radionuclide studies and radioiodine therapies for thyroid diseases

In vivo Thyroid function Tests &

Radioiodine Therapy

Jiraporn Sriprapaporn, M.D. Division of Nuclear Medicine Department of Radiology Siriraj Hospital

THYROID_MD4_JIRAPORN_July 2015

Outlines

In-vivo Thyroid Function Tests

RAIU

Thyroid scan

I-131 total body scan

Radioiodine Therapy

Hyperthyroidism

Thyroid Cancer


I. In-vivo Thyroid Function Tests

RAIU

Thyroid scan


II. Hyperthyroidism

III. Thyroid Cancer

THYROID Outlines

Hypothalamic-pituitary-thyroid axis THYROID_MD4_JIRAPORN_July 2015

ROUTINE:

1. Begin with clinical history and physical examination.

2. In-vitro TFT (LAB)

If satisfied Definite Diagnosis Treatment

If not, What are you going to do?

Diagnosis of thyroid disorders


In-vitro TFT is equivocal.

In-vitro TFT does not get along with the clinical

context.

In-vitro TFT does not provide the information

needed.

When to perform in-vivo TFT?


Indications :

Confirm hyperthyroidism in case questionable serum TFT

DDx hyperthyroidism VS thyroiditis

Calculate RAI Rx dose for hyperthyroidism

Radiotracer : I-131 10 µCi, oral

Patient preparation :

Withdraw anti-thyroid drug for 1 wk.

Withdraw thyroid hormone at least 2 wk.

Avoid factors producing iodine overload :

• No prior contrast study 4-6 wk.

• No amiodarone, betadine, KI

Fasting ~ 2 hr.

Radioactive Iodine Uptake (RAIU)


Radioactive Iodine Uptake (RAIU)

Hypothyroid

Typical Curves of 24-hr Radioiodine Uptake

Normal

Hyperthyroid

Hours after tracer dose I-131 24 hr

% Uptake

80

0

Rapid Turnover


Normal: 15%-45% (Siriraj)

Increased uptake :

Hyperthyroidism

Iodine deficiency/ starvation

Others: early Hashimoto’s thyroiditis, rebound effect after discontinuing

antithyroid drugs, hypoalbuminemia (pregnancy, CKD, lithium, hCG)

Decreased uptake - 4 mechanisms

Block trapping : Iodine overload, exogenous iodine (thyrotoxicosis

factitia), endogenous iodine (struma ovarii)

Block organification : PTU, MMI

Parenchymal destruction : Subacute thyroiditis

Hypothyroidism : post-Sx, post RAI Rx, other causes

RAIU: Interpretation


Radiopharmaceuticals: Tc-99m & Iodine isotopes

Mechanism : iodine is more specific than Tc-99m

Indications for thyroid scan: ATA guideline

Tc-99m vs radioiodine

Patient Preparation

Imaging Techniques

Image Interpretation


Thyroid Scan

Radionuclides I-123 I-131 Tc-99m pertechnetate

Decay Electron capture Beta-minus decay Isomeric transition

T ½ 13 hrs. 8 days 6 hrs.

Energy keV 159 364 140

Radiation emitted only & β only

Localization by Active transport: Trapping & Organification

Active transport: T & Org Active transport: Trapping only

Administration Oral Oral IV

Dose 100-400 µCi 50-100 µCi 2 mCi

Imaging Time 3-4 hr. and/or 24 hr. 24 hr. 20 min.

Strength

-Test both trapping & organification -Pure gamma ray -No beta ray

-Test both trapping & organification -Substernal goiter

-Pure gamma ray -Rapid result, Low radiation

Weakness -Cyclotron produced not widely available

-Beta ray -Slow result

-Test only trapping function

Thyroid Scan: Radionuclides

ATA Guideline 2009:Thyroid Nodule

Thyroid nodule TSH

Low TSH Thyroid scan to

R/O toxic adenoma

Not low U/S –FNA to R/O

thyroid malignancy

If FNA suggests or

suspicious for malignancy

Surgery

ATA: American Thyroid Association

Cooper et al. THYROID 2009 THYROID_MD4_JIRAPORN_July 2015

Evaluate cause of hyperthyroidism in case presenting with a palpable thyroid nodule (suspected toxic adenoma)

