Guidelines for radioiodine therapy of differentiated thyroid cancer

Introduction  The purpose of the present guidelines on the radioiodine therapy (RAIT) of differentiated thyroid cancer (DTC) formulated by the European Association of Nuclear Medicine (EANM) Therapy Committee is to provide advice to nuclear medicine clinicians and other members of the DTC-treating community on how to ablate thyroid remnant or treat inoperable advanced DTC or both employing large 131-iodine (¹³¹I) activities. Discussion  For this purpose, recommendations have been formulated based on recent literature and expert opinion regarding the rationale, indications and contraindications for these procedures, as well as the radioiodine activities and the administration and patient preparation techniques to be used. Recommendations also are provided on pre-RAIT history and examinations, patient counselling and precautions that should be associated with ¹³¹I iodine ablation and treatment. Furthermore, potential side effects of radioiodine therapy and alternate or additional treatments to this modality are reviewed. Appendices furnish information on dosimetry and post-therapy scintigraphy.     

Low-dose radioiodine therapy for patients with intermediate- to high-risk differentiated thyroid cancer

Annals of Nuclear Medicine - The efficacy of low-dose radioiodine therapy (RIT) for intermediate-risk or high-risk differentiated thyroid cancer (DTC) patients is controversial. Because of the...     

Testicular function after radioiodine therapy for thyroid carcinoma

Radiotherapy can cause infertility in both men and women. However, few data are available concerning the effects of radioiodine therapy for thyroid carcinoma on testicular function. We investigated 25 men (age 23-73 years) with differentiated thyroid carcinoma in a longitudinal prospective trial. Follicle-stimulating hormone (FSH), inhibin B, luteinising hormone (LH) and testosterone were measured before (n = 25) and 3 months (n = 11), 6 months (n = 18), 12 months (n = 22), and 18 months (n = 18) after radioiodine therapy [radioiodine dose (mean +/- SEM): 9.8+/-0.89 GBq]. Before therapy, FSH was 5.4+/-0.77 IU/l; it increased significantly (P<0.001) to 21.3+/-2.4 IU/l after 6 months and fell to 7.4+/-1.3 IU/l after 18 months (normal range: 1.8-9.2 IU/l). Inhibin B was significantly decreased (P<0.001) from 178+/-25.3 pg/ml before therapy to 22.2+/-5.5 pg/ml after 3 and 29.4+/-5.7 pg/ml after 6 months and rose to 154+/-23.3 pg/ml after 18 months (normal range 75-350 pg/ml). LH and testosterone were within the normal range during the whole study (1.6-9.2 IU/l and 10.4-34.7 nmol/l, respectively). LH was significantly increased (P<0.001) from 2.8+/-0.33 IU/l before therapy to 5.9+/-0.69 IU/l 6 months after therapy and then fell slowly to 4.0+/-0.45 IU/l after 18 months. Total testosterone was significantly increased (P<0.01) from 12.8+/-0.99 nmol/l at baseline to 19.8+/-1.7 nmol/l after 12 months and 19.6+/-1.7 nmol/l after 18 months. The testosterone/LH ratio (normal range: 3.3-17.9 nmol/IU) fell from 5.8+/-0.66 nmol/IU to 3.0+/-0.36 nmol/IU after 3 months (P<0.01); it remained close to the latter value after 6 months (3.4+/-0.49 nmol/IU) and then rose to 5.5+/-0.6 nmol/IU after 18 months. In conclusion, 3 and 6 months after radioiodine therapy all patients showed elevated FSH and decreased inhibin B levels, reflecting severely impaired spermatogenesis. At the same time a compensated insufficiency of the Leydig cell function was observed. Eighteen months after the last radioiodine therapy, mean values of gonadal function had completely recovered.     

Cytokinesis-block micronucleus test in patients undergoing radioiodine therapy for differentiated thyroid carcinoma

Cytokinesis-blocked micronucleus assay (MNT) was applied in the peripheral blood lymphocytes of patients undergoing radioiodine-131 ((131)I) therapy for differentiated thyroid carcinoma (DTC) after thyroidectomy to assess the genotoxic risk of this therapy. The amount of administered (131)I activity varied from 3,330 to 4,030 MBq. Blood samples were taken immediately before (131)I administration and one month later, along with routine blood tests. Twenty-six patients underwent radioiodine ablation (RIA) or radioiodine therapy (RIT) after radical thyroidectomy. The aim of this therapy was to ablate residual thyroid tissue, to treat lymph node metastases and/or distant lung metastases. The amount of orally administered activity of (131)I ranged between 3,330 and 4,030 MBq according to the kind of therapy (RIA or RIT). In five patients the cytogenetic analysis was performed immediately before and one month after the second therapy which was given to them 6 months to 1 year after the first. Three patients were male and 23 female. The age of the patients ranged between 23 and 76 years (mean age: 48.6 years). Results show that after radioiodine therapy there is a significant increase in the frequency of micronuclei. Comparing the average frequency of micronuclei in the patients studied before and after (131)I, a more than doubling increase was found. Mean values +/- SD of the patients before and after (131)I therapy were 10.72 per thousand +/- 5.84 per thousandand 25.28 per thousand +/- 12.6 per thousand respectively. These findings indicate a genotoxic activity of (131)I therapy estimated after a period of one month.     

