THE THYROID GLANDTHEORY AND NUCLEAR MEDICINE PRACTICE
George N. Sfakianakis MDProfessor of Radiology and Pediatrics
Director, Division of Nuclear MedicineUM/JMMCMiami FL
October 2009
ENDONCRINE GLANDSRADIOISOTOPE IMAGING AND THERAPY
THYROID GLAND TRAPPING MECHANISM : 99mTc-04Na (γ)IODINATION: 123I (γ), 131I (β), 125I (Auger e-)METABOLISM: 18FDG, 201TI (x), 99mTcMIBI (γ)
PARATHYROIDS METABOLISM (K): 201TI(x), 99mTc-MIBI (γ)
ADRENAL CORTEX STEROIDOGENESIS: 131I(123I) CHOLESTEROL
ADRENAL MEDULLA NORADRENALIN SYNTHESIS: 131I(123I) MIBG
PITUITARY GLAND RECEPTORS: 18F-BROMOCTYPTINE111In- 99mTc-OCTREOTIDE
RVH (RENIN) ACE-INHIBITORS 99mTc-MAG3/LASIX
SOMATOSTATIN RECEPTOR IMAGING: 111In-OCTREOTIDE
EMBRYOLOGYOF THE
THYROID ANDPARATHYROID
GLANDS
THYROID ANATOMY VARIATIONS: SHAPE
THYROXINE AND TRI-IODOTHYRONINE
TRAPPING AND IODINATION
THYROID PHYSIOLOGY: T3,T4 RELEASE
TRH TSH FEEDBACK
THE THYROID GLAND RADIOISOTOPE STUDIES AND THERAPY
CONGENITAL (ACQUIRED) HYPOTHYROIDISMEtiology, PrognosisACUTE THYROIDITIS Diagnosis GOITERSSimple, Toxic, Multinodular Non-Toxic: DiagnosisNODULESNon-Functioning (Cold), Functioning, Toxic: Diagnosis THYROTOXICOSISGrave’s, Toxic Nodule(s): Diagnosis and TherapyTHYROID CANCERPrimary and Metastatic, Diagnosis and Therapy
THYROID GLAND CLINICAL CORRELATION
History and clinical Examination are essentialThyroid Hormonal Profile should be availableThe Thyroid Gland must be examined before
any attempt to interpret the scans
RADIOPHARMACEUTICALS
131INa, 123INa , 99mTcO4Na, 18FDG, 201TlCl, 99mTcMIBI,111In-OCTREOTIDE
STUDIES: THYROID GLAND UPTAKE AND IMAGINGTOTAL BODY IMAGING (METASTASIS)
THERAPY with 131INa : THYROTOXICOSISCARCINOMA
DOSIMETRY
RADIOISOTOPIC STUDIESOF THE THYROID GLAND
RADIO-IODINE UPTAKE BY THE THYROID
(4 and) 24hr thyroid uptake of 131/123 INa (for Therapy)
THYROID GLAND SCINTIGRAPHY131/123 INa or 99mTc04Na (Sodium Pertechnetate)
for functional Imaging
TOTAL BODY SCINTIGRAPHY FOR TUMOR131/123 INa Total Body Imaging
to detect Functioning Thyroid Cancer Metastasis
also18FDG, 201TlCl, 99mTcMIBI for non-functioning tumors
RADIOIODINE THYROID UPTAKE
5-10 µCi 131INa po; 24hr UPTAKE (with PROBE): 10-35%250 µCi 123INa po; (4-)24 hr UPTAKE (corrections ): 10-35%5-10mCi 99mTcO4Na iv; 30 min UPTAKE (with CAMERA): 3-5%
THE PROBE
THYROID SCINTIGRAPHY ANDTOTAL BODY SCINTIGRAPHY
PINHOLE COLLIMATOR PARALLEL HOLE COLLIMATORMagnified image of thyroid Total Body Imaging
NORMAL SCINTIGRAM NEONATE
500 µCi 99mTcO4Na IV: 30 min PINHOLE IMAGING
NORMAL SCINTIGRAM CHILD
500-100 µCi 99mTcO4Na IV: 30 min PINHOLE IMAGING123INa 100-200 µCi PO: 2-4hr PINHOLE IMAGING
NORMAL SCINTIGRAM ADULT
60µCi 131INa
123INa 250-500 µCi PO: 2-4hr PINHOLE IMAGING 131INa 60-100 µCi PO: 24h PINHOLE IMAGING
NORMAL SCINTIGRAM ADULT
99mTcO4Na 5-10 mCi IV: 30 min PINHOLE IMAGING
DRUG INTERFERANCE
a) Iodine contamination in any form, including radiographic contrast media
b) Exogenous Thyroxine for therapy or weight loss (thyrotoxicosis factitia)
THYROID GLAND STUDIES AND THERAPY
