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Parissa TabrizianParissa Tabrizian
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55 F referred to endocrine surgery for a palpable55 F referred to endocrine surgery for a palpable
thyroid nodule on physical exam by PMDthyroid nodule on physical exam by PMD
No dysphonia, dysphagia, odynophagia, change inNo dysphonia, dysphagia, odynophagia, change invoice.voice.
No smoking history.No smoking history.
No fevers, chills, weight loss.No fevers, chills, weight loss.
No hx of radiation to neckNo hx of radiation to neck
No PMHx/PSHx, no FHx caNo PMHx/PSHx, no FHx ca
Exam: palpable R thyroid noduleExam: palpable R thyroid nodule
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Labs: TSH, PTH, T4, T3, TBG wnlLabs: TSH, PTH, T4, T3, TBG wnl
Thyroid US: 2 nodules R thyroid (
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Management Guidelines of thyroid nodules?Management Guidelines of thyroid nodules?
Total vs. Hemithyroidectomy?Total vs. Hemithyroidectomy?
Extent of surgery for small papillary ca ?Extent of surgery for small papillary ca ?
Use of radioactive iodine post thyroidectomy?Use of radioactive iodine post thyroidectomy?
Use of thyroxine suppression therapy?Use of thyroxine suppression therapy?
Long Term Follow upLong Term Follow up
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Large population studiesLarge population studies--Framingham study showed clinicallyFramingham study showed clinically
significant nodules in 6.4% F and 1.5% M ages 30significant nodules in 6.4% F and 1.5% M ages 30--59.59.
UltrasoundsUltrasounds-- 20% to 76% F had at least one thyroid nodule20% to 76% F had at least one thyroid nodule
Autopsy surveys show up to 35% clinically silent carcinomaAutopsy surveys show up to 35% clinically silent carcinoma
Nodules: 9 million adults in the USNodules: 9 million adults in the US
New nodules appear at a rate of 0.8%/yrNew nodules appear at a rate of 0.8%/yr
Thyroid cancer is rare 4/100,000 perThyroid cancer is rare 4/100,000 per
1% of all malignancies1% of all malignancies
0.5% of all cancer deaths0.5% of all cancer deaths--mortality rates decreasedmortality rates decreasedOverall 10 year survival rate papillary/follicular ca: 93 vs.Overall 10 year survival rate papillary/follicular ca: 93 vs.
85% (30yrs mortality local:12%, distant:43%)85% (30yrs mortality local:12%, distant:43%)
Recurrence rate 40 yr 35% (2/3 within the first decade afterRecurrence rate 40 yr 35% (2/3 within the first decade after
initial treatment)initial treatment)
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Benign (>90%):Benign (>90%):
Multinodular goiterMultinodular goiter
Hashimotos thyroiditisHashimotos thyroiditis
Simple or Hemorrhagic cystsSimple or Hemorrhagic cystsFollicular adenomasFollicular adenomas
Subacute thyroiditisSubacute thyroiditis
Malignant (6%):Malignant (6%):
Papillary, Follicular cancer ( 93%)Papillary, Follicular cancer ( 93%)
Medullary (5%)Medullary (5%)
Hurthle cellHurthle cell
Anaplastic (1%)Anaplastic (1%)
Lymphoma or metsLymphoma or mets
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History of head and neck radiationHistory of head and neck radiationExposure to radiation, especially in childhood is associatedExposure to radiation, especially in childhood is associated
with increased prevalence of thyroid nodules andwith increased prevalence of thyroid nodules and
malignancy 2%/yr increased risk with peak incidence 15malignancy 2%/yr increased risk with peak incidence 15--2020
yearsyears
Presence of a nodule in a child is 2x as likely to bePresence of a nodule in a child is 2x as likely to becarcinomacarcinoma