Testicular function after radioiodine therapy for thyroid carcinoma

Radiotherapy can cause infertility in both men and women. However, few data are available concerning the effects of radioiodine therapy for thyroid carcinoma on testicular function. We investigated 25 men (age 23–73 years) with differentiated thyroid carcinoma in a longitudinal prospective trial. Follicle-stimulating hormone (FSH), inhibin B, luteinising hormone (LH) and testosterone were measured before (n=25) and 3 months (n=11), 6 months (n=18), 12 months (n=22), and 18 months (n=18) after radioiodine therapy [radioiodine dose (mean ± SEM): 9.8±0.89 GBq]. Before therapy, FSH was 5.4±0.77 IU/l; it increased significantly (P<0.001) to 21.3±2.4 IU/l after 6 months and fell to 7.4±1.3 IU/l after 18 months (normal range: 1.8– 9.2 IU/l). Inhibin B was significantly decreased (P<0.001) from 178±25.3 pg/ml before therapy to 22.2±5.5 pg/ml after 3 and 29.4±5.7 pg/ml after 6 months and rose to 154±23.3 pg/ml after 18 months (normal range 75– 350 pg/ml). LH and testosterone were within the normal range during the whole study (1.6–9.2 IU/l and 10.4–34.7 nmol/l, respectively). LH was significantly increased (P<0.001) from 2.8±0.33 IU/l before therapy to 5.9±0.69 IU/l 6 months after therapy and then fell slowly to 4.0±0.45 IU/l after 18 months. Total testosterone was significantly increased (P<0.01) from 12.8±0.99 nmol/l at baseline to 19.8±1.7 nmol/l after 12 months and 19.6±1.7 nmol/l after 18 months. The testosterone/LH ratio (normal range: 3.3–17.9 nmol/IU) fell from 5.8±0.66 nmol/IU to 3.0±0.36 nmol/IU after 3 months (P<0.01); it remained close to the latter value after 6 months (3.4±0.49 nmol/IU) and then rose to 5.5± 0.6 nmol/IU after 18 months. In conclusion, 3 and 6 months after radioiodine therapy all patients showed elevated FSH and decreased inhibin B levels, reflecting severely impaired spermatogenesis. At the same time a compensated insufficiency of the Leydig cell function was observed. Eighteen months after the last radioiodine therapy, mean values of gonadal function had completely recovered. Received 5 October and in revised form 27 December 1999     

Evaluation of low-dose radioiodine ablation therapy in postsurgical thyroid cancer patients

Nineteen patients with differentiated thyroid carcinoma were given low dose (30 mCi) radioiodine therapy for the ablation of residual thyroid tissue following total thyroidectomy. Using 5- to 10-mCi diagnostic I-131 scans, ablation was achieved in two of 19 patients following the first low dose and three of 12 patients following the second low-dose therapy. The ablation response was 53% (ten of 19) following one large dose (100 mCi) in another concurrent group of 19 patients. The ablation response following the first low dose when compared with the first high-dose therapy was significantly lower (P = 0.015). The combined ablation response following first and second low doses (five of 14) when compared to a single large dose was not significantly different (P = 0.534). The use of low-dose-I-131 therapy, although not as effective as large dose therapy, may be warranted in patients resistant to entering the hospital for therapy. However, ablation as defined by a five- to ten-mCi I-131 scan can be expected to occur in only one third of the patients after two attempts at ablation, while a single 100-mCi regimen can be successful in achieving ablation in over one half of the patients after the first attempt.     

Respiratory distress caused by radioiodine therapy in patients with differentiated thyroid cancer

Respiratory distress accompanied by stridor is an uncommon complication of 131I radioiodine therapy for differentiated thyroid cancer that occurs within 48 hours of treatment. This report presents three cases with papillary thyroid carcinoma in which 131I therapy caused this acute complication. One of them had no apparent risk for this complication such as the existence of remnant thyroid tissue or laryngeal problems before the treatment. These cases remind physicians that 131I therapy is not a simple, riskless procedure.     

