Comparison of Normocalcemic vs Hypercalcemic Primary Hyperparathyroidism in a Hypercalciuric Renal Stone Population

Abstract

Context: Primary hyperparathyroidism (PHPT) is commonly diagnosed in the setting of hypercalcemia, whereas normocalcemic primary hyperparathyroidism (NHPT) may be misdiagnosed.

Objective: Our objective was to compare patients with hypercalcemic hyperparathyroidism (HPHPT) vs patients with NHPT hypercalciuric renal stones.

Methods: We took advantage of a routine calcium load test performed in patients with hypercalciuric renal stones to assess retrospectively among patients with PHPT the prevalence and characteristics of NHPT and HPHPT under a calcium-restricted diet.

Results: Among 1671 patients with hypercalciuria, 91 patients had a final diagnosis of PHPT (postload ionized calcium [iCa] > 1.31 mmol/L and parathyroid hormone [PTH] > 30 pg/mL). Prevalence of NHPT is 40% of all PHPT; however, according to total serum calcium, 4/35 NHPT and 7/56 HPHPT cases would have been misclassified in the other group. Eighteen of 35 NHPT and 40/56 HPHPT cases underwent parathyroidectomy. No significant characteristics relating to parathyroid weight, stone composition, or bone remodeling biomarkers were detected between groups. Although iCa is higher in HPHPT in the fasting state and after calcium load, we found no difference for calcium diet, 24-hour calciuria, or calcitriol. Renal calcium excretion postload increased by 303% in NHPT but only 176% in HPHPT (P = .01) likely explained by a lesser PTH decrease (P = .02). However, a strong negative association (P < .0001) detected between pooled preload and postload iCa and PTH only in the NHPT group suggests a persistent efficient PTH-CaSR control within the parathyroid glands in this group.

Conclusion: Our data show the relevance of dynamic tests to unmask NHPT in patients with hypercalciuric renal stones.

Keywords: CaSR; hypercalcemic primary hyperparathyroidism; hypercalciuria; normocalcemic primary hyperparathyroidism; primary hyperparathyroidism.

Figure 1.

Flow chart. Among 1671 patients with hypercalciuria and renal stones referred to our department for a calcium load test over a 10 years. PHPT, primary hyperparathyroidism; NHPT, normocalcemic primary hyperparathyroidism; HPHPT, hypercalcemic primary hyperparathyroidism; PTX, parathyroidectomy.

Figure 2.

Distribution of iCa in the studied population in a fasting state after (A) a calcium-restricted diet and (B) following a calcium load test. As shown, all patients experienced a postload iCa >1.31 mmol/L. Relationship between PTH and iCa (C) before and (D) after a calcium load test. Dotted lines represent the iCa normal upper limit. In (C) the solid line represents the serum PTH normal upper limit. In (D) the solid line represents serum the PTH upper limit in the context of hypercalcemia (see “Material and Methods”).

Figure 3.

Comparison between NHPT and HPHPT groups of preload and postload total calcemia (A), iCA (B), PTH (C), and postload iCa, PTH FECa variation (D) (*P < 0.05). Results are expressed in percentage from baseline value (fasting value = 100%).

Figure 4.

Association between iCa and serum PTH in NHPT (A) and HPHPT groups (B). Association between iCa and FECa in NHPT (C) and HPHPT groups (D). Patients’ preload and postload data are pooled.