Indications for and basic principles of the surgical treatment of thyroid diseases

Surgical treatment is indicated for patients with nodular goiter if malignancy seems possible, if there are mechanical reasons, or on request from the patient. In patients with goiter and hyperthyroidism, surgery and radioiodine are alternatives. In contrast, thyroid autonomy always requires surgery. The treatment of patients suffering from differentiated thyroid cancer includes thyroidectomy and radioiodine, and in those with anaplastic thyroid cancer external radiation and surgery should be performed. Apart from the classic indications and surgical procedures, in recent years selective resection of multinodular goiter, more conservative surgery of small papillary thyroid cancer and surgical treatment of iodine-induced thyrotoxicosis have become established.     

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.     

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.     

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.     

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.     

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.     

131Ⅰ治疗非Graves'甲状腺功能亢进及非毒性甲状腺肿后诱发Graves'病

~(131)I治疗非Graves’甲亢及非毒性甲状腺肿后数月,少部分患者体内出现促甲状腺激素受体抗体并诱发Graves’病(GD),发病率在0．05%～5%之间。其发病机制假说有通过自身免疫反应介导等。通过监测体内甲状腺自身抗体水平变化、甲状腺显像,可以预测~(131)I治疗后GD的发生。其治疗方法有抗甲状腺药物治疗、再次放射性~(131)I治疗、手术治疗。     

Therapy for non-toxic multinodular goiter: radioiodine therapy as attractive alternative to surgery

The need for therapy for nodular goiter results from the growth of thyroid nodules over decades and from the possibility of tracheal compression and worsening of respiratory function. Given the high prevalence of non-toxic goiter, the epidemiologically low incidence of clinically apparent thyroid cancer justifies non-surgical strategies. Randomised studies have shown that levothyroxine offers limited therapeutic effects and is inferior to radioiodine therapy regarding goiter shrinkage. When indication for a definitive therapy is given, the choice between resection and radioiodine therapy should consider volume of goiter, severity of clinical symptoms, thyroid uptake, patient's age, co-morbidity, previous resection of goiter, patient's profession and patient's wish. Even in large goiters between 100 and 300 ml radioiodine therapy showed consistent results with goiter size reduction from 35-40% one year and 40-60% two years after radioiodine therapy. Thyroid hormones to prevent recurrence of goiter are not necessary. Recurrent goiters were seldom observed after radioiodine therapy and resulted from initially very large goiters or uptake in dominate nodules or from low (131)I activities. Recombinant human TSH (rhTSH) offers the opportunity to enhance the effect of radioiodine therapy. Observational studies have shown that rhTSH increases low (131)I uptake in case of high alimentary iodine-supply by the factor 4, causes a more homogenous (131)I distribution within the goiter and improves goiter reduction. A phase I study for dose finding is running in the USA. Conclusion: Radioiodine therapy for shrinkage of large non-toxic goiter should not be restricted to elderly patients, or to patients with co-morbidity or high operative risk, but is an attractive alternative to surgery in patients with special professions (singer, teacher, speaker) or with the wish for a non-invasive treatment modality.     

131I治疗非毒性甲状腺肿的研究进展

非毒性甲状腺肿是无甲状腺功能亢进症的甲状腺肿大,症状性非毒性甲状腺肿用甲状腺制剂抑制治疗的疗效不肯定,部分患者因各种原因禁忌或拒绝外科治疗。131I治疗非毒性甲状腺肿具有安全、简便、疗效好、副作用少的特点,越来越多的患者选择131I治疗。     

Prevention, screening and therapy of thyroid diseases and their cost-effectiveness

