ESPE Abstracts

Introduction: In cases of congenital and acquired hypothyroidism, there can be a development of resistance to Levothyroxine (LT4) over time. The cause of this clinical picture is unknown and often improves later in life. However, in some cases or receptor expression disorders, it may be necessary to add T3 to the treatment to overcome this condition.

Aim: This study aims to determine the characteristics of cases where persistent high TSH levels were detected under LT4 treatment due to hypothyroidism, and T3 therapy was added.

Method: Our study included cases from the Pediatric Endocrinology outpatient clinic at Gazi University Faculty of Medicine. These cases were being followed up for hypothyroidism and receiving LT4 treatment. Despite normal and/or high sT4 and sT3 levels, they had persistent high TSH levels, prompting the initiation of T3 therapy. Anthropometric measurements, diagnoses, follow-up durations, and thyroid hormone levels of the cases were recorded retrospectively. Data were evaluated using IBM SPSS Statistics 28.

Results: Of the 15 cases included in the study, 8 (53.3%) were female. The distribution of diagnoses among the cases was as follows: 46.6% (n = 7) had thyroid dysgenesis, 46.6% (n = 7) had thyroid dyshormonogenesis, and 6.7% (n = 1) was an ALL case receiving radiotherapy. Genetic mutations identified included NKX2-1 (n = 1), DUOX1 (n = 1), DUOX2 (n = 1), TPO (n = 1), and TSHR (n = 1). All cases initially received LT4 treatment. The mean duration of LT4 monotherapy was 10.91 ± 3.48 years. The mean age at the start of T3 therapy was 7.25 ± 2.24 years. Median (minimum-maximum) values before starting T3 therapy were TSH 9.9 (6.3-28.2) µIU/ml, sT4 1.3 (1.03-1.81) ng/dl, and sT3 4 (3-4.9) pg/ml. Median (minimum-maximum) values after adding T3 to the treatment were TSH 2.1 (0.5-6.2) µIU/ml, sT4 1.01 (1.0-1.9) ng/dl, and sT3 4.34 (3.3-5.26) pg/ml.

Discussion and Conclusion: The reason for the resistance developed to L-Thyroxine therapy is unknown. Dysfunctional deiodinase activity, leading to inadequate conversion of LT4 to T3, has been suggested as an underlying cause. However, the normal range of sT3 levels in all our cases indicates sufficient deiodinase activity, suggesting a potential functional resistance to T3 at the pituitary level. Literature has documented variants in TSHR, GLIS, DUOX2, and SLC26A4 genes in a series of nine cases. Combined application of T4 and T3 in the treatment of resistance to hypothyroidism therapy should be considered.