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Medicine » "Radionuclide Treatments", book edited by Cigdem Soydal, ISBN 978-953-51-3380-3, Print ISBN 978-953-51-3379-7, Published: July 12, 2017 under CC BY 3.0 license. © The Author(s).

Chapter 2

Radioiodine Therapy of Malignant Thyroid Diseases

By Derya Cayir and Mine Araz
DOI: 10.5772/intechopen.68574

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Radioiodine Therapy of Malignant Thyroid Diseases

Derya Cayir and Mine Araz
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Radioiodine-131 (I-131) is used in the treatment of thyroid diseases: hyperthyroidism and differentiated thyroid cancer (DTC: papillary, follicular, Hurthle cell cancer). Treatment success depends on several factors. The most fundamental factor affecting the success of treatment is the susceptibility to target tissue I-131. In patients with differentiated thyroid cancers following total thyroidectomy, I-131 is given for ablation of residual thyroid tissue and treatment of metastatic disease. Physical and biological characteristics of I-131, uptake and effect mechanisms of the iodine in the thyroid follicular cells, indications and contraindications for I-131 therapy, patient preparation and administration of I-131, follow-up and precautions on possible side effects, and an overview on the clinical studies about I-131 therapy are presented.

Keywords: iodine, thyroid diseases, therapeutics, radiation, neoplasms

1. Introduction

Radioiodine-131 (I-131) is successfully used in treatment of thyroid diseases: hyperthyroidism and differentiated thyroid cancer for several years. I-131 is available as sodium iodine in gelatine capsules and drinking solution for oral application and intravenous injections. Advantages of this therapy are good tolerability, easy application, safety, and efficacy of treatment. The critical organ for I-131 is the thyroid gland. I-131 is taken up by follicular cells. Retention of I-131 in the cells depends on the metabolic activity of the cells. I-131 simultaneously emits two types of radiation: beta minus (β) radiation used for the therapy and gamma (γ) used for diagnosis. Due to the penetration of beta particles in the tissue, damaging effect of β radiation is limited to thyroid cells. The physical and biological characteristics of I-131, uptake and effect mechanisms of the iodine in the thyroid follicular cells, indications and contraindications for I-131 therapy, patient preparation and administration of I-131, follow-up and precautions on possible side effects, and an overview on the clinical studies about I-131 therapy are presented under this title.

2. Epidemiology

Thyroid cancer constitutes 1.4% of all cancers and 15% of all endocrinologic malignancies. Thyroid cancer is responsible from 0.2 to 0.5% of cancer-related death. About 90–95% of thyroid cancers are differentiated thyroid cancers of follicular cell origin. Annual incidence is 1.2–2.6/100,000 in men and 2.0–3.8/100,000 in women. Mortality rates have been reported as 0.2–1.2/100,000 in men and 0.4–2.8/100,000 in women [1].

3. Treatment options: role of radioiodine

Front-line therapy of differentiated thyroid cancer (DTC) is surgery. Because multifocality and multicentricity is frequent, total or near-total thyroidectomy is the treatment of choice. Samaan et al. have reported that recurrence rates were lower and survival rates were higher in total thyroidectomized patients [2]. Following total thyroidectomy, I-131 is given for ablation of residual thyroid tissue and treatment of metastatic disease. To achieve a successful ablation and treatment, I-131 should be taken up by residual thyroid and metastatic tumors. The function of cancerous follicular cells is poorer than normal follicular cells. While normal thyroid tissue concentrates 0.5–1.0% of the administered I-131 dose, cancerous cells concentrate 0.01–0.02%.

Papillary cancer (the largest histopathologic group of thyroid cancers), follicular cancer, less than 10% of Hurthle cell variant papillary cancer, and mixed variant medullary cancer show I-131 uptake [3]. Ablation is defined as the radioiodine therapy given for destruction of functional residual thyroid tissue in or out of the thyroid bed. Therapy is the term used for sterilization of residual functional tumoral cells. As the volume of residual thyroid decreases, success of ablation increases. If residual thyroid tissue weighed <2 grams (gr), ablation efficiency was reported as 94%, while this rate may fall as low as 64% in larger residues [4].

