Effects of long-term lithium infusion on normal parathyroid tissue.
BACKGROUND
Approximately 10% of patients taking lithium for manic-depressive disorders become hypercalcemic. It remains unclear whether lithium initiates disease or promotes underlying hyperparathyroidism. We have previously demonstrated that at therapeutic concentrations lithium stimulates in vitro incorporation of both tritiated thymidine and bromodeoxyuridine into abnormal human parathyroid tissue, reflecting growth-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 implantable subcutaneous pumps into normal rats for 3 months and measured levels of serum lithium, serum calcium, and serum parathyroid hormone (PTH) (with a radioimmunoassay specific for rat PTH 1-34.) On completion of the infusion, bromodeoxyuridine (30 mg/kg) was administered intraperitoneally. The parathyroid glands were removed and measured in two dimensions to calculate gland volume [V = (pi/6) x (d1) x (d2)2.] Parathyroid incorporation of bromodeoxyuridine was assessed by using immunocytochemistry.


RESULTS
Serum lithium level was significantly (p < 0.05) different between groups and constant within groups. Levels of serum calcium and PTH were inversely related to each other; however, no significant differences were noted between groups with respect to level of serum calcium or serum PTH at any measurement. Similarly, no significant differences were noted between groups with respect to gland size or number of bromodeoxyuridine-positive cells.


CONCLUSIONS
Long-term lithium infusion in rats for a period representing approximately 15% of their life span failed to evoke changes in parathyroid gland size or function. These data are consistent with (1) lithium as a promoter of hyperparathyroidism and (2) resection of abnormal parathyroid tissue and resumption of lithium for patients requiring long-term therapy.
Saxe
A
A
DeRoy Surgical Research Laboratory, Sinai Hospital, Detroit, Mich. 48235, USA.
Gibson
G
G
Silveira
E
E
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002118:Calcium / Q000097:blood; D007150:Immunohistochemistry; D007260:Infusion Pumps; D008094:Lithium / Q000008:administration & dosage* / Q000494:pharmacology; D018021:Lithium Chloride / Q000097:blood; D008297:Male; D009994:Osmolar Concentration; D010280:Parathyroid Glands / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010281:Parathyroid Hormone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D010281:Parathyroid Hormone; D008094:Lithium; D001973:Bromodeoxyuridine; D018021:Lithium Chloride; D002118:Calcium