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

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.

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.

A prospective study with a single-center design in menopausal adults, who were enrolled between December 2024 and May 2026.

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).

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.