Jiraporn SriprapapornJiraporn Sriprapaporn,, MM..DD..Division of Nuclear MedicineDivision of Nuclear Medicine

Department of RadiologyDepartment of RadiologySIRIRAJ HOSPITALSIRIRAJ HOSPITAL

ANATOMYANATOMY

22 lobes connecting with lobes connecting with ““isthmusisthmus””Anterior to 2Anterior to 2ndnd--44thth tracheal tracheal ringsrings-- C5C5--T1 vertebraeT1 vertebraeThyroid tends to increase Thyroid tends to increase weight with age weight with age ((NN=20=20gg))ArteriesArteries:: SuperiorSuperior,, inferior inferior thyroid Athyroid A..VeinsVeins:: SuperiorSuperior,, middlemiddle,, &&inferior thyroid Vinferior thyroid V..

THYROID HISTOLOGYTHYROID HISTOLOGYThyroid capsule

Thyroid Follicles

Colloid

F

Follicular cells: secrete hormones- T3 (triidothyronine), T4 (thyroxine)Parafollicular cells (C-cells): secrete hormone- calcitonin

PHYSIOLOGYPHYSIOLOGY

HYPOTHALAMUS

PITUITARY GLAND

THYROID

T3,T4

TRH

TSH

HypothalamicHypothalamic--pituitarypituitary--thyroid axisthyroid axis

feedback

Iodide trappingIodide trapping -- into follicular cells into follicular cells OrganificationOrganification -- Tyrosine Tyrosine ++ II-- inactive inactive iodotyrosinesiodotyrosines:: 33--monoiodotyrosine monoiodotyrosine ((MITMIT)) && 3,53,5--diido diido tyrosine tyrosine ((DITDIT).). incorporated into Tg incorporated into Tg &&stored as colloidstored as colloid..CouplingCoupling–– MIT MIT ++ DITDIT TT33–– DIT DIT ++ DIT TDIT T44

Proteolysis or releaseProteolysis or release -- proteolysis of Tg produces proteolysis of Tg produces the active hormones Tthe active hormones T44 && TT3,3, then secreted into the then secreted into the bloodblood..

Thyroid Hormone SynthesisThyroid Hormone Synthesis

Peroxidase

DiagnosisDiagnosis of Diseasesof Diseases

Clinical diagnosisClinical diagnosisLAB investigationLAB investigationNonradiologicalNonradiological exam exam egeg. U/S, MRI. U/S, MRIRadiological exam Radiological exam –– Diagnostic Radiology Diagnostic Radiology egeg. X. X--ray, CTray, CT–– Nuclear MedicineNuclear Medicine

OthersOthers

Nuclear Medicine Studies

Radiopharmaceuticals: radionuclide +/-compoundsRadionuclide*:- not stable and emit radiation with specific half lifeGamma rays imagingBeta rays treatment

* Not stable Not used LOSS !

THYROID FUNCTION TESTSTHYROID FUNCTION TESTS::INDICATIONSINDICATIONS

Confirm clinical DxConfirm clinical DxExclude Dx in unexplained Exclude Dx in unexplained clinical symptomsclinical symptomsFollowFollow--upupScreening for neonatal Screening for neonatal hypothyroidismhypothyroidism

TERMINOLOGY

THYROID FUNCTION STATUS– Euthyroid state– Hyperthyroid state– Hypothyroid state

HYPERTHYROID STATE– Thyrotoxicosis– Hyperthyroidism

Definition: Definition: ThyrotoxicosisThyrotoxicosisvsvs HyperthyroidismHyperthyroidism

Thyrotoxicosis is the hypermetabolic condition associated with elevated levels of FT4), FT3, or both. Hyperthyroidism includes diseases that are asubset of thyrotoxicosis that is caused by excess synthesis and secretion of thyroid hormone by the thyroid. (excludes exogenous thyroid hormone intake and subacute thyroiditis)Most clinicians, exclusive of endocrinologists, use the terms hyperthyroidism and thyrotoxicosisinterchangeably.

