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Jiraporn Sriprapaporn, M.D.Division of Nuclear Medicine   Department of Radiology         SIRIRAJ HOSPITAL
ANATOMY2 lobes connecting with“isthmus”Anterior to 2nd-4th trachealrings- C5-T1 vertebraeThyroid tends to increaseweight w...
THYROID HISTOLOGY   Thyroid capsule                                    Colloid Thyroid Follicles                          ...
PHYSIOLOGYHypothalamic-pituitary-thyroid axis              HYPOTHALAMUS                     TRH             PITUITARY GLAN...
Thyroid Hormone SynthesisIodide trapping - into follicular cells                                 PeroxidaseOrganification ...
Diagnosis of DiseasesClinical diagnosisLAB investigationNonradiological exam eg. U/S, MRIRadiological exam– Diagnostic Rad...
Nuclear Medicine StudiesRadiopharmaceuticals: radionuclide +/-compoundsRadionuclide*:- not stable and emitradiation with s...
THYROID FUNCTION TESTS:         INDICATIONS   Confirm clinical Dx   Exclude Dx in unexplained   clinical symptoms   Follow...
TERMINOLOGYTHYROID FUNCTION STATUS– Euthyroid state– Hyperthyroid state– Hypothyroid stateHYPERTHYROID STATE– Thyrotoxicos...
Definition: Thyrotoxicosis     vs HyperthyroidismThyrotoxicosis is the hypermetabolic conditionassociated with elevated le...
CAUSES OF THYROTOXICOSIS Common                    Rare  – Graves’ disease         – Trophoblastic tumors                 ...
DDx CAUSES OF THYROTOXICOSISDiagnosis       Thyroid       TFT           Antibodies   UptakeGraves’         Impalpable    H...
THYROID FUNCTION TESTSIN VITRO THYROID FUNCTION TESTSIN VIVO THYROID FUNCTION TESTS
IN VITRO THYROID FUNCTION TESTSThyroid Function            Thyroid Diseases                          Thyroglobulin (Tg) **...
INDICATIONSTo evaluate thyroid function– Hyperthyroid– Euthyroid– Hypothyroid : TSH*    High TSH   primary    Low or norma...
PHYSIOLOGYHypothalamic-pituitary-thyroid axis           HYPOTHALAMUS                  TRH          PITUITARY GLAND        ...
TYPES OF HYPOTHYROIDISM              TertiaryHypo          Hypothyroidism       TRHPitu              Secondary            ...
THYROID FUNCTION TESTSIN VITRO THYROID FUNCTION TESTSIN VIVO THYROID FUNCTION TESTS
IN VIVO THYROID FUNCTION TESTS Radioiodine uptake (RAIU)* Perchlorate discharge test Thyroid scan* I-131 Total-body scan (...
RADIOACTIVE IODINE UPTAKE(RAIU)Stop thyroid medications– Thyroxine for > 2 wks– Antithyroid drugs for > 1 wkIntake small a...
24-HR. RADIOACTIVE IODINE UPTAKE            Typical Curves of 24-hr Radioiodine Uptake%Uptake   80                        ...
RADIOACTIVE IODINE UPTAKE (RAIU):          INDICATIONSTo determine the cause of thyrotoxicosis*   The most useful role of ...
Causes of Thyrotoxicosis         Common Forms       (85-90% of cases)           RAIU over neck•   Diffuse toxic goiter (Gr...
Increased RAIUHyperthyroidismEnzyme defectsIodine deficiency or starvation
Decreased RAIUBlocked Trapping:             Parenchymal Destruction: – Iodine load***              – Subacute thyroiditis–...
Perchlorate Discharge Test Aim: To identify organification defects, most commonly involving the enzyme iodide peroxidase. ...
Perchlorate Discharge Test      Method & InterpretationUi = Baseline uptakePotassium perchlorate (KClO4) 300 mg is thenadm...
Perchlorate Discharge Test                 Discharge < 5%                 Normal, no org.                 defect          ...
Jiraporn Sriprapaporn, M.D.            Siriraj Hospital
Radionuclides for Thyroid ImagingRadionuclides          I-123             I-131             Tc-99mProduction            Cy...