Family History of MCT or MEN 2Family History of MCT or MEN 2
Age < 20 or > 70 yearsAge < 20 or > 70 years
MaleMale
Growing noduleGrowing nodule
Firm or hard consistencyFirm or hard consistency
Cervical adenopathyCervical adenopathy
Fixed noduleFixed nodule
Persistent hoarseness, dysphonia, dysphagia, or dyspneaPersistent hoarseness, dysphonia, dysphagia, or dyspnea
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SignificantSignificant selectionselection biasbias inin surgicalsurgical seriesseries
NorthNorth CarolinaCarolina studystudy inin aa communitycommunity hospitalhospital ptsptswithwith nodulesnodules werewere referredreferred toto surgerysurgery withoutwithout
biopsybiopsy andand 66..55%% ofof excisedexcised nodulesnodules werewere
carcinomascarcinomas
Catania,Catania, ItalyItaly 23272327 ptspts withwith nodulesnodules werewere
evaluatedevaluated byby FNAFNA andand ofof thosethose 391391 werewere selectedselected
forfor surgerysurgery.. CarcinomasCarcinomas werewere foundfound inin 2828 whichwhich
waswas 55%% ofof totaltotal
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Complete history and physical examComplete history and physical exam
Thyroglobulin levels are nonThyroglobulin levels are non--specific/nonspecific/non--sensitivesensitive
USUS: Is it truly a nodule that corresponds to the exam?: Is it truly a nodule that corresponds to the exam?
Is the nodule > 50% cysticIs the nodule > 50% cystic
Is it located posteriorly in the thyroid gland?Is it located posteriorly in the thyroid gland?
Other nodules?Other nodules?
Position/shape/size/margins/content/echogenic/vascuPosition/shape/size/margins/content/echogenic/vascular pattern/risk of malignancylar pattern/risk of malignancy
1919--67% of nodules detected in randomly selected67% of nodules detected in randomly selected
individualsindividuals
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FNAFNA::
Sensitivity/SpecificitySensitivity/Specificity:: 8383%%//9292%%
Simple,Simple, safesafe officeoffice procedureprocedure
TissueTissue samplesample obtainedobtained byby 2525 gaugegauge needleneedle
WithWith experienceexperience adequateadequate samplesample maymay bebe obtainedobtained inin
9090 --9797%% ofof aspiratesaspirates ofof solidsolid nodulesnodules
FalseFalse negativenegative raterate (FNA(FNA benignbenign butbut nodulenodule turnturn outout
malignant)malignant) isis 00--55%% usuallyusually duedue toto samplingsampling errorerrorFalseFalse positivepositive ratesrates (malignant(malignant butbut turnsturns outout benign)benign)
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MostMost commoncommon thyroidthyroid cancercancerAfterAfter radiationradiation exposure,exposure, RETRET protoproto--oncogeneoncogeneOverexpressionOverexpression ofof TRK,TRK, MAPK,MAPK, DNADNA hypermethylation,hypermethylation, andand activatingactivating
mutationsmutations ofof RASRAS
BestBest prognosisprognosis:: 55%% mortalitymortality atat 2020 yearsyears ifif nono locallocal invasioninvasionLateralLateral aberrantaberrant thyroidthyroid cervicalcervical lymphlymph nodenode infiltratedinfiltrated withwith
metastaticmetastatic thyroidthyroid cancercancer
2020--5050%% cervicalcervical lymphlymph nodenode involvementinvolvement (( USUS identificationidentification 2020--3131 %%))
MicrometastasisMicrometastasis upup toto 9090 %%CanCan spreadspread toto lunglung (also(also bone,bone, liver,liver, brain)brain)VeryVery rarerare conversionconversion toto anaplasticanaplastic typetype
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PsammomaPsammoma bodiesbodies:: laminatedlaminated calcifiedcalcified spheres,spheres, diagnosticdiagnostic ofof