CONGENITAL HYPOTHYROIDISM
Etiology, Prognosis
GOITERS
Simple, Toxic, Multinodular Non-Toxic: Diagnosis
ACUTE THYROIDITIS
Diagnosis
NODULES
Non-Functioning (Cold), Functioning, Toxic: Diagnosis
THYROTOXICOSIS
Grave’s, Toxic Nodule(s): Diagnosis and Therapy
THYROID CANCER
Primary and Metastatic, Diagnosis and Therapy
Clinical and Laboratory Presentationfor the most frequent Indications Thyroid Scintigraphy
NEONATE• High TSH and/or Low T4 (Heel Stick)• Goiter by Clinical Examination• Suspicion of Hypothyroidism
INFANT/CHILD/ADULT• Hypothyroidism• Hyperthyroidism• Pain (Acute Thyroiditis)• Goiter• Nodule(s) • Thyroid Cancer
THYROID GLAND STUDIES AND THERAPY
CONGENITAL HYPOTHYROIDISM
Etiology, Prognosis
GOITERS
Simple, Toxic, Multinodular Non-Toxic: Diagnosis
ACUTE THYROIDITIS
Diagnosis
NODULES
Non-Functioning (Cold), Functioning, Toxic: Diagnosis
THYROTOXICOSIS
Grave’s, Toxic Nodule(s): Diagnosis and Therapy
THYROID CANCER
Primary and Metastatic, Diagnosis and Therapy
NON-TREATED NEONATAL
HYPOTHYROIDISM RESULTS IN CRETINISM
NEONATAL HYPOTHYROIDISM
INCIDENCE: 1:4000 LIVE BIRTHS
CRETINISM IS PREVENTABLE:
by neonatal screening for T4, TSH levels
and oral Thyroxine replacement therapy
PREVENTION IS COST EFFECTIVE:
it costs more to support a cretin
than to run the neonatal screening program
PRIMARY CONGENITAL HYPOTHYROIDISM
Diagnosis by Heal-stick
Blood Levels of T4 (low) and TSH (high)
Thyroxine Replacement Therapy
Prompt and full Dose
to prevent Cretinism and
to assure normal Development
Mental and Physical
PRIMARY CONGENITAL HYPOTHYROIDISM
Duration of Thyroxine therapy depends on the etiology
Transient Hypothyroidism:
Maternal Antibodies: Temporary therapy
Potentially Transient Hypothyroidism:
Dyshormonogenesis: Potentially Temporary therapy
Permanent Hypothyroidism:
Agenesis, Hypoplasia, Destruction: Lifelong Therapy
PRIMARY CONGENITAL HYPOTHYROIDISM
Stratification by Tc-PT Scintigraphy
Non-visualization:
( Maternal Antibodies or Agenesis )
Re-testing at 3yo after T4 withdrawal
Dyshormonogenesis:
Re-testing at 3yo after T4 withdrawal
Hypoplasia/Ectopia:
Therapy for Life
NORMAL SCINTIGRAM NEONATE
500 µCi 99mTcO4Na IV: 30 min PINHOLE IMAGING
A neonate with heal stick found
Decreased Thyroxine and
Increased TSH
NON VISUALIZATION OF THYROID
500 µCi 99mTcO4Na IV: 30 min PINHOLE IMAGING
NON VISUALIZATION OF THYROID
1) AGENESIS (developmental or auto-antibodies)
2) SUPPRESSION by maternal antibody
3) DESTRUCTION by 131I maternal treatment
4) TRH/TSH DEFICIENCY (low TSH in heel stick blood)
THERAPY
Immediate Thyroxine Replacement Therapy
Additional Hormonal Replacement ( #4)
At Age 3-5 Year Thyroxine withdrawal ( #2)
A neonate with heal stick found
Decreased Thyroxine and
Increased TSH
HYPOPLASIA + ECTOPIA ( lingual thyroid )
500 µCi 99mTcO4Na IV: 30 min PINHOLE IMAGING
HYPOPLASIA + ECTOPIA ( lingual thyroid )ECTOPIC ( RUDIMENTARY ) THYROID
ECTOPIA + HYPOPLASIA =
=CONGENITAL HYPOTHYROIDISM
IMMEDIATE THYROXINE REPLACEMENT THERAPY
FOR LIFE
A neonate with heal stick found
