Background: First line treatment for thyrotoxicosis is thionamide (TA) antithyroid drug therapy. The TA used is usually Carbimazole in the UK. TA can be administered in a relatively large 'blocking' dose that prevents endogenous thyroid hormone synthesis, requiring thyroid hormone replacement (block and replace or BR), or in a smaller dose that renders the patient euthyroid (dose titration or DT). The American Thyroid Association (ATA) recommends DT because of the reduced risk of side effects on the lower TA dose. Whether BR provides advantages in terms of improved biochemical stability in the young, growing patient is unknown.
Method: We conducted a multi-centre phase III, open-label randomised trial comparing BR with DT in newly diagnosed patients with thyrotoxicosis less than 17years (y) old who were recruited at 15 United Kingdom units. 81 patients (12 aged 2 to 9y and 69 aged 10 to 16y) were randomised to BR or DT shortly after diagnosis and then treated with ATD for 3 years. The primary outcome for each patient was the proportion of TSH levels in the local reference range for visits (scheduled every 3 months) between 6 months and 3 years. Secondary outcomes included the proportion of FT4 levels in the reference range, frequency of adverse events and outcome (remission/relapse) at 4y.
Results: 81 patients (62 Female) were randomised, 40 to BR (20 with a FT4 >50pmol/l) and 41 to DT (19 with a FT4 >50pmol/l); 7 were lost to follow-up, 3 withdrew from the trial with 1 ineligible. The mean proportion of serum TSH within reference range was 60.2% (BR patients) compared to 63.8% (DT patients); adjusted difference 4.3%, P=0.48, 95% CI (-7.8,16.4). Corresponding quantities for FT4 were 79.2% (BR patients) compared to 85.7% (DT patients); adjusted difference 6.8%, P=0.13, (-0.2,15.6). 45 patients (23 BR, 22 DT) reported at least one adverse event related or possibly related to ATD: for these patients the median number of such AEs was 3 (BR) & 2 (DT). 3 patients developed neutropenia in the BR group (none in DT). 6 BR and 10 DT patients were in remission at 4y. 17 BR and 24 DT patients relapsed. 13 remained on ATD beyond 3 years (9BR, 3DT).
Conclusions: This trial has shown no evidence to suggest that BR is associated with improved biochemical stability. DT, as recommended by the ATA, is the preferred approach to TA administration in growing people with thyrotoxicosis in the longer term.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology