Analysis of circulating bone-glucose profile and exerkine irisin across parathormone quartiles in patients with primary hyperparathyroidism.

Abstract

BACKGROUND: Parathyroid tumors, mostly single or multiple adenomas, cause a hormonal imbalance via parathormone (PTH) excess, that further increases serum calcium (primary hyperparathyroidism) with both PTH- and calcium-related multi-organ consequences. Testing the bone turnover markers (BTM) profile might capture the essence of associated bone turnover anomalies with practical applications in the clinical setting. OBJECTIVE: Our objective was to compare the BTM across mineral metabolism panel, glucose profile, as well as circulating irisin levels in patients with primary hyperparathyroidism vs. (tumor-free) controls by refining the analysis based on PTH values quartiles. PATIENTS, MATERIALS AND METHODS: A prospective study with a single-center design in menopausal adults, who were enrolled between December 2024 and May 2026. RESULTS: 148 enrolled across four PTH quartiles (mean age 63.39 years and menopause length 16.55 years): 27.09±5.56 pg∕mL (Q1), 38.33±2.58 pg∕mL (Q2), 46.34±2.93 pg∕mL (Q3) and 65.78±16.51 pg∕mL in Q4 (p<0.001 for each). Glycated hemoglobin (HbA1c) was lower (statistically significantly): Q4 of 5.74±0.32% compared to non-Q4 of 5.98±0.67% (p=0.006), as well as triglycerides of 103.39±36.34 vs. 124.41±66.26 mg∕dL (p=0.017). Fasting insulin was also different among PTH quartiles, with the highest median value in Q4 of 8.35 (6.47, 11.49) μIU∕mL (p=0.027). Median homeostatic model assessment for insulin resistance (HOMA-IR) was higher in Q2 vs. Q1 (p=0.034), Q3 vs. Q1 (p=0.016) and Q4 vs. Q1 (p=0.005). Osteocalcin was statistically significantly different among quartiles (p=0.036). Receiver operating characteristic (ROC) curve analysis of osteocalcin to predict primary hyperparathyroidism revealed area under the curve (AUC) 0.645 (p=0.006). The cut-off osteocalcin with the highest Youden index was for the value of 21.26 ng∕mL (sensitivity 63.90%; specificity 63.10%). In Q4, irisin associated a statistically significant and positive correlation with the value of calculated body mass index (BMI) (r=0.361, p=0.042). CONCLUSIONS: In this PTH-based quartiles analysis of menopausal females with/without primary hyperparathyroidism, we found a distinct interpretation of the glucose profile and BTM depending on quartiles, while irisin positive corelated with BMI in cased with parathyroid tumors.