Decreased Thyroxine and
Increased TSH
DYSHORMONOGENESIS
Large Thyroid with high Tc-pt trapping
500 µCi 99mTcO4Na IV: 30 min PINHOLE IMAGING
DYSHORMONOGENESIS LARGE THYROID WITH HIGH Tc-PT TRAPPING
DYSHORMONOGENESIS (partial or total)
( trapping, organification, coupling or deiodination defect)
DEFECTIVE thyroglobulin synthesis or thyroxine release
ASSOCIATION WITH NERVE DEAFNESS
MAY APPEAR IN OTHER MEMBERS OF FAMILY
THYROXINE REPLACEMENT THERAPY PROMPTLY
AT 3-5 YEAR OF AGE THYROXINE WITHDRAWAL BECAUSE
SOME CASES RECOVER FUNCTION
HEARING PROBLEMS awareness and f/u
GENETIC COUNSELLING
A lady with a nodule high in the neck
Blood Thyroxine and TSH normal
THYROGLOSSAL DUCT CYST v/s ECTOPIA
22yo with a Single Nodule
She is Euthyroid
ECTOPICTHYROID GLAND
TcPT scan. Possibility #1
The only thyroid tissue she hasand should not be excised
THYROID ANATOMY VARIATIONS: ECTOPIA
THYROGLOSSALDUCT CYST
TcPT scan. Possibility #2
There is a normal thyroid gland; therefore the lesion (cyst) is not“the thyroid gland” and can safely be excised
THYROID GLAND STUDIES AND THERAPY
CONGENITAL HYPOTHYROIDISM
Etiology, Prognosis
GOITERS
Simple, Toxic, Multinodular Non-Toxic: Diagnosis
ACUTE THYROIDITIS
Diagnosis
NODULES
Non-Functioning (Cold), Functioning, Toxic: Diagnosis
THYROTOXICOSIS
Grave’s, Toxic Nodule(s): Diagnosis and Therapy
THYROID CANCER
Primary and Metastatic, Diagnosis and Therapy
GOITERS
ISSUES:Thyroid FunctionCosmeticCompression
A Euthyroid young ladyhas a goiter
SIMPLE GOITER
Enlargement of the gland with some asymmetry
TcPT thyroid scan
SIMPLE GOITER
TcPT thyroid scan
SIMPLE GOITER
• MORE FREQUENT IN YOUNG FEMALES
• MILD DEGREE OF DYSHORMONOGENESIS
(COMPENSATED BY) INCREASED TSH
• EUTHYROID OR MILDLY HYPOTHYROID
• THYROXINE REPLACEMENT (PARTIAL) THERAPY
USUALLY FOR COSMETIC PURPOSES
NON TOXIC MULTINODULAR GOITER
A 55 yo lady comes with a goiter and borderline low blood thyroid hormonal levels
NON TOXIC MULTINODULAR GOITER
The gland: nodular The salivary glands: relatively hyperactive
Enlargement and nodularity of the gland with relatively decreased TcPT accumulation (salivary gland enhancement)
NON TOXIC MULTINODULAR GOITER
I-131 Thyroid Scan
A 45 yo lady with enlargement of the right side of the thyroid gland
and some difficulty in swallowing
RETROSTERNAL NON TOXIC GOITER
TcPT thyroid scan
Enlargement of the right side of the thyroid gland andExtension of the gland into the mediastinum
NON TOXIC MULTINODULAR GOITER
MORE FREQUENT IN MATURE/ELEDERLY FEMALES
FOCAL DEGENERATIVE/FIBROTIC PROCESS
FOCAL PRESERVATION/HYPERTROPHY (NODULES)
EUTHYROID OR HYPOTHYROID (T4, TSH)
(EXCLUDE SUBCLINICAL SUPERIMPOSED GRAVE’S)
THYROXINE REPLACEMENT THERAPY
THERAPY OF THENON TOXIC MULTINODULAR GOITER
A. THYROXINE SUPPRESSION TREATMENT (T4 or T3)
B. THYROIDECTOMY SURGICAL (DECOMPRESSION)
C. LARGE DOSAGES OF RADIOIODINE 131INa
(200-300mCi on an inpatient basis)
THYROID GLAND STUDIES AND THERAPY
CONGENITAL (ACQUIRED) HYPOTHYROIDISM
Etiology, Prognosis
GOITERS
