{"id":4422347,"date":"2025-01-11T14:33:53","date_gmt":"2025-01-11T20:33:53","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/topics\/graves-disease\/"},"modified":"2025-01-13T06:11:26","modified_gmt":"2025-01-13T12:11:26","slug":"graves-disease","status":"publish","type":"oen_topic","link":"https:\/\/myendoconsult.com\/learn\/topics\/graves-disease\/","title":{"rendered":"Graves Disease"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">GRAVES DISEASE<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Definition and Key Features<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Autoimmune thyroid syndrome<\/strong> characterized by:\n<ol class=\"wp-block-list\">\n<li><strong>Hyperthyroidism<\/strong> (elevated T3 and T4)<\/li>\n\n\n\n<li><strong>Diffuse <a href=\"https:\/\/myendoconsult.com\/learn\/goiter\/\" data-wpil-monitor-id=\"112\">goiter<\/a><\/strong><\/li>\n\n\n\n<li><strong>Ophthalmopathy<\/strong> (eye involvement, including proptosis)<\/li>\n\n\n\n<li><strong>Occasionally Dermopathy<\/strong> (pretibial myxedema, also called localized myxedema)<\/li>\n<\/ol>\n<\/li>\n\n\n\n<li><strong>Important Distinction<\/strong>: Graves disease is not synonymous with hyperthyroidism:\n<ul class=\"wp-block-list\">\n<li>Some patients may have ophthalmopathy <strong>without<\/strong> hyperthyroidism.<\/li>\n\n\n\n<li>Other causes of hyperthyroidism also exist (e.g., toxic multinodular goiter, toxic adenoma).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Pathophysiology<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Caused by <strong>TSH receptor autoantibodies<\/strong> (also called thyroid-stimulating immunoglobulins, TSI) that <strong>stimulate<\/strong> thyroid growth and hormone production (T4, T3).<\/li>\n<\/ul>\n<\/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\">Epidemiology<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Female : Male ratio<\/strong> \u2248 <strong>8 : 1<\/strong><\/li>\n\n\n\n<li>Most common during <strong>childbearing years<\/strong>, but can occur at any age (infancy \u2192 elderly).<\/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\">Thyroid Gland Changes<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>Goiter<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Diffusely enlarged, up to several times normal size.<\/li>\n\n\n\n<li>Right lobe often slightly larger than left.<\/li>\n\n\n\n<li><strong>Pyramidal lobe<\/strong> commonly enlarged.<\/li>\n\n\n\n<li>Rarely, no palpable enlargement (occult or \u201cclinically inapparent\u201d goiter).<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Vascularity<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Increased blood flow \u2192 a <strong>bruit<\/strong> heard with stethoscope; sometimes a <strong>thrill<\/strong> by palpation over the upper poles.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Histology<\/strong>:\n<ul class=\"wp-block-list\">\n<li><strong>Follicular hyperplasia<\/strong> with <strong>papillary infoldings<\/strong>.<\/li>\n\n\n\n<li><strong>Loss of colloid<\/strong> in follicle lumens.<\/li>\n\n\n\n<li><strong>Lymphocytic infiltration<\/strong> (T cells, occasionally B-cell follicles) in chronic or advanced disease.<\/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\">Hypermetabolic State and Clinical Manifestations<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong><a href=\"https:\/\/myendoconsult.com\/learn\/thyroid-hormone-synthesis\/\" data-wpil-monitor-id=\"113\">Thyroid Hormones<\/a><\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Elevated T4 and T3<\/strong>.<\/li>\n\n\n\n<li>Increased <a href=\"https:\/\/myendoconsult.com\/learn\/radioactive-iodine-uptake-and-scan\/\" data-wpil-monitor-id=\"114\">radioactive iodine uptake<\/a> and turnover.<\/li>\n\n\n\n<li>Increased oxygen consumption (basal metabolic rate).<\/li>\n\n\n\n<li>Decreased total and HDL cholesterol levels.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Neuro-Psychological Changes<\/strong>\n<ul class=\"wp-block-list\">\n<li>Nervousness, agitation, insomnia, emotional lability.<\/li>\n\n\n\n<li>Difficulty concentrating, confusion, poor immediate recall.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Tremor<\/strong>\n<ul class=\"wp-block-list\">\n<li>Often subtle; best seen by placing a piece of paper on outstretched fingers.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Cardiovascular Effects<\/strong>\n<ul class=\"wp-block-list\">\n<li>Palpitations, sinus tachycardia, <strong>atrial fibrillation<\/strong> (in ~15%, especially in older patients), possible high-output heart failure.