Propylthiouracil Reduces the Effectiveness of Radioiodine Treatment in Hyperthyroid Patients with Graves' Disease

Santos, Rejane Barbosa; Romaldini, João Hamilton; Ward, Laura Sterian

doi:10.1089/1050725041517093

Cited by 65 publications

(39 citation statements)

References 31 publications

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“…There is controversy over whether their effect on radioiodine treatment is similar in both diseases. Thiamazoles and thiouracils have been found to reduce the success of radioiodine treatment in Graves' disease [3,5,[23][24][25][26]. In contrast, studies including both patients with Graves' disease and patients with toxic nodular goitre revealed propylthiouracil or multiple thyrostatics to have no effect in Graves' disease but an adverse influence in toxic nodular goitre [21,22].…”

Section: Discussionmentioning

confidence: 99%

Outcome of radioiodine therapy without, on or 3 days off carbimazole: a prospective interventional three-group comparison

Walter

Christ‐Crain

Schindler

et al. 2006

Eur J Nucl Med Mol Imaging

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Abstract. Purpose: Carbimazole ameliorates hyperthyroidism but reduces radioiodine uptake and adversely affects the outcome of simultaneous radioiodine therapy. We explored whether withdrawal of carbimazole for 3 days can restore the outcome of radioiodine treatment without concurrent exacerbation of hyperthyroidism. By generating three groups with comparable radioiodine uptake, we also investigated whether the effect of carbimazole depends on the radioiodine uptake. Methods: Stratified by a radioiodine uptake >30%, 227 consecutive adult patients were prospectively assigned to radioiodine therapy (target dose 200 Gy) without, on or 3 days off carbimazole. Patients were clinically (CrooksWayne score) and biochemically (T 3 , fT 4 , TSH) followed up after 3, 6 and 12 months. Primary endpoint was outcome 12 months after radioiodine therapy. Results: A total of 207 patients completed follow-up (toxic nodular goitre, n=117; Graves' disease, n=90). The overall success rate was 71.5%. Patients without and 3 days off carbimazole had similar biochemical (81.4% and 83.3%, respectively; p=0.82) and clinical outcomes [median (range) Crooks-Wayne score 0 (0-16) and 1 (0-10), respectively; p=0.73], which were both higher than in patients on carbimazole [42.6%, p<0.001; Crooks-Wayne score 3 (0-30), p<0.03]. Time to achieve cure was delayed on carbimazole. No changes in thyroid hormone levels occurred after 3 days' discontinuation of carbimazole. Logistic regression revealed that all observed cure rates were independent of entity, sex, age, thyroid volume, radioiodine uptake, radioiodine half-life, fT 4 , T 3 and TSH. Conclusion: Patients under carbimazole treatment can be referred for radioiodine therapy after withdrawal of carbimazole for only 3 days. Three days of carbimazole withdrawal is long enough to restore the success of radioiodine therapy and short enough to avoid the risk of exacerbation of hyperthyroidism.

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Section: Discussionmentioning

confidence: 99%

Outcome of radioiodine therapy without, on or 3 days off carbimazole: a prospective interventional three-group comparison

Walter

Christ‐Crain

Schindler

et al. 2006

Eur J Nucl Med Mol Imaging

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“…The NIS expression level is already high in Graves' patients (51); therefore, we assume that PTU treatment will not further increase NIS expression and as such not worsen Graves' disease. Pretreatment with MMI has no effect on either the time required for cure or the one-year success rate of radioactive iodine therapy (2), whereas PTU pretreatment reduces the effectiveness of radioactive iodine therapy in Graves' disease patients (14,52). This study may shed some light on the differential use of antithyroid drugs.…”

Section: Discussionmentioning

confidence: 99%

Propylthiouracil Increases Sodium/Iodide Symporter Gene Expression and Iodide Uptake in Rat Thyroid Cells in the Absence of TSH