Simple, Toxic, Multinodular Non-Toxic: Diagnosis
ACUTE THYROIDITIS
Diagnosis
NODULES
Non-Functioning (Cold), Functioning, Toxic: Diagnosis
THYROTOXICOSIS
Grave’s, Toxic Nodule(s): Diagnosis and Therapy
THYROID CANCER
Primary and Metastatic, Diagnosis and Therapy
ACUTETHYROIDITIS
THYROIDITIS
Thyroiditis releases large quantities of T4+T3
The patient becomes thyrotoxic
But the thyroid gland is sick and the TSH suppressed:
There is little or no Iodine or Tc-pertechnetate uptake andThe Thyroid Gland is faintly or Not at all Visualized
Non-visualization of the gland
THYROIDITIS
ACUTE (SUBACUTE)
• Swelling and pain in the thyroid area
• Hyperthyroid (T4 release) or Euthyroid
• Antibodies
• Decreased RAI uptake
• Steroids and thyroxine replacement later
CHRONIC
• Different types, Diffuse or Focal
• Hypothyroidism
• Decreased uptake or Non-visualization
• Thyroxine replacement therapy
CHRONICTHYROIDITIS
HASHIMOTO’S THYROIDIS
Patient presents with hypothyroidism and a hard thyroid gland
HYPOTHYROIDISMOR
MYXEDEMA
ETIOLOGYOF
HYPOTHYROIDISM
CAUSES OF HYPOTHYROIDISM
WITHOUT GOITER
Congenital (Agenesis, Hypoplasia)
Resection - RAI - Trauma - Radiation
Secondary and Tertiary Hypothyroidism
(decreased pituitary TSH, or hypothalamic TRH)
WITH GOITER
Dyshormonogenesis (familial)
Iodoprivic (endemic)
Thyroiditis (acute or chronic)
Non-Toxic Multinodular Goiter
THERAPY OF HYPOTHYROIDISM
GOAL: TO ACHIEVE TSH LEVELS 0.03-3 µU/ml
DOSE: 0.1-0.2 THYROXINE per DAY
THYROID GLAND STUDIES AND THERAPY
CONGENITAL (ACQUIRED) HYPOTHYROIDISM
Etiology, Prognosis
GOITERS
Simple, Toxic, Multinodular Non-Toxic: Diagnosis
ACUTE THYROIDITIS
Diagnosis
NODULES
Non-Functioning (Cold), Functioning, Toxic: Diagnosis
THYROTOXICOSIS
Grave’s, Toxic Nodule(s): Diagnosis and Therapy
THYROID CANCER
Primary and Metastatic, Diagnosis and Therapy
A Patient with history of neck radiation for lymphoma
RADIATION EFFECT
Tc-PT scan
For Acne or a large Thymus Gland a practice of the 1940s and 1950swas to irradiate the neck
The Irradiated Thyroid Gland developed Nodules, Tumors and Fibrotic Changes
Atrophy of the left lobe
OPTIONS for the SINGLE THYROID NODULE
1. SCINTIGRAPHIC EVALUATION (99mTcPT, 123I SCAN): a) Normal activity: follow upb) No activity (cold): biopsy/surgery:
cancer 5%-20% (40% children) c) Increased activity (hot): 131i therapy (if toxic)
(issues: low specificity of “cold nodule”, few cancers have trapping function)
2. MEASURE TSH (T4)
a) Normal: biopsy (5% cancer)b) Decreased: thyroid scintigraphyc) Increased: evaluation for goiter
(issues: inconclusive, FP, FN. Solution: combine the 2 approaches)
3. ULTRASOUND: Useless, because even cystic lesions can harbor cancers
A 55 yo lady with incidentally found nodule
COLD NODULE Biopsy Indicated
The use of markers to identify the nodules
SOLITARY COLD NODULE
External Marker to outline the palpable nodule
Final Image
SOLITARY PALPABLE NODULE
COLD PALPABLE NODULE + A HOT NODULE NON-PALPABLE
What about this cold nodule?
A nodule is palpable. Is it a hot nodule?
