BACKGROUND
Down syndrome (DS) is a genetic condition where a baby is born with an extra chromosome (trisomy 13). Chromosomes are like small parts of our body’s instruction manual, they carry genetic information. The extra information in children born with DS makes them look and grow differently. Children with DS are also at increased risk of having thyroid problems. Mild underactive thyroid (hypothyroidism) with high TSH and normal thyroid (free T4 and free T3) hormone levels can be seen up to 60% of children with DS. However, it is difficult to understand the thyroid function in children with DS because we do not have clear rules for what’s normal. We don’t know for sure if the TSH level is higher because thyroid works abnormally or whether this may be a normal level for a child with DS. Because we don’t have clear levels for what’s normal in this situation, the doctors may be checking the thyroid function too often or giving treatments too early.

The researchers planned this study to figure out the normal ranges for TSH, free T3 and free T4 in children with DS at different ages. They wanted to see how much these levels change over time and whether TSH levels could predict if the child would develop hypothyroidism later on.

THE FULL ARTICLE TITLE
Cattoni A et al 2023 Thyroid function tests in children and adolescents with trisomy 21: Definition of syndromespecific reference ranges. J Clin Endocrinol Metab. Epub 2023 Jun 3. PMID: 37279507.

SUMMARY OF THE STUDY
Researchers studied the health records from a single hospital in Italy. They looked at thyroid test results collected over 30 years from children with DS between the ages of 0-18. Patients who were born with hypothyroidism (congenital hypothyroidism), who had autoimmune thyroid disease, abnormal thyroid structure, who were on thyroid hormone or medications that can affect the thyroid and who were exposed to radiation treatment were excluded from the study. The children had blood tests every 3–6 months during the first year and yearly after that. A total of 3748 TSH, 986 free T3, and 2974 free T4 results were included in the final analysis. Information was compared to normal ranges for children and adolescents without DS. The best TSH level that could predict the possibility of hypothyroidism in the future was identified.

There were 548 patients in the study, 53% were boys and 47% were girls. The first tests were done when they were 0.9 to 3.3 years old, and the last evaluations were done when they were 5.4 to 12.5 years old. The average follow up was about 6 years. Many children with DS (44%) did not have associated health problems.

The average TSH level for children with DS was 4.6 uU/ ml which was significantly higher than children without DS. About 30% of TSH levels during the first year of life and 21% between ages 11-18 were higher than 97.5% of TSH levels from children without DS. Free T3 levels were significantly lower in children with DS aged 0-11. Free T4 levels were higher in children with DS ages 0-6 but they decreased as the children got older and became lower than unaffected children after the age of 11.

TSH levels changed the most between measurements. However, if a single TSH level was greater than 75% of the TSH levels in children with DS, it predicted development of hypothyroidism in 15% of children at the next test. On the other hand, if a single TSH level was lower than 75% of the TSH levels, it predicted the next measurement would not show hypothyroidism in 91% of children with DS. The authors developed a web based tool to rank the values of TSH of children with DS, to help doctors make treatment decisions (https:// b4-uni25-5627493duksfy852qr80fewbsn3986g43jkgkz ie8.shinyapps.io/Percentile-Thyroid-ChildrenTrisomy21).

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The researchers conclude that the tests for thyroid function are different between children with and without DS. We don’t know the reasons for this difference, but the findings from this study will help doctors make decisions when they test the thyroid in children with DS. The researchers point out that there wasn’t very much information for very young children (0-29 days old) and doctors should still use same ranges used for children without DS for those. Mild hypothyroidism is very common in children with DS and sometimes the levels go back to normal without treatment. But if they don’t get better, it is a condition that needs to be treated lifelong. The findings from this study are most helpful in this situation. The study identified a TSH level that can tell if a child will have hypothyroidism at the next test. This information and the online comparison tool will help doctors make better decisions and improve the care of children with DS.

— Ebru Sulanc, MD

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