Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Syndrome of Inappropriate Antidiuretic Hormone Secretion Medication

  • Author: Christie P Thomas, MBBS, FRCP, FASN, FAHA; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
 
Updated: Oct 28, 2015
 

Medication Summary

Vasopressin receptor antagonists inhibit the V2 receptor, reducing the number of aquaporin-2 water channels in the renal collecting duct and decreasing the water permeability of the collecting duct.

The use of a combination of a loop diuretic (eg, furosemide) and the replacement of urine output with a solution that contains a higher Na+ concentration (ie, 3% sodium chloride solution) can be dramatically successful in some patients. Concomitant use of furosemide increases free water excretion relative to Na+ excretion by the kidneys, thus correcting fluid expansion induced by hypertonic sodium chloride solution.

Next

Vasopressin-Related

Class Summary

The potential benefits of these drugs include the predictability of their effect, rapid onset of action, and limited urinary electrolyte excretion. Conivaptan and tolvaptan are currently the only vasopressin receptor antagonists that are commercially available in the United States and FDA-approved for the treatment of euvolemic hyponatremia in hospitalized patients. These medications should be initiated in a closely monitored setting to prevent rapid correction of serum Na+, which can result in central pontine myelinolysis (CMP).[31]

Conivaptan (Vaprisol)

 

Conivaptan is a parenteral nonselective vasopressin receptor antagonist used for the treatment of euvolemic hyponatremia in hospitalized patients. Conivaptan increases urine output of mostly free water, with little electrolyte loss. It is indicated for hospitalized patients with more severe euvolemic or hypervolemic hyponatremia.

Tolvaptan (Samsca)

 

Tolvaptan is an oral selective vasopressin V2-receptor antagonist. It is indicated for hypervolemic and euvolemic hyponatremia (ie, serum Na level < 125 mEq/L) or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction. It is used for hyponatremia associated with CHF, liver cirrhosis, and syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Initiate or reinitiate the drug in a hospital environment only since there may be overly rapid correction of the hyponatremia. However, it increases thirst (potentially limiting its effects) and is expensive.

Previous
Next

Diuretics, Loop

Class Summary

These agents are often used in the treatment of hypervolemic hyponatremia. In patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) with euvolemic hyponatremia, diuretics are usually used in conjunction with normal saline to replenish the Na+ excreted with the diuresis.

Furosemide (Lasix)

 

Furosemide increases excretion of water by interfering with the Na+-K+-Cl- (Na-K-2Cl) transporter; that, in turn, results in inhibition of Na+ and Cl- reabsorption in the ascending loop of Henle. Na+ is reabsorbed more distally and the excreted urine is hypo-osmolar in relation to serum.

Previous
Next

Diuretics, Osmotic Agents

Class Summary

These agents induce diuresis by elevating the osmolarity of the glomerular filtrate, thereby hindering the tubular reabsorption of water. The overall effect is an increase in free water excretion by the kidneys. Concomitantly, Na+ and Cl- excretion also increase, but to a lesser extent than water excretion.

Urea

 

Urea is used for the treatment of SIADH refractory to or in patients noncompliant with other therapies or when other therapies are not available. Urea is known to promote diuresis. It decreases brain edema, restores medullary tonicity, and induces Na+ retention. Isosmotic concentration of dextrose or invert sugar is coadministered with urea to prevent hemolysis produced by pure solutions of urea.

Mannitol (Osmitrol)

 

Mannitol promotes a rapid free-water diuresis by elevating the osmolarity of the glomerular filtrate, thereby hindering the tubular reabsorption of water. Concomitantly, Na+ and Cl- excretion also increase but to a lesser extent than water excretion. It is typically used intravenously, as a 15-20% solution.

Previous
Next

Tetracyclines

Class Summary

Demeclocycline is an older tetracycline. One of its adverse effects is nephrogenic diabetes insipidus and polyuria, which can correct the excess of water seen in SIADH. It is no longer available in most countries and may be nephrotoxic in patients with liver failure.

