Background The chief clinical characteristics of Graves' disease are hyperthyroidism and ophthalmopathy. The relation between the two and the effect of treatment for hyperthyroidism on ophthalmopathy are unclear. Methods We studied 443 patients with Graves` hyperthyroidism and slight or no ophthalmopathy who were randomly assigned to receive radioiodine, radioiodine followed by a 3-month course of prednisone, or methimazole for 18 months. The patients were evaluated for changes in the function and appearance of the thyroid and progression of ophthalmopathy at intervals of 1 to 2 months for 12 months. Hypothyroidism and persistent hyperthyroidism were promptly corrected. Results Among the 150 patients treated with radioiodine, ophthalmopathy developed or worsened in 23 (15 percent) two to six months after treatment. The change was transient in 15 patients, but it persisted in 8 (5 percent), who subsequently required treatment for their eye disease. None of the 55 other patients in this group who had ophtha...

Relation between therapy for hyperthyroidism and the course of Graves' ophthalmopathy.

Radioiodine ((131)I) therapy of benign thyroid diseases was introduced 70 yr ago, and the patients treated since then are probably numbered in the millions. Fifty to 90% of hyperthyroid patients are cured within 1 yr after (131)I therapy. With longer follow-up, permanent hypothyroidism seems inevitable in Graves' disease, whereas this risk is much lower when treating toxic nodular goiter. The side effect causing most concern is the potential induction of ophthalmopathy in predisposed individuals. The response to (131)I therapy is to some extent related to the radiation dose. However, calculation of an exact thyroid dose is error-prone due to imprecise measurement of the (131)I biokinetics, and the importance of internal dosimetric factors, such as the thyroid follicle size, is probably underestimated. Besides these obstacles, several potential confounders interfere with the efficacy of (131)I therapy, and they may even interact mutually and counteract each other. Numerous studies have evaluated the effect of (131)I therapy, but results have been conflicting due to differences in design, sample size, patient selection, and dose calculation. It seems clear that no single factor reliably predicts the outcome from (131)I therapy. The individual radiosensitivity, still poorly defined and impossible to quantify, may be a major determinant of the outcome from (131)I therapy. Above all, the impact of (131)I therapy relies on the iodine-concentrating ability of the thyroid gland. The thyroid (131)I uptake (or retention) can be stimulated in several ways, including dietary iodine restriction and use of lithium. In particular, recombinant human thyrotropin has gained interest because this compound significantly amplifies the effect of (131)I therapy in patients with nontoxic nodular goiter.

Radioiodine Therapy in Benign Thyroid Diseases: Effects, Side Effects, and Factors Affecting Therapeutic Outcome

There is little consensus regarding the most appropriate dose regimen for radioiodine (131I) in the treatment of hyperthyroidism. We audited 813 consecutive hyperthyroid patients treated with radioiodine to compare the efficacy of 2 fixed-dose regimens used within our center (185 megabequerels, 370 megabequerels) and to explore factors that may predict outcome. Patients were categorized into 3 diagnostic groups: Graves' disease, toxic nodular goiter, and hyperthyroidism of indeterminate etiology. Cure after a single dose of 131I was investigated and defined as euthyroid off all treatment for 6 months or T4 replacement for biochemical hypothyroidism in all groups. As expected, patients given a single dose of 370 megabequerels had a higher cure rate than those given 185 megabequerels, (84.6% vs. 66.6%, P < 0.0001) but an increase in hypothyroidism incidence at 1 yr (60.8% vs. 41.3%, P < 0.0001). There was no difference in cure rate between the groups with Graves' disease and those with toxic nodular goiter (69.5% vs. 71.4%; P, not significant), but Graves' patients had a higher incidence of hypothyroidism (54.5% vs. 31.7%, P < 0.0001). Males had a lower cure rate than females (67.6% vs. 76.7%, P = 0.02), whereas younger patients (<40 yr) had a lower cure rate than patients over 40 yr old (68.9% vs. 79.3%, P < 0.001). Patients with more severe hyperthyroidism (P < 0.0001) and with goiters of medium or large size (P < 0.0001) were less likely to be cured after a single dose of 131I. The use of antithyroid drugs, during a period 2 wk before or after 131I, resulted in a significant reduction in cure rate in patients given 185 megabequerels 131I (P < 0.01) but not 370 megabequerels. Logistic regression analysis showed dose, gender, goiters of medium or large size, and severity of hyperthyroidism to be significant independent prognostic factors for cure after a single dose of 131I. We have demonstrated that a single fixed dose of 370 megabequerels 131I is highly effective in curing toxic nodular hyperthyroidism as well as Graves' hyperthyroidism. Because male patients and those with more severe hyperthyroidism and medium or large-sized goiters are less likely to respond to a single dose of radioiodine, we suggest that the value of higher fixed initial doses of radioiodine should be evaluated in these patient categories with lower cure rates.

