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.     

Graves' disease nd toxic nodular goiter--radioiodine therapy

At the 15th conference on the human thyroid in Heidelberg in 2001 the following aspects of the radioiodine therapy of benign thyroid disorders were presented: General strategies for therapy of benign thyroid diseases, criterions for conservative or definitive treatment of hyperthyroidism as first line therapy and finally preparation, procedural details, results, side effects, costs and follow-up care of radioiodine therapy as well as legal guidelines for hospitalization in Germany. The diagnosis Graves' hyperthyroidism needs the decision, if rather a conservative treatment or if primary radioiodine therapy is the best therapeutic approach. In the USA 70-90% of these patients are treated with radioiodine as first line therapy, whereas in Germany the conservative therapy for 1-1.5 years is recommended for 90%. This review describes subgroups of patients with Graves' disease showing a higher probability to relapse after conservative treatment. Comparing benefits, adverse effects, costs, and conveniences of both treatment strategies the authors conclude that radioiodine therapy should be preferred as first line therapy in 60-70% of the patients with Graves' hyperthyroidism.     

Antithyroid drugs as a factor influencing the outcome of radioiodine therapy in Graves' disease and toxic nodular goitre?

There is controversy over the factors that may influence the outcome of radioiodine therapy for benign thyroid diseases. Antithyroid medication has been claimed to negatively influence the effectiveness of radioiodine therapy in Graves' disease. In a longitudinal study, we assessed the influence of sex, age, antithyroid drugs, target radiation dose, target mass, applied activity, delivered dose, interval between last meal and application, and TSH, FT3 and FT4 levels on the outcome of radioiodine therapy. One hundred and forty-four patients (111 female, 33 male) suffering from Graves' disease (GD) and 563 patients (434 female, 129 male) with toxic nodular goitre (TNG) were entered in the study and followed up until 8 months after therapy. Treatment was defined as successful when the TSH level was found to be normal or elevated. Ninety-eight GD patients and 418 TNG patients were successfully treated. Forward stepwise multiple regression analysis models retained only the target mass in GD and the applied activity in TNG as significantly associated with the outcome of therapy. The predictive value of all variables involved was extremely low in both disease groups. Whereas concomitant antithyroid medication had no influence in GD, it adversely influenced radioiodine therapy of TNG. This effect may be attributed to a radioiodine "steal phenomenon" induced by TSH-stimulated normal thyroid tissue, which causes overestimation of the uptake in toxic nodules.     

Antithyroid drugs as a factor influencing the outcome of radioiodine therapy in Graves' disease and toxic nodular goitre?

There is controversy over the factors that may influence the outcome of radioiodine therapy for benign thyroid diseases. Antithyroid medication has been claimed to negatively influence the effectiveness of radioiodine therapy in Graves' disease. In a longitudinal study, we assessed the influence of sex, age, antithyroid drugs, target radiation dose, target mass, applied activity, delivered dose, interval between last meal and application, and TSH, FT₃ and FT₄ levels on the outcome of radioiodine therapy. One hundred and forty-four patients (111 female, 33 male) suffering from Graves' disease (GD) and 563 patients (434 female, 129 male) with toxic nodular goitre (TNG) were entered in the study and followed up until 8 months after therapy. Treatment was defined as successful when the TSH level was found to be normal or elevated. Ninety-eight GD patients and 418 TNG patients were successfully treated. Forward stepwise multiple regression analysis models retained only the target mass in GD and the applied activity in TNG as significantly associated with the outcome of therapy. The predictive value of all variables involved was extremely low in both disease groups. Whereas concomitant antithyroid medication had no influence in GD, it adversely influenced radioiodine therapy of TNG. This effect may be attributed to a radioiodine "steal phenomenon" induced by TSH-stimulated normal thyroid tissue, which causes overestimation of the uptake in toxic nodules.     