CAUSES OF THYROTOXICOSISCAUSES OF THYROTOXICOSIS

CommonCommon–– GravesGraves’’ diseasedisease–– Toxic MNGToxic MNG–– Toxic adenomaToxic adenoma–– Subacute thyroiditisSubacute thyroiditis–– Iatrogenic Iatrogenic

((factitiousfactitious))

RareRare–– Trophoblastic tumors Trophoblastic tumors

hCGhCGExtremely rareExtremely rare–– TSHTSH--secreting secreting

pituitary tumorpituitary tumorDrugsDrugs–– AmiodaroneAmiodarone

DDx CAUSES OF THYROTOXICOSISDDx CAUSES OF THYROTOXICOSIS

Diagnosis Thyroid TFT Antibodies Uptake

Graves’ disease

Impalpable or enlarged

High T3 High T4

-ve or weakly +ve

Increased

Toxic MNG Nodular High T3 High T4

Negative Increased

Toxic adenoma

Hot nodule High T3 High T4

Negative Increased

Subacute thyroidistis

Impalpable or enlarged

High T3 High T4

Negative Reduced

Iatrogenic or factitious

Impalpable High T4 but T3 often N

Negative Reduced

THYROID FUNCTION TESTSTHYROID FUNCTION TESTS

IN VITRO THYROID FUNCTION TESTSIN VITRO THYROID FUNCTION TESTS

IN VIVO THYROID FUNCTION TESTSIN VIVO THYROID FUNCTION TESTS

IN VITRO THYROID FUNCTION TESTS

T4T3TSH

Thyroglobulin (Tg) **Thyroid Ab

Anti Tg Ab- Hashimoto thyroidistis & DTCAnti-microsomal or Anti-TPO Ab (TBII)- Hashimoto thyroidistis & Graves’TSHR Ab or TSI- Graves’

FT4FT3

Techniques: RIA-IRMA* (I-125), ELISA,

Electrochemiluminescence

LAB เคมีนิวเคลียร

Thyroid Function Thyroid Diseases

INDICATIONS INDICATIONS

To evaluate thyroid functionTo evaluate thyroid function–– HyperthyroidHyperthyroid–– EuthyroidEuthyroid–– Hypothyroid Hypothyroid :: TSH*

High TSH primaryLow or normal TSH Low or normal TSH 22oo or or 33oo

To DDx To DDx 22o o vs vs 33oo hypothyroidismhypothyroidism–– TRH stimulation testTRH stimulation test

PHYSIOLOGYPHYSIOLOGY

HypothalamicHypothalamic--pituitarypituitary--thyroid axisthyroid axis

HYPOTHALAMUS

PITUITARY GLAND

THYROID

T3,T4

TRH

TSH

feedback

TYPES OF HYPOTHYROIDISMTYPES OF HYPOTHYROIDISM

Secondary Hypothyroidism

Hypo

Pitu

Thyr

TRH

TSH

Tertiary Hypothyroidism

Primary Hypothyroidism

THYROID FUNCTION TESTSTHYROID FUNCTION TESTS

IN VITRO THYROID FUNCTION TESTSIN VITRO THYROID FUNCTION TESTS

IN VIVO THYROID FUNCTION TESTSIN VIVO THYROID FUNCTION TESTS

IN VIVO THYROID FUNCTION TESTSIN VIVO THYROID FUNCTION TESTS

Radioiodine uptake (RAIU)*

Perchlorate discharge test

Thyroid scan*

I-131 Total-body scan (I-131 TBS)

RADIOACTIVE IODINE UPTAKE RADIOACTIVE IODINE UPTAKE ((RAIURAIU))

Stop thyroid medicationsStop thyroid medications–– ThyroxineThyroxine for for >> 2 wks2 wks–– AntithyroidAntithyroid drugs for drugs for >> 1 wk1 wk

Intake small amount of IIntake small amount of I--131131Measure % of IMeasure % of I--131 uptake at 131 uptake at thyroid glandthyroid gland–– Early uptakeEarly uptake–– Late Late uptakeuptake--24 hr24 hr

Normal 24hr: 15%Normal 24hr: 15%--45% 45% ((sirirajsiriraj))

2424--HRHR.. RADIOACTIVE IODINE UPTAKERADIOACTIVE IODINE UPTAKE

Hypothyroid

Typical Curves of 24-hr Radioiodine Uptake

Normal

Hyperthyroid

Hours after tracer dose I-131 24 hr

%Uptake 80

0

Rapid Turnover

RADIOACTIVE IODINE UPTAKE RADIOACTIVE IODINE UPTAKE ((RAIURAIU):):INDICATIONSINDICATIONS

To determine the cause of To determine the cause of thyrotoxicosisthyrotoxicosis* *

