Nuclear Medicine in Endocrinology (Thyroid Diseases)

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Nuclear Medicine in Endocrinology(Thyroid
Diseases)

• A. Hussein Kartamihardja

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Nuclear Medicine In Thyroidology
Radiopharmaceutical

• 1940 130I 131I
• 1960 125I
• 1970 99mTc 201Tl-201
• 1980 123I 111In 18FDG

• Rectilinear scanner
• Gamma/beta counter
• Planar Gamma camera
• SPECT camera
• PET camera

Physician
Instrumentation
Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Characteristic of Nuclear Medicine

• Unsealed sources
• Gamma or beta emission
• Based on physiology and pathophysiology of the
  organ
• Radiopharmaceutical following the normal
  metabolism of the organ
• Field of nuclear medicine
• Diagnostic
• In-vivo
• In-vitro (RIA/IRMA)
• Treatment
• Research

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Nuclear Medicine Techniques in Thyroidology

• In-vivo non-imaging
• Thyroid uptake
• Iodine
• Technetium
• Supression test
• Stimulation test
• Perchlorate discharge test
• Urinary iodine excretion

• Hormonal assay
• T4 (fT4)
• T3 (fT3)
• TSHs
• Thyroglobulin
• Thyroid antibody

• Radionuclide iodine therapy
• Hyperthyroidism
• Differentiated thyroid cancer
• Multinodular goiter

• In-vivo imaging
• Thyroid scintigraphy
• Whole body scintigraphy

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Thyroid scintigraphy

• Indication for Thyroid scintigraphy
• Assessment of thyroid nodules
• Diagnosis of causes of thyrotoxicosis
• Assessment of goiter
• Evaluation of ectopic thyroid
• Assessment of thyroid cancer
• To determine the nature of retrosternal mass
• Work up of neonates with low T4 and/or high TSH

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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• 1 month-old with TSHs 52.3 µIU/ml)
• A Tc-99m pertechnetate study reveals radiotracer
  uptake in the neck, in the expected location and
  configuration of the thyroid gland.
• Dyshormonogenesis.

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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• 27-day old female with TSHs gt 60 µIU/ml
• Tc-99m pertechnetate images show no tracer uptake
  in the expected location of the thyroid gland.
  There is, however, a round focal region of tracer
  accumulation in the posterior aspect of the
  mouth, consistent with a lingual thyroid.

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
9

• 24 days old with TSHs gt 60 µIU/ml and T4 lt 0.25
  µg/dl.
• A Tc-99m study reveals there is no radiotracer
  uptake in the neck
• Agenesis.

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Autoimmune thyroid disease is a spectrum
Hyperthyroidism
Graves disease
Euthyroidism
Hashimotos disease
Hypothyroidism
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Thyroid dysfunction
Hyperthyroidism (0.5 - 2)
Hypothyroidism (2 - 5)
Causes
Causes
Autoimmune thyroid disease most common cause of
thyroid dysfunction
High Radioiodine Uptake Graves disease Toxic
Adenoma Toxic Multinodular Goiter Trophoblastic
disease TSH mediated hyperthyroidism Low
Radioiodine Uptake Subacute thyroiditis Thyrotox
icosis factitia Iodine induced hyperthyroidism
1. Hashimotos thyroiditis 2. Radioactive iodine
for Graves disease 3. Subtotal
thyroidectomy for Graves disease/nodular
goitre 4. Subacute thyroiditis 5. Iodide
deficiency 6. Drugs ( amiodarone, lithium) 7.
Congenital athyreosis/inborn errors of
thyroid hormone metabolism
80
80
Vanderpump et al. Clin Endocrinol 1995
(43)55-68 Varies with iodine ingestion
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• Treatment of Graves hyperthyroidism
• Antithyroid Drugs (ATD)
• Thyroidectomy
• Radioactive iodine
• Immunosuppressive (?)

