ERS15 Introduction Of Radiology Of Thyroid + The Use Of Radioactive Iodine Therapy Flashcards
Thyroid gland
- Bilobed across trachea
- Joined by Isthmus
- Binded by Pretracheal fascia
- Pyramidal lobe (Accessory lobe) (50%, from Isthmus)
Thyroid malignancy
- Carcinoma (most common)
- Papillary (75%)
- Follicular (10%)
- Medullary (5%)
- Anaplastic (<5%) - Lymphoma (<5%)
- Metastasis (lung, breast, kidney)
- Sarcoma (rare)
Imaging techniques
- Plain film (limited value)
- Ultrasound (most common)
- CT
- Radionuclide scan
- MRI
Purpose of Thyroid imaging
- Confirm enlargement (US, CT, MRI)
- Characterise nodules / masses within gland (US)
- Investigation of thyroid function (radionuclide scan)
If known thyroid carcinoma
- Evaluate local disease (US, CT, MRI)
- Surveillance after Thyroidectomy / treatment (US, CT, MRI, radionuclide scan)
Plain film
Soft tissue density / Opacity around thyroid region
- Goitre
Limitations:
- Cannot evaluate local invasion
- Cannot characterise thyroid lesion
Ultrasound
- Most useful, Most common
- Hypoechoic (dark) vs Hyperechoic (bright)
- Acoustic shadowing: a signal void behind structures that strongly absorb or reflect ultrasonic waves, most frequently with solid structures
Image:
- Homogeneous echogenicity
- Smooth outlines
- Colloid cyst: Hypoechoic lesion, Acoustic enhancement (increased echogenicity (whiteness) posterior to cystic area), Comet tail artefact (colloid calcification)
- Hyperplastic nudules / Adenoma: Hypoechoic rim, Heterogeneous
- Graves’ disease: **Diffuse enlargement, **Increased vascularity on colour doppler
- Follicular adenoma / carcinoma: Hypoechoic, Heterogeneous
- Anaplastic carcinoma (most aggressive): Infiltrative margin with local invasion
Use:
- ***Characterise nodule: Solid vs Cystic
- ***Vascularity (colour doppler)
- ***Guide needle aspiration / biopsy
Advantages: 1. No radiation 2. ***Excellent for evaluating superficial structures e.g. thyroid gland —> high frequency probe (12 MHz) 3. ***Excellent spatial resolution —> sensitive in detecting tiny nodule
Calcifications within Thyroid
- Benign / Malignant
- may see shadowing secondary to calcifications
- Malignant: more vascular
Punctate calcifications (***Psammoma bodies)
- specificity >85%
- common in ***Papillary carcinoma: irregular lesion with microcalcification, heterogeneous
Coarse calcifications
- long standing multinodular goitre
- ***Medullary carcinoma: ill-defined border, heterogeneous
***Sonographic signs implying benign / malignancy of lesion
- Margin / Contour
- ***Ill-defined —> malignancy (53-89%)
- ↑ AP/transverse ratio (i.e. taller than its width) (向前後發展) —> 93% malignant - Vascularity
- Complete avascular —> unlikely to malignant
- ***Intrinsic vascularity —> 69-74% malignant
- Perinodular vascularity —> 22% malignant - Hypoechoic
- **darker appearance —> ↑ risk of malignancy
- **completely anechoic —> Cystic lesion - Size
- non-specific (>4 cm, slightly favour malignancy but no absolute) - Number
- non-specific (comparable risk of malignancy between MNG and solitary nodule, follicular carcinoma frequently found in MNG) - Metastatic LN
- assess neck for LN metastasis
Sonographic features of malignancy
- **1. Invasion into surrounding tissues
- **2. Ill-defined margin
- **3. Microcalcification
- **4. Cystic change
- **5. Intrinsic vascularity
Limitation of Fine needle aspiration cytology (FNAC)
Cannot distinguish between Follicular Adenoma / Carcinoma
—> Histology required (study whole tissue) —> Capsular / Vascular invasion
Summary of Ultrasound
When ***combined with FNAC
—> most sensitive and specific imaging technique in differentiating benign vs malignant thyroid nodule
CT, MRI
Cross sectional anatomy
Use:
- ***Intrathoracic extension of goitre
- Evaluate locoregional, distant disease
- ***Post surgical / radioactive treatment surveillance for recurrence
MRI:
- Superior ability for **soft tissue differentiation
—> Excellent for assessment of **head + neck structures
E.g. Retrosternal goitre, Metastatic LN
Radionuclide scans
- Provide ***functional / metabolic information
