{"id":4422343,"date":"2025-01-11T14:26:04","date_gmt":"2025-01-11T20:26:04","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/topics\/concise-physiology-of-the-thyroid-gland\/"},"modified":"2025-01-12T19:38:16","modified_gmt":"2025-01-13T01:38:16","slug":"concise-physiology-of-the-thyroid-gland","status":"publish","type":"oen_topic","link":"https:\/\/myendoconsult.com\/learn\/topics\/concise-physiology-of-the-thyroid-gland\/","title":{"rendered":"Concise Physiology of The Thyroid Gland"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">EFFECTS OF TSH ON THE THYROID GLAND<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Overview: Hypothalamic\u2013Pituitary\u2013Thyroid Regulation<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Hypothalamic Role<\/strong>\n<ul class=\"wp-block-list\">\n<li>Secretes <strong>thyrotropin-releasing hormone (TRH)<\/strong>, a modified tripeptide (pyroglutamyl-histidyl-proline-amide).<\/li>\n\n\n\n<li>TRH <strong>increases<\/strong> transcription of TSH \u03b1 and \u03b2 subunits.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Pituitary Role (Thyrotrophs)<\/strong>\n<ul class=\"wp-block-list\">\n<li>Synthesize and secrete <strong>thyrotropin (TSH)<\/strong>, a <strong>glycoprotein<\/strong> hormone.<\/li>\n\n\n\n<li>TSH has an <strong>\u03b1 subunit<\/strong> (common to LH, FSH, hCG) and a <strong>\u03b2 subunit<\/strong> (specific to TSH).<\/li>\n\n\n\n<li><a href=\"https:\/\/myendoconsult.com\/learn\/thyroid-hormone-synthesis\/\" data-wpil-monitor-id=\"104\">Thyroid hormones<\/a> <strong>T4<\/strong> and <strong>T3<\/strong> provide <strong>negative feedback<\/strong> by suppressing TRH and TSH subunit transcription.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Thyroid Hormones<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>T4 (thyroxine)<\/strong> and <strong>T3 (triiodothyronine)<\/strong> are the main output of the thyroid.<\/li>\n\n\n\n<li>Serum TSH exhibits an <strong>inverse log-linear relationship<\/strong> with serum free T4.\n<ul class=\"wp-block-list\">\n<li>Small changes in free T4 can cause large changes in TSH.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">TSH: Normal Range and Alterations<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Reference Range<\/strong>: ~0.3\u20135.0 mIU\/L in healthy individuals (lab-dependent).<\/li>\n\n\n\n<li><strong>Elevations in TSH<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Primary hypothyroidism (loss of negative feedback).<\/li>\n\n\n\n<li>Secondary hyperthyroidism due to a <strong>TSH-secreting pituitary adenoma<\/strong> (rare).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Decreased TSH<\/strong>: Primary hyperthyroidism (excess T4\/T3 suppresses pituitary TSH secretion).<\/li>\n<\/ul>\n\n\n\n<h4 class=\"wp-block-heading\">Circadian and Pulsatile Secretion<\/h4>\n\n\n\n<ul class=\"wp-block-list\">\n<li>TSH <strong>rises<\/strong> (surges) nocturnally, preceding sleep onset.<\/li>\n<\/ul>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">TSH Receptor and Mechanism of Action<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>TSH Receptor<\/strong>\n<ul class=\"wp-block-list\">\n<li>A <strong>G protein\u2013coupled receptor<\/strong> in <a href=\"https:\/\/myendoconsult.com\/learn\/normal-thyroid-follicular-cells\/\" data-wpil-monitor-id=\"100\">thyroid follicular cells<\/a>.<\/li>\n\n\n\n<li>Couples primarily to <strong>Gs<\/strong> (cAMP\u2013protein kinase A pathway) and also activates <strong>phospholipase C<\/strong>\/Ca\u00b2\u207a pathways.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Downstream Effects<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Iodine Uptake<\/strong> (via sodium\u2013iodide symporter transcription).<\/li>\n\n\n\n<li><strong>Thyroglobulin and Thyroperoxidase<\/strong> gene transcription.<\/li>\n\n\n\n<li><strong>Colloid Resorption<\/strong> and <strong>Release<\/strong> of T4 and T3.<\/li>\n\n\n\n<li><strong>H2O2 Production<\/strong>, iodide efflux, and organification of iodide.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Other Ligands<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Thyroid-Stimulating Immunoglobulins (TSI)<\/strong> in Graves disease \u2192 stimulate TSH receptor \u2192 hyperthyroidism.<\/li>\n\n\n\n<li><strong>Thyroid-Blocking Antibodies<\/strong> in Hashimoto thyroiditis \u2192 reduce thyroid function.