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Syndrome of Inappropriate Antidiuretic Hormone Secretion

Syndrome of Inappropriate Antidiuretic Hormone Secretion is a topic covered in the 5-Minute Pediatric Consult.

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Inappropriate secretion of antidiuretic hormone (ADH) or ADH-like peptide in the presence of low serum sodium, low serum osmolality, and high urine osmolality and in the absence of renal, adrenal, or thyroid pathology



The syndrome of inappropriate ADH secretion (SIADH) can occur at any age. Its incidence depends on the various possible etiologies.

Risk Factors


Genetic causes of SIADH are exceedingly rare. However, rare cases have been described with gain-of-function mutations in the vasopressin-2 receptor contributing to SIADH and undetectable serum ADH levels.


  • ADH is synthesized within the neurons of the hypothalamus, transported in conjunction with neurophysin down the supraopticohypophyseal tract, and stored in the posterior pituitary.
  • ADH acts on the renal collecting ducts.
  • Interaction of ADH with its receptors forms intracellular cyclic AMP (cAMP), which increases water permeability through insertion of aquaporins (water channels) in renal collecting ducts and consequently enhances reabsorption of free water.
  • SIADH results when elevated ADH or ADH-like peptide concentrations cause free water retention and hypervolemia, leading to hyponatremia; three possible mechanisms include
    • Increased hypothalamic production of ADH (e.g., CNS disorders such as stroke or meningitis)
    • Independent production of ADH or ADH-like substances from ectopic sources (e.g., oat cell carcinoma of the lung or olfactory neuroblastoma)
    • Decreased venous return that stimulates atrial volume receptors and thereby leads to ADH release (e.g., heart failure, cirrhosis; pulmonary and intrathoracic diseases, such as tuberculosis)


  • Idiopathic
  • CNS pathology, causing increased secretion of ADH or ADH-like peptides: meningitis, head trauma, neurosurgical procedures, encephalitis, brain tumor, brain abscess, hydrocephalus, hypoxia, subarachnoid hemorrhage, cerebral venous thrombosis
  • Ectopic production of ADH or ADH-like peptides: oat cell carcinoma of the lung, bronchogenic carcinoma, olfactory neuroblastoma, and pancreatic carcinoma
  • Pulmonary disease (leading to secondary elevation in ADH secretion or ADH-like peptides): tuberculosis, viral or bacterial pneumonia, asthma, cystic fibrosis, pneumothorax, positive pressure ventilation
  • Drugs (which mimic ADH or stimulate its release): vincristine, cyclophosphamide, carbamazepine, chlorpropamide, phenothiazines, clofibrate, nicotine, selective serotonin reuptake inhibitors (SSRIs)
  • Iatrogenic exogenous ADH administration: vasopressin infusion for treatment of diabetes insipidus, excess desmopressin (DDAVP®) in conjunction with fluid intake
  • Severe, prolonged nausea
  • Postoperative patient (e.g., as part of triple-phase response after hypothalamic-pituitary surgery, after transsphenoidal pituitary surgery)
  • Rocky Mountain spotted fever
  • Stem cell transplantation

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Cabana, Michael D., editor. "Syndrome of Inappropriate Antidiuretic Hormone Secretion." 5-Minute Pediatric Consult, 8th ed., Wolters Kluwer, 2019. Pediatrics Central, peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617587/all/Syndrome_of_Inappropriate_Antidiuretic_Hormone_Secretion.
Syndrome of Inappropriate Antidiuretic Hormone Secretion. In: Cabana MD, ed. 5-Minute Pediatric Consult. 8th ed. Wolters Kluwer; 2019. https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617587/all/Syndrome_of_Inappropriate_Antidiuretic_Hormone_Secretion. Accessed April 24, 2019.
Syndrome of Inappropriate Antidiuretic Hormone Secretion. (2019). In Cabana, M. D. (Ed.), 5-Minute Pediatric Consult. Available from https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617587/all/Syndrome_of_Inappropriate_Antidiuretic_Hormone_Secretion
Syndrome of Inappropriate Antidiuretic Hormone Secretion [Internet]. In: Cabana MD, editors. 5-Minute Pediatric Consult. Wolters Kluwer; 2019. [cited 2019 April 24]. Available from: https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617587/all/Syndrome_of_Inappropriate_Antidiuretic_Hormone_Secretion.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Syndrome of Inappropriate Antidiuretic Hormone Secretion ID - 617587 ED - Cabana,Michael D, BT - 5-Minute Pediatric Consult UR - https://peds.unboundmedicine.com/pedscentral/view/5-Minute-Pediatric-Consult/617587/all/Syndrome_of_Inappropriate_Antidiuretic_Hormone_Secretion PB - Wolters Kluwer ET - 8 DB - Pediatrics Central DP - Unbound Medicine ER -