Parathyroid histology in normocalcemic and hypercalcemic primary hyperparathyroidism with hypercalciuric renal stones

Abstract Context Hypercalcemic (HPHPT) and normocalcemic primary hyperparathyroidism (NHPT) are distinct conditions with different biological and histological characteristics. Understanding their histological patterns could improve disease characterization. Objective This study aimed to compare the histological features of NHPT and HPHPT parathyroid glands, but also rims of normal tissue, focusing on the expression of calcium-sensing receptor (CaSR), 1-α hydroxylase (CYP27B1), and vitamin D receptor (VDR). Methods A retrospective observational study was conducted on histological and immunohistochemical data from parathyroid gland samples. The study included 50 hypercalciuric renal stone patients, of whom 18 had NHPT and 32 had HPHPT. Histological and immunohistochemical analyses were performed to evaluate cell distribution and marker expression. Parathyroid gland weight, cell distribution, and CaSR, CYP27B1, and VDR expression were analyzed and compared between NHPT, HPHPT, and rim biopsies. Results Parathyroid gland weight and cell distribution were similar in both groups. A rim of normal tissue was more frequent in HPHPT (69% vs 37%; P = .02). In HPHPT, CaSR expression was decreased, while CYP27B1 and VDR expressions were increased in chief cells compared to rim tissue (P = .005, .004, and <.001, respectively). NHPT showed no CaSR or CYP27B1 alterations but a decreased VDR expression in oxyphil cells compared to HPHPT (P = .02). Conclusion The NHPT hallmark phenotype is normal CaSR, CYP27B1/VDR expression in chief cells, with decreased VDR expression in oxyphil cells. HPHPT chief cell patterns show a marked CaSR decreased expression along with an increased CYP27B1/VDR expression, suggesting an appropriate autocrine/paracrine counterregulation to hypercalcemia/high PTH.