Primary Congenital Hypothyroidism in Children Below 3 Years Old - Etiology and Treatment With Overtreatment and Undertreatment Risks, a 5-Year Single Centre Experience

Abstract

Worldwide neonatal screening for congenital hypothyroidism (CH) is a gold standard of active surveillance in newborns. Prompt diagnosis, subsequent timely treatment implementation, and proper dosage of levothyroxine (L-T4) are crucial for normal growth and development, especially of the central nervous system. However, overtreatment may have a potential negative impact on further neurodevelopment. We retrospectively analysed data of 99 newborns with CH diagnosis, referred to the Endocrinology Outpatient Clinic of the Institute of Mother and Child in Warsaw, Poland from the CH screening program from 2017 to 2021. We evaluated the diagnostic process and treatment up to the age of 3 years. We compared groups of children from the first and the second screening groups (FSG, SSG) in the neonatal screening with an evaluation of ultrasound examination (thyroid dysgenesis vs. gland in situ, GIS). The overtreatment and undertreatment risks were assessed and an analysis of the new TSH thresholds was performed. Treatment was implemented at a median of 9 days of life (3 – 27); 8 days (3 – 17) in FSG and 19 (6 – 27) in SSG. The dose of L-T4 differed between FSG and SSG at all three analysed time points (start of the therapy, 12 months, and 3 years) with significantly higher doses in FSG. The same was observed for the patients with thyroid dysgenesis vs. GIS. Screening TSH level was ≥ 28mIU/l in 91.7% of patients with thyroid dysgenesis in comparison to 74.0% of patients with GIS (p= 0.038). The optimally treated group (fT4 in the upper half of the reference range, according to the guidelines) was up to 58.0% of the children during the follow-up. The risk for overtreatment was present in 1/5 of the study group after 12 months and 1/4 after 3 years of L-T4 therapy. Analysis of new TSH thresholds showed an increased prevalence of mild hypothyroidism, GIS, and either euthyroid state or overtreatment while treating with lower L-T4 doses in comparison to the rest of the cohort. The study confirmed the general efficacy of the CH diagnostic pathway and the timely implemented L-T4 therapy. The suspected overtreatment after the first 12 months of L-T4 therapy requires consideration of the earlier diagnosis re-evaluation.

Evaluation of the First Three Years of Treatment of Children with Congenital Hypothyroidism Identified through the Alberta Newborn Screening Program

“…A retrospective study of a Polish CH newborn screening program between 2017 and 2021 demonstrated that 51 (58%) out of 88 patients were optimally treated, while approximately 25% were overtreated. The authors of this study suggested that overtreatment may have occurred among those with transient or milder forms of hypothyroidism who did not require as much exogenous thyroid hormone [ 23 ]. A belief exists among some clinicians that overtreatment may be more acceptable than undertreatment, but overtreatment may be associated with inattention, hyperactivity, anxiety, and deficits in cognitive function [ 24 ].…”

Cognitive Changes Associated With Congenital Hypothyroidism: A Literature Review

“…Thyroid hormone deficiency during pregnancy, as well as its severity and duration, are determining factors in the formation and organization of the fetal brain (UCHIDA K.; SUZUKI M., 2021). In addition, some other risk factors include the baby's gender, premature birth, country of origin, health condition of the newborn and being small for gestational age (LIPSKA E. et al, 2022).…”

“…Thyroid dysgenesis, which encompasses agenesis, hypotrophy, hemiagenesis and ectopy of the thyroid gland, is responsible for more than 50% of cases. Other causes include thyroid dyshormonogenesis, which is caused by mutations in genes involved in the synthesis and metabolism of thyroid hormones (LIPSKA E. et al, 2022).…”

“…Genetic analyzes have shown that dyshormonogenesis, a defect in the production of thyroid hormones, is involved in CH and its frequency seems to be increasing (LIPSKA E. et al, 2022). These analyzes revealed genetic variants associated with isolated congenital central hypothyroidism in a high proportion of tested patients, with emphasis on variants in the IGSF1, TBL1X and IRS4 genes.…”