Comparison of Different Doses of 131I in Severe Graves' Hyperthyroidism

Study Overview
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Brief Summary
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The purpose of this study is to determine whether higher doses of radioiodine increase treatment efficacy in severe Graves' disease.

Detailed Description
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Graves' disease (GD) is the most frequent cause of hyperthyroidism, affecting mainly women aged 40-60 years. Radioiodine (¹³¹I), introduced in 1941, has become a cornerstone in the treatment of GD hyperthyroidism. Because of its safety, low costs and rapid effect, it is considered a first line therapy in the United States. However, treatment failure occurs in about 15-25% of patients treated with radioiodine. Patients not cured with the first dose of radioiodine usually present severe hyperthyroidism, characterized by large goiter, high 24-hour radioiodine uptake (24h-RAIU) and very high levels of thyroid hormones. We have previously shown that large goiter (≥48ml) is an independent predictor of treatment failure. In these patients, the therapeutic failure was 40.0% while in patients with smaller goiter was only 6.5% (P=0.005; unpublished). It is generally accepted that higher doses of radioiodine improves cure rates. Indeed, a recent meta-analysis found a correlation between radioiodine dose and therapeutic success in GD patients. To our knowledge, there are no published studies evaluating cure rates with different radioiodine doses in severe GD.

Official Title
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Comparison of Different Doses of 131I in Severe Graves' Hyperthyroidism: A Clinical Trial With Historical Control

Conditions
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Graves Disease

Intervention / Treatment
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* Radiation: Radioiodine
* Radiation: Radioiodine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consecutive patients with a recent diagnosis of Graves' disease and goiter ≥ 48 ml, attending the Endocrine Division at Hospital de Clinicas de Porto Alegre are eligible. Exclusion Criteria: Patients with previous treatment with radioiodine or thyroidectomy, Signs of moderate or severe ophthalmopathy (proptosis > 22 mm, ophthalmoplegia, chemosis, or lagophthalmos), Severe heart disease (symptomatic coronary heart disease, class III heart failure, New York Heart Association criteria), Debilitating conditions, and Large and compressive goiters (> 150 g).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Radiodine-200µCi<br>A subgroup of patients with Graves' Disease and goiter ≥48ml treated with 200µCi of ¹³¹I/ml thyroid tissue, corrected by 24h-RAIU, from a randomized controlled trial run at our institution between February 1997 and March 2000, serves as a historical control. | Radiation: Radioiodine<br>* A unique dose of 200µCi of ¹³¹I/ml/24-RAIU<br>|
| Experimental: Radiodine-250µCi<br>Patients with Graves' Disease and goiter ≥48ml, prospectively assigned to receive 250 µCi of ¹³¹I/ml thyroid tissue, corrected by 24h-RAIU. | Radiation: Radioiodine<br>* A unique dose of 250µCi of ¹³¹I/ml/24-RAIU<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cure, defined as euthyroidism or permanent hypothyroidism based on FT4 measurements. |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Euthyroidism |  | 12 months | 
| Permanent hypothyroidism |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Graves Disease, Hyperthyroidism, Radioiodine, Clinical trial