Guidelines for the treatment of childhood-onset Graves’ disease in Japan, 2016

Abstract

Abstract.Purpose behind developing these guidelines: Over one decade ago, the “Guidelines for the Treatment of Graves’ Disease with Antithyroid Drug, 2006” (Japan Thyroid Association (JTA)) were published as the standard drug therapy protocol for Graves’ disease. The “Guidelines for the Treatment of Childhood-Onset Graves’ Disease with Antithyroid Drug in Japan, 2008” were published to provide guidance on the treatment of pediatric patients. Based on new evidence, a revised version of the “Guidelines for the Treatment of Graves’ Disease with Antithyroid Drug, 2006” (JTA) was published in 2011, combined with the “Handbook of Radioiodine Therapy for Graves’ Disease 2007” (JTA). Subsequently, newer findings on pediatric Graves’ disease have been reported. Propylthiouracil (PTU)-induced serious hepatopathy is an important problem in pediatric patients. The American Thyroid Association’s guidelines suggest that, in principle, physicians must not administer PTU to children. On the other hand, the “Guidelines for the Treatment of Graves’ Disease with Antithyroid Drug, 2011” (JTA) state that radioiodine therapy is no longer considered a “fundamental contraindication” in children. Therefore, the “Guidelines for the Treatment of Childhood-Onset Graves’ Disease with Antithyroid Drug in Japan, 2008” required revision.

Thyroid‐stimulating hormone receptor antibodies during follow‐up as remission markers in childhood‐onset Graves' disease treated with antithyroid drugs

“…The criteria for ATD discontinuation were normal thyroid function with a maintenance dose of MMI (≤5 mg/day) or CBZ (≤10 mg/day) for more than 6 months . The terms used in this study were defined as follows:

Good initial response to ATD —time from diagnosis to keeping maintenance dose within six months. Remission —normal FT4, T3, and TSH levels without symptoms of hyperthyroidism for more than one year after ATD discontinuation. Relapse —high serum FT4 and T3 levels with low TSH levels after ATD discontinuation. A decrease in TRAb levels during the first year or the second year —TRAb levels at the end of the first year or the second year less than 50% of the levels at diagnosis. An increase in TRAb levels during the second year —TRAb levels at the end of the second year more than 50% greater than the levels at the end of the first year.

Commercial kits were used to measure hormone levels and the TBII index.…”

How do paediatricians use and monitor antithyroid drugs in the UK? A clinician survey

“…We reviewed the NICE “Important Safety Information” for carbimazole, and the advice pertaining to safe prescribing of ATDs within international guidelines . We then developed 27 questions that examined both adherence to published advice and the use and interpretation of related diagnostic tests, and compiled these into an online survey using “Google Forms” (Google Drive Office Suite, Alphabet inc, Mountain View, CA, USA).…”

“…Only CBZ and PTU are available in the UK. The United States Food and Drug Administration released a warning in 2010 regarding the increased risk of hepatotoxicity associated with PTU in children and, as a result, CBZ is recommended as first‐line treatment, with the exception of the first trimester of pregnancy . ETA (European Thyroid Association) and ATA (American Thyroid Association) guidelines advise on treatment for adults and children.…”

“…The ATA recommends a treatment duration of 12‐24 months, and the ETA a treatment duration of 36 months prior to stopping ATD therapy in children to check for remission . JTA (Japanese Thyroid Association) guidelines are paediatric‐specific and recommend treatment with methimazole for a duration of 18‐24 months …”

“…ETA guidelines do not advocate one treatment regimen over the other but the ATA recommends DT. JTA guidelines recommend avoiding BR, citing the 2010 Cochrane Collaboration review that identified an increased risk of adverse reactions with this treatment strategy when compared to DT . However, it has been highlighted that some of the studies included in the Cochrane review, and in the BR section of the analyses, used an ATD dose that was much higher than routinely used in clinical practice .…”