Abnormalities of Thyroid functiion npmcn [Autosaved].pdf

Abnormalities of Thyroid Function by Dr Nabilah Datti Abubakar, Consultant Chemical Pathologist at the National Hospital, Abuja, Nigeria

1. Abnormalities of Thyroid
function.
Dr Nabilah Datti Abubakar
MB;BS FMCPath
Consultant Chemical Pathologist
National Hospital, Abuja.

2. Pre test
•A45yearoldNigerianwomanpresentstotheGOPD
withmenstrualirregularities,headache,hotflushes,
andslowmentation.Shealsocomplainedofmood
changes,andforgetfulness.TheGPreassuredand
counselledheronpremenopausalsymptoms,shewas
giventheoptionofHRTandcounselledonitsside
effects.Sherepresentedamonthlaterwith,cold
intoleranceandweightgain.TSHwasrequestedwhich
waselevated.
•Whatisthemostprobablediagnosisinthispatient?
•Howwouldyoufurtherinvestigatethispatient?
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3. Pretest2
•A55femaleyearoldcivilservantbeing
managedforgravesdisease,onCarbimazole
15mgthricedailyforamonthpresentedto
thefollowupclinicwiththefollowingresults;
–Thyroidstimulatinghormone(TSH)<0.1mU/L(0.3–5)
–FreeThyroxine(fT4)<5pmol/L(10–27)
–FreeTriiodothyronine(fT3)2.5pmol/L(3.0–9.0)
•Whatwouldbeyourcommentonthisresult.
•Whatisthenextmostappropriatelineofactionin
managingthispatient?
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4. Pretest3
•A 67 year old woman is referred for treatment
of hyperlipidaemia to your metabolic clinic.
Her Cholesterol and Triglyceride levels remain
high despite being on the maximum dosage
recommendation by the ATP treatment panel.
She later on complains of thinning and loss of
hair and hoarseness of her voice, in addition
to memory loss.
•How would you manage this patient?
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5. Outline
•Introduction
•Anatomy/ Histology of the Thyroid gland
•Physiology
•Disorders of the Thyroid gland
•Investigating Thyroid disorders
•Physiological changes in Thyroid gland
•Conclusion
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6. Introduction
Diseasesofthethyroidareamongthemost
prevalentofmedicalconditions,ofgreatpublic
healthconcernisIodinedeficiency,itis
estimatedthat2billionpeopleworldwidehave
insufficientiodineintake,theconsequencesof
thisrangefromincreasedpregnancyloss,
cretinism,increasedriskofthyroidmalignancies.
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7. Introduction
•Technologicaladvancementsinthefieldof
immunoassayhaveevolvedsignificantlyand
assuchhighlyspecificandsensitivetestsfor
thyroidfunctionarenowavailable.
•Forthisreason,cliniciansrelymajorlyonthe
laboratoryforassistanceinthescreening,
diagnosisandmanagementofthyroid
disorders.
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10. Hypothalamo Pituitary Thyroidal axis
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11. Thyroid Releasing hormone/Thyroid
stimulating hormone
•TRHatripeptide,synthesizedinthesupraoptic
andparaventricularnuclei,andstoredinthe
medianeminenceofthehypothalamus.Itis
transportedtotheanteriorpituitary,to
controlsynthesisandreleaseofTSH.
•TSHis28-kDglycoproteinwithαandβ
subunits,theαsubunitiscommontoFSH,LH
andhCG,βsubunitisuniqueconferring
specificactivity.
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12. Thyroid stimulating hormone
•TSHhalflife30minutes,andthedaily
productionrateisabout40–150mU/d.
•Theαsubunitisoftenelevatedinpatients
withTSH-secretingpituitarytumoursandin
normalpostmenopausalwomen.
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13. Thyroglobulin
•Thyroglobulinisthemostabundantproteininthe
thyroidgland;itsconcentrationis200-300g/L.It
providesthepolypeptidebackboneforsynthesis
andstorageofthyroidhormones.Italsooffersa
convenientdepotforiodinestorageandretrieval
whenexternaliodineavailabilityisreduced.
