Thyroid Anatomy/Physiology/Thyroid scintigraphy principles

NMT631

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Thyroid - position

• The thyroid is a butterfly shaped gland that sits in front of the trachea, midway between the thyroid cartilage (“Adam’s apple”) and the top of the sternum

Supra Sternal Notch

SSN

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Thyroid - Anatomy

A. Normal Adult Thyroid weighs 20-25g

B. Components

1) Two Lateral lobes 2) Isthmus centrally connects the

lobes

3) A Pyramidal lobe in 50% of the population

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Thyroid – Cellular Anatomy

• Epithelial cells arranged in spheres called thyroid follicles.

• Follicles are filled with colloid - Contains two active hormones, T3 and T4- bound to thyroglobulin

• Parafollicular or C cells secrete hypercalcemia hormone calcitonin.

Microscopic structure of Thyroid follicles

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Thyroid Hormone Synthesis1) Absorption

2) Trapping

3) Organification

4) Coupling

5) Release

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Absorption

• Typical diet contains 300 -1000 μg of Iodine/day

• Iodine ingested in food is reduced to iodide, then absorbed into the blood

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Trapping – Iodide pump/trap

• Iodine Pump:

30-50% of the circulating iodine taken up (rest lost in urine)

“Iodine trapping” achieved by active transport (iodide pump).

Iodide pump works against both electrical and concentration gradients.

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Trapping

• Iodide then trapped by follicular cells

• Trapped iodide ions are oxidized by peroxidase enzyme.

IP – Iodide Pump

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Organification – Thyroglobulin’s (TG) role

• TG is a large protein in the colloid

• It has 140 molecules of aminoacid tyrosin used for thyroid hormone synthesis

• Synthesis takes place within the TG molecules in the colloid.

• The trapped iodine is now capable of combining with tyrosine

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Organification• Iodine is linked to tyrosine (an amino acid) on thyroglobulin molecule

• Iodine + tyrosine MIT & DIT

MIT = monoiodotyrosine DIT = diiodotyrosine

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Coupling• With the help of an enzyme, MIT and DIT combine to

form T3 and T4 (thyroxine)

MIT + DIT T3

DIT + DIT T4• Both hormones are stored in thyroid follicular cells and bound to thyroglobulin

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Release• In response to TSH (thyroid stimulating hormone),

T3 and T4 split from thyroglobulin to be sent into the circulation

Steps:

1) TG taken up by thyroid cells by pinocytosis

2) Lysosomes digest thyroglobluin, thereby liberating T3, T4, MIT & DIT.

3) Fee thyroid hormones (T3 & T4) diffuse out through the cell membrane into blood

4) In the circulation, T3 and T4 are bound to TBG (thyroxine-binding globulin)

5) MIT & DIT are deiodinated by an enzyme and is recycled.

13 TSH stimulates iodide trap, thyroid hormone synthesis & release

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Thyroid Hormone synthesis - Summary

• A normal thyroid produces about 10x more T4 than T3

Concise Human Physiology M. Y. Sukkar, H. a. El-Munshid, M. S. M. Ardawi

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Thyroid hormone regulation

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Thyroid Hormone Regulation

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Hypothalamus – Pituitary – Thyroid feedback system

• The activity of the thyroid gland regulated by neuroendocrine negative feedback loop

• maintains a stable amount

of thyroid hormones in the circulation.

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THYROID IMAGING

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Thyroid Imaging

Clinical Indications

Radiopharmaceutical used

Dosage & Administration

Technique

The Normal Scan

Artifacts & Pitfalls

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1) Relate structure to function

2) Evaluation of thyroid nodules

3) Location of ectopic tissue

4) Follow-up exams (post therapy, post surgery)

Clinical Indications

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1) Tc-99m pertechnetate

2) I-123 sodium iodide

3) (I-131 sodium iodide)

Radiopharmaceuticals used

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1) Tc-99m Pertechnetate (99mTcO4-)

• Can substitute for iodide in the iodide transport channel in follicular cells

• Trapped but not organified• Released from cells over time

Radiopharmaceuticals used

• Only 1– 5% of injected dose trapped (↑ Bkg) • Ideal physical characteristics (140keV; T1/2 - 6hrs) • Readily available & cheap• Low dose to thyroid• Preferred over iodine when:

- patient on thyroid blocking agents- patient unable to take meds orally- study must be completed in < 2hrs

