Thyroid imaging function studies Radioiodine therapy 蔡碧瑜 李永隆 陳修弘 Textbook reading Thyroid imaging function studies Radioiodine therapy 蔡碧瑜 李永隆 陳修弘

Thyroid imaging and function studies Evaluation for clinical palpable nodules Thyroid scintigraphy and radiotracer uptake studies U.S. and F.N.A Laboratory data

Thyroid scintigraphy Determining the functional status of the thyroid nodules. Detection of the extra-thyroid metastasis form thyroid carcinoma. The thyroid tissue origins from mediastinal masses. Correcting the physical finding with abnormalities in the image.

Radiopharmaceuticals Iodine-131 Iodine-123 Technetium-99m

Radiopharmaceuticals Iodine a precursor of thyroid hormone . concentration (100:1 than plasma) Organification. Bound to thyroglobulin. Pertechnetate ion (TcO4-) concentration

Physics and dosimetry iodine-131

Iodine-131 not good choice for routine thyroid scintigraphy The presence of beta particle emissions The relative high energy of the principal gamma ray emissions for gamma camera. The long half-life Setal penetration of the collomator and poor detection sensitivity in the relative thin sodium iodine crystal of the gamma camera. But suits for delay studies at 24,48,72hr For thyroid cancer metastasis and mediastinal masses

Physics and dosimetry iodine-123

Iodine-123 Better for thyroid image Electron capture Gamma energy is ideally suited for gamma camera(159 keV) Half-life is suitable (13.2hr)

Iodine-123 Disadvantage Prepared from I-124 and I-125 Higher radiation precursors Short half-life Commercial limited Higher cost

Physics and dosimetry Technetium-99m

Technetium-99m Better for thyroid scintigraphy Reliably available from molybdenum-99 /Tc99m generator system Ideal half-life (6hr) Suitable energy (only gamma ray 140KeV)

Pharmacokinetics radioiodine GI absorbs ion by Oral administration Into circulation Rapid uptake and Organification of iodine Detectable within minutes. Reached the follicular lumen within 20-30 minutes Normal range for uptake is 10%-30% of the administered dose at 24 hr

Pharmacokinetics radioiodine Detection after several hours delay I-131 Detection after 1 day delay For background clearance but nor for the slow uptake

Pharmacokinetics Technetium-99m Iv administration Rapid uptake by thyroid but not organification Optimal uptake for imaging is 20-30 min with the 0.5-3.75% of the reagent

Technetium-99m & radioiodine Concordant localization and identical scintigraphy Dis-concordant in a small percentage of thyroid nodules for the loss of the organification

Precautions Breast feeding Pregnancy Interference of stable iodine contained in foods and medications

Breast feeding I-123 Resumed after several days if the amount used if no more than 30 uCi used Usual imaging dosage is 100-400 uCi I-131 Should be terminated for several weeks Tc99m pertechnetate Resumed in 24 hr

radioiodine precaution for pregnancy Radioiodine can cross placenta Fetal thyroid can concentrate iodine after 10th -12th gestation weeks. Resulting in hypothyroidism and cretinism.

Interference for radioiodine uptake Several non-iodine drug can affect that. 1 mg of stable iodine can cause significant reduction of the 24 hr radioiodine uptake 10 mg can effectively block the gland, with 98% reduction uptake.

Normal thyroid scintigraphy In the euthyroid adult the thyroid gland weights 15-20 g. Butterfly shape with lateral lobe extending along each side of the thyroid cartilage of the larynx The lateral lobes are connected by an isthmus that crosses the trachea anteriorly below the level of the cricoid cartilage.

The right lobe is often larger than the left. The lateral lobes typically measure 4-5 cm from superior to inferior poles and 1.5-2 cm wide. The pyramidal lobe is a paramedian structure that arises from the isthmus, either to the right or left lobe of the middle, and represents functioning thyroid tissue in the thyroglossal duct tract.

Normal thyroid scintigraphy Homogeneous Uniform distribution Variation Middle or medial of the lateral lobes owing to the thickness Activity of the Isthmus varies greatly among patients, with little or no activity and prominent activity Activity at Graves’ disease for the hyperplasia of the tissue in the duct

TC-99m pertechnetate Thyroid tissue Salivary gland Esophagus activity seen to the left of middle and can confirm by having patient swallow, hollowed by a repeat image. I-123 the salivary gland are not usually seen

Clinical applications indication for thyroid scintigraphy Further evaluation of findings on physical examination Detection of metastases with thyroid carcinoma Follow-up of radioiodine therapy for differentiated thyroid cancer Determination of functional status of thyroid nodules Differential diagnosis of mediastinal masses Detection of extra thyroidal tissue (lingual thyroid) Screening after dead and neck irradiation.