Demeclocycline

 

Demeclocycline is a tetracycline derivative that induces diabetes insipidus by impairing the generation and action of cAMP, thus interfering with the action of AVP on the collecting duct. The drug's onset of action may be delayed by over a week; thus, it is not indicated for the emergency management of symptomatic hyponatremia.

Previous
 
Contributor Information and Disclosures
Author

Christie P Thomas, MBBS, FRCP, FASN, FAHA Professor, Department of Internal Medicine, Division of Nephrology, Departments of Pediatrics and Obstetrics and Gynecology, Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics

Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, Royal College of Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Mony Fraer, MD, FACP, FASN Associate Professor, Division of Nephrology, Department of Medicine, University of Iowa Hospitals and Clinics; Staff Physician, Iowa City Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Specialty Editor Board

Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the Advancement of Science, International Society of Nephrology, American Society for Biochemistry and Molecular Biology, American Federation for Medical Research, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, Kentucky Medical Association, National Kidney Foundation, Phi Beta Kappa

Disclosure: Received grant/research funds from Dept of Veterans Affairs for research; Received salary from American Society of Nephrology for asn council position; Received salary from University of Louisville for employment; Received salary from University of Louisville Physicians for employment; Received contract payment from American Physician Institute for Advanced Professional Studies, LLC for independent contractor; Received contract payment from Healthcare Quality Strategies, Inc for independent cont.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.

Acknowledgements

Howard A Bessen, MD Professor of Medicine, Department of Emergency Medicine, UCLA School of Medicine; Program Director, Harbor-UCLA Medical Center

Howard A Bessen, MD is a member of the following medical societies: American College of Emergency Physicians

Disclosure: Nothing to disclose.

Keenan Bora, MD Fellow, Medical Toxicology, Detroit Medical Center; Attending Physician, Medical Center Emergency Services, Detroit

Keenan Bora, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, and American Medical Association

Disclosure: Nothing to disclose.

Meher Chaudhry, MD Chief Resident, Department of Emergency Medicine, Detroit Receiving Hospital, University Health Center

Disclosure: Nothing to disclose.

Sonali Deshmukh, MBBS Consulting Staff, Omaha Nephrology, Nebraska

Sonali Deshmukh, MBBS is a member of the following medical societies: American Society of Nephrology

Disclosure: Nothing to disclose.

obert J Ferry Jr, MD Chief, Division of Pediatric Endocrinology and Metabolism, Le Bonheur Children's Hospital; Professor, Department of Pediatrics, University of Tennessee Health Science Center at Memphis; St. Jude Children's Research Hospital, Memphis, TN; Brigade Surgeon, 36th Sustainment Brigade, U.S. Army; Adjunct Professor, Pediatric Surgery Department, King Saud University, Riyadh, Saudi Arabia

Robert J Ferry Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society

Disclosure: Nutropin Speakers Bureau Honoraria Speaking and teaching; Genotropin Speakers Bureau Honoraria Speaking and teaching; Eli Lilly & Co. Grant/research funds Investigator; MacroGenics, Inc. Grant/research funds Investigator; Ipsen, S.A. (formerly Tercica, Inc.) Grant/research funds Investigator; NovoNordisk SA Grant/research funds Investigator; Diamyd Investigator

Stephen Kemp, MD, PhD Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas College of Medicine and Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Eleanor Lederer, MD Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa

Disclosure: Dept of Veterans Affairs Grant/research funds Research

Lynne Lipton Levitsky, MD Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor of Pediatrics, Harvard Medical School

Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Pfizer Grant/research funds P.I.; Tercica Grant/research funds Other; Eli Lily Grant/research funds PI; NovoNordisk Grant/research funds PI

Chike Magnus Nzerue, MD Associate Dean for Clinical Affairs, Vice-Chairman of Internal Medicine, Meharry Medical College

Chike Magnus Nzerue, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Society of Nephrology, and National Kidney Foundation

Disclosure: Nothing to disclose.

