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    Maimun ZA

    Clinical Pathology Dept Medical

    Faculty Brawijaya Univ

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    Structure of thyroid follicle -Euthyroid follicle

    Thyroid C-cell

    Basal membrane of epithelialcellsApical membrane of epithelialcells

    Cuboidal epithelialcells

    Basementmembrane

    Colloid(glycoprotei

    n)

    Capillary(Rich blood

    supply)

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    Physiology

    The thyroid follicles secretes tri-iodothyronine(T)andthyro!in(T")synthesis in#ol#es combination ofiodine $ith tyrosine group to form mono and di-iodotyrosine $hich are coupled to form T andT"%

    The hormones are stored in follicles bound tothyrogobulin %

    &hen hormones released in the blood they arebound to plasma proteins and small amountremain free in the plasma %

    The metabolic e'ect of thyroid hormones are due tofree (unbound)T and T"%

    *of secreted hormones is T" but Tis the acti#ehormone so+ T"is con#erted to T peripherally%

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    Synthesis and libration of T and T" iscontrolled by thyroid stimulatinghormone(TS,)secreted by anterior pituitary

    gland%TS, release is in turn controlled by thyrotropin

    releasing hormone (TR,)from hypothalamus %Circulating Tand T" e!ert #e feedbac.

    mechanism on hypothalamus and anterior

    pituitary gland %So+ in hyperthyroidism $here hormone le#el in

    blood is high +TS, production is suppressedand #ice #ersa

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    Hormone properties T4

    T3

    Total serum concentrations / 0g1dl %2"0g1dl

    3raction of total hormone in

    free form (serum)

    %4 * % *

    3ree (unbound hormone) inserum

    42 5 2-24

    67 5 2-24

    6

    Serum half life 8 d %89 d

    3raction directly from thethyroid

    2 * 4 *

    Production rate+ includingperipheral con#ersion

    0g1d 4 0g1d

    :ntracellular hormone fraction ; 4 * ; 8 *

    Characteristics of Circulating T"

    and T

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    3unctions

    ofthyroid hormones

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    3unctions of thyroid hormones

    Generally, THs:

    2% :ncreases metabolic rate% Stimulates increased

    consumption of glucose+ fattyacids and other molecules%

    4% :ncreases metabolic heat+ by mitochondrial no < acti#ity ATP+

    % Stimulates rate of cellularrespiration by=

    Production of uncouplingproteins%

    :ncrease acti#e transport by>a? @? um s%

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    "% >ecessary for normal gro$th recycle synthesis of !IT< ITaccumulate%

    !IT< IT$ill not be used for ne$T,s formation

    THs%

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    ::= ,ypothyroidism (my!edema) cont%

    Symptoms o Hypothyroidism:- Jecreased metabolic rate%

    - Slo$ heart rate < pulse% - Slo$ muscle contractions

    - appetite+ $eight gain+ eed to loo. for other pituitarydeMciencies%

    :f TS, is h < 3T" < 3T are normal $e call this condition

    s$'clinical hypothyroidism

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    ::= ,ypothyroidismChildren (Cretinism)

    ,ypothyroidism in childrenT,s%

    ,ypothyroid from end of 2st

    trimester to 7 monthspostnatally+ or in the 2stfe$

    years of life%

    T3< T4ree! TSH% %dditional Si"ns * Symptoms:

    + Se#ere mental retardation% + Short stature (due to gro$th of

    bones+ muscle+ < brain)%

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    Thyroid >odule

    ery common

    7 years old Q "%4* ( Palpation)

    2 78* by ultrasound

    Autopsy Q 9*

    Thyroid Cancer is rare Q " 1 2+

    cult thyroid cancer in 7 4" *autopsy

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    Thyroid >odule 4

    Thyroid nodule #ery common

    Thyroid cancer #ery rare butcurable

    AIM IS NOT MISS THYROID CANCER

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    Thyroid nodule Risk factors

    E!posure to radiation as child

    3amily history

    Lnder 4 years

    #er 7 years

    O male se!

    ,ourseness

    3i!ed hard nodule Similar ris. for multinodular and

    single nodule

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    Thyoid >oduleInvesigations

    T3Ts

    Lltra sound scan

    Thyroglobulin and Calcitonin notrecommended ( LS uidelines)

    3ine needle Aspration(3>A)

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    ,ashimotoDs Thyroiditis

    Symptoms * Si"ns:

    Lsually presents $ith goitre in a patient $ho iseuthyroid or has mild hypothyroidism

    Se! distribution= four females to one maleThe process is painless

    lder patients may present $ith se#erehypothyroidism $ith only a small+ Mrm atrophicthyroid gland

    Transient symptoms of thyroto!icosis can occurduring periods of hashito!icosis (spontaneously

    resol#ing hyperthyroidism)

