Radioiodine Treatment for Benign Thyroid Diseases Teofilo O.L. San Luis, Jr., MD, MPA Professor, Faculty of Medicine & Surgery, University of Santo Tomas Chief, Section of Nuclear Medicine, UST Hospital, Manila, Philippines Dean, Asian School of Nuclear Medicine

I131 Treatment Indicated for Hyperthyroidism (Graves’ Disease, Toxic Nodular Goiter), recurrent disease, those with contraindications to anti-thyroid drugs & surgery Not indicated for: “Destruction-induced thyrotoxicosis” Thyroiditis (acute, subacute, postpartum) Thyrotoxicosis factitia Hyperthyroxinemia Used in shrinking euthyroid goiters or nodules

What happens inside the Thyroid Follicular Cell? Steps in Thyroid Hormone Biosynthesis Iodide trapping by the thyroid follicular cells Translocation of iodide to the apex of the cells Transport of iodide into the colloid Oxidation of inorganic iodide to an inorganic form (I+) and incorporation of iodine into tyrosine residues within thyroglobulin molecules in the colloid Combination of two diiodotyrosine (DIT) molecules to form tetraiodothyronine (thyroxine,T4) or of monoiodotyrosine (MIT) with DIT to form triiodothyronine (T3) Uptake of thyroglobulin from the colloid into the follicular cell by endocytosis, fusion of the thyroglobulin with a lysosome, and proteolysis and release of T4, T3, DIT and MIT Release of T4 and T3 in the circulation Deiodination of DIT and MIT to yield tyrosine ***T3 is also formed from monodeiodination of T4 in the thyroid and in the peripheral tissues REFERENCE Modified from Scientific American Medicine, Scientific American, New york, 1995

What happens inside the Thyroid Follicular Cell with I131? Steps in Thyroid Hormone Biosynthesis Iodide trapping by the thyroid follicular cells Translocation of iodide to the apex of the cells Transport of iodide into the colloid Oxidation of inorganic iodide to an inorganic form (I+) and incorporation of iodine into tyrosine residues within thyroglobulin molecules in the colloid Combination of two diiodotyrosine (DIT) molecules to form tetraiodothyronine (thyroxine,T4) or of monoiodotyrosine (MIT) with DIT to form triiodothyronine (T3) Uptake of thyroglobulin from the colloid into the follicular cell by endocytosis, fusion of the thyroglobulin with a lysosome, and proteolysis and release of T4, T3, DIT and MIT Release of T4 and T3 in the circulation Deiodination of DIT and MIT to yield tyrosine ***T3 is also formed from monodeiodination of T4 in the thyroid and in the peripheral tissues REFERENCE Modified from Scientific American Medicine, Scientific American, New york, 1995

I131 Treatment I131 emits beta rays (0.61 MeV); max range in tissue = 2.4mm Beta rays  destruction of thyroid follicular cells  decreased thyroid cell mass  reduced thyroid hormones over a period of time Variability in how long a time is the effect of I131? how much cell mass is destroyed? how much thyroid hormone can still be produced?

Factors affecting I131 effectiveness: Dose itself Over-all gland size (or weight) Uptake into the thyroid Transit through the thyroid Status of iodine sufficiency (or deficiency) “Radiation sensitivity”

FACTOR # 1: DOSE ITSELF Dose Calculation Dose = Gland Weight x uCi/gm x 100 % Uptake (24 hrs) Considerable variation in any of the entries Fixed Dose vs. Calculated Dose vs. Empirical Dose 5 mCi; 10 mCi; 15 mCi 100 – 160 uCi / gm 5,000 – 15,000 rads or 50 – 150 Gy Physician subjective factors: clinical contingencies, urgency for treatment, severity of disease, etc.) Regulatory requirements: out-patient vs. in-patient

FACTOR # 2: GLAND SIZE (WEIGHT) Variability in gland size (weight estimation) Clinical palpation estimate (based on “experience”) Thyroid scan image estimate (“eye-balling”) Thyroid scan planimetry RL = Length x Width, e.g. 6 cm x 2.5 cm = 15.0 LL = Length x Width, e.g. 5.5 cm x 3 cm = 16.5 31.5 31.5 cm2 x “constant” (thickness) “1.44” = 45.3 cm3 or 45 gms Ultrasound volume (machine-derived) RL = Length x Width x Depth x “correction factor” LL = Length x Width x Depth x “correction factor” 6 x 2.5 x 2.5 x “0.52” = 19.5 5.5 x 3 x 2.5 x “0.52” = 21.5 41 gms

FACTOR # 3: UPTAKE INTO THE ORGAN Hyperthyroid uptake ranges from 30 – 90% Distribution: uniform vs. non-uniform 24 hr RAIU & scan as appropriate indicators Therapy uptake decreased by iodine contaminants (food, drugs) FACTOR # 4: TRANSIT THROUGH THYROID (Biologic half-life) Hyperthyroid patients: very rapid thyroidal turnover of iodine = short biologic half-life Depleted thyroidal iodine pool (in 15% of pts) Rapid transit  decreased thyroid radiation dose (but increased blood & marrow radioactivity)  effectiveness?

FACTOR # 5: STATUS OF IODINE SUFFICIENCY (or DEFICIENCY) Intra-thyroidal iodine stores In iodine sufficient areas: 10 – 20 mg (mean: 15 mg) In iodine deficient areas: 2 – 5 mg (mean 3.5 mg) Competition of stable iodine vs. radioiodine “Iodine-poor” diet list, etc FACTOR # 6: RADIATION SENSITIVITY Difficult to measure Prior use of anti-thyroid drugs (PTU but not Methimazole) confers “radio-resistance”  treatment failure vs use higher I131 dose

I131 Treatment Outcomes Effects on Thyroidal Physical Configuration Decrease in global size (for diffuse enlargement) Decrease in nodule number & dimensions (for nodular enlargement) Effects on Thyroidal Function Desired: Euthyroidism Inevitable: Hypothyroidism Unintended: Persistent hyperthyroidism Unfortunate / Inadvertent: Thyroid storm

I131 Treatment Outcomes Clinical Thyroidal Outcomes Hypothyroidism: early (within 1st year): 20%; 2 – 3% / annum; 50% within decade; +5% every 2 decades Clinical Non-Thyroidal Outcomes Risk for carcinogenesis: very little Other effects: hardly, if at all Non-Clinical Outcomes Safety & Efficiency Economic (Cost-Benefit)

I131 Treatment: Summary I131 has definitive role in the management of hyperthyroidism and other benign thyroid conditions, as appropriate Radiation effects influenced by several factors Effects on thyroidal physical configuration & function with projected variable outcomes I131 therapy is safe, efficient, cost-beneficial

Thank you! Salamat Po! Muchas gracias! Merci beaucoup! Vielen Dank! Obrigado! Terimah kasih! Shoukran! Shukriya! Mamnun! Spaciba! Arigato gozaimas! Xie xie! Mesi! Kab Khun! Dank!