papillarypapillary cancercancerCertainCertain histologicalhistological variantsvariants havehave higherhigher riskrisk ofof recurrencerecurrence::TallTall cell,cell, columnarcolumnar cell,cell, diffusediffuse sclerosingsclerosing cellcell
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RAS mutations, chromosomal rearrangements (PAX8RAS mutations, chromosomal rearrangements (PAX8
fused to PPARfused to PPAR--gammagamma--1)1)
Older population, advanced tumor stageOlder population, advanced tumor stage
Hurthle cell variant of FCCHurthle cell variant of FCC
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Neck imagingNeck imaging::
preop neck USpreop neck US
routine use of other imaging studiesroutine use of other imaging studies( CT/MRI/PET) not recommended( CT/MRI/PET) not recommended
Serum thyroglobulinSerum thyroglobulin::
routine preop measurement not indicatedroutine preop measurement not indicated
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Total thyroidectomyTotal thyroidectomy:: ++
Papillary foci are b/l in 60Papillary foci are b/l in 60--85% of patients85% of patients
55--10% recurrence rates for papillary ca after10% recurrence rates for papillary ca after
unilateral surgery for microcarcinomaunilateral surgery for microcarcinoma
Effectiveness of treatment with 131I and f/uEffectiveness of treatment with 131I and f/u
with serum Tg are highest with maximalwith serum Tg are highest with maximal
resectionresection
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Total thyroidectomy:Total thyroidectomy: --
Minimal benefit for more extensive surgeryMinimal benefit for more extensive surgery
Higher risk of hypoparathyroidismHigher risk of hypoparathyroidism
Higher risk of injury to recurrent laryngealHigher risk of injury to recurrent laryngeal
nervenerve
Tumor multicentricity seems to have littleTumor multicentricity seems to have littleprognostic significanceprognostic significance
If recurrence, usually those lesions are treatableIf recurrence, usually those lesions are treatable
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MostMost concensusconcensus guidelinesguidelines statestate::
ForFor papillarypapillary caca::
IfIf >> 11 cm,cm, oror mets,mets, oror extendsextends beyondbeyond
thyroid,thyroid, contralateralcontralateral disease,disease, oror hxhx ofof
irradiationirradiation totaltotal thyroidectomythyroidectomy
IfIf
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RegionalRegional lymphlymph nodenode metsmets atat timetime ofof
diagnosisdiagnosis::2020--9090%%
ConsiderationConsideration ofof routineroutine centralcentral--compartmentcompartment(level(level VI)VI) neckneck dissectiondissection inin papillarypapillary
ca/suspectedca/suspected HurtleHurtle caca
LateralLateral neckneck (( IIII--IV)IV) andand posteriorposterior triangletriangle (( V)V)LNLN dissectiondissection forfor nodalnodal diseasedisease reducesreduces
recurrencerecurrence andand mortalitymortality ratesrates..
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National Cancer Data Base (19851998)
52,173 patients with surgery for PTCSurvival estimated by Kaplan-Meier method, compared using log-rank tests
Cox Proportional Hazards modeling stratified by tumor size used to assessimpact of surgical extent on outcomes
Results: 43,227 (82.9%) underwent total thyroidectomy, 8946 (17.1%)
underwent lobectomy. For PTC1 cm, lobectomy resulted in higher risk of recurrence and
death (P = 0.04, P = 0.009)
1 to 2 cm lesions were examined separately: lobectomy again resulted
in a higher risk of recurrence and death (P = 0.04, P = 0.04).