Cost-effectiveness analyses focused on benign thyroid diseases are under-represented in the literature. The calculation of costs per additionally gained life year is difficult: The benefit of prevention is shifted into the distant future. The influence of an untreated subclinical thyroid disease on life expectancy can only be demonstrated by a long-term follow-up and by epidemiological databases. Iodine supplementation and programs for the prevention of tobacco smoking (primary prevention) are very cost-effective. Smoking increases the risk both of multinodular goiter and of Graves' disease. Screening programs (secondary prevention) are discussed for the laboratory parameters thyrotropin (TSH), calcium and calcitonin. TSH testing seems to be very cost-effective for epidemiological considerations in a certain lifespan (newborn, pregnancy, postpartal, older persons, hospitalisation due to acute diseases) and in persons with previously elevated TPO-antibodies or TSH-values >2 mU/l, but dedicated cost-effectiveness analyses are lacking. On the other hand, the cost-effectiveness of a routine TSH testing beyond the age of 35 years has been shown by a high-quality decision analysis. Therapeutic strategies (tertiary prevention) aim at the avoidance of complications (atrial fibrillation, myocardial infarction, death for cardiac reasons) and of iatrogenic complications. Examples of a tertiary prevention are: firstly the definitive therapy of Graves' disease in patients who have an increased risk of relapse after antithyroid drugs (ATD), secondly the radioiodine therapy for subclinical hyperthyroidism and the radioiodine therapy of large goiters in older patients or in patients suffering from a relevant comorbidity. Cost-effectiveness analyses for different therapeutic strategies of Graves' disease were published using a lifelong time-horizon. The ablative radioiodine dose-regime is cost-effective as a first line therapy if the risk of relapse after ATD exceeds 60%.     

Primary hyperthyroidism--diagnosis and treatment. Indications and contraindications for radioiodine therapy

Isotope therapy is one of the methods used in primary hyperthyroidism. The therapy is based on short-range beta radiation emitted from radioactive iodine. Radioiodine administration must always be preceded by pharmacological normalization of thyroid function. Otherwise, post-radiation thyrocyte destruction and thyroid hormones release may lead to hyperthyroidism exacerbation. Indications for radioiodine therapy in Graves-Basedow disease include recurrent hyperthyroidism after thyrostatic treatment or thyroidectomy and side-effects observed during thyrostatic treatment. In toxic nodule, isotope therapy is the first choice therapy. Radioiodine is absorbed only in autonomous nodule. Therefore, it destroys only this area and does not damage the remaining thyroid tissue. In toxic goitre, radioiodine is used mostly in recurrent nodules. Absolute contraindications for radioiodine treatment are pregnancy and lactation. Relative contraindications are thyroid nodules suspected of malignancy and age under 15 years. In patients with thyroid nodules suspected of malignancy, radioiodine treatment may be applied as a preparation for surgery, if thyrostatic drugs are ineffective or contraindicated. In children, radioiodine therapy should be considered in recurrent toxic goitre and when thyrostatic drugs are ineffective. In patients with Graves-Basedow disease and thyroid-associated orbitopathy, radioiodine treatment may increase the inflammatory process and exacerbate the ophthalmological symptoms. However, thyroid-associated orbitopathy cannot be considered as a contraindication for isotope therapy. The potential carcinogenic properties of radioiodine, especially associated with tissues with high iodine uptake (thyroid, salivary glands, stomach, intestine, urinary tract, breast), have not been confirmed.     

Therapeutic options in the management of toxic and nontoxic nodular goiter

Nodular goiter is present in 500 to 600 million people and is usually secondary to endemic iodine deficiency. Despite adequate iodine intake, 4% to 6% of American adults are goitrous. Sporadic nodular goiter ensues from the natural heterogeneity of thyroid follicular cells, which, when amplified by yet unidentified trophic stimuli, results in episodes of proliferating, rapidly dividing micronodules. The initial small diffuse goiter evolves into a multinodular goiter (MNG) with 1 or more dominant nodules that may or may not be autonomous. An autonomous functioning thyroid adenoma (AFTA) usually possesses a somatic gain-of-function mutation of the thyrotropin (TSH) receptor associated with rapid growth, hemorrhagic necrosis, and reparative fibrosis that accentuate goiter nodularity. Diagnostic evaluation consists of patient history and physical examination, serum TSH determination, free thyroxine and free triiodothyronine measurements, and imaging studies assessing goiter function, size, and anatomy. If treatment is required, L-thyroxine, thionamides, surgery, radioiodine (I-131), and percutaneous ethanol injection (PEI) are effective in selected patients. In euthyroid patients, L-thyroxine reduces goiter size in some patients, but continued therapy is required to prevent regrowth. Thionamides control the hyperthyroidism of toxic nodular goiter in preparation for more definitive therapy, but are rarely used long term. Surgery and I-131 are most commonly selected for definitive therapy for the toxic AFTA, and the toxic or euthyroid MNG, but PEI is effective in selected toxic AFTAs.     