Clinical applications Goiter Refers to an enlargement of the thyroid gland Endemic goiters Iodine deficiency-induced hyperplasia Colloid nodular goiters Nontoxic goiters Graves’ disease Toxic goiter Thyroid carcinoma Other neoplasm-lymphoma Active phase of thyroiditis

Scintigraphy of Goiter multinodular colloid goiters Inhomogeneous uptake of tracer Cold areas of various sites Carcinoma changes rate is low (1-5%) Highly suspicion: out of proportion in size to other cold areas or enlarging suddenly.

Scintigraphy of Goiter Graves’ disease Uniform with intensely increased uptake The pyramidal lobe is frequently seen Not generally considered an indication for obtaining a thyroid scinitigram (?)

Clinical applications thyroid nodules Extremely common The incidence increases with age More common in women Likehood of malignancy: Multiple nodule (multiple nodular goiters, less than 5%) Solitary cold nodule (5-40%)

Scintigraphy for thyroid nodules Cold nodules-nonfunctioning The majority of the thyroid nodules As small as 3 cm can be detected by pinhole collimator Hot nodules-functioning Function equal to the surrounding normal thyroid Indeterminate Need to close to correct between physical examination and scintigraphy findings. Oblique view with a pinhole collimator The management is the same as the cold nodules. Oblique view with a pinhole collimator can be helpful in separation the nodule from adjacent thyroid tissue

Cold nodules Risk factors of malignancy prior history of radiation to the head and neck or mediastinum >1000-1500 rads Solitary cold nodules in young female Multiple nodular goiters in elderly

Hot nodules Hyper functioning Autonomous Out of negative feedback control

Hot nodules Autonomous nodules Thyroid gland produces much hormone Greater than 3-4 cm suppress pituitary TSH Extra-nodular thyroid tissue is not visualable Small nodules Extra-nodular thyroid tissue is visualable Spontaneous involution Cystic degeneration

Hot nodules Hot nodules with hyperthyroidism Large(3-4 cm), multiple nodules Autonomous hot nodule with Thyrotoxicosis Plummer’s disease

Discordant nodules Possibility of discordant between radioiodine and Tc-99m pertechnetate Radioiodine-cold Tc-99m pertechnetate-hot 2-3 % in Tc-99m pertechnetate hot nodules

Substernal thyroid D.D mediastinal masses Goitrous enlargement with downward extension Abnormal migration during develop

Substernal thyroid I-131 is better than Tc99m Delayed performed (48-72 hr) Function and tracer uptake in sternal thyroid is poor Blood clearance of the background activity Cervical thyroid should also be noted

Clinical applications other ectopic thyroid tissue The thyroglossal duct runs from the foramen cecum at the base of the tongue to the thyroid Lingual thyroid –complete failure to migrate Absence of tracer uptake in the expected cervical area Thyroid tissue may be found along the tract of the thyroglossal duct.

Clinical applications thyroiditis Acute thyroiditis Suppurative bacterial infection Focal abscess subacute thyroiditis Granulomatous thyroiditis De Quervain’s disease Non-suppurative Etiology unproved-virus infection (URI, neck tenderness) Initial phase would be a Thyrotoxicosis Chronic thyroiditis Hashimoto’s thyroiditis Lymphocytic infiltration More common in women with goiter or hypothyroidism Rarely with hyperthyroidism-hashitoxicosis

Scintigraphy for acute & subacute thyroiditis Cold nodule for the focal abscess Subacute thyroiditis Decrease or absent uptake of radioiodine in the affected part of the gland Gallium-67 imaging :inflammatory process

Scintigraphy for chronic thyroiditis Highly variable and depend on the stage in the natural history Normal in the early stage Later, diffuse enlargement Eventually, hypothyroidism, inhomogeneous with hot and cold areas

Clinical applications thyroid cancer metastasis Follicular carcinoma Mixed papillary-follicular carcinoma Papillary carcinoma Medullary carcinoma Ana plastic carcinoma

Thyroid cancer metastasis The most common sites of metastasis are locally in the lymph nodes of the neck, lung ,and bone. nodal activity is focal ,intense, starburst pattern on parallel-hole collimators

Thyroid cancer metastasis Imaging is performed 48-72 hr after radioiodine administration. More lesion are demonstrated in this time than at 24 hr.

I-131 follow-up imaging The preparations and dosage are controversial. Thyroid hormone replacement is withdraw for 4-6 weeks to stimulate TSH secretion. Use bovine TSH before imaging. Not satisfactory for increasing I-131 uptake allergy

Scanning dosages for follow-up imaging Controversial More metastasis deposits are seen with higher doses 5-10 mCi of I-131 for detecting metastasis As little as 5 mCi with less satisfactory uptake of sequent therapeutic dose Diagnostic dose should be limited 1-2 mCi

Tumor imaging Thalium-201 chloride Tc-99m sestamibi For location metastasis in patients with increased thyroglobulin and negative radioiodine whole body scintigraphy

Iodine -131 MIBG for Medullary carcinoma meta-iodo-benzyl-guanidine Neurosecretory storage vesicles of chromaffin cells Sensitivity is low (30%) Soft tissue metastasis is more visualized than bone metastasis.

