Lithium Stimulates the Release of Human Parathyroid Hormonein Vitro

Abstract

The effect of lithium on PTH release from human parathyroid tissue was studied using a perifusion system and an immunoradiometric assay for intact human PTH. Tissue was obtained from three patients undergoing surgery for thyroid disease, three patients with secondary hyperparathyroidism due to chronic renal insufficiency, and four patients with primary hyperparathyroidism due to a parathyroid adenoma. Addition of lithium in concentrations equivalent to the therapeutic serum levels normally attained in man (1.3 mmol/L) resulted in a significant (P less than 0.05) increase in PTH release under normocalcemic (1.15 mmol/L) conditions from normal and hyperplastic tissues. The magnitude of the lithium-induced response of PTH release ranged from a 1.4- to 5.3-fold increase above basal levels (perifusion with 1.15 mmol/L calcium alone) and was comparable to the response during a low calcium (0.42 mmol/L) perifusion. Although the response to lithium was delayed compared to that of hypocalcemia, PTH returned to basal levels immediately after removal of either stimulator. In contrast, parathyroid adenomas did not respond to either lithium or hypocalcemia in a characteristic manner, but, rather, functioned in an autonomous fashion with repeated pulsatile bursts of PTH release that were not suppressible even under hypercalcemic (1.70 mmol/L) conditions. These in vitro studies suggest that lithium therapy may elevate serum PTH levels in some patients and could, thus, be responsible for hypercalcemia in them.

Normal Hemodynamic and Coagulation Responses to 1 -Deamino-8-<i>D</i>-Arginine Vasopressin in a Case of Lithium-Induced Nephrogenic Diabetes insipidus

“…Li was indeed the sole etiologic factor since the patient had never taken other drugs and had no chronic renal disease, hypokalemic nephropathy, adrenal insufficiency or stigmas of CNDI. Hypercalcemia could have been discussed but was mild and variable: it is a wellknown side effect of chronic Li-therapy, perhaps related to slight chronic dehydration or to primary hyperparathy roidism, not found here [13][14][15], This LINDI was persistent for more than 8 weeks after withdrawal of Li. This is not very common; 14 cases are reviewed by Boton et al…”

Lithium and Fibromyalgia

“…The mechanism for this effect is unknown, but the increase in PTH can be significant. In experiments on human parathyroid tissue, lithium was about as potent a stimulator for the release of PTH as was hypocalcemia, with levels increasing from 1.4 to 5.3 times normal (5). Could the elevated PTH resulting from lithium therapy have been responsible for the relief of fibromyalgia symptoms experienced by the three patients described above?…”

Other Secondary Hyperparathyroid States

“…154 Another possible mechanism is that lithium directly stimulates PTH release by the parathyroid glands. 155 Others have postulated that lithium may unmask preexisting parathyroid pathology by affecting the calcium set point. 156 Recently, it has been proposed that lithium may inhibit the action of glycogen synthase kinase 3b (GSK-3b), which in turn inhibits PTH transcription, thus leading to increased transcription and overproduction of PTH.…”