Congenital Hypothyroidism Workup

Updated: Oct 14, 2017
  • Author: Maala S Daniel, MBBS; Chief Editor: Sasigarn A Bowden, MD, FAAP  more...
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Approach Considerations

Screening of neonates

Screening for congenital hypothyroidism is recommended when a baby is 3 days old. Testing should be performed before discharge or within 7 days of birth. False-positive TSH elevations may be found in specimens collected at 24-48 hours after birth, and false-negative results may be found in critically ill newborns or post-transfusion infants. Particular care should be taken not to miss screening in infants receiving emergency care. [56]

There are 3 screening strategies for the detection of congenital hypothyroidism [56] :

  • Primary TSH measurement with backup thyroxine (T4) determination in infants with high TSH levels
  • Primary T4 measurement with backup TSH assessment in infants with low T4 levels
  • Simultaneous measurement of T4 and TSH levels (preferred)

Primary TSH measurement with backup T4 assessment misses delayed TSH elevation in infants with thyroxine-binding globulin (TBG) deficiency, central hypothyroidism, or hypothyroxinemia. In addition, the normal postnatal increase in TSH can be a problem when patients are discharged early. Primary T4 measurement with backup TSH misses hyperthyroxinemia in infants with delayed TSH increase and initial normal T4.

The European Society for Paediatric Endocrinology (ESPE) guidelines recommend performing a second screening for the following infants [57] :

  • Preterm, low-birth weight (LBW) and very low-birth weight (VLBW) neonates
  • Infants admitted to neonatal intensive care units (NICU)
  • Infants originally tested within the first 24 hours of life
  • Multiple births (particularly same-sex twins) 

According to the American Academy of Pediatrics guidelines, any infant with a low T4 concentration and TSH concentration greater than 40 mU/L is considered to have primary hypothyroidism. Confirmatory serum testing should be performed to verify the diagnosis and treatment intiated immediately and before the results of the confirmatory tests are available. [56]

Infants with modestly elevated TSH levels between 17 and 19.9 mIU/L have a significant risk (24%) of having congential hypothyroidism. [58] Testing should be repeated. It is important that age-appropriate normative values be used. The reference range for TSH for the most common time of TSH reevaluation (between 2 and 6 weeks of age) is 1.7 to 9.1 mU/L. [56]


Laboratory Studies

Diagnosis of primary hypothyroidism is confirmed by demonstrating decreased levels of serum thyroid hormone (total or free T4) and elevated levels of thyroid-stimulating hormone (TSH).

If maternal antibody–mediated hypothyroidism is suspected, maternal and neonatal antithyroid antibodies may confirm the diagnosis. [12] Such antibodies are an uncommon cause of congenital hypothyroidism. [13]

Low or low-normal serum total T4 levels in the setting of a serum TSH within the reference range suggests TBG deficiency. This congenital disorder causes no pathologic consequence; however, it should be recognized to avoid unnecessary thyroid hormone administration. Thyroid-binding globulin (TBG) deficiency affects 1 individual per 3000 population; therefore, occurrence is nearly as frequent as that in congenital hypothyroidism. TBG deficiency results in low serum total T4 levels; however, serum TSH and serum-free T4 concentrations are normal. Assessment of the serum TBG concentration, preferably with simultaneous serum free and serum total T4 concentrations, confirms the diagnosis.

TBG levels can be measured in infants with suspected TBG deficiency. This condition does not require treatment, but appropriate diagnosis and parental counseling can avoid later confusion and misdiagnosis.

Routine laboratory testing in patients with TBG deficiency shows a low total T4 level and a TSH level within the reference range. Free T4 and T3 levels are within the reference range. Congenital nephrotic syndrome is a rare cause of TBG deficiency or congenital hypothyroidism. [59, 60]

Laboratory results similar to infants with TBG deficiency can be found in infants who have hypopituitarism or hypothalamic disease, but these children have normal TBG levels.


Imaging Studies

Ultrasonography and scintigraphy

Ultrasound and thyroid scintigraphy help determine the anatomy and function of the thyroid gland as well as the etiology of congential hypothyroidism. Both the American Academy of Pediatrics (AAP) and the European Society for Paediatric Endocrinology (ESPE) recommend both ultrasound and scintigraphy be included in the initial workup but treatment should not be delayed. [57, 56] Ultrasound lacks sensitivity for detecting small ectopic glands but is the gold standard for measuring thyroid dimensions. [61]   Scintigraphy (using technetium-99m or iodine-123) provides an etiologic diagnosis in most cases and can aid in distinguishing congenital hypothyroidism from transient hyperthyrotropinemia. [62, 4]

The absence of radionuclide uptake suggests sporadic athyreotic hypothyroidism but can also be seen when uptake is blocked by excess iodide or thyroid receptor–blocking antibodies. If no uptake is found on isotope scanning, thyroid ultrasonography may demonstrate thyroid tissue in these patients. [4, 63] One study of 210 scanned infants stated a preference for using iodine-123 over pertechnetate. [64]

Thyroid scans can also demonstrate the presence of an ectopic thyroid, such as a lingual or sublingual gland, which is also sporadic. The presence of a bilobed thyroid in the appropriate position or a goiter would suggest either an inborn error of thyroid hormone production or transient hypothyroidism or transient hyperthyrotropinemia. 


A lateral radiograph of the knee may be obtained to look for the distal femoral epiphysis. This ossification center appears at about 36 weeks' gestation. Its absence in a term or postterm infant indicates prenatal effects of hypothyroidism. [57]


Other Tests

Neonatal hypothyroidism screening, using TSH levels, has proven helpful in countries with mild to no iodine deficiency. It has not been found useful in countries with moderate-to-severe levels of iodine deficiency disorders (IDD), because resources are insufficient to deal with the problem, and efforts here should be made to supply sufficient iodine to the population as a whole.

In infants with suspected dyshormonogenesis, radioactive iodine uptake (iodine-123) and perchlorate flush testing (KCIO2) can be performed to determine the presence of an iodide uptake or organification defect.