Introduction: Normocalcaemic hyperparathyroidism (nHPT) is a persistently elevated parathyroid hormone (PTH) with normal ionised calcium levels in the absence of secondary hyperparathyroidism. nHPT is proposed to be an earlier phase of hypercalcaemic primary hyperparathyroidism (PHPT). nHPT patients can present with progressive complications such as osteoporosis and nephrolithiasis. Currently, there is no diagnostic test to confirm primary hyperparathyroidism in nHPT patients, leading to a delay in curative parathyroidectomy. The aims of this study were to determine:
1) if the oral calcium-loading test (OCLT) can predict the progression of nHPT to PHPT
2) if the OCLT results are better predictors of PHPT progression than baseline calcium and PTH.
Methods: A retrospective data analysis of nHPT patients who underwent the OCLT between August 2016 and January 2019. Adjusted-calcium and PTH levels were evaluated at 0, 60, 120 and 180 min after calcium ingestion. Two-hours urine calcium: creatinine ratio was measured at baseline and 120240 min post-calcium ingestion. On analysis, patients were classified as; 12 PHPT; having progressed to PHPT, 8 nHPT and 8 normal.
Results: Baseline calcium was significantly higher in the PHPT compared to the nHPT group, with a large overlap between the groups. Nadir PTH, 3-h PTH, and Product-P (nadir PTH x peak calcium concentration) were significantly higher while percentage PTH decrease was significantly lower in the PHPT group compared to the nHPT and normal groups (P<0.01). No statistical differences were found between the PHPT and nHPT groups in other parameters.
Conclusion: The OCLT can predict PHPT progression in nHPT patients, with; nadir PTH, Product-P, 3-h PTH, and percentage PTH decrease. These are better predictors than baseline calcium and PTH. Prospective studies are needed to establish the diagnostic threshold for primary hyperparathyroidism in nHPT patients. The implication being that these patients could be offered early surgery to reduce the risk of complications.