Predictive Value of a Thyroid-Absorbed Dose with a Shorter Effective Half-Life on Efficacy in Graves Disease Patients Receiving Iodine-131 Therapy.

BACKGROUND Although radioiodine therapy (RIT) efficacy is thoroughly validated for Graves disease (GD), there is a lack of research on the predictive factors of RIT, especially the optimal thyroid-absorbed dose (TD) with a shorter effective half-life (Teff ≤5 days). The goal of this study was to explore the predictive value of TD in GD patients receiving RIT with a shorter Teff. MATERIAL AND METHODS We studied 208 GD patients receiving RIT with a shorter Teff. Plotting the receiver-operating characteristic (ROC) curve verified the accuracy of TD for predicting RIT efficacy in GD patients. In addition, we conducted univariate and multivariate analyses to investigate the influence of 14 factors, including thyroid weight, TD, 24-h radioiodine uptake rate (RAIU), the highest RAIU, thyrotrophin receptor antibody level, thyroglobulin antibody level, thyroid peroxidase antibody level, and others, on curative effects of RIT. RESULTS Of the 208 study participants, complete remission and the total effectiveness rates were 68.3% and 92.3%, respectively. The threshold value of TD to predict RIT efficacy was 70.2 Gy, based on ROC analysis. Univariate analysis showed that 24-h RAIU, Teff, total iodine dose, iodine dose per gram of thyroid tissue, TD, and thyrotropin receptor antibody level were significantly associated with RIT efficacy. Multivariate analysis indicated that 24-h RAIU, total iodine dose, iodine dose per gram of thyroid tissue, and TD were significant independent predictors of RIT efficacy. CONCLUSIONS Predicting RIT efficacy from TD with a shorter Teff was feasible in GD patients, and TD above 70.2 Gy had an especially high predictive accuracy.

Radioactive iodine 1311 (RAI) treatment. The nearest to the "magic bullet" but should always be preceded by a risk assessment, especially in the pediatric patient.

Radioactive iodine treatment is very frequently the best approach, but it should be optimized by dosimetric and risk considerations.

[Chronological change in the national health insurance reimbursement based on the DPC package payment system regarding 131I internal therapy].

The national health reimbursement in 131I internal therapy for thyroid cancer and Graves' disease has increased by introducing the DPC package payment system. The thyroid cancer administration fee for shield room should be increased because of the strict regulation for 131I internal therapy, expensive equipments, confinement of radiopharmaceutical supply, and low efficiency in admission to shield rooms. In addition, the Graves' disease administration fee for shield room should be introduced since the inpatients undergo the same administration and care as the thyroid cancer inpatients.

[Treatment of Graves-Basedow's disease with 131I. Assessment of a "modulated fixed activity" protocol]. / Tratamiento de la enfermedad de Graves-Basedow con I. Valoración de un protocolo de "actividades fijas moduladas".

PURPOSE: The purpose of this study was to retrospectively evaluate the hypothyroidism rate, persistence of hyperthyroidism and the complications after the administration of 131I in 3 cohorts defined according to the activity of 131I administered. METHODS: We consecutively treated 659 patients diagnosed with Graves-Basedow disease (GBD) with 131I. The activity was determined on the basis of a protocol that we called "modulated fixed activity". A total of 45 patients (Group 1) who had previously undergone surgery were given small 131I activities of between 111-185 MBq (3-5 mCi), 247 patients (Group 2) with normal or almost normal-sized thyroids were given activities of between 222-333 MBq (6-9 mCi) and the 367 patients with diffuse goiters (Group 3) activities of between 370-555 MBq (10-15 mCi). RESULTS: A total of 69.2 % of the patients presented hypothyroidism at the end of the follow-up period. By groups, the percentages of hypothyroidism at the end of the follow-up period were 69 %, 68.8 % and 69.6 % respectively. The average time for the patients to present hypothyroidism was 2.7 years with a maximum de 12.3 years and a minimum of 2 months. No severe precocious complications after the administration of 131I were noted. CONCLUSION: The choice of the modulated fixed doses of 131I for treatment of the GBD is a simple method and permit treatment in only one day.

