Overview
Clinical Meaning
Hypothyroidism results from insufficient production of thyroid hormones (T4 and T3) by the thyroid gland, affecting virtually every organ system.
Hypothyroidism results from insufficient production of thyroid hormones (T4 and T3) by the thyroid gland, affecting virtually every organ system. The hypothalamic-pituitary-thyroid (HPT) axis regulates thyroid hormone production: the hypothalamus secretes thyrotropin-releasing hormone (TRH), which stimulates the anterior pituitary to release thyroid-stimulating hormone (TSH). TSH binds to TSH receptors on thyroid follicular cells, activating the sodium-iodide symporter (NIS) to trap iodide, which is then organified by thyroid peroxidase (TPO) and coupled to thyroglobulin to form T4 (thyroxine, ~80% of production) and T3 (triiodothyronine, ~20%). T4 is a prohormone converted to active T3 by type 1 and type 2 deiodinases in peripheral tissues (liver, kidneys, muscle). T3 binds nuclear thyroid hormone receptors (TR-α and TR-β) to regulate gene transcription controlling basal metabolic rate, thermogenesis, protein synthesis, lipid metabolism, cardiac contractility, and CNS development. In primary hypothyroidism (95% of cases), the thyroid gland itself is impaired — most commonly from Hashimoto thyroiditis (chronic lymphocytic thyroiditis), an autoimmune condition where anti-TPO antibodies and anti-thyroglobulin antibodies mediate lymphocytic infiltration and progressive destruction of thyroid follicular cells, leading to fibrosis and goiter formation (initially) followed...