Evaluate function of thyroid nodule in euthyroid patients : solitary or dominant thyroid nodule (suspected cold nodule or to R/O thyroid cancer)

Evaluate anatomy & location of thyroid gland: neonatal hypothyroidism, suspected ectopic thyroid

Tc-99m thyroid scan Indications


Evaluate substernal mass or mediastinal mass to

R/O substernal goiter

Planning for I-131 treatment : Differentiated

thyroid cancer (DTC). I-131 total body scan is

preferred.

I-131 thyroid scan Indications


Thyroid Scan: Techniques

Tc-99m thyroid scan

For routine use !!

2 mCi TcO4- IV injected

Imaging at 20 mins later

I-131 thyroid scan

For special purposes

60-100 uCi I-131 orally given

Imaging at 24 hr. later

Withdraw T4 at least 2 wks before thyroid scan


Normal Thyroid Scan

X Tc-99m I-123


Ectopic Thyroid

Lingual thyroid

X


Thyroid Nodules: Incidence of CA

Solitary thyroid nodule : 15-20%

Multinodular goiter :5%

Hot nodule: < 1%

REF: The Requisites, 4th edition, 2014 THYROID_MD4_JIRAPORN_July 2015

Solitary Cold Nodule


Multinodular Goiter


Hot Nodule

S

Autonomous nodule


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


Solitary Thyroid Nodules

F:M = 4:1 but % CA in M > F

Cold nodules: Incidence of CA upto 20%

Warm nodules: 4%

Hot nodules: < 1%


Indication: Differentiated thyroid cancer (DTC)

Evaluate residual thyroid tissue

Evaluate functioning metastasis

Evaluate treatment response

Patient preparation

Thyroid hormone withdrawal for 4 weeks TSH > 30 mIU/L

Low-iodine diet 1-2 weeks.

I-131 whole/total body scan


Technique

Diagnostic WBS/TBS

I-131 5 mCi oral

Imaging at 48-72 hr. later

Post-therapeutic WBS/TBS

- I-131 100-200 mCi oral for treatment

Imaging 3-7 days later

I-131 whole/total body scan


Normal : Physiologic uptake -thyroid tissue,

salivary glands, nasal mucosa, oropharynx, GI

tract, liver, urinary bladder, choroid plexus

Abnormal : tumor recurrence, metastasis (I-131

avid)

Interpretation


Negative I-131 TBS

Post total thyroidectomy and I-131 ablation

C = Colon

B = Urinary bladder

Thyroid bed

Bladder B

C


Intense uptake at thyroid bed residual thyroid

tissue or thyroid remnant.

Physiologic I-131 distribution

PostRx I-131 TBS


RxTBS: Multiple foci of uptake in the left thyroid bed, lungs, right humerus, ribs, acetabulum, and femurs

Follicular thyroid carcinoma with multiple bone metastases

Anterior Posterior


FTC PO & multiple RAI Rx with distant metastases

KW 27-2-2012


Planar RxTBS:

Thyroid remnant uptake

Faint uptake at right

upper medistinum

SPECT/CT:

A small Rt paratracheal

node with I-131 uptake

RxTBS in a thyroidectomized PTC Patient: SPECT/CT confirmed nodal met.

Sriprapaporn J, JMAT 2015


A 65-y-old woman with thyroidectomized PTC

Planar 131I imaging detected only 1 focus of radioiodine uptake, corresponding to residue in thyroglossal tract (arrow).

SPECT/CT image fusion (C) confirmed residue (arrow) but also showed 1 radioiodine-avid LN metastasis (arrow, D) in right submandibular region.

Diagnosis was confirmed at surgery to be PTC lymph node metastasis.

SPECT/CT confirm thyroglossal duct remnant & revealed Rt submandibular LN metas.

