Syndrome of inappropriate antidiuretic hormone (SIADH) is defined as euvolemic, hypotonic hyponatremia secondary to impaired free water excretion, usually from excessive arginine vasopressin (AVP) release.
Severe neurologic symptoms, such as altered mental status, seizure, and coma, may result from SIADH and these are always treated with hypertonic saline, with close monitoring to avoid overcorrection of serum sodium.
Central pontine myelinolysis (osmotic demyelination syndrome) may occur with rapid correction of serum sodium in excess of 12 mEq/L/day.
Vasopressin receptor antagonists (also known as vaptans) are a class of medications that compete with the antidiuretic hormone AVP for binding at the vasopressin receptor, permitting free water excretion.
The syndrome of inappropriate antidiuretic hormone (SIADH) is characterized by hypotonic hyponatremia, concentrated urine, and a euvolemic state. The impairment of free water excretion is caused by increased arginine vasopressin (antidiuretic hormone or AVP) release. Pseudohyponatremia due to hyperglycemia, hyperlipidemia, or hyperproteinemia should be ruled out first. Renal failure, adrenal insufficiency, and appropriate release of AVP secondary to extracellular volume depletion (hypovolemia, due to gastrointestinal or renal loss) or intravascular volume depletion (hypervolemia due to congestive heart failure, cirrhosis of the liver, or nephrotic syndrome) must be ruled out in order to diagnose SIADH.
History and exam
Key diagnostic factors
- absence of hypovolemia
- absence of hypervolemia
- absence of signs of adrenal insufficiency or hypothyroidism
- altered mental status
Other diagnostic factors
- no history of recent diuretic use
- age >50 years
- pulmonary conditions (e.g., pneumonia)
- nursing home residence
- postoperative state
- medication associated with SIADH induction
- central nervous system (CNS) disorder
- endurance exercise
1st investigations to order
- serum sodium
- serum osmolality
- serum BUN
- urine osmolality
- urine sodium
Investigations to consider
- diagnostic trial with normal saline infusion
- serum uric acid
- fractional excretion of sodium
- fractional excretion of urea
- serum TSH
- serum cortisol level
- serum arginine vasopressin (AVP)
mild to moderate symptoms
asymptomatic with sodium ≥125 mEq/L
persistence of chronic SIADH
Megan Dixon, MD
Arizona Kidney Disease and Hypertension Center
MD declares that she has no competing interests.
Howard Lien, MD, PhD
Professor Emeritus of Medicine
Division of Nephrology
University of Arizona
HL is an author of a reference cited in this topic.
Judith H. Veis, MD
Washington Hospital Center
JHV declares that she has no competing interests.
Laurie Solomon, MD, FRCP
Lancashire Teaching Hospitals
LS declares that he has no competing interests.
- Cerebral salt-wasting
- Clinical practice guideline on diagnosis and treatment of hyponatraemia
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