Mild Hypothyroidism in Childhood

Who, When, and How Should Be Treated?

Maria Cristina Vigone; Donatella Capalbo; Giovanna Weber; Mariacarolina Salerno


J Endo Soc. 2018;2(9):1024-1039. 

In This Article

Management of Mild Hypothyroidism in the Neonatal Period

According to ESPE guidelines[2] L-T4 treatment is recommended if serum FT4 concentration is below the normal values for age, regardless of TSH concentration, and if venous TSH concentration is persistently >20 mIU/L, even if serum FT4 concentration is normal.

When venous TSH concentration is between 6 and 20 mIU/L in a healthy baby with FT4 concentration within the normal limits for age, the optimum management is debated. The decision to start treatment with L-T4 depends on multiple factors, such as the age of the patient, the duration of the thyroid dysfunction, the trend of TSH values, the etiology, the presence of syndromes and/or other pathologies, and the parents' choice and reliability.

When venous TSH concentration is between 6 and 20 mU/L in a well baby for more than 3 to 4 weeks, ESPE guidelines suggest, after discussion with the family, either starting L-T4 supplementation immediately and retesting off treatment at a later stage or retesting 2 weeks later without treatment in particular if TSH value is <10 mIU/L.

If treatment is started, TSH should be maintained in the age-specific reference range and serum concentrations of FT4 in the upper half of the age-specific reference range. Thyroid function should be assessed 1 to 2 weeks after the start of L-T4 treatment, with frequent monitoring during the first year of life. In special risk categories (preterm, LBW, twins, infants from mothers affected by autoimmune thyroiditis, twins), mild alteration of TSH may regress, persist, or even worsen and should be carefully monitored. Reevaluation of the thyroid axis, off treatment, should normally take place after the age of 3 years, but earlier reevaluation may be indicated if transient increases in TSH concentration are highly probable.[2]

In most children with a mildly elevated TSH level at neonatal screening, a progressive normalization of thyroid function is generally observed even though a mild TSH increase may persist in up to 32% of these patients.[48] Indeed, in a prospective study on 44 children with a mildly elevated TSH level at neonatal screening, thyroid function normalized in 56.8% of children at an average age of 5.3 years and in 68.8% of children at 7.2 to 9.5 years of age.[48]

In cases with known genetic etiology, the management of SH is also controversial. In patients heterozygous for TSHR mutations, SH is generally considered a compensated thyroid dysfunction with an appropriately adjusted set point for pituitary-thyroid feedback and does not require treatment.[49] Nevertheless, if heterozygous mutations of TSHR are detected in patients belonging to special categories (preterm infants, small for gestational age neonates, infants born after multiple pregnancies and/or conceived by assisted reproduction techniques), L-T4 supplementation might be considered.[44]

In contrast, in carriers of biallelic mutations, a trend toward an increase in TSH levels with a concomitant decline in FT4 concentrations has been observed, suggesting the need for long-term follow-up and/or L-T4 therapy.[49]

Most patients with DUOX2 mutations are identified at neonatal screening for CH and start L-T4 treatment soon after birth for either mild or severe hypothyroidism. The wide clinical variability suggests that all patients with CH due to DUOX2 mutations should undergo reevaluation after the age of 3 years. Indeed, after reevaluation, most heterozygous patients show normal thyroid function; however, it remains to be investigated whether these patients are at risk for hypothyroidism in other periods of life characterized by high thyroid hormone requirements such as puberty or pregnancy.[50]