The SEON Laboratory (George Leight, M.D., Sanford Garner, Ph.D., and Kenneth McCarty, Ph.D.) is pursuing several lines of research that have evolved from our primary interest in regulation of parathyroid hormone (PTH) secretion and calcium homeostasis.
1) We have developed a reverse transcription-polymerase chain reaction (RT-PCR)-based assay for the expression of mRNA for the calcium-sensing receptor (CaR) of the parathyroid gland and other tissues. This recently described protein has already been shown to be involved in some inherited abnormalities of calcium homeostasis. We have measured the level of expression of this gene in parathyroid tissue from patients undergoing surgery for primary hyperparathyroidism, and an abstract on the results is being submitted to the American Association of Endocrine Surgeons. Additional analyses of both normal parathyroid tissue and parathyroids removed from patients with secondary hyperparathyroidism will be performed in the coming year. This project is also proposed to eventually include assay of expression levels of mRNAs for the vitamin D receptor and PTH. Coupled with characterization of in vitro secretion of PTH over a range of calcium concentrations, information on expression of these genes will allow a more complete exploration of the etiology of hyperparathyroidism and possible treatment of these disorders.
2) Another clinically-related project in our laboratory is the rapid, intraoperative assay of PTH that can be completed within 15 minutes after blood sampling during surgery for either primary or secondary hyperparathyroidism. The half-life of circulating PTH is <3 minutes; therefore a sample taken 5 minutes after tissue excision has already proven to be informative of completeness of removal of adenomatous or hyperplastic parathyroid tissue. We have accumulated data during 1996 on a total of 49 cases of parathyroid surgery, 38 for primary hyperparathyroidism and 11 for secondary hyperparathyroidism. The utility of this assay in the surgical treatment of hyperparathyroidism has been clearly demonstrated. We are currently applying to the Diagnostic Technology Committee for recognition of this test procedure at Duke University Medical Center as a billable test. Significant reductions in the cost of parathyroid surgery are anticipated as a result of implementing this test for all cases. The time required for surgical exploration in primary hyperparathyroidism can be reduced by approximately one hour per case. In addition, the assay provides additional information beyond that currently obtained from frozen section pathology, and the need for this expensive test will be greatly reduced. Finally, the shorter time for surgery and the less extensive exploration made possible by the information obtained with the intraoperative PTH procedure will allow many (approximately 50% by published report) to be completed on an outpatient basis. The cumulative effect of these various savings and the higher reimbursement percentage for outpatient vs. inpatient surgery will result in a net savings of approximately $100,000 to DUMC even after the cost of the procedure is factored in.
3) An additional basic research project that is ongoing in our laboratory is an exploration of the mechanism of hyperparathyroidism in animal models using neonatal and lactating rats that exhibit relatively nonsuppressible PTH secretion in the presence of elevated serum calcium concentrations. The role of vitamin D as a physiologic inhibitor of PTH secretion is also being explored in these models, in addition to the modulation of the parathyroid calcium receptor. A grant proposal was submitted to NIH in June of 1996 on this project. The proposal was not submitted to complete review, but the comments of the initial reviewers should be helpful in revising and resubmitting this proposal with additional data.
Education and Training
- Chief Resident, Surgery, Duke University, 1978 - 1979
- Senior Resident in Surgery, Surgery, Duke University, 1976 - 1978
- Resident, Surgery, Duke University, 1973 - 1974
- Intern, Surgery, Duke University, 1972 - 1973
- M.D., Duke University, 1972