Radionuclides forThyroid Imaging
Thyroid Scan: TechniquesTc-99m thyroid scan          I-131 thyroid scan – For routine use !!         – For special purpose...
Thyroid Scan: IndicationsAnatomical & functional evaluation of palpablethyroid nodules*-Solitary nodule ordominant N. (eut...
Normal Thyroid Scan    Tc-99m   I-123                     X
Ectopic Thyroid          Lingual thyroid  X
Thyroid Nodules:                Incidence of CA       Solitary nodule : 5-10%       Multinodular :1-7%       Hot nodule: 0...
Solitary Cold Nodule
Multinodular Goiter
Hot Nodule        S
Subacute Thyroiditis           Female (PJ), 40 yo           TFT:            –   T3=164.9 (80-180)            –   T4= 11.69...
Solitary Thyroid NodulesF:M = 4:1 but % CA in M > FCold nodules: Incidence of CA  upto 20%Warm nodules:    4%Hot nodules: ...
ATA Guideline 2009          1. TSH             1. Low     Thyroid scan                to R/O toxic                adenoma ...
Hot NodulesMostly are thyroid adenomaAutonomous function– not depend on TSH– not suppressed by T3                         ...
I-131 Total-body Scan (TBS):         IndicationsDetection of tumor recurrence or distantmetastases of thyroid carcinoma (D...
I-131 Total-body Scan (TBS):          TechniquesPatient preparation: Withdraw thyroid H (T4) 4-6wks prior to TBS, TSH > 30...
Negative I-131 TBS                         Off T4 = 4-6 wks, orThyroid          T              off T3 = 2 wks             ...
Thyroid Cancer with Lung       Metastasis           CA thyroid s/p TT           I-131 TBS (5 mCi):           Thyroid remna...
Other Radionuclide ImagingTumor SPECT/CT imaging – Tl-201 – Tc-99m MIBIPET/CT scan: F-18 FDG
Tc-99m MIBI vs Tl-201 SCAN  Non-specific tumor imaging  TSH level dose not affect tumor  uptake.  No thyroid H withdrawal ...
Tc-99m MIBI vs Tl-201 SCANRapid evaluation of tumor recurrence ordistant metastasis (PE, Tg, CXR, others)Helpful for risin...
Tc-99m MIBI vs Tl-201 SCANBetter image resolution      Poorer image resolutionShorter physical T 1/2       Longer physical...
I-131              Tc-99m MIBI & Tl-201Specific for thyroid     Nonspecific for thyroidtissue                   tissueGuid...
Tc-99m MIBI Whole-body Scan         Normal          Abnormal
A 62-year-old man withpapillary thyroid carcinoma                s/p total                thyroidectomy and               ...
I-131 TBS vs                  F-18 FDG PETAnterior   I-131   Posterior   MIP                Coronal PET                   ...
Thyroid 1_Thyroid function tests
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  1. 1. Jiraporn Sriprapaporn, M.D.Division of Nuclear Medicine Department of Radiology SIRIRAJ HOSPITAL
  2. 2. ANATOMY2 lobes connecting with“isthmus”Anterior to 2nd-4th trachealrings- C5-T1 vertebraeThyroid tends to increaseweight with age (N=20g)Arteries: Superior, inferiorthyroid A.Veins: Superior, middle, &inferior thyroid V.
  3. 3. THYROID HISTOLOGY Thyroid capsule Colloid Thyroid Follicles FFollicular cells: secrete hormones- T3 (triidothyronine), T4 (thyroxine)Parafollicular cells (C-cells): secrete hormone- calcitonin
  4. 4. PHYSIOLOGYHypothalamic-pituitary-thyroid axis HYPOTHALAMUS TRH PITUITARY GLAND TSH THYROID T3,T4 feedback
  5. 5. Thyroid Hormone SynthesisIodide trapping - into follicular cells PeroxidaseOrganification - Tyrosine + I - inactiveiodotyrosines: 3-monoiodotyrosine (MIT) & 3,5-diidotyrosine (DIT). incorporated into Tg &stored as colloid.Coupling– MIT + DIT T3– DIT + DIT T4Proteolysis or release - proteolysis of Tg producesthe active hormones T4 & T3, then secreted into theblood.
