Radiation-associated hyperparathyroidism: comparison of adenoma growth rates, inferred from weight and duration of latency, with prevalence of mitosis

Abstract

In sporadic parathyroid adenomas, the birth rate of new cells, based on the proportion of S-phase cells at the time of surgical excision, is much too low to account for growth of the tumor from a single cell, as is required by monoclonal origin, even if the mutation occurred in utero, indicating that the rate of cell proliferation has slowed down during the course of the disease. In radiation-associated hyperparathyroidism, the age at irradiation provides a more accurate upper limit to the age of the tumor. The purpose of this study was to relate this age to the prevalence of mitosis as an alternative index of current cell proliferation. In 56 such patients, the geometric mean for the minimum cell birth rate needed for growth from a single cell to the observed size in the time available was 54.4%. In 44 patients, including 31 of the previous 56 and an additional 13, sampling an average of 220,000 cell profiles, 15 mitoses were found, an overall prevalence of 0.15/10(5), which corresponds to a cell birth rate of 2.7%/yr, assuming the duration of mitosis to be 0.5 h. If cases with no mitosis were assigned a value of half the detection limit, the geometric mean mitotic index was 0.360/10(5), and the corresponding cell birth rate was 6.4%/yr. This is more than 8 times smaller than the minimum birth rate required and 20 times smaller than the cell birth rate in meningiomas, suggesting that such extreme reduction of cell birth rate is a unique feature of parathyroid adenomas, rather than a general feature of all benign tumors. The data support the set-point hypothesis, which reconciles the earlier concept of focal hyperplasia with monoclonal origin and provides an alternative nonneoplastic mechanism of etiology for the usual nonprogressive form of the disease.