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  • Updated 11.27.2022
  • Released 08.03.1994
  • Expires For CME 11.27.2025




Hyponatremia is the most common electrolyte disorder in hospitalized patients (01) and is associated with increased morbidity and mortality (34; 07). Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is a leading cause of euvolemic hyponatremia in hospitalized patients (30). It occurs with an independent release of arginine vasopressin (also known as ADH) not in response to baroreceptor or osmole sensing receptor changes. Clinically, it is distinguished from other hyponatremic states by apparent euvolemia, as opposed to hypovolemic or fluid overload states. By labs, the urine appears inappropriately concentrated compared to the fluid status of the patient. SIADH is typically the clinical manifestation of another underlying disease state, most commonly malignancy, pulmonary disease, or central nervous system disease. Treatment of SIADH requires treatment of the underlying etiology for definitive management. Hyponatremia may be acutely corrected for symptom management while other diagnostic studies or treatments are underway.

Key points

• SIADH can only be diagnosed after excluding other forms of hyponatremia, adrenal insufficiency, and hypothyroidism.

• Most common etiologies of SIADH include malignancy, medications, CNS disorders, and pulmonary disorders.

• Hyponatremia is associated with increased morbidity and mortality.

• Urgency of sodium correction depends on acuity of hyponatremia and presence of symptoms.

• Some genetic mutations have been identified that lead to a syndrome of antidiuresis.

• Vasopressin antagonists can be considered for treatment, but controversy exists regarding dosing and strength of recommendation.

• Overcorrection of chronic hyponatremia may lead to osmotic demyelination.

Historical note and terminology

Hyponatremia has been described in association with pulmonary and central nervous system disease states since the 1930s. In 1957, Bartter and Schwartz published a description of 2 patients with bronchogenic carcinoma and hyponatremia in the setting of inappropriately high urine sodium content and euvolemia. In their study of these patients they identified that correction of serum sodium was achieved with fluid restriction (26). They posited an inappropriate secretion of antidiuretic factor as the etiology of hyponatremia, and a decade later this became known as syndrome of inappropriate antidiuretic hormone and clinical criteria were described (03).

Science has now come to recognize that the etiologies of hyponatremia related to the vasopressin system go beyond abnormal secretion of the hormone and may include genetic mutations of receptors which respond to ADH. A broader term to include these etiologies is syndrome of inappropriate antidiuresis or SIAD. In this article, the terminology SIADH will be used.

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