Seminars in Nephrology
Volume 29, Issue 3 , Pages 239-256 , May 2009

The Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH)

  • Guy Decaux, MD, PhD

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Dr Guy Decaux, MD, PhD, General Internal Medicine, University Hospital Erasme, Route de Lennik, 808, B-1070 Brussels, Belgium

References 

  1. Edelman IS, Leibman J, O'Meara MP, Birkenfeld L. Interrelations between serum sodium concentration, serum osmolality and total exchangeable sodium, total exchangeable potassium and total body water. J Clin Invest. 1958;37:1236
  2. Anderson RJ, Chung HM, Kluge R, Schrier RW. Hyponatremia: a prospective analysis of its epidemiology and the pathogenic role of vasopressin. Ann Intern Med. 1985;102:164–168
  3. Sterns RH, Ocdol H, Schrier RW, Narius RG. Hyponatremia: pathophysiology, diagnosis and therapy. In:  Narius RD editors. Clinical disorders of fluid and electrolyte metabolism. 5th ed.. New York: Mc Graw-Hill; 1995;p. 615–883
  4. Bloth B, Christensson T, Mellstedt H. Extreme hyponatremia in patients with myelomatosis: an effect of cationic paraproteins. Acta Med Scand. 1978;203:273–275
  5. Steenberger BA, Ford SM, Coleman TA. Intravenous immuno-globulin therapy results in post-infusional hyperproteinemia, increased serum viscosity, and hyponatremia. Am J Hematol. 2003;73:97–100
  6. Itkin YM, Trujillo TC. Intravenous immunoglobulin associated acute renal failure: case series and literature review. Pharmacotherapy. 2005;25:886–892
  7. Daphnis E, Styliamon K, Alexandrakis M, Xylouri I, Varolaki E, Stratigis S, et al. Acute renal failure, translocational hyponatremia and hyperkaliemia following intravenous immunoglobulins therapy. Nephron Clin Pract. 2007;106:C143–C148
  8. Palewsky PM, Rendulic D, Diven WF. Maltose-induced hyponatremia. Ann Intern Med. 1993;118:526–528
  9. Hillier TA, Abbott RD, Barrett EJ. Hyponatremia evaluating the correction factor for hyperglycemia. Am J Med. 1999;106:399–403
  10. Rhymer JC, Bell TJ, Perry KC, Ward JP. Hyponatremia following transurethral resection of the prostate. Br J Urol. 1985;57:450–452
  11. Silver SM, Kozlowski A, Baer JE, Rogers SJ, Sterns RH. Glycine induced hyponatremia in the rat: a model of post-prostatectomy syndrome. Kidney Int. 1995;47:262–268
  12. Istre O, Bjoennes J, Naess R, Hornbaek K, Forman A. Post-operative cerebral oedema after transcervical endometrial resection and uterine irrigation with 1.5% glycine. Lancet. 1994;344:1187–1189
  13. Agarwal R, Emmet M. The post-transurethral resection of prostate syndrome: therapeutic proposal. Am J Kidney Dis. 1994;24:168–171
  14. Issa MM, Young MR, Bullock AR, Bonet R, Petros JA. Dilutional hyponatremia of TURP Syndrome: a historical event in the 21st century. Urology. 2004;64:298–301
  15. Rose BD. New approach to disturbances in the plasma sodium concentration. Am J Med. 1986;81:1033–1040
  16. Watson PE, Watson ID, Batt RD. Total body water volumes for adult males and females estimated from simple anthropometric measurements. Am J Clin Nutr. 1980;33:27–39
  17. Bartter FC, Schwartz WB. The syndrome of inappropriate secretions of antidiuretic hormone. Am J Med. 1967;42:790–806
  18. Michelis MF, Warms PC, Eusco RD, Dais BB. Hypouricemia and hyperuricosuria in Laennec cirrhosis. Arch Intern Med. 1994;134:681–683
  19. Chung HM, Kluge R, Schrier RW, Anderson RJ. Clinical assessment of extra-cellular fluid volume in hyponatremia. Am J Med. 1987;83:905–908
