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Evaluation and Management of Thyroid Nodules WuXiaohongWuXiaohongEndocrinologyDepartment,EndocrinologyDepartment,FirstAffiliatedofNanjingMedicalFirstAffiliatedofNanjingMedicalUniversityUniversityEvaluation and Management of TPrevalencelTheTheFraminghamstudyFraminghamstudyinUS:inUS:6.4%6.4%offemalesandoffemalesand1.6%1.6%ofmalesofmaleshadoneormorethyroidnodules,hadoneormorethyroidnodules,anannualincidenceofanannualincidenceof1.4%1.4%overtheoverthefollowing15years.following15years.Prevalence The Framingham studl lTheTheTheTheWhickhamsurveyWhickhamsurveyWhickhamsurveyWhickhamsurveyinEngland:inEngland:inEngland:inEngland:palpablegoitres-palpablegoitres-palpablegoitres-palpablegoitres-8.6%8.6%8.6%8.6%;palpableandvisiblegoitres-palpableandvisiblegoitres-palpableandvisiblegoitres-palpableandvisiblegoitres-6.9%6.9%6.9%6.9%;females:males=females:males=females:males=females:males=4:14:14:14:1;Follow-upfor20years,amongstwomen,70%Follow-upfor20years,amongstwomen,70%Follow-upfor20years,amongstwomen,70%Follow-upfor20years,amongstwomen,70%hadnogoitre,hadnogoitre,hadnogoitre,hadnogoitre,20%20%20%20%hadagoitreatfirstsurveyhadagoitreatfirstsurveyhadagoitreatfirstsurveyhadagoitreatfirstsurveybutnotatfollow-up,butnotatfollow-up,butnotatfollow-up,butnotatfollow-up,6%6%6%6%hadgoitresatbothhadgoitresatbothhadgoitresatbothhadgoitresatbothsurveysandsurveysandsurveysandsurveysand4%4%4%4%developedgoitres;developedgoitres;developedgoitres;developedgoitres;The Whickham survey in Englandl lPostmortemstudiesPostmortemstudieshaveshownthatuphaveshownthatuptoto50%50%ofthepopulationhaveeitherofthepopulationhaveeithersingleormultiplenodulesinthethyroid,singleormultiplenodulesinthethyroid,manyofwhichareverysmall;manyofwhichareverysmall;l lHighresolutionultrasoundHighresolutionultrasoundscansscansrevealeddiscretenodulesinuptorevealeddiscretenodulesinupto50%50%ofofthosebeyondthefifthdecadeoflife;thosebeyondthefifthdecadeoflife;Postmortem studies have shown l lNodularthyroiddiseaseisfoundinNodularthyroiddiseaseisfoundin5%5%ofofthepopulationatpalpationscreeningandthepopulationatpalpationscreeningandisisten-foldten-foldmorefrequentatechographicmorefrequentatechographicscreening.screening.l lThyroidnodulesarerareinchildrenandThyroidnodulesarerareinchildrenandadolescentsandincreaselinearlywithadolescentsandincreaselinearlywithage;females/malesareage;females/malesare24;24;l lNodularthyroiddiseaseisaNodularthyroiddiseaseisaheterogeneousheterogeneousdisorder:nodulesmaybedisorder:nodulesmaybesingleormultiple,hyper-orhypo-singleormultiple,hyper-orhypo-functioning,benignormalignant.functioning,benignormalignant.Nodular thyroid disease is foul lThyroidcancerThyroidcancerThyroidcancerThyroidcancerisrare:israre:israre:israre:lessthan0.5%ofallnewmalignancies;lessthan0.5%ofallnewmalignancies;lessthan0.5%ofallnewmalignancies;lessthan0.5%ofallnewmalignancies;lessthan0.5%ofallcancerdeaths;lessthan0.5%ofallcancerdeaths;lessthan0.5%ofallcancerdeaths;lessthan0.5%ofallcancerdeaths;l lThyroidcancerisThyroidcancerisThyroidcancerisThyroidcanceris614%614%614%614%ofsinglethyroidofsinglethyroidofsinglethyroidofsinglethyroidnodulesselectedforsurgery.nodulesselectedforsurgery.nodulesselectedforsurgery.nodulesselectedforsurgery.l