Symptom-Based Diagnosis in Pediatrics (CHOP Morning Report) 1st Ed.

CASE 12-4

Twelve-Month-Old Girl



The patient, a 12-month-old girl, was brought to her pediatrician for evaluation of constipation. She usually stooled once per day, but recently she was stooling only once per week. There had been no apparent change in her appetite or activity level. She had no fevers or emesis, and her review of systems was otherwise negative. She has had normal growth and development.


The patient had a normal birth history. Her birth weight was 3600 g. She passed meconium in the first 24 hours of life. She has not required previous hospitalization. She does not receive any medications.


T 36.2°C; HR 90 bpm; RR 17/min; BP 90/50 mmHg

Height 25th percentile; Weight 50th percentile

On examination, the patient is a well-appearing girl. Her HEENT examination was significant for a 1 × 1 cm fleshy mass at the base of her tongue that did not appear to cause her any discomfort. The heart and lung sounds were normal. Her abdomen had an easily reducible umbilical hernia with a 1 cm fascial defect. There was a 2 × 2 cm macular area of hypopigmentation on her lower abdomen. Her tone was slightly decreased symmetrically but she was able to sit without support. The neurologic examination was otherwise normal.


A nuclear medicine test confirmed the diagnosis (Figure 12-5).


FIGURE 12-5. Radionuclide scan. (Photo courtesy of Dr. Martin Charron.)



As with any child who goes from a normal to a constipated stooling pattern, major causes of constipation can be divided into functional versus organic. As in this case, findings on physical examination, that is, the mass at the base of the tongue, umbilical hernia, and hypotonia, may lead to the diagnosis. However, in a 1-year-old with constipation, other causes should be considered.

The patient was on no medication, had no evidence of spinal trauma or abnormalities, and no history of lead ingestion or exposure to botulinum.


Laboratory studies revealed: thyroid-stimulating hormone (TSH) 24.0 U/mL (normal range, 0.6-6.2); free thyroxine (T4) 5.4 mcg/dL (normal range, 6.8-13.5); T4 6.2 mcg/dL (normal range, 5.3-10.8); resin triiodothyronine (T3) uptake 36.9% (normal range, 28.0-47.0%); resin T3 uptake ratio 0.92 (normal range, 0.70-1.18). The patient has an ectopic thyroid gland leading to hypothyroidism. Thyroid scintigraphy (Figure 12-4) revealed increased uptake at the base of the tongue, confirming the diagnosis of hypothyroidism due to an ectopic thyroid gland.


Causes of congenital hypothyroidism include dyshormonogenesis (deficiency of an enzyme involved in the formation of thyroid hormones), transient congenital hypothyroidism, disorders of thyroxine synthesis, thyroid hormone resistance, and thyroid dysgenesis. Iodide transport defects and iodine organification defects are included among the 15 known disorders of thyroxine synthesis. Thyroid dysgenesis is the most frequent cause of hypothyroidism in infancy. Common types of thyroid dysgenesis include aplasia, hypoplasia, and ectopia (ectopic thyroid). The thyroid gland can be totally absent or, as in this case, ectopic. Furthermore, in some cases the deficiency of thyroid hormone can be severe and symptoms will develop in the first weeks of life. As in this case, lesser degrees of deficiency can occur and manifestations are delayed for months. In North America, the incidence of congenital hypothyroidism is 1 in 2000-3000 live births with a 2:1 female to male ratio. One study found a threefold higher incidence of congenital hypothyroidism in multiple (10.1 per 10 000 live births) compared with single (3.2 per 10 000 live births) deliveries. The reason for this finding is unclear, however, the low concordance rate in twins (4.3%) suggests that environmental factors may act as a trigger among those with a susceptible genetic background.


Most infants with congenital hypothyroidism are asymptomatic at birth, even if there is complete agenesis of the thyroid gland. This is attributed to the transplacental passage of moderate amounts of maternal T4, which accounts for 33% of the infant’s T4 levels at birth.

Soon after birth, children with congenital hypothyroidism often develop poor feeding, prolonged hyperbilirubinemia (>7 days), hypotonia, large posterior fontanelle (>1 cm), and macroglossia. Within the first 2 months of life, children who are hypothyroid usually develop constipation and are seen as sedate or placid infants. They also have abdominal distention and an umbilical hernia. There are several other common clinical manifestations: subnormal temperature, edema of the genitals and extremities, slow pulse, cardiac murmurs, cardiomegaly, and goiter. By 3-6 months these symptoms often progress. Development will be delayed as children who are hypothyroid often appear lethargic and are late in learning to sit or stand. Growth retardation is one of the main manifestations in childhood. This growth retardation is accompanied by delayed skeletal maturation.

Children with an ectopic thyroid gland usually have some viable thyroid tissue and symptoms of hypothyroidism are mitigated. These children represent a spectrum of severity of thyroid deficiency.


While neonatal screening programs vary from state to state, most in North America measure levels of T4 and run TSH levels on the lowest 10th percentile for a given day. The false negative rate is 5%-10%. Abnormal tests on a state screen should prompt immediate evaluation of T4 and TSH levels to confirm the diagnosis of hypothyroidism.

Thyroid function tests. Initial evaluation includes TSH and T4. T3 may be performed if ectopic thyroid is suspected initially. A normal or near-normal circulating level of T3 in the presence of a low T4 suggests the presence of residual thyroid tissue.

Thyroid scintigraphy. All children with proven congenital hypothyroidism should undergo radionuclide scanning if possible. The thyroid gland is the only organ in the body that stores iodine to any significant extent, making radioactive isotopes of iodine (e.g., sodium iodide 123, 123I) and ions of similar charge and radius to iodine (e.g., technetium pertechnetate, 99mTc) useful for thyroid imaging. No uptake of 123I or 99mTc occurs when the thyroid gland is absent. Ectopic thyroid glands are usually characterized by areas of increased uptake at the base of the tongue but other potential locations include the larynx, mediastinum, and lateral neck. Therefore, images must be obtained from the oropharynx to the upper mediastinum to exclude an ectopic gland. Ectopic thyroid glands are usually hypofunctioning and hence 123I, which produces less background activity than 99mTc, is the preferred isotope. The demonstration of ectopic thyroid is diagnostic for thyroid dysgenesis and establishes the need for evaluation and treatment of hypothyroidism. A normally placed thyroid with a normal or active uptake of radioisotope in the context of hypothyroidism suggests a defect in thyroid hormone biosynthesis.


The treatment of choice for children with hypothyroidism is L-thyroxine administered orally. The goal of therapy is to normalize T4 levels as quickly as possible. Levels of T3 and T4 rapidly return to normal in treated infants. TSH levels may not come into the normal range for several weeks even with good T4 values. Treatment is lifelong. If a child was even mildly symptomatic at the time of diagnosis, parents may notice an increase in activity, improvement in feeding, and increased urination and bowel movements soon after treatment begins. If bone maturation was delayed at the time of diagnosis, it will normalize within approximately 1 year. Early diagnosis and treatment usually results in normal IQ and motor development. Delayed diagnosis may result in variable deficits in intelligence that amount to several IQ points for every week of delayed treatment.

To guarantee adequate hormone replacement, T4 levels should be maintained in the upper half of the normal range during therapy. Low T4, high TSH, and poor growth suggest poor compliance or undertreatment. Excessive L-thyroxine over a prolonged period of time (3-6 months) may cause osteoporosis, premature synostosis of cranial sutures, and advancement of bone age. Prognosis is excellent if treatment is begun in the first 4 weeks of life.


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