[Radioiodine treatment of Graves' disease --for its wider indication and application in Japan].

Radioiodine treatment has been well established as an effective and safe therapeutic modality for Graves' disease. To promote more efficient use of this treatment in Japan, a working group has been organized in the Japan Thyroid Association and preparation of guidelines for its clinical use is under way. The treatment using upto 13.5 mCi of I-131 is feasible on out-patient basis. In comparison to the antithyroid drug treatment, the treatment has no side effects, brings in good control of hyperthyroidism and decrease the size of goiter. It is contraindicated in pregnant and lactating women. Patients treated should be carefully monitored for the possible worsening of ophthalmopathy and neonatal Graves' disease. Recent studies revealed the cost-effectiveness of the treatment. Its application to autonomously functioning thyroid nodules and toxic multinodular goiters is also discussed.

Tratamento clínico com drogas antitireoidianas ou dose terapêutica de iodo-131 no controle do hipertireoidismo na doença de graves: avaliação dos custos e benefícios / Anti-thyroid drugs or 131I therapy to control the hyperthyroidism of graves disease: a cost-effectiveness analysis / Anti-thyroid drugs or 131I therapy to control the hyperthyroidism of graves disease: a cost-effectiveness analysis

Com o objetivo de avaliar os custos e a efetividade das 2 formas de tratamento mais utilizadas em nosso meio para a Doença de Graves, iodo radioativo e tratamento clínico prolongado, analisamos pacientes submetidos a essas terapias na região de Maringá, PR. Foram estudados 23 pacientes, 7 homens e 16 mulheres, com idade média de 35,4 anos, submetidos ao tratamento clínico, e 34 pacientes, 5 homens e 29 mulheres, com idade média de 39,4 anos, submetidos à dose terapêutica com iodeto de sódio (iodo-131). Após 2 anos de tratamento clínico com tiamazol (Tapazol®), 21 pacientes atingiram o eutireoidismo e dois permaneceram hipertireóideos. No grupo da dose terapêutica com iodeto de sódio (iodo-131), 21 pacientes evoluíram para o hipotireoidismo, enquanto que 13 atingiram o eutireoidismo. Para o cálculo do custo de cada modalidade de tratamento, analisamos o número de consultas necessárias durante o seguimento, exames complementares solicitados e medicações utilizadas, como tiamazol e/ou tiroxina. O grupo submetido ao tratamento clínico necessitou de maior número de consultas e exames, sendo que o custo médio foi de R$ 1.345,81 neste período de dois anos, enquanto que no grupo com iodeto de sódio (iodo-131) o valor médio foi de R$ 622,94. Assim, os custos da dose terapêutica com iodeto de sódio (iodo-131) foram 53,7 por cento menores do que o tratamento clínico com drogas antitireoidianas. Este trabalho demonstra que o tratamento com dose terapêutica com iodeto de sódio (iodo-131) apresenta um menor custo, sendo bastante efetivo no controle do hipertireoidismo na doença de Graves.

In this study, we set out to evaluate the costs and effectiveness of the 2 most used therapies in our region, ATD or RAI. 23 patients, 6 men and 16 women, with a mean age of 35.4 years, treated with ATD, and 35 patients, 5 men and 30 women, mean age of 39.4 years, treated with RAI, were studied. After 2 years receiving ATD, 21 patients achieved euthyroidism and 2 remained hyperthyroid. In the RAI group, 21 patients presented hypothyroidism and 13 became euthyroid. To calculate the costs of each therapy, we analyzed the number of visits during this period, the laboratory data and the drugs needed, such as tiamazol and/or thyroxine. The group treated only with ATD needed a higher number of visits and laboratory measurements, with the mean total cost of R$ 1,345.81, while the RAI group spent a mean amount of R$ 622.94. Therefore, the costs of the RAI treatment were 53.5 percent lower than clinical therapy with ATD. The present study demonstrates that RAI treatment has a lower cost than ATD, being very effective in controlling the hyperthyroidism of Graves disease.