Dosage & Administration

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Drugs - hyperthyroidism:• Propylthiouracil • Tapazole® (methimazole)

Drugs - hypothyroidism: • LEVOTHROID®/ SYNTHROID ®

(synthetic T4)• Cytomel® (synthetic T3)

Thyroid drug abstinence before imaging

(blocks thyroperoxidase)

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123I Sodium iodide (Na123I)• Trapped & organified

• 159keV gamma emission and excellent trapping makes it ideal imaging agent with low background

• Cyclotron produced (↑ cost, problems with availability & delivery)

• 200-600 μCi capsules

• T1/2 - 13 hrs; maximum uptake at 24hrs

Radiopharmaceuticals usedDosage & Administration

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131I Sodium Iodide (Na131I)

• Same uptake principles as Na123I

• Used for imaging (50 – 200 μCi) & therapy

• β emission & T1/2 of 8 days - ↑ radiation dose to thyroid (disadvantages for imaging/ advantages for therapy followed by delayed imaging)

• 364keV gamma emission used for imaging

• High energy collimator required

• ↓ cost & readily available

medic.usm.my

Administered as solution (Tx) or capsules (Dx/Tx)

Radiopharmaceuticals usedDosage & Administration

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Tc-99m pertechnetate

I-123 sodium iodide

I-131 sodium iodide

Activity 2-10 mCi 200-600 μCi 50-200 μCi

Route IV Oral Oral

Localization Trapped but not organified

Trapped and organified

Trapped and organified

Time to Imaging 20 mins – 1 hr 4 – 24 hrs 4 – 24 hrs

Half-life 6 hrs 13 hrs 8 days

Gamma energy 140 keV 159 keV 364 keV

Radiation dose 0.13 rad/mCi 0.007 rad/μCi 1-3 rads/μCi

Thyroid Imaging Radiopharmaceuticals PropertiesRadiopharmaceuticals used

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1) ID patient; verify physician’s order; review clinical indication for thyroid imaging

2) Explain procedure to patient; obtain relevant medical history

Technique

Clinical Procedure

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Relevant Medical History

• Physical findings (neck palpation, vital signs)

• Symptoms of hyper/hypothyroidism

• Medications/dietary supplements/birth control pills

• Surgery, esp neck, upper chest

• Malignancies• Changes in ability to

swallow/voice• Previous medical

imaging• Lab values: thyroid

hormone levels• Pregnancy/lactation

– TcO4-: Stop for 12h– I-123: Stop for 3d– I-131: Stop for 3m

Technique

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Symptoms of Hyper/HypothyroidismHyperthyroidism• Nervousness• Palpitations• Diarrhea• Sweating• Increased appetite• Heat intolerance

Either• Fatigue• Dyspnea• Weight change up or

down

Hypothyroidism• Coarse hair• Puffy eyelids• Dry skin• Myxedema• Constipation• Paresthesia• Decreased appetite• Cold intolerance

Technique

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Clinical Procedure (cont’d)

3) Prepare patient- ensure that female patients are not pregnant or breast feeding (if breast feeding provide instructions)- rule out substances that may affect radioiodine uptake into thyroid gland

Technique

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Factors Influencing Thyroid Uptake of Iodine

Decreased Uptake• Iodine-rich foods (shellfish)• Radiographic contrast containing iodine• Iodine-containing medications (vitamin/mineral

supplements, cough medicines, certain skin ointments)• Non-iodine containing medications (penicillin, steroids,

antithyroid drugs)• Thyroid hormones

Technique

Steroid Tyrosine

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Factors Influencing Thyroid Uptake of Iodine

Increased Uptake• Iodine deficiency• Pregnancy• Renal failure

Technique

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Clinical Procedure (cont’d)4) Administer radiopharmaceutical

5) Image patient

Imaging time post tracer administration:Tc-99m pertechnetate: 15-30 minI-123 sodium iodide: 4-6 hrs/16-24 hrsI-131 sodium iodide: 16-24 hrs

Patient positioning: supine with neck hyperextended

Views: anterior, obliques

Pinhole collimator

Mark anatomical landmarks

Technique

Pinhole collimator

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Marking anatomical landmarks

• supra sternal notch• thyroid cartilage• chin (approx.)

