Hashimoto’sDisease

Hashimoto’sDisease

• AkaChronicLymphocyticThyroiditis• Autoimmunediseasecausingprimaryhypothyroidism• PrimarycauseofhypothyroidisminUS

• 1in1000• ThirdmostprevalentautoimmunediseaseintheUS• Atleast 7timesmorecommoninwomenthanmen

Hakaru Hashimoto- 1912

• Firstrecognizedautoimmunedisease• DiscoveredbyJapanesespecialistHakaru Hashimoto• Publishedin1912

Symptoms

• Fatigue• Weightgain• Pale/puffyface• Feelingcold• Joint/musclepain• Constipation• Dry/thinninghair• Memoryproblems

Pathophysiology• Immunesystemattacksthethyroidgland,causinginflammationandpreventingitfromproducingthyroidhormones• T3=triiodothyronine• T4=thyroxine

• Autoantibodiesagainstthyroidperoxidase(TPO),thyroglobulin,TSHreceptorsattackfolliclesofthyroidgland

• InvasionofthyroidtissuebyT-lymphocytes

• ThyroidStimulatingHormone(TSH)increasesbypituitaryasT4decreases(nonegativefeedback)

• Enlargementofthethyroidisduetolymphocyticinfiltrationandfibrosisratherthantissuehypertrophy.

Hashimoto’sHistology

• Massiveinfiltrationoflymphocytes+plasmacellsintothyroidgland• Germinalcentersform(notpresentinnormalthyroidgland)• Thyroidfolliclesdisappear(presentinnormalthyroidtoproduceT3/T4)

ContrastwithGrave’sDisease(Hyperthyroid)

• Bothdiseasesresultinantibodiesattackingthyroidgland,preventingnegativefeedback

• Bothcausegoiter• Hashimoto’sisduetoinfiltrationbylymphocytes• Grave’sisduetoexcessiveT3/T4production

• Onecanprogresstotheother (oftenGraves->Hashimoto’s)

RiskFactors

• Familyhistory• HLA-DR5gene• CTLA-4gene(CytotoxicT-lymphocyteAntigen-4)=negativeregulationofTCells

• AlsoassociatedwithType1DM

• EnvironmentalFactors• Highiodine intake?• Seleniumdeficiency

• ChromosomalDisorders• TurnersSyndrome,DownSyndrome, Klinefelter Syndrome

• OtherAutoimmuneDiseases

Diagnosis

• History+Physicalexam+Presenceofagoitre

• BloodtestingforThyroid-Stimulatinghormone(TSH),freeT3/T4• HighTSHandlowT3/T4

• Presenceofantibodies(anti-Tg,anti-TPO,TPOab)

• FineNeedleAspirationtoexcludemalignancy

• Oftenmisdiagnosedasdepression,chronicfatiguesyndrome,anxietydisorder,PMS,…

Treatment

• ThyroidHormoneReplacements(syntheticT4)• Levothyroxine,triiodothyronine, desiccatedthyroidextract• Oral,onceperdaytokeepTSHunder3.0• Mustbechecked~every6months(toomuchcancauseosteoporosisandarrhythmias)

• Other:• Selenium• Low-levellasertherapy• Glutenfreediet

Prognosis

• Excellentwithmedication• 5%progresstothyroidfailureeveryyear• RarelyprogressestohyperthyroidBasedow-GravesDisease• HigherriskofBcelllymphoma• Susceptibletootherautoimmunediseases• Vitiligo,Rheumatoidarthritis,Addison’s disease,DMType1,PerniciousAnemia,CeliacDisease,Autoimmune Hepatitis

Sources

• https://en.wikipedia.org/wiki/Hashimoto's_thyroiditis#Pathophysiology

• http://www.niddk.nih.gov/health-information/health-topics/endocrine/hashimotos-disease/Pages/fact-sheet.aspx

• http://www.omim.org/entry/140300

• http://www.omim.org/geneMap/8/401?start=-3&limit=10&highlight=401

• http://ghr.nlm.nih.gov/gene/HLA-DRB1

• http://emedicine.medscape.com/article/120937-overview