Syndrome of inappropriate antidiuretic hormone secretion

Last updated: March 24, 2022

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Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of euvolemic hypotonic hyponatremia. SIADH is an endocrine disorder caused by increased antidiuretic hormone (ADH) secretion in the pituitary gland (e.g., due to infection, drugs), ectopic production of ADH (e.g., in small cell lung carcinoma), or enhanced ADH receptor activation in the kidneys as a result of a genetic mutation (i.e., nephrogenic SIADH). Patients with SIADH present with hyponatremia caused by increased renal water retention. Diagnosis requires confirmation of serum hyponatremia and hypoosmolality, increased urine salt excretion and urine osmolality, clinical euvolemia, and exclusion of other causes of euvolemic hypotonic hyponatremia (e.g., hypothyroidism, adrenal insufficiency, diuretic use). Treatment involves managing symptoms of acute hyponatremia with hypertonic saline, addressing underlying causes (e.g., infection, cancer, medications), reducing free water intake with fluid restriction, and, if needed, increasing free water excretion with pharmacological treatments.

For detailed information on hyponatremia management, see “Treatment of hyponatremia.”

Increased pituitary ADH secretion [1]

CNS conditions

Chronic disease

Drugs

Paraneoplastic ectopic ADH production [1]

Nephrogenic SIADH [4]

Symptoms of hyponatremia

Chronic hyponatremia may be asymptomatic and CNS symptoms are less common.

Other clinical features

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).

Approach [5]

SIADH is a diagnosis of exclusion. Rule out other causes of euvolemic hypotonic hyponatremia before making a diagnosis of SIADH.

Diagnostic criteria [5][6][7][8]

Diagnostic criteria for SIADH [5][6][7][8]
Clinical and/or laboratory findings
Hyponatremia
Hypoosmolality
Euvolemia
Concentrated urine
Elevated urinary sodium
  • Urine sodium concentration > 20–30 mEq/L [5][6][9]
No alternative causes

Hyponatremia caused by hypothyroidism is usually accompanied by signs of myxedema coma and/or TSH > 50 mU/mL. Mild hypothyroidism should still prompt evaluation for another cause of hyponatremia. [5][10]

Additional findings [5][6][7][8]

These findings are not required to make a diagnosis, but may further support SIADH as the cause of euvolemic hypotonic hyponatremia.

FEUA and FEUrea values are not affected by diuretic use. [9][11]

See “Hyponatremia.”

The differential diagnoses listed here are not exhaustive.

For patients with acute hyponatremia and/or who are severely symptomatic; , initiate immediate 3% hypertonic saline administration; and start ICU monitoring; a loop diuretic (e.g., furosemide) may be added in severe cases. See also “Treatment of hyponatremia” for detailed information and dosages. [5]

In patients with acute and severely symptomatic hyponatremia, immediate use of hypertonic saline can treat and/or prevent serious neurologic complications (e.g., cerebral edema, brain herniation, seizures, altered mental status). [5]

Approach [5][8]

The following management applies to patients with nonacute, nonsevere hyponatremia associated with SIADH and after the initial stabilization of patients with acute and/or severely symptomatic hyponatremia.

For patients with chronic hyponatremia, the maximum limit (not goal) for serum sodium level increase is 10–12 mEq/L per 24 hours. Use a lower maximum limit of 8 mEq/L per 24 hours for patients with high-risk factors for osmotic demyelination syndrome. [7]

In patients with chronic hyponatremia, sodium overcorrection can lead to osmotic demyelination syndrome. [5][7]

Fluid restriction [5][8]

Restriction of all fluids (e.g., PO intake, IV fluids, medications, IV flushes) is the first-line treatment for SIADH.

  • Recommend < 1000 mL/day for most patients. [7][8]
  • Adjust based on the patient's response (i.e., serum sodium levels and urine output).

Ideally, daily fluid intake should be 500 mL less than daily urine output. [5]

Pharmacotherapy [5][6][7][8]

These agents are used to increase free water excretion. Medications should be ordered in consultation with a specialist.

  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. Verbalis JG, Goldsmith SR, Greenberg A, et al. Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013; 126 (10): p.S1-S42. doi: 10.1016/j.amjmed.2013.07.006 . | Open in Read by QxMD
  6. Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant. 2014; 29 (suppl_2): p.i1-i39. doi: 10.1093/ndt/gfu040 . | Open in Read by QxMD
  7. 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
  8. Ellison DH, Berl T. The Syndrome of Inappropriate Antidiuresis. N Engl J Med. 2007; 356 (20): p.2064-2072. doi: 10.1056/nejmcp066837 . | Open in Read by QxMD
  9. Nicole Nigro, Bettina Winzeler, Isabelle Suter-Widmer, Philipp Schuetz, Birsen Arici, Martina Bally, Claudine A. Blum, Christian H. Nickel, Roland Bingisser, Andreas Bock, Andreas Huber, Beat Müller, Mirjam Christ-Crain. Evaluation of copeptin and commonly used laboratory parameters for the differential diagnosis of profound hyponatraemia in hospitalized patients: ‘The Co-MED Study'. Clin Endocrinol (Oxf). 2016; 86 (3): p.456-462. doi: 10.1111/cen.13243 . | Open in Read by QxMD
  10. Tee K, Dang J. The suspect - SIADH.. Aust Fam Physician. 2017; 46 (9): p.677-680.
  11. Fenske W, Störk S, Koschker A-C, et al. Value of Fractional Uric Acid Excretion in Differential Diagnosis of Hyponatremic Patients on Diuretics. J Clin Endocrinol Metab. 2008; 93 (8): p.2991-2997. doi: 10.1210/jc.2008-0330 . | Open in Read by QxMD

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