Immunohistochemical Expression of CaSR, VDR, and AMA in Parathyroid Tumors Linked to Hypercalcemia Severity in Primary Hyperparathyroidism

Background: Primary hyperparathyroidism (PHPT) is usually caused by parathyroid tumors, resulting in hypercalcemia due to excessive PTH secretion. While disease severity correlates with calcium blood levels, the molecular mechanisms driving clinical variability remain unclear. The role of the calcium-sensing receptor (CaSR), the vitamin D receptor (VDR) and parathyroid cells mitochondrial activity in the pathogenesis of hyperparathyroidism is of particular interest. Methods: This retrospective study included 96 patients with PHPT who underwent parathyroidectomy. Patients were stratified by albumin-corrected calcium blood levels (≤ 2.8; 2.8<Ca _corr .≤ 3.0; 3.0 ≤ Ca _corr. < 3.5 Ca _corr. ≥ 3.5 mmol/L). Immunohistochemical expression (IHC) was estimated with CaSR, VDR, and antimitochondrial antibodies (AMA).Statistical analysis was performed using the Statistica v. 13.3 software package (TIBCO Software Inc., USA). Results: Strong CaSR expression was observed in 95.8% of tumors, whereas VDR expression was reduced in 46.9%. AMA staining was heterogeneous, with high reactivity in oxyphilic cells. No significant differences in CaSR, VDR, or AMA expression were found across groups with different hypercalcemia severity. No significant correlations were identified between IHC markers expression and parameters of calcium-phosphorus metabolism, as well as cinacalcet treatment response. Conclusions: Despite their established roles in parathyroid regulation, CaSR and VDR expression did not correlate with hypercalcemia severity in PHPT. These findings suggest that alternative molecular mechanisms, rather than receptor expression levels, contribute to clinical heterogeneity. Further research is required.