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Skin Changes<\/strong>\n<ul class=\"wp-block-list\">\n<li>Warm, velvety, sometimes flushed.<\/li>\n\n\n\n<li><strong>Excess sweating<\/strong> from increased calorigenesis.<\/li>\n\n\n\n<li><strong>Vitiligo<\/strong> (autoimmune) in some patients.<\/li>\n\n\n\n<li><strong>Onycholysis<\/strong> (\u201cPlummer <a href=\"https:\/\/myendoconsult.com\/learn\/plummers-nails\/\" data-wpil-monitor-id=\"110\">nail<\/a>s,\u201d nail loosening).<\/li>\n\n\n\n<li><strong>Infiltrative Dermopathy (Pretibial Myxedema)<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Nonpitting, rubbery swelling over the lower legs (often lateral side) with violaceous discoloration, sometimes nodular lesions.<\/li>\n\n\n\n<li>Usually associated with severe ophthalmopathy.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Other Autoimmune Associations<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Hair changes<\/strong>: Finer hair or local hair loss over myxedematous areas.<\/li>\n\n\n\n<li>Coexistence of other autoimmune findings.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Ophthalmic Findings<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Eyelid Retraction<\/strong> (stare), <strong>eyelid lag<\/strong> (see also \u201cGraves Ophthalmopathy\u201d section).<\/li>\n\n\n\n<li>Unique to Graves: true <strong>inflammatory ophthalmopathy<\/strong> with proptosis.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Muscle and Weight Changes<\/strong>\n<ul class=\"wp-block-list\">\n<li>Weight loss despite increased appetite.<\/li>\n\n\n\n<li>Muscle wasting and weakness (especially in proximal muscle groups such as quadriceps).<\/li>\n\n\n\n<li>Possibly increased respiratory effort due to muscle weakness.<\/li>\n\n\n\n<li>Mixed effects on glucose metabolism; often fasting hyperglycemia.<\/li>\n\n\n\n<li>Possible hyperdefecation or malabsorption.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Reproductive Hormone Effects<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>In women<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Increased total estradiol (due to elevated sex hormone\u2013binding globulin).<\/li>\n\n\n\n<li>Decreased free estradiol, \u2191 LH \u2192 oligomenorrhea or amenorrhea.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>In men<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Increased total testosterone, low free testosterone, mild \u2191 LH.<\/li>\n\n\n\n<li>\u2191 Aromatization to estradiol \u2192 <a href=\"https:\/\/myendoconsult.com\/learn\/topics\/gynecomastia\/\" data-wpil-monitor-id=\"343\">gynecomastia<\/a>, low libido, erectile dysfunction.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Bone Metabolism<\/strong>\n<ul class=\"wp-block-list\">\n<li>Excess T4 and T3 stimulate <strong>bone resorption<\/strong> (\u2191 osteocalcin, \u2191 bone-specific alkaline phosphatase).<\/li>\n\n\n\n<li>Leads to <strong>reduced bone density<\/strong>, potential <strong><a href=\"https:\/\/myendoconsult.com\/learn\/topics\/hypercalcemia\/\" data-wpil-monitor-id=\"344\">hypercalcemia<\/a><\/strong>, and <strong>osteoporosis<\/strong> over time.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Cardiac Effects<\/strong>\n<ul class=\"wp-block-list\">\n<li>High-output state, short circulation time, potential for <strong>heart failure<\/strong>.<\/li>\n\n\n\n<li>Systolic hypertension common.<\/li>\n\n\n\n<li>Atrial fibrillation may revert to sinus rhythm after return to euthyroidism.<\/li>\n\n\n\n<li>\u03b2-blockers can relieve many sympathetic-driven symptoms (palpitations, tremor, eyelid retraction) independently of T4\/T3 changes.<\/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\">GRAVES OPHTHALMOPATHY<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Clinical Features<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong><a href=\"https:\/\/myendoconsult.com\/learn\/eye-signs-of-thyroid-disease\/\" data-wpil-monitor-id=\"111\">Eye Signs<\/a><\/strong> (in addition to eyelid retraction\/lag common in hyperthyroidism):\n<ul class=\"wp-block-list\">\n<li><strong>Proptosis (Exophthalmos)<\/strong>: Confirmed via exophthalmometer (normal: &lt;20 mm in whites, &lt;22 mm in blacks).<\/li>\n\n\n\n<li><strong>Periorbital Edema<\/strong> (swelling around the orbit).<\/li>\n\n\n\n<li><strong>Conjunctival Injection<\/strong> and <strong>Chemosis<\/strong> (edema).