- Normal, Uniform uptake
- Hot: ↑ uptake
- Cold: no uptake
(Multinodular goitre: Both Hot + Cold nodules) - Show position of ***ectopic thyroid gland
- failure of descent of thyroid gland along thyroglossal duct tract from foramen caecum - Follow-up after treatment
- Whole body 131Iodine scan
—> discontinue thyroid hormones before (T4: 4 weeks, T3: 2 weeks)
—> low iodine diet 7 days before
—> increased detection rate if scan after 7 days of injection of 131Iodine
- Negative 131Iodine scan but Elevated Thyroglobulin after Thyroidectomy (suspicion of recurrence)
—> 18F-FDG PET/CT (94% sensitivity)
2 types:
- 99m-Tc pertechnetate
- Iodide scan
99m-Tc pertechnetate:
- ***trapped by thyroid tissue but NOT incorporated into thyroglobulin
- imaging at 20mins after injection
- anterior, left, right oblique views
- Normal thyroid: ***Uniform uptake
Iodide scan:
- trapped + ***organified (iodine incorporated into thyroglobulin to form T3, T4)
- 2 isotopes for use: 123Iodine + 131Iodine
Others:
- 201TI —> perfusion
- 99mTc MIBI —> perfusion + mitochondrial density
Relationship between Clinical, In Vivo, In Vitro results
Primary Hyperthyroidism:
- Low TSH
- High T4
- High uptake
Hypothyroidism:
- High TSH
- Low T4
- Low uptake
Iodine deficiency:
- Normal TSH
- Normal T4
- ***High uptake
- **Acute / Subacute thyroiditis (initial destruction of thyroid gland):
- Low TSH
- ***High T4 (transient)
- Low uptake
Cold nodules
Example: Papillary carcinoma
- **Almost all cancers are Cold nodules
- carcinoma
- lymphoma
- metastasis
Majority of Cold nodules are benign (only 10-25% solitary cold nodule is malignant)
- colloid nodules
- adenomas
- thyroiditis
**Likelihood of malignancy ↑ if solitary lesions
—> **ALWAYS require needle biopsy / aspiration to confirm diagnosis
Hot nodules
Example: Functioning hot ***adenoma
- 30% of solitary nodules
- ***Virtually exclude cancer (<1% are hot)
- 33%-50% are autonomous (independent of TSH)
Decreased uptake
Thyroiditis
—> Enlarged gland with non-uniform patchy decreased uptake of tracer
***Summary
US and Radionuclide scan are usual imaging modalities
US: Sensitive and Specific
- useful for guiding FNAC of nodules
CT, MRI are reserved for evaluation of:
- intrathoracic extension
- post-resection / therapy evaluation
Metabolism of Iodine
Dietary iodide absorbed in GI tract —> Iodide into Follicular cells via Na/I co-transport system —> Oxidised by Peroxidase in follicle lumen —> Iodine —> Organification —> Incorporation into Thyroglobulin —> production of thyroid hormones —> removed mainly by kidneys
Medically used Iodine
I-123, I-124, I-125, I-131
I-131:
- most commonly for management of thyroid diseases (Diagnostic / Therapy)
I-125:
- nuclear imaging tracer
- radioactive treatment for prostate cancer
I-123, I-124:
- nuclear imaging tracer for thyroid diseases
Iodine 131
Rapidly and efficiently trapped by thyroid via Na/I co-transporter
***Beta + Gamma-emitting radionuclide
Principle gamma ray: 364 KeV (10%)
- quantified by external detection —> ***measure thyroid function
Principle beta particles:
- maximum energy of 0.61 MeV
- average energy of 0.192 MeV
- range in tissue: 0.8 mm
- destructive beta-particles originate within follicles —> ***act exclusively upon parenchymal cells of thyroid —> little / no damage to surrounding tissue
Physical t1/2:
- ~ 8 days
Use:
- Benign thyroid disease (Hyperthyroidism)
- Well-differentiated thyroid cancer (e.g. Papillary thyroid cancer, Follicular thyroid cancer)
- Radioactive label for certain radiopharmaceuticals (e.g. 131I-MIBG for Phaeochromocytoma and Neuroblastoma)
Administration: - ***Oral Sodium iodide - Capsule / Liquid —> capsule safer, less radioactive released into air during handling —> less oral mucosal irritation
- **Tissues that take up Iodine:
- Salivary glands
- Esophagus (result of swallowing radioactive saliva)
- Thymus gland
- Breasts in some women
- Liver, Stomach, Colon, Bladder
Disadvantage:
—> SE to these tissues
—> ***Misinterpret as metastasis during scanning
Causes of hyperthyroidism
- Graves’ disease
- Toxic adenoma
- Toxic multinodular goitre
