High Rate of Occult Urolithiasis in Normocalcemic Primary Hyperparathyroidism

Abstract

Introduction: Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevations in serum parathyroid hormone levels in the presence of normal serum calcium concentrations after exclusion of secondary hyperparathyroidism. We have previously demonstrated no differences in the prevalence of clinically active urolithiasis between NPHPT and hypercalcemic asymptomatic PHPT, and that it is significantly higher in postmenopausal osteoporotic women with NPHPT in comparison to women with normal serum PTH and calcium concentrations. Few studies have addressed the occurrence of silent or occult kidney stones in asymptomatic hypercalcemic PHPT, but no data are available for NPHPT. Objective: To determine the presence of occult urolithiasis in NPHPT patients using routine abdominal ultrasonography. Methods and Results: We studied 35 patients with NPHPT (mean age 63.2 ± 10.7 years, 96% women; serum PTH 116.5 ± 39.2 pg/mL, 25OHD 38.5 ± 6.82 ng/mL, total calcium 9.1 ± 0.56 mg/dL; albumin 4.02 ± 0.37 g/dL; BUN 34.35 ±10.23 mg/dL; p = 3.51 ± 0.60 mg/dL; estimated glomerular filtration rate 88.44 ± 32.45 mL/min/1.73 m2, and 24-h urinary calcium excretion 140.6 ± 94.3 mg/24 h). The criteria for the diagnosis of NPHPT were as follows: serum PTH above the reference range (11–65 pg/mL), normal albumin-corrected serum calcium concentrations, normal 24-h urinary calcium excretion, serum 25OHD above 30 ng/mL, estimated GFR (MDRD) above 60 mL/min/1.73 m2 (with the exclusion of medications such as thiazide diuretics, lithium, bisphosphonates, and denosumab), a history of clinical symptoms of urolithiasis, and a family history of kidney stones. Thirty-five patients were evaluated and 25 of them met the inclusion criteria. Five patients presented nephrolithiasis corresponding to 20% of the study population. There were no statistically significant differences in any of the clinical or laboratory variables studied between patients with or without urolithiasis, although mean serum PTH levels were higher in patients with stones (180.06 ± 126.48 vs. 100.72 ± 25.28 pg/mL, p = 0.1). The size of the stones ranged from 0.6 to 0.9 cm and all of the stones were located in the renal pelvis. Conclusion: We found a high prevalence of occult kidney stones in NPHPT patients, similar to what is observed in clinically manifested urolithiasis, in hypercalcemic PHPT.

Occult Renal Calcifications in Patients with Normocalcemic Primary Hyperparathyroidism and Their Association with the Parathyroid Hormone-Vitamin D Axis

“…Of note, using US only, another study from our group was unable to show any differences in serum PTH or urinary calcium between NPHPT patients with or without kidney stones [ 10 ]. Although there was no statistically significant difference, this pilot study was carried out in a smaller sample which showed a trend towards higher PTH levels in stone formers patients.…”

“…In the last decade, an increase in the prevalence of NPHPT has been observed, in addition to the recognition of clinical complications that were previously found in the classic and hypercalcemic forms of primary hyperparathyroidism (PHPT) [ 7 – 10 ]. The most common renal complication of hypercalcemic PHPT is calcification, which includes urolithiasis, with formation of stones in the calyx, pelvis, and ureters, and nephrocalcinosis, with diffuse deposition of calcium phosphate complexes in the renal parenchyma [ 11 ].…”

Effects of Parathyroidectomy on Normocalcemic Primary Hyperparathyroidism and the Role of Intraoperative PTH Measurement

“…10,12-14 This could be a reflection of the higher incidence of smaller adenomas, parathyroid hyperplasia, and multiglandular disease (MGD). 8,10,14,15…”

Normocalcemic Primary Hyperparathyroidism: Need for a Standardized Clinical Approach

“…Most studies have used different assays and criteria to define normal serum calcium. Nevertheless, independent of how normal serum calcium is defined, rates of complications are highly variable across referral cohorts [20][21][22][23][24][25][26][27][28][29][30][31]. Table 1 shows classical complication rates in referral cohorts of NHPT according to how serum calcium was assessed.…”

“…A study from Brazil reported that 20% of patients with NHPT undergoing abdominal ultrasound imaging had kidney stones [ 31 ]. This prevalence is higher than that reported in the general population of approximately 10.6% in the United States [ 34 ], but might be affected by selection bias, for example, caused by previous kidney stones.…”