Graves病药物治疗后TSH增高伴摄99Tcm增强患者131I治疗

目的：探讨甲状腺功能亢进症（甲亢）抗甲状腺药物（ATD）治疗后促甲状腺激素（TSH）增高伴摄99Tcm增强患者131I治疗的可能性和必要性。方法：27例经临床ATD治疗后TSH增高伴摄99Tcm增强患者分3组，治疗组15例，及时进行131I治疗；随访观察组12例，仅作随访观察，均随访年，结果：治疗组15例中9例血清游离三碘甲状腺原氨酸（FT3），游离甲状腺激素（FT4），TSH水平及甲状腺显像均恢复正常。有2例5－6个月复查甲亢复发，第2次治疗后恢复正常，1例为早发甲低，甲低发生率为6．7％，随访观察组12例在1－4个月内均复发为典型甲亢，复发率100％，结论：甲亢ATD治疗后TSH增高伴摄99Tcm增强患者宜及时进行131I治疗。     

Results of a risk adapted and functional radioiodine therapy in Graves' disease

Aim of this study was to find out, if results of a functional orientated radioiodine therapy in Graves' disease could be optimized using a risk adopted dose concept. PATIENTS, METHOD: 351 patients with Graves' disease were treated for the first time between 11/97 and 8/01. The basic dose was 125 Gy, which was increased up to 250 Gy in a cumulative manner depending on clinical parameters (initial thyroid metabolism, thyroid volume, immunoreactivity). Two different methods of dosimetry were used. Occasional thyreostasis was withdrawn two days before the radioiodine test was started. Follow up was done on average 8 +/- 2.4 (4-17.2) months. TSH > or = 0.27 microIU/mL confirmed as a measure of the success. RESULTS: With improved pretherapeutic dosimetry and a mean target dose of 178 +/- 31 Gy (n=72) therapeutic success occurred in 66.7%, in 51.4% euthyreosis was restalled and in 15.3% of patients hypothyroidism was seen (TSH > 4.20 microIU/mL). With simplified pretherapeutic dosimetry and a mean target dose of 172 +/- 29 Gy (n=279) results were moderately impaired (63.8%, 40.1% and 23.7%). With increasing target dose therapeutic failure increased, as insufficiently adopted risk factors for therapeutic failure turned out the initial thyroid metabolism, the TcTU(s) as the (h)TRAb titer. CONCLUSION: Functional orientated RIT can be optimized by including illness specific characteristics, principal limitations are a high initial thyroid metabolism, a large thyroid volume and a high (h)TRAb-titer.     

The present status of I-131 therapy for Graves' hyperthyroidism in Japan (survey by questionnaire)

A survey on the I-131 therapy of Graves' hyperthyroidism was undertaken by questionnaire in 1,246 hospitals of Japan. One thousand and ninety seven of them (88.0%) responded to the questionnaire. In this paper, we report the results and analysis of the replies to the questionnaire. In the 121 hospitals (11.03%) of the respondents, I-131 therapy is being performed for Graves' hyperthyroidism. A gradual increase was observed in the annual number of I-131 treated Graves' disease patients during the period of 1998-2001, from 1,740 to 2,484. I-131 treatment was selected mainly for the cases with side effects from antithyroid drug (ATD) therapy, followed by the cases with complication of heart or hepatic diseases, recurrences of hyperthyroidism after surgery, radioiodine treatment, and long-term ATD treatment. The 41% of respondents used I-131 in order to restore euthyroidism, 34% aimed for hyperthyroidism and 41% used the dose properly between the two according to the patients. Administration dosage of I-131 was estimated mainly on the basis of thyroid uptake and volume in 93% of the respondents and 48% calculated the radiation dose by also determining the effective half-life in the thyroid gland. Thyroid size was estimated by scintigram (51%), US (33%), CT (22%) and palpation (12%). ATD treatment was used before I-131 administration by 70% of the respondents and 34% after radioiodine therapy. A low-iodine diet was given to the patients for a week (46%) or two weeks (47%) before I-131 administration. However, after treatment only 46% of the respondents continued low-iodine diet for a week.     

Health effects of therapeutic use of 131I in hyperthyroidism.

