In contrast, 8 of 20 patients in group B were unimproved clinically and chemically at 3 months (Table 2). These eight patients remained the same at 6 months. Three of six patients who had residual symptoms at 3 months deteriorated to join the unimproved category at 6 months. In addition, two of five patients who did not come to their 3-month visit came back at 6 months and reported that they were unimproved. This increased the number of patients in the unimproved category to 13 of 20 patients. The difference in the number of the unimproved patients at 3 and 6 months between the two groups was significant (P < 10-6). None of the patients in group B were normal or hypothyroid at 3 or 6 months (Fig. 2).
The trend in the use of antithyroid medications was also different between the two groups. Both groups had comparable use of antithyroid medications before the initial dose of RAI. There were 56 patients (70%) in group A and 13 patients (65%) in group B. After RAI treatment, the use of antithyroid medications decreased in group A patients from 26% to 10% and increased in group B from 55% to 70% at 3 and 6 months, respectively. The difference in the use of antithyroid medications after RAI treatment between the two groups was significant (P < 0.014 at 3 months and P < 1.6 × 10-7 at 6 months).
The results of our study clearly identify a significant difference in the response to the initial dose of RAI treatment in patients who require a single dose and those who require a second dose. Patients who did not respond to an initial treatment dose of RAI tend to continue with the same symptoms and signs or partially improve early after treatment and subsequently deteriorate again to their original hyperthyroid state by 6 months. The most important finding is that the eight patients in group B who were unimproved at 3 months remained the same at 6 months. This supports the need for earlier retreatment with a second dose of RAI in such patients. Our data suggest that the 3-month interval is an adequate period to identify nonresponders to an initial dose of RAI and to consider retreatment with a second dose. The rationale behind a 6-month waiting period before considering retreatment with RAI has not been adequately studied and there is insufficient data to support it.
None of the patients who responded to a single dose of RAI was unimproved at the 3- and 6-months intervals. This provides a safety measure against unnecessary retreatment with RAI in slow responders to an initial dose. Thus, if a patient shows any degree of improvement at 3 months, repeated evaluation at 6 months is warranted. Conversely, patients who are unimproved at 3 months can be retreated safely with RAI.
None of the patients who required a second dose of RAI were normal or hypothyroid at 3 or 6 months, even when 70% of the patients were taking antithyroid medications. Patients who became normal or hypothyroid as early as 3 months after RAI treatment are unlikely to represent treatment failures at 6 months. The distinction between treatment failure and recurrence of hyperthyroid disease may be based on the response of the patient in the few months after RAI treatment. Patients who do not improve or do so only partially and then rebound to their original hyperthyroid state in the first 6 months are considered treatment failures. Hyperthyroid patients who become subclinically hyperthyroid, euthyroid, or hypothyroid for longer periods ranging from 12 months to years and then return to their hyperthyroid state may be considered to have recurrent disease (9).
Although this was a retrospective study with possible inaccuracies in estimating gland size by palpation, the fact that the same physician performed the examinations and estimates supports consistency in gland size estimation in the two groups (14,22,23).
Variability in the number of days the antithyroid medication was discontinued before RAI treatment and its effect on outcome is one of the shortcomings of a retrospective study (21). However, the focus of this study was to determine the appropriate timing for repeated treatment with RAI after initial treatment failure, regardless of the causes of the failure (28). We found that RAI failure is associated with a greater frequency of continued use of antithyroid medications past the 3-month visit.
Patients with hyperthyroid disease who are unimproved at 3 months after an initial dose of RAI treatment can be retreated with a second dose of RAI with no further delay.
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