Spanu A, JNM 2009 THYROID_MD4_JIRAPORN_July 2015


RAIU

Thyroid scan


II. Hyperthyroidism

III. Thyroid Cancer

Contents


Terminology:

Thyrotoxicosis = increased thyroid hormones in the circulation, any causes.

Hyperthyroidism = Increased production of thyroid hormones

Cause of hyperthyroidism

Graves’ disease (diffuse toxic goiter)

Toxic multinodular goiter (Toxic MNG or Plummer’s disease)

Toxic adenoma (solitary autonomous nodule)

II. Hyperthyroidism


1. Medical treatment

2. Surgical treatment

3. Radioiodine treatment

4. Combined medical & RAI Rx **

Choices of Rx Hyperthyroidism


Antithyroid drugs Surgery I-131

Indication

1. Children, teenagers

2. Pregnant women

3. Not severe symptoms

4. Thyroid is not much

enlarged.

1. Marked thyroid enlargement with compressive symptoms ex. dysphagia, airways obstruction

2. Suspected coexisting thyroid cancer

3. Not respond to medical Rx & C/I for I-131 treatment

1. Severe A/E of ATD 2. Failed medical Rx 3. Relapse after medical Rx or

surgery 4. Poor compliance 5. Elderly 6. U/D eg. CAD, CHF

ขอ้ด ี

1. Available 2. Low cost

1. Rapid result 2. Immediate reduction of gland

size 3. High remission rate

1. Total cost is not high. 2. Painless 3. Gradual reduction of gland

size 4. Low side effect 5. High remission rate

ขอ้เสยี

1. Long-term administration

2. Low remission rate 3. Adverse drug effects:

fever, rash pruritus, arthralgia, hepatitis, agranulocytosis

1. High cost 2. Painful, needs hospitalization 3. May be impossible in cases

with lots of comorbid conditions.

4. Possible surgical complications eg. recurrent laryngeal n. injury

1. Radiation exposure 2. C/I pregnancy, lactating

women, small children 3. Slow action (few wks.) 4. Chance to develop

permanent hypothyroidism & needs long-life thyroid hormone replacement

Treatment options


Medical Treatment of Hyperthyroidism

Titrate the antithyroid drug dose every 4 weeks until thyroid

functions normalize.

Remission rate is ~ 60 % when therapy is continued for 2 years [15]

and the drug can be discontinued.

Notably, half of the patients who go into remission have a

recurrence of hyperthyroidism within the following year.

Nodular forms of hyperthyroidism (toxic MNG and toxic

adenoma) are permanent conditions and will not go into

remission. RAI Rx or surgery

eMedicine.com

15: Harper MB, Mayeaux EJ Jr. Thyroid disease. In: Taylor RB. Family medicine: principles and practice. 6th ed. New York: Springer, 2003:1042–52.


Radioactive Iodine Therapy

Radioactive iodine therapy [7] is the most common treatment for hyperthyroidism in adults in the United States.

Although the effect is less rapid than it is in antithyroid medication or thyroidectomy, it is effective and safe and does not require hospitalization.

eMedicine.com THYROID_MD4_JIRAPORN_July 2015

RAI Treatment for

Hyperthyroidism

RAI is widely used for > 70 yrs., since early 1940s

No evidence of increased risk to develop malignancies

I-131 solution vs capsule

I-131 solution is less expensive than I-131 capsule

No patient isolation/admission is necessary but precaution is

advised.

Need birth control for women in reproductive life during the

course of RAI treatment !!


RAI Treatment for Hyperthyroidism: Indications

Failed medical/surgical treatment-relapse

Serious adverse effects of antithyroid drugs: drug allergy,

agranulocytosis

Progressive enlargement of thyroid gland during medical therapy

Inconvenience for frequent contact

Poor compliance of medications

Poor socioeconomic problems

Presence of serious associated medical illness eg. heart failure THYROID_MD4_JIRAPORN_July 2015

RAI Rx for Hyperthyroidism: Contraindications

Pregnant

Lactating

Precaution: Severe hyperthyroidism


I-131 Dose Calculation

Dose determination - formula below

Gland size, % uptake, dose of I-131 /gram thyroid tissue

Other factors

Severity of hyperthyroidism

Types of hyperthyroidism: nodular* vs diffuse

Other clinical parameters

RAI Dose = [Thyroid mass (g) x 80-200 uCi/gm]/% uptake


RAI Rx Guideline for Hyperthyroidism

Stop antithyroid drugs for 5-7 days

24 hr. I-131 uptake

I-131 Rx dose according to calculation.

