Thiazide diuretics for hypertensive treatment induced severe hyponatremia with consciousness disturbance in two elderly cases

Abstract

The salt intake of the Japanese is among the highest in the world, leading to a high prevalence of salt-sensitive hypertension. To prevent this, salt restriction, surpression of the rennin-angiotensin-aldosterone system, and natriuresis are important. Therefore, the use of a combination of an angiotensin II receptor blocker and thiazide diuretics is used for antihypertensive treatment. Some randomized controlled studies suggested that thiazide diuretics are useful not only to lower blood pressure, but also to prevent cardiovascular events and improve prognosis in the elderly, who are prone to being salt-sensitive.
We encountered 2 elderly patients referred to our emergency room because of severe hyponatremia and consciousness disturbance, who had been treated with thiazide diuretics for 1 and 2 months, respectively. In both, hypernatriuria despite hyponatremia, slight dehydration, and refractory antidiuretic hormone (ADH) excess were obsereved, but activation of the rennin-angiotensin-aldosterone system was absent. Thyroid and adrenal functions were unremarkable.
Theses phenomena have much in common with the condition called mineralcorticoid-responsive hyponatremia of the elderly (MRHE). Several weeks after discontinuation of diuretics, serum sodium values returned to normal levels, but transtubular potassium concentration gradient (TTKG) values were depleted despite slight hyperkalemia, and relative ADH excess was sustained, which suggested mineralocorticoid dysfunction and distal renal tubulointerstitial injury.
Distal tubulointerstitial dysfunction is one of the most important causes of MRHE. On the basis of these 2 cases, we speculated whether distal tubulointerstitial injury may accelerate hyponatremia in the elderly. We need to check not only serum potassium, but also sodium levels, especially in elderly persons with suspected tubulointerstitial injury.