<\/li>\n\n\n\n<li><strong>High LH\/hCG Levels<\/strong> (e.g., early pregnancy) can weakly activate the TSH receptor \u2192 mild physiologic hyperthyroidism.<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">Changes in Thyroid Mass and Function with TSH Variations<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Normal TSH, Intact Axis<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong><a href=\"https:\/\/myendoconsult.com\/learn\/normal-thyroid-ultrasound-images\/\" data-wpil-monitor-id=\"101\">Normal thyroid<\/a> mass<\/strong>.<\/li>\n\n\n\n<li>Follicular cells: <strong>Cuboidal<\/strong>.<\/li>\n\n\n\n<li><strong>Euthyroid<\/strong> hormone levels, normal <a href=\"https:\/\/myendoconsult.com\/learn\/radioactive-iodine-uptake-and-scan\/\" data-wpil-monitor-id=\"105\">radioactive iodine uptake<\/a>.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Low TSH (Hypothalamic or Pituitary Dysfunction)<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong><a href=\"https:\/\/myendoconsult.com\/learn\/primary-vs-secondary-hypothyroidism\/\" data-wpil-monitor-id=\"106\">Secondary Hypothyroidism<\/a><\/strong>.<\/li>\n\n\n\n<li><strong>Decreased thyroid size<\/strong> (atrophy).<\/li>\n\n\n\n<li>Follicular cells: <strong>Flattened<\/strong> appearance.<\/li>\n\n\n\n<li><strong>Low T4\/T3<\/strong>, low <a href=\"https:\/\/myendoconsult.com\/learn\/radioactive-iodine-treatment-and-scanning\/\" data-wpil-monitor-id=\"107\">radioactive iodine<\/a> uptake, TSH inappropriately low\/normal.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Inappropriately Normal or <a href=\"https:\/\/myendoconsult.com\/learn\/falsely-elevated-tsh\/\" data-wpil-monitor-id=\"102\">Elevated TSH<\/a> (TSH-Secreting Adenoma)<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Excess thyroid growth<\/strong> \u2192 <a href=\"https:\/\/myendoconsult.com\/learn\/goiter\/\" data-wpil-monitor-id=\"108\">goiter<\/a> (thyroid feels firm on palpation).<\/li>\n\n\n\n<li>Follicular cells: <strong>Columnar<\/strong>, colloid typically reduced (active hormone synthesis).<\/li>\n\n\n\n<li><strong>High T4\/T3<\/strong> levels, often with increased <a href=\"https:\/\/myendoconsult.com\/learn\/radioactive-iodine-treatment-thyroid-cancer\/\" data-wpil-monitor-id=\"109\">radioactive iodine<\/a> uptake.<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h2 class=\"wp-block-heading\">PHYSIOLOGY OF THYROID HORMONES<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Iodine Metabolism in Thyroid Hormone Synthesis<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Iodine Uptake<\/strong>\n<ul class=\"wp-block-list\">\n<li>Dietary <strong>iodide (I\u207b)<\/strong> absorbed via GI tract; taken up by the <strong>thyroid<\/strong> (and salivary glands) or excreted in urine.<\/li>\n\n\n\n<li><strong>Sodium\u2013Iodide Symporter (NIS)<\/strong> moves iodide into follicular cells (against a gradient).\n<ul class=\"wp-block-list\">\n<li><strong>TSH<\/strong> upregulates NIS transcription.<\/li>\n\n\n\n<li><strong>Perchlorate (ClO4\u207b)<\/strong> and <strong>pertechnetate (TcO4\u207b)<\/strong> can compete with iodide at NIS.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Iodide Transport to Colloid<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Pendrin<\/strong> (apical transporter) carries iodide into follicular lumen.<\/li>\n\n\n\n<li>Iodide is <strong>oxidized<\/strong> by <strong>thyroid peroxidase (TPO)<\/strong>, enabling <strong>iodination<\/strong> of tyrosyl residues on <strong>thyroglobulin<\/strong>.<\/li>\n\n\n\n<li>Antithyroid drugs (e.g., <strong>propylthiouracil<\/strong>, <strong>methimazole<\/strong>) <strong>inhibit TPO<\/strong>.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Hormone Formation<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>MIT<\/strong> (monoiodotyrosine) + <strong>DIT<\/strong> (diiodotyrosine) \u2192 T3.<\/li>\n\n\n\n<li><strong>DIT + DIT<\/strong> \u2192 T4.<\/li>\n\n\n\n<li>Both stored in <strong>thyroglobulin<\/strong> (Tg) in the colloid (3\u20134 T4 molecules per Tg).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Release into Circulation<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>TSH<\/strong> stimulates micropinocytosis of colloid \u2192 Tg proteolysis in phagolysosomes \u2192 release of T4, T3, MIT, DIT.