  20. Musch W, Thimpont J, Vandervelde D, Vanhaeverbeke I, Berghmans T, Decaux G. Combined fractional excretion of sodium and urea better predicts response to saline in hyponatremia than do usual clinical and biochemical parameters. Am J Med. 1995;99:348–355
  21. Musch W, Decaux G. Utility and limitations of biochemical parameters in the evaluation of hyponatremia in the elderly. Intern Urol Nephrol. 2001;32:475–493
  22. Ellison DH, Berl T. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007;356:2064–2072
  23. Musch W, Decaux G. Treating the syndrome of inappropriate secretion of ADH with isotonic. QJM. 1998;91:749–753
  24. Diringer MN, Wu KC, Verbalis JG, Hanley DF. Hypervolemic therapy prevents volume contraction but not hyponatremia following subarachnoid haemorrhage. Ann Neurol. 1992;31:543–550
  25. Maesaka JK, Venkatesan J, Piccione JM, Decker R, Drisach AW, Wetherington J. Plasma natriuretic factor(s) in patients with intra-cranial disease, renal salt wasting and hyperuricasuria. Life Sci. 1993;52:1875–1882
  26. Sherlock M, O'Sullivan E, Agha A, Behan LA, Ravluk D, Brennan P, et al. The incidence and pathophysiology of hyponatremia after subarachnoid haemorrhage. Clin Endocrinol. 2006;64:250–254
  27. Brimouille S, Orellana-Jimenez C, Aminian A, Vincent JL. Hyponatremia in neurological patients: cerebral salt wasting versus inappropriate anti-diuretic hormone secretion. Intensive Care Med. 2008;34:125–131
  28. Friedman E, Shadel M, Halkin H, Farfel Z. Thiazide-induced hyponatremia. Ann Intern Med. 1989;110:24–30
  29. Decaux G, Schlesser M, Coffernils M, Prospert F, Namias B, Brimouille S, et al. Uric acid, anion gap and urea concentration in the diagnostic approach to hyponatremic patients. Clin Nephrol. 1994;42:102–108
  30. Fenske W, Stork S, Koschker AC, Bleckschmidt A, Lorenz D, Wortmann S, et al. Value of fractional uric acid excretion in differential diagnosis of hyponatremic patients on diuretics. J Clin Endocrinol Metab. 2008;93:2991–2997
  31. Musch W, Verfaillie L, Decaux G. Age-related increase in plasma urea level and decrease in fractional urea excretion: clinical application in the syndrome of inappropriate secretion of antidiuretic hormone. Clin J Am Soc Nephrol. 2006;1:909–914
  32. Choukroun G, Schmit F, Martinez F, Drücke T, Bankir L. Low urine flow rate reduces the capacity to excrete a sodium load in man. Am J Physiol. 1997;273:R1726–R1733
  33. Bankir L, Trinh-Trang-Tan MM. Urea and the kidney. In:  Brenner BM,  Rector F editor. The kidney. Philadelphia: WB Saunders; 1999;p. 637–679
  34. Musch W, Hedeshi A, Decaux G. Low sodium excretion in SIADH patients with low diuresis. Nephron Physiol. 2004;96:11–18
  35. Rose BD. Hypoosmolal states—hyponatremia. In:  Jeffers JD,  Navrozov M editor. Clinical physiology of acid-base and electrolyte disorders. 5th ed.. New York: McGraw-Hill; 2001;p. 699–723
  36. Helden T, Svenden TL. Electrolyte disturbances in beer drinkers. Lancet. 1975;2:245–246
  37. Thaler S, Teitlebaum I, Berl T. “Beer potomania” in non-beer drinkers: effect of low dietary solute intake. Am J Kidney Dis. 1998;31:1028–1031
  38. Verhoeven A, Musch W, Decaux G. Treatment of the polydipsia-hyponatremia syndrome with urea. J Clin Psychiatry. 2005;66:1372–1375