<\/li>\n\n\n\n<li><strong>Extraocular Muscle Weakness<\/strong> or palsies \u2192 diplopia, blurred vision.<\/li>\n\n\n\n<li><strong>Excess tearing<\/strong>, photophobia, gritty eye sensation.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Measurement<\/strong>\n<ul class=\"wp-block-list\">\n<li><strong>Exophthalmometer<\/strong> used to measure anterior projection of the cornea.<\/li>\n\n\n\n<li>Firmness of orbital tissues assessed by gently pushing back on the globe over the closed lid.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Severe Cases<\/strong>\n<ul class=\"wp-block-list\">\n<li>Inability to fully close eyelids \u2192 corneal ulceration, infection.<\/li>\n\n\n\n<li>Rarely optic nerve compression \u2192 blindness.<\/li>\n<\/ul>\n<\/li>\n<\/ol>\n\n\n\n<figure class=\"wp-block-image size-full\"><img decoding=\"async\" src=\"https:\/\/myendoconsult.com\/learn\/wp-content\/uploads\/TED-stare-1.jpg\" alt=\"\" class=\"wp-image-1810451\"\/><figcaption class=\"wp-element-caption\">Classic lid retraction (hyperthyroid stare) of Graves Disease<\/figcaption><\/figure>\n\n\n\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n\n\n\n<h3 class=\"wp-block-heading\">Pathogenesis of Graves Ophthalmopathy<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Autoimmune Inflammation<\/strong> of retro-orbital tissues, extraocular muscles.<\/li>\n\n\n\n<li><strong>Glycosaminoglycan (GAG) accumulation<\/strong> \u2192 osmotic swelling, infiltration by T lymphocytes, especially around TSH receptor\u2013related antigens.<\/li>\n\n\n\n<li><strong>Strong correlation<\/strong> of severe ophthalmopathy with high TSH receptor antibody titers.<\/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\">Risk Factors and Clinical Course<\/h3>\n\n\n\n<ol class=\"wp-block-list\">\n<li><strong>TSH Receptor Antibody Titer<\/strong>: Higher \u2192 more severe ophthalmopathy.<\/li>\n\n\n\n<li><strong>Gender<\/strong>: More common in women (as with hyperthyroidism), but men tend to have more severe disease if present.<\/li>\n\n\n\n<li><strong>Cigarette Smoking<\/strong>: Strongly linked to increased risk and severity; believed to enhance GAG production and adipogenesis.<\/li>\n\n\n\n<li><strong>Radioiodine Therapy<\/strong>: May worsen or precipitate ophthalmopathy more than surgery or antithyroid drugs.<\/li>\n\n\n\n<li><strong>Hyperthyroidism Onset<\/strong>: Eye disease may precede (20%), coincide (40%), occur during treatment (~20%), or arise within 6 months after diagnosis (20%).<\/li>\n\n\n\n<li><strong>Euthyroid Restoration<\/strong>: Improves eyelid retraction but usually does <strong>not<\/strong> reverse established ophthalmopathy.<\/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\">Management of Graves Ophthalmopathy<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Mild Cases<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Raise head of bed (reduce periorbital edema), frequent saline eye drops, sunglasses for photophobia.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li><strong>Moderate to Severe Symptoms<\/strong>:\n<ul class=\"wp-block-list\">\n<li><strong>Glucocorticoid therapy<\/strong> (e.g., IV methylprednisolone) if chemosis, diplopia, or threatened vision.<\/li>\n\n\n\n<li><strong>Orbital decompression surgery<\/strong> if vision endangered, corneal exposure worsens, or severe cosmetic exophthalmos.<\/li>\n\n\n\n<li><strong>Teprotumumab<\/strong>. An antibody that blocks the Insulin-like growth factor 1 receptor present on fibroblast cells. <\/li>\n<\/ul>\n<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>GRAVES DISEASE Definition and Key Features Epidemiology Thyroid Gland Changes Hypermetabolic State and Clinical Manifestations GRAVES OPHTHALMOPATHY Clinical Features Pathogenesis of Graves Ophthalmopathy Risk Factors and Clinical Course Management of Graves Ophthalmopathy<\/p>\n","protected":false},"featured_media":0,"template":"","oen_topic_chapter":[683],"class_list":["post-4422347","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\/4422347","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":6,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422347\/revisions"}],"predecessor-version":[{"id":4422862,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422347\/revisions\/4422862"}],"wp:attachment":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media?parent=4422347"}],"wp:term":[{"taxonomy":"oen_topic_chapter","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic_chapter?post=4422347"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}