The European Association of Nuclear Medicine (EANM) recommends I-131 ablation for all differentiated thyroid cancer patients who have a tumor size >1 cm [5]. For patients with tumor size smaller than <1 cm with no other risk factors like capsular invasion, lymphovascular invasion, lymph node (LN) or distant metastasis, history of radiation exposure, and diffuse sclerosing subtypes, radioiodine ablation is debatable. The American Thyroid Association (ATA) does not recommend radioiodine in low-risk disease [6].

Ablation provides higher thyroglobulin (Tg) sensitivity, treatment of undetectable micrometastatic disease, and a higher survival. Increase in thyroid-stimulating hormone (TSH) levels for ablation helps detection of metastatic disease on the postablative scan. In a prospective study of 25 years of follow-up, it was reported that none of the patients who were totally ablated died of thyroid cancer, but in seven patients in whom ablation failed, the reason of death was thyroid cancer [7]. Thyroid hormone replacement may not be started after surgery to achieve high TSH levels before I-131 therapy performed 4–6 weeks later [89]. However, because euthyroidism augments tissue repair and prevents from postsurgical complications, tetraiodothyronine (T4) replacement therapy is generally started after total thyroidectomy [10].

4. Patient preparation for radioiodine therapy

T4 is stopped before radioiodine therapy and triiodothyronine (T3) can be started instead (25–75 μg/day), making sure that T3 is also withdrawn 2 weeks before I-131 administration [10]. The reason why T3 is given is that T3 has a shorter half-life than T4 (0.8 days versus 7 days) and yields a faster TSH elevation after withdrawal compared to T4. Thus, hypothyroid period is shortened, and potential tumor growth rate stimulated by TSH is decreased.

Low-iodine diet is recommended for 3 weeks before radioiodine treatment, and drugs with stable iodine content should be ceased (Tables 1 and 2).

Iodized salt
Milk and derivatives (cheese, yoghurt, ice-cream, etc.)
Processed meat products (salami, sausage, etc.)
Packed food (chips, cookies, biscuits, etc.)
Canned vegetables and fruits
Green vegetables (spinach, lettuce, etc.)
Red pepper
Red food dye

Table 1.

Avoided food.

Drug or moleculeRecommended withdrawal time
Propylthiouracil, perchlorate, sulfonamides, tapazole, thiocyanate, penicillin, nitrates, antihistamines, and anticoagulants1 week
Iodine-containing solutions (Lugol’s solution, Betadine), antitussives, and vitamin preparates
Triiodothyronine (T3)
2 weeks
Tetraiodothyronine (T4)4–6 weeks
Amiodarone4–12 weeks
Intravenous contrast agents1–3 weeks
Oral cholecystographic agents2–3 weeks

Table 2.

Drugs decreasing radioiodine uptake in thyroid cells and recommended withdrawal time.

In cases of inadequate TSH elevation (pituitary disease, pituitary insufficiency of the elderly, extensive functioning thyroid cancer metastasis), recombinant human TSH (rhTSH: thyrotropin alpha, Thyrogen®) can be used. 0.9 mg rhTSH is intramuscularly injected for two consecutive days. Twenty-four hours later than the second dose of rhTSH administration, I-131 is given orally. Its safety and efficacy have been found noninferior to endogenous hypothyroidism [11, 12]. There are a few publications mentioned in the use of rhTSH after redifferentiation therapy with retionic acid (13-cis-retinoic acid, isotretinoin) in undifferentiated thyroid cancer to increase radioiodine uptake [13, 14].

Preablative TSH and Tg levels are measured. If TSH is >30 μU/ml, then I-131 can be given [10]. Thyroglobulin is a glycoprotein produced by functioning follicular cells. Detectable Tg after total thyroidectomy is a marker of persistent or recurrent diseases. In subtotal thyroidectomized patients, Tg measurement is not reliable. Thyroglobulin levels should not be used as a single criterion for determining necessity of radioiodine treatment. However, Tg levels >5–10 mg/dL point out that there exists an amount of functioning thyroid tissue to be ablated. Conversely, Tg < 1 ng/dL does not exclude radioiodine avid disease either [6].