Since 1942, therapy with radioiodine (Na131I) has gained a major role in the treatment of benign thyroid disorders, notably hyperthyroidism caused by Graves' disease or toxic multinodular goiter. The very large series of patients treated so far offer the opportunity for an assessment of both benign and malignant side effects. Hyperthyroidism is sometimes observed after radioiodine therapy due to radiation induced thyroid hormone or by an immunological mechanism. Despite the numerous attempts to design dosage schedules aiming at euthyroidism, hypothyroidism occurs in the majority of patients throughout life. Transient hypothyroidism may be observed within the first year after therapy and is caused by an immunological mechanism. Radioiodine therapy in Graves' disease may induce or worsen ophthalmopathy, which can be prevented by steroids effectively. Hypoparathyroidism and hyperparathyroidism have been reported after radioiodine therapy but probably do not exceed the normal incidence. Sialitis is commonly observed but mostly in patients treated with radioiodine for thyroid cancer. There are no indications for induction of genetic abnormalities after radioiodine therapy although no definite conclusion can be reached. Much attention has been paid to malignant disease. In very large series, no effects of radioiodine therapy on survival have been observed. Some studies report an increased relative risk for certain types of cancer (notably thyroid cancer, stomach cancer, bladder and kidney cancer or hematological malignancies). However, these observations were not confirmed by other large studies, so that no definite conclusion with respect to risk for certain types of malignant disease can be drawn. However, radioiodine therapy for benign thyroid disorders has generally been considered safe and without major side effects, hypothyroidism being the most frequent one.     

Strategies of radioiodine therapy for Graves' disease

Several therapeutic options are available for the treatment of Graves' disease (GD), including long-term antithyroid drug medication (ATD), near-total resection (NTR) and radioiodine therapy (RIT). These treatments are used with different frequencies depending on geographical location, size of the goitre, age of the patient and experience of the physician. It should be noted that RIT is still being applied more frequently in the United States than in Europe. Despite the fact that RIT was introduced as long ago as 1941, several questions are still the subject of debate: Should a fixed dose or a calculated dose be used. If the dose is calculated, how many Grays (Gy) should be delivered to the thyroid? What is the goal of RIT in GD? Which factors, including ATD, influence the outcome of RIT? Is RIT appropriate in GD with Graves' ophthalmopathy (GO)? Although not all these questions have been answered yet, conclusions can be derived regarding a general strategy for use of RIT in GD. As with surgery, the goal of RIT in GD is euthyroidism with or without L-thyroxine medication. There is a clear advantage of dose calculation over use of a fixed dose because the only factor influencing the outcome is the dose delivered to a certain thyroid volume. To minimise recurrent hyperthyroidism, an ablative approach using a delivered dose of 250 Gy is widely accepted. Beside pretherapeutic T(3) levels, thyroid volume and 24-h thyroid uptake, ATD may influence the outcome of RIT. Today it is accepted by most thyroidologists that, if ATD medication is necessary in overt hyperthyroidism, it should be withdrawn at least 2 days before RIT. In patients with GD and GO, RIT may worsen GO. If RIT is performed in GO it should be done under a 3-month steroid medication regimen. In conclusion, RIT can be considered an appropriate and cost-effective therapy in GD, although the decision regarding treatment should be taken on an individual basis, paying due respect to the course and severity of disease, the presence of GO and, last but not least, the wishes of the patient.     

不同方法治疗Graves病的回顾性对比研究

 目的 通过对Graves病患者服用抗甲状腺药物(ATD)、放射碘(RAI)或手术治疗后甲状腺功能改变的长期回顾性队列研究,了解上述方法 的疗效及并发症,为Graves病治疗方案的选择提供依据.方法 病例选自在我院门诊及住院的既往Graves病88例,根据治疗方法 的不同将研究对象分为ATD组、RAI组和甲状腺手术组.收集治疗后的甲状腺功能转归情况,进行回顾性的对比研究.结果　(1)Graves病患者治疗后甲减的发生率在RAI组(38.9%)和手术组(30.0%)均明显高于ATD治疗组(6.3%,均P＜0.05);(2)3种方法 中,ATD组的甲亢未治愈比例最高为21.9%;(3)3组间甲功恢复正常的比率无明显差异(P＞0.05);(4)TPOAb或TgAb阳性者在RAI或手术治疗后更易于发生永久性甲减.结论 ATD、131I和手术治疗Graves病的有效率相仿,但手术或RAI也是导致甲减的危险因素,甲状腺抗体阳性者更易发生治疗后甲减.     

