ESPE Abstracts (2015) 84 P-2-557

Potentially Excessive Levothyroxine Doses in Cases of Congenital Hypothyroidism with Eutopic Thyroid Gland

Hidetoshi Satoh, Keisuke Nagasaki, Youhei Ogawa & Akihiko Saitoh


Division of Pediatrics, Niigata University Medical and Dental Hospital, Niigata, Japan


Background: The intelligence prognosis of congenital hypothyroidism (CH) is remarkably improved by early detection and optimal levothyroxine (LT4) treatment. Some groups have reported that initial LT4 overtreatment results in a subsequent decrease of cognitive function. In universal guidelines, an initial dose of 10–15 μg/kg per day of LT4 is recommended. However, there are cases of LT4 overdosing.

Objective and hypotheses: The purpose of this study is to investigate the influence of the initial LT4 dosage on the frequency of LT4 overdosing during infancy.

Method: Of 95 patients, there were 54 cases of mild CH (thyroid stimulating hormone (TSH) 15–30 μIU/ml) and 45 cases of moderate-severe CH (TSH ≧30 μIU/ml), treated by either a high initial dose of levothyroxine (≧9 μg/kg per day) or a low initial dose (<9 μg/kg per day). Serum free thyroxine (fT4) and TSH levels were measured before treatment (initial visit) and after initial treatment. We defined CH cases with <0.5 μIU/ml TSH and with >2.5 ng/dL fT4 after initial treatment as cases of LT4 overdosing. We investigated the LT4 overtreatment ratio in each group by calculating the odds ratio.

Results: The LT4 overtreatment ratios after initial treatment for the mild/low-dose, moderate-severe/low-dose, mild/high-dose, and moderate-severe/high-dose group were 2.5% (1/40), 15.0% (3/20), 37.5% (5/14), and 48.0% (12/25) respectively. The odds ratio between mild/low-dose and mild/high-dose were 14.29 (P<0.05) and between moderate-severe/low-dose and moderate-severe/high-dose were 3.20 (P<0.05), while the LT4 overtreatment ratio was significantly higher in each high-dose groups.

Conclusion: Cases of CH with eutopic thyroid gland often do not eventually show significant clinical manifestations and lasting hypothyroidism as compared with thyroid dysgenesis cases. Even if these cases show remarkably high TSH value and are considered severe case, these clinical conditions may be often transient such as excess of iodine or DUOX2 mutation. Thus, discursive long-term high-dose administration may result in LT4 overtreatment. The initial dosage of LT4 of 10–15 μg/kg per day for neonatal-screening-positive CH cases with eutopic thyroid gland may raise the risk of LT4 overtreatment.

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