Graves disease is the most common form of hyperthyroidism, occurring most frequently between the ages of 20 and 50. It is 10 times more common in women than in men. This autoimmune disorder is characterized by the production of activating autoantibodies against the TSH receptor. Hyperthyroidism, driven by these antibodies, often leads to a diffuse goiter due to gland hyperplasia and hypertrophy. The follicular epithelial cells become tall columnar cells, and the colloid exhibits a scalloped periphery indicating rapid turnover.

The primary clinical state found in Graves disease is thyrotoxicosis, which is the state of excessive thyroid hormone in the blood and tissues. Patients with thyrotoxicosis present with a striking picture in clinical medicine. The large increase in metabolic rate is manifested as weight loss despite increased food intake. Excess heat production causes discomfort in warm environments, sweating, and increased water intake. The increase in adrenergic activity results in a rapid heart rate, hyperkinesis, tremor, nervousness, and a wide-eyed stare. Weakness is caused by loss of muscle mass and impaired muscle function. Other symptoms include an emotional state that fluctuates, breathlessness during exercise, and difficulty swallowing or breathing due to compression of the esophagus or trachea by the enlarged thyroid gland. The most common cardiovascular sign is sinus tachycardia.

Thyroid hormone has significant actions on cardiovascular physiology, with T3 increasing cardiac output. This ensures sufficient oxygen delivery to tissues, while also increasing the resting heart rate, stroke volume, and the speed and force of myocardial contractions. Additionally, diastolic relaxation is increased, resulting in an increased cardiac output associated with a widened pulse pressure due to a positive inotropic effect coupled with decreased systemic vascular resistance. Exophthalmos (abnormal protrusion of the eyeball) and periorbital edema are major clinical signs of Graves disease. These are caused by autoantibodies binding to the TSH receptor expressed on orbital fibrocytes, leading to the production of inflammatory cytokines.

Graves disease is usually diagnosed by elevated serum free and total T4 and T3 levels, along with the clinical signs of diffuse goiter and ophthalmopathy. Serum TSH levels are low due to inhibition by the high levels of T4 and T3. In most cases, radioiodine uptake by the thyroid is excessive and diffuse. Differentiating Graves disease (a primary disorder) from a rare adenoma of pituitary thyrotrophs (a secondary disorder) that produces high levels of TSH can be done through the assay of TSH levels and the presence of circulating thyroid stimulating immunoglobulin.

The treatment of Graves disease usually involves the removal of thyroid tissue, followed by lifelong replacement therapy with T4. Thyroid tissue can be removed either by radioablation with 131I or by surgery. In the case of surgical removal, precautions must be taken to avoid a massive, potentially life-threatening release of thyroid hormones known as thyroid storm. An alternative to the removal of thyroid tissue is the administration of antithyroid drugs that inhibit TPO activity.
Graves disease isthemostcommonformofhyperthyroidism. Itoccursmostfrequentlybetweentheagesof20and50andis10timesmorecommoninwomenthaninmen.GravesdiseaseisanautoimmunedisorderinwhichactivatingautoantibodiesareproducedagainsttheTSHreceptor.Hyperthyroidismdrivenbytheantibodyisoftenaccompaniedbyadiffusegoiterasaresultofhyperplasiaandhypertrophyofthegland.Thefollicularepithelialcellsbecometallcolumnarcells,andthecolloidshowsascallopedperipheryindicativeofrapidturnover.
TheprimaryclinicalstatefoundinGravesdiseaseisthyrotoxicosis—thestateofexcessivethyroidhormoneinbloodandtissues.Apatientwiththyrotoxicosispresentsoneofthemoststrikingpicturesinclinicalmedicine.Thelargeincreaseinmetabolicrateismanifestedasweightlossdespiteincreasedfoodintake.Excessheatproductioncausesdiscomfortinwarmenvironments,sweating,andgreaterintakeofwater.Theincreaseinadrenergicactivityproducesarapidheartrate,hyperkinesis,tremor,nervousness,andawide-eyedstare.Weaknessiscausedbyalossofmusclemassaswellasimpairedmusclefunction.Othersymptomsincludealabileemotionalstate,breathlessnessduringexercise,anddifficultyswallowingorbreathingbecauseofcompressionoftheesophagusortracheabytheenlargedthyroidgland.Themostcommoncardiovascularsignissinustachycardia.There
Perhaps the most clinically important actions of thyroid hormone are those on cardiovascular physiology. T3 increases cardiac output, thereby ensuring sufficient O2 delivery to tissues (
Fig. 42.11). The resting heart rate and stroke volume are increased. The speed and force of myocardial contractions are enhanced (positive chronotropic and inotropic effects, respectively), and the diastolic relaxation isincreasedcardiacoutputassociatedwithawidenedpulsepressuresecondarytoapositiveinotropiceffectcoupledwithdecreasedsystemicvascularresistance.AmajorclinicalsigninGravesdiseaseisexophthalmos (abnormalprotrusionoftheeyeball)andperiorbital edema. ThisiscausedbyautoantibodybindingtotheTSHreceptorexpressedonorbitalfibrocytes,leadingtoproductionofinflammatorycytokines.
GravesdiseaseisusuallydiagnosedbyelevatedserumfreeandtotalT4andT3andtheclinicalsignsofdiffusegoiterandophthalmopathy.SerumTSHlevelsarelowbecausethehypothalamusandpituitaryareinhibitedbythehighlevelsofT4andT3.Inmostcases,radioiodineuptakebythethyroidisexcessiveanddiffuse.AssayofTSHlevelsandthepresenceofcirculatingthyroidstimulatingimmunoglobulinwilldistinguishGravesdisease(aprimarydisorder)fromarareadenomaofpituitarythyrotrophs(asecondarydisorder)thatproduceshighlevelsofTSH.
TreatmentofGravesdiseaseisusuallyremovalofthethyroidtissue,followedbylifelongreplacementtherapywithT4.Thyroidtissuecanberemovedeitherbyradioablationwith131Iorbysurgery.Withsurgicalremovalofthegland,precautionsmustbetakentoavoidamassive,potentiallylife-threateningreleaseofthyroidhormonesknownasthyroid storm. Analternativetoremovalofthyroidtissueisadministrationofantithyroid drugs thatinhibitTPOactivity.