lPostmortemstudies:Postmortemstudies:Postmortemstudies:Postmortemstudies:OccultcancerinuptoOccultcancerinuptoOccultcancerinuptoOccultcancerinupto5%5%5%5%ofthyroidglandsofthyroidglandsofthyroidglandsofthyroidglandsnormaltopalpation;Mostaresmall,onlynormaltopalpation;Mostaresmall,onlynormaltopalpation;Mostaresmall,onlynormaltopalpation;Mostaresmall,onlyseveralmillimetresindiameter,withoutclinicalseveralmillimetresindiameter,withoutclinicalseveralmillimetresindiameter,withoutclinicalseveralmillimetresindiameter,withoutclinicalsignificance.significance.significance.significance.Thyroid cancer is rare:l lThyroidcancercanbeaThyroidcancercanbeaThyroidcancercanbeaThyroidcancercanbeamortalmortalmortalmortaldisease:disease:disease:disease:welldifferentiatedtumors-mortality10%;welldifferentiatedtumors-mortality10%;welldifferentiatedtumors-mortality10%;welldifferentiatedtumors-mortality10%;poorlydifferentiatedandmedullary-50%;poorlydifferentiatedandmedullary-50%;poorlydifferentiatedandmedullary-50%;poorlydifferentiatedandmedullary-50%;anaplastictumors-100%.anaplastictumors-100%.anaplastictumors-100%.anaplastictumors-100%.l lMalignantnodulesaccountforMalignantnodulesaccountforMalignantnodulesaccountforMalignantnodulesaccountfor5%5%5%5%ofallnodules.ofallnodules.ofallnodules.ofallnodules.well-differentiatedcarcinomasin75%;well-differentiatedcarcinomasin75%;well-differentiatedcarcinomasin75%;well-differentiatedcarcinomasin75%;poorlydifferentiatedoranaplasticin15%;poorlydifferentiatedoranaplasticin15%;poorlydifferentiatedoranaplasticin15%;poorlydifferentiatedoranaplasticin15%;medullarycancerin10%cases.medullarycancerin10%cases.medullarycancerin10%cases.medullarycancerin10%cases.Thyroid cancer can be a mortalAetiological factors lTSHTSHlGrowthstimulatingimmunoglobulinsGrowthstimulatingimmunoglobulinslIodinedeficiencyIodinedeficiencylExposuretoionizingradiationExposuretoionizingradiationAetiological factors TSH Differential diagnosis of the thyroid nodulelColloid(adenomatoid)noduleColloid(adenomatoid)nodulelThyroidadenomaThyroidadenomaFollicularadenomaFollicularadenomaHurthlecellHurthlecelllThyroidcancerThyroidcancerPrimary-Primary-Papillary,Follicular,Medullary,AnaplasticPapillary,Follicular,Medullary,AnaplasticDifferential diagnosis of the Meetastatic/directinvasionMeetastatic/directinvasionRenalcell,Breast,Lung,Melanoma,ColonRenalcell,Breast,Lung,Melanoma,Coloncancer,Gastriccarcinoma,Pancreaticcancer,Gastriccarcinoma,Pancreaticcarcinoma,Headandnecktumors,carcinoma,Headandnecktumors,Hodgkinsdisease;Hodgkinsdisease;ThyroidlymphomaThyroidlymphomalThyroidcyst-pure,complexThyroidcyst-pure,complexlThyroiditis-Acute,Subacute,Hashimotos;Thyroiditis-Acute,Subacute,Hashimotos;lRiedelsdiseaseRiedelsdiseaselGravesdiseaseGravesdiseaselInfectious-Abscess,Tuberculosis;Infectious-Abscess,Tuberculosis;Meetastatic/direct invasilInfiltrative/granulomatousdiseaseInfiltrative/granulomatousdiseaseSarcoidosis,AmyloidosisSarcoidosis,AmyloidosislDevelopmentalabnormalitiesDevelopmentalabnormalitiesThyroidhemiagenesisThyroidhemiagenesisThyroglossalductcystThyroglossalductcystTeratomaTeratomalNeckstructuressimulatingthyroidnodulesNeckstructuressimulatingthyroidnodulesAberrantsubclavianarteryandveinAberrantsubclavianarteryandveinLipomasLipomasExtrathyroidalhematomaExtrathyroidalhematomaEsophagealdiverticulumEsophagealdiverticulumParathyroidadenoma,cyst,orcarcinomaParathyroidadenoma,cyst,orcarcinomaInfiltrative/granulomatous disClassification of thyroid