•IodinationofthetyrosylresiduesinTg,to
produceMITandDIToccursattheapicalplasma
membrane-follicleandinvolvesH
2O
2,iodide,
TPO.
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14. Thyroid hormone synthesis
–ActivetransportofI
–
acrossthebasementmembraneinto
thethyroidcell(trapping).
–Oxidationofiodideandiodinationoftyrosylresiduesin
thyroglobulin(organification);
–Linkingpairsofiodotyrosinemoleculeswithin
thyroglobulintoformtheiodothyroninesT
3andT
4
(coupling);
–Proteolysisofthyroglobulin,withreleaseoffree
iodothyroninesandiodotyrosinesintothecirculation;
–Deiodinationofiodotyrosineswithinthethyroidcell,with
conservationandreuseoftheliberatediodide;and
–Intrathyroidal5'-deiodinationofT
4toT
3.
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15. Thyroid hormone synthesis
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16. Thyroid hormone synthesis
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17. Thyroid Receptors
•Thyroidhormonesbindwithhighaffinitytonuclearthyroid
hormonereceptors(TRs)αandβ.TRαandTRβare
expressedinmosttissues,buttheirrelativeexpression
levels;
•TRαisfoundinbrain,kidneys,gonads,muscle,andheart,
whereasTRβisabundantinthepituitaryandliver.
•TheTRβ2isoform,isselectivelyexpressedinthe
hypothalamusandpituitary,andcausesfeedbackcontrolof
thethyroidaxis.
•T3andT4bindwithsimilaraffinitiestoTRαandTRβ.T3is
boundwith10–15timesgreateraffinitythanT4,
accountingforitsincreasedhormonalpotency.
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18. Characteristics of circulating Thyroid
hormones T4 and T3
Hormone Property ThyroxineT4 TriiodothyronineT3
Serum concentrations
Total hormone
Fraction of total
hormone in the free
form
Free (unbound)
hormone
Serum half-life
Fraction directly from the
thyroid
Production rate, including
peripheral conversion
Intracellular hormone
fraction
Relative metabolic potency
8 μg/dL
0.02%
21 ×10−12M
7 days
100%
90 μg/d
∼20%
0.3
0.14 µg/dL
0.3 %
6 ×10−12M
0.75 days
20 %
32 μg/d
∼70%
1
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19. Thyroid hormones
•Thyroidhormonesaretransportedinplasma
almostentirelybound,(T
499.96%andT
3
99.6%)tolargelyThreeplasmaproteins;
Thyroxinebindingglobulin(TBG)-70%,
Transthyretin-15%,Albumin10-15%.
•Thenormalthyroidglandsecretes;100nmol
ofT
4;5nmoleachofT
3,andmetabolically
inactivereverseT
3(rT
3).
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20. Peripheral deiodination
•DeiodinasesinliverandkidneysconvertT
4to
T
3byremovalofaniodineresiduefromthe
outerβ-ringorreverset
3fromtheinnerα-
ring.
•Deiodinases,arelowinsystemicillness,
prolongedfasting,useofdrugse.g.β-blockers,
amiodaroneandareincreasedbyhepatic
inducerse.g.phenytoin.
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21. Characteristics of Deiodinases
D1 D2 D3
Source, Liver, kidneys,
thyroid
Brain, pituitary,
skeletal muscle
Brain, placenta,
fetal tissues
Substrates rT3 < T4> T3 T3 > T4 rT3 > T4
Role Plasma T3
production, rT3
clearance,
clearance of
hormone
Local T3
production, ?
plasma
T3 production
T3 degradation,
prevents
exposure of fetus to
T3
InHypothyroidismDecreases Increases Decreases
In HyperthyroidismIncreases Decreases Increases
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22. Metabolic effects of Thyroid hormones
•Thyroidhormones(specificallyT
3)regulaterateofoverall
bodymetabolism;increasesBMR.