[Clinical treatment with anti-thyroid drugs or iodine-131 therapy to control the hyperthyroidism of graves disease: a cost-effectiveness analysis]. / Tratamento clínico com drogas antitireoidianas ou dose terapêutica de iodo-131 no controle do hipertireoidismo na doença de graves: avaliação dos custos e benefícios.

In this study, we set out to evaluate the costs and effectiveness of the 2 most used therapies in our region, ATD or RAI. 23 patients, 6 men and 16 women, with a mean age of 35.4 years, treated with ATD, and 35 patients, 5 men and 30 women, mean age of 39.4 years, treated with RAI, were studied. After 2 years receiving ATD, 21 patients achieved euthyroidism and 2 remained hyperthyroid. In the RAI group, 21 patients presented hypothyroidism and 13 became euthyroid. To calculate the costs of each therapy, we analyzed the number of visits during this period, the laboratory data and the drugs needed, such as tiamazol and/or thyroxine. The group treated only with ATD needed a higher number of visits and laboratory measurements, with the mean total cost of R dollars 1,345.81, while the RAI group spent a mean amount of R dollars 622.94. Therefore, the costs of the RAI treatment were 53.5% lower than clinical therapy with ATD. The present study demonstrates that RAI treatment has a lower cost than ATD, being very effective in controlling the hyperthyroidism of Graves disease.

[Cost-utility analysis of antithyroid drug therapy versus 131I therapy for Graves' disease].

There is no comparative cost-utility study between 131I therapy and antithyroid drugs (ATD) therapy for Graves' disease, though 131I therapy has higher remission rate and less side effects. The objective of the study was to analyze the cost-utility of ATD therapy versus 131I therapy by calculating life-long medical costs and utility, based on the responses of Graves' disease patients to questionnaires. To determine the expected cost and expected utility, a decision tree analysis was designed on the basis of the 2 competing strategies of ATD therapy versus 131I therapy. A simulation of 1000 female patients weighing > or =50 kg who assumed to experience the onset of Graves' disease at the age of 30, to first complain of thyrotoxic symptoms and moderate goiter 2-3 mo. previously, and to undergo a 40-years-long cohort study, was created for each strategy using a decision tree and baselines of other relevant variables. The variables and costs were based on the literature and hospital bills. The maximum and minimum values of utility were defined as 1.0 and 0.0, respectively. Future costs and utilities were discounted 5%. The medical costs and utilities were 85,739-88,650 yen/patient/40 years and 16.47-16.56/patient/40 years, respectively, for the ATD therapy strategy, and 81,842 yen/patient/40 years and 17.41/patient/40 years, respectively, for the 131I therapy strategy. These results quantitatively demonstrated that the 131I therapy strategy was superior to the ATD therapy strategy in terms of both cost and utility. 131I therapy should be used more widely in Japan because of its greater utility and lower cost.

[Radioiodine therapy for Graves' disease: problems and new developments]. / Die Radioiodtherapie des Morbus Basedow-- Probleme und neue Entwicklungen.