The most useful role of RAIU test The most useful role of RAIU test

To confirm hyperthyroidism To confirm hyperthyroidism

To calculate therapeutic dose of ITo calculate therapeutic dose of I--131 131 treatmenttreatment

Causes of Causes of ThyrotoxicosisThyrotoxicosis

Common FormsCommon Forms(85(85--90%90% of cases)of cases) RAIURAIU over neckover neck

• Diffuse toxic goiter (Graves disease) Increased

• Toxic multinodular goiter (Plummer disease) Increased

• Thyrotoxic phase of subacute thyroiditis Decreased

• Toxic adenoma Increased

Increased RAIUIncreased RAIU

Hyperthyroidism Hyperthyroidism

Enzyme defectsEnzyme defects

Iodine deficiency or starvationIodine deficiency or starvation

Decreased RAIUDecreased RAIU

Blocked Trapping:Blocked Trapping:–– Iodine load***Iodine load***

–– Exogenous thyroid H Exogenous thyroid H replacement***replacement***

–– Endogenous ectopic Endogenous ectopic thyroid H: Struma thyroid H: Struma OvariiOvarii

Blocked Blocked OrganificationOrganification::

–– AntithyroidAntithyroid medication medication (PTU): (PTU): (Tc(Tc--99m uptake 99m uptake should not be affected)should not be affected)

ParenchymalParenchymal Destruction:Destruction:–– SubacuteSubacute thyroiditisthyroiditis

Hypothyroidism:Hypothyroidism:

–– Primary or secondary Primary or secondary (insufficient pituitary TSH (insufficient pituitary TSH secretion) secretion)

–– Surgical/RAI ablation of Surgical/RAI ablation of thyroidthyroid

Perchlorate Discharge Test

Aim: To identify organification defects, most commonly involving the enzyme iodide peroxidase.

Indications:Enlarged thyroid gland with hypothyroidism or elevated TSHPendred’s syndrome: familial goiter and hearing loss

DyshormonogenesisDyshormonogenesis

Perchlorate Discharge TestPerchlorate Discharge TestMethod Method && InterpretationInterpretation

UiUi = Baseline uptake= Baseline uptakePotassium Potassium perchlorateperchlorate (KClO(KClO44) 300 mg is then ) 300 mg is then administered orally and a repeat measurement of administered orally and a repeat measurement of RAIU(UfRAIU(Uf) performed in 60 ) performed in 60 minsmins. . MechMech: ClO4: ClO4-- is competitive with Iis competitive with I-- resulting resulting washout of Iwashout of I-- from thyroid glandfrom thyroid gland

Discharge Discharge == {({(UiUi--UfUf)/)/UiUi}}x x 100100–– % Discharge < % Discharge < 5%5% =>=> NormalNormal,, no orgno org.. defectdefect–– % Discharge > % Discharge > 5%5% =>=> Positive for orgPositive for org.. defectdefect

Perchlorate Discharge TestPerchlorate Discharge Test

Discharge Discharge << 5%5%NormalNormal,, no orgno org..defectdefect

Discharge Discharge >> 5%5%Positive for orgPositive for org..defectdefect

Jiraporn Sriprapaporn, M.D.

Siriraj Hospital

Radionuclides Radionuclides ffor Thyroid Imagingor Thyroid Imaging

Radionuclides I-123 I-131 Tc-99m

Production Cyclotron Reactor Reactor/GeneratorMode Of Decay Electron capture Beta decay Isomeric transitionPhysical T1/2 13 hours 8 days 6 hoursRadiation Emitted γ γ, β γGamma Ray Energy 159 keV 364 keV 140 keVDose 100-400 uCi 60-100 uCi 2 mCiRoute of Adm. Oral Oral IVImaging Property Yes Yes YesTreatment Property No Yes NoMechanism of Uptake Active transport

Trapping &organification

Active transportTrapping &organification

Active transport Trapping only

Radionuclides Radionuclides ffor or Thyroid ImagingThyroid Imaging

Thyroid ScanThyroid Scan:: TechniquesTechniques

TcTc--9999m thyroid scanm thyroid scan–– For For routineroutine use use !!!!–– 22 mCi TcOmCi TcO44