•Calorigeniceffects;T
3increasesoxygenconsumptionbymost
peripheraltissues
•Stimulateslipolysis,stimulatesformationofproteins
•Essentialforneuraldevelopmentandmaturationandfunction
oftheCNS
•Importantfornormalreproductivefunction.
•T
3isthemajorregulatorofmitochondrialactivity.
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23. Metabolism of Thyroid hormones
•About80%ofT
4ismetabolizedbydeiodination,
35%toT
3and45%torT
3.Therestisinactivated
mainlybyglucuronidationintheliverandby
sulfationintheliverorkidney.
•10%ofthetotalplasmaT
4poolisclearedeach
day,andtheplasmahalf-lifeofT
4is7days.
•TheturnoverofT
3ismorerapidduetoitslesser
affinityforplasmaprotein,withaplasmahalf-life
of1day.ThetotalbodypoolofrT
3isaboutthe
samesizeasthatofT
3,butrT
3hasanevenmore
rapidturnover,withaplasmahalf-lifeof-0.2day.
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24. Iodine metabolism
•Essentialmicronutrientconsumedasiodineoriodate,and
convertedtoiodideinthestomach.TheWorldHealth
OrganizationRDAof150gforadults,200gforpregnant
andlactatingwomen,and50to120gforchildren.
•Asmostiodideisexcretedbythekidneys,urinaryiodide
excretionisanexcellentindexofdietaryintake.
•Dietaryiodinedeficiencyaffectsanestimated100million
peopleintheworld.Wheniodideintake<50g/day,the
thyroidcannotsustainadequatehormoneproduction,
leadingto(goiter)and,ultimately,hypothyroidism.The
consequencesarediretothedevelopingfetusand
children,withabnormalneurologicdevelopmentand
growth.
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25. Auto regulation
•Auto-regulationmaybedefinedasthecapacityof
thethyroidglandtomodifyitsfunctiontoadapt
tochangesintheavailabilityofiodine,
independentofpituitaryTSH.
•Themajoradaptationtolowiodideintakeisthe
preferentialsynthesisofT
3ratherthanT
4.
•Iodideexcess,inhibitsiodidetransport,cAMP
formation,peroxidegeneration,hormone
synthesisandsecretion,andthebindingofTSH
andTSHreceptorautoantibodies.
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26. Thyroid disorders
•Thyroiditis
•Hypothyroidism
•Hyperthyroidism
•Autoimmune thyroid disorders –Graves
disease and Hashimotos thyroiditis
•Iodine deficiency disorder
•Neoplasms
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27. Hypothyroidism
•Hypothyroidismisdefinedasadeficiencyin
thyroidhormoneproductionorsecretion
producingavarietyofclinicalsignsand
symptomsofhypo-metabolism.
•Worldwide,themostcommoncauseof
hypothyroidismisiodinedeficiency,whereiodine
fortificationiswidespread,itusuallyoccursdue
toHashimotothyroiditis.
•Hypothyroidismismorecommoninwomenthan
men,increaseswithage,andishigherinwhites
thaninblacks.
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28. Causes of Hypothyroidism
•Primary Hypothyroidism
Chronic autoimmune thyroiditis:
Subtotal and total thyroidectomy
Infiltrative diseases of the thyroid (amyloidosis, sarcoid,
lymphoma)
Iodine deficiency
Drugs with antithyroidactions: lithium, iodine containing
drugs,
•Central Hypothyroidism (Secondary Hypothyroidism)
Pituitary disease or Hypothalamic disease
•Transient Hypothyroidism
Silent (painless) thyroiditis including postpartum thyroiditis
Subacutethyroiditis(De Quervainsyndrome)
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29. Chronic autoimmune Thyroiditis
(Hashimotos Thyroiditis)
•Themostcommoncauseofhypothyroidism.Characterizedby
destructionofthethyroidglandbyautoantibodiesagainst
thyroglobulin,thyroperoxidase.
•Histologicalhallmarkisdiffuselymphocyteinfiltration,atrophic
follicularcells,granulatedthyrocytes,andfibroticthyroidtissues.
•Moreprevalentinareaswithahighdietaryiodinizedsaltintake,
andsmokingincreasestherisk.