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299299 casescases (( 19751975--20012001))
MultivariateMultivariate analysisanalysisRecurrentRecurrent local/distantlocal/distant metsmets associatedassociated
lymphlymph nodenode metsmets
bilateralbilateral tumortumor
sclerosantsclerosant variantvariant
TumorTumor sizesize (
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SpecificSpecific uptakeuptake intointo follicularfollicular cellscells
UndergoesUndergoes --decay,decay, releasingreleasing highhigh energyenergy
electronselectronsradiationradiation cytotoxicitycytotoxicity
GOALGOAL::
DestroysDestroys residualresidual thyroidthyroid tissue/decreasetissue/decrease
recurrence/mortalityrecurrence/mortality
IncreasesIncreases specificityspecificity ofof futurefuture scansscans forfor residualresidualcaca
ImprovesImproves sensitivitysensitivity ofof futurefuture TgTg screenscreen
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RestrictedRestricted toto patientspatientsstagestage IIIIII andand IVIV diseasedisease
stagestage IIII andand
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ForFor maximummaximum radioiodineradioiodine uptakeuptake afterafter
thyroidectomy,thyroidectomy, wantwant TSHTSH >>3030--5050 mU/LmU/L (no(no
controlledcontrolled study)study)
StopStop thyroxinethyroxine forfor 44--66 weeksweeks iatrogeniciatrogenic
hypothyroidismhypothyroidism
BecauseBecause liothyronineliothyronine hashas aa shortershorter tt11//22,, cancan givegiveuntiluntil 22 weeksweeks priorprior toto treatmenttreatment
AvoidAvoid iodinatediodinated contrastcontrast forfor CTCT forfor 11--33 monthsmonths priorprior
toto treatmenttreatment
LowLow idodineidodine dietdiet forfor 11--22 weeksweeks priorprior RIARIA
TheseThese samesame principlesprinciples applyapply toto radioiodineradioiodine
scanningscanning forfor f/uf/u
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Persistent disease and tumor stage cannot bePersistent disease and tumor stage cannot beidentified shortly after surgery when there is aidentified shortly after surgery when there is alarge thyroid remnantlarge thyroid remnant
Without RA, half of lung metastases in childrenWithout RA, half of lung metastases in childrencannot be identifiedcannot be identified
But:But: Transient loss of tasteTransient loss of taste
Acute and chronic radiationAcute and chronic radiation--induced parotitisinduced parotitis Sialadenitis with possible xerostomiaSialadenitis with possible xerostomia Transient testicular damageTransient testicular damage Side effects tend to be doseSide effects tend to be dose--relatedrelated
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11--33 months/months/66--1212 monthsmonths afterafter initialinitial ablationablation
IfIf negativenegative 9090%% 1010 yearyear relapserelapse--freefree survivalsurvival
IfIf consecutivelyconsecutively negativenegative xx22 >>9595%% 1010 yearyear
relapserelapse--freefree survivalsurvival
ConsensusConsensus guidelinesguidelines:: surveillancesurveillance scanningscanningbeyondbeyond thisthis periodperiod onlyonly indicatedindicated if if
clinical/diagnosticclinical/diagnostic findingsfindings occuroccur
WBSWBS
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ProducedProduced exclusivelyexclusively byby thyroidthyroid follicularfollicular cellscells
UsedUsed toto detectdetect residual,residual, recurrent,recurrent, oror metastaticmetastaticdiseasedisease (( levelslevels >> 22ng/mL)ng/mL)
MeasurementMeasurement everyevery 66--1212 monthsmonths inin totaltotalthyroidectomy,thyroidectomy, periodicperiodic inin hemythyroidectomyhemythyroidectomyandand totaltotal w/ow/o RIARIA
SensitivitySensitivity ofof 8585--9595%% forfor detectiondetection ofof diseasediseaseduringduring thyroidthyroid hormonehormone withdrawalwithdrawal
SensitivitySensitivity ofof 5050%% withwith TSHTSH suppressionsuppression oror
dedifferentiateddedifferentiated tumorstumors
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ReportedReported TgTg concentrationsconcentrations cancan bebe falselyfalselyloweredlowered byby autoAbsautoAbs thatthat bindbind TgTg andandpreventprevent detectiondetection byby immunoassaysimmunoassays
TheseThese antithyroglobulinantithyroglobulin AbsAbs areare presentpresent ininasas manymany asas 2525%% ofof ptspts withwith thyroidthyroid cancer,cancer,andand 1010%% ofof generalgeneral populationpopulation
MethodsMethods toto detectdetect TgTg mRNAmRNA areare inindevelopmentdevelopment thoughthough theirtheir utilityutility hashas beenbeenquestionedquestioned
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MetaMeta--analysisanalysis:: constantconstant suppressionsuppression ofof TSHTSH
(
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