COLD NODULE IN THE ISTHMUS
Use the marker
Without patient examination this scan may be read normal
But the patient has a palpable nodule at the middle line
GRAVE’S DISEASE WITH COLD NODULE
cold nodule
COLD NODULE (Tc-PT or 131/123I)Carcinoma 5-20% ( 40% in children) Solid + + +
Lymphoma or Metastatic tumor (rare) Solid + + +
Adenoma (frequent) Solid + + -
Fibrosis/Hemorrhage Solid? - - -
Cyst Cystic - - -
Cyst with Carcinoma Cystic + +/- +/-
Thyroiditis (rare) Solid - - -
Destroyed Toxic Nodule (hemorrhage) Solid? - - -
(To have correct Biopsy results you need to hit the lesion; US helps)
US FDG MIBI Biopsy
Differential Diagnosis of COLD NODULE
COLD NODULE WITH MIBI UPTAKE
99mTc-Pertechnetate 99mTc-Sestamibi
35yo female with “cyst” removal 8y ago and a right neck noduleFunctioning Nodule: Adenoma v/s Carcinoma
METASTATIC THYROID CANCER: PELVIS18F Deoxy Glucose Positron Emission Tomography
Patient with history of Pelvic Mass histologically mixed thyroid cancer s/p total thyroidectomy (normal thyroid) and 3 times RAI Therapy
High intensity FDG uptake in the area of the METASTATIC THYROID TUMOR
Image without attenuation correction
FDG PET IN METASTATIC THYROID CANCER
Patient with history of papillary thyroid cancer, sp thyroidectomy and X 3 treatment with RAI returns with a rib fractureCT: micronodular mets, chest wall and mediastinal masses
High intensity FDG uptake in LUNGS, a right RIB and the MEDIASTINUM c/w METASTATIC TUMOR
Image without attenuation correction
THYROID GLAND STUDIES AND THERAPY
CONGENITAL (ACQUIRED) HYPOTHYROIDISM
Etiology, Prognosis
GOITERS
Simple, Toxic, Multinodular Non-Toxic: Diagnosis
ACUTE THYROIDITIS
Diagnosis
NODULES
Non-Functioning (Cold), Functioning, Toxic: Diagnosis
THYROTOXICOSIS
Grave’s, Toxic Nodule(s): Diagnosis and Therapy
THYROID CANCER
Primary and Metastatic, Diagnosis and Therapy
All your patients have come with the diagnosis of thyrotoxicosis with high thyroxine and low TSH plasma levels
THYROTOXICOSIS
• DIFFUSE TOXIC GOITER
(GRAVE’S OR BASEDOW’S DISEASE)
• TOXIC NODULE
SINGLE
MULTIPLE (PLUMMER’S DISEASE)
• GRAVE’S DISEASE ON MULTINODULAR GOITER
• THYROTOXICOSIS FACTITIA
DIFUSE TOXIC GOITEROR GRAVE’S (BASEDOW’S) DISEASE
DIFFUSE TOXIC GOITER OR GRAVE’S (BASEDOW’S) DISEASE
Etiology: Autoimmune - Antibodies - Exophthalmos
Laboratory: Increased T4, T3, RAI Uptake, Low TSH
Thyrostatic Therapy: (PTU – TPZ) has Serious Side Effects
Scan: Enlarged Thyroid with Diffused Increased Activity
Radioactive 131 Iodine Therapy
(Low Doses 10-30 mCi Outpatient)
GRAVE’S DISEASE
Iodine Scan
Enlarged gland with Diffused Increased Activityand a Small Pyramidal Lobe
GRAVES DISEASE
Enlarged gland with Diffused Increased Activityand a Large Pyramidal Lobe. Rectilinear Scan
GRAVE’S DISEASE
Tc-99m Pertechnetate scan
Enlarged gland with Diffused Increased Activity
TOXIC NODULAR GOITER (SINGLE or MULTIPLE = PLUMMER’S DISEASE)
PRESENTATION
• Thyrotoxicosis- Benign Adenoma(s)
• No Exophthalmos or Pretibial Myxedema
• Nodule Palpable + Focal Increased Activity by Scintigraphy
• Increased T4, T3, RAI Uptake, Low TSH
THERAPY
• Surgical Removal of the Adenoma(s) (Dangers)
• Thyrostatic Therapy: (PTU – TPZ: Serious Side Effects)
• Radioactive 131 Iodine Therapy
(High Doses 30-300 mCi, inpatient basis)
TOXIC NODULE
The salivary glands
The hyperactive nodule
The suppressed gland
TOXIC ADENOMA: TSH STIMULATION
Is it indeed a toxic adenoma?