Results of radioiodine therapy in patients with pulmonary metastases of differentiated thyroid cancer

Factors affecting the effect of 131I treatment and survival after pulmonary metastases in patients with differentiated thyroid cancer, were studied. Between 1984-1999, pulmonary metastases was observed in 51 out of 153 patients with differentiated thyroid cancer at our institution. Of these 41 patients had papillary and 10 follicular thyroid cancer. There were 37 females and 14 males with mean age (+/- S.D.) of 50.5 +/- 19.0 years. These 51 patients were subjected to 131I therapy. The effect of 131I treatment and the prognostic values of the following variables were examined: sex, age at the time of 131I treatment, histologic type of cancer, size of pulmonary metastases on CT, total-body scintigraphy with 201Tl and 131I, serum thyroglobulin levels and presence of metastases in distant sites other than lung. The effect of 131I treatment was evaluated by means of changes in the number and size of metastatic shadows on chest CT and by serum thyroglobulin levels. The minimum duration of follow-up was 12 months. Therapeutic 131I dose scans revealed detectable uptake in 25 of 51 patients. Therapeutic 131I dose uptake was achieved more frequently in patients under 40 years of age and in those with follicular cancers. Of the 51 patients, 13 were evaluated to be treated successfully. Those under 40 years of age, with 131I uptake in the lung and presence of other metastases showed a good response to treatment than others. Follicular cancer showed a more significant association with coarse type of lung metastases (> 5 mm in diameter on chest CT) and good 131I uptake than papillary cancer. Of all the variables studied, the best prognosis for survival was demonstrated by increased 131I uptake in pulmonary metastases. These results indicate that age, 131I uptake and presence of other metastases are important factors in predicting the effect of 131I treatment for pulmonary metastases of differentiated thyroid cancer.     

Visualization of nasolacrimal drainage system after radioiodine therapy in patients with thyroid cancer

The objective of this study was to report three cases with an accumulation of ¹³¹I in the nasolacrimal duct after radioiodine therapy for papillary thyroid cancer. A whole-body scan was taken 3 days after the administration of 3.7 GBq of ¹³¹I. Single-photon emission computed tomography (SPECT)/CT images were added when the location of a focal tracer uptake was undetermined on whole-body scans. In case 1, a 62-year-old woman complained of epiphora of the left eye after nine radioiodine therapies with a cumulative dose of 31.08 GBq. The left nasolacrimal duct was visualized at her tenth treatment with ¹³¹I. In case 2, a series of three radioiodine therapies had been given to a 73-year-old woman with a cumulative dose of 11.1 GBq. The accumulation of ¹³¹I was noted in the left nasolacrimal duct at her fourth treatment. She complained of epiphora of the left eye. In case 3, bilateral nasolacrimal ducts were visualized at the second radioiodine therapy in a 75-year-old woman. The patient had received 3.7 GBq of ¹³¹I at the first therapy. She did not complain of epiphora. It is possible that radiation from ¹³¹I that is secreted in tears and/or actively accumulated in the nasolacrimal duct may induce nasolacrimal duct obstruction. ¹³¹I in tears would be responsible for the visualization of nasolacrimal duct in the first two cases. ¹³¹I actively accumulated in the nasolacrimal duct might have been visualized in the third case. In summary, ¹³¹I is excreted in tears and is actively accumulated in the nasolacrimal duct. Obstruction of the lacrimal drainage system could occur after high-dose radioiodine therapy.     

Dosimetry study in patients with autonomous thyroid nodule who are candidates for radioiodine therapy.

A dosimetry study was performed on 26 patients with an autonomous thyroid nodule and suppressed serum thyroid-stimulating hormone, to determine the dose to extranodular tissue when the nodule receives 300 Gy for 131I therapy. METHODS: Parameters of radioiodine turnover to be used in the dosimetry formula were separately obtained for the nodule and the contralateral lobe, as a measurable example of the extranodular tissue, using 55 MBq 123I and a computer-assisted gamma camera. The biologic half-life of 123I was then converted into the effective half-life of 131I, and the volumes of the nodule and the lobe were obtained by scintigraphy or sonography. RESULTS: The mean dose to the contralateral lobe from uptake and irradiation by the nodule was calculated to be 32 Gy, and that to the ipsilateral lobe was estimated to be 34 Gy. CONCLUSION: During radioiodine therapy for autonomous thyroid nodules, the extranodular tissue receives a higher dose than is generally assumed, which explains the relatively high rate of post-treatment hypothyroidism reported in the literature.     

