Lithium increases tritiated thymidine uptake by abnormal human parathyroid tissue

Patients receiving lithium for the management of manic depressive disorders appear to be at increased risk for development of hypercalcemia. Some (but not all) clinical studies and several in vitro studies suggest that lithium alters release of parathyroid hormone. Because hypercalcemia may result from an increase in the mass of parathyroid tissue, we studied the in vitro effect of lithium on tritiated thymidine (3H-TdR) incorporation as a measure of DNA synthesis. Dispersed cells from previously cryopreserved tissue from 18 patients undergoing surgery for single-gland hyperparathyroidism (adenoma) and five patients with secondary hyperparathyroidism were incubated with graded concentrations of lithium chloride and, after a 5-day incubation, were pulsed with 3H-TdR. Adenoma cells exposed to 2.0 mmol/L lithium (therapeutic level is approximately 0.8 to 2.0 mmol/L) demonstrated increased 3H-TdR incorporation compared with cells not exposed to lithium (average increase 56%). Secondary hyperplasia cells exhibited a similar but less striking response. There was no lithium-induced 3H-TdR incorporation in four preparations with normal bovine parathyroid cells. We conclude that lithium in therapeutic doses increases 3H-TdR incorporation into adenoma cells, may serve as a mitogen for human parathyroid adenoma, and could promote or accelerate hyperparathyroidism.