Thiazide-induced hyponatraemia: distinguishing hypovolaemic and euvolaemic subtypes to guide management strategies.

Abstract

Hyponatraemia is the most prevalent electrolyte imbalance observed in acute clinical settings, occurring in up to 30% of inpatients. Thiazide-induced hyponatraemia (TIH) is common, accounting for approximately one quarter of hyponatraemia cases among hospitalised patients. TIH presentations may occur with either a diuretic-induced volume depletion and subsequent hypovolaemic hyponatraemia or with a syndrome of inappropriate antidiuresis (SIAD)-like presentation with euvolaemic hyponatraemia (which is more common). Hyponatraemia is associated with prolonged hospital length of stay and greater risk of readmission and, hence, a significant driver of additional inpatient healthcare costs. Similarly, TIH can lengthen hospital stay, underscoring the importance of early and accurate differentiation between its subtypes to guide management. Thiazides induce diuresis by inhibiting the sodium-chloride cotransporter in the distal convoluted tubule of the kidneys, thus leading to natriuresis, increased urinary chloride, aquaresis and mild volume depletion. However, thiazides can lead to a compensatory euvolaemic state through various mechanisms. Discriminating hypovolaemic from euvolaemic presentations can be challenging when using traditional approaches to assessing and managing hyponatraemia. Volume status assessment by physical examination can be unreliable, and since thiazides promote natriuresis, urine sodium levels provide limited diagnostic value. Thus, assessing serum (sodium, potassium, chloride) and urine (chloride, potassium) biochemistry in greater detail is useful for distinguishing between the two subtypes of TIH, which have different management strategies. We present a narrative review of TIH and propose a practical diagnostic approach to assist in clinical judgement for early and accurate determination of the subtypes, enabling prompt management.