Levothyroxine Dosage as Predictor of Permanent and Transient Congenital Hypothyroidism: A Multicenter Retrospective Study in Japan

Abstract

<b><i>Background:</i></b> Congenital hypothyroidism (CH) can be divided into 2 types, transient CH (T-CH) and permanent CH (P-CH), depending on the requirement of levothyroxine (LT4) for life-long treatment. Several studies have recently reported that the LT4 dosage is useful for predicting the LT4 requirement, but none of the studies followed their patients to puberty. <b><i>Objective:</i></b> To determine the cutoff value for the LT4 dosage as a predictor of the LT4 requirement after puberty in patients with CH. <b><i>Methods:</i></b> The LT4 dosage and clinical data on 99 patients with CH who were followed at the participating hospitals from the neonatal period to 15 years of age or older were retrospectively analyzed. Based on their LT4 requirement at their last hospital visit, the participants were divided into the P-CH group (<i>n</i> = 75), who were treated with LT4, and the T-CH group (<i>n</i> = 24), who were not. <b><i>Results:</i></b> At age 1 year, a higher LT4 dosage was required for the P-CH group (median 3.75 vs. 2.88 µg/kg/day; <i>p</i> < 0.001). When the LT4 dosage cutoff value at age 1 year was set at 4.79 and 1.74 µg/kg/day, the specificity of P-CH and T-CH (for denying T-CH and P-CH, respectively) was 100 and 97%, respectively. <b><i>Conclusions:</i></b> An LT4 dosage above 4.7 µg/kg/day and below 1.8 µg/kg/day at age 1 year may help predict P-CH and T-CH, respectively.

Increase in doses of levothyroxine at the age of 3 years and above is useful for distinguishing transient and permanent congenital hypothyroidism

“…We also detected the mean of L-T 4 dosages at the age of 3 yr were 3.9 µg/kg/d and 2.2 µg/kg/d in group P and group T, respectively. These were similar to the cutoff values in previous foreign studies ( 6 , 9 ), and on the other hand slightly higher than the cutoff of T-CH in Japanese patients ( 11 , 12 ). This difference may be caused by the relatively small sample size and lack of data, especially body weight, in some patients in our study.…”

“…Recent studies have also demonstrated the cutoff of L-T 4 dosages with P-CH and T-CH ( 6 , 9 , 11 , 12 ). In Japanese patients, Higuchi et al showed the cutoff of L-T 4 dosages suspicious of T-CH as 2.4 µg/kg/d at the age of 1 yr and 1.3 µg/kg/d at the age of 3 yr ( 11 ).…”

“…In Japanese patients, Higuchi et al showed the cutoff of L-T 4 dosages suspicious of T-CH as 2.4 µg/kg/d at the age of 1 yr and 1.3 µg/kg/d at the age of 3 yr ( 11 ). Itonaga et al detected that an L-T 4 dosage above 4.7 µg/kg/d and below 1.8 µg/kg/d at age of 1 yr helps the prediction of P-CH and T-CH, respectively ( 12 ). Consequently, the combination of an increasing L-T 4 dosage and the dose of L-T 4 should be considered to predict the presence of P-CH or T-CH.…”

“…Although previous studies have reported the cutoff values of thyroid function tests (TFTs) or L-T 4 dosages at certain ages ( 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ), the exact conclusion is still unclear. First, there is a significant overlap between permanent CH (P-CH) and T-CH ( 4 , 5 , 6 , 7 , 9 , 10 ).…”

“…First, there is a significant overlap between permanent CH (P-CH) and T-CH ( 4 , 5 , 6 , 7 , 9 , 10 ). Second, in the majority of the studies, the definition of P-CH or T-CH was based on the condition of withdrawing treatment or morphological screening of thyroid glands ( 4 , 6 , 7 , 10 , 12 ) without re-evaluation tests. Consequently, in this study, we aimed to identify the factors that help to differentiate P-CH and T-CH earlier than re-evaluation tests by comparing the initial TFTs and the changes in L-T 4 dosages in two groups that were rigorously diagnosed by re-evaluation tests.…”