Medullary carcinoma of thyroid Indium -111 somatostatin receptor scintigraphy for Medullary carcinoma Iodine -131 MIBG FDG-PET

Thyroid function studies Thyroid percent uptake Suppression test Stimulation test Per chlorate discharge test

Thyroid percent uptake The earliest applications radiotracer in medicine. The degree of radioiodine uptake parallels the functional activities of the thyroid hormone produced Normal uptake range 10-30% Sensitivity and specific test of serum T3 T4

Thyroid percent uptake DD hyperthyroidism Increase uptake Graves’ disease Plummer’s disease Decrease uptake Subacute thyroiditis Thyrotoxicosis factitia

Suppression test Not used in current routine practice. Autonomous functioning glands TSH level is a sensitivity test now

Suppression test Receiving 25 mg T3 qid for 8 day 24hr uptake is repeated beginning at 7th day. It is fall in the percentage of uptake to less 50% of the baseline and less the 10% overall.

Stimulation test Infrequent use now. D.D primary and secondary (pituitary) hypothyroidism Primary-failure to response to exogenous TSH Secondary-increasing radioactivity after TSH administration

Stimulation test Receiving 10 units of TSH iv The radiotracer repeats beginning the next day. Primary-no response Secondary-radiotracer doubling

Per chlorate discharge test to detect defects in Intra-thyroidal iodide organification

Per chlorate discharge test Dissociation of the trapping and organification function Congenital enzyme deficiency associated with deafness (Pendred's syndrome), Some chronic thyroiditis During the treatment of PTU

Per chlorate discharge test I is "trapped" by the thyroid gland through an energy-requiring active transport mechanism Once in the gland, it is rapidly bound to thyroglobulin

Per chlorate discharge test inhibit active iodide transport cause the release of the intrathyroidal iodide not bound to thyroid protein thiocyanate (SCN-) perchlorate (ClO4-)

Per chlorate discharge test administration of radioiodine orally counts are obtained at frequent intervals (every 10 or 15 minutes). Two hours later, 1g of KClO4 orally repeated epithyroid counts continue to be obtained for an additional 2 hours

In normal individuals little loss of the thyroidal radioactivity accumulated prior to induction of the "trapping" block radioiodine accumulation in the thyroid gland ceases after the administration of the iodide transport inhibitor

Per chlorate discharge test Less than 10% discharge of radioiodine: Normal Hyperthyroidism on inadequate antithyroid drug therapy Greater than 10% washout: Organification defect

Radioiodine treatment Hyperthyroidism Thyroid cancer

Hyperthyroidism indications for iodine-131 therapy Graves’ disease (diffuse toxic goiter) Plummer’s disease (toxic nodular goiter) Functioning thyroid cancer (metastasis)

Hyperthyroidism Contraindication for iodine-131 therapy Thyrotoxicosis factitia Subacute thyroiditis Silent thyroiditis (atypical ,subacute, lymphocytic, transient, postpartum) Struma ovarii Thyroid hormone resistance Secondary hyperthyroidism Thyrotoxicosis associated with Hashimoto’s disease (hashitoxicosis) Jod-Basedow phenomenon (iodine-induced hyperthyroidism)

Radioiodine treatment Goal Euthyroid in a reasonable length of time with a single radioiodine dose Graves’diseas-80-120 uCi/g Standard dose:5-10mCi Higher for Graves’ opthalmopathy More than 90% patients are cured with a single dose Hypothyroidism-hormone replacement I-131 can be used in any age

Radioiodine treatment Plummer’s disease Hyperthyroidism caused by toxic nodules More radio-resistant Inhomogenity, rapidly radioiodine turnover ,low retain dose Increase dose to 15-29 mCi

Radioiodine treatment Metastases from differentiated thyroid cancer Controversial with small , early stage lesions Residual, recurrence differentiated thyroid cancer - improved survival rate with I-131

Radioiodine treatment Metastasis more common at neck, lung and bone Bone metastasis is more difficult eradicated than lung metastasis Initial dose 150-200mCi Repeated doses up to 1Ci

Radioiodine treatment Follow-up imaging is performed yearly until the metastatic lesions are elimination Serum thyroglobulin –tumor marker If the level is increase in a post-op patient. it may be a recurrence Then performed imaging to localize the lesion

Radioiodine treatment Not statistically significances of leading the secondary cancer by radioiodine Tx Not reduce fertility Congenital defects are not increased in the child of treated patients

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