neoplasmslPrimaryepithelialtumorsPrimaryepithelialtumorsTumorofTumoroffollicularfollicularcellscellsBenign:follicularadenomaBenign:follicularadenomaMalignant:carcinomaMalignant:carcinomaDifferentiated-papillary,folllicularDifferentiated-papillary,folllicularPoorlydifferentiated-insular,othersPoorlydifferentiated-insular,othersUndifferentiated(anaplastic)Undifferentiated(anaplastic)Classification of thyroid neopClassification of thyroid neoplasmsTumorofTumorofC Ccells-Medullarycarcinomacells-MedullarycarcinomaTumorofTumoroffollicularandCfollicularandCcellscellsMixedmedullary-follicularcarcinomaMixedmedullary-follicularcarcinomalPrimarynonepithelialtumorsPrimarynonepithelialtumorsMalignantlymphomasMalignantlymphomasSarcomasSarcomasOthersOtherslSecondarytumorsSecondarytumorsClassification of thyroid neopSubtypes of follicular adenomalConventionalConventionalTrabecular/Trabecular/solidsolid(embryonal)adenoma(embryonal)adenomaMicrofollicular(fetal)adenomaMicrofollicular(fetal)adenomaNormofollicular(simple)adenomaNormofollicular(simple)adenomaMacrofollicular(Macrofollicular(colloidcolloid)adenoma)adenomalVariantsVariantsHyalinizingtrabecularadenomaHyalinizingtrabecularadenomaOncocytic(oxyphilicorHurthlecell)tumorOncocytic(oxyphilicorHurthlecell)tumorAdenomaswithpapillaryhyperplasiaAdenomaswithpapillaryhyperplasiaHyperfunctioning(Hyperfunctioning(toxictoxic)adenoma)adenomaAtypical(hypercellular)adenomaAtypical(hypercellular)adenomaSubtypes of follicular adenomaHistory l lPriorexposuretoradiationPriorexposuretoradiationPriorexposuretoradiationPriorexposuretoradiationl lage:age:age:age:childhood,childhood,childhood,childhood,65years-undifferentiatedthyroidcancer65years-undifferentiatedthyroidcancer65years-undifferentiatedthyroidcancer65years-undifferentiatedthyroidcancerl lSex:Sex:Sex:Sex:cancer-malesratherthanfemalescancer-malesratherthanfemalescancer-malesratherthanfemalescancer-malesratherthanfemalesl lfamilyhistory:familyhistory:familyhistory:familyhistory:multipleendocrineneoplasiasyndrometypeIImultipleendocrineneoplasiasyndrometypeIImultipleendocrineneoplasiasyndrometypeIImultipleendocrineneoplasiasyndrometypeIIfamilialmedullarythyroidcancerfamilialmedullarythyroidcancerfamilialmedullarythyroidcancerfamilialmedullarythyroidcancerHistory Prior exposure to radiHistorical feature for benign diseaselAfamilyhistoryofHT,benignthyroidAfamilyhistoryofHT,benignthyroidnodule,orgoiter;nodule,orgoiter;lSymptomsofhypothyroidismorSymptomsofhypothyroidismorhyperthyroidism;hyperthyroidism;lPainortendernessassociatedwiththePainortendernessassociatedwiththenodule.nodule.Historical feature for benignHistorical feature for maligancylYoung(70yearsold)Young(70yearsold)patientage;patientage;lMalesex;Malesex;lHistoryofexternalneckradiationduringHistoryofexternalneckradiationduringchildhoodoradolescence;childhoodoradolescence;lPrevioushistoryofthyroidcancer;Previoushistoryofthyroidcancer;lRecentchangesinspeaking,breathing,orRecentchangesinspeaking,breathing,orswallowing;swallowing;lAfamilyhistoryofthyroidcancerortype2Afamilyhistoryofthyroidcancerortype2MEN.MEN.Historical feature for maligaSymptoms and signs l ldysphagia,dyspnoeaorhoarsenessdysphagia,dyspnoeaorhoarsenessdysphagia,dyspnoeaorhoarsenessdysphagia,dyspnoeaorhoarsenessl lfirmness,fixationtoadjacentstructures,vocalfirmness,fixationtoadjacentstructures,vocalfirmness,fixationtoadjacentstructures,vocalfirmness,fixationtoadjacentstructures,vocalcordparalysisandcervicallymphadenopathycordparalysisandcervicallymphadenopathycordparalysisandcervicallymphadenopathycordparalysisandcervicallymphadenopathyl