Patients should be fasting for 2–4 hours before I-131 administration. The aim of fasting is to increase I-131 absorption and decrease risk of vomiting.

5. Radioiodine for ablation

Ablation doses are still a matter of debate. Beierwaltes et al. have reported that 3.7 GBq (100 mCi) I-131 ablates 85% of thyroid remnants [15]. Lower doses of 1.11 GBq (30 mCi) have been shown to be noninferior; however, there are conflicting results [1619]. There are three approaches for determination of I-131 dose: low dose, fixed high dose, and optimal dose. Low dose refers to 1.11 GBq (30 mCi). If ablation could not be maintained by a single dose, repeated doses can be given by 3–6 months of intervals. Although it depends on local radiation protection rules, hospitalization can be avoided in some regions in the world by dose administration. Lower whole-body and gonadal radiation doses and lower risk of side effects of radioiodine are other advantages. However, if ablation failed, repeated therapies cause long span of hypothyroidism. Stunning is another important disadvantage in secondary ablation doses. Stunning is defined as decrease of radioiodine uptake due to previous I-131 administrations for diagnostic or treatment purposes. Park et al. have reported that diagnostic doses between 111 and 370 MBq (3–10 mCi) I-131 caused stunning in a dose-dependent manner and this effect was overcome by the use of I-123 [20]. I-123 is a good alternative for scanning before I-131 treatment if preablative whole-body scan is necessary, as it gives a lower absorbed dose and provides better image quality and high accuracy [21]. Fixed high doses for ablation are given as 277.5–555 MBq (75–150 mCi). This is an effective and easy method to achieve ablation at a single step, and hypothyroid state is shorter. Nemec et al. have reported that over 85% of the patients ablation was maintained eradicating the need for a second dose [22].

Approach of optimal dose ablation aims to provide ablation of the whole residual thyroid tissue with the lowest radiation burden possible to extrathyroidal tissues [9]. For optimal dose calculation, formulations considering the weight of residual tissue and radioiodine uptake are used:

Administeredactivity:Planneddose×Glandweight×6.67Teff×% uptake24hour

Teff: effective half-life

Dose calculation approach may be theoretically reasonable, but it is troublesome to calculate biological half-life by collecting samples of urine and gaita from the patients, and interobserver variabilities in the measurement of residual tissue may cause mistakes. Ablation success rates of fixed high-dose and dose calculation methods are similar. So, fixed high-dose administration is the preferred method with regard to dose calculation.

As I-131 is primarily excreted by urine, dose reduction in renal failure and dialysis should be concerned. Kaptein et al. have reported that in patients who undergo continuous abdominal peritoneal dialysis, radioiodine clearance decreased five times and in order to optimize whole-body and bone marrow dose, radioiodine dose should be reduced by 5 [23]. By dialysis, effective half-life is shortened and tumoral dose is decreased. I-131 administration should be postponed after dialysis. Other situations which cause a change in distribution and increase retention are peritoneal ascites, pleural effusion, and extensive functioning metastasis.

Whole-body I-131 scan should be performed on postablative 2–6 days or after whole-body radiation dose is measured below 370 MBq (10 mCi). This study is important in determination of prognosis, as the absence of detectable metastases decreases risk of recurrence.

6. Adjuvant radioiodine therapy and treatment of metastasis

Postsurgical administration of I-131 provides a significant decline in recurrence rates. This is attributable to adjuvant usage of radioiodine which aims destruction of unknown micrometastasis rather than ablation of residual thyroid [10, 24, 25]. For apparent metastases detected before surgery or in the follow-up, the primary requirement is radioiodine avidity. Fixed high doses are frequently used for treatment of thyroid cancer metastases (Table 3).