TSH injection (first effect)
TSH injection (full effect)
TOXIC NODULAR GOITERSPECTRUM OF PLUMMER’S DISEASE
TOXIC NODULAR GOITER
Suppressed left lobe
TOXIC NODULARGOITER
TOXICADENOMA
THERAPY OF THYROTOXICOSIS(131INa orally)
GRAVE’S DISEASE: 12-30 mCi
(7,000-25000 Rads) x (Weight in gr)(900) x (RAI Uptake %)
SINGLE TOXIC ADENOMA: 30-100 mCi
MULTINODULAR TOXIC GOITER: 30-150 mCi
mCi =
GRAVE’S DISEASE RAI TREATMENT and SIDE EFFECTS
POST THERAPY HYPOTHYROIDISM
SURGERY: 15% in 2 years + 1.8% per year
RADIOIODINE: 20-100% in 2 years ( 3% per year)
THERAPY: THYROXINE REPLACEMENT
GRAVE’S DISEASE RAI TREATMENT POST THERAPY HYPOTHYROIDISM
TOXIC NODULAR GOITER TREATMENT
NO SIDE EFFECTS
TOXIC ADENOMA
PRE THERAPY POST 131I THERAPY
The Normal thyroid gland
The effect of the nodule
The patient was treated with 29.2 mCi of I-131-Na. FU 8mo SP Therapy
TUMORS OF THE THYROID GLAND
Primary Thyroid Tumors:
Benign AdenomasNon-functioningHyperfunctioning (Toxic)
CarcinomasFollicularMixed PapillaryMedullaryUndifferentiated
Lymphomas primary
Metastatic Tumors
Parathyroid Tumors
TUMORS OF THE THYROID GLAND
131INa Tl-MIBI DMSA 111InOCTR 18FDG
Benign Adenomas Non-functioning - - - - -Hyperfunctioning + + - + +
CarcinomasFollicular + + - - +Mixed Papillary + + - - +Medullary - + + + +Undifferentiated - + - - +
Lymphomas primary - + - - +
Metastatic Tumors - + - - +
Parathyroid Tumors - + - - +
IMAGING OF CARCINOMAS OF THE THYROID
DIFFERENTIATED: 131INa Tl-MIBI DMSA 111InOCTR 18FDG
FOLLICULAR + (+) +
PAPILLARY (mixed) + (+) +
PAPILLARY (pure) - (+) +
UNDIFFERENTIATED:
MEDULLARY - (+) + + +
ANAPLASTIC - (+) +
Participation 8a
A patient with thyroid cancer is reevaluated
Thyroid CancerPrognosis following Total Thyroidectomy
Late Recurrences Even 20-30 years post diagnosis
Local Recurrence, Lymph Node or Lung Metastasis:Complete Response (Cure) with 131I Therapy
Skeletal Metastasis: Partial Response to 131I Therapy
Tumors with No 131I Uptake: External Beam Radiation and Chemotherapy :
Brief Partial ResponseResearch on Redifferention
STAGING TUMORS of the THYROID GLAND
PAPILLARY THYROID CANCERTNM STAGING
AGE AGE<45 >45
TUMOR SIZE: < 1 cm I I1-4 cm I II>4 cm II III
EXTRATHYROIDAL INVASION II IIICERVICAL NODES (+) I IIIDISTANT METASTASES III IV
PROGNOSIS for TUMORS of the THYROID GLAND
PAPILLARY THYROID CANCERTNM STAGE & PROGNOSIS
(Otuan ICEM 82:1997)
STAGE RECURRENCE (%) DEATH (%)
I 15.4 1.7
II 22 15.8
III 46 30
IV 66.7 60.9
OPTIONS in THYROID CANCER THERAPY
• Thyroxine (T4 or T3) Suppression Alone
• Surgical Resection and Thyroxine Suppression
• Resection, RAI Therapy, and Suppression :
(Tumors accumulating RAI: Papillary/Follicular)
• Resection, External Beam Radiation, Chemotherapy
(Tumors non-accumulating RAI)
THYROID CANCER THERAPYIMPACT OF 131I-THERAPY ON RECURRENCE & SURVIVAL
J Clin Endocrinol Metab 1992;75:714-720
131I THERAPY OF THYROID CANCERHAS NO SERIOUS COMPLICATIONS
(mean dose 195 mCi followed for a mean 18.7 yrs)
Lack of significant harmful effectsNo risk of leukemia(20 years experience - 1 year rest interval)No increased incidenence of second cancersNo decreased fertility in women or men No congenital anomalies in offspring
Acute and/or chronic sialoadenitis/gastritis/anorexia/loss taste
Azoospermia - transient
RECOMMENDED THERAPYFOR FUNCTIONING THYROID CANCER
1) Resection of Tumor and Total Thyroidectomy
2) Thyroid Gland Remnant Ablation (RAI)
3) Initiation of T4 Replacement/TSH Suppression
4) Post Therapy Total Body Scan
5) Follow up Clinical, Thyroglobulin, Imaging
6) Therapy with RAI in recurrence or metastasis
7) Alternative therapy if tumor does not respond to RAI
ADEQUATE SURGERY IS IMPORTANT:TOTAL THYROIDECTOMY