Sue

Akama

Kawashima

et al. 2012

Thyroid

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Background: Propylthiouracil (PTU) and methimazole (MMI) are drugs that are widely used to treat Graves' disease. Although both exert an antithyroid effect primarily by blocking thyroid peroxidase activity, their molecular structure and other actions are different. We hypothesized that PTU and MMI may have differential effects on thyroid-specific gene expression and function. Methods: The effects of PTU and MMI on thyroid-specific gene expression and function were examined in rat thyroid FRTL-5 cells using DNA microarray, reverse transcriptase (RT)-polymerase chain reaction (PCR), real-time PCR, Western blot, immunohistochemistry, and radioiodine uptake studies. Results: DNA microarray analysis showed a marked increase in sodium/iodide symporter (NIS) gene expression after PTU treatment, whereas MMI had no effect. RT-PCR and real-time PCR analysis revealed that PTUinduced NIS mRNA levels were comparable to those elicited by thyroid-stimulating hormone (TSH). PTU increased 5¢-1880-bp and 5¢-1052-bp activity of the rat NIS promoter. While PTU treatment also increased NIS protein levels, the size of the induced protein was smaller than that induced by TSH, and the protein localized predominantly in the cytoplasm rather than the plasma membrane. Accumulation of 125 I in FRTL-5 cells was increased by PTU stimulation, but this effect was weaker than that produced by TSH. Conclusions: We found that PTU induces NIS expression and iodide uptake in rat thyroid FRTL-5 cells in the absence of TSH. Although PTU and MMI share similar antithyroid activity, their effects on other thyroid functions appear to be quite different, which could affect their therapeutic effectiveness.

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“…Santos e cols. (19) demonstraram este efeito radioprotetor em análise prospectiva utilizando 14 dias de suspensão dos ATs e com dose de radioiodo fixa em 10 mCi. Bonnema e cols.…”

Section: Discussionunclassified

Efeito do propiltiouracil sobre a eficácia da dose terapêutica de iodo radioativo (I-131) no hipertiroidismo por doença de graves

Souza

Buescu

Souza

et al. 2006

Arq Bras Endocrinol Metab

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RESUMOCom objetivo de avaliar a influência das drogas antitiroidianas (AT) sobre a eficácia da dose terapêutica de iodo radioativo (DT), avaliamos retrospectivamente 226 prontuários de pacientes portadores de doença de Graves submetidos à DT no período entre 1990 e 2001: 58 pacientes sem antitiroidiano (AT), 119 em uso de propiltiouracil (PTU) e 49 em uso de metimazol (MMI). O estado funcional tiroidiano 9-12 meses pós-DT dividia os pacientes entre curados e não curados. Níveis elevados de T4 livre, captação de 131 I em 24 h tiveram influência negativa sobre a taxa de cura, assim como menor dose de iodo administrada e maior volume do bócio (p< 0,05). O percentual de pacientes curados em uso de PTU previamente à DT foi de 70,2% (84/119), enquanto nos pacientes em uso de MMI foi de 85,7% (42/49), e de 84,5% (49/58) nos pacientes sem AT pré-DT (p= 0,034). Em modelo de regressão multivariado, T4 livre > 4 ng/dl, maior volume do bócio, dose terapêutica < 10 mCi e o uso prévio de PTU tiveram relação com menores taxas de cura. Quando comparado ao grupo sem AT, concluímos que PTU implica em maior risco de falência pós-DT (OR= 3,13), o mesmo não ocorrendo com MMI (OR= 1,28). ABSTRACTThe Effect of Propylthiouracil on the Efficacy of Radioiodine (I-131) Therapy in Graves' Hyperthyroidism. Aiming at evaluating the effect of antithyroid drugs on the efficacy of radioiodine treatment (RAI) we retrospectively analyzed 226 patients with Graves' disease hyperthyroidism submitted to RAI between 1990 and 2001: 58 patients without any antithyroid drug (ATD) prior to RAI, 119 patients using propylthiouracil (PTU) and 49 patients using methimazole (MMI) prior to RAI. Clinical and laboratory parameters 1 year after RAI defined their clinical status (cured or not cured). High serum free T4 and 131-iodine uptake were negatively related with cure as well as lower RAI doses (mCi) and larger goiters (p< 0.05). The percentage of cured patients on PTU prior to RAI was 70.2% (84/119), while those on MMI was 85.7% (42/49), and 84.5% (49/58) of those without ATD prior to RAI (p= 0.034). On logistic regression analysis, free T4 > 4 ng/dl, large goiter, RAI dose < 10 mCi and PTU prior to RAI were related to lower cure rates. Compared to patients with no ATD prior to RAI, we concluded that the previous use of PTU implies in higher failure rates after RAI (OR= 3.13), an effect not observed in patients on MMI (OR= 1.28).

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Propylthiouracil Reduces the Effectiveness of Radioiodine Treatment in Hyperthyroid Patients with Graves' Disease

Cited by 65 publications

References 31 publications

Outcome of radioiodine therapy without, on or 3 days off carbimazole: a prospective interventional three-group comparison

Outcome of radioiodine therapy without, on or 3 days off carbimazole: a prospective interventional three-group comparison

Propylthiouracil Increases Sodium/Iodide Symporter Gene Expression and Iodide Uptake in Rat Thyroid Cells in the Absence of TSH

Efeito do propiltiouracil sobre a eficácia da dose terapêutica de iodo radioativo (I-131) no hipertiroidismo por doença de graves

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