Iodine-containing hormones produced by the thyroid gland that regulate basal metabolic rate, thermogenesis, growth, and development. T4 (thyroxine, inactive) is converted to T3 (triiodothyronine, active form) peripherally by deiodinases. Act via nuclear thyroid hormone receptors (TR) regulating gene transcription.
TSH from pituitary stimulates thyroid follicular cells to produce thyroglobulin, which is iodinated to form MIT and DIT, coupled to form T4 (predominant) and T3. T4 is converted to active T3 by type 1 and 2 deiodinases (D1/D2) or inactive rT3 by type 3 deiodinase (D3). T3 enters cells, binds thyroid receptors (TRα, TRβ) on DNA, regulating expression of metabolic genes (increased mitochondrial biogenesis, glucose uptake, lipolysis, protein synthesis). Effects include increased BMR, thermogenesis, cardiac output, CNS development, and protein synthesis.
Thyroid dysfunction affects every system. Hypothyroidism causes fatigue, weight gain, cold intolerance, depression, constipation, and cognitive slowing. In cPNI, functional hypothyroidism (normal TSH, low T3) common due to inflammation (↑rT3), chronic stress (suppressed HPT axis), nutrient deficiencies (iodine, selenium, zinc, iron), or liver dysfunction (impaired T4→T3 conversion). Assessment requires free T3, free T4, reverse T3, TSH, and thyroid antibodies. Treatment addresses root causes, not just hormone replacement.
- T4 is 80-90% of thyroid output; T3 is more potent (3-5x)
- Peripheral conversion: T4 → T3 (active) or rT3 (inactive)
- Selenium required for deiodinase enzymes
- Iodine deficiency is #1 cause of hypothyroidism globally
- Inflammation increases D3 activity → more rT3 (blocks metabolism)
- TSH alone insufficient for diagnosis; need fT3, fT4, rT3
- Thyroid receptors: TRα (heart, muscle, bone), TRβ (liver, brain, pituitary)
- Increases BMR by 60-100% in hyperthyroidism
- Essential for brain development (cretinism if deficient in utero)
- Autoimmune thyroid disease most common endocrine disorder
- TSH — Pituitary hormone stimulating thyroid hormone production
- HPT axis — Hypothalamic-pituitary-thyroid axis regulating thyroid function
- T3 — Active thyroid hormone; more potent than T4
- T4 — Predominantly secreted thyroid hormone; converted to T3 peripherally
- reverse T3 — Inactive form; elevated in inflammation and stress
- deiodinases — Enzymes converting T4 to T3 or rT3
- selenium — Essential cofactor for deiodinase enzymes
- iodine — Essential substrate for thyroid hormone synthesis
- metabolism — Thyroid hormones regulate basal metabolic rate
- mitochondrial biogenesis — T3 induces mitochondrial biogenesis via PGC-1α
- inflammation — Increases D3 activity, raising rT3 and lowering T3
- chronic stress — Suppresses HPT axis via cortisol and cytokines
- hypothyroidism — Deficiency of thyroid hormones causing metabolic slowing
- hyperthyroidism — Excess thyroid hormones causing metabolic acceleration
- Hashimoto's thyroiditis — Autoimmune destruction of thyroid causing hypothyroidism
- Graves' disease — Autoimmune hyperthyroidism via TSH receptor antibodies
- depression — Hypothyroidism mimics or exacerbates depression
- thermogenesis — Thyroid hormones essential for heat production
- brain development — Critical for myelination and neurodevelopment
- immune system — Thyroid hormones modulate immune function; autoimmune thyroid disease common