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ThyroidClinic2017

DianaMcNeillMD,FACPProfessorofMedicine

DivisionofEndocrinologyandMetabolismDukeUniversityMedicalCenter

Disclosures

• Ihavenoconflictsofinteresttoreportatthistime

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Intheclinic…

• 35yearoldfemalewithnosignificantpastmedicalhistory.

• Notes“lump”onherneckonemorningwhilebrushingherteeth

• Hasnothadanydifficultyswallowingorneckpain

• Nohistoryofneckirradiation• Motherhadsomethyroidproblems

Whatotherquestionswouldyouasktoassessthyroidstatus?(Checkallthatapply.)• Skinorhairchanges• Temperatureintolerance• Discoloredurine• Weightchanges• Emotionallability• Decreasedhearing• Changesinbowelpatterns• Useofcomplementaryoralternativemedications

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Physicalexam

• Wellappearing• BP110/70P72RR16• HEENT:nolidretractionorstare• Thyroid:visiblerightthyroidnodule;moveseasilywithswallowing

• 1.5cmindiameter;nolymphadenopathy• Cardiac:regularrateandrhythm,nomurmur• Remainderofexamnormal

Laboratory

• WBC7,500• TSH3.2uIU/ml(0.34-5.66uIU/ml)• FT40.9ng/dl(0.52- 1.21ng/dl)• Antimicrosomalthyroidantibody-negative

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Whatisthenextstepinhermanagement?

• ThyroidUS• USdirectedFineNeedleAspirate(FNA)ofnodule

• Recheckthyroidexamandlabsin6mos• Reassureandtellpatienttohavethyroidcheckedagaininoneyear

1. 1/15 women have a thyroid nodule2. 1/40 men have a thyroid nodule3. 90% benign4. Thyroid cancer incidence has been increasing

Haugen,Alexander,etal., Thyroid.Jan2016,26(1):1-133.

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ThinkBENIGN

• FamilyhistoryofHashimoto’sthyroiddisease• Hyperorhypothyroidism• Pain• Mobile,softnodule• CystonUS• Hotnoduleonthyroidscan

BenignThyroidNodules

• Cysts• Adenomas• Thyroiditis• Other:Riedelsstruma,painlessthyroiditis

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SuppressiveTherapy

• Novalueofsuppressivetherapy• (3meta-analysis,severalrandomizedcontroltrials)

• Benefitiniodine-depleteddiets

Thyroid,TheAmericanThyroidAssociationGuidelinesTaskforce.2006,109-142.

ThinkMALIGNANT

• Agelessthan20orgreaterthan70• Male• Hoarseness• Externalneckirradiation• Firmfixednodule• Coldonscan• Cervicallymphnodes

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2017Guidelines

• Norecommendationtoscreenunlesshighrisk

USPTF

WorrisomeUltrasoundFindings

• Microcalcifications• Hypervascularity• Hypoechogenicity(Darker)• Irregularborders• Tallerthanwide

Haugen,Alexander,etal., Thyroid.Jan2016,26(1):1-133.

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Followup

• PatientunderwentUSdirectedFNAofrightthyroidnodule

• Pathology:colloidnodule• RepeatthyroidUSinoneyeartoconfirmstabilityofnodule

FNA

• Nondiagnostic:REPEATwith50%successonrepeat;Nosoonerthan3months

• Benignwithcolloid:GOOD• Malignant:ExceptfollicularandHurtleCellcarcinomacannotbediagnosedbyFNA

• Suspicious:SURGERY…25%malignant

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ThyroidCancer

• Papillary60%• Follicular12%• FollicularVariantofpapillary6%• Medullary• Anaplastic• Lymphoma

MultinodularGoiter

• Sameriskofmalignancyasthosewithsolitarynodule

• Aspirationofonlypredominantnodulemaymissmalignancy

• Ultrasoundcharacteristicssuperiortosizeindiagnosingmalignancy

.Haugen,Alexander,etal., Thyroid.Jan2016,26(1):1-133.

