The Thyroid Axis
The hypothalamic-pituitary-thyroid (HPT) axis regulates metabolic rate, growth, and development through thyroid hormones T3 and T4. The hypothalamus produces thyrotropin-releasing hormone (TRH), which stimulates thyroid-stimulating hormone (TSH) secretion from the anterior pituitary. TSH then drives the thyroid gland to synthesize and secrete thyroid hormones. This cascade is governed by negative feedback — rising T3 and T4 suppress both TRH and TSH release.
T4-to-T3 Conversion
The thyroid gland produces primarily T4, which circulates as a reservoir. Peripheral tissues convert T4 to the more active T3 via deiodinase enzymes. Type 1 deiodinase in liver and kidney provides most circulating T3, while Type 2 deiodinase in brain and pituitary provides local T3 for feedback regulation. The conversion rate is a critical parameter — conditions like non-thyroidal illness ("sick euthyroid syndrome") reduce conversion, lowering T3 despite normal T4.
Clinical Thyroid Disorders
Reduce thyroid mass to 20% to model severe hypothyroidism — watch TSH rise dramatically as the pituitary compensates. Increase TRH drive and reduce feedback sensitivity to simulate TSH-secreting pituitary adenoma. The characteristic inverse log-linear TSH-T4 relationship means a 50% drop in T4 can produce a 10-fold TSH increase, explaining why TSH is the most sensitive screening test for thyroid dysfunction.
Pharmacological Interventions
Levothyroxine replacement therapy effectively increases the T4 pool, which can be modeled by adjusting thyroid mass upward. Antithyroid drugs like methimazole reduce thyroid hormone synthesis, modeled by decreasing thyroid mass. The simulation reveals why dose titration requires weeks — the long half-life of T4 (7 days) means steady state takes 4-6 weeks to achieve after any parameter change.