Evaluation of a standardized short-time calcium suppression test in healthy subjects: interest for the diagnosis of primary hyperparathyroidism

Abstract

Objective: The diagnosis of primary hyperparathyroidism (PHP) can be difficult in patients with normal plasma calcium or parathyroid hormone (PTH) levels. We perfected a standardized short-time i.v. calcium loading test in healthy controls (HC) and compared the results with those of patients with PHP. Methods: Sixteen HC received 0.33 mmol/kg calcium gluconate intravenously for 3 h. Plasma calcium and serum PTH levels (assayed with immunoluminescent sandwich methods) were measured before, at the end of the infusion and 3 h later. Results were compared with those of 16 PHP patients. Results: In HC, basal total plasma calcium (meanGS.E.M.) was 2.33G0.02 mmol/l. At the end of calcium loading, calcemia reached 3.21G0.05 mmol/l and decreased to 2.94G0.08 mmol/l 3 h later. In PHP patients, basal plasma calcium was 2.54G0.03 mmol/l and reached similar values as in HC during the testing. Basal serum PTH levels were 32.5G3.3 ng/l in HC and 86.9G6.3 ng/l in PHP. At the end of calcium loading, they dropped to 8.8G0.6 ng/l (HC) and to 31.4G4.2 ng/l (PHP). Three hours later, they were 11.6G0.8 and 39.8G4.0 ng/l respectively. There was a cut-off in serum PTH values between the two groups at the end of calcium loading and 3 h later. Conclusion: The standardized short-time PTH suppression test appears reliable to differentiate healthy subjects from PHP whose serum PTH levels remain O14 and O23 ng/ml respectively at the end of loading and 3 h later. This well-tolerated and easily performed test could be used for the diagnosis of PHP in patients suspected for the disease despite the normality of some basal biological markers.

A step towards cinacalcet testing for the diagnosis of primary hyperparathyroidism: comparison with the standardized intravenous calcium loading. A pilot study

“…Per cent decrease from basal values of serum PTH 1‐84 levels (mean ± SEM ) in response to either a standardized intravenous calcium loading or to an intake of a single dose of cinacalcet 30 or 60 mg. (□) healthy controls (HCs), (■) patients with primary hyperparathyroidism. () Data from the previous study from Titon et al . HCs vs patients with hyperparathyroidism, ** P < 0.01, cinacalcet 30 mg vs cinacalcet 60 mg in HCs, ## P < 0.05.…”

“…By comparison with normal parathyroid cells, parathyroid adenoma cells seem to express a less number of calcium‐sensing receptors, to have an alteration in the transduction system or both, leading to a decrease in sensitivity to calcium . This short‐time PTH suppression test, using an intravenous calcium load, is easily performed and allows to clearly differentiate patients with PHPT and subjects with normal parathyroid function . However of interest, this calcium loading test has some drawbacks.…”

“…After taking the drug, blood was drawn at the same time as in controls. Because this test was evaluated in a previous study and to avoid the potential side effects of a sharp increase in plasma calcium levels in patients with overt PHPT, a calcium loading test was not performed in this group of patients included in this study.…”

“…A calcium loading test was performed in nonfasting HC as previously described . After an initial blood sampling performed to measure basal biological parameters, 0·33 mmol/kg of 10% calcium gluconate was added to 0·9% NaCl to obtain a total volume of 500 ml, which was infused in 3 h. Blood was drawn before, then hourly for 4 h and finally, 6 h after starting the test.…”

“…Different modalities using various markers have been proposed . We previously evaluated a standardized short‐time PTH suppression test using a standardized intravenous calcium loading which was reliable to differentiate patients with PHPT from healthy subjects . This test needs to infuse intravenously calcium gluconate to increase plasma calcium levels high enough to inhibit PTH secretion.…”