The role of hyperplasia in multiple parathyroid adenomas

Background. Parathyroid adenoma is the most common cause of primary hyperpa rathyroidism (pHPT). Adenomas usually involve only a single gland, and the remaining glands are normal or suppressed. Multiple parathyroid adenomas ha ve been reported to occur in as high as 11% of patients with pHPT. The sign ificant incidence of multiple adenomas with histologic similarities to hype rplasia has raised the possibility that adenoma is a continuation of the hy perplasia state. To test this theory, we used molecular genetics to compare clonality and proliferative activity of parathyroid adenoma with its corre sponding normal glandular tissue. Furthermore, we devised a scheme to defin itively distinguish between the different parathyroid states on a molecular level, because histologic distinction is unreliable. Methods. The study included three patients with a diagnosis of singular par athyroid adenoma and three with double parathyroid adenomas. Paraffin-embed ded surgical specimens of both adenomas and normal glands were retrieved fr om each patient. Clonal analysis of the phosphoglycerolkinase (PGK) gene ha s suggested that parathyroid adenomas are monoclonal. Clonality of parathyr oid adenomas and normal parathyroid glands was studied by polymerase chain reaction-based restriction fragment length polymorphic analysis for the PGK gene. Proliferative activity of the specimens was also analyzed using the immunohistochemical markers PCNA and Ki-67. Results. All adenomas were monoclonal and all normal parathyroid glands wer e polyclonal for the PGK gene in both the single and double adenoma specime ns. All adenomas stained positive for proliferative activity. In the three patients with singular adenoma, proliferative activity was not detected in the normal parathyroid tissue. However, in the double adenoma group, two of the three patients showed hyperproliferative activity in the normal glands . Conclusion. Proliferative activity consistent with hyperplasia was present in some normal glands of multiple adenoma patients. Our observation support s the theory that multiple adenomas may be a continuation of the hyperplasi a state. (C) 2001 John Wiley & Sons, Inc.