How Is SIADH Diagnosed and Managed?

KEY POINTS

  • Clinical assessment of volume status is often inaccurate.
  • Acute symptomatic hyponatremia is treated with 3% hypertonic saline.
  • Chronic hyponatremia is managed with fluid restriction and salt tablets.
  • Vasopressin receptor antagonists might play a role in chronic hyponatremia management.

ADDITIONAL READING

  • Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW, Sterns RH. Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med. Nov 2007;120(11 Suppl 1):S1-21.
  • Ellison DH, Berl T. The Syndrome of Inappropriate Antidiuresis. N Engl J Med. 2007;357:941-942.
  • Milionis HJ, Liamis GL, Elisaf MS. The hyponatremic patient: a systematic approach to laboratory diagnosis. CMAJ. Apr 16 2002;166(8):1056- 1062.

Case

A 70-year-old woman with hypertension presents after a fall. Her medications include hydrochlorothiazide. Her blood pressure is 130/70 mm/Hg, with heart rate of 86. She has normal orthostatic vital signs. Her mucus membranes are moist and she has no jugular venous distension, edema, or ascites. Her plasma sodium (PNa) is 125 mmol/L, potassium 3.6 mmol/L, blood urea nitrogen (BUN) 30 mg/dL, and creatinine 0.8 mg/dL. Additional labs include serum thyroid stimulating hormone 1.12 mIU/L, cortisol 15 mcg/dL, serum osmolality 270 mOsm/kg, uric acid 4 mg/dL, urine osmolality 300 mOsm/kg, urine sodium (UNa) 40 mmol/L, fractional excretion of sodium 1.0%, and fractional excretion of urate (FEUrate) 13%. She receives 2 L isotonic saline intravenously over 24 hours, with resulting PNa of 127.

What is the cause of her hyponatremia, and how should her hyponatremia be managed?

Overview

Hyponatremia is one of the most common electrolyte abnormalities; it has a prevalence as high as 30% upon admission to the hospital.1 Hyponatremia is important clinically because of its high risk of mortality in the acute and symptomatic setting, and the risk of central pontine myelinolysis (CPM), or death with too rapid correction.2 Even so-called “asymptomatic” mild hyponatremia is associated with increased falls and impairments in gait and attention in the elderly.3

Hyponatremia is a state of excess water compared with the amount of solute in the extracellular fluid. To aid in diagnosing the etiology of hypotonic hyponatremia, the differential is traditionally divided into categories based on extracellular fluid volume (ECV) status, as shown in Table 1 (below), with syndrome of inappropriate antidiuretic hormone secretion (SIADH) being the most common cause of euvolemic hyponatremia.2 However, data show that clinical determination of volume status is often flawed,4 and an algorithmic approach to diagnosis and treatment yields improved results.5

Review of the Data

Diagnosis of SIADH. The original diagnostic criteria for SIADH, with minor modifications, are presented in Table 2, page 18).6,7,8 However, applying these criteria in clinical settings presents several difficulties, most notably a determination of ECV. The gold standard for assessing ECV status is by radioisotope, which is not practically feasible.9 Therefore, clinicians must rely on surrogate clinical markers of ECV (orthostatic hypotension, skin turgor, mucus membrane dryness, central venous pressure, BUN, BUN-creatinine ratio, and serum uric acid levels), which lack both sensitivity and specificity.4 Astoundingly, clinical assessment of ECV has been demonstrated to be accurate only 50% of the time when differentiating euvolemic patients from those with hypovolemia.4

Table 1.  Etiologies of Hyponatremia Classified by Volume Status

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Table 1. Etiologies of Hyponatremia Classified by Volume Status

Another challenge lies in the interpretation of UNa, which frequently is used as a surrogate for extra-arterial blood volume (EABV) status.10 Unfortunately, in the setting of diuretic use, UNa becomes inaccurate. The FEUrate, however, is unaffected by diuretic use and can be helpful in distinguishing between etiologies of hyponatremia with UNa greater than 30 mmol/L.11 The FEUrate is about 10% in normal euvolemic subjects and is reduced (usually <8%) in patients with low effective arterial blood volume.11,12 A trial of 86 patients demonstrated that a FEUrate of 12% had a specificity and positive predictive value of 100% in accurately identifying SIADH from diuretic-induced hyponatremia in patients on diuretics.11,12 Therefore, the UNa is a valid marker of EABV status when patients are not on diuretics; however, the FEUrate should be used in the setting of diuretic use.

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