Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a disorder of water balance in which antidiuretic hormone is released despite normal or low plasma osmolality, causing the kidney to retain water and producing dilutional hyponatraemia. It is one of the most common causes of low serum sodium and links the posterior pituitary axis to systemic fluid regulation.

Definition

SIADH is the secretion of antidiuretic hormone (vasopressin) that is not suppressed by low plasma osmolality, leading to renal water retention and euvolaemic, dilutional hyponatraemia in the absence of other causes such as volume depletion, adrenal, thyroid, or renal disease.

Scope

This topic covers the physiology of antidiuretic hormone, the mechanism by which its inappropriate secretion produces euvolaemic hyponatraemia, and the principal categories of underlying cause. It is a reference overview of the entity and does not provide diagnostic cut-offs, correction rates, or treatment regimens.

Core questions

• How does antidiuretic hormone normally regulate water balance?
• Why does inappropriate antidiuretic hormone secretion cause euvolaemic hyponatraemia?
• What categories of disease underlie SIADH?

Key concepts

• Antidiuretic hormone (vasopressin)
• Plasma osmolality and osmoregulation
• Euvolaemic (dilutional) hyponatraemia
• Free water retention
• Inappropriately concentrated urine
• Diagnosis of exclusion

Mechanisms

Antidiuretic hormone, released from the posterior pituitary, normally promotes renal free-water reabsorption only when plasma osmolality rises or volume falls. In SIADH this regulation is uncoupled: antidiuretic hormone is secreted despite normal or low osmolality, so the kidney retains free water and the urine remains inappropriately concentrated relative to the dilute plasma, producing hyponatraemia without oedema or volume depletion (Ellison & Berl, 2007). Because total body sodium is largely preserved and the excess is water, patients are clinically euvolaemic. Causes include central nervous system disorders, pulmonary disease, certain medications, and ectopic antidiuretic hormone production by tumours; SIADH is diagnosed after excluding other causes of hyponatraemia (Verbalis et al., 2013).

Clinical relevance

SIADH is a leading cause of hyponatraemia, and its recognition depends on demonstrating euvolaemic low sodium with inappropriately concentrated urine after excluding other causes. This topic describes the mechanism and the diagnostic concept; it is a reference and does not provide correction targets, rates, or pharmacologic management.

Epidemiology

SIADH is among the most frequent causes of hyponatraemia encountered in hospitalised patients, arising from a broad range of neurological, pulmonary, neoplastic, and drug-related conditions; detailed frequencies are addressed in the cited expert recommendations (Verbalis et al., 2013).

History

The syndrome was characterised in 1957 by Schwartz, Bartter, and colleagues, who linked inappropriate antidiuretic hormone secretion to hyponatraemia in patients with lung cancer, giving rise to the eponym Schwartz-Bartter syndrome. Later work clarified the osmoregulatory defect and established the diagnostic criteria reflected in modern reviews and recommendations (Ellison & Berl, 2007; Verbalis et al., 2013).

Key figures

• David Ellison
• Tomas Berl
• Joseph Verbalis
• Frederic Bartter
• William Schwartz

Seminal works

• ellison-berl-2007
• verbalis-2013

Frequently asked questions

Why does SIADH lower the blood sodium level?

Inappropriate antidiuretic hormone secretion makes the kidneys retain water, which dilutes the sodium already in the blood; the sodium is not so much lost as diluted by the retained free water, producing hyponatraemia.

How is SIADH distinguished from other causes of low sodium?

SIADH characteristically occurs in a clinically euvolaemic patient who has inappropriately concentrated urine despite low plasma osmolality, and it is diagnosed only after other causes such as volume depletion and adrenal, thyroid, or kidney disease have been excluded.