Syndrome of Inappropriate Antidiuretic Hormone Secretion Clinical Presentation
- Author: Christie P Thomas, MBBS, FRCP, FASN, FAHA; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
Hyponatremia is usually detected by laboratory testing.
Depending on the magnitude and rate of development, hyponatremia may or may not cause symptoms. In general, slowly progressive hyponatremia is associated with fewer symptoms than is a rapid drop of serum Na+ to the same value. Patients with moderate, chronic hyponatremia may have decreased reaction times, cognitive slowing, and ataxia resulting in frequent falls.[14, 17]
Signs and symptoms of acute hyponatremia do not precisely correlate with the severity or the acuity of the hyponatremia. Some patients with profound hyponatremia may be relatively asymptomatic. Anorexia, nausea, and malaise are early symptoms and may be seen when the serum Na+ level is less than 125 mEq/L. A further decrease in the serum Na+ level can lead to headache, muscle cramps, irritability, drowsiness, confusion, weakness, seizures, and coma. These occur as osmotic fluid shifts result in cerebral edema and increased intracranial pressure.
Important considerations related to the history are symptoms that reflect the cause of SIADH. Patients may have symptoms that suggest increased secretion of ADH, such as chronic pain, symptoms from CNS or pulmonary tumors (eg, hemoptysis, chronic headaches), or head injury, and drug use. It is important to determine if the patient has had excessive fluid intake because of inappropriate thirst or psychogenic polydipsia or because hypotonic fluids were administered in a healthcare setting. The history may also give important information about the chronicity of the condition, which may, in turn, influence the rate of correction of hyponatremia.
After the identification of hyponatremia, the approach to the patient depends on the clinically assessed volume status. In SIADH, the patient is typically euvolemic and normotensive. Peripheral and pulmonary edema, dry mucous membranes, reduced skin turgor, and orthostatic hypotension are usually absent. Edema in a hyponatremic patient warrants consideration of another hyponatremic state, such as congestive heart failure (CHF) or cirrhosis, or chronic kidney disease.
Prominent physical examination findings may be seen only in severe or rapid-onset hyponatremia and can include confusion, disorientation, delirium, generalized muscle weakness, myoclonus, tremor, asterixis, hyporeflexia, ataxia, dysarthria, Cheyne-Stokes respiration, pathologic reflexes, generalized seizures, and coma.
Bartter FC, Schwartz WB. The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med. 1967 May. 42(5):790-806. [Medline].
Sterns RH. Disorders of plasma sodium--causes, consequences, and correction. N Engl J Med. 2015 Jan 1. 372 (1):55-65. [Medline].
Verbalis JG, Berl T. Disorders of water balance. Brenner BM. Brenner & Rector's The Kidney. 8th ed. Saunders; 2007. Vol 1: 459-491.
Elhassan EA, Schrier RW. Hyponatremia: diagnosis, complications, and management including V2 receptor antagonists. Curr Opin Nephrol Hypertens. 2011 Mar. 20(2):161-8. [Medline].
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].
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].
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].
Schrier RW. Body water homeostasis: clinical disorders of urinary dilution and concentration. J Am Soc Nephrol. 2006 Jul. 17(7):1820-32. [Medline].
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].
Upadhyay A, Jaber BL, Madias NE. Incidence and prevalence of hyponatremia. Am J Med. 2006 Jul. 119(7 Suppl 1):S30-5. [Medline].
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].
Kumar S, Fowler M, Gonzalez-Toledo E, Jaffe SL. Central pontine myelinolysis, an update. Neurol Res. 2006 Apr. 28(3):360-6. [Medline].
Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007 May 17. 356(20):2064-72. [Medline].
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].
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].
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].
Decaux G. Is asymptomatic hyponatremia really asymptomatic?. Am J Med. 2006 Jul. 119(7 Suppl 1):S79-82. [Medline].
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].
Sterns RH, Silver SM. Cerebral salt wasting versus SIADH: what difference?. J Am Soc Nephrol. 2008 Feb. 19(2):194-6. [Medline].
Yee AH, Burns JD, Wijdicks EF. Cerebral salt wasting: pathophysiology, diagnosis, and treatment. Neurosurg Clin N Am. 2010 Apr. 21(2):339-52. [Medline].
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].
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].
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].
[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].
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].
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].
Decker BC. Disorders of Water Excess: Hyponatremia. Dale DC, Federman DD, eds. ACP Medicine. BC Decker; 2007. Vol 1:
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].
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].
Gross P. Treatment of hyponatremia. Intern Med. 2008. 47(10):885-91. [Medline].
Marik PE, Rivera R. Therapeutic effect of conivaptan bolus dosing in hyponatremic neurosurgical patients. Pharmacotherapy. 2013 Jan. 33(1):51-5. [Medline].