Abstract
Recent studies suggest that calcium-sensing receptors (CaSR) play a crucial role in the regulation of parathyroid hormone (PTH) secretion and may also have some association with parathyroid cell proliferation. To investigate the possible involvement of CaSR as well as vitamin D receptor (VDR) in the regulation of parathyroid cell proliferation, we performed the immunohistochemical examination using sections obtained from a patient with severe secondary hyperparathyroidism.
A 34-year-old man on maintenance hemodialysis caused by chronic glomerular nephritis was referred to us for the control of severe secondary hyperparathyroidism. He suffered from severe bone pain and arthralgia. Corrected serum Ca was 10.9mg/dl, intact PTH 3500pg/ml and serum levels of biochemical bone markers markedly high (ALP: 13729IU/L, osteocalcin: 3140ng/ml, TRAP: 44.0IU/L). Oral vitamin D pulse therapy was not effective. In 1997, total parathyroidectomy with autotransplantation was performed. Postoperatively, his clinical symptoms, severe anemia and radiographic findings were dramatically improved.
Total weight of the four parathyroid glands was 2.5g and the histological examination revealed diffuse hyperplasia with nodular formation. Using formalin fixed paraffin embedded sections, immunohistochemical staining was examined with specific antibodies against VDR, CaSR and Ki 67 as a marker of cell proliferative activity. The immunoreactive expressions of VDR and CaSR were much lower in parathyroid from this patient than in those from control. Parathyroid cells from this patient possessed high proliferative activity, especially in the nodular area. Not only VDR but also CaSR expressions were more clearly decreased in the more highly proliferative lesion.
The pathological state caused by a markedly elevated PTH level would be associated with reduced expressions of VDR as well as CaSR, resulting in increased proliferative activity of parathyroid cells.
