EVIDENCE-BASED ANSWER
Congenital hypothyroidism is a critical cause of elevated thyroid-stimulating hormone (TSH) in newborns; evaluate all neonates with an elevated TSH for congenital hypothyroidism (strength of recommendation [SOR]: A).
Other causes of an elevated TSH include transient hypothyroidism due to neonatal illness, prematurity, iodine excess or deficiency, and maternal medication or maternal thyroid disease.
Clinical commentary
Another cause of elevated TSH? Drawing the TSH too early
Grant Hoekzema, MD
Mercy Family Medicine Residency, St. Louis, Mo
I practice in a state that screens newborns using TSH levels instead of T4 levels. In my experience, the most common reason for an elevated TSH is that the metabolic screen was drawn too early, before the initial physiologic peak after birth has returned to the screening cutoff level. In these cases, a repeat TSH is almost always normal.
However, there have been several children with transient hypothyroidism that I have seen over the years with mild TSH elevations on repeat testing. The developmental implications for the infant are serious enough in these children to warrant endocrinology follow-up.
Evidence summary
Feeding difficulties, inadequate weight gain, and unusual physical exam findings may lead providers to assess thyroid function in newborns. Additionally, while measurement of free T4 is more common, some states use TSH as the required newborn screening assay to evaluate for congenital hypothyroidism. Whether ordered as a screening test or in response to symptoms, an elevated TSH in a newborn requires further investigation.
Congenital hypothyroidism is the most serious cause of an elevated TSH in a newborn. If left untreated, congenital hypothyroidism leads to developmental delay and mental retardation; however, with early treatment, intellectual outcomes are greatly improved. Newborns with an elevated TSH should be evaluated with repeat TSH and free T4 measurements in order to assess for congenital hypothyroidism.
TSH >50 mU/L increases chances of congenital hypothyroidism
Not surprisingly, higher levels of TSH increase the likelihood of congenital hypothyroidism. A study from the Netherlands examined diagnoses of infants with an increased TSH on newborn screening heelstick. Of 112 newborns with a TSH >50 mU/L, 110 (98%) had congenital hypothyroidism on further examination. However, only 34 of 594 (5.7%) newborns with a TSH between 9 and 20 mU/L were diagnosed with congenital hypothyroidism. Nineteen of 46 newborns (41%) with levels between 20 and 50 mU/L had congenital hypothyroidism.1
Common causes of elevated TSH in newborns
- congenital hypothyroidism
- Transient hypothyroidism due to neonatal illness
- Prematurity
- Iodine excess or deficiency
- Improper screening technique
- Incorrect normal result intervals for age
- Maternal medication or maternal thyroid disease
Other common causes of hypothyroidism
While TSH is generally an accurate measurement of thyroid function, other factors can also lead to an elevated level. The same Dutch study mentioned above explored the presumed causes of elevated TSH among children who were diagnosed with transient hypothyroidism (initially elevated TSH level found to be normal on follow-up testing). The most common causes were thyroid-binding globulin deficiency (200/548 or 36% of newborns with transient hypothyroidism), severe illness (36%), prematurity (8%), and errors in screening procedures (4%).
Another study confirmed that TSH levels were higher in infants born preterm; babies with the earliest gestational ages had the highest TSH levels. The same study also found that TSH levels increased with increasing degrees of illness. Very preterm babies, those with cerebral pathology, low Apgar scores, respiratory distress syndrome, persistent ductus arteriosus requiring treatment, and necrotizing enterocolitis were at highest risk for having abnormally elevated TSH levels in this study.2 If a sample is drawn from a newborn exhibiting symptoms (such as poor feeding or hypotonia), the TSH level may be elevated in spite of normal thyroid function.