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BenignThyroidNoduleFollow-up

• Palpable- 6-18monthclinicalfollow-up• Notpalpable- serialUS6-18monthsafterFNA

• Ifstablesize- subsequentfollow-upmaybelonger

• Iflargernodule- repeatFNA

Haugen,Alexander,etal., Thyroid.Jan2016, 26(1):1-133.

TakeHomePoints

• 7-15%ofthyroidnodulesaremalignant• Incidenceofthyroidcancerincreasinginpartduetoimprovedimagingtechniques

• ThyroidUScanhelpidentifyhighrisknodules• FNAofnodulenecessaryfordiagnosisbasedonsize,shape,appearance,otherriskfactors.

Haugen,Alexander,etal., Thyroid.Jan2016,26(1):1-133.

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27yearoldfemaleG3P3Ab0withgoiter

• 6monthspostpartum• Notbreastfeeding,mensesnotyetresumed• Isbeingtreatedforpostpartumdepression

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Physicalexam

• Anxiousappearingfemale,jittery• BP150/70P110regularRR18T99°F• Bilateralstarewithlidretraction• Visiblethyroid• Thyroidbruitappreciated• COR:RRR,S1S2noS3,S4• Bilateralrestingtremorupperextremities

• FT46ng/dl(0.52-1.21ng/dl)• FT3normalrange• TSHundetectable• Positivethyroidstimulatingimmunoglobulin• Positivethyroidperoxidaseantibodies• WBC9,400Hemoglobin12• Negativeurinepregnancytest

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Whatarethepossiblecausesofherabnormalthyroidlaboratories?

• Grave’sDisease• Post-partumthyroiditis• Laberror• Toxicmultinodulargoiter• Depression

Clinicalevaluation

• Nodulargland• Thyroidscananduptake-1-2%(low)

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Thyroidchangesinpregnancy

• TSHhassimilarstructuretopregnancyhormoneBHCG,whichmayhaveslighteffectonthyroid

• Increaseinthyroidbindingglobulinwhichincreasestotalhormonelevels

• FT4andFT3levelsremainunaffected

Fetalthyroid

• Notsynthesizingthyroidhormoneuntil18weeksgestation

• Priortothattimedependsonmother’sthyroidhormone

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Abnormalthyroidfunctioninpregnancy

• Earlyrecurrentmiscarriage• Subclinicalhypothyroidism(elevatedTSHwithnormalFT4andFT3)mayneedtobetreated.

CurrentOpinioninObstetrics&Gynecology:December2015- Volume27- Issue6- p406–415

Thyroidlevelsinpregnancy

• FirsttrimesterTSH<2.5mIU/ml• SecondtrimesterTSH<3.0mIU/ml• 15%ofpregnantwomenhavesubclinicalhypothyroidism.

Thyroid.2011.21:1081-1125

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ShouldSubclinicalhypothyroidismbetreatedinpregnancy

• Cochranereview-No2013• SystematicReview- maybe2016

Thyroid.2016.26:580-589CochraneDatabaseSystRev5:CD007752

Diagnosis

• Thyroiditis:Postpartum• Needtor/oGrave’sdisease• Grave’sDiseaseoftenhasanelevatedFT3/FT4

• Treatmentisdifferentdependentondiagnosis

TagamiT.,etal.TheincidenceofgestationalhyperthyroidismandpostpartumthyroiditisintreatedpatientswithGraves'disease.

Thyroid. 2007;17:767–772.

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ButifshehadGrave’sdisease…Whatarethesideeffectsof

methimazole?

• Rash• Transaminitis(abnormalliverfunctiontests)• Photosensitivity• Idiosyncraticleucopenia(rare)

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BreastFeeding?

• Canbreastfeedonmethimazoleupto20mgdaily

Stagnaro-GreenA,etal.GuidelinesoftheAmericanThyroidAssociationforthediagnosisandmanagementofthyroiddiseaseduringpregnancyandpostpartum.Thyroid.2011;21:1081-125,

PostpartumthyroiditisandDepression

• Noevidenceofclearassociation• NoevidencethattreatmentwithT4orT3hormonescanresolvedepressivesymptoms.

