A patient-specific model of the HPT axis in Hashimoto's Thyroiditis

The purpose of modeling the negative feedback control mechanism of the hypothalamus-pituitary- thyroid (HPT) axis in autoimmune thyroiditis is to describe the clinical course of euthyroidism subclinical hypothyroidism and overt hypothyroidism for patients. Thyroid hormone unbound thyroxine (FT4) levels are controlled by negative feedback control through thyroid stimulating hormone(TSH). Autoimmune thyroiditis is a disease in which the thyroid-infiltrating lymphocytes attack autoantigens in follicle cells destroying them over a long time. To describe the operation of the feedback control we developed a deterministic mathematical model involving four clinical variables - TSH FT4 anti-thyroid antibodies and the thyroid gland’s functional size. The problem of two different time scales for circulating hormones and thyroid damage is addressed using singular perturbation theory. Analysis of the mathematical model establishes stability and conditions under which the diseased state can maintain the slow movement toward diseased state equilibrium. To validate the model predictions a dataset obtained from a Sicilian adult population has been employed.