EFFECTS OF LONG-TERM LITHIUM INFUSION ON NORMAL PARATHYROID TISSUE

Background. Approximately 10% of patients taking lithium Sor manic-dep ressive disorders become hypercalcemic. it remains unclear whether lit hium initiates disease or promotes underlying hyperparathyroidism. We have previously demonstrated that at therapeutic concentrations lithiu m stimulates in vitro incorporation of both tritiated thymidine and br omodeoxyuridine into abnormal human parathyroid tissue, reflecting gro wth-promoting properties. Whether lithium has similar growth-promoting properties in normal parathyroid tissue remains unresolved. Methods. We infused lithium (0 mmol/L, 3 mmol/L, or 10 mmol/L) through implanta ble subcutaneous pumps into normal rats for 3 months and measured leve ls of serum lithium, serum calcium, and serum parathyroid hormone (PTH ) (with a radioimmunoassay specific Sor rat PTH 1-34.) On completion o f the infusion, bromodeoxyuridine (30 mg/kg) was administered intraper itoneally. The parathyroid glands were removed and measured in two dim ensions to calculate gland volume [V = (pi/6) X (d(1)) X (d(2))(2)] Pa rathyroid incorporation of bromodeoxyuridine was assessed by using imm unocytochemistry. Results. Serum lithium level was significantly (p < 0.05) different between groups and constant within groups. Levels of s erum calcium and PTH were inversely related to each other; however, no significant differences were noted between groups with respect to lev el of serum calcium or serum PTH at any measurement. Similarly, no sig nificant differences were noted between groups with respect to gland s ize or number of bromodeoxyuridine-positive cells. Conclusions. Long-t erm lithium infusion in rats for a period representing approximately 1 5% of their life span Sailed to evoke changes in parathyroid gland siz e or function. These data are consistent with (1) lithium as a promote r of hyperparathyroidism and (2) resection of abnormal parathyroid tis sue and resumption of lithium for patients requiring long-term therapy .