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