lmultinodulargoitreandsolitarythyroidmultinodulargoitreandsolitarythyroidmultinodulargoitreandsolitarythyroidmultinodulargoitreandsolitarythyroidnodulesnodulesnodulesnodulesl lThesensitivityandspecificityratesforThesensitivityandspecificityratesforThesensitivityandspecificityratesforThesensitivityandspecificityratesfordetectingthyroidmalignancybyhistoryanddetectingthyroidmalignancybyhistoryanddetectingthyroidmalignancybyhistoryanddetectingthyroidmalignancybyhistoryandphysicalexaminationwerearound60%andphysicalexaminationwerearound60%andphysicalexaminationwerearound60%andphysicalexaminationwerearound60%and80%,respectively.80%,respectively.80%,respectively.80%,respectively.Symptoms and signs dysphagia,laboratory evaluation l lThyroidhormonesandTSHThyroidhormonesandTSHl lTPO-Ab,TgAb,TRAbTPO-Ab,TgAb,TRAbl lThyroglobulinThyroglobulinitsroleinthelong-termfollowupofitsroleinthelong-termfollowupofpatientstreatedfordifferentiatedthyroidpatientstreatedfordifferentiatedthyroidcancerisclear;cancerisclear;l lCalcitoninCalcitoninlaboratory evaluation Thyroid Serum Tg concentrations reflect three factorsl lThemassofdifferentiatedthyriodtissureThemassofdifferentiatedthyriodtissurepresentpresentl lAnyphysicaldamageto,orinflammationAnyphysicaldamageto,orinflammationof,thethyroidglandof,thethyroidglandl lThelevelofthyroid-stimulatingThelevelofthyroid-stimulatinghormone(TSH)-receptorstimulationhormone(TSH)-receptorstimulationSerum Tg concentrations reflecAssessment of thyroid nodule l lPlainX-rayexaminationofthetracheaPlainX-rayexaminationofthetracheal lCTscanningandMRICTscanningandMRIl lAssessmentofarespiratoryflowvolumeAssessmentofarespiratoryflowvolumelooploopl lRadionuclideimagingRadionuclideimagingTechnetium-99m(99mTc)pertechnetateTechnetium-99m(99mTc)pertechnetateIodine-123Iodine-123l lUltrasoundscanningUltrasoundscanningl lFineneedleaspirationcytologyFineneedleaspirationcytology Assessment of thyroid nodule PRadionuclide imaging l lColdColdColdColdnodules:cancerouslesionslessthan20%;nodules:cancerouslesionslessthan20%;nodules:cancerouslesionslessthan20%;nodules:cancerouslesionslessthan20%;80%beingduetocolloidnodules,80%beingduetocolloidnodules,80%beingduetocolloidnodules,80%beingduetocolloidnodules,haemorrhage,cystsorinflammatorylesionshaemorrhage,cystsorinflammatorylesionshaemorrhage,cystsorinflammatorylesionshaemorrhage,cystsorinflammatorylesionssuchasHT;suchasHT;suchasHT;suchasHT;l lHotHotHotHotnodulesareassociatedwithalowincidencenodulesareassociatedwithalowincidencenodulesareassociatedwithalowincidencenodulesareassociatedwithalowincidenceofmalignancy;ofmalignancy;ofmalignancy;ofmalignancy;l lWarmWarmWarmWarmlesionmaybeambiguoussincealesionmaybeambiguoussincealesionmaybeambiguoussincealesionmaybeambiguoussinceahypofunctioningmalignantnodulemaybehypofunctioningmalignantnodulemaybehypofunctioningmalignantnodulemaybehypofunctioningmalignantnodulemaybeobscuredbyoverlyingnormaltissue.obscuredbyoverlyingnormaltissue.obscuredbyoverlyingnormaltissue.obscuredbyoverlyingnormaltissue.l lThisapproachdoesnotspecificallydistinguishThisapproachdoesnotspecificallydistinguishThisapproachdoesnotspecificallydistinguishThisapproachdoesnotspecificallydistinguishbenignfrommalignantlesions.benignfrommalignantlesions.benignfrommalignantlesions.benignfrommalignantlesions.Radionuclide imaging Cold noduUltrasonography l lItisofvalueindistinguishingItisofvalueindistinguishingItisofvalueindistinguishingItisofvalueindistinguishingsolidsolidsolidsolidfromfromfromfromcysticcysticcysticcystic