System analysis and estimation of key parameters of thyroid hormone metabolism in sheep

Certain system modeling and analysis methods, including identifiability analysis, were applied to the design of experiments and the processing of a posteriori humoral data for quantifying the dynamics of thyroid hormone (both T3 and T4) metabolism in sheep. Two sheep were studied: one euthyroid, and one abnormal; and several alternative hypotheses concerning system structure were tested by fitting alternative models to the resulting data. For the normal sheep, the results indicated that the plasma hormone pool contained 40% of the total T4 with 14% in liver-kidneys-gut, and 47% in muscle-skin; T3 was distributed with 12-20% in plasma, 8-18% in liver-kidneys-gut, and 62-80% in muscle-skin. Also, 40-52% of the normal sheep T3 was generated by conversion of 11-17% of the T4. Compared to the euthyroid sheep, the abnormal animal lacked T4 to T3 conversion, demonstrated a higher T3/T4 secretion rate ratio, and had plasma-liver T3 kinetics increased 2-3 times. The ranges indicated are consistent with all hypotheses tested. A number of other parameters of thyroid hormone metabolism in these sheep also were computed from the data.