Combined medical Rx in severe thyrotoxic pts.

Peak result of RAI Rx needs about 3-4 months.

Long term F/U, monthly after 1st RAI Rx & reevaluate before reRx.

Repeat RAI Rx: usually 3-6 mo interval if still hyper.

Thyroid H. replacement if permanent hypothyroidism is developed.


Seem very low-nausea/vomiting is not common.

No increase in cancer incidence

Not cause infertility; mostly related to hyper- or hypothyroid conditions.

Sisson JC, et al. (2011). Radiation safety in the treatment of patients

with thyroid diseases by radioiodine 131I: Practice recommendations of the American Thyroid Association. From the American Thyroid Association Taskforce on Radioiodine Safety. Thyroid, 21(4): 335–346.

Side Effects of RAI Rx for Hyperthyroidism



RAIU

Thyroid scan


II. Hyperthyroidism

III. Thyroid Cancer

Thyroid


Classification of thyroid cancer

Well-differentiated thyroid cancer:

Derived from follicular cells uptake iodine ***

Papillary thyroid cancer (PTC) or mixed papillary-follicular,

Follicular (FTC), Hurthle cell carcinoma (variant of FTC)

Medullary carcinoma

Derived from C-cells does not uptake iodine

Undifferentiated or anaplastic thyroid cancer

III. Thyroid cancer


Types of Thyroid Cancer http://www.endocrineweb.com/guides/thyroid-cancer/incidence-

types-thyroid-cancer

Papillary Thyroid Cancer1-4

Most common type of thyroid cancer: 70% to 80% of all thyroid cancers are papillary thyroid cancer

Commonly diagnosed between the ages of 30 and 50

Females are affected 3 times more often than males

Usually not aggressive

Lymphatic spreading, but usually not beyond the neck

Papillary cells resemble finger-like projections

Tumor development can be related to radiation exposure

Follicular Thyroid Cancer1-4

Makes up about 10% to15% of all thyroid cancers

Often diagnosed between the ages of 40 and 60

Females are affected 3 times more often than males

Cancer cells may invade blood vessels and travel to other body parts such as bone or lung tissues (hematogenous spreading)

Follicular cells are sphere-shaped

Can be more aggressive in older patients

Medullary Thyroid Cancer1-4

Makes up about 5 % to 10% of all thyroid cancers

More likely to run in families and associated with other endocrine disorders

Develops from the C Cells or parafolicullar cells that produce calcitonin (regulates calcium and phosphate blood levels and promotes bone growth)

An elevated calcitonin level can indicate cancer

Often diagnosed between the ages of 40 and 50

Females and males are equally affected

Forms of medullary thyroid cancer include sporadic (not inherited), MEN 2A and MEN 2B (multiple endocrine neoplasia, genetic syndromes that involve other parts of the endocrine system), and familial (genetic, but not linked to other MEN-related endocrine tumors)

Anaplastic Thyroid Cancer1-4

Very rare—affects fewer than 5% of thyroid cancer patients

Usually occurs in patients older than 65 years

Females are affected more often than males

Aggressive and invasive

Least responsive to treatment

Anaplastic (anaplasia) means the cells lose normal structure and organization

References 1. National Cancer Institute. SEER Stat Fact Sheet: Thyroid Cancer. Available at: http://seer.cancer.gov/statfacts/html/thyro.html. Accessed October 28,

2013. 2. Thyroid Cancer page. National Cancer Institute, Web site. Available at: http://www.cancer.gov/cancertopics/types/thyroid. Accessed January 18, 2010. 3. Lal G, O'Dorisio T, McDougall R, Weigel RJ. Cancer of the Endocrine System. In: Abeloff MD, Armitage JO, Niedernuber JE, Kastan MB, McKenna WG,

eds. Abeloff's Clinical Oncology. 4th ed. Philadelphia, PA: Churchill Livingston; 2008. 4. Prinz RA, Chen E. Thyroid Cancer. In: Bope ET, Rakel RE, Kellerman RD, eds. Conn's Current Therapy 2010. Maryland Heights, MO: W. B. Saunders,