  6. 6. Diagnosis of DiseasesClinical diagnosisLAB investigationNonradiological exam eg. U/S, MRIRadiological exam– Diagnostic Radiology eg. X-ray, CT– Nuclear MedicineOthers
  7. 7. Nuclear Medicine StudiesRadiopharmaceuticals: radionuclide +/-compoundsRadionuclide*:- not stable and emitradiation with specific half lifeGamma rays imagingBeta rays treatment * Not stable Not used LOSS !
  8. 8. THYROID FUNCTION TESTS: INDICATIONS Confirm clinical Dx Exclude Dx in unexplained clinical symptoms Follow-up Screening for neonatal hypothyroidism
  9. 9. TERMINOLOGYTHYROID FUNCTION STATUS– Euthyroid state– Hyperthyroid state– Hypothyroid stateHYPERTHYROID STATE– Thyrotoxicosis– Hyperthyroidism
  10. 10. Definition: Thyrotoxicosis vs HyperthyroidismThyrotoxicosis is the hypermetabolic conditionassociated with elevated levels of FT4), FT3, orboth.Hyperthyroidism includes diseases that are asubset of thyrotoxicosis that is caused by excesssynthesis and secretion of thyroid hormone by thethyroid.(excludes exogenous thyroid hormone intake andsubacute thyroiditis)Most clinicians, exclusive of endocrinologists, usethe terms hyperthyroidism and thyrotoxicosisinterchangeably.
  11. 11. CAUSES OF THYROTOXICOSIS Common Rare – Graves’ disease – Trophoblastic tumors hCG – Toxic MNG Extremely rare – Toxic adenoma – TSH-secreting – Subacute thyroiditis pituitary tumor – Iatrogenic Drugs (factitious) – Amiodarone
  12. 12. DDx CAUSES OF THYROTOXICOSISDiagnosis Thyroid TFT Antibodies UptakeGraves’ Impalpable High T3 -ve or Increaseddisease or enlarged High T4 weakly +veToxic MNG Nodular High T3 Negative Increased High T4Toxic Hot nodule High T3 Negative Increasedadenoma High T4Subacute Impalpable High T3 Negative Reducedthyroidistis or enlarged High T4Iatrogenic or Impalpable High T4 but Negative Reducedfactitious T3 often N
  13. 13. THYROID FUNCTION TESTSIN VITRO THYROID FUNCTION TESTSIN VIVO THYROID FUNCTION TESTS
  14. 14. IN VITRO THYROID FUNCTION TESTSThyroid Function Thyroid Diseases Thyroglobulin (Tg) **T4 FT4 Thyroid AbT3 FT3 Anti Tg Ab- Hashimoto thyroidistis & DTCTSH Anti-microsomal or Anti- TPO Ab (TBII)- Hashimoto thyroidistis & Graves’ TSHR Ab or TSI- Graves’ LAB เคมีนิวเคลียร Techniques: RIA-IRMA* (I-125), ELISA, Electrochemiluminescence
  15. 15. INDICATIONSTo evaluate thyroid function– Hyperthyroid– Euthyroid– Hypothyroid : TSH* High TSH primary Low or normal TSH 2o or 3oTo DDx 2o vs 3o hypothyroidism– TRH stimulation test
  16. 16. PHYSIOLOGYHypothalamic-pituitary-thyroid axis HYPOTHALAMUS TRH PITUITARY GLAND TSH THYROID feedback T3,T4
  17. 17. TYPES OF HYPOTHYROIDISM TertiaryHypo Hypothyroidism TRHPitu Secondary Hypothyroidism TSH PrimaryThyr Hypothyroidism
  18. 18. THYROID FUNCTION TESTSIN VITRO THYROID FUNCTION TESTSIN VIVO THYROID FUNCTION TESTS
  19. 19. IN VIVO THYROID FUNCTION TESTS Radioiodine uptake (RAIU)* Perchlorate discharge test Thyroid scan* I-131 Total-body scan (I-131 TBS)
  20. 20. RADIOACTIVE IODINE UPTAKE(RAIU)Stop thyroid medications– Thyroxine for > 2 wks– Antithyroid drugs for > 1 wkIntake small amount of I-131Measure % of I-131 uptake atthyroid gland– Early uptake– Late uptake-24 hrNormal 24hr: 15%-45%(siriraj)