HarrisB.,etal.,Randomizedtrialofthyroxinetopreventpostnataldepressioninthyroid-antibody-positivewomen. BrJPsychiatry.2002;180:327–330.

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Backtoourpatient…

• Diagnosedwiththyroiditis• Propranolol10mgevery6hoursasneededforsymptomsofhyperthyroidism

• Rechecklabsin4-6weeks• Noindicationtostartantithyroidmedications

Takehomepoints

• Thyroiddiseaseismorecommoninwomen• Synthroiddosesneedtobeadjustedbothduringandafterpregnancyduetochangesinthyroidbindingprotein

• Autoimmunethyroiddiseaseoftencanpresentduringorafterpregnancy

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48y/ofemalewithhistoryofHypothyroidism

• Feelspoorly• 20poundweightgainoverpasttwoyears• Noenergy• Poorsleeppattern• Losinghair

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Medications

• Levothyroxine50microgramsdaily• Atorvastatin10mgdaily• Women’sMultivitaminonedaily

Physicalexam

• Tiredappearing,flataffect• BP110/75P80afebrile• HEENT:noexophthalmos• Neck:firmthyroidwithoutpalpablenodule• COR:RRRnoS3,S4,Nomurmur• Neuro:Brachioradialisreflexesslightlydelayed• Skin:norash• Remainderofexamnormal

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Whatwouldyoudotobeginevaluationofthispatient’sconcerns?

• TSH• FSH• TSHandFT4• Sed rate• 2and3

• TSH12uIU/ml(0.34-5.66uIU/ml)• FSH50uIU/ml(postmenopausal)• CBCnormal• Chemistriesacceptable

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Whatdoyounowaskthepatientbeforeadjustingherlevothyroxine

dose?

• Misseddoses• Takingseparatelyfromcalcium,statin,iron,protonpumpinhibitor

• Changedbrandsofthyroidhormonereplacement

• Additionalsymptoms:missedmenses,hotflushes,checkforpregnancy

• Biotinuse

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ThyroidPhysiology

• Thyroxine(T4)andtriiodothyronine(T3)arereleasedbythethyroidgland.

• MostoftheT3isfromperipheralconversionofT4toT3.

• FreeT4andfreeT3(notboundtoproteins)feedbacktothepituitaryandhypothalamustoaffectthyroidstimulatinghormonerelease(TSH)fromthepituitary.

Hypothyroidismtreatment

• T4usedbecauseoflonghalflife• T3(Cytomel)mustbegivenseveraltimesaday

• NogoodevidenceforcombinationT4/T3replacement

JonklaasJ,etal.Thyroid. 2014Dec;24(12):1670-751.ThyroidAssociationTaskForceonThyroidHormoneReplacement.

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ThyroxineDose

• 1.6ug/kgdaily• Staywithsamebrandorgeneric(mayhavedifferentcosts)

• Increasethedoseforpregnancyorotherconditionswithincreasedbindingglobulin

• Decreasedosefor– Elderly– Patientswithknownheartdisease– Patientswithsignificantcomorbidhealthissues

Whentorecheckthyroidlabs

• 6-12weeks• TSHrecoverylagsbehindT4normalization

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MenopauseandtheThyroid

• Decreasingestrogenlevelsleadtodecreaseinthyroidbindingglobulin

• TherewillbemorefreehormoneavailablesooftenT4dosemayneedtobedecreased.

Otherthyroidpreparations

• Grains• Compoundedformulations• T3• Other

JonklaasJ,etal.Thyroid. 2014Dec;24(12):1670-751.ThyroidAssociationTaskForceonThyroidHormoneReplacement.

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Backtoourpatient

• Pregnancytestisnegative• Menopausalsymptomsdiscussedwithpatient

• Exerciseencouraged• Levothyroxineincreasedto75mcgdaily• Repeatthyroid(TSH)labsorderedfor3mos.

Takehomepoints

• Hypothyroidismsymptomsarecommontomanyotherconditions.

• T4istheacceptedreplacementhormoneatthistimeforhypothyroidism.

• T4replacementmustbetakenatseparatelyfromothermedicationsthatmaydelayabsorption