Elsevier; 2009.


http://www.endocrineweb.com/conditions/multiple-endocrine-neoplasia-men-types-1-2





Objectives:

Remnant ablation : To ablate thyroid remnant

facilitate detection of recurrent disease and tumor staging

Adjuvant therapy : To destroy suspected, but unproven metastasis

RAI therapy : To treat known persistent disease

I-131 treatment Targeted Therapy


Primary tumor (T)

TX Primary tumor cannot be assessed

T0 No evidence of primary tumor is found

T1 Tumor size ≤ 2 cm in greatest dimension and is limited to the thyroid

T1a Tumor ≤ 1 cm, limited to the thyroid

T1b Tumor > 1 cm but ≤ 2 cm in greatest dimension, limited to the thyroid

T2 Tumor size > 2 cm but ≤ 4 cm, limited to the thyroid.

T3

Tumor size >4 cm, limited to the thyroid or any tumor with minimal extrathyroidal extension (eg, extension to sternothyroid muscle or perithyroid soft tissues)

T4a

Moderately advanced disease; tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve

T4b Very advanced disease; tumor invades prevertebral fascia or encases carotid artery or mediastinal vessel


2010, 7th ed AJCC TNM Classification System for Differentiated Thyroid Carcinoma

Regional lymph nodes (N)

Regional lymph nodes are the central compartment, lateral cervical, and upper mediastinal lymph nodes:

NX Regional nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Regional lymph node metastasis

N1a Metastases to level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes)

N1b Metastases to unilateral, bilateral, or contralateral cervical (levels I, II, III, IV, or V) or retropharyngeal or superior mediastinal lymph nodes (level VII)

Distant metastasis (M)

M0 No distant metastasis is found

M1 Distant metastasis is present

http://emedicine.medscape.com/article/2006643-overview Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, et al. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer-Verlag; 2010.


Staging of Differentiated Thyroid Carcinoma

Papillary and follicular thyroid cancer (age < 45y):

Stage T N M

I Any T Any N M0

II Any T Any N M1

Papillary and follicular; differentiated (age ≥ 45y):

Stage T N M

I T1 N0 M0

II T2 N0 M0

III T3 N0 M0

IVA T1-3 N1a M0

T4a N1b M0

IVB T4b Any N M0

IVC Any T Any N M1

Table 1. ATA Strata for Recurrence Risk11

Risk Stratum Characteristics Risk for PD or recurrence (Tuttle RM 2010)

Low

•No local or distant metastases •All macroscopic tumor has been resected •No tumor invasion of locoregional tissues or structures •No aggressive histology (e.g., tall cell, insular, columnar cell carcinoma) or vascular invasion •If 131I is given, there is no uptake outside the thyroid bed on the first RxWBS

3 %

Intermediate

•Microscopic invasion of tumor into the perithyroidal soft tissues at initial surgery •Cervical lymph node metastases or 131I uptake outside the thyroid bed on the RxWBS done after thyroid remnant ablation •Tumor with aggressive histology or vascular invasion

21 %

High

•Macroscopic tumor invasion •Incomplete tumor resection •Distant metastases •Thyroglobulinemia out of proportion to what is seen on the RxWBS

68 %

11. 2009 ATA GUIDELINE http://online.liebertpub.com/doi/full/10.1089/thy.2009.0110 12. Tuttle RM, Tala H, Shah J, Leboeuf R, Ghossein R, Gonen M, Brokhin M, Omry G, Fagin JA, Shaha A. Estimating risk of recurrence in differentiated thyroid cancer after total thyroidectomy and radioactive iodine remnant ablation: using response to therapy variables to modify the initial risk estimates predicted by the new American Thyroid Association staging system. Thyroid. 2010; 20:1341-1349.



