Thiazide-Associated Hyponatremia, Report of the Hyponatremia Registry: An Observational Multicenter International Study

Abstract

Background: Hyponatremia is a frequent and potentially life-threatening adverse side effect of thiazide diuretics. This sub-analysis of the Hyponatremia Registry database focuses on current management practices of thiazide-associated hyponatremia (TAH) and compares differences between TAH and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Methods: We analyzed 477 patients from 225 US and EU sites with euvolemic hyponatremia ([Na⁺] ≤130 mEq/L) who were receiving a thiazide diuretic. Of these, 118 met criteria for true thiazide-induced hyponatremia (TIH). Results: Thiazide was withdrawn immediately after hyponatremia was diagnosed only in 57% of TAH; in these patients, the median rate of [Na⁺] change (Δ_daily[Na⁺]) was significantly higher than those with continued thiazide treatment (3.8 [interquartile range: 4.0] vs. 1.7 [3.8] mEq/L/day). The most frequently employed therapies were isotonic saline (29.6%), fluid restriction (19.9%), the combination of these two (8.2%), and hypertonic saline (5.2%). Hypertonic saline produced the greatest Δ_daily[Na⁺] (8.0[6.4] mEq/L/day) followed by a combination of fluid restriction and normal saline (4.5 [3.8] mEq/L/day) and normal saline alone (3.6 [3.5] mEq/L/day). Fluid restriction was markedly less effective (2.7 [2.7] mEq/L/day). Overly rapid correction of hyponatremia occurred in 3.1% overall, but in up to 21.4% given hypertonic saline. Although there are highly significant differences in the biochemical profiles between TIH and SIADH, no predictive diagnostic test could be derived. Conclusions: Despite its high incidence and potential risks, the management of TAH is often poor. Immediate withdrawal of the thiazide is crucial for treatment success. Hypertonic saline is most effective in correcting hyponatremia but associated with a high rate of overly rapid correction. We could not establish a diagnostic laboratory-based test to differentiate TIH from SIADH.

Severe Hyponatremia Presenting with Minimal Symptoms

“…Thiazide-associated hyponatremia can occur within a few days or years of taking the medication [ 2 - 7 ]. Risk factors include older age, low body mass, and female gender [ 2 , 4 , 7 ].…”

Altered Prostaglandin Signaling as a Cause of Thiazide-Induced Hyponatremia

“…This study should remind clinicians that patients with hyponatremia on thiazide therapy may present with clinical findings indicative of SIADH, and yet distinguishing SIADH from hypovolemic hyponatremia on clinical grounds can be difficult. 15 Sodium-depleted patients may retain water, which will partly repair the volume deficit, making it difficult to diagnose by physical examination and preventing the development of azotemia. Urine studies may also be difficult to interpret, especially in elderly patients who often have slower adaptation to hypovolemia with sodium retention.…”

Emergencies in Lung Cancer

“…Küçük hücreli dışı akciğer kanserinde (KHDAK) nadirdir. Ayrıca, beyin, başboyun ve meme kanseri gibi tümörlerde de UADHS görülebilir (67) . Vinkristin, vinblastin ve sisplatin gibi sitotoksik ilaçlar farklı mekanizmalarla UADHS gelişimine neden olabilir (68,69) .…”