ENDOCRINOLOGICAL STUDIES ON PATHOGENESIS OF UROLITHIASIS

V. Effect of Calcitonin in Urinary Electrolytes Excretion and Serum Electrolytes

Abstract

In an earlier paper of this series, it is shown that calcitonin influences on the calcium metabolism of patients with urolithiasis, especially hypercalciuric patients. However little work has been done to evaluate effects of calcitonin on the urinary excretion of electrolytes and renal calcitonin metabolism.
Effect of calcitonin was studied in patients with primary hyperparathyroidism, hypercalcemic malignant tumors, and urinary calculi. We further investigated the calcitonin metabolism in intact and parathyroidectomized (PTX) rats.
Forty or eighty MR Cunits of eel calcitonin which has the highest biological activity, was injected into the patients intramuscularly every morning. Every two-hour urine samples were collected after injection, and blood was collected three hours after injections.
The results were as follows:
1) Patients with malignant tumors had a serum calcitonin level significantly higher than those with hyperparathyroidism (209.8±41.2pg/ml, 63.2±38.8pg/ml respectively, p<0.001). However, both parathyroid hormone and urinary cyclic AMP levels were significantly lower in the former than the latter. (parathyroid hormone 0.315±0.260ng/ml, 6.10±7.63ng/ml respectively, p<0.05), (Urinary cyclic AMP 6.0±5.0μmoles/g.cr, 12.4±6.4μmoles/g.cr p<0.05).
2) Single injections of calcitonin induced a highly significant increase of the urinary excretion of calcium, phosphate, magnesium, and sodium after two hours. It returned to the previous level after eight hours. The preadministration serum calcium levels were directly proportional to the degrees of the decreases after administration.
3) The injection for several days caused a decrease of urinary calcium excretion in 8 of 11 cases, but minimal or no changes were observed in urinary phosphate excretion. There was no difference between malignant tumors and hyperparathyroidism.
4) Administration of eel calcitonin showed that there was minimal or no changes in serum calcitonin levels. Single injections of calcitonin caused moderate increases of parathyroid hormone in some cases, but no changes in the other cases.
5) Single injections of calcitonin resulted in a marked increase of urinary cyclic AMP excretion in patients with hyperparathyroidism, and there were moderate increase in those with malignant tumors. The cause of the increase remains unexplained, whether it is attributable to the calcitonin direct action or the parathyroid action followed by serum calcium reduction.
The following experiment was made to investigate this problem. Eel calcitonin was administered into intact and PTX rats, weighing about four hundred grams, intraperitoneally at a dose of 0.3MR-Cunits/100g body weight. Sample collection methods in this study was the same as that described in human beings. In this experiment slight to moderate increases in urinary cyclic AMP excretion was noted in intact rats as well as PTX rats. Based on this finding it is logical to believe that the increase is due to the calcitonin direct action, i. e, cyclic AMP may be the second messenger of calcitonin.
6) Injections of calcitonin for several days resulted in a marked reduction of urinary calcium excretion in four of five hypercalciuric patients (more than 200mg/day). But there was minimal or no changes in all normocalciuric patients. These results suggest that calcitonin is useful to investigate calcium metabolism in urolithiasis as well as to treat patients with urinary calculi.