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Syndrome of inappropriate antidiuretic hormone secretion

Last updated: April 21, 2021

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Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is an endocrine disorder caused by increased ADH secretion in the pituitary gland (e.g., due to infection, drugs), ectopic production of ADH (e.g., small cell lung carcinoma), or enhanced stimulation of ADH in the kidneys as a result of a gene mutation. Hyponatremia develops as a result of increased water retention by the kidneys (not due to sodium deficiency) and systemic fluid overload. SIADH is usually asymptomatic and hyponatremia is often an incidental finding in laboratory results. In mild cases, symptoms include loss of appetite and nausea; in severe cases, seizures and altered consciousness can occur. Treatment depends on the severity of the disease and ranges from fluid restriction (asymptomatic patients) to hypertonic saline administration (severe cases).

Increased pituitary ADH secretion [1]

CNS conditions

Chronic disease

Drugs

Paraneoplastic ectopic ADH production [1]

Nephrogenic SIADH [4]

Symptoms of hyponatremia

Other clinical features

  • Normotension
  • Symptoms of the underlying condition

SIADH patients are usually euvolemic, normotensive, and have no edema. A hyponatremic patient with edema should raise suspicion for other conditions (e.g. congestive heart failure).

Laboratory studies

Blood

Urine [5]

See “Hyponatremia.”

The differential diagnoses listed here are not exhaustive.

Approach

  • In general: treatment of the underlying condition
  • Specific measures depend on whether the patient is symptomatic or not.

Asymptomatic patients

  • Fluid restriction
  • Increased salt intake

Symptomatic patients

Sodium serum levels should increase by a maximum of 10 mmol/L within 24 hours or 0.5 mmol/L per hour.

A rapid increase in serum sodium can lead to osmotic demyelination syndrome!

Vasopressin (ADH) antagonists (vaptans)

Demeclocycline

  1. Sahay M, Sahay R. Hyponatremia: A practical approach. Indian Journal of Endocrinology and Metabolism. 2014; 18 (6): p.760. doi: 10.4103/2230-8210.141320 . | Open in Read by QxMD
  2. Solares I, Tejedor M, Jericó D, et al. Management of hyponatremia associated with acute porphyria—proposal for the use of tolvaptan. Annals of Translational Medicine. 2020; 8 (17): p.1098-1098. doi: 10.21037/atm-20-1529 . | Open in Read by QxMD
  3. Farah R, Farah R. Ecstasy (3,4-Methylenedioxymethamphetamine)-Induced Inappropriate Antidiuretic Hormone Secretion. Pediatr Emerg Care. 2008; 24 (9): p.615-617. doi: 10.1097/pec.0b013e3181850c91 . | Open in Read by QxMD
  4. Feldman BJ, Rosenthal SM, Vargas GA, et al. Nephrogenic Syndrome of Inappropriate Antidiuresis. N Engl J Med. 2005; 352 (18): p.1884-1890. doi: 10.1056/nejmoa042743 . | Open in Read by QxMD
  5. Hoorn EJ, Zietse R. Diagnosis and Treatment of Hyponatremia: Compilation of the Guidelines. J Am Soc Nephrol. 2017; 28 (5): p.1340-1349. doi: 10.1681/asn.2016101139 . | Open in Read by QxMD
  6. Blair HA. Tolvaptan: A Review in Autosomal Dominant Polycystic Kidney Disease. Drugs. 2019; 79 (3): p.303-313. doi: 10.1007/s40265-019-1056-1 . | Open in Read by QxMD
  7. Kortenoeven MLA, Sinke AP, Hadrup N, et al. Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla. American Journal of Physiology-Renal Physiology. 2013; 305 (12): p.F1705-F1718. doi: 10.1152/ajprenal.00723.2012 . | Open in Read by QxMD