Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
The syndrome of inappropriate antidiuretic hormone secretion is a disorder of excess antidiuretic hormone (ADH) activity leading to impaired water excretion, dilutional hyponatraemia, and reduced plasma osmolality. Despite low serum sodium levels, total body sodium is typically normal, and intravascular volume appears clinically euvolaemic. In SIADH fluid balance becomes distorted, sodium concentration falls without overt fluid overload, and neurological symptoms are often the most prominent clinical feature.
What You Need to Know
Syndrome of inappropriate antidiuretic hormone secretion develops when antidiuretic hormone, also called vasopressin, is released despite normal or low plasma osmolality and adequate circulating volume. ADH normally acts on the renal collecting ducts to conserve water when the body is dehydrated. In SIADH, this regulatory control is lost, and water reabsorption continues even when it is not physiologically required.
Persistent ADH activity leads to progressive expansion of total body water without a matching increase in sodium content. As water accumulates, serum sodium concentration falls and plasma osmolality decreases. Importantly, sodium handling by the kidneys remains largely appropriate, so the body does not retain sodium alongside water. This produces dilutional hyponatraemia rather than true sodium loss.
The key physiological changes in SIADH include:
Increased water reabsorption in the renal collecting ducts
Expansion of total body water with normal or near-normal circulating volume
Dilution of serum sodium and reduced plasma osmolality
Absence of peripheral oedema despite water excess
Because volume expansion is modest and distributed evenly, classical signs of fluid overload such as peripheral oedema, ascites, or pulmonary congestion are usually absent. Instead, clinical manifestations arise primarily from falling serum sodium and reduced osmolality, particularly within the central nervous system. The brain is especially vulnerable to these changes, as water shifts into neurons in response to hypotonic plasma, impairing cellular function and leading to neurological symptoms as hyponatraemia worsens.
Beyond the Basics
ADH dysregulation and free water retention
Antidiuretic hormone acts on V2 receptors in the renal collecting ducts, promoting insertion of aquaporin-2 water channels into the tubular membrane. In SIADH, ADH secretion continues despite normal or low plasma osmolality, keeping these channels persistently active. This allows ongoing reabsorption of free water regardless of hydration status.
As free water accumulates, plasma becomes progressively diluted. The kidneys continue to excrete sodium in an appropriate manner, so sodium content does not rise alongside water. This produces dilutional hyponatraemia while masking the degree of water excess, which explains why patients often appear clinically euvolaemic despite significant biochemical disturbance.
Dilutional hyponatraemia and cellular swelling
Falling serum sodium lowers extracellular osmolality, creating an osmotic gradient that drives water into cells. Neurons are particularly vulnerable to this shift because the skull limits expansion. As water moves intracellularly, brain cells swell, increasing intracranial pressure and disrupting neuronal signalling.
Neurological manifestations such as headache, confusion, seizures, and reduced consciousness arise from cerebral oedema, rather than direct neuronal injury. Symptom severity depends not only on how low the sodium level falls, but also on how rapidly the decline occurs, as rapid shifts leave little time for cellular adaptation.
Renal adaptation and masked volume expansion
Water retention triggers release of atrial natriuretic peptide, which promotes renal sodium excretion. This secondary natriuresis limits intravascular volume expansion and prevents overt signs of fluid overload such as peripheral oedema or pulmonary congestion. Continued sodium loss, however, further worsens hyponatraemia. This adaptive response preserves near-normal circulating volume at the expense of worsening dilution, contributing to diagnostic uncertainty when physical examination suggests normal volume status despite severe biochemical abnormality.
Chronic SIADH and neural adaptation
With sustained hyponatraemia, brain cells adapt by extruding intracellular osmolytes, small solutes that help regulate cell volume. This process reduces cellular swelling and limits cerebral oedema over time, allowing some patients with chronic SIADH to remain relatively asymptomatic despite very low sodium levels.
This adaptation creates vulnerability during treatment. If serum sodium is corrected too rapidly, extracellular osmolality rises before neurons can reaccumulate osmolytes. Water then shifts out of brain cells abruptly, risking osmotic demyelination. The resulting injury reflects failure of cellular adaptation rather than direct toxicity of therapy, underscoring the need for controlled and gradual correction.
Clinical Connections
SIADH often presents with vague and evolving neurological symptoms such as lethargy, confusion, headache, nausea, and reduced concentration. Because intravascular volume is usually close to normal, physical examination may not show oedema or other obvious signs of fluid excess. As serum sodium falls further or declines rapidly, cerebral oedema worsens, and patients may develop seizures, reduced consciousness, or coma. In many cases, the neurological presentation is out of proportion to other clinical findings, making biochemical assessment critical for recognition.
The clinical course is strongly influenced by both the degree and the rate of sodium decline. Features that should raise concern include:
Worsening confusion or reduced level of consciousness without clear cause
New-onset seizures in the setting of hyponatraemia
Normal or near-normal volume status despite significant electrolyte disturbance
Sodium levels continuing to fall despite standard fluid administration
Management centres on correcting free water excess while avoiding rapid shifts in plasma osmolality. Fluid restriction limits further dilution and allows gradual normalisation of sodium levels. In more severe cases, additional strategies may be required, but correction must remain controlled and closely monitored. Rapid sodium correction risks osmotic demyelination due to abrupt reversal of neuronal adaptation, leading to potentially irreversible neurological injury.
Treatment decisions are guided by sodium trends, rather than single values and frequent monitoring is essential. Careful, staged correction protects the brain from secondary injury and is central to safe and effective management of SIADH.
Concept Check
Why does SIADH cause hyponatraemia without overt fluid overload?
How does excess ADH lead to free water retention at the renal level?
Why are neurological symptoms prominent in SIADH?
How does chronic hyponatraemia alter neuronal adaptation?
Why can rapid sodium correction cause neurological injury?