Clustering Based Parameter Estimation of Thyroid Hormone Pathway.

Abstract

An ordinary differential equation (ODE) model of the working of the thyroid system for euthyroidism has been presented. As clinical data for thyroid hormones is relatively scarce, such modelling offers potential benefits over wet lab procedures. Genetic algorithms developed for determining of parameters of the ODE system using the available data have been presented and evaluated. This approach enables subject specific parameter estimation towards characterisation of individual thyroid operation. Initially, a simple steady state model was used. Later a cosinor model for the circadian variation of thyroid hormones was used to obtain more reliable results, as indicated through sensitivity analysis in conjunction with other statistical methods. Our parameter determination method has been tested on groups of patients with similar observed values of thyroid stimulating hormone (TSH), free T 3 and free T 4 (identified through clustering) to determine their parameter values jointly. This approach appears to produce parameter sets with lower variation than parameters determined independently, thus leading to better parameter determination.