/pdf/radioiodine-treatment-of-hyperthyroidism-prognostic-factors-54qeryjp7q.pdf

Radioiodine Treatment of Hyperthyroidism—Prognostic Factors for Outcome

Antithyroid drugs have been in use for over half a century, and much is now known about their mechanism of action, pharmacokinetics, and clinical pharmacology (1). Somewhat surprisingly perhaps, clinicians are still challenged on a regular basis by numerous questions related to their optimal use. Choice of antithyroid agent, duration of use, proper dosage, patient selection for primary antithyroid drug therapy, and pretreatment of patients before radioiodine administration are just some of the issues that confront busy practitioners on an almost daily basis. Although there have been published guidelines addressing the general subject of hyperthyroidism therapy (2–4), they are not evidenced-based, nor do they confront these specific, practical questions. To try to address these specific issues in a rigorous way, the following discussion will use an evidence-based approach. The American Academy of Family Physicians (5) and most other organizations rate levels of evidence according to the following scheme. • Level A: a high-quality randomized controlled trial (RCT) that considers all important outcomes, and high-quality metaanalysis (quantitative systematic review) using comprehensive search strategies. • Level B (other evidence): a well-designed, nonrandomized clinical trial; and a nonquantitative systematic review with appropriate search strategies and well-substantiated conclusions. Level B includes lower quality RCTs, clinical cohort studies, and case-controlled studies with nonbiased selection of study participants and consistent findings. Other evidence, such as high-quality, historical, uncontrolled studies, or well-designed epidemiological studies with compelling findings, is also included. • Level C: consensus viewpoint or expert opinion. The cases of two prototypical patients that are likely to be seen frequently in any busy clinical endocrinologist’s office will be presented. A series of questions about each case will be raised and then answered using level A evidence, wherever possible. Unfortunately, for many of the questions under consideration, the highest levels of evidence are not available, and data that are less rigorously obtained must be used. A 1998 British review (6) discussed some of the same issues using a similar format.

/pdf/antithyroid-drugs-in-the-management-of-patients-with-graves-3pg8cilpui.pdf

Antithyroid Drugs in the Management of Patients with Graves’ Disease: An Evidence-Based Approach to Therapeutic Controversies

Ninety-three hyperthyroid patients were treated with 1 dose of iodine-131 (131I) during the past 10 years. Thirty-three were pretreated with propylthiouracil (PTU), 22 with methimazole (MMI), and 38 received no antithyroid drugs (ATD). ATD were discontinued 5-55 days before 131I therapy in three fourths of the cases and more than 4 months before therapy in one fourth of the cases. The frequency of cures in the 3 groups, 6-8 months after radioiodine therapy, was retrospectively studied. The cure rate among those who discontinued PTU for 5-55 days before 131I was significantly reduced (24%), compared with those who discontinued MMI for the same duration (61%) or those who received no ATD (66%). When PTU was discontinued for more than 4 months, the cure rate was similar to those who received no ATD. It is concluded that if ATD are used as initial therapy for hyperthyroidism, then PTU (but not MMI) may reduce the therapeutic efficacy of subsequent 131I. The reduction in cure rate was observed even when PTU was discontinued for as long as 55 days before 131I therapy. To our knowledge, this is the first report to compare, in one study, the effects of pretreatment with PTU and MMI on 131I therapy.

Pretreatment with propylthiouracil but not methimazole reduces the therapeutic efficacy of iodine-131 in hyperthyroidism

The outcome of radioiodine therapy of Graves’ hyperthyroidism was retrospectively evaluated in 274 consecutive patients treated from 1975 to 1984. At 1-yr follow-up, permanent hypothyroidism occurred in 36.9% of patients and the cumulative incidence of hypothyroidism progressively increased up to 79.3% after 7–10 yr. At the end of the follow-up period, 148 patients (54%) were hypothyroid, 115 (42%) euthyroid and 11 (4%) still hyperthyroid. The prevalence of hypothyroidism was significantly higher in patients with small goiters (≤ 50 g) than in those with large goiters (> 90 g). Moreover, hypothyroidism was more frequent in patients with high thyroglobulin antibodies titers (≥ 1: 25,600) than in those with low titers or negative tests, and occurred earlier in the former group than in the latter ones Correction of thyrotoxicosis was obtained after the administration of a single dose of 131I in 187 patients (63.6%); 69 patients required two doses and 11 three or more doses. Seven patients refused further treatment with 131I after the first dose. In an effort to identify possible factors affecting the efficacy of 131I therapy, we avaluated the results obtained after the administration of the first dose of radioiodine. We found that large goiters, rapid iodide turnover and adjunctive therapy with methimazole shortly after radioiodine were associated with a higher rate of persistence of thyrotoxicosis, whereas an increased prevalence of hypothyroidism was observed in patients with small goiters and in those not treated with methimazole up to one week after 131I. On the other hand pretreatment with methimazole before radioiodine administration did not affect the outcome of treatment. Thus, if correction of thyrotoxicosis, irrespective of the occurrence of hypothyroidism, has to represent the goal of radioiodine therapy of Graves’ disease, the following points should be kept in mind: i) Large goiters and goiters with a rapid iodine turnover should receive larger 131I doses/g thyroid tissue; ii) Methimazole should not be given shortly after radioiodine: if thyrotoxicosis is severe, the antithyroid drugs may be given prior to 131I therapy to restore euthyroidism, without limiting the efficacy of radiodiodine.

A reappraisal of the role of methimazole and other factors on the efficacy and outcome of radioiodine therapy of Graves’ hyperthyroidism

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A reappraisal of the role of methimazole and other factors on the efficacy and outcome of radioiodine therapy of Graves’ hyperthyroidism