MORPHOLOGYInthetypicalcaseofGravesdisease,thethyroidglandisenlarged(usuallysymmetrically)duetodiffusehypertrophyandhyperplasiaofthyroidfollicularepithelialcells.Theglandisusuallysmoothandsoft,anditscapsuleisintact.Onmicroscopicexamination,thefollicularepithelialcellsinuntreatedcasesaretall,columnar,andmorecrowdedthanusual.Thiscrowdingoftenresultsintheformationofsmallpapillae,whichprojectintothefollicularlumen(
Fig.20.10 ).Suchpapillaelackfibrovascularcores,incontrastwiththoseofpapillarycarcinoma.Thecolloidwithinthefollicularlumenispale,withscallopedmargins.Lymphoidinfiltrates,consistingpredominantlyofTcells,withfewerBcellsandmatureplasmacells,arepresentthroughouttheinterstitium;germinalcentersarecommon.
Changesinextrathyroidaltissuesincludegeneralizedlymphoidhyperplasia.Inindividualswithophthalmopathy,thetissuesoftheorbitareedematousbecauseofthepresenceofhydrophilicglycosaminoglycans.Inaddition,thereisinfiltrationbylymphocytes,mostlyTcells.Orbitalmusclesinitiallyareedematousbutmayundergofibrosislateinthecourseofthedisease.Thedermopathy,ifpresent,ischaracterizedbythickeningofthedermis,asaresultofdepositionofglycosaminoglycansandlymphocyteinfiltration.
Fig.20.10Gravesdisease.Thefolliclesarelinedbytallcolumnarepithelialcellsthatareactivelyresorbingthecolloidinthecentersofthefollicles,resultingina“scalloped”appearanceofthecolloid.
The clinical manifestations of Graves disease include those common to all forms of thyrotoxicosis (discussed earlier), as well as those associated uniquely with Graves disease: diffuse hyperplasia of the thyroid, ophthalmopathy, and dermopathy. The degree of thyrotoxicosis varies from case to case, and the related changes may sometimes be less conspicuous than other manifestations of the disease. Increased flow of blood through the hyperactive gland often produces an audible bruit. Sympathetic overactivity produces a characteristic wide, staring gaze and lid lag. The ophthalmopathy of Graves disease results in abnormal protrusion of the eyeball (exophthalmos). The exophthalmos may persist or progress despite successful treatment of the thyrotoxicosis, sometimes resulting in corneal injury. The extraocular muscles often are weak. The infiltrative dermopathy most commonly involves the skin overlying the shins, where it manifests as scaly thickening and induration of the skin (pretibial myxedema). The skin lesions may be slightly pigmented papules or nodules and often have an orange peel texture. Laboratory findings in Graves disease include elevated serum free T4 and T3 and depressed serum TSH. Because of ongoing stimulation of the thyroid follicles by TSIs, radioactive iodine uptake is increased diffusely.
•Gravesdisease,themostcommoncauseofendogenoushyperthyroidism,ischaracterizedbythetriadofthyrotoxicosis,ophthalmopathy,anddermopathy.
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GravesdiseaseisanautoimmunedisordercausedbyautoantibodiestotheTSHreceptorthatmimicTSHactionandactivateTSHreceptorsonthyroidepithelialcells.