Jose F Pascual-y-Baralt, MD Chief, Division of Pediatric Nephrology, San Antonio Military Pediatric Center; Clinical Professor, Department of Pediatrics, University of Texas Health Science Campus

Jose F Pascual-y-Baralt, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, American Society of Pediatric Nephrology, Association of Military Surgeons of the US, and International Society of Nephrology

Disclosure: Nothing to disclose.

Alexandr Rafailov, MD Staff Physician, Department of Emergency Medicine, State University of New York Downstate/Kings County Hospital

Disclosure: Nothing to disclose.

Arlan L Rosenbloom, MD Adjunct Distinguished Service Professor Emeritus of Pediatrics, University of Florida; Fellow of the American Academy of Pediatrics; Fellow of the American College of Epidemiology

Arlan L Rosenbloom, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Epidemiology, American Pediatric Society, Endocrine Society, Florida Pediatric Society, Lawson-Wilkins Pediatric Endocrine Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Erik D Schraga, MD Consulting Staff, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates; Consulting Staff, Permanente Medical Group, Kaiser Permanente, Santa Clara Medical Center

Disclosure: Nothing to disclose.

Richard H Sinert, DO Associate Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center

Richard H Sinert, DO is a member of the following medical societies: American College of Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, Medscape

Disclosure: Nothing to disclose.

References
  1. Bartter FC, Schwartz WB. The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med. 1967 May. 42(5):790-806. [Medline].

  2. Sterns RH. Disorders of plasma sodium--causes, consequences, and correction. N Engl J Med. 2015 Jan 1. 372 (1):55-65. [Medline].

  3. Verbalis JG, Berl T. Disorders of water balance. Brenner BM. Brenner & Rector's The Kidney. 8th ed. Saunders; 2007. Vol 1: 459-491.

  4. Elhassan EA, Schrier RW. Hyponatremia: diagnosis, complications, and management including V2 receptor antagonists. Curr Opin Nephrol Hypertens. 2011 Mar. 20(2):161-8. [Medline].

  5. Kohen I, Voelker S, Manu P. Antipsychotic-induced hyponatremia: case report and literature review. Am J Ther. 2008 Sep-Oct. 15(5):492-4. [Medline].

  6. Vitting KE, Gardenswartz MH, Zabetakis PM, et al. Frequency of hyponatremia and nonosmolar vasopressin release in the acquired immunodeficiency syndrome. JAMA. 1990 Feb 16. 263(7):973-8. [Medline].

  7. Hoorn EJ, Lindemans J, Zietse R. Development of severe hyponatraemia in hospitalized patients: treatment-related risk factors and inadequate management. Nephrol Dial Transplant. 2006 Jan. 21(1):70-6. [Medline].

  8. Schrier RW. Body water homeostasis: clinical disorders of urinary dilution and concentration. J Am Soc Nephrol. 2006 Jul. 17(7):1820-32. [Medline].

  9. Stelfox HT, Ahmed SB, Khandwala F, Zygun D, Shahpori R, Laupland K. The epidemiology of intensive care unit-acquired hyponatraemia and hypernatraemia in medical-surgical intensive care units. Crit Care. 2008. 12(6):R162. [Medline]. [Full Text].

  10. Upadhyay A, Jaber BL, Madias NE. Incidence and prevalence of hyponatremia. Am J Med. 2006 Jul. 119(7 Suppl 1):S30-5. [Medline].

  11. Ayus JC, Varon J, Arieff AI. Hyponatremia, cerebral edema, and noncardiogenic pulmonary edema in marathon runners. Ann Intern Med. 2000 May 2. 132(9):711-4. [Medline].

  12. Kumar S, Fowler M, Gonzalez-Toledo E, Jaffe SL. Central pontine myelinolysis, an update. Neurol Res. 2006 Apr. 28(3):360-6. [Medline].

  13. Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007 May 17. 356(20):2064-72. [Medline].

