Thyroid hormone homeostasis loop. Hypothalamic TRH → anterior pituitary TSH → thyroid follicle cells → T4 (primary secretory product, ~80% of output) + T3 (~20%; the active hormone at TR-α/β). Peripheral conversion of T4 → T3 by deiodinases (D1 liver/kidney, D2 brain/pituitary, D3 inactivator). Negative feedback: T3 (intracellular pituitary) suppresses TSH. Therapeutic Rx: levothyroxine (T4) — long t½ (~7 d) allows daily dosing; liothyronine (T3) used selectively. Methimazole / PTU block thyroid peroxidase (organification step). Amiodarone disrupts thyroid status in 2-3 ways (iodine load + D1 inhibition + direct thyroiditis).
Organ Systems
endocrine
Pathway Steps
trh → tsh — via pituitary thyrotrophs. Hypothalamic thyrotropin-releasing hormone (TRH) stimulates the anterior pituitary to secrete thyroid-stimulating hormone (TSH). Pituitary TSH is the most sensitive clinical marker of thyroid status because of the steep, logarithmic feedback relationship between TSH and thyroid hormone.
tsh → thyroxine — via thyroid follicle TSH-R → thyroglobulin iodination → T4 + T3 secretion. TSH drives the thyroid to synthesize and release thyroid hormone, predominantly thyroxine (T4) — the main circulating form but largely a prohormone. TSH also promotes iodide uptake and thyroid growth, which is why goiter develops when TSH is chronically elevated.
thyroxine → triiodothyronine — via peripheral deiodinase D1 (liver/kidney) + D2 (brain/pituitary). In peripheral tissues, deiodinases convert T4 to the far more active triiodothyronine (T3), the form that binds nuclear thyroid receptors. This local activation (and its reverse-T3 alternative) lets tissues control their own thyroid exposure — and is suppressed in illness (sick-euthyroid) and by propylthiouracil.
Known Modulators
levothyroxine (substrate) — T4 replacement (most common indication: primary hypothyroidism)