• Adjunctive treatment
• beta-blockers
• steroids
• lithium

• Treatment of choice ?
• Depends on
• Background and Experience of physician
• Patients choice
• Facilities

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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The current objective of treatment To restore
eumetabolic status by lowering thyroid hormone
level through inhibiting hormogenesis by using
drugs or by thyroid ablation (surgery or
radioactive iodine)
The rational objective should be To restore
eumetabolic status by lowering thyroid hormone
level through suppressing or intervening immune
response
Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Treatment of Graves Hyperthyroidism with
Radioactive Iodine
Historical Perspective Joseph G. Hamilton and
John H. Laurence (Berkeley Calif). Recent
Clinical Development in the Therapeutic
Application of Radio-phosphorus and Radio-iodine.
J. Clin Invest 194221624 Saul Hertz and A.
Roberts (Boston, Mass). Application of
Radioactive Iodine Therapy of Graves Disease. J.
Clin Invest 194221624
Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Radioiodine I-131

• Physical properties
• Physical half life 8.04 days (well suited o the
  biological half life)
• Medium energy beta-particle emission (Emax0.61
  mev) with a path length of about 0.5 mm tissue.
• Gamma emission have both benefits and
  disadvantage
• Has been recommended as a treatment modality
  (adjunctive therapy) for thyroid cancer after
  initial treatment (near-total or total
  thyroidectomy) since last 5 decades.
• Ablation of residual thyroid tissue and
  recurrence or metastatic lesions
• Ablation therapy is generally recognized as
  necessary for the complete management of
  well-differentiated thyroid cancer

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Percentage relapse of hyperthyroidism
Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Factor affecting response to radioactive iodine
treatment Larger dose rapid remission, higher
hypothyroidism rate

• Size and nature of the gland
• Big gland and nodularity more resistant
• Race
• Black American more resistant
• Sex and age
• Man and old people more resistant
• Iodine intake
• High iodine consumption more resistant
• Antithyroid drug treatment
• More resistant

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Treatment of hyperthyroidism with Radioactive
Iodine
Malignant and benign neoplasms of thyroid in
patients treated for hyperthyroidism. A report of
the cooperative thyrotoxicosis therapy follow-up
study. Dubyns BM et al. J Clin Endocrinol Metab
197438976-998 Long-term follow-up results in
children and adolescents with radioactive iodine
(I-131) for hyperthyroidism. Safa AM et al. N
Engl J Med 1975292167-171. Iodine 131
Optimal therapy for hyperthyroidism in children
and adolescent. Freitas JE et al.J Nucl Med
197920847-850. Radioiodine treatment of
hyperthyroidism-a more liberal policy ? Halnan
KE. J Clin Endocrinol Metab 198514467-489
Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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• Side effects of radioactive iodine treatment
• Hypothyroidism
• Hypoparathyroidism (rare and transient)
• Radiation thyroiditis (transient)
• Exacerbation of thyrotoxicosis
• Worsening of active ophalmopathy
• Radiation induced gastritis

• Hypothyroidism rate
• Differ between centers due to different
  treatment protocol, population, environment etc
• Average (moderate dose 100 uCi/g)
• 10 / year first 2 years, then 3 per year

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Treatment preferences of hyperthyroidism
Antithyroid drugs
Japan
Europe
USA
Radioiodine
Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Radioactive iodine treatment Bandung experience
moderate dose (Masjhur, 1993) Cure rate
59.1 (6th month) 72.7 (12th month) 92.0
(24th month) Permanent hypothyroidism 5.7
(1st year) 9.5 (2nd year)
Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Thyroid cancer

• Incidence of thyroid cancer is increasing
  (anaplastic cancer decreasing)
• Mortality rate of 2-5
• Recurrence rate post-lobectomy 5 - 20
• No doubt that surgery is the primary treatment
• Total thyroidectomy is the choice
  (Siperstein and Clark, 1991)
• Surgery alone has remained inadequate to ensure
  cure

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Whether the remnant normal thyroid tissue should
at all be ablated or not
Recurrence post-lobectomy 5-24 Recurrence
less after total thyroidectomy Total
thyroidectomy is operation of choice (Siperstein
and Clark, 1991)

• Radioiodine ablation is to destroy any remaining
  normal thyroid tissue

Routine radioiodine ablation after
thyroidectomy ( preventive thyroablation ) Nemec
et al, 1979
Low risk do not need radioiodine ablation High
risk aggressive ablation Dulgeroff et al, 1994
Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Treatment of thyroid cancer with Radioactive
Iodine

• Decreased recurrence and death rates in the
  following ways
• Destroyed remaining normal thyroid tissue
• Destroys occult microscopic cancer
• The use of higher doses of I-131 treatment
  permits post-ablative total body scanning

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Who to treat with radioiodine I-131 ?

