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Clinical signs and symptoms are not usually helpful in the early diagnosis of CH.
Only about 5% of newborn infants with CH are diagnosed on the clinical grounds.
Early S/S include prolonged hyperbilirubinemia (> 7 days), hoarse voice, distended
abdomen, umbilical hernia, hypotonia, a large posterior fontanelle, macroglossia,
and thyroid enlargement. Apositive screening result is followed by serum testing
to confirm the diagnosis of primary CH.22-24,49 In the neonatal period serum T4
concentrations below 84 nmol/L(6.5 µg/dL) and TSH values above 9 mU/L (9 µU/ml)
suggest hypothyroidism. 90 % of infants with proven CH have serum TSH concentrations
above 50 mU/L and 75 % have T4 concentrations below 84 nmol/L. About 20 % of
hypothyroid infants have T4 levels in the 84–165 nmol/L (6.5 to 13 µg/dL) range,
usually with clearly elevated TSH concentrations (>30 mU/L). 3–5% of infants will
manifest serum T4 values in the low normal range (84–165 nmol/L) with only modestly
elevated TSH concentrations (9–30 mU/L) with a delayed postnatal TSH increase
to clearly hypothyroid levels. These infants usually require repeat testing and
clinical evaluation to establish a definitive diagnosis of CH. Serum T3 or
rT3 measurements have limited practical value in the diagnosis of CH. Automated
immunoassay systems for free T4 measurements are gradually replacing total T4 for
diagnostic purposes; cutoff values have to be established for the individual
methods. Defining the etiology of CH may not be possible in the neonatal period because of the urgency of early treatment to optimize IQ. In many instances differential diagnosis is postponed to age 2–3 years when definitive studies can be safely conducted after 1–2 months off thyroid replacement. It is possible to diagnose thyroid dysgenesis in the neonatal period if facilities are available for isotopic or ultrasound studies. For neonatal radioiodine scanning I123 is the isotope of choice to minimize radiation exposure. Technetium may be used, but although concentrated by thyroid follicular cells, it is not organified. The confirmation of an ectopic thyroid gland provides a definitive diagnosis of thyroid dysgenesis. The absence of uptake of radioisotope suggests thyroid gland agenesis, but some infants may have low radioisotope uptake and a nondetectable gland by scan due to a TSH receptor or iodide trapping defect, or TSH receptor blockade by maternal TSH receptor blocking antibody (TBA). These infants or the mother should have blood drawn for measurement of TBAif there is a history of maternal autoimmune thyroid disease. Thyroid ultrasound may be helpful to conmanifest firm thyroid gland agenesis or ectopia. A serum Tg measurement may be helpful in infants with absent uptake or normal scans. A very low or absent serum Tg level indicates thyroid agenesis in an infant with absent radioisotope uptake, and suggests a defect in Tg synthesis in infants with a normal imaging study. Infants with thyroid dysgenesis have elevated serum Tg concentrations which relate to the mass of residual thyroid tissue and degree of stimulation. However, levels usually do not exceed 1000 pmol/L (660 ng/mL). Very high Tg levels (>1000 pmol/L) may be observed in infants with CH due to defective thyroxine synthesis not involving the capacity for Tg production. Serum calcitonin levels also are low in CH infants with thyroid agenesis but offer no advantage over the Tg measurement in diagnosis. Abone age measurement (x-ray examination of the knee and foot) also is useful as a sign of possible intrauterine hypothyroidism. Hypothalamic-pituitary hypothyroidism is more difficult to diagnose and is not detected in screening programs reporting only elevated TSH levels. The disorder is characterized by a low serum T4 and/or free T4 concentration with a normal or low normal range TSH value. However, this pattern most commonly reflects prematurity or a low TBG concentration. Measurements of serum TBG and free T4 concentrations will distinguish these possibilities. Careful physical examination should be conducted for evidence of hypothyroidism, and tests of pituitary function are indicated in suspect infants. A subnormal TSH response to TRH confirms a diagnosis of pituitary TSH deficiency. If the peak level of TSH is normal and/or prolonged, and there is a good 4-hour T4 (thyroid) response to TSH, hypothalamic TRH deficiency is more likely. The TSH deficiency may be isolated or associated with other pituitary hormone deficiencies. |
