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

Apoptosis in parathyroid hyperplasia of patients with primary or secondary uremic hyperparathyroidism.BackgroundChronic 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.MethodsParathyroid 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.ResultsThe 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.ConclusionThese 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