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    ,ashimotos Thyroiditis

    a': >ormal or lo$ thyroid hormone

    le#els+ and if lo$+ TS, is ele#ated

    ,igh Tg Ab and1or TP Ab titres 3>A b! re#eals a large inMltrationof lymphocytes PKLS ,urthle cells

    -omplications:

    Permanent hypothyroidism (occursin 2-29* of young pts)

    Rarely+ thyroid lymphoma

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    Thyroid 3unction Tests

    TS, Thyro!ine (T") (free 1 total)

    Ttriiodothyronine (T) (free 1 total)

    Thyroid Antibodies= Autoimmune

    thyroid disease is detected bycirculating antibodies against TP andTg%

    :maging

    Thyroid Lltrasound scan

    Thyroid :sotope Scan

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    uidelines The diagnosis of primary hypothyroism

    reuires the measurement of both TS, andT" Patients $ith type-2 diabetes should ha#e a

    chec. of thyroid function included in their

    annual re#ie$% Patients $ith type-4 diabetes

    should ha#e their function chec.ed atdiagnosis but routine annual thyroid functiontesting is not recommended

    Patients stabilised on long term thyro!ine

    treatment should ha#e TS, chec.ed annually

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    uidelines The thyroid status of hypothyroid patients

    should be chec.ed $ith TS, ? T" during eachtrimester:deally the follo$ing seuence of T3T should be

    performed in the hypothyroid $omen duringpregnancy

    Before conception At time of diagnosis of pregnancy At antenatal boo.ing At least once in 4ndand rdtrimester Again after deli#ery at 4 " $ee.s post partum

    >e$ly diagnosed hypothyroid $ill need testinge#ery " 7 $ee.s until stable

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    Thyroid Antibodies

    Thyroid Pero!idase(thyroid microsomal)

    100% in Hashimato thyroiditis

    87% with graves disease

    Thyroglobulin Antibody 76% of Graves Disease

    Thyroid receptor antibody

    Normally resent in 1! "18 % offemale o#lation

    6 TS,

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    6easure TS,

    Ele#ated

    >ormal

    6easure unbound T" Pituitary disease

    suspected

    >ormal yes>oKo$

    6ild

    hypothyroidism

    Primaryhypothyroidi

    sm

    >o

    furthertest

    6easure

    unboundT"

    TP Ab(?)or

    symptomatic

    TP Ab(-)

    or no

    symptoms

    TPAb(?)

    TPAb (-)

    >o

    furthertest

    >ormal

    Ko$

    Rule out drug e'ects+sic. euthyroid

    syndrome+ then

    E#aluate anterior

    Rule out othercauses of

    hypothyroidismAutoimmune

    hypothyroidismT" treatment

    Annual follo$up T" treatment

    Application of TS, e!amination

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    I-%s. /01

    ioassayary insensitiityInconinient

    RI%sSensitiity 1m$-ross reaction . 15Hypothyroid

    IR%sSensitiity

    1/ + 2// x RI%s Hypo 6e$thyroid

    HyperthyroidTSH /0/7 + /011m$

    8$thyroid/04 9 40/

    Hypothyroid4 m

    !etection

    Imm$noassayI : 7 9 ; m

    II: /01 9 /02

    Imm$noassayIII:/0/1 9 /0/2

    I: /0//1 9 /0//2

    I II

    Application of TS, e!amination

    Autoimmune Thyroiditis (A:T)

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    AutoimmuneThyroiditis (A:T)

    Anti Tg

    Cytoplasma

    follicular

    Complemen

    t acti#ation

    (-)

    Anti TP

    29 .Ja+ microsomal

    Thyroid pero!idase

    enNyme

    Pos correlation= anti TP

    < PPTJ

    Complement acti#ation

    (?)

    AntiTS,-R

    ,yperthyroid

    ,ypothyroid :n J

    Ab bispeciMc= Ab TP more freuent < higher than ant

    nly anti TP (?)= rare

    Anti TP < anti Tg in J= not established (discussion)

    Routine detection Ab thyroid= only anti TP

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    Ab

    bispeciMcPPTJ= 27 *

    > population= 2%"

    *

    Pre#alence of anti

    TPPPTJ (post partum

    thyroiditis)= 27 *

    ra#eDs disease= "%7 *

    ,asimoto thyroiditis= "%9 *Anti TP < A:T

    Clinical rele#ancy= not clearly

    Correlation $ith acti#e clinical

    disease

    Strong correlation $ith ris. of

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    Anti TP for predict PPTJ

    ariation of sensiti#ity < speciMcity

    Jepend on $hen anti TP e!amined

    PPTJ (-) $hen anti TP (-)

    Screening anti TP in early pregnancy

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    Serum Tg E!amination

    >ot distinguished= PPTJ < J

    :nterference= serum anti Tg

    (reaction of anti Tg ? anti Tg

    antibody in immunoassay .it)+

    e!amination simultaneously Tg? anti Tg

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