Aims:
Thyroid hormones have profound effects on neurological development and function, but detailed studies of thyroid function in children with autism spectrum disorder (ASD) are lacking.
Methodology:
A cross-sectional, case control study was performed of participants in the Australian Autism Biobank with a confirmed ASD diagnosis and neurotypical controls. Plasma TSH, free T4 and free T3 were measured by automated immunoassay, and total T4, total T3 and thyroid hormone metabolites by customised liquid chromatography-tandem mass spectrometry (LCMS/MS). Regression analysis was performed, adjusting for age and sex.
Results:
There were 803 cases with ASD (mean age 7.6 ± 3.9 years, 78% male) and 306 controls (mean age 7.8 ± 4.0 years, 48% male). Nine cases were excluded due to a history of thyroid disease or clinically significant thyroid dysfunction (TSH <0.1 or >10 mU/L).
Median TSH did not differ significantly between ASD and controls (2.3 vs. 2.1 mU/L, P=0.7783). Free T4 was significantly lower in cases than controls (18.4 vs. 18.7 pmol/L, P=0.0003), as was free T3 (7.0 vs. 7.1 pmol/L, P <0.0001), with no significant difference in the FT4:FT3 ratio (P=0.1890). Median total T4 as measured by LCMS/MS was significantly lower in ASD cases than controls (179 vs. 194 nmol/L, P=0023, as was total T3 (2.2 vs. 2.4 nmol/L, P=0.0152), with no significant difference in the T4:T3 ratio (P=0.0805). Reverse T3 did not differ significantly between groups. Two metabolites had significantly lower concentrations in cases than controls: 3,5-T2 (0.01 vs. 0.021 nmol/L, P<0.0001) and 3,3'-T2 (0.12 vs. 0.16 nmol/L, P<0.0001).
Conclusions:
Circulating thyroid hormones and certain metabolites show small but significant differences between ASD and controls. Further research is warranted as to whether subtle alterations in thyroid hormone economy contribute to the pathogenesis of ASD.