  21. 21. 24-HR. RADIOACTIVE IODINE UPTAKE Typical Curves of 24-hr Radioiodine Uptake%Uptake 80 Hyperthyroid Normal Rapid Turnover Hypothyroid 0 Hours after tracer dose I-131 24 hr
  22. 22. RADIOACTIVE IODINE UPTAKE (RAIU): INDICATIONSTo determine the cause of thyrotoxicosis* The most useful role of RAIU testTo confirm hyperthyroidismTo calculate therapeutic dose of I-131treatment
  23. 23. Causes of Thyrotoxicosis Common Forms (85-90% of cases) RAIU over neck• Diffuse toxic goiter (Graves disease) Increased• Toxic multinodular goiter Increased (Plummer disease)• Thyrotoxic phase of subacute Decreased thyroiditis• Toxic adenoma Increased
  24. 24. Increased RAIUHyperthyroidismEnzyme defectsIodine deficiency or starvation
  25. 25. Decreased RAIUBlocked Trapping: Parenchymal Destruction: – Iodine load*** – Subacute thyroiditis– Exogenous thyroid H Hypothyroidism: replacement*** – Primary or secondary – Endogenous ectopic (insufficient pituitary TSH thyroid H: Struma Ovarii secretion)Blocked Organification: – Surgical/RAI ablation of– Antithyroid medication thyroid (PTU): (Tc-99m uptake should not be affected)
  26. 26. Perchlorate Discharge Test Aim: To identify organification defects, most commonly involving the enzyme iodide peroxidase. Dyshormonogenesis Dyshormonogenesis Indications: Enlarged thyroid gland with hypothyroidism or elevated TSH Pendred’s syndrome: familial goiter and hearing loss
  27. 27. Perchlorate Discharge Test Method & InterpretationUi = Baseline uptakePotassium perchlorate (KClO4) 300 mg is thenadministered orally and a repeat measurement ofRAIU(Uf) performed in 60 mins.Mech: ClO4- is competitive with I- resultingwashout of I- from thyroid glandDischarge = {(Ui-Uf)/Ui}x 100– % Discharge < 5% => Normal, no org. defect– % Discharge > 5% => Positive for org. defect
  28. 28. Perchlorate Discharge Test Discharge < 5% Normal, no org. defect Discharge > 5% Positive for org. defect
  29. 29. Jiraporn Sriprapaporn, M.D. Siriraj Hospital
  30. 30. Radionuclides for Thyroid ImagingRadionuclides I-123 I-131 Tc-99mProduction 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 Active transport Active transport Trapping & Trapping & Trapping only organification organification
  31. 31. Radionuclides forThyroid Imaging
  32. 32. Thyroid Scan: TechniquesTc-99m thyroid scan I-131 thyroid scan – For routine use !! – For special purposes – 2 mCi TcO4- IV – 60-100 uCi I-131 is injected orally given – Imaging at 20 mins – Imaging at 24 hr. later later Withdraw T4 at least 2 wks before thyroid scan
  33. 33. Thyroid Scan: IndicationsAnatomical & functional evaluation of palpablethyroid nodules*-Solitary nodule ordominant N. (euthyroid vs hyperthyroid Pts)Evaluation of Pts w congenital hypothyroidismEvaluation of mediastinal mass; R/O substernalgoiterDetection of primary tumor in Pts with possiblethyroid cancer (eg.hoarseness of voice) or knownthyroid metastasisEvaluation of thyroid remnant post surgery
  34. 34. Normal Thyroid Scan Tc-99m I-123 X
  35. 35. Ectopic Thyroid Lingual thyroid X
  36. 36. Thyroid Nodules: Incidence of CA Solitary nodule : 5-10% Multinodular :1-7% Hot nodule: 0.43%(Decreased or absent function of entire lobe most likely thyroiditis)
  37. 37. Solitary Cold Nodule