Management of DTC

SURGERY

RADIOIODINE Rx

HORMONAL Rx

Long-term Follow-up

Near-total or Total thyroidectomy

Cervical LN dissection for gross nodal enlargement

Lobectomy with isthmectomy: micropapillary CA,

unifocal, low-risk, no CLN metastasis followed by

TSH suppression (Result of treatment ~ Total

thyroidectomy with I-131 ablation)

Management of DTC:Surgery


Risk I-131 Dose

(mCi) Note

Low 30-100

* <30 mCi No admission required

* > 30 mCi Require admission for isolation

Intermediate-to-high 150-200

* LN, Lung metastasis – 150 * Bone metas. – 200 * Lung + Bone -150-200 // lung

uptake

I-131 Treatment Dose for DTC


1. Surgery, Not start thyroid hormone

2. Patho = DTC, planned for RAI Rx

3. 1-2 weeks: Tc-99m thyroid scan & 24-hr I-131 uptake to assess residual thyroid remnant

4. PO 4 weeks wo thyroid hormone medication, TSH > 30 mU/L : RAI Rx

5. Follow up with T4 (FT4), TSH, Tg, & TgAb, Tot calcium; CXR U/S, CT, PET/CT (as necessary)

6. Diagnostic TBS at 6-12 months after RAI Rx to see Rx response.

7. If DxTBS +ve another RAI Rx

Steps of Management of DTC

Tg = Tumor marker of DTC. Tg is most reliable when the Pt had total thyroidectomy followed by I-131 ablation. (no thyroid remnant) & no TgAb

Patient preparation: withdraw thyroxine for 4 weeks before RAI Rx

Low iodine-containing diet intake for 1-2 Wks.

Admission for patient isolation for 2-3 days.

On admission, prepare sour candies or fruits, etc to reduce I-131 retention in the salivary glands to reduce radiation

sialoadenitis.

Encourage water intake & frequent voiding after Rx esp. in the first few days to reduce radiation to bladder wall.

Laxatives in case with constipation to reduce radiation to

the bowel wall.

Avoid radioactivity contamination to the body and the room

RAI Treatment Procedure for DTC:


Thyroid Cancer with Lung Metastasis

PTC s/p total thyroidectomy

I-131 TBS (5 mCi): Thyroid remnant

& bilateral lung metastases

Tg = 65 ng/ml

CXR: Negative

Rx: RAI 150 mCi


Thyroid Cancer with Lung Metas. After one session of RAI treatment

ANT POST ANT POST


Negative physical examination

Negative DxTBS

Low stimulated Tg level, < 2

Negative neck U/S

Remission Criteria


Status/ TSH level (mIU/L)

Not Remission Remission

Low risk DTC 0.1-0.5 0.3-2

Non-low risk DTC < 0.1 0.1-0.5

Level of TSH recommended

NR: Thyroid hormone Rx = Suppressive dose Reference range of TSH : 0.27-4.20 mIU/L


Complications of RAI Treatment for DTC

Early complications

Acute radiation sickness: nausea/vomiting

Radiation thyroiditis

Acute sialoadenitis

Pain, hemorrhage & swelling in the metastases

Transient BM suppression

Late complications

Pulmonary fibrosis

Permanent BM suppression

Secondary primary malignancies: bone, GI cancer, colorectal, and salivary gland cancers, (// high accumulation dose) and leukemia.

Impaired male fertility [18832945] THYROID_MD4_JIRAPORN_July 2015

Summary of DTC Management

Total or near-total thyroidectomy

Suppressive dose of LT4 (If not in remission)

Small or Big dose (//staging & risk of recurrence)

Clinical Hx, PE, LAB TFT + Tg & TgAb, U/S, CT

SURGERY

RADIOIODINE Rx

HORMONAL Rx

Long-term Follow-up

radionuclide studies and radioiodine therapies for thyroid diseases

Health & Medicine

thyroid axisthyroid

thyroid hormone

function thyroid scan

rapid turnover thyroid

antithyroid drug

iodine overload

iodine isotopes mechanism

vitro tft lab