Identification of histologically undetectable parathyroid hyperplasia by flow cytometry

Abstract

Recurrent hyperparathyroid disease is a continuing surgical problem resulting in a controversy about how much parathyroid tissue to excise initially. We studied the DNA content of parathyroid cells and analyzed the differences found in normal, hyperplastic, and adenomatous glands with the new technique of flow cytometry. By staining DNA with an intercalating fluorescent dye, propidium iodide, and passing the nuclei through an exciting laser beam, the amount of DNA per nucleus can be measured. The resultant DNA histogram can be analyzed to provide information on the per cent of cells in the cell cycle phases (G0 + G1, S, and G2 + M). Histograms from normal parathyroids (parathyroids from nonhyperparathyroid patients) were statistically compared with histograms from adenomatous parathyroids. A significant difference (p < 0.04) in the tetraploid region (G2 + M) was identified. The computer exploited this difference to calculate the per cent chance of any sample being an adenoma. In all parathyroid samples tested from 54 patients, there were no false positives in the normal parathyroid group and twelve false negatives (15 per cent) in the adenomatous group. Biopsies from histologically and grossly “normal” glands from hyperparathyroid patients in which an adenoma had been excised showed varied DNA patterns typical of both groups. Seventy-one per cent of these parathyroid glands appeared normal and had virtually no activity in the tetraploid region. Some glands were in an indeterminate range and a few definitely had DNA content typical of an adenomatous parathyroid. This study describes a clinically adaptable, quantitative method for analyzing biopsied parathyroid glands that has the potential of identifying previously undetectable hyperplasia at the initial surgical procedure. The ability to selectively excise these hyperplastic glands may reduce the late recurrence sometimes seen with excision of only an enlarged adenoma and prevent hypoparathyroidism after excessive ablation of normal parathyroid tissue.