What is the mechanism of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion in respiratory illness?

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Last updated: June 19, 2025View editorial policy

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From the Guidelines

SIADH in respiratory illness occurs primarily through the excessive secretion of antidiuretic hormone (ADH) due to inflammatory and hypoxic mechanisms, leading to euvolemic hyponatremia and impaired free water clearance. The mechanism involves the stimulation of ADH secretion from the posterior pituitary by inflammatory cytokines released in response to pulmonary infections and diseases, as well as hypoxemia, which is a common feature in respiratory conditions 1. Additionally, positive pressure ventilation can increase intrathoracic pressure, reducing venous return and cardiac output, which is interpreted by baroreceptors as volume depletion, further stimulating ADH release.

Some key features of SIADH include:

  • Hyponatremia (serum sodium < 134 mEq/L)
  • Hypoosmolality (plasma osmolality < 275 mosm/kg)
  • Inappropriately high urine osmolality (> 500 mosm/kg)
  • Inappropriately high urinary sodium concentration (> 20 mEq/L)
  • Absence of hypothyroidism or adrenal insufficiency or volume depletion 1.

The diagnosis of SIADH can be made by assessing the effective arterial blood volume with the fractional excretion of urate, which can approach 95% accuracy 1. Laboratory findings in SIADH include urine osmolality of > 300 mosm/kg, urinary sodium level of > 40 mEq/L, serum osmolality of < 275 mosm/kg, and serum uric acid concentration of < 4 mg/dL 1.

It is essential to distinguish SIADH from other causes of hyponatremia, such as paraneoplastic hyponatremia secondary to elevated atrial natriuretic peptide, sodium wasting due to drug nephrotoxicity, and iatrogenic IV infusion of hypotonic fluid 1. The management of SIADH includes fluid restriction, demeclocycline, and vasopressin receptor inhibitors, such as conivaptan and tolvaptan 1. The primary goal of treatment is to correct hyponatremia and prevent severe complications, such as seizures, coma, and death.

From the Research

Mechanism of SIADH in Respiratory Illness

The mechanism of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion in respiratory illness involves the inappropriate release of antidiuretic hormone (ADH), leading to water retention and hyponatremia.

  • The etiology of SIADH is complex and can result from various diseases, including respiratory illnesses, as well as the use of certain drugs 2.
  • In patients with respiratory illness, SIADH can occur due to the inappropriate secretion of ADH, resulting in hyponatremia and impaired water excretion 3.
  • The pathophysiologic mechanism of SIADH in respiratory illness is not fully understood, but it is thought to involve the disruption of normal osmoregulation, leading to the excessive release of ADH 4.

Key Features of SIADH

  • Hyponatremia and hyposmolality are characteristic features of SIADH, along with continued urinary loss of sodium and excretion of an inappropriately concentrated urine 5.
  • The retention of excess water caused by the inappropriate secretion of ADH is central to the development of SIADH, and fluid restriction is vital in preventing the development of symptomatic SIADH 6, 5.
  • Diagnosis of SIADH is confirmed by demonstration of a high urine osmolality with a low plasma osmolality, in the absence of diuretic use 2.

Treatment of SIADH

  • Treatment of SIADH consists of elimination of underlying causes and restriction of fluid intake; if these measures are unsuccessful or poorly tolerated, long-term drug therapy may be indicated 2.
  • Fluid restriction alone will also result in the correction of serum electrolyte composition in patients with SIADH, and hypertonic saline should be used only in severely symptomatic patients 5, 3.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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