AND LYMPH NODE RESECTION
Recurrence after nodulectomy/Subtotal thyroidectomy > 40%
Lymph nodes in papillary carcinoma involved in high percentage
Death form invasion of superior thoracic inlet
High death rate form “AnaplasticTransformation”
Recurrence rate shown to be lower after total thyroidectomy and
Tumor may be Visualized by RAI scan and adequately treated
The larger the remnant (>5% uptake) the more difficult to ablate
Remnants may produce confusing high thyroglobulin levels
BENEFITS OF 131I ABLATION OF REMNANTS
• Increased sensitivity for search for metastases
(In 40% of pts with metastases outside neck, metastasis was detected
within 4 years post surgery)
• Ablation provides adjuvant therapy for occult metastasis
Lower death rate in group successfully ablated
( 3.1%, v/s 58.5% among those who have persistent remnants)
• It is important to achieve goals with One Dose because suboptimal
radiation Decreases Effectiveness of Therapy
INITIAL THERAPY WITH RADIO-IODINE( remnant ablation )
1) Resection of Tumor and (sub)Total Thyroidectomy
2) Endogenous or Exogenous TSH Stimulation
(a) 4-6 weeks off T4 or (b) Recombinant hTSH
3) (For Dosimetry only: Total Body RAI Scan)
(a) 131I: 2 -5 mCi, (b) 123I: 1-10 mCi
4) Thyroid Gland Remnant Ablation (RAI)
5) Initiation of T4 Replacement/TSH Suppression (day 2)
6) Post Therapy Total Body Scan (day 6-8)
Remarks on RAI Uptake by the Thyroid Gland and by the “Functioning” Tumors
Before Thyroidectomy
After Thyroidectomy
Normal Thyroid Tissue: 1% of dose per gram of tissue
Follicular or Mixed Papillary Cancerwith Low TSH: 0.01% of dose per gram = COLD NODULE
With High TSH: 0.1-1% of dose per gram = HOT SPOT(Thyroidectomy allows Imaging and Therapy)
(Other Tumors: Always No Uptake - Cold Nodule)
PATIENT PREPARATION FOR TOTAL BODY RADIOIODINE SCAN
AFTER THYROIDECTOMY FOR ABLATION
Wait until endogenous TSH levels rise>20µU/L
FOR TREATMENT OF RECURRENCE/METS
a) Thyroxine withdrawal until TSH rises
b) Use of Recombinant Human TSH (rhTSH)
Images of patients with follicular/papillary cancera) for evaluation Before Ablation
b) immediately (within 10 days) After Therapy c) or for recurrence
THYROID CANCER METASTASIS:Effect of Thyroidectomy on Iodine Uptake by Metastases
After Thyroidectomy
Before Thyroidectomy
Cancerous thyroid
Thyroid removed
TSH increased and stimulated the metastasis
Keeps TSH low
THYROID CANCER METASTASIS:Effect of bovine TSH on Iodine Uptake by Metastases
Metastases
Thyroid gland
Metastases
THYROXINE WITHDRAWAL SYMPTOMS
RECOMBINANT HUMAN TSHFOR THYROID CANCER IMAGING
Total Body 131I Imaging
RECOMBINANT HUMAN TSH (THYROGEN)PROTOCOL FOR TOTAL BODY 131I IMAGING
DOSE OF RADIO-IODINE 131INa po
A) Remnant Ablation
(a) Arbitrary/Empirical Dose: 150 mCi
(b) Dosimetric Evaluation Approach:
deliver 30,000 rads to Remnant
B) Therapy of Cancers Accumulating RAI :
(a) Arbitrary/Empirical Dose: 150-300 mCi
(b) Dosimetric Evaluation Approach
( i) Maximum Permissible Dose (200 rads - Marrow)
(ii) Less than 80mCi in lung metastases
(ii) Minimum Effective Dose (10,000 rads - Tumors)
THYROID CANCER THERAPY
TOTAL BODY 123/131INa SCINTIGRAPHY
The test of choice for functioning follicular, or mixed (follicular/ papillary)
thyroid carcinoma
Requires total thyroidectomy/ablation + 4-6weeks no therapy
or 4-6 weeks withdrawal of replacement thyroxine therapy
or patient preparation with Human Recombinant TSH
If positive uptake by tumor, patients are treated with large dosages of 131INa,
then placed on thyroxine suppression
Highest Sensitivity when large dose of RAI are given(stunning)
Thyroglobulin levels (Tg), a good marker for recurrence, or new metastasis.
Issue: Can Tg replace imaging?