Prediction of remission in Graves' disease treated with long-term carbimazole therapy: Evaluation of technetium-99m thyroid uptake and TSH concentrations as prognostic indicators

Computerized technetium-99m thyroid uptake and thyrotropin (TSH) estimation using a sensitive immunoradiometric assay were performed at presentation and following completion of an 18-month course of antithyroid drug therapy in 45 patients with Graves' disease. All patients had increased^99mTc thyroid uptake and subnormal TSH levels before the start of treatment. Twenty-two patients developed recurrent hyperthyroidism in a 3-year follow-up period. Of these 22 patients with relapse, 20 had had a persistently increased^99mTc thyroid uptake at the end of the course of carbimazole treatment, whereas TSH had remained subnormal in 18 of the 22. All 23 patients who remained in remission until the end of the 3-year follow-up had had normal^99mTc thyroid uptake following completion of antithyroid drug treatment. TSH levels had reverted to normal in 19 cases, but remained subnormal in four cases in this group at the end of treatment. The results suggest a high likelihood of relapse in patients who have persistently increased^99mTc thyroid uptake and subnormal TSH after a full course of carbimazole treatment. Patients whose^99mTc thyroid uptake and TSH levels have reverted to normal are likely to stay in long-term remission. Assessment of^99mTc thyroid uptake and TSH levels following completion of carbimazole therapy for Graves' disease offers useful information regarding long-term prognosis.     

Graves' ophthalmopathy and 131I therapy.

Graves' ophthalmopathy is an autoimmune process initiated and maintained by antigen(s) shared by the thyroid and the orbit. A matter of argument concerns the choice of the method of treatment for Graves' hyperthyroidism when clinically evident ophthalmopathy is present. Restoration of euthyroidism appears to be beneficial for ophthalmopathy. On the other hand the continuing disease activity associated with the recurrence of hyperthyroidism appears to adversely affect the course of ophthalmopathy. For these reasons it is our opinion that in patients with Graves' hyperthyroidism and ophthalmopathy the permanent control of thyroid hyperfunction by ablation of thyroid tissue should be obtained by radioiodine therapy or thyroidectomy. The rationale for an ablative strategy is the following: i) permanent control of hyperthyroidism avoids exacerbations of eye disease associated with recurrence of hyperthyroidism; ii) hypothyroidism, which follows thyroid tissue ablation, should be regarded as a therapeutic end point rather than as an undesirable result; iii) ablation of thyroid tissue may result in the removal of both the thyroid-orbit cross-reacting antigen(s) and the major source of thyroid-autoreactive lymphocytes. The relationship between radioiodine therapy and the course of GO is a matter of controversy, and some authors have suggested that radioiodine administration may be associated with a worsening of preexisting ophthalmopathy. This was not observed when radioiodine treatment was associated with a 3-month oral course of prednisone. The development or progression of GO after radioiodine therapy might be due to the release of thyroid antigens following radiation injury and to subsequent exacerbations of autoimmune reactions directed towards antigens shared by the thyroid and the orbit. The view that radioiodine therapy may be associated with a progression of ophthalmopathy is not shared by some authors who claim that the apparent link between progression of ophthalmopathy and radioiodine therapy might simply be coincidental, reflecting the natural history of the disease. The radioiodine-associated exacerbation of eye disease might be used as an argument against the use of radioiodine therapy in patients with ophthalmopathy. We do not share this view, since the outward effects of radioiodine on eye disease can easily be prevented by concomitant administration of glucocorticoids. Glucocorticoid treatment should be limited, in our opinion, to patients with clinically evident eye disease and to those without ophthalmopathy but with other known risk factors, such as smoking.     

