Clinical trial NCT01039818: Comparison of Different Doses of 131I in Severe Graves' Hyperthyroidism
Official title: Comparison of Different Doses of 131I in Severe Graves' Hyperthyroidism: A Clinical Trial With Historical Control
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Graves Disease
Keywords: Graves Disease
Hyperthyroidism
Radioiodine
Clinical trial
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
Collaborators: name: Federal University of Rio Grande do Sul
First posted: 2009-12-25
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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 In these patients, the therapeutic failure was 40.0% while in patients with smaller goiter was only 6.5% (P=0.005; unpublished).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.

Eligibility criteria: 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).

Primary outcomes:
measure: Cure, defined as euthyroidism or permanent hypothyroidism based on FT4 measurements.
timeFrame: 12 months
Secondary outcomes:
measure: Euthyroidism
timeFrame: 12 months
measure: Permanent hypothyroidism
timeFrame: 12 months
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Thyroid Unit, Endocrine Division, Hospital de Clínicas de Porto Alegre
state: RS
Study officials:
affiliation: Thyroid Unit, Endocrine Division, Hospital de Clínicas de Porto Alegre
name: Ana L Maia, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Andrade VA, Gross JL, Maia AL. Effect of methimazole pretreatment on serum thyroid hormone levels after radioactive treatment in Graves' hyperthyroidism. J Clin Endocrinol Metab. 1999 Nov;84(11):4012-6. doi: 10.1210/jcem.84.11.6149.
citation: Andrade VA, Gross JL, Maia AL. The effect of methimazole pretreatment on the efficacy of radioactive iodine therapy in Graves' hyperthyroidism: one-year follow-up of a prospective, randomized study. J Clin Endocrinol Metab. 2001 Aug;86(8):3488-93. doi: 10.1210/jcem.86.8.7707.
citation: Andrade VA, Gross JL, Maia AL. Serum thyrotropin-receptor autoantibodies levels after I therapy in Graves' patients: effect of pretreatment with methimazole evaluated by a prospective, randomized study. Eur J Endocrinol. 2004 Oct;151(4):467-74. doi: 10.1530/eje.0.1510467.
citation: Andrade VA, Gross JL, Maia AL. [Radioactive iodine therapy in Graves' hyperthyroidism]. Arq Bras Endocrinol Metabol. 2004 Feb;48(1):159-65. doi: 10.1590/s0004-27302004000100017. Epub 2004 Jun 1. Portuguese.
citation: Dora JM, Escouto Machado W, Andrade VA, Scheffel RS, Maia AL. Increasing the radioiodine dose does not improve cure rates in severe graves' hyperthyroidism: a clinical trial with historical control. J Thyroid Res. 2013;2013:958276. doi: 10.1155/2013/958276. Epub 2013 Jul 31.