<\/li>\n\n\n\n<li><strong>MIT<\/strong>\/DIT are deiodinated by Dhal-1; the freed iodide is recycled.<\/li>\n\n\n\n<li>Excess iodide <strong>inhibits<\/strong> many of these steps (used clinically to manage hyperthyroidism).<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"3000\" height=\"2100\" src=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/thyroid-hormone-synthesis-info.png\" alt=\"\" class=\"wp-image-4422847\" srcset=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/thyroid-hormone-synthesis-info.png 3000w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/thyroid-hormone-synthesis-info-300x210.png 300w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/thyroid-hormone-synthesis-info-768x538.png 768w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/thyroid-hormone-synthesis-info-1536x1075.png 1536w, https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/thyroid-hormone-synthesis-info-2048x1434.png 2048w\" sizes=\"auto, (max-width: 3000px) 100vw, 3000px\" \/><figcaption class=\"wp-element-caption\">Thyroid Hormone Synthesis<\/figcaption><\/figure>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">T4 and T3 Distribution and Metabolism<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Proportions<\/strong>\n<ul class=\"wp-block-list\">\n<li>~10:1 ratio of T4:T3 released.<\/li>\n\n\n\n<li><strong>Majority of T3<\/strong> (\u223c75%) is formed by <strong>peripheral 5\u2032-deiodination<\/strong> of T4.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Binding in Plasma<\/strong>\n<ul class=\"wp-block-list\">\n<li>Mostly bound to <strong>thyroxine-binding globulin (TBG)<\/strong>, <strong>transthyretin<\/strong>, or <strong>albumin<\/strong>.<\/li>\n\n\n\n<li>TBG has a <strong>high affinity<\/strong> for T4, less for T3.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Cellular Mechanism of Action<\/strong>\n<ul class=\"wp-block-list\">\n<li>T4\/T3 <strong>enter cells<\/strong> \u2192 T3 (active form) binds to <strong>thyroid <a href=\"https:\/\/myendoconsult.com\/learn\/types-of-hormone-receptors\/\" data-wpil-monitor-id=\"103\">hormone receptors<\/a><\/strong> on DNA \u2192 regulates gene transcription and influences <strong>basal metabolic rate<\/strong>.<\/li>\n\n\n\n<li>T3 has ~15-fold <strong>higher affinity<\/strong> for the receptor than T4.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Inactivation Pathways<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Inner Ring (5-deiodination)<\/strong> forms <strong>reverse T3 (rT3)<\/strong> from T4, or T2 from T3.<\/li>\n\n\n\n<li>Conjugation in the <strong>liver<\/strong> (e.g., glucuronidation) \u2192 excretion in bile, reabsorption in GI tract.<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">Unique Thyroid Hormone Storage<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>The thyroid gland stores large amounts of T4\/T3 in <strong>colloid<\/strong> (as part of thyroglobulin).<\/li>\n\n\n\n<li>About <strong>5 mg<\/strong> of T4 can be stored in a 20-g gland.<\/li>\n\n\n\n<li><strong>Inflammatory damage<\/strong> (e.g., subacute thyroiditis) often leads to a <strong>surge<\/strong> of hormones \u2192 transient thyrotoxicosis.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>EFFECTS OF TSH ON THE THYROID GLAND Overview: Hypothalamic\u2013Pituitary\u2013Thyroid Regulation TSH: Normal Range and Alterations Circadian and Pulsatile Secretion TSH Receptor and Mechanism of&hellip;<\/p>\n","protected":false},"featured_media":0,"template":"","oen_topic_chapter":[683],"class_list":["post-4422343","oen_topic","type-oen_topic","status-publish","hentry","oen_topic_chapter-thyroid-gland"],"_links":{"self":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422343","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic"}],"about":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/types\/oen_topic"}],"version-history":[{"count":4,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422343\/revisions"}],"predecessor-version":[{"id":4422848,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422343\/revisions\/4422848"}],"wp:attachment":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media?parent=4422343"}],"wp:term":[{"taxonomy":"oen_topic_chapter","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic_chapter?post=4422343"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}