Tumour dosimetry and response in patients with metastatic differentiated thyroid cancer using recombinant human thyrotropin before radioiodine therapy

The development of recombinant human thyrotropin (rhTSH) has given clinicians new options for diagnostic follow-up and treatment of patients with differentiated thyroid cancer (DTC). This paper evaluates the tumour dosimetry and response following -iodine-131 treatment of metastatic thyroid cancer patients after rhTSH stimulation instead of classical hormone withdrawal-induced hypothyroidism. Nineteen consecutive (131)I treatments in 16 patients were performed after rhTSH stimulation. All patients had undergone a near-total thyroidectomy followed by an ablative dosage of (131)I. They all suffered from metastatic or recurrent disease showing tumoral (131)I uptake on previous post-treatment scintigraphy. Dosimetric calculations were performed using (131)I tumour uptake measurements from post-treatment (131)I scintigrams and tumour volume estimations from radiological images. Response was assessed by comparing pre-treatment serum thyroglobulin (Tg) level with the Tg level 3 months post treatment. In 18 out of 19 treatments, uptake of (131)I in metastatic or recurrent lesions was seen. The median tumour radiation dose was 26.3 Gy (range 1.3-368 Gy), and the median effective half-life was 2.7 days (range 0.5-6.5 days). Eleven of 19 treatments (10/16 patients) were evaluable for response after 3 months. (131)I therapy with rhTSH resulted in a biochemical partial response in 3/11 or 27% of treatments (two patients), biochemical stable disease in 2/11 or 18% of treatments and biochemical progressive disease in 6/11 or 55% of treatments. Our study showed that although tumour doses in DTC patients treated with (131)I after rhTSH were highly variable, 45% of treatments led to disease stabilisation or partial remission when using rhTSH in conjunction with (131)I therapy, without serious side-effects and with minimal impact on quality of life. RhTSH is therefore adequately satisfactory as an adjuvant tool in therapeutic settings and is especially suitable in advanced recurrent or metastatic DTC patients who may be intolerant to TSH stimulation by levothyroxine withdrawal.     

Results of radioiodine therapy in 47 patients with distant metastases of differentiated thyroid carcinoma

In the last ten years, 47 patients with distant metastases of differentiated thyroid carcinoma have been treated with 131I following total thyroidectomy. Post-therapy whole body 131I scans revealed detectable uptake in the metastatic lesions in 23 (62%) of 37 patients with lung metastases, 10 (67%) of 15 patients with bone metastases five (71%) of seven patients with mediastinal metastases, and neither of two patients with brain metastases. The concentration of 131I in the metastases was significantly correlated with serum T3 and T4 concentrations, and inversely correlated with serum TSH concentrations. Most of the patients with a strong positive scan were euthyroid, suggesting that thyroid hormones produced by the tumor compensated for hypothyroidism following total thyroidectomy. There was no significant relationship between serum thyroglobulin concentration during T4 replacement therapy and 131I uptake or the efficacy of therapy. Twenty patients with lung (54%), five with bone (33%), two with mediastinal (29%), and none with brain metastases showed tumor regression after treatment. Significantly increased 131I uptake in lung metastases, better therapeutic results and better prognosis were demonstrated in young patients. In conclusion, age, 131I whole body scanning and serum thyroid hormone concentrations are considered to be useful in predicting the efficacy of 131I treatment for distant metastases, especially in the lung.     

Guideline for radioiodine therapy for benign thyroid diseases (version 3)

The version 3 of the guideline for radioiodine therapy for benign thyroid diseases presents first of all a revision of the version 2. The chapter indication for radioiodine therapy, surgical treatment or antithyroid drugs bases on an interdisciplinary consensus. The manifold criteria for decision making consider the entity of thyroid disease (autonomy, Graves' disease, goitre, goitre recurrence), the thyroid volume, suspicion of malignancy, cystic nodules, risk of surgery and co-morbidity, history of subtotal thyroidectomy, persistent or recurrent thyrotoxicosis caused by Graves' disease including known risk factors for relapse, compression of the trachea caused by goitre, requirement of direct therapeutic effect as well as the patient's preference. Because often some of these criteria are relevant, the guideline offers the necessary flexibility for individual decisions. Further topics are patients' preparation, counseling, dosage concepts, procedural details, results, side effects and follow-up care. The prophylactic use of glucocorticoids during radioiodine therapy in patients without preexisting ophthalmopathy as well as dosage and duration of glucocorticoid medication in patients with preexisting ophthalmopathy need to be clarified in further studies. The pragmatic recommendations for the combined use of radioiodine and glucocorticoids remained unchanged in the 3rd version.