Euthyroid Submedian Free T4 and Subclinical Hypothyroidism May Have a Detrimental Clinical Effect in Down Syndrome

Background: Aberrant thyroid function is highly prevalent in Down syndrome (DS). We aimed to find whether subclinical hypothyroidism (SCH) or low-normal free T4 (FT4) are associated with a detrimental clinical outcome in untreated DS patients. Methods: 157 patients assessed at Hadassah Down Syndrome Center between 2004 and 2010 by comprehensive clinical evaluation and tests for hemoglobin, FT4 and thyroid-stimulating hormone (TSH) were subdivided into subgroups including: clinical hypothyroidism, SCH, euthyroid submedian or supramedian FT4, and alternatively for euthyroidism and TSH levels (submedian or supramedian TSH). Results: Hypothyroidism was found in 21.7% and SCH in another 14.9% of the patients. Moderate/severe hypotonia were more frequent among SCH patients compared to euthyroid patients (52.6 vs. 16.4%, p = 0.002). Patient's hemoglobin levels were lower in the euthyroid submedian FT4 group compared to the euthyroid supramedian FT4 group (10.9 vs. 0% below the normal range, p = 0.001). Interestingly, FT4 levels correlated negatively with increasing age among euthyroid DS patients (Pearson's correlation coefficient = -0.324, p = 0.009). Conclusion: SCH and euthyroid submedian FT4 may have significant clinical sequelae, such as hypotonia and anemia. Interventional studies with l-thyroxine replacement may be indicated in these subpopulations. Our finding that FT4 levels decrease with age in DS (contrasting the general population trend) may indicate redefining the normal FT4 levels range in DS.