Renal stone disease, elevated iPTH level and normocalcemia

Background: There is a well established relationship between primary hyperparathyroidism and recurrent calcium-containing calculi. Traditionally, the diagnosis is confirmed by the presence of elevated intact parathyroid hormone (iPTH) and serum ionised calcium levels. The prevalence and role of elevated iPTH in the presence of normocalcemia in patients with renal stone disease is poorly understood. The aim of the present study was to describe the findings in patients who had renal stone disease, an elevated iPTH level and normocalcemia. Methods: During the last decade, 414 patients, who had normal renal function, were investigated and treated for renal calculi in the Renal Stone Clinic of the Toronto Western Hospital. Of these 414 patients, 40 (9.6%) had an elevated intact iPTH level and normal serum calcium (total and ionised) on repeated measurements. In all these patients we performed detailed clinical and laboratory investigations to determine risk factors for stone formation. Correlation analysis was done using Pearson test and the weights of factors influencing iPTH level were compared using multiple regression analysis. Results: The average duration of a history of stone disease was 12.0 ± 10.5 years. Most of these patients had passed their stones spontaneously, 15 underwent lithotripsy, in six the stones were removed by basket catheters and one patient each had partial nephrectomy, nepholithotomy or uretero-lithotomy. Twelve had a positive family history, two had history of intestinal malabsorption and one patients had a history of immobilisation. All of these patients had elevated serum parathyroid hormone in the range of 3% to 134% (median 20.5%) above upper limit of normal (F = M); all had normal serum total and ionised calcium and normal urine excretion of calcium (except in one). Additional risk factor for stone formation included: low level of 25-hydroxyvitamin D in four patients, low output and high urine osmolality in four patients, high urine sodium in nine and high oxalate excretion in eight patients. Citrate excretion was low in seven, magnesium excretion in six patients and tubular reabsorption of phosphate in 22 patients. Urine hydroxyprolin was increased in two and decreased in four patients. Combined abnormalities were found in 14 while 17 patients did not have any abnormality apart from elevated iPTH level. Multiple regression analysis did not suggest that any of the selected predictors had a significant influence on PTH release. Conclusions: 9.6% of patients with recurrent kidney stones had normocalcemia nd elevated iPTH level in the presence of normal renal function. The study did not show any distinct pattern of abnormalities that would suggest a mechanism of stone disease in these patients. Further investigations are necessary to determine the significance of elevated iPTH in normocalcemic patients with renal stone disease and establish whether we should consider neck exploration for parathyroidectomy in these patients.