Screening for Congenital Hypothyroidism
Recommendation
Screening for congenital hypothyroidism with thyroid
function tests on dried-blood spot specimens is recommended for all newborns in
the first week of life (see Clinical Intervention).
Burden of Suffering
In the U.S., congenital hypothyroidism occurs in 1 of 3,600-4,000 infants.1,2 Clinical diagnosis occurs in <5% of newborns with
hypothyroidism because symptoms and signs are often minimal.1
Without prompt treatment, most affected children gradually develop growth
failure, irreversible mental retardation, and a variety of neuropsychologic
deficits, comprising the syndrome of cretinism.1,2 These
complications have become rare since the introduction in the 1970s of
routine neonatal screening and early treatment of congenital hypothyroidism.
Accuracy of Screening Tests
In the U.S., screening for congenital hypothyroidism in neonates is almost
always done by the radioimmunoassay of serum thyroxine
(T4) and thyroid-stimulating hormone (TSH) from dried-blood spot specimens
collected by heelstick and adsorbed onto filter paper.3,4
Laboratories in most of the U.S. measure T4 on all specimens, and TSH only
if the T4 level is low; in several states, most of Europe, and elsewhere in the
world, TSH is the initial screening test.3,5
Simultaneous measurement of both T4 and TSH has greater
sensitivity for congenital hypothyroidism than either of the two sequential
methods currently used,6 but it is not considered cost-effective by most programs at this time.5,7 The T4 assay
appears to have greater precision and reproducibility than the TSH assay, but
false- negative rates are similar with the two methods.6 Both
types of screening may miss the 3-5% of
cases of congenital hypothyroidism that are caused by pituitary dysfunction, as
well as the 3-14% of cases in which patients present with hypothyroxinemia
and delayed TSH elevation.8-10 The
primary T4-supplemental TSH approach also misses some patients with residual thyroid
tissue (i.e., ectopic gland) that results in
initially normal T4 with elevated TSH; sensitivity for these cases can be improved by repeat
screening at 2-6 weeks.11 Using a higher cutoff point to define abnormal T4
results in fewer false negatives due to these biologic factors. In one population,
using a cutoff of the lowest 5% of T4 values
to define "low" missed 3.5% of cases, whereas using the
lowest 10% resulted in 1.5% being missed.12 Only 0.2% of cases were missed using the lowest 20% as a
cutoff, but at substantially increased cost in terms of repeat testing.
False negatives also occur due
to screening errors. Such failures occur in specimen collection, laboratory
procedures (e.g., failure to record an abnormal result), or follow-up.13
Standards for adequate blood collection on filter paper for neonatal screening
programs have been published.13a Infants at increased risk for
false negatives from screening errors include those born at home, ill at birth,
or transferred between hospitals early in life.2 In
North America, an estimated 6-12% of
neonates with congenital hypothyroidism are not detected in screening programs
as a result of biologic factors or screening errors.8,13
In established U.S.
screening programs, there are 4-8 false
positives for every proven case,8
although follow-up testing readily corrects these. Screening with primary TSH
instead of T4-supplemental TSH may result in fewer false-positive tests.8,14 False-positive results
are more likely when screening is done in the first 24-48 hours
of life, since normal TSH values in the first 2 days
of life may exceed the standard cutoff used by most programs.15
Evidence for long-term adverse psychologic effects
from falsely positive screening test results is limited by methodologic
flaws.16-19
Effectiveness of Early
Detection
Most cases of congenital hypothyroidism present clinically during the first
year of life.20 Retrospective studies of patients with congenital hypothyroidism have
reported that delay of diagnosis and treatment beyond the first 1-3 months
of life is likely to result in irreversible neuropsychologic
deficits.21-25 More recent prospective studies show that screening neonates and treating
affected infants within the first weeks of life results, on average, in normal
or near-normal intellectual performance and growth at ages 5-12 years.26-34 These
children appear to have somewhat lower cognitive and motor development compared
to sibling or classmate controls, however, and continue to manifest subtle
deficits in language, perception, and motor skills.27,28,31-35 Both
age at onset of therapy and quality of therapeutic control achieved during the
first year of life affect long-term intellectual outcome, supportive evidence
for a benefit from earlier detection and treatment.27,28,31-33,35 The
reduced incidence of severe neuropsychologic effects
observed with early, adequate treatment has prompted most Western governments
to require routine screening for all neonates.
Screening at birth may, in
fact, occur too late to prevent important neurodevelopmental
deficits in some infants. Observational studies suggest that infants affected
more severely in utero, as evidenced by greater delay
in bone age at diagnosis, lower T4 at screening, or a diagnosis
of thyroid agenesis, have significantly poorer developmental outcomes compared
to those with milder disease or to normal controls, even when detected and
treated in the newborn period.28,31-36
Recommendations of Other Groups
Screening of newborns for hypothyroidism is offered in all states, but mandated
in 46 states and the District of Columbia.3 Five states and the District
of Columbia require or strongly recommend a routine second screening test, from
1 to 4 weeks later.3 Screening is recommended by the Canadian Task Force on the Periodic
Health Examination,37 the American Academy of Family Physicians,38 Bright
Futures,39 and jointly by the American Academy of Pediatrics and the American
Thyroid Association.5
Discussion
The natural history of congenital hypothyroidism has changed dramatically since
newborn screening was instituted in this country.2 Before
screening was available, many children with this disorder were at least
moderately, and sometimes profoundly, retarded, while recent prospective
studies have demonstrated normal or near-normal intelligence in virtually all
of those detected by screening and treated early in life. There is thus good
evidence to support screening for congenital hypothyroidism in the newborn.
CLINICAL INTERVENTION
Screening for congenital hypothyroidism with thyroid function tests performed
on dried-blood spot specimens is recommended for all newborns, optimally
between days 2 and 6, but in all cases before newborn nursery discharge ("A"
recommendation). Blood specimens should be collected by heelstick,
adsorbed onto filter paper, and air dried using standard technique.13a The
choice of which thyroid function test or tests to perform is generally
determined by individual state requirements.3
Testing procedures and follow-up treatment for abnormal results should follow
current guidelines.5 Care should be taken to ensure that those born at home, ill at birth, or
transferred between hospitals in the first week of life are appropriately
screened before 7 days of age. Normal newborn screening results should not preclude
appropriate evaluation of infants presenting with clinical symptoms and signs
suggestive of hypothyroidism.