- Thyroiditis
- Iodine-induced hyperthyroidism (e.g. Amiodarone)
- Excessive TSH / Trophoblastic disease
- Excessive ingestion of Thyroid hormone (Thyrotoxicosis factitia)
- Ectopic thyroid production / Functional metastatic CA thyroid
Treatment of hyperthyroidism
- Anti-thyroid medication
- 131Iodide radioactive iodine treatment
- Surgery
131-I therapy for hyperthyroidism
Indications:
- SE / recurrence / poor compliance after a course of Anti-thyroid drug
- Complications of hyperthyroidism e.g. Cardiac arrhythmia, Heart failure, Thyrotoxic periodic paralysis
- ***Preferred definitive treatment for Graves’ disease, Toxic nodular goitre
Outcome:
- 80-90% euthyroid within 8 weeks after single dose
- some may need 2-3 times of RAI for remission (each dose 6-9 months apart)
- Reduce goitre size by 40% in Toxic multinodular goitre
- RAI not CI in large goitre (even retrosternal / intrathoracic) —> unless compressive symptoms —> surgery more suitable
Caution:
- ***Graves’ ophthalmopathy may develop / worsen after treatment with 131-I
CI:
- Pregnancy, lactation
- Children, adolescents (relatively CI)
SE:
- mild, well tolerated (e.g. mild neck swelling, pain on swallowing)
Long term safety:
- no effect on fertility
- no increased incidence of congenital malformations
- no increased risk of developing cancer
Monitoring:
- Regular serum ***Thyroid function test for Hypothyroidism —> Thyroxine replacement
- Incidence rate of hypothyroidism after 1st year of RAI: <50% (highly correlate with dose)
- Followed by yearly hypothyroidism rate of 3-5% (independent of RAI dose)
- Post-therapy thyroid storm (extremely rare) —> palpitations etc.
Anti-thyroid drugs vs Radioactive iodine vs Surgery
1. Favourable patient factors Anti-thyroid drugs: - ***Pregnancy, lactation - children, adolescents - moderate-severe active ophthalmopathy - not able to follow radiation safety precautions RAI: - high risk of relapse - ***Recurrent Graves’ Surgery: - ***Compressive symptoms
- Onset of effect
Anti-thyroid drugs: 2-4 weeks (4-12 weeks achieve normal function)
RAI: 4-8 weeks (90% cure within 6 months)
Surgery: immediate - Success of treatment
Anti-thyroid drugs: long term remission 33-50%, high risk of relapse
RAI: 50-80%, low - intermediate risk of relapse
Surgery: 100% with total Thyroidectomy - Risk of long term hypothyroidism
Anti-thyroid drugs: low risk
RAI: intermediate to high (50% at 12 months, more over time)
Surgery: 100% with total Thyroidectomy —> Thyroxine replacement - Advantages
Anti-thyroid drugs: **non-invasive, cheap
RAI: **cost effective, few SE, out-patient therapy
Surgery: ***rapid and effective - Disadvantages
Anti-thyroid drugs: **low rate of remission, SE: fever, rash, arthralgia, agranulocytosis
RAI: radiation exposure, risk of exacerbation of ophthalmopathy, **need to delay pregnancy and avoid breastfeeding
Surgery: high cost, painful, scar, need hospitalisation, ***surgical complications: Recurrent laryngeal nerve damage, Hypoparathyroidism
131-I therapy for well-differentiated thyroid cancer
Well-differentiated
- Papillary (most common, 75-85%)
- Follicular (15%)
Less well-differentiated
3. Medullary (3%)
Poorly differentiated
4. Anaplastic (1%)
Treatment of differentiated thyroid cancer
Lobectomy
—> Surveillance only
Total Thyroidectomy
—> Radioactive iodine (depend on pathology, risk group)
—> External beam radiotherapy (for high risk / residual disease)
(TSH suppression therapy throughout)
Radioactive Iodine treatment of Post-op differentiated thyroid cancer
Use:
1. **Eradicate remnant thyroid cells (any residual microscopic tumour cells / residual normal thyroid tissue):
—> ↑ sensitivity of using serum thyroglobulin for disease monitoring (一有上升就代表relapse)
—> facilitate future surveillance for relapse / metastasis with 131-I whole body scan (WBS)
2. **↓ Risk of local / distant tumour recurrence
3. Prolong survival
Dose:
- Low risk group (no LN metastasis): 1.1 GBq
- Intermediate risk group (LN metastasis without distant spread): 3.7 GBq
- High risk group (metastatic disease): 5.5 GBq
Preparation and precautions of 131-I therapy
