{"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 Action Changes in Thyroid Mass and Function with TSH Variations PHYSIOLOGY OF THYROID HORMONES Iodine Metabolism in Thyroid Hormone Synthesis T4 and T3 Distribution and Metabolism Unique Thyroid Hormone Storage<\/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","post-wrapper","thrv_wrapper"],"_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}]}}