Technique

One or more landmarks and palpable nodules may be marked with the help of a radioactive/ radioopaque source:

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The Normal Scan

Right Lobe Left Lobe

IsthmusNormal:

Butterfly-shaped gland with uniform, symmetrical tracer distribution

Normal radioiodine Image

Normal pertechnetate image

Chin

SSN

Anterior w/ markers

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THYROID

Non-Imaging Procedures

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Thyroid Uptake Study

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Radioiodine Uptake Study (RAIU)

• A measure of thyroid function(hyperthyroid, hypothyroid, euthyroid)

• What % of the administered radioiodine is taken up by the thyroid gland?

(Thyroid uptake can also be determined using i.V. administered 99mTcO4

- & gamma camera but is less preferred)

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Clinical Procedure1) At 4-6 hrs and/or 24 hrs following radioiodine

administration, collect counts over the following areas using an uptake probe:

patient’s neckpatient’s thighstandard (neck phantom)room background

neck phantom

Standard Capsule Method

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Thyroid Neck Phantom• designed to simulate a patient’s

neck • made of lucite• Has two part insert that allows

counting from a bottle, vial or capsule

• capsule holder enables counting capsules directly

• phantom’s cylinder and carrier have scribelines for accurate alignment

• flat surface on the cylinder allows either vertical or horizontal positioning

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Clinical Procedure (cont’d)

2) Place all counts in counts/minute (cpm). Calculate net patient and standard counts by subtracting the appropriate background counts.

CountsC1

(cpm)

CountsC2

(cpm)

Average(C1+C2)/2

(cpm)

Net(Avg – Bkg)

(cpm)

Capsule counts 90 110 100 100 – 10 =

90

Room Bkg* 9 11 10

Neck counts @

4 hrs40 50 45 45 – 25 =

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Thigh bkg* counts @

4 hrs 30 20 25

Neck counts @

24 hrs 60 70 65 65 – 20 =

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Thigh bkg* counts @

24 hrs15 25 20

* Bkg - Background

Sample uptake work sheet

Standard Capsule Method

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Uptake calculation3) Calculate the % radioiodine uptake using the

following formula:

% uptake = neck cpm - thigh cpm x100 standard cpm - room bkg cpm

= Net neck cpm x 100 Net capsule cpm

Standard Capsule Method

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ExampleThe following data were collected 24 hrs afteradministration of two 100 μCi I-123 capsules.

Avg Counts Time (min) cpmNeck 15380 5 3076Thigh 860 5 172Standard 12600 2 6300(1 capsule)

Room bkg 350 5 70

Standard Capsule Method

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% uptake = neck cpm - thigh cpm . x 100 standard cpm - room bkg cpm

= 3076 cpm - 172 cpm . x 100 2(6300 cpm – 70 cpm)

= 23%

Standard Capsule Method

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Avg. counts CPM Net counts

Capsule(Std.1+Std.2)

12600 + 12600 25200 / 2 min

12600 12530

RoomBKG

350 / 5min 70

Neck 15380 / 5min 3076 2904Thigh 860 / 5min 172

Net Neck cpm X 100

Net Capsule cpm% Thyroid Uptake =

at 24hrs

2904 X 100

12530

= 23%

Standard Capsule Method

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Normal Ranges(may vary from dept to dept)

4 hr uptake 6 - 18%

24 hr uptake 10 - 35%

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Using same capsule for both patient and standard

• Count capsule with uptake probe before administering to patient; note counts and time

• When patient counts are collected, decay correct initial capsule counts to be used in calculation

Net neck cpm x 100 Net capsule(s) cpm x Decay Factor

Capsule Decay Method

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Sources of Error

• Patient contains residual radioactivity from previous test/therapy

• Counting geometry must remain constant for patient and standard

• Elevated room background

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Perchlorate Discharge Test

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Why is it done?

• Used to evaluate any organification defect – thyroid traps iodide but it does not combine with tyrosine

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Clinical Procedure1) Patient receives radioiodine capsule

2) Two hrs following radioiodine administration, a baseline uptake is performed. Then potassium perchlorate (KClO4) is administered orally.

3) Sixty to ninety minutes later, another thyroid uptake is performed.

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Interpretation of Results

• If an organification defect is present, the perchlorate ion (ClO4

-) displaces the iodide ion (I-) that has not been organified and the post-perchlorate uptake will be lower (10-15%) than the initial value.