SIADH (syndrome of inappropriate ADH secretion)

Definition

The syndrome of inappropriate ADH secretion (SIADH), also called Schwartz-Bartter syndrome, is defined as less than maximally dilute urine in the presence of low serum osmolality (hyponatremia). It requires the absence of volume depletion, hypervolaemia, hypotension or other physiological stimuli for vasopressin release, together with normal cardiac, hepatic, renal, adrenal and thyroid function. SIADH is an important cause of euvolaemic hyponatremia.

Aetiopathogenesis

Vasopressin (ADH) is released from the posterior pituitary and increases water reabsorption in the distal nephron. Physiological stimuli are raised plasma osmolality, reduced blood volume, low blood pressure, stress and certain drugs; low osmolality normally suppresses release. In SIADH, vasopressin is secreted despite normal or low osmolality and normal blood volume. The retained water dilutes the plasma, while total body sodium and extracellular volume remain near normal. In one variant, vasopressin release is suppressed only at a lower than normal osmolality ("reset osmostat"). Despite the name, not all affected people actually have raised vasopressin levels.

• Tumors: above all small cell lung carcinoma with ectopic vasopressin production, as well as tumors of the pancreas, duodenum and CNS, and lymphomas.
• Nervous system disorders: meningitis, encephalitis, brain abscess, head injury, stroke, subarachnoid or subdural hemorrhage, Guillain-Barré syndrome, acute intermittent porphyria and acute psychosis.
• Lung disorders: pneumonia, tuberculosis, lung abscess and aspergillosis.
• Drug-induced: most often analgesics (opioids, NSAIDs), antidepressants (certain SSRIs), antiepileptic drugs, antipsychotics and cytotoxic agents.
• Other causes: HIV infection and protein-energy undernutrition.

Clinical features

Symptoms are those of hyponatremia and mainly involve the central nervous system. They usually appear when effective plasma osmolality falls below about 240 mOsm/kg: nausea, unsteadiness, falls, personality change, confusion and lethargy. When serum sodium falls below 115 mmol/L, stupor, neuromuscular hyperexcitability, hyperreflexia, seizures and coma may occur. Edema or signs of volume depletion are typically absent; symptoms of the underlying disease, such as lung cancer or pneumonia, are added.

Diagnosis

• Laboratory tests: low serum sodium and low serum osmolality (below 275 mOsm/kg) with inappropriately high urine osmolality (not maximally dilute, i.e. above 100 mOsm/kg).
• Urine sodium: usually above 30 mmol/L, with fractional sodium excretion above 1%.
• Other typical findings: clinical euvolaemia or mild hypervolaemia, normal urea and creatinine, low serum uric acid.
• Exclusion of other causes: thyroid and adrenal function (TSH, cortisol), renal, cardiac and hepatic function and a drug history. Other causes remain possible even when a suspect drug is being taken.
• Search for the cause: chest X-ray (infiltrate, pulmonary edema, mass); cerebral imaging if a brain disorder is clinically suspected or no other cause can be found.

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Further reading (open access)

1. MSD Manual Professional: Syndrome of Inappropriate ADH Secretion (SIADH)
2. MSD Manual Professional: Hyponatremia

Cross-references