•Goitercanbeseenonpresentation,butthyroidatrophyismore
common.
•AssociatedwithAddison’sdisease,type1diabetesmellitus,and
hypogonadism,inpolyglandularautoimmunefailuresyndrome
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30. Clinical features of Hypothyroidism
•Signs
–Delayedrelaxationphaseofdeeptendonreflex
testing,bradycardia,diastolichypertension,coarsened
skin,yellowingofskin(carotenemia),periorbital
edema,thinningofeyebrows/lossoflateralaspectof
brows,slowedmovements/speechpleural/pericardial
effusionascites.
•Symptoms
–Coldintolerance,depression,mentalretardation
(infants),slowedcognition,menorrhagia,growth
failure(children),pubertaldelay,dryskin,oedema,
constipation,dyspneaonexertion.
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31. Hyperthyroidism
•Thyrotoxicosisisaconstellationoffindings
thatresultwhenperipheraltissuesare
presentedwith,andrespondto,anexcessof
thyroidhormone.
•Thyrotoxicosiscanbetheresultofexcessive
thyroidhormoneingestion,leakageofstored
thyroidhormonefromstorageinthethyroid
follicles,orexcessivethyroidglandproduction
ofthyroidhormone.
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32. Signs and Symptoms
•SignsTachycardia,Tremor,Warm,moistskin,
Ophthalmopathy(Graves’disease),Goiter,Brisk
deeptendonreflexes,Musclewastingand
weakness,Dermopathy/pretibialmyxoedema
(Graves’disease)Osteopenia,osteoporosis
•Symptoms Nervousness, irritability,
anxiety,Tremor,PalpitationsFatigue,weakness,
decreasedexercisetolerance,Weightloss,Heat
intolerance,Hyperdefecation,Menstrualchanges
(oligomenorrhea),Prominenceofeyes.
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33. Subclinical Hypothyroidism
•An isolated elevated TSH level in the setting of
normal T
3and T
4levels
•Symptoms may be present or absent.
•Worldwide prevalence between 1% and 10%
•Highest rates are in women older than 60
years of age
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34. Subclinical Hypothyroidism and
Cardiovascular disease
•Cardiac manifestations
–Left ventricular systolic and diastolic dysfunction
–Increased systolic time interval
–Myocardial infarction
•Coronary artery disease
–Elevated total cholesterol levels, LDL-C levels, and
triglyceride levels
–Aortic atherosclerosis
–Hyperhomocysteinemia
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35. Subclinical Hyperthyroidism
•Insubclinicalhyperthyroidism,theTSHissuppressedin
thepresenceofnormallevelsoffT4
•SubclinicalhyperthyroidismislessInpatientsoverage60
withsubclinicalhypothyroidism,therelativeriskforatrial
fibrillationincreasesthreefold,highercardiovascularrisk
andanincreasedriskoffracture..
•Post-menopausal women with subclinical
hyperthyroidismmayhaveanincreasedrateofbone
loss.
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36. Non-Thyroidal Illness
(Sick Euthyroidsyndrome)
•Almostanyconditionthatcanmakeapersonillcan
causeSickEuthyroidSyndromeandtheelderlyare
moresusceptible.
•Thesyndromeisacuteandspontaneouslyreverses.
Canoccuraftersurgery,duringfasting,acutefebrile
illnesses,andafteracutemyocardialinfarction.
•Malnutrition,renalandcardiacfailure,hepatic
diseases,uncontrolleddiabetes,cerebrovascular
diseases,andmalignancycanalsoproduce
abnormalitiesinthyroidfunctiontests
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37. Non Thyroidal Illness
•ThelaboratorypatternisoneoflowtotalT4,freeT4,
and(sometimes)TSH.
•Asillnessdecreases5-monodeiodinaseactivity,lessT4
isconvertedtoactiveT3.Thisleadstodecreasedlevels
ofT3andhigherlevelsofreverseT3.
•Otherfactorsincludecentralhypothyroidismand
thyroidhormone–bindingchangesassociatedwith
severeillness.