• Follicular thyroid cancer demonstrate a
  capability of taking up iodine, although less
  than that of normal thyroid cells.
• 50 of papillary carcinomas are also able to take
  up iodine and the presence of follicular elements
  on histology is an indicator of iodine uptake
  capabilities. (Mazaferri et all )
• Sharma et all 54.3
• Medullary, anaplastic carcinomas and lymphomas of
  the thyroid do not take up I-131, which therefore
  has no role in therapy following ablation of
  remnant thyroid tissue.
• Medullary thyroid cancer could be treated with
  I-131 MIBG (metaiodobenzylguanidine)

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Optimal dose

• Ablation dose 30 200 mCi
• Metastatic lesions 150 300 mCi
• Conservative approach 150 mCi
• 150 mCi may deliver between 50,000 to 25,000 cGy
  to thyroid remnant (20-83 treated)
• Minimum effective dose is 30,000 cGy
• Repeated treatments were given but not exceeding
  a cumulative dose of 1000 mCi

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Patient preparation

• Whole body scan 4-6 weeks after surgery using
  Tc-99m pertechnetate or MIBI or Tetrofosmin
• Thyroid hormones are not administered during this
  interval
• Iodide pool depletion by dietary iodine
  restriction or diuretic administration (3 days
  prior treatment)
• Routine chest x-ray and blood test

• Low iodine diet
• Sea food
• All other types of fish-fresh, frozen, canned,
  smoke or salted
• All fish products
• Vegetable spinach-fresh or frozen, lettuce,
  watercress
• Iodized salt in cooking

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Defining the successful ablation

• Problem during follow-up is the presence of a
  detectable serum Tg concentration without
  pathological uptake on whole body I-131 scan
• Negative scan with detectable Tg
• Anti-Tg antibodies may falsely elevate or
  decrease the results of serum Tg measurement
• Low TSH
• Iodine contamination
• Tumor does not or weakly trap I-131
• to small to visualize with diagnostic dose

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Radiation complication
Late
Acute

• Radiation thyroiditis 20 off those receiving
  50,000 rad (50 Gy), 4 days after I-131
• painless edema of the neck, usually within 48 hrs
  of I-131 therapy.
• 12 radiation sialadenitis
• Nausea, gastrointestinal discomfort, tongue pain,
  or reduce taste that is not severe and quickly
  passes are rare.
• Treatment on brain and spinal cord metastases is
  hazardous

• infertility (12)
• miscarriage (1.4)
• prematurity (8) and
• major congenital anomaly (1.4)
• Leukemia in patients receiving doses exceeding 1
  mCi with intervals less than 6 months (Benua et
  al, 1962, Edmonds et al, 1986)
• was not significantly different from that in the
  general population

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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F 59 yrs, Tg-on 2,9 ng/ml and Tg-off 5,8 ng/ml.
Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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F 59 yrs, Tg-on 39,3 ng/ml and Tg-off 102,6/ml.
Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Dr. Hasan Sadikin Hospital Protocol
Near/total thyroidectomy
RSHS Success rate 86.7
4-6 week post-surgery
Preventive ablation
Thyroid/whole body scan
Positive scan
Negative scan
Hormone substitution/suppression
Radiothyroablation 80-100 mCi

• Tg
• Whole body scan

5 months 1 month hormone off
Positive
Negative
Radioiodine therapy 100-150 mCi

• Survival rate
• 91 (322 patients) up to 15 yrs (Sharma, 1985)
• 90-100 up to 7 yrs with or without local or
  regional
• metastases (Padhy et al, 1988)

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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• Key to success
• Early detection
• Adequate thyroidectomy
• Appropriate radioiodine therapy
• Meticulous follow-up surveillance

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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PET in Thyroid Cancer Reading the Biochemical
Signals

• Staging. Extent of Aggressive Ca for optimal
  treatment planning
• Prognosis high-risk (FDG positive) and low-risk
  (FDG negative)
• Dosimetry. Individual lesions with 124I
• Response. Predict susceptibility to treatment and
  monitor treatment effect

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• Concluding remarks
• Scintigraphy has important role in thyroidology
• There is no standard treatment for Graves
  hyperthyroidism. The alternatives are OAT,
  surgery and radioactive iodine
• The choice of treatment varies according to
• Physicians training and personal experience
• Local and national practice patterns
• Patient, physician and societal attitudes toward
  radiation exposure
• Biologic factors age, reproductive status and
  severity of disease
• Radioactive Iodine recommended as an adjunctive
  therapy (ablation / preventive) for thyroid
  cancer after thyroidectomy for the complete
  management of well-differentiated thyroid cancer

Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital
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Thank you !
Department of Nuclear Medicine Padjadjaran
University Dr. Hasan Sadikin Hospital