Thyroid function test ( TFT) in simple way

Thyroid function test ( TFT) in simple way

1. Thyroid function test
Binaya Tamang

2. Learning objectives
•Function of thyroid hormones
•Biochemistry of thyroid hormones
•Thyroid stimulating hormone
•Diseases of thyroid glands
•Non-thyroid illness
•Classification of thyroid function test

3. Thyroid Gland: Basic intro
•Butterfly shaped
•Weighs: 15-20 gm
•Cell types: Thyroid follicular cells produce
thyroid hormones (TH) Parafollicular (Or
C ) cells secrete calcitonin
•Increased activity vs decreased activity:
columnar follicular cell vs flattening cell.
•Secrets two hormones : thyroxine(T4) and
triiodothyronine(T3),
•in addition, small amount of rT3, MIT and
DIT

4. Biological Function of TH
•At molecular level:
1.Increaseoxygenconsumptionwithintissuesviaincreasedmembrane
transport
2.Enhancemitochondrialmetabolism(stimulationofmitochondrial
respirationandoxidativephosphorylation)
3.IncreasesensitivitytocatecholamineswithincreasedHRand
myocardialcontractility
4.Stimulateproteinsynthesisandcarbohydratemetabolism
5.Increasesynthesisanddegradationofcholesterolandtriglycerides
(e.g.,regulationofLDLreceptorexpressionbytheliver)
6.Increasevitaminrequirements;regulatecalciumandphosphorous
metabolism
OVERALL:BMR,calorigenesis,neuraldevelopment,normal
growth,sexualmaturation,adregenicactivity.

5. Biochemistry of Thyroid Hormone
•Approx.40-45%ofT4isdeiodinisedbyperipheraltissuestoT3and
rT3.
•100nmol(80mg)dailyà26mgT3and29mgrT3.
•T3is4to5timesmorepotentinbiologicalsystemthanT4
•1/3ofallT4isconvertedtoT3(T4isprohormone).

6. Brief Biosynthesis

7. •T3has
higher
binding
affinity
forTRs
thanT4,
explainin
gits
function
asactive
TH
Mechanism of TH Action

8. Thyroid Stimulating Hormone (TSH)
•Thyrotrophs cell of Ant. pituitary
•Mol.wt: 30 kda.
•Aka. thyrotropin.
•Majorregulatorofmorphologic&functionalstatesofthyroid
•Glycosylationforfullbiologicactivity
•t1/2~30mins;displayspulsatile&circadianvariations;
nocturnalsurgeprecedesonsetofsleep
•Composedofα-subunit-92aacommontoLH,FSH,hCG,&specificβ-subunitof112aa.

9. TSH, although not thyroid hormone but has a great
Role
•Stimulatesiodinepump(NIS)
•Increasesthyroglobulinsynthesis
•Colloidaluptakebyfollicle
•IncreasesrateofproteolysisofTG
•Inducesanincreaseinsizeandnumberofcell
•ProlongedTSHstimulationleadstoincreasedvascularity
andeventualhypertrophicenlargementofTH.gland

10. •SerumTSHconcnisexquisitelysensitiveindicatorofthyroidstateofpts.
•ReciprocallogLinearrelationshipbetnfT4concn&logofTSH-
describes
•2foldchangesinfT4elicits100foldschangeinTSHexplainswhysome
ptshavenormalfT3,fT4orbothandfewclinicalsignsbuthaveTSH
abnormal
•Subclinical condition is detected by TSH changes

11. Free and Bound concept: An important base for TFT
•ThyroidglandreleaseàT4andT3àcarrierprotein(
circulation)
•ThoseproteinareTBG,TBPAandAlbumin
•Binds99.97%ofT4and99.7%ofT3.
•So,verysmallfractionunbound(freeforbiological
function)i.e0.03%fT4and0.3%fT3
•Proteinboundcannotdiffuseintocellànofunctionbutcan
actasstorage
•FluctuationofbindingproteinsàfluctuatestotalT4andalsoT3butnotinseverelikeT4.

13. DISEASES OF THE THYROID GLAND
A. Hypothyroidism (under activity)
B. Hyperthyroidism (over activity)
C. Anatomical abnormalities/disorders of thyroid
–Goitre
1.Endemic goitre
2.Diffuse goitre
3.Multinodular goitre
–Lingual thyroid
–Thyroglossal duct cyst
–Tumors
1. Thyroid adenoma
2. Thyroid cancer
»Papillary
»Follicular
»Medullary
»Anaplastic
D. Lymphomas and metastasis from elsewhere (rare)

14. Hypothyroidism
•DeficiencyinTHsecretion&action.
•2-15%population
•F>M;butriskincreasesinbothwithageing
•Clinicalsymptoms:lethargy,fatigueandcoldintolerance.
Forexample:
•Myxedema:severeformàaccumulation(Mucopolysachharides)inskin
andothertissuesàthickeningoffacialfeaturesanddoughyindurationof
skin.
•Cretinism:severehypothyroidisminChildren-severegrowthfailureand
mentalretardation