Metastatic regionDose GBq (mCi)
Residual thyroid cancer in the thyroid bed3.7 (100)
Cervical LN metastases5.55–6.47 (150–175)
Lung metastases6.47–7.4 (175–200)
Distant metastases7.4 (200)

Table 3.

Doses used in the treatment of functioning thyroid cancer metastasis.

Another approach in treatment of metastasis is dose calculation according to the upper limits of blood and whole-body dosimetry and quantitative tumor or lesional dosimetry.

Five hundred fifty-five MBq (150 mCi) treats 95% of metastases in the thyroid bed. Upper limit of radioiodine dose for a single administration is determined as 740 MBq (200 mCi), set for a blood radiation dose below 200 rad (200 cGy) (maximum tolerated dose) [9]. In order to provide enough radiation to the tumor, formulations concerning radioiodine uptake value, tumor volume, and effective half-life are used:

DGy/mCi:%uptake24hr×152×TeffTumormass gram

For lymph node metastases, surgery is the first treatment to try, especially in bulky disease. Small LN metastases with adequate radioiodine uptake can be treated with I-131.

Adjunctive radioiodine therapy after surgery is generally recommended. Published in a retrospective series is that, a delay in radioiodine therapy for 6 months or more caused disease progression, and survival rates were decreased [26].

Cervical lymph node involvement doesn’t increase mortality but morbidity. The lymph node is common especially in papillary carcinoma, and its incidence has been reported 48 and 17% below and over age 40 [27]. Recurrence rates are twice as much in nodal metastatic disease [10]. It has been proved that recurrent metastases decrease by treatment of metastatic lymph nodes by I-131 [28].

Distant metastasis significantly reduces survival rates. Mortality rates are higher in brain and skeletal metastasis. In a series, distant metastasis was detected in 19% of the patients who received radioiodine treatment. Of these, 44% were to lungs, 31% to mediastinum, and 23% to the skeletal system [29]. Pulmonary metastasis is seen in 2–12% of the cases, and its frequency is less in patients who had undergone total thyroidectomy and radioiodine therapy [28, 30].

Pulmonary metastasis occurs by lymphogen, whereas skeletal metastasis occurs by microinvasion and hematogen way. The fact that there is a correlation between cervical lymph node and pulmonary metastasis and a reverse correlation between nodal and skeletal metastasis supports this opinion. Skeletal metastasis has a worse prognosis than lung metastasis. Skeletal metastasis is seen five times more frequent in follicular carcinoma patients than in papillary carcinoma patients and in the elderly. The cranium, vertebral column, and costae are generally involved [22].

3.7–7.4 GBq (100–200 mCi) I-131 is recommended to be administered by 6–12 months of intervals. Therapy should be continued till all radioiodine avid lesions are ablated or an intolerable complication is likely to arise. For iodine avid disease, there is no upper limit for cumulative dose. However, due to high complication risks, doses over 22.2 GBq (600 mCi) should be evaluated on a patient basis. If complete response can’t be achieved but disease stays stable, then intervals between doses can be extended, or therapy can be stopped with close monitoring [5].

7. Differentiated thyroid carcinoma derived from ectopic tissue

Sublingual area is the most common place for ectopic thyroid development. Insufficient T4 production in ectopic tissue may cause TSH elevation and thus hyperplasia by stimulation. Long-term and intense TSH stimulation is blamed for carcinoma development in these cases. Thyroglossal canal originated papillary carcinoma may have an invasive character in 10% of the cases [31]. In 3% of the cases, ectopic thyroid tissue is found in ovarian teratoma (struma ovarii). Low-grade malignant tumor may arise from struma ovarii (5–20%), and some may metastasize [32]. Although management approaches are still uncertain, treatment of cancer of an aberrant thyroid tissue is the excision of the tumor followed by radioiodine therapy.