-- IV IV injectedinjected

–– Imaging at Imaging at 2020 mins mins laterlater

II--131131 thyroid scanthyroid scan–– For special purposesFor special purposes–– 6060--100100 uCi IuCi I--131131 is is

orally givenorally given–– Imaging at Imaging at 2424 hrhr..

laterlater

Withdraw T4 at least 2 wks before thyroid scan

Thyroid ScanThyroid Scan:: IndicationsIndications

Anatomical Anatomical && functional evaluation of palpable functional evaluation of palpable thyroid nodulesthyroid nodules**--Solitary nodule or Solitary nodule or dominant Ndominant N.. (euthyroid vs hyperthyroid Pts)Evaluation of Pts w Evaluation of Pts w congenital hypothyroidismcongenital hypothyroidismEvaluation of Evaluation of mediastinal massmediastinal mass;; RR//O O substernal substernal goitergoiterDetection of primary tumor in Pts with possible Detection of primary tumor in Pts with possible thyroid cancer thyroid cancer ((egeg..hoarseness of voicehoarseness of voice)) or known or known thyroid metastasisthyroid metastasisEvaluation of Evaluation of thyroid remnant post surgerythyroid remnant post surgery

Normal Thyroid ScanNormal Thyroid Scan

XTc-99m I-123

Ectopic ThyroidEctopic Thyroid

Lingual thyroidLingual thyroid

X

Thyroid NodulesThyroid Nodules::Incidence Incidence oof CAf CA

Solitary nodule Solitary nodule :: 55--10%10%

Multinodular Multinodular :1:1--7%7%

Hot noduleHot nodule:: 0.43%0.43%

(Decreased or absent function of entire lobe most likely thyroiditis)

Solitary Cold NoduleSolitary Cold Nodule

Multinodular GoiterMultinodular Goiter

Hot Nodule

S

Subacute ThyroiditisSubacute Thyroiditis

Female (PJ), 40 Female (PJ), 40 yoyoTFT: TFT: –– T3=164.9 (80T3=164.9 (80--180)180)–– T4= 11.69 (4.5T4= 11.69 (4.5--11.7)11.7)–– TSH=0.05 (0.73TSH=0.05 (0.73--4)4)

ESR= 110 (0ESR= 110 (0--20)20)SxSx: Thyroid enlargement off : Thyroid enlargement off & on for 2 Mo & on for 2 Mo –– dev neck lump 3 Wksdev neck lump 3 Wks–– 1 Wk dev pain and fatigue1 Wk dev pain and fatigue

PE: Thyroid enlarged 3 cm Lt PE: Thyroid enlarged 3 cm Lt with firmwith firm--toto--hard consistency hard consistency and mild tendernessand mild tendernessScan: Poor or low uptakeScan: Poor or low uptake

Solitary Thyroid NodulesSolitary Thyroid Nodules

FF::M M == 4:14:1 but but %% CA in M CA in M >> FFCold nodulesCold nodules:: Incidence of CA Incidence of CA

upto upto 20%20%

Warm nodulesWarm nodules:: 4%4%

Hot nodulesHot nodules:: << 11--2%2%

ATA Guideline 2009

1. TSH1. Low Thyroid scan

to R/O toxic adenoma

2. Not low U/S -FNA

2. If FNA suggests or suspicious for malignancy Surgery

Cooper et al. THYROID 2009

Hot Nodules

Mostly are thyroid adenoma

Autonomous function – not depend on TSH– not suppressed by T3

50% ass. with hyperthyroidism

S

II--131131 TotalTotal--body Scan body Scan ((TTBSBS):):IndicationsIndications

Detection of tumor recurrence or distant Detection of tumor recurrence or distant metastases of thyroid carcinoma metastases of thyroid carcinoma ((DTCDTC))

Localization of tumor evidence in Pts with Localization of tumor evidence in Pts with rising Tg levelrising Tg level

Monitoring the treatment of DTCMonitoring the treatment of DTC

II--131131 TotalTotal--body Scan body Scan ((TTBSBS):):TechniquesTechniques

Patient preparationPatient preparation:: Withdraw thyroid H Withdraw thyroid H ((TT4)4) 44--66wks prior to TBSwks prior to TBS,, TSH TSH >> 3030 mIUmIU//LLDiagnostic dose of IDiagnostic dose of I--131:131: 22--55 mCi orally givenmCi orally givenAnterior and posterior wholeAnterior and posterior whole--body imaging at body imaging at 7272hrs laterhrs laterTBS can also performed after TBS can also performed after 33--77 d of RAI Rx d of RAI Rx dosedose (post therapeutic TBS)(post therapeutic TBS)

