Nuclear Medicine in Endocrinology (Thyroid Diseases)

1. Nuclear Medicine in Endocrinology(Thyroid Diseases) • A. Hussein Kartamihardja Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

2. 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

3. 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

4. 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

5. 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

6. Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

7. 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

8. 27-day old female with TSHs > 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 > 60 µIU/ml and T4 < 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

10. Autoimmune thyroid disease is a spectrum Hyperthyroidism Grave’s disease Euthyroidism Hypothyroidism Hashimoto’s disease

11. Thyroid dysfunction Hyperthyroidism (0.5 - 2%)* Hypothyroidism (2 - 5%)* Causes Causes Autoimmune thyroid disease most common cause of thyroid dysfunction 1. Hashimoto’s 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 • High Radioiodine Uptake: • Graves’ disease • Toxic Adenoma • Toxic Multinodular Goiter • Trophoblastic disease • TSH mediated hyperthyroidism • Low Radioiodine Uptake: • Subacute thyroiditis • Thyrotoxicosis factitia • Iodine induced hyperthyroidism 80% 80% Vanderpump et al. Clin Endocrinol 1995 (43):55-68 * Varies with iodine ingestion

12. 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 • Patient’s choice • Facilities Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

13. 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

14. 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 1942;21:624 Saul Hertz and A. Roberts (Boston, Mass). Application of Radioactive Iodine Therapy of Graves’ Disease. J. Clin Invest 1942;21:624 Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

15. Radioiodine I-131 • Physical properties : • Physical half life : 8.04 days (well suited o the biological half life) • Medium energy beta-particle emission (Emax=0.61 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

16. Percentage relapse of hyperthyroidism Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

17. 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

18. 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 1974;38:976-998 Long-term follow-up results in children and adolescents with radioactive iodine (I-131) for hyperthyroidism. Safa AM et al. N Engl J Med 1975;292:167-171. Iodine –131: Optimal therapy for hyperthyroidism in children and adolescent. Freitas JE et al.J Nucl Med 1979;20:847-850. Radioiodine treatment of hyperthyroidism-a more liberal policy ?Halnan KE. J Clin Endocrinol Metab 1985;14:467-489 Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

19. 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

20. Treatment preferences of hyperthyroidism Antithyroid drugs Japan Europe USA Radioiodine Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. 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

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

30. Department of Nuclear Medicine Padjadjaran University – Dr. Hasan Sadikin Hospital

31. 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

32. 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

33. Dr. Hasan Sadikin Hospital Protocol RSHS Success rate : 86.7% Near/total thyroidectomy 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

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

35. 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

36. 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 : • Physician’s 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

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