Clinical Characteristics and Risk Factors of Normocalcemic Primary Hyperparathyroidism

Abstract

Background Normocalcemic primary hyperparathyroidism (NCPHPT), as a new phenotype of primary hyperparathyroidism (PHPT), has gained increasing attention. NCPHPT is easily misdiagnosed in clinical practice, and its risk factors need to be evaluated further. Objective To investigate the clinical features of NCPHPT and to explore its risk factors. Methods Patients diagnosed with PHPT (n=153) were retrospectively selected from Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School from January 2016 to December 2021, and divided into an experimental group (NCPHPT group) and a hypercalcemia PHPT group according to the corrected total serum calcium level. Meanwhile, individuals undergoing physical examination with normal parathyroid function were selected as the control group. The differences in clinical characteristics, glucose and bone metabolism, imaging and pathology results among the groups were compared. Multivariate Logistic regression analysis was used to analyze the risk factors of NCPHPT. Results The number of cases in NCPHPT, hypercalcemia PHPT and control groups was 36, 117 and 50, respectively. For biochemical indices, compared with healthy control group, the levels of alkaline phosphatase (AKP), uric acid (UA), and parathyroid hormone (PTH) were much higher in NCPHPT group, while serum phosphorus was much lower (P<0.05). Compared with hypercalcemia PHPT group, the NCPHPT group had notably lower levels of serum calcium, AKP, serum creatinine (Scr), UA and PTH, and significantly higher serum phosphorus level and estimated glomerular filtration rate (eGFR) (P<0.05). In terms of glucose metabolism, the glycated hemoglobin (HbA1c), and insulin resistance index (HOMA-IR) in NCPHPT group were much higher than those in the control group (P<0.05), the FPG, fasting insulin (FIns) and HOMA-IR in hypercalcemia PHPT were much higher than that in control group (P<0.05). In terms of bone metabolism indices and bone mineral density, the NCPHPT group had much higher levels of P1NP, serum β-crosslaps (β-CTX), osteocalcin (OC) and calcitonin (CT), and obviously lower bone mineral density of the L1-4 lumbar vertebrae and femoral neck than the control group (P<0.05). Compared with hypercalcemia PHPT group, the levels of P1NP, β-CTX, OC and CT were much lower while the bone mineral density of femoral neck was much higher in the NCPHPT group (P<0.05). Parathyroid occupying lesions in both the NCPHPT group and the hypercalcemia PHPT group were more prevalent in the lower pole. There was no statistically significant difference in diameter, location and ectopia between the NCPHPT group and the hypercalcemia PHPT group (P<0.05). The rate of multiglandular lesions was higher in the NCPHPT group than the hypercalcemia PHPT group (P<0.05). There was no statistically significant difference between the two groups when comparing the types of pathology (χ2=8.556, P>0.05). Multivariate Logistic regression analysis showed that urolithiasis〔OR=2.462, 95%CI (1.178, 3.552), P=0.011〕, decreased serum phosphorus〔OR=0.027, 95%CI (0.001, 0.711), P=0.031〕and increased AKP〔OR=2.809, 95%CI (1.422, 8.020), P=0.037〕were relevant factors for NCPHPT. Conclusion Patients with NCPHPT have many clinical symptoms such as elevated blood pressure, abnormal glucose metabolism, abnormal bone mineral density and urolithiasis. The presence of urolithiasis, hypophosphatemia and increased AKP indicates the possible existence of NCPHPT, which can be used for early Screening of NCPHPT to reduce the misdiagnosis rate.

Keywords

• hyperparathyroidism, primary|normocalcemic primary hyperparathyroidism|bone metabolism|glucose metabolism disorders|root cause analysis|disease attributes