Response to an oral calcium load in nephrolithiasis patients with fluctuating parathyroid hormone and ionized calcium levels

Abstract

The response to an oral calcium load test was assessed in 17 hypercalciuric nephrolithiasis patients who presented elevated parathyroid hormone (PTH) irrespective of the ionized calcium (sCa 2+ ) levels. Blood samples were collected at baseline (0 min) and at 60 and 180 min after 1 g calcium load for serum PTH, total calcium, sCa 2+ , and 1.25(OH) 2 D 3 determinations. According to the sCa 2+ level at baseline, patients were classified as normocalcemic (N = 9) or hypercalcemic (N = 8). Six healthy subjects were also evaluated as controls. Bone mineral density was reduced in 14/17 patients. In the normocalcemic group, mean PTH levels at 0, 60 and 180 min (95 ± 76, 56 ± 40, 57 ± 45 pg/ml, respectively) did not differ from the hypercalcemic group (130 ± 75, 68 ± 35, 80 ± 33 pg/ml) but were significantly higher compared to healthy subjects despite a similar elevation in sCa 2+ after 60 and 180 min vs baseline in all 3 groups. Mean total calcium and 1.25(OH) 2 D 3 were similar in the 3 groups. Additionally, we observed that 5 of 9 normocalcemic patients presented a significantly higher concentration-time curve for serum PTH (AUC 0',60',180' ) than the other 4 patients and the healthy subjects, suggesting a primary parathyroid dysfunction. These data suggest that the individual response to an oral calcium load test may be a valuable dynamic tool to disclose a subtle primary hyperparathyroidism in patients with high PTH and fluctuating sCa 2+ levels, avoiding repeated measurements of both parameters.

Metabolic Evaluation: Place of the Calcium Load Test: How, When, For Whom, and Why?

“…A PTH-IR cutoff at 73% has been proposed to differentiate normocalcemic early-stage PHPT patients (PTH-IR <73%) from healthy subjects (PTH-IR >73%) with sensitivity of 95% and specificity of 99.9% [13]. These findings are in agreement with earlier studies on the calcium dependency of PTH secretion [7][8][9][10][11]18]. In fact, PHPT is considered as a biphasic disease, whereby PTH rises first, followed by a rise in serum calcium in later stages of the disease [19].…”

“…The clinical relevance of the CLT was questioned shortly after publication of the original protocol by Pak et al in 1975 [22]. Since then, more recent studies with refined methodology reliably demonstrated the diagnostic benefits of the CLT, as discussed above [5,[7][8][9][10][11][12][13][14]18,20,21]. However, the therapeutic impact of CLT findings still needs to be evaluated in dedicated studies.…”

“…Oral CLT may be favored over intravenous CLT, since oral administration of calcium is more physiological and takes into account enteric regulation of calcium. Another advantage of oral CLT is its safety profile, as the resulting increase in serum calcium is kept within a safe range (<0.3 mmol/l) [8][9][10]12,18], whereas intravenous CLT may cause hazardous hypercalcemia [7,18]. However, oral CLT is prone to variability because of individual kinetic differences in intestinal calcium absorption.…”

“…There are slight variations in CLT study protocols in the literature in terms of the following parameters: content and duration of the low-calcium diet and fasting period; content and route of administration of the calcium load; duration of urine collection; and time points for blood withdrawal [5,[7][8][9][10][11][12][13][14]. The CLT protocol described above together with Figure 1 should be understood as a comprehensive summary from our review of the various protocols and pathophysiological mechanisms presented in all the published studies on CLT in adults to date [5,[7][8][9][10][11][12][13][14]. The impact of CLT protocol variations has not been evaluated in any dedicated study to date.…”

Renal stone disease: causes, evaluation and medical treatment

“…Since primary hyperparathyroidism has to be ruled out, serum PTH can be determined either in the same single blood collection or in a further sample in case hypercalcemia has been detected in the former, in order to reduce costs. However, intermittent high levels of serum calcium may represent mild forms of subtle primary hyperparathyroidism (27). A qualitative colorimetric test in spot urine samples to evidence the presence of high amounts of cystine with sodium nitroprussiate can serve as a screening method for cystinuria.…”