•Thesechangesarethoughttobeappropriate
adaptationtoillness.
•Thyroidhormonereplacementtherapyisnotindicated
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38. Drug induced Thyroid dysfunction
•Amiodaronecontains39%iodineperweightof200mgtab.
Patientstreatedwithamiodaronemaymanifestaltered
thyroidhormoneprofilewithoutthyroiddysfunction,or
presentwithclinicallysignificantamiodarone-induced
hypothyroidismoramiodarone-inducedthyrotoxicosis.
–Jodbasedoweffect;hyperthyroidismfromincreasediodine
uptakeinapatientwithlongtermthyroiddisease.
–WolffChiakoffeffect;Anautoregulatoryphenomenon
Hypothyroidismresultsfromexcessiodinetransientlyinhibiting
thyroiduptake.
•Hypothyroidismisoftenseeninpatientsbeingtreatedwith
TKIdrugsfornon-thyroidalcancers,thedevelopmentof
hypothyroidisminthesepatientsmaybelinkedto
improvedsurvivals.
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39. Iodine Deficiency Disorder
•Iodinedeficiencyisthecommonestcauseof
thyroiddisordersindevelopingcountries.Itis
definedasamedianurinaryiodineconcentration
lessthan50μg/Linapopulation.
•Featuresincludegoiter,subclinical
hypothyroidism,impairedmentalfunction,
retardedphysicaldevelopment.
•Seleniumdeficiencycontributestothe
occurrenceofendemicgoiterinAfricaor
persistenceofendemicgoiteriniodinedeficient
areasevenaftercorrectingforiodinedeficiency
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40. Investigating Thyroid Disease
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41. Recommendations
•Routinethyroidfunctiontestingisnotrecommendedin
asymptomaticpatients.
•Testingmaybeindicatedwhensymptomsorsignsare
presentinpatientsatriskforthyroiddisease.
•ATSHvaluewithinthereferenceintervalexcludesthe
majorityofcasesofprimarythyroiddysfunction.
•IfTSHtestingisnormal,repeattestingmightbeunnecessary.
•MeasurementoffT3israrelyindicatedinsuspectedthyroid
disease.
•Screeningforthyroiddiseaseshouldnotbeperformedin
hospitalizedpatientsorduringacuteillness.
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42. Risk factors for Thyroid disease
(Indications for screening)
•Men:age≥60years
•Women:age≥50years
•Historyorstrongfamilyhistoryofthyroiddisease
•Autoimmunediseases
•Neckirradiation
•Thyroidectomyorradioactiveiodineablation
•Drug-lithiumandamiodarone
•Dietaryfactors(iodineexcessandiodinedeficiency)
•Chromosomalorgeneticdisorders(e.g.,Turner
syndrome,Downsyndromeandmitochondrial
disease).
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43. Thyroid Stimulating Hormone
TSH
•TSHthefirst-linethyroidfunctiontesttoassess
thyroidstatusformostclinicalcasesduetoa
physiologicalinverselog-linearrelationship
betweencirculatingTSHandfreeT4(FT4)
concentrations.
•AderrangedTSHisthefirstabnormalityto
appearinthyroiddisease,whereotherthyroid
testscanbenormal.
•UsingTSHasasinglecriterionhasbeenshownto
accuratelyclassifythethyroidstateofapatientin
over95%ofcases.
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44. TSH -limitations
•Non-thyroidalillness(NTI),pituitarydiseaseandvarious
drugscanallaffecttheHPTaxis,glucocorticoids,dopamine
canallsuppressTSHsecretionandcausediscrepantTSH
levels.
•Thediscrepancybetweentheserumhalf-lifeofTSH(1
hour)andthatofT4(1week)canleadtodiscordant
TSH/FT4valuesinpatientsontreatment.
•BothserumandplasmaareacceptablesubstratesforTSH
immunoassay.TSHisstableinserumforatleastfivedaysat
4°C,andatleast29yearsat−25°C.
•AbnormalTSHlevelscanpersistforweeksorevenmonths
afterinitiationoftreatmentforthyroiddisorders.