High pre-therapy [99mTc]pertechnetate thyroid uptake, thyroid size and thyrostatic drugs: predictive factors of failure in [131I]iodide therapy in Graves' disease

BACKGROUND AND OBJECTIVE: Several factors may interfere with the success rate of radioiodine therapy (RIT) in Graves' disease. Our aim was to evaluate, retrospectively, some of these factors in the outcome of RIT. METHODS: Patient gender, age at diagnosis, ophthalmopathy, disease duration, thyroid size, drug used as clinical treatment, thionamide withdrawal period during RIT preparation, FT4, TSH and [99mTc]pertechnetate thyroid uptake prior to RIT were studied as potential interference factors for RIT success. Eighty-two Graves' disease patients were submitted to RIT after thionamide treatment failure. Prior to RIT, 67 patients were receiving methimazole and 15 propylthiouracil. Thirty-three patients received thionamides during RIT; in 49 patients the medication was withdrawn for 2-30 days. [99mTc]pertechnetate thyroid uptake was determined before RIT. Fixed doses of 370 MBq of [131I]iodide were administered to all patients. RESULTS: Eleven patients became euthyroid; 40 became hypothyroid and 31 remained hyperthyroid. There was no association between outcome and age at diagnosis, gender, ophthalmopathy, pre-RIT FT4, TSH, antithyroid antibodies or thyrostatic drug. Multiple logistic regression showed higher probability of treatment success in patients with thyroid mass <53 g (odds ratio (OR)=8.9), with pre-RIT thyroid uptake <12.5% (OR=4.1) and in patients who withdrew thionamide before RIT (OR=4.9). CONCLUSIONS: Fixed doses of 370 MBq of radioiodine seem to be practical and effective for treating Graves' disease patients with [99mTc]pertechnetate uptake <12.5% and thyroid mass <53 g. This treatment is clearly not recommended for patients with large goitre. In contrast to what could be expected, patients with a high pre-RIT thyroid uptake presented a higher rate of RIT failure.     

Radioiodine-treatment (RIT) of functional thyroidal autonomy

Since 1942, therapy with radioiodine (RIT) has gained a major role in the treatment of benign thyroid disorders, notably hyperthyroidism caused by Graves' disease or toxic multinodular goitre (thyroid autonomy). In iodine deficient areas thyroid autonomy accounts for 40-50% of all cases with hyperthyroidism. RIT has become a cost-effective first-line procedure in autonomy-patients with latent or overt hyperthyroidism, especially in the absence of a large goitre, after thyroid surgery and in elderly patients with associated conditions who carry a high intra- or perioperative risk. Decisions concerning the definitive treatment of thyroid autonomy should take into account previous episodes of hyperthyroidism, objective parameters of risk stratification in euthyroid patients as well as concomitant diseases and the probability of iodine exposure in the future. In Central Europe the majority of investigators prefer to estimate the therapeutic activity individually by a radioiodine test. TCTUs (global 99m-Tc-pertechnetate thyroid uptake under suppression)-based dose concepts have been proven to be highly effective in the elimination of autonomy and carry a low (< 10%) risk of post-radioiodine-therapeutic hypothyroidism. Radioiodine therapy for autonomy has been found to be both effective and safe and without major early or late side effects. The most frequent complication is hypothyroidism requiring lifelong follow-up.     

Influence of therapy with iodine-131 on thyroid tissue pattern in colour and power Doppler sonography

AIM: The aim of this study was to evaluate the influence of radioiodine therapy on sonographic thyroid patterns using power Doppler (PD) and colour Doppler (CD) sonography in hyperthyroid patients with autonomous nodules (AN) and Graves' disease (GD). METHOD: B-mode, colour, and power Doppler sonography, (99m)Tc scintigraphy, and laboratory analyses (free thyronine fT(3), free thyroxine fT(4), thyroid stimulating hormone TSH) were performed in 55 patients (AN = 27, GD = 28) before and 6 months following therapy with (131)I radioiodine therapy (RIT). RESULTS: In patients with an AN (but not in GD), a significant reduction in thyroid vascularization was subjectively noted following radioiodine therapy on both CD and PD ultrasound (Wilcoxon matched pairs, P < 0.05). The pre-therapeutic grade of hypervascularization in the periphery of autonomous nodules correlated closely with the laboratory parameters of hyperthyroidism. As expected, PD indicated a higher grade of vascularization when compared with CD due to its greater sensitivity to flow. CONCLUSIONS: Radioiodine therapy led to a significant reduction in hypervascularization in patients with AN (but not in GD) corresponding to the normalization of serological values. Comparing CD and PD, PD detected a greater number of vessels. CD and PD are not able to replace scintigraphy and/or laboratory analyses in the management of patients with hyperthyroidism.     

