Increasing the radioiodine dose does not improve cure rates in severe graves' hyperthyroidism: a clinical trial with historical control.

Objective. It is generally accepted that higher doses of radioiodine ((131)I) improve cure rates in Graves' disease (GD). In this trial we sought to evaluate whether very high (131)I doses increase the efficacy of treatment in severe GD. Design. Clinical trial with historical control. Patients with GD and a goiter ≥48 mL were eligible for the study. The patients in the contemporaneous intervention cohort were treated with 250 µ Ci of (131)I/mL thyroid tissue, corrected by 24-RAIU values (Group 1; n = 15). A subgroup of patients with GD and a goiter ≥48 mL who were treated with 200 µ Ci of (131)I/mL/24-RAIU in a previously published randomized controlled trial served as a historical control group (Group 2; n = 15). The primary outcome evaluated was the one-year cure rate. Results. There were no significant baseline differences regarding age, gender, body mass index, smoking status, pretreatment with methimazole, thyroid volume, or thyroid hormone levels of the two treatment groups. The cumulative 12-month cure rate for the patients in Group 1 was 66.6%, a figure similar to the 12-month cure rate observed in Group 2 (60.0%; P = 0.99). Conclusions. Our results suggest that increasing the (131)I dose does not improve cure rates in severe GD. This trial is registered with ClinicalTrials.gov NCT01039818.

[Radioactive iodine therapy in Graves' hyperthyroidism]. / Iodo radioativo no manejo do hipertireoidismo da doença de Graves.

Graves' disease is the most frequent cause of hyperthyroidism. Clinical thyrotoxicosis is directly caused by autoantibodies that activate the TSH receptor. The etiology is multifactorial, with genetic and nongenetic factors involved. Current treatment options are antithyroid drugs (ATD), radioiodine (131I) and surgery. Radioactive iodine is increasingly being used as definitive therapy, because it long has proven to be a safe, nonexpensive and effective treatment. Recent publications have discussed the use of 131I associated with ATD as well as the identification of predictors of treatment failure, which are discussed in this review. Antithyroid drugs are still the first choice therapy in patients with mild disease, small goiters, children, adolescents, and in pregnancy. Surgery is now rarely performed. It is indicated only in cases where ATD have not been effective and radioiodine is contraindicated or not acceptable by the patients.

Serum thyrotropin-receptor autoantibodies levels after I therapy in Graves' patients: effect of pretreatment with methimazole evaluated by a prospective, randomized study.

OBJECTIVE: Radioiodine therapy (131I) in hyperthyroid Graves' disease is generally followed by a transitory increase in levels of thyrotropin receptors antibodies (TRAb). Immunosuppressive effects of antithyroid drugs are still a matter of debate. In this study we evaluated the effect of methimazole pretreatment on the TRAb boost induced by 131I. DESIGN: A randomized, prospective clinical trial. METHODS: 61 patients were randomly assigned to receive 131I alone (32 patients) or 131I plus pretreatment with methimazole (30 mg/day; 29 patients). Serum TRAb levels were measured on the day of 131I dosing (D0), and at 1, 3, 6 and 12 months after 131I administration. RESULTS: The mean serum TRAb levels decreased significantly from baseline to D0 in patients treated with methimazole (80.8 vs 48.8 U/l; P<0.05). After 131I treatment, TRAb levels increased at 3 months (48.8 to 60 U/l; 19%) and they were still elevated at 6 months compared with D0 values (99.9 U/l; 105%). Thereafter, TRAb levels decreased to baseline values (47.8 U/l) at 12 months. In hyperthyroid patients, TRAb levels increased significantly from D0 to 1 month (45.0 to 78 U/l; 73%) reaching their highest levels at 3 months (225 U/l; 400%). After this, we observed a progressive decrease to the baseline levels at 12 months (40.0 U/l). The course of TRAb levels after 131I treatment was significantly different between the two groups (P<0.05). Multiple regression analysis identified serum TRAb levels on D0 as independent predictors of TRAb increment after 131I therapy (r2=0.34; P=0.001). A higher increment in serum TRAb levels was associated with hypothyroidism after 1 year of follow-up. CONCLUSION: Methimazole pretreatment attenuates the 131I-induced rise in serum TRAb levels. The effects of methimazole could be attributed to a direct immunomodulatory action or may be due to its effects on the control of hyperthyroidism, which is a known cause of immune dysregulation.

Iodo radioativo no manejo do hipertireoidismo da doença de Graves / Radioactive iodine therapy in Graves' hyperthyroidism

O hipertireoidismo da doença de Graves, a forma mais comum de hipertireoidismo, é diretamente causado por auto-anticorpos que ativam o receptor do TSH. A etiologia parece ser multifatorial, envolvendo fatores genéticos e não genéticos. As opções terapêuticas atualmente disponíveis são as drogas antitireoidianas (DAT), a cirurgia e o iodo radioativo (131I), sendo que nenhuma delas é considerada ideal, visto que não atuam diretamente na etiologia/patogênese da disfunção. O 131I tem sido cada vez mais utilizado como primeira escolha terapêutica por tratar-se de um tratamento definitivo, de fácil administração e seguro. A associação com DAT, fatores prognósticos de falência e o cálculo da dose administrada são alguns dos aspectos controversos na utilização do 131I, sendo este o principal foco desta revisão. As DAT ainda são utilizadas como primeira escolha nos casos de pacientes com bócios pequenos, crianças e adolescentes, e na gravidez. A tireoidectomia é, atualmente, quase um tratamento de exceção, com indicação restrita para casos em que as DAT ou o 131I sejam contra-indicados.

Tratamento do hipertireoidismo da doença de Graves / Hyperthyroidism treatment of the Graves'disease

A Doença de Graves constitui a forma mais comum de hipertireoidismo e três abordagens terapêuticas säo atualmente utilizadas: drogas antitireoidianas (DAT), cirurgia e iodo radioativo (1311). As DAT continuam como tratamento de primeira escolha em pacientes com doença leve, bócios pequenos, crianças e adolescentes, e em situaçöes especiais como na gravidez. Por outro lado, o 1311 tem sido cada vez mais utilizado, porque é considerado um tratamento seguro, definitivo e de fácil aplicaçäo. O risco de exacerbaçäo do hipertireoidismo após administraçäo do 1311, os fatores prognósticos de falência e o cálculo da dose administrada têm sido alguns dos aspectos discutidos na literatura recentemente, e säo particulamente comentados nesta revisäo. O tratamento cirúrgico constitui quase um tratamento de exceçäo, com indicaçäo para os casos em que as terapias anteriores näo possam ser utilizadas.