lesionsofthethyroidlesionsofthethyroidlesionsofthethyroidlesionsofthethyroidl lClassifynodulesasClassifynodulesasClassifynodulesasClassifynodulesassolid,mixedcysticsolid,mixedcysticsolid,mixedcysticsolid,mixedcysticandandandandsolidsolidsolidsolidororororcysticcysticcysticcysticwithgreaterthan90%accuracywithgreaterthan90%accuracywithgreaterthan90%accuracywithgreaterthan90%accuracyl lMalignantnodulesareMalignantnodulesareMalignantnodulesareMalignantnodulesarehypoechoichypoechoichypoechoichypoechoiccomparedwithcomparedwithcomparedwithcomparedwiththeremainderofthegland,whilebenignlesionstheremainderofthegland,whilebenignlesionstheremainderofthegland,whilebenignlesionstheremainderofthegland,whilebenignlesionsarearearearehyperechoichyperechoichyperechoichyperechoicwithasonolucentrim(halowithasonolucentrim(halowithasonolucentrim(halowithasonolucentrim(halosign).sign).sign).sign).l lTherearenosonographiccriteriawhichareableTherearenosonographiccriteriawhichareableTherearenosonographiccriteriawhichareableTherearenosonographiccriteriawhichareabletodefinebenignormalignantdisease.todefinebenignormalignantdisease.todefinebenignormalignantdisease.todefinebenignormalignantdisease.Ultrasonography It is of valueThyroid hormone suppression l lAttemptstodistinguishbenignfromAttemptstodistinguishbenignfrommalignantnodulesbyseekingachangeinmalignantnodulesbyseekingachangeinsizeinresponsetothyroxine,perhapssizeinresponsetothyroxine,perhapsrelatedtodependencyonTSHforgrowth.relatedtodependencyonTSHforgrowth.l lSomecarcinomasmayrespondtoSomecarcinomasmayrespondtosuppressionbyreducinginsize.suppressionbyreducinginsize.l lTheincidenceofcancerinnon-Theincidenceofcancerinnon-respondersbeingbetween12and40%.respondersbeingbetween12and40%.Thyroid hormone suppression AtFine needle aspiration cytologylfirstdescribedin1948andpioneeredbyfirstdescribedin1948andpioneeredbyScandinavian;Scandinavian;lnowgainedwideacceptanceasthemostaccuratenowgainedwideacceptanceasthemostaccuratediagnosticprocedurefordistinguishingbenigndiagnosticprocedurefordistinguishingbenignfrommalignantthyroidnodulesfrommalignantthyroidnoduleslitgiveslimitedinformationinapproximately25itgiveslimitedinformationinapproximately25%ofcasesbecauseofinsufficientcellularyieldor%ofcasesbecauseofinsufficientcellularyieldorindeterminatediagnoses.indeterminatediagnoses.Fine needle aspiration cytologFine needle aspiration cytology lThisinpartisduetodifficultyindistinguishingThisinpartisduetodifficultyindistinguishingbenignadenomasfrommalignantfollicularbenignadenomasfrommalignantfollicularneoplasms;surgicalexcisionofallsuchlesionsneoplasms;surgicalexcisionofallsuchlesionsisthereforerequiredisthereforerequiredlThecytopathologistcanreportthatanThecytopathologistcanreportthatanadequatesmearcontainsnormalcellsonly,cellsadequatesmearcontainsnormalcellsonly,cellsfrombenignnon-tumorousconditionssuchasfrombenignnon-tumorousconditionssuchaslymphocyticthyroiditis,orsuspiciouslymphocyticthyroiditis,orsuspicious(indeterminate)orfranklymalignantcells.(indeterminate)orfranklymalignantcells.Fine needle aspiration cytologStrategy for treatment of nodular thyroid disease l lFollowup(waitandseepolicy)Followup(waitandseepolicy)l lSclerotherapywithtetracyclineorethanol;Sclerotherapywithtetracyclineorethanol;l lThyroxinetherapy;Thyroxinetherapy;l lRadioiodinetreatment;Radioiodinetreatment;l lSurgery.Surgery.Strategy for treatment of nodu
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