated)
- Urine sodium >40 mEq/L
- Euvolemia : No signs of dehydration, edema, or volume overload
- Normal renal, adrenal, and thyroid function
- Correction of hyponatremia with fluid restriction
Investigations
- Serum sodium , osmolality
- Urine sodium and urine osmolality
- Serum cortisol , TSH to rule out other causes
- ADH levels (confirmatory but not always practical)
- Water loading test (historical use; rarely done today)
Management
General Principles
- Identify and treat underlying cause
- Discontinue offending drugs
Treatment by Severity
| Severity | Management |
|---|---|
| Mild/Chronic | - Fluid restriction (800–1000 mL/day) - Salt and protein supplementation |
| Moderate | - Oral salt tablets - Loop diuretics with saline to promote free water excretion |
| Severe/Symptomatic | - Hypertonic saline (3%) , administered slowly - Monitor for osmotic demyelination |
| Refractory/Chronic SIADH | - Demeclocycline (induces nephrogenic DI) - Vaptans (ADH receptor antagonists: conivaptan, tolvaptan) |
Complications
- Cerebral edema (acute, severe hyponatremia)
- Seizures , coma
- Osmotic demyelination syndrome (ODS) or central pontine myelinolysis :
- Risk when serum sodium is corrected too rapidly
- Presents with quadriplegia, pseudobulbar palsy, locked-in syndrome
- Non-cardiogenic pulmonary edema
High-Yield Points
- SIADH is euvolemic hyponatremia with inappropriately concentrated urine .
- Most common causes: small cell lung cancer , CNS disorders , and SSRIs .
- Fluid restriction is first-line in asymptomatic or mild cases.
- Correct sodium slowly (<8–10 mEq/L/day) to prevent ODS .
- Hypertonic saline is reserved for symptomatic/severe cases.
Mnemonic: “S-I-A-D-H”
- S odium low
- I ncreased ADH
- A bsent dehydration (euvolemic)
- D ilutional hyponatremia
- H igh urine osmolality
