Hyperparathyroidism and long-term lithium therapy--a cross-sectional study and the effect of lithium withdrawal

To assess in patients with long-term lithium treatment the incidence and prevalence of hypercalcaemia and hyperparathyroidism, and to evaluate the relationship between parathyroid function and renal function: also, to examine the effect of treatment discontinuation.

Part 1. An epidemiological cross-sectional study covering defined catchment areas. Part 2. A lithium withdrawal study in a subgroup of the patients who were examined after a mean of 8.5 (4-16) weeks off lithium. Comparisons were made with a group of psychiatric non-lithium patients matched for sex and age.

Outpatient treatment at nine psychiatric departments in southern Sweden.

Inclusion criterion was 15 years or more on lithium. Excluded from Part 2 were patients with a high risk of relapse. Out of 215 identified patients. 142 (66%) entered and completed Part 1, while 13 of the latter entered and completed Part 2.

The point prevalence of persistent hypercalcaemia was 3.6% and of surgically verified hyperparathyroidism 2.7%. The observed incidence of hyperparathyroidism over 19 years was 6.3%. It was significantly higher than expected in females. In the withdrawal group serum calcium was significantly increased compared to controls, and did not change during 8.5 weeks without lithium. Isostenuria was significantly more common among patients with than without hyperparathyroidism.

The point prevalence, and the 19-year incidence of hyperparathyroidism, were increased. The point prevalence of hypercalcaemia was also increased, and not reversible during 8.5 weeks off lithium. The findings support the hypothesis of a causal relationship between lithium treatment and hyperparathyroidism. Hypercalcaemia and hyperparathyroidism are sometimes aetiologically related to reduced renal function in long-term lithium patients.