Radioiodine treatment in patients with Graves' disease at outpatient clinic: special reference to safety and short-term outcome

PURPOSE: This retrospective study was aimed at revealing the safety and short-term outcome of radioiodine treatment in patients with Graves' disease at outpatient clinic. METHODS: From July 1999 to April 2002, 511 patients with Graves' disease were treated with radioiodine at the outpatient clinic of Tajiri Thyroid Clinic, Kumamoto. Of them, 73 patients dropped out or were referred to another medical institution. In the remaining 438 patients [100 men and 338 women; 44.6 +/- 15.4 (mean +/- SD) (14-82) years old], the safety of radioiodine treatment at the outpatient clinic and the treatment outcome until April 2003 was examined. The dosage was determined based on radioactive iodine uptake (3 hours) and thyroid volume measured by ultrasound. The initial dosage was 6.7 +/- 3.3 (1.2-13.5) mCi. Five months later, it was evaluated whether or not radioiodine should be administered a second time. All patients were treated at the outpatient clinic. RESULTS: There was no particular problem associated with treatment. Patients with a large goiter could be successfully treated with divided doses. After 12-45 (30.1 +/- 9.3) months of radioiodine, thyroid function status was as follows; hyperthyroidism: 7 patients (1.6%), subclinical hyperthyroidism: 78 patients (17.8%), euthyroidism: 108 patients (24.7%), subclinical hypothyroidism: 116 patients (26.5%), hypothyroidism: 129 patients (29.4%). CONCLUSION: It was concluded that radioiodine treatment in patients with Graves' disease at outpatient clinic was safe and showed a satisfactory short-term outcome.     

Radioiodine treatment of hyperthyroidism using a simplified dosimetric approach. Clinical results

PURPOSE: To evaluate the clinical effectiveness of a simplified dosimetric approach to the iodine-131 treatment of hyperthyroidism due to Graves' disease or uninodular and multinodular toxic goiter. MATERIAL AND METHODS: We enrolled 189 patients with biochemically confirmed hyperthyroidism and performed thyroid ultrasonography and scintigraphy obtaining the diagnosis of Graves' disease in 43 patients, uninodular toxic goiter in 57 patients and multinodular toxic goiter in 89 patients. In 28 patients we found cold thyroid nodules and performed fine-needle aspiration with negative cytology for thyroid malignancy in all cases. Antithyroid drugs were stopped 5 days till radioiodine administration and, if necessary, restored 15 days after the treatment. Radioiodine uptake test was performed in all patients and therapeutic activity calculated to obtain a minimal activity of 185 MBq in the thyroid 24 hours after administration. The minimal activity was adjusted based on clinical, biochemical and imaging data to obtain a maximal activity of 370 MBq after 24 hours. RESULTS: Biochemical and clinical tests were scheduled at 3 and 12 months posttreatment and thyroxine treatment was started when hypothyroidism occurred. In Graves' disease patients a mean activity of 370 MBq (distribution 259-555 MBq) was administered. Three months after treatment and at least 15 days after methimazole discontinuation 32 of 43 (74%) patients were hypothyroid, 5 of 43 (11%) euthyroid and 6 of 43 (15%) hyperthyroid. Three of the latter were immediately submitted to a new radioiodine administration while 32 hypothyroid patients received thyroxine treatment. One year after the radioiodine treatment no patient had hyperthyroidism; 38 of 43 (89%) were on a replacement treatment while 5 (11%) remained euthyroid. In uni- and multinodular toxic goiter a mean activity of 444 MBq (distribution 259-555 MBq) was administered. Three months posttreatment 134 of 146 (92%) patients were euthyroid and 12 of 146 (8%) patients hyperthyroid. Two patients were immediately submitted to a new radioiodine administration. One year posttreatment 142 of 146 (97%) patients were euthyroid while only 4 of 146 (3%) patients showed TSH levels above the normal range. Only 2 of them required thyroxine treatment. CONCLUSIONS: The simplified dosimetric method illustrated in our paper is very effective in clinical practice because it permits to avoid resorting to sophisticated but also imprecise quantitative methods. Hypothyroidism should not be considered as a major collateral effect of radioiodine treatment, particularly in Graves' disease. In fact, the pathogenesis of the disease requires an ablative treatment with both surgery and radioidine treatment and the control of hyperthyroidism and the prevention of relapse are the major clinical targets. Vice versa, hypothyroidism was very uncommon in uni- and multinodular toxic goiter when our dosimetric approach was applied.     

