medwireNews: A randomised trial of children receiving treatment for thyrotoxicosis shows no difference in biochemical stability between block-and-replace and dose-titration strategies.
“This trial is the largest prospective study comparing the two [anti-thyroid drug] regimens […] that has ever been conducted in young people and is the first to provide level-1 evidence”, say the researchers.
All 81 patients recruited to the trial initially received carbimazole at a dose of 0.75 mg/kg per day, which the researchers explain “was expected to abolish endogenous thyroid hormone production in the majority of patients”.
Patients randomly assigned to the block-and-replace strategy received supplementary thyroid hormone as they became hypothyroid, whereas those assigned to undergo dose titration had their carbimazole dose reduced until they achieved euthyroid status.
Approximately 75% of the study participants were female and the majority were older than 10 years at diagnosis. They were seen every 4 weeks for the first 16 weeks, with visits becoming less frequent until they were seen every 3 months between week 26 and the end of year 3.
A total of 77 patients were included in the primary analysis – 39 from the block-and-replace group and 38 from the dose-titration group. During the study analysis period between month 6 and the end of year 3, the average percentage of thyroid-stimulating hormone measurements within the reference range (determined locally) was 60.2% for children in the block-and-replace group and 63.8% for those receiving dose titration, which was not significantly different.
Tim Cheetham (Royal Victoria Infirmary, Newcastle-upon-Tyne, UK) and co-researchers note that the trial was powered to detect a difference of at least 10% between the two regimens.
Statistically, their findings show “that the difference in favour of [block and replace] is no greater than 8% and that in favour of [dose titration] could be as large as 16%”, they write in the European Journal of Endocrinology.
There was also no evidence of any difference in the proportion of within-range free thyroxine measurements between the two groups.
The average carbimazole dose during the monitoring period was 0.61 versus 0.30 mg/kg in the block-and-replace versus dose-titration groups.
There were 78 non-serious adverse events thought to be related or possibly related to treatment in the block-and-replace group, and 57 in the dose-titration group. There were three treatment-related serious adverse events in the block-and-replace group, all of which were neutropenia. The two potentially related serious events in the dose-titration group involved fever with sore throat and hospital admission for excessive vomiting and headache.
The researchers note that these findings offer some support to American Thyroid Association recommendations to avoid block-and-replace due to the higher risk for side effects.
And they conclude that their study does not provide “any evidence to refute the current guidelines that recommend [dose titration] in most growing people with thyrotoxicosis.”
Commenting on the findings for medwireNews, Martin Savage (Barts and the London School of Medicine & Dentistry, UK) said that “this exhaustive study deserves congratulations due to its difficulty and its balanced conclusions.”
However, he also sounded a note of caution, observing that there was “no mention of therapeutic response in the context of the size of the goitre at initial presentation”, explaining that “clinical experience suggests that patients with large goitres respond more satisfactorily to a block and replacement strategy.”
In addition, Savage noted that “the speed of induction of remission is usually faster when block and replace is used.”
He therefore concluded that “it is likely that doubt will remain in the minds of many paediatric endocrinologists about which strategy is likely to induce greater stability to, as the authors rightly state, a challenging clinical problem.”
By Eleanor McDermid
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