Congenital hypothyroidism
Objectives of this lecture: Definition Causes Clinical features Diagnosis Treatment prognosisHypothyroidism Hypothyroidism results from deficient production of thyroid hormone or a defect in thyroid hormone receptor activity .The disorder may be congenital or acquired. CONGENITAL HYPOTHYROIDISM Most cases of congenital hypothyroidism result from thyroid dysgenesis. Some cases may be familial, usually caused by one of the inborn errors of thyroid hormone synthesis, and may be associated with a goiter. EPIDEMIOLOGY. The prevalence of congenital hypothyroidism based on neonatal screening is 1/4,000 infants . male : female = 1:2 AETIOLOGY Thyroid Dysgenesis. (aplasia, hypoplasia, or an ectopic gland) is the most common cause of congenital hypothyroidism, accounting for 85% of cases; 10% are caused by an inborn error of thyroxine synthesis, and 5% are the result of transplacental maternal thyrotropin-receptor blocking antibody (TRBAb).
CLINICAL MANIFESTATIONS. Most infants with congenital hypothyroidism are asymptomatic at birth, even if there is complete agenesis of the thyroid gland due to the transplacental passage of moderate amounts of maternal T4, which provides fetal levels that are approximately 33% of normal at birth. These low serum levels of T4 and concomitantly elevated levels of TSH make it possible to screen and detect hypothyroid neonates. The clinician is dependent on neonatal screening tests for the diagnosis of congenital hypothyroidism. Laboratory errors occur, however, and awareness of early symptoms and signs must be maintained.
Birthweight and length are normal, but head size may be slightly increased because of myxedema of the brain. Prolongation of physiologic jaundice, caused by delayed maturation of glucuronide conjugation, may be the earliest sign. Feeding difficulties, especially sluggishness, lack of interest, and choking spells during feeding, are often present during the 1st mo of life. Respiratory difficulties, due in part to the large tongue, include apneic episodes, noisy respirations, and nasal obstruction. Affected infants cry little, sleep much, have poor appetites, and are generally sluggish. There may be constipation that does not usually respond to treatment. The abdomen is large, and an umbilical hernia is usually present.
If congenital hypothyroidism goes undetected and untreated, these manifestations progress, Retardation of physical and mental development becomes greater during the following months, and by 3–6 months of age the clinical picture is fully developed.The child's growth will be stunted, the extremities are short, and the head size is normal or even increased.The anterior and posterior fontanels are open widely; observation of this sign at birth may serve as an initial clue to the early recognition of congenital hypothyroidism.The eyes appear far apart, and the bridge of the broad nose is depressed. The palpebral fissures are narrow and the eyelids swollen. The mouth is kept open, and the thick, broad tongue protrudes. Dentition will be delayed.
The neck is short and thick, and there may be deposits of fat above the clavicles and between the neck and shoulders (buffalo hump). The skin is dry and scaly, and there is little perspiration. Myxedema is manifested, particularly in the skin of the eyelids, the back of the hands, and the external genitals. The skin shows general pallor. Carotenemia may cause a yellow discoloration of the skin, but the sclera remain white. The hairline reaches far down on the forehead, which usually appears wrinkled, especially when the infant cries. Development is usually retarded. Hypothyroid infants appear lethargic and are late in learning to sit and stand. The voice is hoarse, and they do not learn to talk. The degree of physical and mental retardation increases with age. Sexual maturation may be delayed.
LABORATORY FINDINGS. Most newborn screening programs measure levels of T4, followed by measurement of TSH when T4 is low (USA). European and Japanese neonatal screening programs are based on a primary measurement of TSH Regardless of the approach used for screening, some infants escape detection because of technical or human errors; clinicians must be careful about the clinical manifestations of hypothyroidism.
Serum levels of T4 or free T4 are low; serum levels of T3 may be normal and are not helpful in the diagnosis. If the defect is primarily in the thyroid, levels of TSH are elevated, often to greater than 100 mU/L. Serum levels of prolactin are elevated, correlating with those of TSH.. Retardation of osseous development can be shown radiographically at birth in about 60% of congenitally hypothyroid infants and indicates some deprivation of thyroid hormone during intrauterine life. The distal femoral epiphysis, normally present at birth, is often absent In undetected and untreated patients, the discrepancy between chronological age and bone age increases.
Ultrasonographic examination of the thyroid is helpful, but studies show it may miss some ectopic glands shown by thyroid scan. Thyroid scan can help to pinpoint the underlying cause in infants with congenital hypothyroidism, but treatment should not be delayed for this study. 123I-sodium iodide is superior to 99mTc-sodium pertechnetate for this purpose. The ECG may show low-voltage P and T waves with diminished amplitude of QRS complexes and suggest poor left ventricular function and pericardial effusion. In children older than 2 yr of age, the serum cholesterol level is usually elevated.
TREATMENT. Levothyroxine given orally is the treatment of choice. In neonates,the initial starting dose is 10–15 μg/kg/ day Levels of T4or free T4 and TSH should be monitored at recommended intervals (approximately monthly in the first 6 mo of life, and then every 2–3 mo between 6 mo and 2 yr) and maintained in the normal range for age. Children with hypothyroidism require about 4 μg/kg/24 hr,adults require only 2 μg/kg/24 hr.
PROGNOSIS. Early diagnosis and adequate treatment from the first weeks of life result in normal linear growth and intelligence comparable with that of unaffected siblings. Approximately 20% of children have a neurosensory hearing deficit. Without treatment, affected infants are profoundly mentally deficient and growth retarded.