Similar preparation for both Hyperthyroidism and Differentiated thyroid cancer
1. Follow legislation, regulation on safe use of radioisotope therapy
- Facilities needed: Trained personnel, storage equipment, radiation protection, waste handling, monitoring, controlling, handling contaminants
- Discussion of treatment options, patient’s consent, instruct patient on post-therapy precaution, follow-up
- In hyperthyroidism, **Stop anti-thyroid medication 4-14 days before RAI
- Carbimazole: 4 days
- Propylthiouracil: 14 days
—> allow ↑ TSH production from pituitary
—> **↑ Iodine uptake by residual thyroid tissue / tumour cells - ALL female: ***stop breastfeeding, practice contraception 4 weeks before RAI
- ***Low iodine diet for >= 2 weeks
- avoid seafood, dairy products, soy products, iodine containing medications
Preparation for RAI in cancer
Method 1:
- withdrawal from T4 for 4 weeks
- switch to T3 20mcg TDS for 2 weeks
- stop all T3/T4
—> **allow ↑ TSH production from pituitary
—> **↑ Iodine uptake by residual thyroid tissue / tumour cells
Method 2 (for elderly, CVS problem):
- no need to stop thyroxine
- Recombinant human TSH (rh-TSH) injection 2 days before RAI
—> **provide exogenous source of TSH
—> **↑ Iodine uptake by residual thyroid tissue / tumour cells
Indications of rh-TSH (Thyrogen)
rh-TSH:
- provide Exogenous source of TSH
- made from recombinant human DNA technology
- better QoL (do not need to stop T4 —> no hypothyroidism symptoms)
Patients who need rh-TSH rather than Thyroxine withdrawal:
(***簡單而言: for those cannot tolerate Low Thyroid hormone)
1. Hypopituitarism (cannot produce TSH even if withdraw Thyroxine)
2. Severe ischaemic heart disease
3. History of psychiatric disturbance precipitated by hypothyroidism
4. Functional metastasis causing TSH suppression
5. Advanced disease / frailty
Administration:
0.9mg deep IM into buttock 2 days before RAI
SE of RAI
- Minimal, transient
- Early SE:
- ***Neck swelling, discomfort (esp. those with residual thyroid tissue after surgery, may need steroid cover)
- Nausea, epigastric discomfort
- Sialadenitis
- Radiation cystitis, radiation gastritis, bleeding and edema in metastasis (∵ other tissues also uptake RAI, extremely rare) - Late SE:
- **Xerostomia (dry mouth)
- Sialadenitis and Lacrimal gland dysfunction (rare)
- Second malignancy (very rare): anaplastic anaemia, leukaemia
- **Radiation fibrosis if diffuse pulmonary metastatic disease (give ***steroid before RAI)
- Bone marrow suppression if very high dose - Specific SE for well-differentiated thyroid cancer
- if vertebral metastases and I-131 therapy given —> uptake of I-131 into spine —> risk of **neurological complications —> give **steroid cover
- small dose to gonads (effect on fertility transient, no hormonal failure, no evidence of genetic defects / malignancy in offspring)
Radiation safety precaution after 131-I therapy
General principles:
- Keep long distance
- Short contact time
- Avoid pregnancy
Within 2 weeks:
- avoid iodine-containing food, medications
- avoid crowded place
- avoid close contact with children under 12 / pregnant women
- avoid sex, body fluid contact
- use own cutlery
- wash linens separately
- flush toilet twice
- not get pregnancy / fathering / breastfeeding within 6 months after RAI
—> radiation exposure to fetus
—> ↑ risk of miscarriage, abnormal development
Long term care after 131-I therapy for well-differentiated thyroid cancer
- Post-therapy 131-I Whole body scan (around 4-10 days after RAI)
—> ***screen for residual thyroid uptake / distant metastasis - Start TSH suppression therapy: **Supra-physiological dose of thyroxine to keep TSH below lower limit of normal range
—> prevent recurrence of cancer
—> **簡單而言: Before treatment: Allow TSH ↑, After treatment: Suppress TSH - 131-I whole body scan 6-12 months after 131-I therapy
—> detect any relapse / metastasis - Regular monitoring with serum thyroglobulin
—> ***↑ thyroglobulin may indicate relapse / metastasis - Avoid pregnancy for 1 year and until disease stable
- Monitor thyroid function during pregnancy