  38. 38. Multinodular Goiter
  39. 39. Hot Nodule S
  40. 40. Subacute Thyroiditis Female (PJ), 40 yo TFT: – T3=164.9 (80-180) – T4= 11.69 (4.5-11.7) – TSH=0.05 (0.73-4) ESR= 110 (0-20) Sx: Thyroid enlargement off & on for 2 Mo – dev neck lump 3 Wks – 1 Wk dev pain and fatigue PE: Thyroid enlarged 3 cm Lt with firm-to-hard consistency and mild tenderness Scan: Poor or low uptake
  41. 41. Solitary Thyroid NodulesF:M = 4:1 but % CA in M > FCold nodules: Incidence of CA upto 20%Warm nodules: 4%Hot nodules: < 1-2%
  42. 42. ATA Guideline 2009 1. TSH 1. 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
  43. 43. Hot NodulesMostly are thyroid adenomaAutonomous function– not depend on TSH– not suppressed by T3 S50% ass. withhyperthyroidism
  44. 44. I-131 Total-body Scan (TBS): IndicationsDetection of tumor recurrence or distantmetastases of thyroid carcinoma (DTC)Localization of tumor evidence in Pts withrising Tg levelMonitoring the treatment of DTC
  45. 45. I-131 Total-body Scan (TBS): TechniquesPatient preparation: Withdraw thyroid H (T4) 4-6wks prior to TBS, TSH > 30 mIU/LDiagnostic dose of I-131: 2-5 mCi orally givenAnterior and posterior whole-body imaging at 72hrs laterTBS can also performed after 3-7 d of RAI Rxdose (post therapeutic TBS)
  46. 46. Negative I-131 TBS Off T4 = 4-6 wks, orThyroid T off T3 = 2 wks Oral adm. of 2-5 mCi I- 131 C Imaging at 48-72 hrBladder B Normal: salivary gland, nasal mucosa, stomach, bowel, bladder
  47. 47. Thyroid Cancer with Lung Metastasis CA thyroid s/p TT I-131 TBS (5 mCi): Thyroid remnant & bilat. lung metastases CXR: Negative Rx: RAI 150 mCi
  48. 48. Other Radionuclide ImagingTumor SPECT/CT imaging – Tl-201 – Tc-99m MIBIPET/CT scan: F-18 FDG
  49. 49. Tc-99m MIBI vs Tl-201 SCAN Non-specific tumor imaging TSH level dose not affect tumor uptake. No thyroid H withdrawal is required. Whole-body evaluation Easy and rapid interpretation SPECT acquisition
  50. 50. Tc-99m MIBI vs Tl-201 SCANRapid evaluation of tumor recurrence ordistant metastasis (PE, Tg, CXR, others)Helpful for rising Tg, negative I-131TBSDoes not guide for RAI treatment.
  51. 51. Tc-99m MIBI vs Tl-201 SCANBetter image resolution Poorer image resolutionShorter physical T 1/2 Longer physical T 1/2Higher dose can be used. Higher dose is limited.Better SPECT image quality Less impressive SPECTMore available (kit) image qualityLess expensive Limited availability More expensive (imported)
  52. 52. I-131 Tc-99m MIBI & Tl-201Specific for thyroid Nonspecific for thyroidtissue tissueGuide for future RAI Not guide for future RAIRx RxDelayed results Rapid results**Thyroid H withdrawal Thyroid H withdrawal isis needed. not necessary.**Higher radiation Lower radiationLower sensitivity* Higher sensitivity*
  53. 53. Tc-99m MIBI Whole-body Scan Normal Abnormal
  54. 54. A 62-year-old man withpapillary thyroid carcinoma s/p total thyroidectomy and cervical node dissection on 11-3-07 and resurgery on 14- 7-10 and 3 doses of RAI Rx last on 21-9- 10. Post-therapeutic I- 131 TBS on 24-9-10 was negative, while Tg was 662.2 ng/ml.
  55. 55. I-131 TBS vs F-18 FDG PETAnterior I-131 Posterior MIP Coronal PET NA 9-11-10
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