Apoptosis in parathyroid hyperplasia of patients with primary or secondary uremic hyperparathyroidism

Abstract

Background. Chronic oversecretion of parathyroid hormone (PTH) is associated with parathyroid hyperplasia, reflecting a disturbed balance between cell proliferation and apoptosis. This study addressed the unsolved issue of apoptosis in hyperparathyroidism. Methods. Parathyroid glands from 19 patients with primary (1°) and 11 patients with secondary (2°) uremic hyperparathyroidism, as well as 13 normal parathyroid glands, were examined. Apoptosis was evaluated by terminal deoxynucleotidyl transferase (Tdt)- mediated dUTP nick end-labeling assay (TUNEL). Because the apoptotic process is regulated by several oncoproteins, the expression of Bcl-2 and Bax was analyzed by immunohistochemistry. Results. The numbers of apoptotic cells in 1° parathyroid adenoma (0.99 ± 0.03 per 1000 cells, mean ± SE, P < 0.009) and 2°parathyroid hyperplasia (1.20 ± 0.54 per 1000 cells, P < 0.005) were significantly higher than in normal parathyroid tissue (0.13 ± 0.06 per 1000 cells). Light microscopy examination of hyperplastic parathyroid tissue from a uremic patient showed the presence of nuclei with dense chromatin characteristic of apoptosis. Bcl-2 staining was strong in normal tissues but weak or negative in several sections of 1°and 2°hyperparathyroid tissues, mostly in nodular areas. Bax staining was homogeneous in normal tissue but patchy in several hyperplastic tissues. Conclusion. These results suggest that hyperparathyroidism is associated with a compensatory increase in apoptosis, possibly favored by a diminished Bcl-2/Bax ratio. This renders highly improbable the hypothesis that parathyroid hyperplasia is due to a decreased rate of apoptosis.