Is thyroid scintigraphy necessary before I-131 therapy for hyperthyroidism? Concise communication

To assess the value of routine thyroid scintigraphy in the differential diagnosis of hyperthyroidism and as a guide to I-131 therapy, we prospectively examined 100 consecutive hyperthyroid patients referred for a 24-hr radioiodine uptake and I-131 therapy. The nuclear medicine physician recorded his preimaging diagnostic impression and therapeutic plan for each patient. After the [ 99mTc ] pertechnetate image, the patient was reassessed to determine whether the image induced any change in the diagnosis or therapeutic plan. Seventy-nine of 80 patients with diffuse goiter to palpation, had scintigrams demonstrating no discrete focal defects and were diagnosed as Graves' disease; thus the scintigram did not contribute useful information. In 17 of 20 patients with uninodular or multinodular goiters, the image was necessary to clarify the final diagnosis and therapeutic plan. Thus, selective use of thyroid scintigraphy should decrease the number of scintigrams performed before I-131 therapy for hyperthyroidism, without compromising diagnostic accuracy or therapeutic success.     

Radioiodine therapy of thyroid autonomy

Over half a century, treatment of thyroid autonomy with an oral dose of iodine-131 has proven to be effective. The optimum management strategy for the patient is, however, still a matter of debate. The article provides an overview of the pathogenesis of functional autonomy and its clinical relevance. According to the guidelines on both sides of the Atlantic, radioiodine treatment is considered the most comfortable and economical approach to the treatment of the toxic nodular goitre. Some differences in the preparation procedures in the guidelines of the American and the German Society of Nuclear Medicine are discussed with respect to therapy results and the subtypes of thyroid autonomy. The results of studies are summarised concerning changes in thyroid function and thyroid volume after a course of radioiodine treatment. Therapy-related risks, such as immunogenic hypothyroidism or thyroid cancer, are discussed. (131)I treatment of functional autonomy and hyperthyroidism is considered an effective and safe procedure.     

Functional results of radioiodine therapy with a 300-GY absorbed dose in Graves' disease

The aim of this study was to assess the results of high-dose radioiodine therapy given to 43 patients with recurrent hyperthyroidism due to Graves' disease between 1986 and 1992. We chose an intrathyroidal absorbed dose of 300 Gy and determined the applied activity individually, which ranged from 240 to 3120 MBq with a median of 752 MBq. Hyperthyroidism was eliminated in 86% of cases after 3 months and in 100% after 12 months. No patient required a second radioiodine treatment. The incidence of hypothyroidism was 63% after 3 months and 93% after 18 months. Neither the pretherapeutic thyroid-stimulating immunoglobulin level nor the degree of co-existing endocrine ophthalmopathy was correlated with the time at which hypothyroidism developed. Patients with previous radioiodine therapy developed hypothyroidism earlier than patients with previous thyroid surgery. The results show that ablative radioiodine therapy with a 300-Gy absorbed dose is a very effective treatment of hyperthyroidism in Graves' disease, but it should be restricted to patients with recurrent hyperthyroidism combined with severe co-existing disorders or episodes of unfavourable reactions to antithyroid drugs. Correspondence to: U.F. Willemsen     

Clinical significance of endogenously labelled thyroid hormones in the diagnosis of thyroidal autonomy

