Diagnosing and Treating the Syndrome of Inappropriate Antidiuretic Hormone Secretion.

BACKGROUND: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatremia in clinical practice, but current management of hyponatremia and outcomes in patients with SIADH are not well understood. The objective of the Hyponatremia Registry was to assess the current state of management of hyponatremia due to SIADH in diverse hospital settings, specifically: which diagnostic and treatment modalities are currently employed and how rapidly and reliably they result in an increase in serum [Na+]. A secondary objective was to determine whether treatment choices and outcomes differ across the United States (US) and the European Union (EU). METHODS: The HN Registry recorded selected diagnostic measures and utilization, efficacy, and outcomes of therapy for euvolemic HN diagnosed clinically as SIADH in 1,524 adult patients with serum sodium concentration ([Na+]) ≤130 mEq/L (1,034 from 146 US and 490 from 79 EU sites). A subgroup of patients with more rigorously defined SIADH via measurement of relevant laboratory parameters was also analyzed. RESULTS: The most common monotherapy treatments for hyponatremia in SIADH were fluid restriction (48%), isotonic (27%) or hypertonic (6%) saline, and tolvaptan (13%); 11% received no active agent. The mean rate of [Na+] change (mEq/L/d) was greater for all active therapies than no active treatment. Hypertonic saline and tolvaptan produced the greatest mean rate of [Na+] change (IQR both 3.0(6.0) mEq/L/d), compared to lower IQR rates of [Na+] change for isotonic saline (1.5(3.0) mEq/L/d) and fluid restriction (1.0(2.3) mEq/L/d). The general pattern of responses was similar in both the US and EU cohorts. At discharge, [Na+] was <135 mEq/L in 75% of patients and ≤130 mEq/L in 43%. Overly rapid correction occurred in 10.2%. CONCLUSIONS: 1) Current treatment of hyponatremia in SIADH often employs therapies with limited efficacy; the most commonly chosen monotherapy treatments, fluid restriction and isotonic saline, failed to increase the serum [Na+] by ≥5 mEq/L in 55% and 64% of monotherapy treatment episodes, respectively. 2) Appropriate laboratory tests to diagnose SIADH were obtained in <50% of patients; success rates in correcting hyponatremia were significantly higher when such tests were obtained. 3) Few outcome differences were found between the US and EU. A notable exception was hospital length of stay; use of tolvaptan was associated with significantly shorter length of stay in the EU but not the US. 4) Despite the availability of effective therapies, most patients with SIADH were discharged from the hospital still hyponatremic.