16. Based on TSH and FT4-classified as:-
I.Primary ( thyroidal ) hypothyroidism: destroyed thyroid
tissue or TH biosynthesis, (low FT4, increased TSH)
•Causes:
A. loss of functional tissue
§Chronic lymphocytic ( Hasimotos’s) thyroiditis ( most
frequent in developed country)
§Radiation injury to neck ( I-131) therapy
§Post operative hypothyroidism ( neck surgery)
§Thyroid gland dysgenesis, developmental defect(
neonatal)
B. Infiltrative diseases of thyroid :
§Viral or bacterial infection

17. C.Defectsinthyroidhormonesynthesis
•Congenitalbiosynthesisdefect(dyshormogensis)
•Endemiciodinedeficiency(mostcommonworldwide)
•Druginduced(li,glucocorticoids,iodine,propranolol)
•Idiopathicprimaryhypo(TSHreceptordefect)
•Antithyroidagents(propylthiouracil)
•Thyroiditiswithautoantibodies
vInmildorsubclinicalhypothyroidism(fT4normalbut
TSHiselevated,6-12weeksorlonger).Thus,theTSHlab
findingsisveryimportantparticularlyinearlydetection.
vAfteroralthyroxineàinitial,ft4adjustquickly,butTSH
stillremainhigh,pituitaryisslowtoregisteracutechanges
inTHhormone(pit.Lag),4to8weeksneededforTSH
normal.

18. II.Transienthypothyroidism-
•Silentthyroiditis,includingpostpartumthyroiditis
•Subacutethyroiditis
•After131ItreatmentorsubtotalthyroidectomyforGraves’disease
III.Secondaryhypothyroidism/Centralhypothyroidism(lowFT4,normalorlowTSH)
•Pituitarydisease-TSHdef
•Hypothalamicdisease-TRHdef(Tertiaryhypothyroidism)
•IsolatedTSHdeficiencyorinactivity:rare;panhypopituitarism
vTRHtest-pitvshypothalamic
Inpatientwithpit.glanddisease,NoTSHresponsewithexo.TRH.But
responsetohypothalamicabnormalities.(usuallylate45to60minvsusual
time20-30min)

19. Hyperthyroidism ( Thyrotoxicosis)
•ClinicalsyndromethatresultsfromelevatedconcnoffreeTHinplasma,a/wclinicalevidenceofhypermetabolism
•Fairlylow:0..3-0.6%inGP
•F>M.
•BasedonTSHandFT4causescanbeclassifiedas:
ØPrimaryhyperthyroidism:elevatedFT4,decreasedTSH
ØSecondaryorCentralHyperthyroidism:elevatedFT4,N/elevated
TSH.forex.Ant.PituitaryAdenoma
•Clinicalhyperthyroidism,evidenceofpituitarymassonCTor
MRI
ØSubclinical Hyperthyroidism: Persistent depression in TSH when
FT4 & T3 normal

20. Causes of hyperthyroidism
•Common causes•Diffuse toxic hyperplasia ( Grave’s disease)•Toxic multi nodular goiter ( Plummersdisease)
•Toxic solitary adenoma.
•Less common causes•Acute or subacute thyroiditis ( viral or bacterial)•Tsh-secreting pituitary tumour•Thyroid carcinoma ( papillary, follicular , anaplastic)•Post partum thyroiditis
•HCG-secreting trophoblastic tumour•Iodine induced hyperthyroidism•Thyrotoxicosis factitia ( exogenous intake)•T3-toxicosis•Drug induced ( amiodarone)
•Ectopic thyroid tissue( Struma ovari, thy. Carcinoma metastasis)

22. Graves’ Disease ,1835 ROBERT Graves
•Agonisticautoantibodies(thyroidstimulatingIgG)bindto,&
activate,TSHreceptor,producingexcessreleaseofTH&
subsequentclinicalhyperthyroidism;
•Alsocalledaslongactingthyroidstimulator(LATS)
•F:Mis5:1
•Riskfactors:Familyhistory,otherautoimmunediseases(likeRAandtype1
DM)
•Classicalclinicaltriad:
(1)Goiter&biochemicalhyperthyroidism
(2)Exophthalmos:autoimmunecause;retro-orbitaltissuesexpressTSHR,
consequenttostimulatoryTSHRautoAb-retro-orbitaltissuehyperplasia
(3)Nonpittingpretibialmyxedema-accumulationofmucopolysaccharidesin
sctissue,visible&palpableswelling

24. T3-Thyrotoxicosis
•IfTSHislowbutfT4isnormal,aT3measurementshould
beperformed,becauseT3concisoftenelevatedtoagreater
degreethanisT4insomeconditionslike:-
•EarlyphasesofGravesdisease
•Solitaryormultinodulartoxicgoiter
•Mildiodinedeficiency
•ClinicalhyperthyroidismwithsuppressedTSH,normalFT4,
elevatedT3orFT3
Dueto:-
•↑↑edperipheralandthyroidalconversionofT4toT3-D1:more
T3conversion
•StimulationofTSHR:enhancesproductionofT3>T4