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45. TSH assay
•TSHassaysensitivityhasimprovedwithsubsequent
testgenerations;Firstgeneration(Sensitivity1.0
IU/L)ISecondgeneration(Sensitivity:0.1mIU/L),
Thirdgeneration(Sensitivity:0.03mIU/L)
•TSHreferenceintervalhasrecentlybecome
controversial.ThelowerTSHreferencelimithasbeen
showntobeapproximately0.3mIU/lbutTSHupper
referencelimithasbecomecontentiouswith
estimatesrangingfrom2.1mIU/lto7.5mIU/l.
•Multiplefactorsinfluencethisincludingsex,
ethnicity,iodineintake,BMI,smoking,age.
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46. Total and Free Thyroxine,
Triiodothyronine
•Currently“freehormonehypothesis,”the
measurementofnon–protein-boundT4incirculation
(fT4)isamoreaccuratereflectionofthyroidstatus
thanthetotalamountofT4
•Directmethods,-physicalseparationofboundfrom
freeT4,egequilibriumdialysisorultrafiltration,
•Indirectmethods,-immunoassaymethodsarealmost
universallyusedinclinicalchemistrylaboratories.
Immunoassaysfurtherdividedintooneandtwo-step
methodsdependingonwhetherawashstepis
includedtoremoveserumconstituentsbeforethe
additionoftheT4immunoassaytracer.
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47. Free thyroid hormones
•FreeThyroxine(FT4)assays-superiorindicator
ofthyroidstatus,independentofchangesin
thyroid-bindingproteins,whichinfluencetotal
hormonemeasurements.
•However,currentfreehormoneimmunoassays
stillappearsensitivetoalterationsinserum
albuminandabnormalbindingproteinsaswellas
certaindrugs,highfreefattyacidlevelsandother
substanceswhichcompeteforbindingsiteson
thyroid-bindingproteins.
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48. Free thyroid hormone assay -
limitations
•Freethyroidhormoneimmunoassaysarealsoproneto
interference.
•Phenytoin,carbamazepine,furosemideandnon-
steroidalanti-inflammatorydrugscompetewith
thyroidhormoneinbindingtoserumbindingproteins
andmayincreaseFT4
•Invivo,heparinliberatesfreefattyacids,which
displacethyroidhormonesfromtheirbindingproteins
andalsoincreaseFT4.
•FT4referenceintervalsvarywidelybetweenmethods,
withage,stageofpregnancyandgeographiclocation.
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49. Total Thyroxineand Triiodothyronine
•Totalthyroidhormonemeasurementsarenow
largelyusedtoconfirmtheresultsoffT4
measurementswhentheyareindoubt.
•Thetotalthyroidhormoneispresentinthe
seruminnanomolarconcentrations,itislessof
ananalyticalchallengethanthemeasurementof
freehormone.
•Massspectrometricmeasurementsarethe
methodofchoicefortotalthyroidhormone
analysis,competitiveimmunoassayisstillin
widespreadclinicaluse.
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50. Thyroid Antibodies
•AntiThyroidperoxidase-TPOassayisavery
sensitivemarkerforHashimotothyroiditis.
•Assaymethods includeagglutination,
immunofluorescence,andImmunometric
methods.
•AntiThyroidreceptorantibodiesTSHRisatarget
forbothblocking(anti-TSHRB)andstimulating
autoantibodies(anti-TSHRS) stimulating
autoantibodies(anti-TSHRS).Gravesdisease,is
causedbyanti-TSHRS.
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51. Thyroglobulin
•Mainlyusedasatumourmarkerinpatientswith
differentiatedthyroidcancer(DTC)post-thyroidectomy.
Itisalsousedinthediagnosisofcongenital
Hypothyroidismandinthedifferentialdiagnosisof
factitioushyperthyroidism.
•Thyroglobulinassaysarecumbersomedifficultdueto
theheterogeneityofthemoleculeandtheprevalence
ofendogenousanti-Tgorantireagentantibodiesthat
interferewiththeimmunoassay.