In Germany, patients with Graves' disease are usually treated with radioiodine after unsuccessful antithyroid drug medication, occurrence of side effects from antithyroid drugs or an increased risk from surgery. In patients with normal or only slightly enlarged thyroid glands (volume < or = 50 ml), radioiodine therapy is particularly effective. Radioiodine is the preferential treatment for Graves' patients with high titres of TSH-receptor antibodies and cigarette smoking. Children are still rarely treated with radioiodine in Germany. In contrast, treatment with radioiodine should be more liberally applied in elderly patients with subclinical hyperthyroidism and cardiac symptoms. Individual dosimetry to determine the therapeutic activity is mandatory in Germany. Patients with large goitres obviously need higher organ doses than patients with smaller goitres or normal thyroid glands. Antithyroid drug treatment may interfere with radioiodine therapy. Therefore, it is recommendable to withdraw antithyroid drugs several days before treatment with radioiodine is initiated (and a preceding radioiodine uptake test is performed). In patients with Graves' orbitopathy prophylaxis with corticosteroids can prevent the worsening of symptoms that may be induced by radioiodine treatment. Currently, a risk adapted procedure is recommended according to which prophylactic medication with corticosteroids before applying radioiodine treatment is not necessary in patients with symptoms of orbitopathy and lack of other risk factors (cigarette smoking, in particular). Present results suggest that the risks of radioiodine treatment in Graves' disease patients are very low, while at the same time the cost-effectiveness of this treatment regimen is high.

A randomized controlled trial of orbital radiotherapy versus sham irradiation in patients with mild Graves' ophthalmopathy.

Radiotherapy is often used in Graves' ophthalmopathy, but its efficacy has been doubted. We compared its efficacy with sham irradiation in mild ophthalmopathy. In a double-blind randomized trial, 44 patients received orbital irradiation, and 44 were sham-irradiated. The primary outcome was assessed using major and minor criteria. As secondary outcome, we used a disease-specific quality of life questionnaire (the GO-QoL) and compared cost-effectiveness and need for follow-up treatment. The primary outcome was successful in 23 of 44 (52%) irradiated patients vs. 12 of 44 (27%) sham-irradiated patients at 12 months after treatment (relative risk, 1.9; 95% confidence interval, 1.1-3.4; P = 0.02). Radiotherapy was effective in improving eye muscle motility and decreasing the severity of diplopia. However, quality of life improved similarly in both groups. In the radiotherapy group there was less need for follow-up treatment; 66% vs. 84% of the patients needed further treatment (P = 0.049). Retrobulbar irradiation did not prevent worsening of ophthalmopathy, which occurred in 14% of the irradiated and 16% of the sham-irradiated patients. Radiotherapy is an effective treatment in mild ophthalmopathy. However, the improvement upon irradiation may not be associated with an increase in quality of life or a reduction in treatment costs.

Assessment of disease activity in Graves' ophthalmopathy by orbital ultrasonography and clinical parameters.

OBJECTIVE: To study if A-mode ultrasonography (US) in combination with the Clinical Activity Score (CAS) and duration of Graves' ophthalmopathy (GO) could predict the response to immunosuppression in Graves' ophthalmopathy. DESIGN: A prospective clinical study. PATIENTS AND METHODS: Fifty-six consecutive patients with moderately severe GO were treated with retrobulbar irradiation (10 fractions of 2 Gy). Before treatment the internal reflectivity in the extraocular eye muscles, the CAS, and the duration of Graves' ophthalmopathy were assessed and related to the therapeutic outcome 26 weeks after irradiation. RESULTS: Twenty-eight (50%) of the patients responded favourably to radiotherapy (four patients became worse, and 24 did not change), and the eye muscle echogenecity indeed tended to be lower in the responders than in the non-responders (P = 0.09). From a receiver operator characteristics curve, a cut-off value of 30% yielded a good positive predictive value of 85%, but the negative predictive value was only 60%. The CAS (>/= 4/10) had a positive predictive value of 65%, and a negative predictive value of 56%. When combining the ultrasound with the CAS, the positive predictive value increased to 74% and the negative predictive value to 72%. Adding the duration of eye symptoms (cut-off 18 months), the prediction of response further improved: positive predictive value 79%, and negative predictive value 89%. CONCLUSIONS: A-mode ultrasonography has a rather good positive predictive value, but its poor negative predictive value precludes its use as sole activity parameter. By adding the Clinical Activity Score and duration of Graves' ophthalmopathy, the negative predictive value increased considerably. By using this combination, inactive disease can be identified more precise, permitting rehabilitative surgery at an earlier stage in these patients.

