ESPE Abstracts

Introduction: Limited research has focused on the potential connection between thyroid function and attention-deficit/hyperactivity disorder (ADHD), particularly beyond prenatal effects. The few studies addressing children and adolescents have important methodological shortcomings, mainly when seeking to establish causality. To clarify this relationship, a combined epidemiological and genetic approach was adopted to overcome the methodological limitations of each method.

Methods: The relationship between subclinical hypothyroidism and hyperthyroidism and the prospective risk of ADHD was investigated in German children and adolescents in a nationwide survey (KIGGS). To this end, a total of 4,432 adolescents were studied over a median follow-up period of 6 years. Data were subjected to a logistic regression approach, accounting for the so far most extensive set of covariates related to thyroid function and ADHD risk. The same approach was chosen to investigate the relationship between quartiles of thyroid stimulating hormone (TSH) and free thyroxine (fT4) levels and incident ADHD in euthyroid participants to test for a dose–response association. This analysis was complemented by Mendelian Randomization (MR), which is robust to inferential problems inherent to epidemiological studies. We utilized between 9 to 86 single nucleotide polymorphisms (SNPs) related to TSH and fT4 levels, hypothyroidism and hyperthyroidism, Hashimoto’s thyroiditis, and Graves’ disease as instrumental variables to clarify their causal relationship with ADHD based on data from 225,534 individuals (38,691 cases and 186,843 controls), employing a variety of conventional and robust MR methods.

Results: Neither the MR nor the epidemiological approach indicated a significant causal relationship between either type of thyroid dysfunction and ADHD, and this also applied to TSH and fT4 levels within the normal range.

Conclusions: Leveraging a combined epidemiological and genetic approach, which allows for reliable directional conclusions, our study found no compelling evidence supporting a relationship between normal range thyroid function, thyroid dysfunction, and ADHD. These findings discourage unnecessary diagnostics, thereby reducing the risk of misleading incidental findings that could divert attention from accurate diagnosis and appropriate treatment in patients with ADHD.