Trisomy 21 and thyroid dysfunction: A study in a cohort of Sri Lankan children

Background: Thyroid dysfunctions are the most common endocrine abnormalities observed in trisomy 21 (T21). The prevalence of thyroid disorders in children with T21 varies between 4% and 40%. Dysregulation of thyroid function, which is specific to T21, is a possible etiology. Thyroid dysfunction can have a significant impact on cognitive development and growth. Transiently abnormal TFTs are frequently observed in T21 and may cause diagnostic confusion. There is a paucity of prevailing literature on transiently abnormal TFTs, gland in situ congenital hypothyroidism and thyroid dysfunctions in children with T21 in resource-limited settings. Methods: Records from the Child Development Clinic dedicated to children with T21 at the university unit of Lady Ridgeway Hospital (LRH) were reviewed retrospectively. The prevalence and patterns of different thyroid dysfunctions were studied. Results: Among the 88 children with T21 (Male: Female ratio of 1.5:1), 35 (39.7%) had thyroid dysfunction. Seventeen (20%) children were managed as congenital hypothyroidism (CH), nine (10.2%) had transiently abnormal TFTs. Acquired hypothyroidism was noted in 8 (9%) children, and two children (2.3%) had hyperthyroidism. Among the 17 children who were managed as CH, 12 (70.5%) were diagnosed during the neonatal period following newborn screening (NBS). The mean TSH level at diagnosis was 22.3 mIU/l (10.6–58). All 17 children had normal ultrasound scans of the thyroid. The average current thyroxine dose in the < 3-year-old group (n=4) was 2.1 µg/kg/day, and in the ≥ 3-year-old group, it was 2.5 µg/kg/day. The average age at diagnosis of acquired hypothyroidism was 10 years and 4 months. In those managed as transiently abnormal TFTs, the time taken for TFTs to normalise (without any treatment) ranged between 6 weeks and 8 months. Conclusion: Thyroid dysfunction is a commonly encountered challenge in managing T21. Transiently abnormal TFTs are common and require close observation. Gland-in situ (GIS) CHs are increasingly being detected among this population. The cost-effectiveness of using genetic analysis in GIS-CH in resource-limited settings needs to be studied. Differentiating transient CH from permanent CH is quite challenging in clinical practice, although the low thyroxine dose requirement, especially after 3 years of age, may provide valuable information. Further longitudinal studies are needed to delineate the prevalence of transient vs permanent CH.