[Cost-effectiveness analysis: radioiodine or antithyroid medication in primary treatment of immune hyperthyroidism]. / Kosten-Effektivitäts-Analyse: Radioiod oder thyreostatische Medikation bei der Primärbehandlung der Immunhyperthyreose.

AIM: As first-line therapy of hyperthyroidism caused by Graves' disease antithyroid drugs are favoured in Europe, while radioiodine therapy is favoured in the USA. Radioiodine therapy has become more economic in Germany since the new recommendations by the Federal German Radiation Protection Committee (SSK) for patient discharge guidelines. METHOD: Sensitivity analyses took into account the long-term relapse rate of conservative or radioiodine therapy, use of diagnostic tests, level of health insurance, drops in productivity and a discount factor. Costing models included the costs of follow-up care over 30 years. The costs of the hospitalisation for radioiodine therapy were calculated for 300 patients, discharged with 250 MBq 1-131 residual activity. RESULT: Antithyroid drugs were considered cost-effective when they achieved relapse rate of 50% or less, a cut in the number of tests needed and reduced working hours. Failure to meet any one of these conditions makes primary radioiodine therapy more cost-effective in 1593 of 1944 calculated costing models. Repeated conservative therapies will increase clearly the overall costs. CONCLUSION: Radioiodine is a cost-effective, first-line therapy in patients with a special risk of relapse after primary conservative therapy (goitre, younger patient, persistent elevated TSH-receptor-antibodies or Tc-uptake).

Assessment of a carcinogenic risk for treatment of Graves' ophthalmopathy in dependence on age and irradiation geometry.

In view of the probable carcinogenic risk due to the irradiation of Graves' ophthalmopathy in young patients the effective dose was assessed for two geometries. Adjusting the field to the conical outline of the orbit resulted in appreciable reduction in dose to uninvolved areas such as brain and bone marrow. In Leiden and in Essen the initial target dose was 20 Gy in 10 fractions of 2 Gy. Since 1996 the target dose in Essen was lowered to 10 fractions of 1.6 Gy with equal positive results. The combined effect of field optimization and 20% reduction in target dose has lowered the effective dose from 65 to 34 mSv. The attributable lifetime risk for fatal malignancies of 0.3% as a population average will be considerably reduced when the exposure occurs at older age.

The use of colour slides in the assessment of changes in soft-tissue involvement in Graves' ophthalmopathy.

There is a need for more reliable and validated methods to assess the eye changes in Graves' disease. Such measurements are now available for the assessment of proptosis, eye muscle dysfunction, and optic nerve involvement. However, no validated objective measurement exists for NO SPECS class II signs. The present study compares the use of colour slides with clinical grading for assessing soft-tissue involvement. Forty-three patients were treated with retrobulbar irradiation. Pre-treatment, and 6 months post-treatment the severity of class II signs was graded from 0 to grade c in two ways; 1) Clinically, by two independent, experienced observers, who recorded their scores on the same day; 2) From colour slides, taken at the same visits, which were graded afterwards in one session independently by the same observers. Inter-observer agreement about clinical grading was low (Kappa 0.32), and was not improved by using the slides (Kappa 0.35). However, by using the clinical scores, the observers disagreed on treatment outcome in 21/43 patients (49%), whereas using the slides disagreement occurred in only 6/43 (14%, p < 0.01). It is concluded that the grading of soft-tissue involvement is highly subjective. However, the use of colour slides does provide a more reliable way to assess a treatment effect and should be used in clinical trials.

[Consequences of new patient discharge guidelines on the cost structure of radioiodine therapy]. / Auswirkungen der neuen Entlassungsrichtwerte auf die Kostenstruktur der Radioiodtherapie.