8. Contraindications

Absolute contraindications are pregnancy and nursing. If I-131 administration is essential, then nursing should be stopped [33, 34]. I-131 passes through the placenta and concentrates in fetal thyroid (<12 weeks). This causes serious hypothyroidism. Maternal bladder activity also causes fetal irradiation. Pregnancy should be avoided for 6–12 weeks after radioiodine therapy. Other relative contraindications for I-131 are bone marrow depression, pulmonary, salivary gland and renal function interruption, possibility of severe edema, and compression symptoms in brain metastasis [5].

9. Complications

There are acute (first 3 months) and chronic (later than 3 months) complications of radioiodine therapy. Acute complications are sialadenitis (most frequent), radiation parotitis and thyroiditis, metallic taste, gastrointestinal symptoms like nausea and vomiting due to radiation gastritis, transient bone marrow depression (anemia in 36% of the patients, leukopenia 10%, thrombocytopenia 3%), radiation pneumonitis and pulmonary fibrosis, radiation cystitis, transient amenorrhea (secondary to pituitary-gonadal hormonal axis), decreased testicular function or fertilization, cerebral edema or spinal compression in metastatic cases, keratoconjunctivitis, and decreased lacrimal function [35]. Chronic complications include secondary malignancies most frequently leukemia, myeloid leukemia, less frequently bladder cancer, salivary gland neoplasia, hypo- and hyperparathyroidism, and hypothyroidism [3638].

10. Radioiodine therapy of pediatric differentiated thyroid cancer

Prognostic factors in differentiated thyroid cancer of the thyroid are not very well known because it is a relatively rare entity (3–4%) compared to thyroid cancer of the adults. In long-term follow-up, survival rates are found to be high despite increased rates of local recurrences and distant metastasis. Neck and pulmonary metastases concentrate and respond to radioiodine well [10]. Aggressive surgery followed by radioiodine is generally the preferred treatment option [39]. Radioiodine decreases recurrence in patients with known residual disease [40]. Disease-free survival rates are shown to be improved by radioiodine ablation without any significant increase in the risk of secondary malignancies [41]. I-131 treatment is recommended in radioiodine avid unresectable locoregional or distant metastasis [42].


