{"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&hellip;<\/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"],"_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}]}}