•Threeassaymethodsused;Competitiveimmunoassay,
Immunometricassay,Peptidemassspectrometric
assay.
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52. Thyroid Antibodies in diseases of the
Thyroid.
ANTIBODY GENERAL
POPULATION
GRAVES’ DISEASE AUTOIMMUNE
HYPOTHYROIDISM
Antithyroglobulin3% 12%–30% 35%–60%
Thyroidperoxidase10%–15% 45%–80% 80%–99%
Anti-TSH receptor 1%–2% 70%–100% 6%–60%
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53. Urinary Iodine Concentration
•Thepopulationstatusofiodineintakeisbestdetermined
bymeasurementsofUICasmostofthebody’siodineis
excretedinurine,UICisconsideredareliableandvalid
biomarkeroftheiodineintakeandiodinedeficiencyofthe
population.
•Thegoldstandardis24-hoururinecollection,randomspot
urinarymeasurementcanalsobedone.
•Method-colorimetricmethod(Sandell–Kolthoffreaction)
inwhichurineisfirstaciddigestedundermildconditions
andiodineisthendeterminedbyacatalyticreductionof
cericammoniumsulfate(yellow)tothecolourlesscerous
forminthepresenceofarseniousacid
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54. Investigating Thyroid Disease
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55. Investigating Thyroid Diseases
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56. Monitoring Hypothyroidism
•HypothyroidismTSHvalueschangeslowly,frequentrepeat
testingisnotindicated.TSHmayberepeatedafter6weeks
followingachangereplacementdoseorinaclinicalstatus.
Avoidovertreatmentwithlevothyroxine,topreventatrial
fibrillation(morecommonlyintheelderly)andbonelossin
postmenopausalwomen.
•WhenTSHnormalizes,checkannuallyunlessanew
indicationarises.Thisconfirmsadequacyoftreatmentdose
andcompliancewiththerapy.
•Patientsonlithiumandamiodaroneareatincreasedrisk
forhypothyroidism,monitoringofTSHisrecommended
every6months.Amiodaronetreatmentmayalsoleadto
amiodarone-inducedthyrotoxicosis.
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57. Monitoring Hyperthyroidism
•Allowatleastonemonthorlongerbefore
repeatingfT4andTSHlevelsaspituitarysecretion
ofTSHmaybesuppressedforprotractedperiods
followinghyperthyroidism.
•UntilTSHsuppressionresolves,initialtreatment
anddosingdecisionsshouldbebasedonfT4,or
inthecaseofT3thyrotoxicosis,onfT3.
•InHypothalamicorpituitarydisease,fT4
measurementisrequiredtomakethediagnosis
orassessadequacyofthyroidreplacement
therapy.
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58. Antibody Interference
•Interferingantibodiesareintrinsicantibodiesthatcan
causeunpredictableresultsonthyroidtesting.
•Theycanbeheterophile(nonspecific)antibodies,human,
anti-animalantibodiesorautoantibodiestoTSH,T4orT3.
•Althoughassaysaredesignedtominimisesuch
interferences,problemsstilloccurinbetween0.03%and
3%ofallsamples.
•Itismostcommonlyfirstsuspectedwhenthereisagross
discordancebetweentheclinicalpresentationandthe
laboratoryresult.
•Whenantibodyinterferenceissuspected,bothTSHandFT4
usingadifferentmanufacturer’splatform.
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59. Physiological changes in Thyroid
function
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60. Thyroid disorders in pregnancy
•Itisestimatedthatapproximately4%of
pregnantwomenhaveahistoryofthyroid
disease,developthyroiddiseaseduringthe
pregnancy,orareforthefirsttimediagnosed
withthyroiddisease5yearsafterapregnancy.
Postpartumthyroiditisisdiscussedearlierin
thesectiononthyroiditis.
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61. Physiological changes in pregnancy
•PlasmatT3andtT4concentrationsincreaseduring
pregnancyduetoanincreaseinTBGconcentration
(enhancedhepaticsynthesisandreducedmetabolismfrom
increasedoestrogenlevels).TSH-R;thereisincreased
stimulationbyHCG.