1 - Schlumberger MJ. Papillary and follicular thyroid carcinoma. N Engl J Med. 1998:29;338(5):297-306.
2 - Samaan NA, Schultz PN, Hickey RC, Goepfert H, Haynie TP, Johnston DA, Ordonez NG. The results of various modalities of treatment of well differentiated thyroid carcinomas: A retrospective review of 1599 patients. Journal of Clinical Endocrinology and Metabolism. 1992;75:714-720
3 - Daniels GH. Radioiodine and thyroid cancer: Some questions, controversies, and considerations. Endocrine Practice. 2001;7:320-323
4 - Ross DS. Subclinical hypothyroidism. In: Braverman LE, Utiger RD, editors. Werner and Ingbar’s The Thyroid, a Fundamental and Clinical Text. 7th ed. Philadelphia-New York: JP Lippincott-Raven Publishers; 1996. pp. 1010-1015
5 - Luster M, Clarke SE, Dietlein M, Lassmann M, Lind P, Oyen WJ, Tennvall J, Bombardieri E, European Association of Nuclear Medicine (EANM). Guidelines for radioiodine therapy of differentiated thyroid cancer. European Journal of Nuclear Medicine and Molecular Imaging. 2008;35:1941-1959
6 - Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26:1-133
7 - Krishnamurthy GT, Blahd WH. Radioiodine I-131 therapy in the management of thyroid cancer. A prospective study. Cancer. 1977;40:195-202
8 - Hurley JR, Becker DV. The use of radioiodine in the management of thyroid cancer. In: Freeman LM, Weissman HS, (eds). Nuclear Medicine Annual. New York: Raven Press; 1983. pp. 329-384
9 - Beierwaltes WH. The treatment of thyroid carcinoma with radioactive iodine. Seminars in Nuclear Medicine. 1978;8:79-94
10 - Harbert JC. Radioiodine therapy of differentiated thyroid carcinoma. In: Harbert JC, Eckelman WC, Neumann RD, (eds). Nuclear Medicine: Diagnostic and Therapy. 5th ed. New York: Thieme Medical Publishers; 1996. pp. 945-1019
11 - Haugen BR, Pacini F, Reiners C, Schlumberger M, Ladenson PW, Sherman SI, et al. A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer. Journal of Clinical Endocrinology and Metabolism. 1999;84:3877-3885
12 - Jarzab B, Handkiewicz-Junak D, Roskosz J, Puch Z, Wygoda Z, et al. Recombinant human TSH-aided radioiodine treatment of advanced differentiated thyroid carcinoma: A single-centre study of 54 patients. European Journal of Nuclear Medicine. 2003;30:1077-1086
13 - Schmutzler C, Kohrle J. Retinoic acid redifferentiation therapy for thyroid cancer. Thyroid. 2000;10:393-406
14 - Boerner AR, Petrich T, Weckesser M, Langen KJ, Knapp WH. Monitoring isotretinoin therapy in thyroid cancer using 18F-FDG PET. European Journal of Nuclear Medicine. 2002;29:231-236
15 - Beierwaltes WH, Rabbani R, Dmuchowski C, Lloyd RV, Eyre P, Mallette S. An analysis of “ablation of thyroid remnants” with I-131 in 511 patients from 1947-1984: Experience at University of Michigan. Journal of Nuclear Medicine. 1984;25:1287-1293
16 - Mallick U, Harmer C, Yap B, Wadsley J, Clarke S, Moss L, Nicol A, Clark PM, Farnell K, McCready R, Smellie J, Franklyn JA, John R, Nutting CM, Newbold K, Lemon C, Gerrard G, Abdel-Hamid A, Hardman J, Macias E, Roques T, Whitaker S, Vijayan R, Alvarez P, Beare S, Forsyth S, Kadalayil L, Hackshaw A. Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer. The New England Journal of Medicine. 2012;366:1674-1685
17 - Kuni CC, Kleingensmith WC 3rd. Failure of low doses of I-131 to ablate residual thyroid tissue following surgery of thyroid cancer. Radiology. 1980;137:773-774
18 - DeGroot LJ, Reilly M. Comparison of 30 and 50 mCi doses of iodine-131 for thyroid ablation. Annals of Internal Medicine. 1982;96:51-53
19 - Johansen K, Woodhouse NJ, Odugbesan O. Comparison of 1073 MBq and 3700 MBq iodine-131 in postoperative ablation of residual thyroid tissue in patients with differentiated thyroid cancer. Journal of Nuclear Medicine. 1991;32:252-254
20 - Park HM, Perkins OW, Edmondson JW, Schnute RB, Manatunga A. Influence of diagnostic radioiodines on the uptake of ablative dose of iodine-131. Thyroid. 1994;4:49-54
21 - Park HM, Park YH, Zhou XZ. Detection of thyroid remnant metastases without stunning: An ongoing dilemma. The diagnostic accuracy of 123I and 131I as scanning agents and their effect on the outcome of radioablation therapy. Thyroid. 1997;7:277-280
