CELL-KINETICS IN PARATHYROID ADENOMAS - EVIDENCE FOR DECLINE IN RATES OF CELL BIRTH AND TUMOR-GROWTH, ASSUMING CLONAL ORIGIN

OBJECTIVE We aimed to provide a cell kinetic explanation for the demonstrated lack of disease progression in most patients with mild, asymptomatic primary hyperparathyroidism. DESIGN We compared cell birth rates, estimated at the time of adenoma excision, with the lowest birth rates needed to grow tumours of the observed size. PATIENTS Sixty-three patients with primary hyperparathyroidism due to a single chief cell adenoma who had normal renal function were followed up for long enough to demonstrate cure after surgical excision. MEASUREMENTS Fresh adenoma tissue was incubated with tritiated thymidine. The proportion of cells synthesizing DNA was determined directly by radioautography in 18 cases, and indirectly from the regression of label index on rate of DNA synthesis in 45 cases. The birth rate of new cells was calculated assuming the duration of S phase to be 12 hours. The number of cells in each adenoma was estimated both from parenchymal weight and from total DNA content, and the minimum birth rate needed to produce this number of cells from a single cell, beginning in utero, was calculated on an exponential model. RESULTS The mean observed birth rate of new cells (mean (SD)) was 17.3 (11.1)%/year, and the minimum needed birth rate was 42.8 (21.6)%/year, significantly, (P < 0.001) higher than the observed birth rate. CONCLUSIONS The rate of mitosis had fallen substantially during the life span of most parathyroid adenomas. To account for this, we propose that the mutation implied by a proliferation, as well as hormone secretion, is influenced by calcium in parathyroid cells, the expected result would be rapid initial growth, slowing down as tumour size reached an asymptotic value corresponding to the total rate of hormone secretion needed to raise the plasma calcium to the new setpoint.