Endocrine Abstracts

JOINT1337

Background and Aim: Primary hyperparathyroidism (PHPT), predominantly caused by parathyroid adenomas, exhibits a broad spectrum of clinical and histopathological manifestations, ranging from mild to severe hypercalcemia. Severe hypercalcemia (Ca >13 mg/dL) is linked with complications such as osteoporosis and nephrolithiasis, while mild hypercalcemia (Ca <12 mg/dL) is often asymptomatic. This study aimed to explore differences in tumor characteristics, clinical outcomes, and histopathological markers between these groups, providing insights into their pathophysiology and prognostic implications.

Subjects and Methods: A retrospective analysis was conducted on 66 patients with PHPT due to parathyroid adenomas. Patients were divided into two age-matched groups: 46 with mild hypercalcemia (Ca <12 mg/dL; mean age 54. 3 ± 11. 3 years) and 20 with severe hypercalcemia (Ca >13 mg/dL; mean age 51. 9 ± 17. 8 years). Immunohistochemical analyses for parafibromin, cyclin D1, TP53, and Ki67 were performed on pathological specimens. Tumor size, mitotic activity, fibrosis, and clinical, hormonal, and biochemical parameters were also evaluated.

Results: The severe hypercalcemia group demonstrated significantly higher median serum calcium and parathormone levels (13. 8 mg/dL [IQR: 13. 3–14. 5], 351. 4 pg/mL [IQR: 216. 9–487. 7]) compared to the mild hypercalcemia group (11. 2 mg/dL [IQR: 10. 9–11. 6], 152. 3 pg/mL [IQR: 121. 3–227. 6]). Despite these differences, no significant variations were found between the groups in tumor size (P = 0. 43), mitotic activity (P = 1. 0), fibrosis (P = 0. 12), or immunohistochemical markers such as parafibromin (P = 0. 47), cyclin D1 (P = 0. 7), beta-catenin (P = 0. 82), and Ki67 (P = 0. 63). Additionally, there were no significant differences in the prevalence of osteoporosis (Ca <12, n = 17; Ca >13, n=2; P = 0. 17) or nephrolithiasis (Ca <12, n = 18; Ca >13, n = 12; P= 0. 18).

Conclusion: Severe hypercalcemia in PHPT reflects greater biochemical disease severity, yet histopathological and molecular profiles of parathyroid adenomas remain comparable across calcium levels. These findings suggest that hypercalcemia severity may stem from factors beyond tumor pathology, including functional variations in adenomas or host-specific influences. Further research is required to uncover mechanisms contributing to disease severity and their clinical implications.