22 - Nemec J, Röhling S, Zamrazil V, Pohunková D. Comparison of the distribution of diagnostic and thyroablative I-131 in the evaluation of differentiated thyroid cancers. Journal of Nuclear Medicine. 1979;20:92-97
23 - Kaptein M, Levenson H, Siegel ME, Gadallah M, Akmal M. Radioiodine dosimetry in patients with end-stage renal disease receiving continuous ambulatory peritoneal dialysis therapy. Journal of Clinical and Endocrinology Metabolism. 2000;85:3058-3064
24 - Waxman A, Ramanna L, Chapman D, Chapman M, Brachman D, Tanasescu D, Berman B, Catz, Braunstein G. The significance of I-131 scan dose in patients with thyroid cancer. Determination of ablation: Concise communication. Journal of Nuclear Medicine. 1981;22:861-865
25 - Nĕmec J, Zamrazil V, Pohunková D, Zeman V, Röhling S. Mode spread of thyroid cancer. Oncology. 1979;36:232-235
26 - Higashi T, Nishii R, Yamada S, Nakamoto Y, Ishizu K, Kawase S, Togashi K, Itasaka S, Hiraoka M, Misaki T, Konishi J. Delayed initial radioactive iodine therapy resulted in poor survival in patients with metastatic differentiated thyroid carcinoma: A retrospective statistical analysis of 198 cases. Journal of Nuclear Medicine. 2011;52:683-689
27 - Schlumberger M, Fragu P, Gardet P, Lumbroso J, Violot D, Parmentier C. A new immunoradiometric assay (IRMA) system for thyroglobulin measurement in the follow-up of thyroid cancer patients. European Journal of Nuclear Medicine. 1991;18:153-157
28 - Mazzaferri EL, Young RL. Papillary thyroid carcinoma: A 10 year follow-up report of the impact of therapy in 576 patients. American Journal of Medicine. 1981;70:511-518
29 - Beierwaltes WH, Nishiyama RH, Thompson NW, et al. Survival time and ‘cure’ in papillary and follicular thyroid carcinoma with distant metastases: Statistics following University of Michigan therapy. Journal of Nuclear Medicine. 1982;23:561-580
30 - Young RL, Mazzaferri EL, Rahe AJ, Dorfman SG. Pure follicular thyroid carcinoma: Impact of therapy in 214 patients. Journal of Nuclear Medicine. 1980;21:733-737
31 - DeGroot LJ, Larsen PR, Refetoff S, Stanbury JB. The Thyroid and Its Diseases. 5th ed. New York: John Wiley & Sons; 1984. p. 633
32 - Fox H, Langley FA. Tumors of the Ovary. England: Heinemann Medical Books; 1976. p. 236
33 - Robinson PS, Barker P, Campbell A, Henson P, Surveyor I, Young PR. Iodine-131 in breast milk following therapy for thyroid carcinoma. Journal of Nuclear Medicine. 1994;35:1797-1801
34 - Mountfort PJ. Restrictions following iodine-131 treatment: A time for charge or more data required?. European Journal of Nuclear Medicine. 1994;22:903-905
35 - Haynie TP, Beierwaltes WH. Hematologic changes observed following I-131 therapy for thyroid carcinoma. Journal of Nuclear Medicine. 1963;4:85-91
36 - Brincker H, Hansen HS, Andersen AP. Induction of leukaemia by I-131 treatment of thyroid carcinoma. British Journal of Cancer. 1973;28:232-237
37 - Refetoff S, Harrison J, Kavanfilski BT, Kaplan EL, De Groot LJ, Bekerman C. Continuing occurrence of thyroid carcinoma after irradiation to the neck in infancy and childhood. The New England Journal of Medicine. 1975;292:171-175
38 - Beierwaltes WH. The treatment of hyperthyroidism with iodine-131. Seminars in Nuclear Medicine. 1978;8:95-103
39 - Jarzab B, Junak DH, Wloch J, Kalemba B, Roskosz J, Kukulska A, Puch Z. Multivariate analysis of prognostic factors for differentiated thyroid carcinoma in children. European Journal of Nuclear Medicine. 2000;27:833-841
40 - Chow SM, Law SC, Mendenhall WM, Au SK, Yau S, Mang O, Lau WH. Differentiated thyroid carcinoma in childhood and adolescence-clinical course and role of radioiodine. Pediatric Blood Cancer. 2004;42:176-183
41 - Jarzab B, Handkiewicz-Junak D, Wloch J. Juvenile differentiated thyroid carcinoma and the role of radioiodine in its treatment: A qualitative review. Endocrine Related Cancer. 2005;12:773-803
42 - Francis GL, Waguespack SG, Bauer AJ, Angelos P, Benvenga S, Cerutti JM, Dinauer CA, Hamilton J, Hay ID, Luster M, Parisi MT, Rachmiel M, Thompson GB, Yamashita S. American Thyroid Association Guidelines Task Force. Management guidelines for children with thyroid nodules and differentiated thyroid cancer. Thyroid. 2015 Jul;25(7):716-759