Endocrine Abstracts

JOINT501

Purpose: Congenital hypothyroidism (CH) is the most common congenital endocrine disorder, affecting approximately 1 in 2-4,000 newborns. Consensus guidelines recommend rapid normalization of thyroid-stimulating hormone (TSH) levels for neurodevelopmental protection. However, this approach may lead to elevated free thyroxine (fT4) levels, raising concerns about overtreatment despite persistently elevated TSH. This lab pattern has been anecdotally noted to be more frequent and persistent in individuals with severe CH, complicating levothyroxine dose titration. We hypothesize that individuals with severe CH require higher levels of fT4 to appropriately suppress TSH compared to those with mild CH, suggesting a potential difference in the thyroid feedback loop between the two groups. A better understanding of this relationship could inform treatment strategies and improve outcomes.

Methods: Patients were included based on a diagnosis code for congenital hypothyroidism, with associated TSH and fT4 (measured by direct dialysis) values extracted. Patients were divided into two subgroups: (1) severe CH (at least one documented TSH >60); (2) mild CH (all TSH values <25). A Student’s t-test with a fixed effects model was used to compare the levels of fT4 relative to TSH between these two groups.

Results: A significant difference in fT4 relative to TSH was observed between the groups, indicating that for the same TSH value, individuals with severe CH have significantly higher fT4 levels compared to those with mild CH (t₍₂₉₁₀₎ = -3.69, P = 0.0002). Additionally, a significant difference was found in the rate at which fT4 changes in response to TSH (i.e., the slope of the relationship between fT4 and TSH) for the two groups (t₍₂₉₁₀₎ = -9.21, P < 0.0001). Individuals with severe CH exhibited a more attenuated response in TSH to changes in fT4, indicating reduced sensitivity to fT4 compared to those with mild CH.

Conclusions: This study demonstrates that individuals with severe CH require higher free T4 to achieve similar TSH suppression, suggesting differences in thyroid regulatory mechanisms. Additionally, the rate at which fT4 changes with respect to TSH differs significantly between the two groups; individuals with severe CH are less responsive to shifts in fT4, further highlighting the variability in thyroid feedback. These findings underscore the importance of understanding variability in thyroid function in order to optimize clinical management. Tailored treatment strategies could be developed based on the severity of CH, ultimately improving long-term outcomes for affected individuals.