•PlacentalhCGsharesthesameαsubunitwithTSHandacts
inearlypregnancyasaTSHagonist,thisleadstoa
physiologicalriseinT4andT3,which,inhibitsTSH
secretion,causingTSHtofall.
•ThedecreaseinserumTSHinthefirsttrimesterisfollowed
byariseduringthesecondandthirdtrimesterswhenthe
hCGconcentrationsfallbutdonotexceedpre-pregnancy
values
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62. Hypothyroidism in Pregnancy
•Thediagnosisofhypothyroidisminpregnancyis,an
elevatedTSHconcentrationwithlowconcentrationsof
fT4,usingtrimester-specificreferenceintervals.
•Untreatedovertmaternalhypothyroidismisassociated
withanincreasedriskofmiscarriage,pretermdelivery,
andpreeclampsiainthemother.
•Inthenewborn,thereisanincreasedriskofneonatal
mortalitycausedbypretermdelivery,riskoflowfor
gestationalagebirthweight,anddecreased.
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63. Thyroid changes in the Foetus
•Beforethefetusdevelopsitsownindependentthyroid
function,itdependsonmaternalthyroidhormonesforearly
neuraldevelopmentby11thweekofgestation,measurable
TSHandTRHarepresent,thefetalthyroidalsobeginstotrap
iodine.
•Thesecretionofthyroidhormonebeginsin18–20weeks.TSH
increasesrapidlytopeaklevelsat24–28weeks,andT
4levels
peakat35–40weeks.T
3levelsremainlowduringgestation
•Withinhoursofbirth,plasmaTSH,T4,andT3concentrations
riserapidlyduetocoldstress.By2to3days,TSH
concentrationsfall.TotalT4fallstoadultconcentrationsby1
to2monthsofage.
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64. Thyroid changes with ageing
•T
4turnoverishighestininfantsandchildren,
andfallstoadultlevelsafterpuberty.
•TheT
4turnoverrateisthenstableuntilafter
age60,whenitagainbeginstodecline.
•Intheelderly,themetabolicclearanceofT
4
decreasesbyupto50%,necessitatinga
reductioninT
4dosefortreatedpatients.
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65. Conclusion
•Thyroiddisordersareverycommon,andcan
presentwithmild,vagueornonspecific
symptoms.
•Duetoadvancementsinassaymethods,
diagnosisofThyroiddisordersisheavily
dependentonlaboratoryinvestigations.
•Althoughdiagnosisisstraightforwardinmajority
ofcases,itisimportanttothephysiological
changesassociatedwiththesehormonesaswell
aschangesassociatedwithpharmocotherapy.
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66. Thank you for listening
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67. 30/01/2020
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Questions?
Comments?
Contributions?

68. Further Reading
•Thyroid disease: thyroid function tests and interpretation This
article aims to review the indications for thyroid function tests and
their interpretation. David Haarburger, MB BCh, MMed, FCPath
Chemical Pathologist, National Health Laboratory Services, Groote
Schuurand Red Cross War Memorial Children’s Hospitals.
Correspondence to: David
Haarburger([email protected])Volume2016|Article
ID2157583|9pages|https://doi.org/10.1155/2016/2157583
•Abnormalities of Thyroid Hormone Metabolism during Systemic
Illness: The Low T3 Syndrome in Different Clinical Settings Arnaldo
MouraNeto
1
andDenise EngelbrechtZantut-Wittmann
1
International journal of Endocrinology
•GreenspansBasic and Clinical Endocrinology. David G. Gardner.
Dolores Shoback. Eight edition
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69. Further reading
•Endotext;Chapter2ThyroidHormoneSynthesis
AndSecretion.BernardRousset,Corinne
Dupuy,FrançoiseMiot,Ph.D.,andJacques
Dumont,M.D.Endotextwww.endotext.org
•TietztextbookofClinicalchemistryandmolecular
diagnostics.
•Clinicalchemistry.6
th
editionbishops
•HarrisonsprinciplesofInternalMedicine.18
th
edition.
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