25. Non thyroid illness
•Anyacute,severeillnesscancauseabnormalitiesinthecirculatingthyroid
hormoneorTSHlevels.(Eveninabsenceofunderlyingthyroiddisease).
•Euthyroidhyperorhypothyroxinemia(SickEuthyroidsyndrome)
•Routinetestingofthyroidfunctioninacutelyillpatientsshouldbeavoided
unlessastrongsuspicionofthyroiddisorders.
•Most common type of sick euthyroid syndrome:
•Earliest : Decreased in total or fT3( sometimes very low)
•Increased in rT3
•Severe: In more ill patients ↓TT4 and fT4
•TSH : usually normal ( mildly depressed in acute and elevated during
recovery phase)
•These fluctuation may demonstrate adaptation to catabolic state.

28. Objectives of TFT
•Toassessthefunctionalstatusofthegland
•Tocharacterizetheanatomicalfeaturesofthethyroidgland,
and
•Topossiblyevaluatethecauseforthethyroiddysfunction.
Single thyroid function test is not absolute in diagnostic
accuracy

29. Thyroid Function Tests

31. vTest based upon the primary function ( substrate
input and primary function)
§Radio iodine uptake study ( RIU)
§Protein bound iodine ( I131) in serum
§T3 suppression test
§TSH and TRH stimulation test
vTest measuring blood levels of thyroid hormone
§Serum T3, T4 ( free and bound) level
§Serum TSH level
§Serum PBI
§Plasma tyrosine level
§In vitro resin uptake of T3
CLASSIFICATION: based on function

32. vTestbaseduponthemetaboliceffectofthyroid
hormone
§BMR,
§Inserum:cholesterol,creatinine,uricacid,creatinekinaseand
calciumlevel.
vScanningandimagingofthyroidgland
vImmunologicaltestforautoantibodies
vOthers:biopsy,thyroglobulin,calcitoninetc.

33. 1. Test measuring blood levels of thyroid hormone
Reference of CLIA
•fT3: 1.21-4.18 pg/ml
•fT4: 8.9-17.2 pg/ml
•TSH: 0.3-4.5 µIU/ml
most popular so called thyroid panel in daily life ( lab)
ØCommonly used techniques are
•Competitive protein binding assay (CPBA)
•Radioimmunoassay (RIA)
•ELISA technique.
•CLIA technique.
•Immunofluorescent technique etc.
HypothyroidHyperthyroid
Serum. PBI↓↑
Plasma. tyrosine↓↑

36. At least remember
flow chart

37. 2. Test based upon the primary function.
v2.1 Radio iodine uptake study ( RIU)-“trapping of iodine”

39. cont.…2.2 TRH-Stimulation Test
vObjective:assess the functional integrity of thyrotropic
cells or the factors that influence the secretory response.
vProcedure :
•200 to 400 μg IV
•blood samples at 0, 20, 40 and 60 mins : TSH measurement.
vInterpretations
Normal:Peak response about 4 X basal TSH (20 and 40
minutes).
Pr. hypo: Response (exaggerated and prolonged).
Sec. hypo: Response (blunted).
Ter. Hypo: the increase in TSH is delayed.

40. 3. Based upon metabolic effects of TH hormones

42. 3. Scanning and imaging of thyroid gland
•visualization of the distribution of radioactive I in the
gland.
•Help us to
§Readily distinguishes the diffuse glandular activity from the patchy
pattern seen in nodular goiters
§Helps in functional classification of nodules as:
§–‘Hot’ or ‘warm’
§–‘Cold’ nodules
§Useful information regarding size, shape, positionof the gland.
§Facilitates identification and localization of functioning thyroid
tissues in “ectopic” or ‘Metastatic’ sites, e.g. in lungs and bones.

44. 4.Immunological test for auto antibodies

45. •Directedagainstthyroidandthyroidhormoneantigens
includingTG,TPO,thyroidmicrosome,TSHreceptor,TSH,
T4andT3
•Ofthese,TPOAbismostcommon,alsofoundinseraof
Type-1DM.
•AntimicrosomalAb:againstaproteinofthyroidcell
microsome.
•TSHRAb/TSI:bindtothyroidcellmembraneatornearTSH
receptorcite.
•Showsheterogeneity(increasesThinGrave’sdz)

47. Others: Thyroglobulin , 660kda
Mostly used as tumor marker or indicator to evaluate the effectiveness
•Thyroid cancer treatment process: Serial measurement to check recurrence, residual or metastasis ( still high). E.g. FC and PC.
•Determine complete thyroidectomy: no TG after complete thyroid gland removal.
•Low Tg: thyrotoxicosis factitia
•BUT NOT medullary carcinoma
•NOT useful as diagnostic tool of Th. Cancer

48. Calcitonin, 32aa, 3400 da
•Produced by C-cell of thyroid gland,
•T1/2 life: 12 min
•Increased : medullary thyroid carcinoma (MTC)
•Diagnosis even in early stage along with increased
carcinoembryonic antigen (CEA )
•monitor MTC recurrence.