The clinical value of the determination of 123I concentration in serum 48 hrs after tracer administration (123I)48 is investigated with special regard to thyroidal autonomy. Serum radioiodine concentration, thyroid radioiodide uptake at 4 and at 48 hrs were measured in 74 healthy subjects and patients with simple goiter, in 36 patients with thyroidal autonomy (diagnosis by thyroid suppression test), and in 20 hyperthyroid patients. 83% of the patients with elevated radioiodine concentration belonged to the group of thyroidal autonomy. The product of radioiodine concentration and thyroid radioiodide uptake is a much better parameter. 95% of the patients in which this product was elevated, belonged to the autonomy group (5% diagnostic error). Also in the control group the diagnostic error was 5%. The combination of (123I)48 with the result of the TRH-test is very useful in excluding thyroidal autonomy, if (123I)48 is normal and the TRH-test is positive (100% of the patients have regulated thyroid glands). 94% of the patients having elevated (123I)48 and a negative TRH-test belonged to the group of thyroidal autonomy. A very useful combination for the diagnosis of borderline hyperthyroidism is the determination of the product of (123I)48 and the uptake48 together with the pulse rate or fine tremor of the fingers (or TRH-test). The results suggest that the determination of (123I)48 is a very good parameter of thyroidal autonomy beside the thyroid suppression test. It may be used alone for the diagnosis of thyroidal autonomy if the suppression test is contraindicated. In the diagnosis of borderline hyperthyroidism its determination makes the suppression test unnecessary in many instances.     

Nonimmunogenic hyperthyroidism: cumulative hypothyroidism incidence after radioiodine and surgical treatment

During 1977, 246 hyperthyroid patients were seen in our departments, 140 (57%) with nonimmunogenic hyperthyroidism (NIH)--101 with a toxic adenoma (TA) and 39 with multifocal functional autonomy (MFA). All patients but one could be followed over 9 yr, 101 after 131I treatment (RIT), another 29 after surgery (S). Ten patients were left untreated. Thirty-four treated (24%) patients died, none as a result of thyroid or post-treatment complications. There was no hyperthyroidism later than 9 mo after therapy. Only 1% (RIT) and 24% (S) were hypothyroid 1 yr after treatment. But 19% of all treated NIH patients were hypothyroid after 9 yr or at the time of their death, 12% after RIT and 41% after S. The cumulative hypothyroidism incidences 1.4%/yr for RIT and 2.2%/yr for S, were not significantly different. Out of the five survivers without RIT or S, two TA patients were hypothyroid. The effect of RIT on goiter related loco-regional complications was not worse than after S. We conclude that RIT is the treatment for NIH, leaving surgery for exceptional cases.     

Dose selection for radioiodine therapy of borderline hyperthyroid patients with multifocal and disseminated autonomy on the basis of 99mTc-pertechnetate thyroid uptake

The aim of this study was to optimise radioiodine therapy of diffuse and nodular toxic goitre by calculation of the radiation dose delivered to the thyroid on the basis of the pretreatment technetium-99m pertechnetate thyroid uptake under thyrotropin suppression (TcTU(s)). The TcTU(s) value serves as a substitute for the non-suppressible iodine turnover and the functional autonomous mass. Marinelli's formula was used to calculate tissue absorbed doses of 150 Gy, 200 Gy, 250 Gy and 300 Gy to the thyroids of 438 patients with multifocal and disseminated autonomy. The mean age of patients was 70+/-9 years, and the mean thyroid volume was 54+/-26 ml. Two hundred and sixty-one of the patients had at least one documented previous episode of overt hyperthyroidism. Tissue absorbed doses were adapted to the pretreatment TcTU(s): 150 Gy for a TcTU(s) of 1.5%-2.49%, 200 Gy for a TcTU(s) of 2.5%-3.49%, 250 Gy for a TcTU(s) of 3.5%-4.49% and 300 Gy for a TcTU(s) of > or =4.5%. Normalisation of TcTU(s) and thyrotropin (TSH), thyroid volume reduction and frequency of hypothyroidism and recurrent hyperthyroidism were evaluated 1 year after a single radioiodine therapy. The presented dose strategy resulted in normalisation of TcTU(s) in 96% and an increase in TSH to the normal range in 92%. Recurrent hyperthyroidism was observed in only five patients. Thyroid volume decreased from 54+/-26 before treatment to 34+/-20 ml, a mean reduction of 37%. The frequency of hypothyroidism, at 0.9%, was encouragingly low. Dose selection in accordance with pretreatment TcTU(s) can be recommended for elimination of functional autonomous tissue with a single radioiodine therapy in patients of advanced age with enlarged thyroid glands and relevant autonomous masses who are at risk of developing iodine-induced hyperthyroidism.     

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.     

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.