Association of Thyroid Hormone and Insulin‐Like Growth Factor‐1 Levels With Autism Spectrum Disorders: A Systematic Review and Meta‐Analysis

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Abstract
The action of the thyroid hormones and insulin‐like growth factor 1 (IGF‐1) is interdependent. The levels of thyroid hormone and IGF‐1 were reported to be altered in individuals with autism spectrum disorder (ASD), but the results were controversial. This study aims to compare levels of thyroxine, triiodothyronine, thyroid stimulating hormone, and IGF‐1 between the ASD group and neurotypical controls. PubMed, Web of Science, Cochrane, and Embase databases were searched for eligible observational studies. We calculated pooled standardized mean difference (SMD) with 95% confidence intervals (CIs) of our data using a random or fixed effect model. The search strategy provided a total of 1710 articles, of which 16 articles were quantitatively analyzed. The total number of included participants was 2399 (1285 cases and 1114 controls). The meta‐analysis revealed no significantly changed blood levels of thyroxine, free triiodothyronine, free thyroxine, and IGF‐1 of subjects with ASD compared to non‐autistic controls. The blood TSH levels were significantly lower in ASD subjects than in controls ( n = 859, Hedges' g = −1.18, 95% CI: −2.17 to −0.20, p = 0.02). Subgroup‐analysis results showed that blood free triiodothyronine ( n = 153, Hedges' g = −0.74, 95% CI: −1.08 to −0.40, p < 0.0001, I 2 = 2%), free thyroxine ( n = 153, Hedges' g = −0.72, 95% CI: −1.31 to −0.14, p = 0.02, I 2 = 66%), and IGF‐1 ( n = 397; Hedges' g = −0.92; 95% CI: −1.30 to −0.55, p < 0.00001, I 2 = 63%) levels were significantly reduced in subjects with severe ASD symptoms. Individuals with severe ASD may experience a dysfunction of the hypothalamic–pituitary–thyroid axis, and further studies are warranted to determine the correlation between thyroid hormone and IGF‐1 levels and disease severity. Trial Registration: ClinicalTrials.gov identifiers: NCT01970345

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