Negative INegative I--131131 TTBSBS

Off TOff T44 == 44--66 wwksks,, or or off Toff T33 == 22 wwksksOral admOral adm.. of of 22--55 mCi ImCi I--131131Imaging at Imaging at 4848--7272 hrhrNormalNormal:: salivary glandsalivary gland,,nasal mucosanasal mucosa,,stomachstomach,, bowelbowel,,bladderbladder

Thyroid

Bladder

T

B

C

Thyroid Cancer Thyroid Cancer withwith Lung Lung MetastasisMetastasis

CA thyroid sCA thyroid s//p TT p TT II--131131 TBS TBS (5(5 mCimCi):):Thyroid remnant Thyroid remnant && bilatbilat..lung metastaseslung metastasesCXRCXR:: NegativeNegativeRxRx:: RAI RAI 150150 mCimCi

Other Radionuclide ImagingOther Radionuclide Imaging

Tumor SPECT/CT imagingTumor SPECT/CT imaging–– TlTl--201201–– TcTc--99m MIBI99m MIBI

PET/CT scan: FPET/CT scan: F--18 FDG18 FDG

TcTc--9999m MIBI vs Tlm MIBI vs Tl--201201 SCANSCAN

NonNon--specific tumor imagingspecific tumor imagingTSH level dose not affect tumor TSH level dose not affect tumor uptakeuptake..No thyroid H withdrawal is requiredNo thyroid H withdrawal is required..WholeWhole--body evaluationbody evaluationEasy and rapid interpretationEasy and rapid interpretationSPECT acquisitionSPECT acquisition

TcTc--9999m MIBI vs Tlm MIBI vs Tl--201201 SCANSCAN

Rapid evaluation of tumor recurrence or Rapid evaluation of tumor recurrence or distant metastasis distant metastasis ((PEPE,, TgTg,, CXRCXR,, othersothers))Helpful for rising TgHelpful for rising Tg,, negative negative II--131131TBSTBSDoes not guide for RAI treatmentDoes not guide for RAI treatment..

TcTc--9999m MIBIm MIBI vs vs TlTl--201201 SCANSCAN

Better image resolutionBetter image resolutionShorter physical T Shorter physical T 1/21/2

Higher dose can be usedHigher dose can be used..Better SPECT image qualityBetter SPECT image qualityMore available More available ((kitkit))Less expensiveLess expensive

Poorer image resolutionPoorer image resolutionLonger physical T Longer physical T 1/21/2

Higher dose is limitedHigher dose is limited..Less impressive SPECT Less impressive SPECT image qualityimage qualityLimited availabilityLimited availabilityMore expensive More expensive ((importedimported))

II--131131 TcTc--9999m MIBI m MIBI && TlTl--201201

Specific for thyroid Specific for thyroid tissuetissueGuide for future RAI Guide for future RAI RxRxDelayed resultsDelayed resultsThyroid H withdrawal Thyroid H withdrawal is neededis needed..Higher radiation Higher radiation Lower sensitivityLower sensitivity**

Nonspecific for thyroid Nonspecific for thyroid tissuetissueNot guide for future RAI Not guide for future RAI RxRxRapid resultsRapid results****Thyroid H withdrawal is Thyroid H withdrawal is not necessarynot necessary.**.**Lower radiationLower radiationHigher sensitivityHigher sensitivity**

TcTc--9999m MIBI Wholem MIBI Whole--body Scanbody Scan

Normal Normal

AbnormalAbnormal

A 62A 62--yearyear--old man with old man with papillary thyroid carcinomapapillary thyroid carcinoma

s/ps/p total total thyroidectomythyroidectomy and and cervical node cervical node dissection on 11dissection on 11--33--07 07 and and resurgeryresurgery on 14on 14--77--10 and 3 doses of 10 and 3 doses of RAI Rx last on 21RAI Rx last on 21--99--10.10.PostPost--therapeutic Itherapeutic I--131 TBS on 24131 TBS on 24--99--10 10 was negative, while was negative, while TgTgwas 662.2 was 662.2 ngng/ml./ml.

I-131 TBS vs F-18 FDG PET

Anterior I-131 Posterior MIP Coronal PET

NA 9-11-10