The diurnal rhythm of plasma potassium: relationship to diuretic therapy

Plasma potassium levels have been implicated in the genesis of cardiac arrhythmias, particularly in patients receiving diuretic therapy. The present study was undertaken to evaluate the stability of plasma potassium levels throughout a 28-h period. Normal volunteers (n = 8) and subjects with essential hypertension (n = 10) were studied in a clinical research center while receiving controlled dietary intakes. Plasma potassium followed a diurnal rhythm in both groups, with a peak level at 12 h and a trough level at 24 h. The average peak-to-trough difference was 0.62 +/- 0.05 mmol/L. Urinary potassium excretion also followed a diurnal rhythm, with the lowest excretory rate during the evening hours, when plasma potassium reached its nadir. Subjects with essential hypertension were restudied after 4 weeks of hydrochlorothiazide (50 mg/day) and then after an additional 4 weeks of hydrochlorothiazide (50 mg/day) and amiloride (5 mg/day). Hydrochlorothiazide alone reduced plasma potassium at all times of measurement without altering the diurnal rhythm. The combination of hydrochlorothiazide and amiloride resulted in higher plasma potassium levels in the morning, but did not significantly affect evening plasma potassium levels. The frequency of hypokalemia (K less than or equal to 3.0 mmol/L) was related to the time at which the plasma potassium was measured. We conclude that plasma potassium undergoes a diurnal rhythm and that diuretics shift this rhythm to uniformly lower values. This rhythm must be considered when defining the frequency of hypokalemia.