AIM: Consequences of the new recommendations by the Federal German Radiation Protection Committee (SSK) for patient discharge guidelines (residual activity of 250 MBq for I-131) were calculated for duration of stay and radioiodine therapy cost management. METHODS: For 601 consecutively admitted patients with hyperthyreosis, actual duration of stay and duration of stay according to previous guidelines (from 1993) were calculated, as well as duration of stay according to recommended values. Following BPflV statutes, cost-analysis considered the cause and volume of goitre, and by using sensitivity analyses included a range of diagnostics, service assessment, and duration of stay. RESULTS: Duration of stay following I-131 therapy (in Germany) is expected to fall by 35-50% (average future stay 4.0 +/- 2.8 days), average costs from DM 4,452 to DM 3,680 (-17.4%). Not including pretreatment diagnostics, cost reduction (service assessment 17-24%) was estimated at 21-25%. Compared to strumectomy, I-131 therapy costs are expected to be lower for goitres (Graves' disease) up to at least 60 ml, toxic nodules of at least 25 ml, and toxic multinodular goitres of at least 90 ml. CONCLUSION: In the future, I-131 therapy will be more cost-effective even with larger goitres. Since reimbursement is determined by the duration of stay, new reimbursement procedures are discussed in this paper.

[Cost minimization analysis for the definitive therapy of hyperthyroidism: comparison of goiter resection with radioiodine therapy]. / Kostenminimierungsstudie zur definitiven Therapie der Hyperthyreose: Vergleich zwischen Strumaresektion und Radiojodtherapie.

AIM: Cost-analysis of strumaresection and radioiodine treatment in patients with hyperthyreosis. METHOD: Matched by age, sex, comorbidity, volume of goiter, and entity of hyperthyreosis 18 patients of a clinic of surgery, and 28 patients of a clinic of nuclear medicine were analysed by the reimbursed costs, and by a retrospective calculation of the real costs. RESULTS: Based on the rate for the reimbursed costs the radioiodine treatment (6450 DM) was more favourably than the strumaresection (7562 DM); based on the calculation of the real costs including regional specialities there was a minimal difference in favour of the strumaresection (5185 DM versus 5562 DM) because of the selection of large goiters (median 53 ml), the longer hospitalisation after radioiodine treatment due to legal reasons (12.5 days), and the frequent controls before and after the radioiodine treatment. Most important cost-factor of the radioiodine treatment was the volume of goiter, most important cost-factor of the strumaresection was the age of the patient. The treatment of Graves disease was more expensive than that of autonomy in surgery as well as in nuclear medicine. CONCLUSION: In order to achieve cost-minimization, radioiodine treatment should be prefered in cases of small goiters or in older patients.

Radioiodine therapy for Graves' disease: case selection and restrictions recommended to patients in North America.

Each of the three major therapies for Graves' disease has its own advantages, disadvantages, indications, and contraindications. Today, radioactive iodine (RAI) therapy is the most commonly employed means of therapy for Graves' disease in the United States, with approximately 70% of patients so treated after initial presentation and an additional fraction of arguably 10-15% treated with RAI after failure of antithyroid drugs or surgery. RAI therapy is acknowledged to have the clear-cut advantage of being safe, with low morbidity and cost. The indications for RAI therapy are clear and noncontroversial for most patients with Graves' disease. Moreover, RAI treatment is employed by some thyroidologists for subclinical thyrotoxicosis (normal T4 or T3 but immeasurable TSH), particularly in patients > age 45 due to risks of atrial fibrillation. RAI therapy is not considered indicated or is contraindicated during breast feeding and in pregnancy, subacute thyroiditis, postpartum thyroiditis, struma ovarii, pituitary (TSH-driven) hyperthyroidism, euthyroid, hyperthyroxinemia, and thyroid hormone resistance. Opinions vary on the use of RAI therapy in children with Graves' disease; generally, a lower age cutoff of 17 years is acceptable in most clinics. Even more controversial is whether RAI therapy in the presence of Graves' ophthalmology constitutes a risk for worsening ophthalmopathy. Resolution of this latter issue awaits more definitive studies, but RAI therapy is likely to remain the first choice for most patients with Graves' disease.