Tarakad S Ramachandran MD (Dr. Ramachandran of SUNY Upstate Medical University has no relevant financial relationships to disclose.)
Arun Ramachandran MD (Dr. Ramachandran of the State University of New York at Syracuse has no relevant financial relationships to disclose.)
Matthew Lorincz MD PhD, editor. (Dr. Lorincz of the University of Michigan has no relevant financial relationships to disclose.)
Originally released August 3, 1994; last updated June 22, 2015; expires June 22, 2018
Notice: This article has expired and is therefore not available for CME credit.

This article includes discussion of SIADH and syndrome of inappropriate secretion of antidiuretic hormone. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was first so named by Bartter and Schwartz in 1967. SIADH must be differentiated from the many other causes of hyponatremia and distinguished from situations of ADH secretion that are compensatory responses to increased plasma osmolality or hypovolemia and hypotension. The urine sodium concentration should be low (less than 30 mmol/L) with reduced effective circulating volume, because sodium-retaining factors, including angiotensin II, catecholamines, the sympathetic nervous system, and aldosterone, are activated and stimulate renal tubular sodium reabsorption. When the urine sodium concentration is high, SIADH should be strongly considered, with 2 important exceptions. The first is diuretic use, which can cause baroreceptor-mediated vasopressin release through reduced effective circulating volume with a high urine sodium concentration. The second is adrenal insufficiency, in which cortisol or aldosterone deficiency can lead to vasopressin secretion. Urine sodium is high because of aldosterone deficiency. Adrenal insufficiency must always be ruled out in cases of severe hyponatremia, because the classic clinical and biochemical features may not be present.

Key points


• In SIADH, hyponatremia results from a pure disorder of water handling by the kidney, resulting in increased total body water, whereas external Na+ balance is usually well regulated.


• Because of the lack of signs of excessive volume of extracellular fluid, diagnosing SIADH based on clinical findings is difficult.


• Renal function and acid-base balance are often preserved.


• Hypouricemia is a distinguishing feature.


• Neurologic impairment may range from subclinical to life-threatening.


• Effective treatment of SIADH consists of water restriction, aquaretics, or hypertonic saline and loop diuretics.


• Tolvaptan is efficacious and safe for the treatment of hyponatremia in patients with SIADH.

Historical note and terminology

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is provisionally diagnosed when: (1) secretion of antidiuretic hormone (also called vasopressin) is not consistent with the plasma osmolality and is not associated with conditions of hypovolemia or hypotension; (2) it has been established that renal function is normal; and (3) there is no disturbance of adrenal or thyroid function. Such pathological secretion of ADH leads to the formation of concentrated urine and serum hyponatremia. SIADH is seen in a variety of clinical circumstances and represents the leading cause of hyponatremia in hospitalized patients (Anderson 1986).

The modern understanding of the role of ADH in the water balance of the body evolved from Claude Bernard's classic 19th century animal experiments relating lesions of the floor of the fourth ventricle to alterations in urine volume. In 1928, an extract of rabbit neurohypophysis was shown to have both pressor and antidiuretic activity (Kamm et al 1928). Verney showed that "antidiuretic substance" secretion in dogs was regulated by the osmolality of the extracellular fluid (Verney 1947). Lysine vasopressin, the ADH in pigs, was synthesized in 1957 and arginine vasopressin, its human counterpart, followed shortly thereafter (du Vigneaud et al 1958).

SIADH was first so named by Bartter and Schwartz in 1967 (Bartter and Schwartz 1967), a decade after their description of 2 patients with bronchogenic carcinoma-associated hyponatremia (Schwartz et al 1957). Hyponatremia as a manifestation of an underlying disease state had been observed since the 1930s, most frequently in cases of pulmonary tuberculosis, bronchogenic carcinoma, and CNS lesions. Bartner and Schwartz hypothesized that the hyponatremia observed in their patients was due to abnormal or “inappropriate” (ie, to the low plasma osmolality) secretion of an antidiuretic factor. In 1963, ADH activity was first demonstrated in desiccated extract from a small cell carcinoma of the lung (Amatruda et al 1963).

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