Multivariate analysis of prognostic factors for differentiated thyroid carcinoma in children

At most centres, the standard treatment for differentiated thyroid cancer (DTC) comprises total thyroidectomy, radioiodine treatment and thyroid-stimulating hormone (TSH) suppressive therapy. There is, however, considerable disagreement over the appropriate treatment for DTC in children. Some dispute the use of total thyroidectomy and/or question the routine application of iodine-131 therapy in children. The aim of this study was to perform a retrospective analysis of treatment results and prognostic factors for DTC in children treated at our centre. The study included 109 children with DTC (aged 6-17 years). The primary treatment comprised total thyroidectomy in 81 cases, radioiodine therapy in 85 cases and TSH suppressive therapy with L-thyroxine in all patients. Uni- and multivariate analysis of prognostic factors for disease-free survival was performed using the Cox regression method. The actuarial survival rate was 100%, and the 5- and 10-year actuarial disease-free survival rates were 80% and 61% respectively. Univariate analysis revealed that older age, total thyroidectomy and radioiodine treatment had a positive impact on disease-free survival whereas there were no statistical differences with regard to the child's sex, histological type of cancer or lymph node status. On multivariate analysis, radical surgery was estimated to be the most significant factor (P=0.007) for disease-free survival, while less than total thyroidectomy increased the relative risk of relapse by a factor of 10. Radioiodine treatment decreased the relative risk of relapse by a factor of 5, but with borderline significance (P=0.07). Permanent postoperative complications were observed in 17% of children: in 11 laryngeal palsy occurred, in six there was hypoparathyroidism, and one suffered from both. It is concluded that total thyroidectomy and radioiodine treatment significantly improve recurrence-free survival in children and should be routinely applied even in young children as the primary treatment of DTC.     

Thyroid cancer prevalence after radioiodine treatment of hyperthyroidism.

The definitive treatment of hyperthyroidism in Europe is quite different from that in the United States. In Europe, the surgical approach is often preferred and considered safer than radioiodine treatment. European doctors usually prefer to surgically remove the thyroid and perform a pathologic examination of it. They consider it to be an essential diagnostic tool to identify possible diseases that might be associated with hyperthyroidism and even to detect the rare thyroid tumors that might be associated with thyroid hyperfunction. The aim of this study was to evaluate whether radioiodine therapy could be a risk factor for the misdiagnosis of thyroid cancer. METHODS: We performed a retrospective revision of data we collected from 6647 patients (1171 [17.5%] men, 5476 [82.5%] women), all of whom underwent 1311 therapy for hyperthyroidism from 1970 to 1997. Of the whole group, 6.5% were younger than 40 y, 33.5% were 40-60 y old, and 60% were older than 60 y. Moreover, 5061 (76%) patients had either an autonomously functioning node or a toxic multinodular goiter. The other 1586 (24%) patients had Graves' disease. RESULTS: After treatment, thyroid cancer was discovered in 10 (0.15%) patients, none of whom belonged to the group of patients with Graves' disease. Five of these patients were treated during a period from 1970 to 1980, when sonography was not routinely available. The incidence of thyroid cancer in the series of radioiodine-treated patients (150/100,000 over a 27-y period) was not significantly different from its incidence in the general population. The expected rate is 124.88 per 100,000 over a 27-y period. CONCLUSION: An accurate preliminary evaluation (clinical examination, sonography, and cytologic evaluation of fine-needle aspiration) is fundamental for a proper choice between radioiodine and surgical therapy.