  39. Musch W, Xhaet O, Decaux G. Solute loss plays a major role in polydipsia-related hyponatremia of both water drinkers and beer drinkers. QJM. 2003;96:421–426
  40. Leaf A, Bartter FC, Santos RF, Wrong O. Evidence in man that urinary electrolytes loss induced by pitrissin is a function of water retention. J Clin Invest. 1955;32:868–878
  41. Schwartz WB, Bennet TW, Curelop S, Bartter FC. A syndrome resulting from inappropriate secretion of anti-diuretic hormone. Am J Med. 1957;23:529–542
  42. Tian Y, Sandberg K, Murase T, Baker EA, Speth RC, Verbalis JG. Vasopressin V2-receptor binding is down-regulated during renal escape from vasopressin-induced anti-diuresis. Endocrinology. 2000;141:307–314
  43. Murase T, Ecelbarger CA, Baker EA, Tian Y, Knepper MA, Verbalis JG. Kidney aquaporin-2 expression during escape from anti-diuresis is not related to plasma or tissue osmolality. J Am Soc Nephrol. 1999;10:2067–2075
  44. Murase T, Tian Y, Fang XY, Verbalis JG. Synergistic effects of nitric oxide and prostaglandin on renal escape from vasopressin-induced anti-diuresis. Am J Physiol Regul Integr Comp Physiol. 2003;284:R354–R362
  45. Verbalis JG. Whole-body volume regulation and escape from anti-diuresis. Am J Med. 2006;119:S21–S29
  46. Robertson GL. Anti-diuretic hormone: normal and disordered function. Endocrinol Metab Clin North Am. 2001;30:671–694
  47. Palm C, Pistorch F, Herbrig K, Gross P. Vasopressin antagonists as aquaretic agents for the treatment of hyponatremia. Am J Med. 2006;119:S87–S92
  48. Greenberg A, Verbalis JG. Vasopressin receptor antagonists. Kidney Int. 2006;69:2124–2130
  49. Decaux G, Soupart A, Vassart G. Non-peptide arginine-vasopressin antagonists: the Vaptans. Lancet. 2008;371:1624–1632
  50. Decaux G, Waterlot Y, Genette F, Mockel J. Treatment of the syndrome of inappropriate secretion of anti-diuretic hormone with Furosemide. N Engl J Med. 1981;304:329–330
  51. Decaux G. Treatment of the syndrome of inappropriate secretion of anti-diuretic hormone by long loop diuretics. Nephron. 1983;35:82–88
  52. Decaux G, Brimouille S, Genette F, Mockel J. Treatment of the syndrome of inappropriate secretion of anti-diuretic hormone by urea. Am J Med. 1980;69:99–106
  53. Decaux G. Long-term treatment of patients with inappropriate secretion of ADH by vasopressin receptor antagonist Conivaptan, urea or Furosemide. Am J Med. 2001;110:582–584
  54. Oelkers W. Hyponatremia and inappropriate secretion of vasopressin in patients with hypopituitarism. N Engl J Med. 1989;321:492–496
  55. Dorhaut Mees EJ, Blom van Assendelf TP, Niewenhuis MG. Elevation of uric acid clearance caused by inappropriate anti-diuretic hormone secretion. Acta Med Scand. 1971;189:69–72
  56. Beck LH. Hypouricemia in the syndrome of inappropriate secretion of ADH. N Engl J Med. 1979;301:258–531
  57. Braghiroli A, Sacco C, Erbetta M, Ruga V, Donner CF. Overnight urinary uric acid : creatinine ratio for detections of sleep hypoxemia. Validation study in chronic obstructive pulmonary disease and obstructive sleep apnea before and after treatment with nasal continuous positive airway pressure. Am Rev Respir Dis. 1993;148:173–178
  58. Decaux G, Genette F, Mockel J. Hypouremia in the syndrome of inappropriate secretion of anti-diuretic hormone. Ann Intern Med. 1980;93:716–717
  59. Decaux G, Prospert F, Cauchie P, Soupart A. Dissociation between uric acid and urea clearances in the syndrome of inappropriate secretion of ADH related to salt excretion. Clin Sci. 1990;78:451–455
