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A System Dynamics Approach for the Development of a Patient-Specific Protocol for Radioiodine Treatment of Graves' Disease
Master of Science in Mechanical Engineering (M.S.M.E.)
Year Degree Awarded
Month Degree Awarded
Graves' Disease, Hyperthyroidism, Radioiodine, System Dynamics, Uncertainty Analysis
The thyroid gland secretes hormones that help to govern metabolism and energy expenditure within the body ; these hormones also affect growth and development. As a result, the regulation of thyroid hormones is vital for maintaining an individual's well being. Graves' disease is an autoimmune disorder and is a major cause of hyperthyroidism or an overproduction of thyroid hormones. Radioactive iodine (RAI) therapy has become the preferred treatment with typical RAI protocols being based on the Marinelli-Quimby equation to compute the dose; however, up to 90 % of subjects become hypothyroid within the first year after therapy. In this thesis we focus on the development of a new computational protocol for the calculation of RAI in the treatment of Graves' hyperthyroidism. The new protocol implements a two-compartment model to describe RAI kinetics in the body, which accounts for the conversion between different RAI isotopes used in diagnostic and therapeutic applications. Thus, by using the measured response of the subject's thyroid to a test dose of 123I, the model predicts what amount of RAI (131I) will be needed to reduce, through ablation, the functional, thyroid volume/mass to an amount that would result in a normal metabolic balance. A detailed uncertainty analysis was performed using both a standard propagation of error method as well as a simulation method. The simulation method consisted of both parametric and nonparametric bootstrapping techniques. Using clinical data consisting of activity kinetics and mass dynamics of 17 subjects and measured final mass values of 7 of the 17 subjects, we were able to validate the protocol as well as quantify the uncertainty analysis. This protocol is the basis of an ongoing pilot study in conjunction with Cooley Dickinson hospital, Northampton, MA.
Yossi Christopher Stuart