Pretibial edema was observed in nine consecutive manic-depressive patients who were ingesting therapeutic amounts of lithium, carbonate. The edema was slight to modest in amount, occurred during periods of high sodium intake, and was associated with sodium retention. In four of the nine cases it spontaneously disappeared, even though the high sodium intake and lithium carbonate treatment continued. The pathogenesis of the edema cannot be specified, since the measurements of renal, cardiovascular, and hepatic functions obtained during the period of edema were not abnormal. Although urinary excretion of aldosterone was not increased by treatment with lithium carbonate, spironolactone, a specific aldosterone inhibitor, temporarily eliminated the edema, indicating that the tubular reabsorption of sodium has some role in the edema formation.
Demers R, Heninger G. Pretibial Edema and Sodium Retention During Lithium Carbonate Treatment. JAMA. 1970;214(10):1845-1848. doi:10.1001/jama.1970.03180100039007