  60. Decaux G, Namias B, Gulbis B, Soupart A. Evidence in hyponatremia related to inappropriate secretion of ADH than V1-receptor stimulation contributes to the increase in uric acid clearance. J Am Soc Nephrol. 1996;7:805–810
  61. Decaux G, Crenier L, Namias B, Gerry C, Soupart A. Normal acid-base equilibrium during acute hyponatremia and mixed alkalosis during chronic hyponatremic induced by AVP or DDAVP in rats. J Lab Clin Med. 1994;123:892–898
  62. Decaux G, Musch W, Penninckx R, Soupart A. Low plasma bicarbonate level in hyponatremia related to adreno-corticotropin deficiency. J Clin Endocrinol Metab. 2003;88:5255–5257
  63. Decaux G, Crenier L, Namias B, Gerry C, Soupart A. Restoration by corticosteroid of the hyperaldosteronism in hyponatremic rats with panhypopituitarism. Clin Sci. 1994;87:435–439
  64. Schneider EG, Taylor RE, Radke KJ, Dairs PH. Effect of sodium concentration on aldosterone secretion by isolated perfused canine adrenal glands. Endocrinology. 1984;115:2195–2204
  65. Namias B, Soupart A, Kornreich A, Decaux G. In human patients, vascular water retention during dAVP related hyponatremia occurs mainly in the plasma volume and not in the erythrocyte. J Lab Clin Med. 1996;128:612
  66. Decaux G, Namias B, Soupart A, Musch W. Indirect evidence to suggest that hyponatremia by itself contributes to the high urate clearance in the SIADH. Am J Kidney Dis. 2000;36:745–751
  67. Verbalis JG. Pathogenesis of hyponatremia in an experimental model of the syndrome of inappropriate anti-diuresis. Am J Physiol. 1994;267:R1617–R1625
  68. Verbalis JG, Drutarsosky MD, Ertel RJ, Vollmen RR. Adaptative responses to sustained volume expansion in hyponatremic rats. J Endocrinol. 1989;122:421–431
  69. Gross P, Lang R, Ketteler M, Hausmann C, Rascher W, Ritz E, et al. Natriuretic factors and lithium clearance in patients with the syndrome of inappropriate anti-diuretic hormone. Eur J Clin Invest. 1989;19:11–19
  70. Decaux G, Van Laethem Y, Van Kuyck M, Mockel J. Hypercaliciuria in the syndrome of inappropriate secretion of antidiuretic hormone. Miner Electrolyte Metab. 1982;7:192–196
  71. Feldman BJ, Rosenthal SM, Vargas GA, Fenwick RG, Huang EA, Matsuda-Abedini M, et al. Nephrogenic syndrome of inappropriate anti-diuresis. N Engl J Med. 2005;358:1884–1890
  72. Takata Y, Sugita K, Saito T, Muroya K, Ishikawa SE, Awazu M, et al. Impaired urinary water excretion in a three-generation family. Pediatr Nephrol. 2001;16:820–822
  73. Bichet DG, Oksche A, Rosenthal W. Congenital nephrogenic diabetes mellitus. J Am Soc Nephrol. 1997;8:1951–1958
  74. Sasaki S. Nephrogenic diabetes mellitus insipidus: update of genetic and clinical aspects. Nephrol Dial Transplant. 2004;19:1351–1353
  75. Decaux G, Vandergheynst FR, Bouko Y, Parma J, Vassart G, Vilain C. Nephrogenic syndrome of inappropriate anti-diuresis in adults: high phenotypic variability in men and women from a large pedigree. J Am Soc Nephrol. 2007;18:606–612
  76. Hirshberg B, Ben-Yehuda A. The syndrome of inappropriate antidiuretic hormone secretion in the elderly. Am J Med. 1997;103:270–273
  77. Soule S, Florkowski C, Potter H, Pattison D, Swan M, Hunt P, et al. Intermittent severe, symptomatic hyponatremia due to the nephrogenic syndrome of inappropriate anti-diuresis. Ann Clin Biochem. 2008;45:520–523
