Syndrome of Inappropriate ADH Secretion (SIADH)

Vasopressin is a hormone produced by the posterior pituitary to help control fluid homeostasis. The hormone increases water reabsorption in the distal nephron, producing a concentrated urine and diluted plasma. Vasopressin release is stimulated by any of the following:

• Increased plasma osmolality

• Decreased blood volume

• Decreased blood pressure

• Stress

• Certain medications

Low plasma osmolality inhibits vasopressin secretion, allowing the kidneys to produce dilute urine. 

Vasopressin release is inappropriate in the presence of normal or low plasma osmolality and normal or high blood volume and blood pressure. In such cases, the water inappropriately retained by the kidneys ultimately causes euvolemic (dilutional) hyponatremia, in which total body sodium and thus extracellular fluid (ECF) volume are normal or near normal; however, total body water is increased.

Overview of the Syndrome of In...

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Vasopressin release can be enhanced by a number of central nervous system disorders. In addition, ectopic vasopressin may be produced by certain cancers or pulmonary disorders (see table Disorders Associated With Syndrome of Inappropriate Antidiuretic Hormone Secretion).

In some patients, vasopressin release is appropriately suppressed but at a lower-than-normal plasma osmolality (reset osmostat).

Symptoms of SIADH are those of hyponatremia, which mainly involve central nervous system dysfunction and generally occur when the effective plasma osmolality falls to < 240 mOsm/kg (< 240 mmol/kg). Symptoms can be subtle and consist mainly of changes in mental status, including altered personality, lethargy, and confusion. As the serum sodium falls to < 115 mEq/L (< 115 mmol/L), stupor, neuromuscular hyperexcitability, hyperreflexia, seizures, coma, and death can result.

• Serum and urine osmolality and electrolyte measurements showing inappropriately high urine osmolality compared to serum osmolality in a euvolemic patient

• Normal adrenal,thyroid,renal, cardiac and hepatic function

SIADH is suspected in patients who have hyponatremia and are euvolemic (ie, neither hyper- nor hypovolemic on physical examination).

Laboratory tests should include serum and urine osmolality and electrolytes. Euvolemic patients should also have thyroid and adrenal function tested. Hypo-osmolality in euvolemic patients should cause excretion of a large volume of dilute urine (eg, osmolality < 100 mOsm/kg [<100 mmol/kg]) and specific gravity < 1.003). Serum sodium concentration and serum osmolality that are low and urine osmolality that is inappropriately high (120 to 150 mmol/L [120 to 150 mOsm/kg])) with respect to the low serum osmolality suggest volume overload, volume contraction, or SIADH. Volume overload and volume contraction are differentiated clinically.

Clinical Calculators

Osmolality Estimator (serum)

When neither volume overload or volume contraction appears likely, SIADH is considered. Patients with SIADH are usually euvolemic or slightly hypervolemic. BUN (blood urea nitrogen) and creatinine values are normal, and serum uric acid is generally low. Urine sodium concentration is usually > 30 mEq/L (30 mmol/L), and fractional excretion of sodium is > 1% (for calculation, see Evaluation of the Renal Patient).

Diagnosis of etiology should be pursued based on symptoms and signs. Because potentially causative medications are relatively commonly used, other etiologies must also be considered even when patients are taking such a medication. In general, a chest x-ray should be done. Central nervous system imaging can be reserved for patients in whom a brain disorder is clinically suspected or no other cause for SIADH can be found.

• Treatment of cause

• Fluid restriction

• Sometimes a vasopressin receptor antagonist

• Sometimes hypertonic saline

When SIADH is present, severe water restriction (eg, 250 to 500 mL/24 hours) is generally required. Additionally, a loop diuretic may be combined with IV 0.9% saline as in hypervolemic hyponatremia.

demeclocycline is not widely used due to the possibility of drug-induced acute kidney injury.

vasopressin receptor antagonist with similar action to conivaptan. Tolvaptan use is limited to less than 30 days due to the potential for liver toxicity and it should not be used in patients with liver or kidney disease

Hypertonic saline infusion should be reserved for patients with severe, symptomatic hyponatremia and should be used cautiously because too-rapid correction risks complication,s such as the osmotic demyelination syndrome. Typically, correction should aim to raise the serum sodium by no more than 8 mEq/L (8 mmol/L) over the first 24 hours with 4 to 6 mEq/L (4 to 6 mmol/L) over the first 4 to 6 hours.