ALTERATIONS IN PARATHYROID DYNAMICS IN LITHIUM-TREATED SUBJECTS

Chronic lithium (Li) therapy, used extensively in the treatment of bip olar affective disorders, is one of psychiatry's most effective treatm ents. The data on the effects of Li on baseline PTH and calcium (Ca) l evels are conflicting. A clear resetting of the PTH set-point to the r ight was documented in vitro; however, the effect of Li on the Ca-PTH axis has not been rigorously studied in vivo. In this study, we used a Ca and citrate infusion protocol to fully characterize PTH dynamics i n seven female patients, 40 +/- 11 yr old, on chronic Li therapy for 5 .23 +/- 4.0 yr, compared with seven controls, 41 +/- 16 yr old (mean /- SD). Baseline ionized Ca (Ca,) and intact PTH levels were 5.2 +/- 0 .06 mg/dL and 38.4 +/- 5.7 pg/mL in the Li group and 4.9 +/- 0.06 mg/d L and 21.2 +/- 5.0 pg/mL in the controls, (mean +/- SEM) P = 0.008 and 0.042, respectively. We defined an inverse sigmoidal curve between Ca -i and the intact biologically active PTH molecule (iPTH) for the two study groups and demonstrated a significant shift in the iPTH set-poin t to the right in the Li-treated patients, compared with controls. The set-point was 5.08 +/- 0.04 for the former group and 4.88 +/- 0.04 mg /dL for the latter, P = 0.004. Patients on Li had significantly higher Ca-i levels during citrate and Ca infusions, P = 0.0008 and 0.012, re spectively; however, iPTH levels were not significantly different betw een the two study groups during either infusion. The shift in the iPTH set-point to the right in the Li-treated patients and the similar iPT H levels, despite higher serum Ca-i levels during both infusions, esta blish the presence of a clear alteration in PTH dynamics in patients o n chronic Li therapy.