When to Repeat Free T4 and TSH in Children with Low Free T4
Immediate Repeat Testing in Acutely Ill Children
If the child is acutely ill or hospitalized, repeat thyroid function tests (TSH and free T4) 4–6 weeks after recovery from the acute illness, as nonthyroidal illness can transiently suppress TSH and alter thyroid hormone levels, making initial results unreliable. 1, 2
- Acute illness, particularly in premature or very low birth weight infants, can cause a "sick euthyroid syndrome" where T4 is depressed and free T4 may be falsely elevated due to altered protein binding 3
- In critically ill children, thyroid function tests obtained during the acute phase often normalize spontaneously once the underlying condition resolves 1, 2
- For children with respiratory distress syndrome or other severe illness, wait until clinical stability is achieved before interpreting thyroid results or initiating treatment 4
Repeat Testing in Clinically Stable Children
For clinically stable children with an isolated low free T4 and normal or elevated TSH, confirm the diagnosis by repeating both TSH and free T4 after 3–6 weeks, as 30–60% of abnormal thyroid values normalize spontaneously on repeat testing. 1, 2
Key Considerations for Stable Children:
- Measure both TSH and free T4 together to distinguish between primary hypothyroidism (elevated TSH, low free T4), central hypothyroidism (low or inappropriately normal TSH with low free T4), and assay artifacts 1
- Free T4 assays are method-dependent and vulnerable to artifacts from abnormal albumin binding, medications, and critical illness—results that are clinically discordant with TSH should prompt use of an alternative free T4 method 5
- In premature infants, low T4 with normal free T4 often reflects decreased thyroxine-binding globulin rather than true hypothyroidism and typically resolves by 6–7 weeks of age 3, 4
Special Population: Children with Type 1 Diabetes
For children with type 1 diabetes, measure TSH at diagnosis when clinically stable or soon after glycemic control has been established; if normal, recheck every 1–2 years, or sooner if the patient develops symptoms, thyromegaly, abnormal growth rate, or unexplained glycemic variability. 1
- Thyroid function tests may be misleading (euthyroid sick syndrome) if performed during diabetic ketoacidosis or severe hyperglycemia 1
- If thyroid tests are slightly abnormal at diabetes diagnosis, repeat them after achieving metabolic stability and glycemic targets 1
- Consider testing for antithyroid peroxidase and antithyroglobulin antibodies soon after diabetes diagnosis, as 17–30% of children with type 1 diabetes develop autoimmune thyroid disease 1
Children with Suppressed TSH and Normal Free T4
For children with TSH <0.1 mIU/L and normal free T4 who are clinically euthyroid, repeat TSH, free T4, and free T3 in 3–6 weeks to confirm persistence before pursuing further evaluation. 6
- In one pediatric series, 61% of children with suppressed TSH (<0.1 mIU/L) and normal free T4 became euthyroid spontaneously within a mean of 3.7 months 6
- Only 9% progressed to overt hyperthyroidism, while 17% developed hypothyroidism (often with positive thyroid antibodies) 6
- Reserve further testing (thyroid antibodies, thyroid ultrasound) for children whose TSH remains suppressed beyond 3–6 months or who develop symptoms 6
Monitoring Children on Levothyroxine Replacement
For children receiving levothyroxine for primary hypothyroidism, recheck TSH and free T4 every 6–8 weeks during dose titration, then every 6–12 months once stable, targeting TSH within the reference range (0.5–4.5 mIU/L). 2, 7, 8
- Assay-specific target ranges for optimal thyroxine therapy are required, as free T4 reference intervals show significant inter-method differences 8
- The lower limit of the free T4 reference interval shifts mildly higher when TSH is restricted to 0.5–2.5 mIU/L compared to 0.5–5.0 mIU/L 8
- In children with central hypothyroidism, TSH cannot be used to monitor adequacy of replacement; instead, target free T4 in the upper half of the reference range 8
Critical Pitfalls to Avoid
- Never treat based on a single abnormal thyroid test in a clinically stable child—confirm with repeat testing after 3–6 weeks 1, 2
- Do not interpret thyroid function tests obtained during acute illness, diabetic ketoacidosis, or severe metabolic derangement as definitive 1, 3
- Recognize that premature infants commonly have low T4 due to decreased binding proteins, not true hypothyroidism, and this typically resolves spontaneously by 6–7 weeks 3, 4
- When free T4 results are discordant with clinical status or TSH, consider method-dependent artifacts and use an alternative assay 5