A Lack of Unique Pathophysiologic Background for Nephrolithiasis of Primary Hyperparathyroidism

The metabolic picture of 32 patients with surgically proven primary hyperparathyroidism presenting with renal stones was compared with that of 37 patients without stones. Between stone-forming and nonstone-forming groups, there was no significant difference in serum 1,25-dihydroxyvitamin D [6.82 ± 2.62 vs. 6.22 ± 2.33 ng/dl (mean ± SD); P > 0.05], fractional (intestinal) calcium absorption (0.726 ± 0.141 vs. 0.690 ± 0.120), urinary clacium (299 ± 139 vs. 284 ± 144 mg/day), serum calcium, phosphorus, and parathyroid hormone, or bone density. Similarly, no differences were found between 29 patients presenting with stones alone and 9 presenting with bone disease alone with respect to the above measures. Moreover, urinary environment was typically supersaturated with respect to stoneforming salts regardless of the presence of stones. The results indicate that there is no unique pathophysiological background for the nephrolithiasis of primary hyperparathyroidism. (J Clin Endocrinol Metab 53: 536,1981) C nephrolithiasis is a frequent complication of primary hyperparathyroidism (1, 2). It is generally recognized that the formation of renal stones is pathogenetically related to the hyperparathyroid state and is not a coincidental occurrence. The most convincing evidence for the existence of this etiological relationship is provided by the favorable response to parathyroid surgery. After successful parathyroidectomy, the new stone formation often ceases, unless there has been a complication by a chronic urinary tract infection. The exact cause of the formation of renal stones in primary hyperparathyroidism has not been elucidated. It has been suggested that the biochemical and clinical picture of patients with primary hyperparathyroidism presenting with nephrolithiasis may be unique from that of patients without stones. Patients with stones were believed to have a longer duration of the disease process, a less severe hypercalcemia, and a smaller size of abnormal parathyroid tissue than patients who present with reduced bone density (3, 4). Hypercalciuria is frequently encountered in stone-forming patients with primary hyperparathyroidism (4,5). This disturbance has often been implicated as one of the causes of renal stone formation, since it is a frequent metabolic derangement associated Received February 9, 1981. Address requests for reprints to: Dr. Charles Y. C. Pak, Department of Internal Medicine, University of Texas Health Science Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235. * This work was supported by USPHS Grants P50-AM20543, R01AM16061, and M01-RR-00633. with calcium nephrolithiasis (6). The hypercalciuria could have resulted from an excessive parathyroid hormone (PTH)-dependent bone resorption and/or an enhanced intestinal absorption of calcium ensuing from the PTH-dependent synthesis of 1,25-dihydroxyvitamin D [1,25-(OH)2D] (7, 8). There is some evidence that the hypercalciuria of intestinal origin may be more critical in the formation of renal stones (9). Thus, an apparent predilection for nephrolithiasis has been reported in the group of patients with primary hyperparathyroidism who possess a high circulating concentration of 1,25-(OH^D (9) and an increased intestinal absorption of calcium (9, 10). The current study was undertaken to determine if the stone-forming patients with primary hyperparathyroidism could be distinguished from their nonstone-forming counterpart on the basis of metabolic and biochemical presentations. It will be shown that the two groups of patients cannot be readily separated from the above criteria. Materials and Methods Sixty-nine patients with primary hyperparathyroidism participated in the study after informed written consent was obtained. These patients represented all of the patients with surgically proven primary hyperparathyroidism who were evaluated by us during the past 7 yr. Before surgery, they underwent an in-patient diagnostic evaluation according to the protocol previously described (5,8). The evaluation permitted an assessment not only of parathyroid function and vitamin D status,