The "new normal" osmotic threshold: Osmostat reset

Abstract

Hyponatremia is the most common electrolyte disorder in hospitalized patients. The syndrome of inappropriate antidiuresis (SIAD) is one of the leading causes of hyponatremia. Although not widely known, SIAD has a vast spectrum of etiologies and differential diagnoses and has been classically divided into four types (A, B, C, D). Frequently, when we use the term SIAD in clinical practice, it refers to subtype A, the so-called classic SIAD. The purpose of reporting this case is to make the clinicians aware of a specific subtype of SIAD, type C, an underdiagnosed entity called osmostat reset (OR). Due to similarities, OR often ends up being misinterpreted as classic SIAD. However, the differentiation between these two entities is crucial due to treatment implications. This manuscript highlights the use of an algorithm, based on the fraction of uric acid excretion, as an approach to the differential diagnosis of hyponatremia.

Keywords: SIAD; hyponatremia; inappropriate ADH syndrome; osmostat reset.

Figure 1.. Water load test. The patient underwent an intravenous infusion of 15 mL/kg of electrolyte-free water (glucose 5%) for 1 hour on day 20 of hospitalization. There was a significant drop (> 80%) in urinary osmolarity (U_OSM) from T0 (646 mOsm/L) to T4 (100 mOsm/L), with no oscillation in plasma sodium concentration (P_Na at T0 = 127, T4 = 128 mEq/L), indicating preserved urinary dilution capacity, confirming the osmostat reset diagnosis. U_Na = urinary sodium concentration; P_OSM = plasma osmolarity.

Figure 2.. Use of FE_URATE as a tool in the differential diagnosis of hyponatremia. Adapted from Imbriano et al. [12]. FE_URATE can be obtained by calculating the product of urinary urate and serum creatinine, divided by the product between plasma uric acid and urinary creatinine, multiplied by 100 (FE_URATE = U_URATE X P_CR / P_AU X U_CR × 100). *The presence of hypouricemia (< 4 mg/dL) is more suggestive of SIAD, but it may also be present in cases of RSW and thiazide-induced hyponatremia. **In cases of hyponatremia in which SIAD and thiazide are the most probable differential diagnosis, Fenske et al. demonstrated that an FE_URATE cut off > 12% had a positive predictive value of 100% in defining SIAD as the cause factor [13]. HCTZ = hydrochlorothiazide; SIAD = syndrome of inappropriate antidiuresis; RSW = renal salt wasting; FE_URATE = fractional excretion of urate; P_UA = plasma uric acid concentration.