Saxe A, Gibson G, Silveira E
DeRoy Surgical Research Laboratory, Sinai Hospital, Detroit, Mich. 48235, USA.
Surgery. 1995 May;117(5):577-80. doi: 10.1016/s0039-6060(05)80258-2.
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.
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.
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.
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.
约10%服用锂盐治疗躁郁症的患者会出现高钙血症。锂盐是引发疾病还是促进潜在的甲状旁腺功能亢进仍不清楚。我们之前已证明，在治疗浓度下，锂盐能在体外刺激氚标记胸腺嘧啶核苷和溴脱氧尿苷掺入异常的人甲状旁腺组织，这反映了其促生长特性。锂盐在正常甲状旁腺组织中是否具有类似的促生长特性仍未明确。
我们通过可植入的皮下泵向正常大鼠输注锂盐（0 mmol/L、3 mmol/L或10 mmol/L），持续3个月，并测量血清锂、血清钙和血清甲状旁腺激素（PTH）水平（采用针对大鼠PTH 1 - 34的放射免疫分析法）。输注结束后，腹腔注射溴脱氧尿苷（30 mg/kg）。取出甲状旁腺，进行二维测量以计算腺体体积[V = (π/6)×(d1)×(d2)²]。通过免疫细胞化学评估甲状旁腺对溴脱氧尿苷的掺入情况。
各组间血清锂水平差异显著（p < 0.05），且组内保持恒定。血清钙和PTH水平呈负相关；然而，在任何测量中，各组间血清钙或血清PTH水平均无显著差异。同样，各组间在腺体大小或溴脱氧尿苷阳性细胞数量方面也无显著差异。
在大鼠中进行为期约占其寿命15%的长期锂盐输注，未能引起甲状旁腺大小或功能的改变。这些数据与以下两点一致：（1）锂盐作为甲状旁腺功能亢进的促进因素；（2）对于需要长期治疗的患者，切除异常甲状旁腺组织并恢复锂盐治疗。
