Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is an endocrine disorder caused by increased ADH secretion in the pituitary gland (e.g., due to infection, drugs), ectopic production of ADH (e.g., small cell lung carcinoma), or enhanced stimulation of ADH in the kidneys as a result of a gene mutation. Hyponatremia develops as a result of increased water retention by the kidneys (not due to sodium deficiency) and systemic fluid overload. SIADH is usually asymptomatic and hyponatremia is often an incidental finding in laboratory results. In mild cases, symptoms include loss of appetite and nausea; in severe cases, seizures and altered consciousness can occur. Treatment depends on the severity of the disease and ranges from fluid restriction (asymptomatic patients) to hypertonic saline administration (severe cases).
- Trauma, bleeding
- Following neurosurgery (e.g., transsphenoidal pituitary surgery)
- Anticonvulsants (e.g., carbamazepine, valproate)
- Antineoplastic agents
- Antipsychotics (e.g., haloperidol)
- Analgesics (e.g., NSAIDS, opioids)
- Illicit substances (e.g., MDMA) 
Paraneoplastic ectopic ADH production 
- Small cell lung carcinoma
- Head and neck cancer
- Extrapulmonary small cell carcinoma
- Olfactory neuroblastoma
Nephrogenic SIADH 
- ↑ ADH secretion → receptor-mediated signaling cascade in the distal convoluted tubules and the collecting ducts of the kidneys → build-up of additional water canals (aquaporin-2) in the luminal cell membrane
- Water is drawn out of the urine and into the hyperosmolar kidney tissue → concentration of urine and ↑ urine osmolality (becomes higher than serum osmolality)
- Water retention → ↓ serum osmolality with transient volume expansion → ↑ ANP, ↑ BNP, and ↓ aldosterone → ↑ urinary sodium and water excretion → euvolemic hyponatremia
- Osmotic fluid shifts → cerebral edema and ↑ intracranial pressure (may occur in patients with extremely low Na+ levels)
- For more information regarding ADH secretion and regulation, see “ .”
Symptoms of hyponatremia
- Muscle weakness
- Altered consciousness
Other clinical features
- Symptoms of the underlying condition
- ↓ Serum osmolality (< 280 mOsm/kg H2O) and ↓ sodium (< 135 mmol/L)
- Plasma ADH normal to elevated
- Normal renal function (indicated by normal creatinine)
- Normal adrenal function (judged by )
- Normal thyroid function
- Frequently ↓ uric acid values
- Urine osmolality > 100 mOsm/kg H2O
- Urinary sodium excretion > 30 mEq/L
The differential diagnoses listed here are not exhaustive.
- In general: treatment of the underlying condition
- Specific measures depend on whether the patient is symptomatic or not.
- Fluid restriction
- Increased salt intake
- Hypertonic saline administration with ICU monitoring to prevent
- A loop diuretic (e.g., furosemide) can be added in severe cases, which is most effective if urine osmolality is > 2x the serum osmolality.
- If initial measures fail: pharmacotherapy with vaptans or demeclocycline
Sodium serum levels should increase by a maximum of 10 mmol/L within 24 hours or 0.5 mmol/L per hour.
A rapid increase in serum sodium can lead to osmotic demyelination syndrome!
- Mechanism of action: antagonism at vasopressin receptors in renal collecting ducts → ↑ aquaresis (i.e., free water excretion)
- Side effects
- Mechanism of action 
- Bacterial infections (primarily an antibiotic)
- SIADH, using one of its side effects
- Side effects