  14. Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med. 2006 Jan. 119(1):71.e1-8. [Medline].

  15. Usala RL, Fernandez SJ, Mete M, Cowen L, Shara NM, Barsony J, et al. Hyponatremia Is Associated With Increased Osteoporosis and Bone Fractures in a Large US Health System Population. J Clin Endocrinol Metab. 2015 Aug. 100 (8):3021-31. [Medline].

  16. Clayton JA, Le Jeune IR, Hall IP. Severe hyponatraemia in medical in-patients: aetiology, assessment and outcome. QJM. 2006 Aug. 99(8):505-11. [Medline].

  17. Decaux G. Is asymptomatic hyponatremia really asymptomatic?. Am J Med. 2006 Jul. 119(7 Suppl 1):S79-82. [Medline].

  18. Hew-Butler T, Noakes TD, Siegel AJ. Practical management of exercise-associated hyponatremic encephalopathy: the sodium paradox of non-osmotic vasopressin secretion. Clin J Sport Med. 2008 Jul. 18(4):350-4. [Medline].

  19. Sterns RH, Silver SM. Cerebral salt wasting versus SIADH: what difference?. J Am Soc Nephrol. 2008 Feb. 19(2):194-6. [Medline].

  20. Yee AH, Burns JD, Wijdicks EF. Cerebral salt wasting: pathophysiology, diagnosis, and treatment. Neurosurg Clin N Am. 2010 Apr. 21(2):339-52. [Medline].

  21. Tian W, Fu Y, Garcia-Elias A, et al. A loss-of-function nonsynonymous polymorphism in the osmoregulatory TRPV4 gene is associated with human hyponatremia. Proc Natl Acad Sci U S A. 2009 Aug 18. 106(33):14034-9. [Medline]. [Full Text].

  22. Feldman BJ, Rosenthal SM, Vargas GA, et al. Nephrogenic syndrome of inappropriate antidiuresis. N Engl J Med. 2005 May 5. 352(18):1884-90. [Medline].

  23. Maesaka JK, Miyawaki N, Palaia T, Fishbane S, Durham JH. Renal salt wasting without cerebral disease: diagnostic value of urate determinations in hyponatremia. Kidney Int. 2007 Apr. 71 (8):822-6. [Medline].

  24. [Guideline] Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant. 2014 Apr. 29 Suppl 2:i1-i39. [Medline].

  25. Sterns RH, Hix JK, Silver S. Treating profound hyponatremia: a strategy for controlled correction. Am J Kidney Dis. 2010 Oct. 56 (4):774-9. [Medline].

  26. Zeltser D, Rosansky S, van Rensburg H, Verbalis JG, Smith N. Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia. Am J Nephrol. 2007. 27(5):447-57. [Medline].

  27. Decker BC. Disorders of Water Excess: Hyponatremia. Dale DC, Federman DD, eds. ACP Medicine. BC Decker; 2007. Vol 1:

  28. Nemerovski C, Hutchinson DJ. Treatment of hypervolemic or euvolemic hyponatremia associated with heart failure, cirrhosis, or the syndrome of inappropriate antidiuretic hormone with tolvaptan: a clinical review. Clin Ther. 2010 Jun. 32(6):1015-32. [Medline].

  29. Schrier RW, Gross P, Gheorghiade M, Berl T, Verbalis JG, Czerwiec FS, et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006 Nov 16. 355(20):2099-112. [Medline].

  30. Berl T, Quittnat-Pelletier F, Verbalis JG, et al. Oral tolvaptan is safe and effective in chronic hyponatremia. J Am Soc Nephrol. 2010 Apr. 21(4):705-12. [Medline]. [Full Text].

  31. Gross P. Treatment of hyponatremia. Intern Med. 2008. 47(10):885-91. [Medline].

  32. Marik PE, Rivera R. Therapeutic effect of conivaptan bolus dosing in hyponatremic neurosurgical patients. Pharmacotherapy. 2013 Jan. 33(1):51-5. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.