  78. Marcialis MA, Faa V, Fanos V, Puddu M, Pintus MC, Cao A, et al. Neonatal onset of nephrogenic syndrome of inappropriate anti-diuresis. Pediatr Nephrol. 2008;12:2267–2271
  79. Bes DF, Mendilaharzu H, Fenwick RG, Arrizurata E. Hyponatremia resulting from arginine-vasopressin-receptor-2 gene mutation. Pediatr Nephrol. 2007;22:463–466
  80. Soupart A, Gross P, Legros JJ, Alfoldis S, Annane D, Heshmati HM, et al. Successful long-term treatment of SIADH with SR121463B, an orally active non-peptide vasopressin V2-receptor antagonist. Clin J Am Soc Nephrol. 2006;1:364–640
  81. Decaux G, Genette F. Urea for long-term treatment of syndrome inappropriate secretion of antidiuretics hormone. BMJ. 1981;283:1081–1083
  82. Huang EA, Feldman BJ, Schwartz ID, Geller DH, Rosenthal SM, Gitelman SE. Oral urea for the treatment of chronic syndrome of inappropriate antidiuresis in children. J Pediatr. 2006;148:128–131
  83. Arthus MF, Lonergan M, Crumbly MJ, Naumova AK, Morin D, DeMarko LA, et al. Report of 33 novel AVPR2 mutations and analysis of 117 families with X-linked nephrogenic diabetes insipidus. J Am Soc Nephrol. 2000;11:1044–1054
  84. Nomura Y, Onigata K, Nagashima T, Yutani S, Mochizuki H, Nagashima K, et al. Detection of skewed X-inactivation in two female carriers of vasopressin type 2 receptor gene mutation. J Clin Endocrinol Metab. 1997;82:3434–3437
  85. Zuker AM, Singer D, Penninger JM, Rosier BC, Firsov D. Increased renal responsiveness to vasopressin and enhanced V2-receptor signalling in RGS2 -/- mice. J Am Soc Nephrol. 2007;18:1672–1678
  86. Abrabi AK, Terryn S, Valenti G, Caron N, Serradeil-Le Gal C, Ransfaste D, et al. PKD1 haploinsufficiency causes a syndrome of inappropriate antidiuresis in mice. J Am Soc Nephrol. 2007;18:1740–1753
  87. Kumar S, Berl T. Sodium. Lancet. 1998;352:220–228
  88. Adrogué HJ, Madias NE. Hyponatremia. N Engl J Med. 2000;342:1581–1589
  89. Decaux G, Soupart A. Treatment of symptomatic hyponatremia. Am J Med Sci. 2003;326:25–30
  90. Van Amelsvoort T, Bakshi R, Devaux CB, Schwabe S. Hyponatremia associated with Carbamazepine and Oxcarbazepine therapy: a review. Epilepsia. 1994;35:181–188
  91. Singer GG, Brenner BM. Harrison's principles of internal medicine. In:  Braunwald E, et al. editor. Fluid and electrolytes disturbances. New York: Mc Graw-Hill; 2001;p. 271–282
  92. Anpalakan M. Chronic idiopathic hyponatremia in older people due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) possibly related to aging. J Am Geriatr Soc. 2001;49:788–792
  93. Rose BD. Hypoosmolal states-hyponatremia. In:  Rose BD,  Post T editor. Clinical physiology of acid-base and electrolyte disorders. 5th ed.. New York: Mc Graw-Hill; 2001;p. 696–746
  94. Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficit. Am J Med. 2006;119:71e1-8
  95. Gankam Kengne F, Andres C, Sattar L, Melot C, Decaux G. Mild hyponatremia and risk of fracture in the ambulatory elderly. QJM. 2008;101:583–588
  96. Renneboog B, Sattar L, Decaux G. Determination of threshold for attention and gait deficits encountered in chronic hyponatremia [abstract]. J Am Soc Nephrol. 2006;17:37A

 This study was supported by a grant from the Fonds National de la Recherche Scientifique, convention 3.45.09.03 (2006).

PII: S0270-9295(09)00021-7

doi: 10.1016/j.semnephrol.2009.03.005

Seminars in Nephrology
Volume 29, Issue 3 , Pages 239-256 , May 2009

Article Tools

* Image Usage & Resolution