CLONAL ANALYSIS OF NODULAR PARATHYROID HYPERPLASIA IN RENAL HYPERPARATHYROIDISM

Although it is well known that chronic renal failure induces parathyro id hyperplasia, the pathogenesis and development of this parathyroid l esion in this disease are poorly understood. Histopathologically, ther e is progression from diffuse to nodular hyperplasia, and each nodule consists of a single cell type with aggressive proliferative potential . Pathophysiologic and clinical investigations have suggested that neo plastic tumors may emerge from nodular hyperplasia. In this study the clonality of parathyroid tissue in nodular and diffuse hyperplasia in renal hyperparathyroidism was analyzed by a method based on restrictio n fragment length polymorphism of the X chromosome-linked phosphoglyce rokinase gene and on random inactivation of the gene by methylation. D NA of peripheral lymphocytes was screened in 43 women undergoing parat hyroidectomy for advanced renal hyperparathyroidism, and 10 of these p atients appeared to be heterozygous. Fourteen specimens from these pat ients were available for clonal analysis. The analysis showed that all four specimens of diffuse hyperplasia were polyclonal, whereas all se ven specimens from nodules in nodular hyperplasia and all three sample s representing parathyroid tissue removed from forearm because of graf t-dependent recurrence were revealed to be monoclonal. It is likely th at the clonal origin of each nodule is independent. These results sugg est that in renal hyperparathyroidism parathyroid glands initially gro w diffusely and polyclonally, and then the cells in the nodules are la ter transformed monoclonally and proliferate aggressively. From the pr esent study it can be concluded that nodular hyperplasia represents mo noclonal parathyroid neoplasia, which might explain why patients with nodular hyperplasia in renal hyperparathyroidism are refractory to med ical treatment, requiring parathyroidectomy. To prevent recurrences, n odular hyperplastic tissue should not be left at surgery.