Ablation: Preparation and Post Therapy
48 hours post I-123 Diagnostic 10 days post Ablation Therapy
Uptake in the remnantUptake in the remnant
Anterior PosteriorAnterior Posterior
Therapy of Recurrence
48 hours post Therapy 10 days post Therapy
Uptake in the recurrence Uptake in the recurrences
Patient A Patient B
Anterior PosteriorAnterior Posterior
Therapy of Diffuse Lung Metastasis
10 days post Therapy 10 days post TherapyUptake in the lungs Uptake in the lungs
Patient A Patient B
Anterior PosteriorAnterior Posterior
Images of patients with follicular/papillary cancera) for evaluation Before Ablation
b) immediately (within 10 days) After Therapy c) or for recurrence
IMAGING 7days post 131INa ABLATION THERAPY
These images are proof of effectiveness of RAI therapy
High RAI uptake in remnants in the thyroid bed
Salivary glands
Markers
THYROID CANCER:S/P (7days) ABLATION THERAPY (150mCi 131INa)
Skeletal MetastasisThyroid gland Remnants
Ant Chest and With markers
Post Chest Post Head
Ant Abdomen Ant Pelvis
Post Chest and Abdomen/Pelvis
IMAGING 7days post 131INa ABLATION THERAPY
High RAI uptake in the thyroid bed(in remnants and residual cancer),in the lungs and in the face
These images are proof of effectiveness of RAI therapy
FOLLOW UP AFTER RAI-ABLATION/RAI THERAPY
1) Effective Suppression of TSH
2) Clinical follow up Every 3 Months
3) Measurements of Thyroglobulin Every 3 Months
4) hrTSH/Tg stimulation test
OPTIONAL USE OF IMAGING
4) Total Body 131I/ 123I every 12 Months
5) Neck Ultrasonography every 6-12 Months
6) Chest X-rays (or CT, When Mets are Known)
Every 6 Months - 1 Year
7) Whole Body Imaging with 201Tl, MIBI, FDG
8) Therapy with Radioactive 131I if RAI scan positive
Total body 131I-Na scan for Reevaluation, 1 year after thyroidectomy and 150 mCi RAI Ablation Therapy
No evidence of abnormal accumulation
Total body 131I-Na scan for Reevaluation (high thyroglobulin), 1 year after thyroidectomy and 150 mCi RAI Ablation Therapy
Neck metastasis Lung Diffuse metastasis Stomach Bladder
Anterior Posterior
CANCER of the THYROID: FDG-PET and Iodine Scan
More positivethe FDG scan
PositiveIodine-131
Different lesions show
the Iodine-131 and the FDG
Participation 23
THYROID CANCER: IODINE v/s GLUCOSE Enters PET/CTPositive
Iodine scanPositive
FDG scan
Different lesions by the two different methods
THYMOUS GLAND VISUALIZATION 2-3%
• S/P 150 mCi 131-I Therapy
SERUM THYROGLOBULIN
• WITHOUT TUMOR POST THYROIDECTOMY LESS THAN 1 ng/ml
• ELEVATED WITH BOTH BENIGN AND MALIGNANT TISSUE
• PARTICULARLY WITH INCREASED TSH
• DETECTS ALSO NON FUNCTIONING METASTASIS
• IS HIGHER WITH BONE AND LUND METASTASIS
• ELEVATED IN 18% WITH NEGATIVE IODINE SCAN
• 44% POSITIVE SCANS HAVE THYROGLOBULIN < 2 ng/ml
• LOW Tg LEVELS WITH POSITIVE IODINE SCAN
THYROGLOBULIN LEVELS IN THYROID CANCER
THYROID CA FOLLOW UP AND THERAPY:THE THYROGLOBULINE APPROACH
Patient on Thyroxine Replacement for TSH Suppression
Follow-up Tg levels (with hrTSH stimulation) increased:
OPTIONS:
1. Imaging first and, if positive, RAI Therapy (300mCi)
2. RAI Therapy, then Imaging to see what was treated
3. RAI Therapy (300mCi), then TGB levels to see the effect
SENSITIVITY IN DETECTING THYROID CANCERTg LEVELS +/- hrTSH, Tg + SCAN on hrTSH
COMBINATION OF Tg AND RAI TOTAL BODY SCAN IS BEST FOR DETECTION OF RECURRENCES
THERAPY WITH RADIOIODINEOF RECURRENCE AND/OR METASTASIS
OPTION A
1. Positive for Tumor Total Body Scan after TSH Stimulation
(thyroxine withdrawal or rhTSH)
2. Dosimetry for Therapy or Empirical Therapy
3. High Dose RAI Administration (150rads MPD)
4. Reinstitution of T4 Replacement/TSH Suppression (Day 2-3)
5. Post Therapy Total Body Scan (Day 6-8)
6. Follow up Tg Levels post therapy
THERAPY WITH RADIOIODINEOF RECURRENCE AND/OR METASTASIS
OPTION B
1. No pretreatment RAI Total Body Scan is performed
2. High Dose RAI Therapy (150rads MPD) after TSH Stimulation
( T4 withdrawal)
3. Reinstitution of T4 Replacement/TSH Suppression (Day 2-3)
4. Post Therapy Total Body Scan (Day 6-8)
5. Follow up Tg Levels post therapy