A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. The condition typically is permanent, although transient hypothyroidism can result from transmission of maternal medications, maternal blocking antibodies, or iodine deficiency or excess.
In addition, the normal postnatal increase in TSH can be a problem when patients are discharged early. Primary T4 measurement with backup TSH assessment detects primary hypothyroidism, TBG deficiency, central hypothyroidism, and, potentially, hyperthyroxinemia (however, this method misses hyperthyroxinemia in infants with delayed TSH increase and initial normal T4).
Simultaneous measurement is the ideal approach, but it is not yet practical on a routine basis.Screening of all infants should be performed between two and four days of birth. If this is not possible, testing should be performed before discharge or within seven days of birth. False-positive TSH elevations may be found in specimens collected at 24 to 48 hours after birth, and false-negative results may be found in critically ill newborns or post-transfusion infants. However, screening before discharge or transfusion is still preferable to missing the diagnosis. Particular care should be taken not to miss screening in infants receiving emergency care.Results and DiagnosisAbnormal test results should be communicated immediately to the responsible physician so that follow-up testing can be arranged. Because of the potential for errors in testing, serum free thyroxine (FT4) and TSH levels should be determined regardless of newborn screening results when clinical symptoms and signs suggest hypothyroidism.LOW T4 AND ELEVATED TSH (PRIMARY HYPOTHYROIDISM)All infants with a low T4 concentration and a TSH concentration greater than 40 mU per L are considered to have congenital hypothyroidism and should have immediate confirmatory serum testing. Replacement levothyroxine (LT4) treatment should be initiated as soon as confirmatory samples have been taken, without waiting for the results (see Management and Treatment sections).If the TSH concentration is slightly elevated but less than 40 mU per L, a second screening test should be performed on a new sample. It may be caused by a transient or permanent thyroid abnormality or delayed hypothalamic-pituitary axis maturation, and it is more common in infants with Down syndrome. The need for therapy is controversial.Although TSH concentrations in the first few months of life typically are higher, persistent basal TSH concentrations of greater than 10 mU per L after two weeks of age generally are considered abnormal and should be treated. Possible causes are hypothalamic immaturity (especially in preterm infants), protein-binding disturbances such as TBG deficiency, central hypothyroidism, or primary hypothyroidism with delayed TSH elevation. Constant infusions of dopamine or high-dose glucocorticoids can inhibit TSH, causing low T4 concentrations.


Midline facial abnormalities, hypoglycemia, microphallus, or visual abnormalities should suggest hypothalamic-pituitary abnormality. Septooptic dysplasia should be suspected in infants with clinical symptoms of hypopituitarism and blindness or midline defects of the brain.The optimal follow-up is unclear.
Options include no further testing, follow-up filter-paper testing until T4 levels are normal, and measurement of FT4 and TSH concentrations on a second blood sample.
However, FT4 values and thyroid function test results usually are normal.Treatment with LT4 has no proven benefit except in infants with central hypothyroidism or delayed TSH elevation. When deciding whether to pursue further testing, physicians should weigh the benefits of detecting rare conditions against the cost and psychological impact on the family.LOW T4 AND DELAYED TSH ELEVATIONDelayed TSH elevation is more common in infants with low birth weight and those who are critically ill. Serum TSH levels in these infants increase in the first few weeks after birth to concentrations characteristic of primary hypothyroidism. Monozygotic twins should have a second specimen drawn at two weeks of age to account for potential fetal blood mixing. Infants with persistent hyperthyrotropinemia after six weeks should receive thyroid hormone replacement therapy, with repeat testing after three years of age.TRANSIENT TSH ELEVATIONRarely, abnormal screening results may be caused by transient hypothyroidism, and results of follow-up T4 and TSH testing are normal.
Causes of transient hypothyroidism include fetal exposure to maternal antithyroid drugs, prenatal or postnatal exposure to excess iodides, and iodine deficiency. Transplacental passage of maternal thyrotropin receptor-blocking antibodies (TRBAbs) is rare but should be suspected if there is a maternal history of autoimmune thyroid disease or previous affected children. Elevated T4 and TSH levels resulting from maternal antithyroid drugs typically return to normal within one to three weeks without treatment.ManagementAll infants with low T4 and high TSH levels should be considered to have congenital hypothyroidism until proved otherwise. Infants with congenital hypothyroidism should be seen by their physician immediately, and consultation with a pediatric endocrinologist is recommended.
A complete history should be taken (including maternal drug history and family history), and a physical examination should be performed.Serum should be tested for TSH and FT4 and results compared with age-appropriate norms.
TRBAb measurement may identify transient hypothyroidism in infants with a maternal history of thyroid disorder. Optional tests include thyroid ultrasonography, thyroid uptake, and scan to identify functioning thyroid tissue. Scanning should not delay treatment initiation and can be performed within the first few days of therapy.


A serum TSH measurement should be taken at the time of the scan.Parents should be educated by trained personnel using booklets or visual aids, if possible.
Education should focus on the etiology of congenital hypothyroidism, the lack of correlation between parental behavior during pregnancy and causes of the condition, the benefit of early diagnosis in preventing mental retardation, appropriate administration of therapy and which substances may interfere with absorption, the importance of treatment adherence, and the importance of follow-up care.TreatmentInfants with hypothyroidism should receive thyroid hormone therapy with the goal of achieving euthyroidism as soon as possible. An initial dosage of 10 to 15 mcg per kg per day has been recommended, depending on the severity of the condition. Soy, fiber, and iron can impair T4 bioavailability and should be avoided.T4 should increase to greater than 10 mcg per dL and FT4 to greater than 2 ng per dL (26 pmol per L) within two weeks after starting therapy, and TSH should normalize within one month. Relative pituitary resistance may delay normalization of serum TSH, resulting in a normal or increased serum T4 concentration with an inappropriately high TSH level. In these cases, the dose should be titrated based on the T4 value after first ruling out nonadherence to treatment.Follow-upLaboratory and clinical evaluations must be performed regularly in infants with congenital hypothyroidism during the first three years to ensure optimal dosing of and adherence to therapy. Serum T4 and TSH should be measured at two and four weeks after treatment initiation, then every one to two months until six months of age, every three to four months from six months to three years of age, every six to 12 months until growth is completed, and four weeks after any dosage change. Measurements should be performed more frequently if non-compliance is suspected or abnormal results are found. Ongoing counseling of parents is important because of the serious consequences of poor compliance.To ensure normal growth and development, serum T4 concentrations should be maintained in the upper half of the reference range in the first year, and serum TSH measurements should be kept in the reference range. If serum FT4 concentration does not increase to the upper half of the reference range by two weeks or if the TSH concentration does not fall below 20 mU per L within four weeks, physicians should evaluate compliance, dosage, and administration method. The adverse effects of excessive medication should always be taken into account, and physicians should be prepared to monitor blood FT4 concentrations at close intervals.ASSESSMENT OF PERMANENCEAn ectopic gland or absent thyroid tissue on thyroid scan or an increase in serum TSH to above 10 mU per L after one year of age indicates permanent congenital hypothyroidism. If no sign of permanence is found, therapy should be discontinued for 30 days after three years of age, and measurements of FT4 and TSH should be obtained.
A diagnosis of transient hypothyroidism can be made if results are in the reference range; otherwise, treatment should be resumed.



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