We all know that essentially all infants born in the United States and Canada have been screened for genetic-metabolic disorders for almost 20 years. These disorders include phenylketonuria, galactosemia, branched-chain ketoaciduria (maple syrup urine disease), sickle cell anemia and other hemoglobinopathies, and congenital hypothyroidism. Cystic fibrosis, biotinidase deficiency, and congenital adrenal hyperplasia are also being screened for in a few states. Each of these disorders is rare. The most common, congenital hypothyroidism, occurs in one of 4000 births among all populations.
The principles of screening that apply to congenital hypothyroidism and the other genetic -metabolic disorders that are otherwise undetectable at the time of screening - in this instance, immediately after birth - are:
* The diagnosis is made more rapidly when screening criteria rather than clinical criteria are used.
* Earlier diagnosis and treatment result in better outcomes.
* An effective treatment (including counseling for patents and unaffected siblings) is available for all who are affected.
* The frequency with which false-negative and falsepositive results occurs is acceptable.
* The screening and treatment procedures are cost effective.1
These principles hold true for all the geneticmetabolic disorder screening tests currently performed on newborns, including those for congenital hypothyroidism; however, for thyroid screening there are additional considerations, as defined by Fisher.2
* Most screening programs in the United States measure thyroxin (T4) levels in newborns, while a few measure thyroid stimulating hormone (TSH) levels, as do most screening programs in western Europe, Scandinavia, Japan, Israel, Australia, and New Zealand. Approximately 12 million infants are currently being screened annually for congenital hypothyroidism by the use of T4 or TSH levels; however, while screening programs for congenital hypothyroidism are being developed in eastern Europe, South America, Asia, and Africa, most infants in these geographic areas are not being screened. The arguments for and against T4 and TSH screening are complex and beyond the scope of this review; each method, however, is acceptable.
* The most accurate screening results, using T4 or TSH levels, occur when screening samples are obtained 3 to 5 days after birth. However, in the United States most infants are discharged from the newborn nursery within 3 days of birth, leading to a higher incidence of false-positive test results, particularly elevated TSH levels due primarily to biologic variants. Thus, follow-up testing by the primary care physician is required. This is also so when low T4 or elevated TSH levels are detected on tests performed at age 3 to 5 days. If follow-up serum T4 and TSH levels are normal, all is well and good. If they are not, other, more sophisticated tests are in order (thyroid scan or ultrasound studies to detect the presence and location of thyroid tissue and serum thyroxin-binding globulin levels) to determine whether true congenital hypothyroidism is present or whether one of the variety of other causes of low T^ or elevated TSH levels are present, as discussed in detail by Grüters in this issue of Pediatrie Annais.3 Needless to say, these tests should be performed under the direction of a pediatrie endocrinologist.
* Of most concern is that approximately 10% of all iniants with congenital hypothyroidism (300 of the 12000000 infants screened annually worldwide) are reported as being normal following T4 or TSH screening. As a result, the primary care physician is lulled into a false sense of security and frequently does not consider congenital hypothyroidism as a cause for the signs of the disease that will soon appear, and thus delays making the diagnosis and instituting treatment. If the diagnosis is made and treatment is started within the first month of life, one can expect normal intellectual development to occur; if treatment is delayed until 3 months of age, only 75% of patients will achieve normal IQ levels; and if treatment is delayed until 6 months of age, only 50% will achieve normal IQ levels.4
Primary care practitioners are deeply involved in the screening process for congenital hypothyroidism. They receive the results of newborn screening tests, are responsible for arranging tests to confirm positive results, and are directly or indirectly involved in the treatment of the disease and in counseling the parents. They should be familiar with the screening tests performed, the interpretation of their results, and the actions that must be taken to ensure that the best possible outcome is achieved. Above all, they must be aware of the possibility that infants with a negative screening test may still have congenital hypothyroidism, be alert to the early clinical signs of the disease, and if need be, be prepared to intervene rapidly.
1. Richards OE. Screening uf newboms for endocrinological disease. Journal of the Children's Memorial Hospital. 1991;9:13-21.
2. Fisher DA, Management of congenital hypothyroidism. Joumil of Clinical Endocrmoiogy and Metabolism. 1991;7Z:523-529.
3. Grüters A. Congenital hypothymidism. Pediatr Ann. 1992;21:15-28.
4. New England congenital hypothyroidism collaborative. Effects of neonatal screening for hypothyroidism: prevention of mental retardation by treatment before clinical manifestations. Lancet. 1981;ii:1095-1098.