ESPE Abstracts (2019) 92 P1-290

Prediction of Permanent and Transient Congenital Hypothyroidism Based on Levothyroxine Dosages in Long-Term Follow-Up Patients: A Multicenter Retrospective Study in Japan

Shinji Higuchi1,2, Tomoyo Itonaga1, Kazuhiro Shimura1, Keisuke Nagasaki3, Mari Satoh4, Noriyuki Takubo5, Ikuko Takahashi6, Hirotake Sawada7, Yukihiro Hasegawa1

1Division of Endocrinology and Metabolism, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan. 2Division of Pediatric Endocrinology and Metabolism, Children's Medical Center, Osaka City General Hospital, Osaka, Japan. 3Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. 4Department of Pediatrics, Toho University Omori Medical Center, Tokyo, Japan. 5Department of Pediatrics and Adolescent Medicine, Juntendo University, Tokyo, Japan. 6Department of Pediatrics, Akita University Graduate School of Medicine, Akita, Japan. 7Department of Reproductive and Developmental Medicine, University of Miyazaki, Miyazaki, Japan

Background: Congenital hypothyroidism (CH) can be categorized into two types: transient CH (group T) and permanent CH (group P). Several studies have recently demonstrated that the levothyroxine (LT4) dosage is useful for predicting LT4 requirement; however, none of the studies followed up their patients to puberty.

Objective: To determine the cutoff value for the LT4 dosage as a predictor of LT4 requirement after puberty in patients with CH.

Methods: This was a multicenter retrospective study. After excluding patients with Down syndrome, among others, the LT4 dosage and clinical data of eligible patients with CH who were followed up at our hospitals from the neonatal period to ≥15 years of age were analyzed. The LT4 dosages at ages 1, 2, and 3 years were compared between the two groups, and receiver operating characteristic analysis for the groups was performed to establish the cutoff dosages of LT4 at those ages. To determine the optimal cutoff values for clinical decision-making, further analyses were performed to identify the LT4 dosage with the highest specificity for groups P and T. Group P was further divided into two subgroups: permanent dysgenesis(PD) and permanent eutopic (PE). Group PD (n=29) included patients with thyroid dysgenesis, such as an ectopic thyroid gland, semilobar deficiency, or athyrosis.

Results: The subjects were classified into groups P (n=75), T (n=24), PD (n=29), and PE (n=46). The LT4 dosages were significantly higher in group P than in group T. The optimal cutoff values at 1, 2, and 3 years of age were 3.26, 2.29, and 2.32 µg/kg/day, respectively. At 1 year of age, higher LT4 dosages were required in group P than in group T (median 3.75 vs. 2.88 µg/kg/day; p < 0.001). When the LT4 dosage cutoff values at 1 year of age were set at 4.79 and 1.74 µg/kg/day, the specificities of P-CH and T-CH (for denying T-CH and P-CH, respectively) were 100% and 97%, respectively. The results between group PE patients and group T patients were not essentially altered. In patients with T-CH, LT4 re-administration was not introduced during the follow-up of ≥12 years after discontinuing LT4 treatment.

Conclusions: LT4 dosages >4.8 µg/kg/day and <1.7 µg/kg/day at 1 year of age may help predict P-CH and T-CH, respectively.