Pediatric Hypothyroidism Workup

Updated: Dec 20, 2016
  • Author: Sunil Kumar Sinha, MD; Chief Editor: Sasigarn A Bowden, MD  more...
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Laboratory Studies

For all measures of thyroid function, age must be considered to interpret the results. In the term neonate, laboratory tests best reflect true thyroid function when performed in infants older than 24 hours.

  • Serum thyrotropin (TSH) concentration remains the most sensitive screening test for hypothyroidism and for establishing the diagnosis of primary hypothyroidism. The sample can be obtained at any time of day. A value within the reference range does not exclude TSH deficiency or TRH deficiency.

    • A physiologic surge of TSH occurs within the first 30 minutes of life and appears to be related to the stress of delivery and exposure to the cold temperature of the extrauterine environment. Serum TSH levels peak at levels as much as 70 mIU/L within the first 24 hours of life and then rapidly drop to less than 10 mIU/L within the first 3 days of life. Beyond the neonatal period, healthy serum levels of TSH are less than 6 mIU/L. Serum TSH levels are elevated in primary hypothyroidism or compensated hypothyroidism and should be low or within the reference range in cases of pituitary (TSH deficiency) or hypothalamic (TRH deficiency) etiologies. Isolated TSH deficiency is far less common than multiple anterior pituitary hormone deficiencies.

    • Serum TSH is the optimal parameter to guide dosing of thyroid hormone replacement, except in patients with secondary or tertiary hypothyroidism. In these patients, measuring serum free T4 by means of equilibrium dialysis is the superior testing method. Adequate thyroid hormone replacement results in normalization of serum TSH. In the rare syndromes of thyroid hormone resistance, serum TSH levels are elevated in the presence of normal-to-high serum total T4 concentration.

    • Serum TSH levels are often mildly abnormal (≤ 7 mIU/L) in children and adolescents who are morbidly obese (>20 lb overweight). If the serum free T4 level is normal, the growth velocity has been normal for at least 6 months, the serum TSH level remains stable (not rising) over at least 3 months, and no other signs of hypothyroidism are present, these children and adolescents do not require routine T4 therapy.

  • T4 is present in both the free state and bound to TBG. Total T4 assays measure T4 in both states and are useful to establish the diagnosis of primary hypothyroidism and to assess response to treatment. Free T4 should be directly measured with the equilibrium dialysis method. Many laboratories report a calculated value termed the free T4 index, which is an estimate of the free T4 concentration, not a measurement. The free T4 index is calculated by multiplying the T4 by the T3 resin uptake. Serum free T4 by equilibrium dialysis should be measured when secondary hypothyroidism (pituitary TSH deficiency) or tertiary hypothyroidism (hypothalamic TRH deficiency) is suggested.

  • Measurement of serum T3 concentration, free or total, is not required to confirm the diagnosis of hypothyroidism.

  • Newborn screening for congenital hypothyroidism includes the following:

    • Required by US law in all 50 states, these programs measure total T4 levels using a filter paper–based assay. In those neonates whose serum T4 level falls within the lowest 10th percentile for newborns screened that day by the program, T4 is reassayed, and TSH is simultaneously determined. Remember that, even with the best screening programs, infants with hypothyroidism can be missed. Therefore, the occurrence of a normal screening result must not preclude thyroid function testing in any infant with signs or symptoms of hypothyroidism.

    • Infants with abnormal or borderline screening results should have total T4 and TSH obtained for definitive testing. Thyroid hormone replacement may be empirically initiated while awaiting the confirmatory studies.

    • In infants, if the serum total T4 is less than 85 nmol/L (< 7 mg/dL), with TSH more than 40 mIU/L, congenital hypothyroidism is likely. If total T4 is low, and serum TSH is not elevated, TBG deficiency, central hypothyroidism, or euthyroid sick syndrome should be considered, and repeat testing may be needed. [5] Serum free T4 concentration is normal in TBG deficiency. Normal TSH (< 20 mIU/L) in the presence of low total T4 and free T4 concentrations suggest secondary or tertiary causes of hypothyroidism. In the latter, signs of associated hypopituitarism (eg, poor feeding, hypoglycemia) and physical findings (eg, midline defects, micropenis) support the diagnosis. All such infants should be screened for other pituitary hormone deficiencies (see Hypopituitarism).

  • Serum antithyroid antibody test findings do not facilitate the diagnosis of hypothyroidism and only serve to establish a diagnosis of CLT and indicate the risk of subsequent development of hypothyroidism. Antithyroid peroxidase and antithyroglobulin antibody titers are elevated in 90-95% of children with CLT. A small proportion of children with test results that are initially negative become positive later. As many as 20% of individuals who have antibody-positive test results do not develop hypothyroidism or hyperthyroidism.

  • Serum total T4 levels and serum free T4 levels are both low in patients with hypothyroidism. In compensated hypothyroidism, total T4 may remain within the reference range in the presence of elevated TSH.

  • Newborns with an elevated TSH should be treated empirically with thyroid hormone replacement until they are aged 2 years to eliminate any possibility of permanent cognitive deficits as a result of hypothyroidism.

  • 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. 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; 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.


Imaging Studies

See the list below:

  • In vivo radionucleotide studies: The iodide-trapping or concentrating mechanism of normal thyroid tissue can be evaluated by radioisotope (iodine-123 or technetium-99m pertechnetate). In children, technetium-99m is a useful radioisotope because it is trapped by the thyroid but not organified; thus, the child is exposed to lower amounts of radiation.

  • In congenital organification defects and lymphocytic thyroiditis, the amount of radioisotope uptake is within reference range; however, the half-life of the radioisotope within the thyroid is decreased because of the lack of organification. This can be demonstrated by means of a perchlorate washout study.

  • Radioisotope-based thyroid scanning is useful to detect the absence or ectopic location of healthy thyroid tissue in congenital hypothyroidism.

  • Iodine-123 scanning of the thyroid can be used to identify ectopic thyroid tissue, such as lingual thyroid. Absence of a signal on this study confirms athyreosis. 

  • X-ray of the knee can provide useful information regarding degree of severity of intrauterine hypothyroidism by the presence or absence of femoral and tibial epiphyses. [6]


Fine-needle aspiration is generally not necessary in children with hypothyroidism.

  • This study, which is designed to evaluate a thyroid nodule, should only be performed by a physician experienced with this procedure.

  • This procedure is most strongly indicated in adolescents or young adults who have a single cold nodule detected by means of iodine-123 scanning.


Histologic Findings

The histologic appearance of CLT includes lymphocytic infiltration, formation of lymphoid follicles, and follicular cell hyperplasia.