Congenital Hypothyroidism

This syndrome results from inadequate thyroid hormone (TH) levels during pregnancy or in the neonatal period and during infancy. Characterized in newborns by failure to thrive and physical and mental retardation.

Cretinism.

1:3000-4000. Eighty-five percent of cases are sporadic, with wide ethnic variations (1:4000 in Caucasians, 1:2000 in Hispanics, 1:32,000 in Blacks). Females are affected twice as often as men.

Varying etiology. Thyroid dysgenesis is occasionally autosomal recessive inherited but mostly is nonhereditary. Inborn errors of TH biosynthesis are most often autosomal recessive transmitted, except for defects in TH receptor actions that are autosomal dominant inherited.

Congenital hypothyroidism can be classified into two groups: endemic cretinism and sporadic cretinism. Endemic cretinism is caused by intrauterine and/or neonatal iodine deficiency frequently occurring in certain areas (e.g., alpine regions of Europe), whereas sporadic cretinism may be the result of basically three different mechanisms:

Thyroid dysgenesis (85% of all cases): Thyroid dysgenesis includes thyroid (hemi-)agenesis, ectopic thyroid tissue, cysts of the thyroglossal duct, and thyroid hypoplasia. In the vast majority of cases, thyroid dysgenesis is sporadic, but is familial in about 2%. The pathogenesis is largely unknown, but suggested mechanisms include mutations in the genes coding for thyroid transcription factor-1 (TTF-1), thyroid transcription factor-2 (TTF-2, which is important for thyroid morphogenesis and differentiation), and paired box 8 transcription factor (PAX-8, involved in the regulation of TH production), and mutations resulting in dysfunction of the thyrotropin (thyroid-stimulating hormone [TSH]) receptor (important for thyroid growth and function).

Inborn errors of TH biosynthesis (dyshormogenesis) (10% of patients): They are the result of a defect in any step of TH synthesis, secretion, and/or action, including mutations in the sodium/iodide symporter, defects in thyroid peroxidase, thyroglobulin, and deiodinase. In fewer than 1% of patients the cause is hypothalamic and/or pituitary failure.

Transplacental transfer of maternal antibodies (5% of patients): Maternal autoimmune thyroid disease (Graves disease, Hashimoto autoimmune thyroiditis) with transplacental passage of thyrotropin receptor-blocking antibodies (TRB Abs).

Based on the clinical findings and laboratory investigations: low levels of total and free thyroxine (T4 and fT4) and triiodothyronine (T3), altered TSH levels (depending on the etiology may be either decreased or increased), and low serum thyroglobulin concentrations can be seen. Serum, salivary, and urine iodine studies are required to confirm errors of biosynthesis, the presence of maternal and neonatal serum TRB-Abs, or low urinary iodine excretion in iodine deficiency. Imaging studies (e.g., nuclear medicine) can be used to determine the location and size of the gland, and to assess skeletal maturation (e.g., conventional radiography of the distal femur epiphysis).

Signs of hypothyroidism usually are difficult to diagnose at or immediately after birth. In severe cases, it may take a few weeks until symptoms become apparent. In milder cases, diagnosis may be delayed for months or even longer. Screening programs with measurement of TSH and T4 are important because congenital hypothyroidism is one of the most common preventable causes of mental retardation. Early signs may include an abnormally high birth weight, delayed passage of meconium, constipation, and a large abdomen. Later symptoms include persistent neonatal icterus, feeding difficulties with little appetite, failure to thrive, choking spells, respiratory distress and apneas (partly as a result of macroglossia and nasal obstruction), wide anterior and posterior fontanelles (an important and common sign), hoarse voice, umbilical hernia, and disturbances in thermoregulation with temperatures often below 35°C, leading to cold and mottled skin. Somnolence and lethargy, bradycardia (despite frequently present anemia) and cardiomegaly, pericardial and pleural effusions, and genital and peripheral edemas are frequent findings. Physical and psychomotor development are delayed and become more obvious at 3 to 6 months of age in severe cases. The changes are more subtle in milder cases and therefore are more difficult to detect. Dysmorphic features may include coarse, brittle hair with low anterior hairline, hypertelorism, depressed nasal bridge, constantly open mouth with protruding tongue secondary to macroglossia, short and thick neck, short stature, wide hands with brachydactyly, and generalized muscular hypotonia with a clumsy gait. The skin often appears dry and scaly. In endemic cretinism, the above described findings are often accompanied by deaf-mutism and motor dysfunction with spasticity.

Evaluate thyroid function (clinically, and serum levels of T3, free T4, and TSH), and obtain a chest radiograph to exclude pleural effusions. Given the possible anomalies mentioned, the airway should be assessed carefully with regard to difficult airway management. Frequent apneas in the neonatal period and in infancy require appropriate postoperative monitoring and care. In addition, anemia, hyponatremia, and hypoglycemia have been described in these patients, so a complete blood count and serum levels of electrolytes and glucose should be checked. Mental retardation may affect patient compliance. Preoperative mild sedation (mild to preserve airway patency) and the presence of the primary caregiver during induction of anesthesia may be helpful.

Difficult airway management is common. Spontaneous ventilation should be maintained until the airway has been secured. However, gastric emptying may be delayed and, depending on the clinical findings, a rapid-sequence induction may be preferred. There is an increased risk of perioperative bradycardia and cardiac failure in these patients. The patients appear to be sensitive to the sedative and respiratory depressing effects of opioids and other anesthetic drugs. Depending on the extent of respiratory symptoms and the planned surgery, prolonged postoperative mechanical ventilation may be necessary or favored. Hypothyroidism and hypothermia result in delayed metabolism and elimination of drugs, so reduced doses may be necessary. Hypoglycemia may occur, hence regular perioperative control is recommended. Because thermoregulation is altered, every effort should be made to keep the patients warm (e.g., forced-air convective warmer, heating blanket). Peripheral venous access may be difficult because of edema and skin changes.

Avoid neuromuscular blockers in patients with suspected difficult airway management until the airway has been secured. Delayed clearance of drugs has been reported (partly because of delayed maturation of glucuronide conjugation).

Akesson Syndrome (Cutis Verticis Gyrata with Thyroid Aplasia and Mental Retardation Syndrome): Characterized by the presence of cutis vertices gyrata, hypothyroidism, mental retardation, skull abnormality, shagreen patch, short stature (occasionally considered dwarfism). The thyroid gland is either ectopic, absent (aplastic), or hypoplastic. Although an X-linked inheritance seems likely, most other cases of cutis verticis gyrata and mental retardation present with an autosomal dominant inheritance. It is important to evaluate the thyroid function (serum T4, T3, T3RU, TSH) and ensure proper therapeutic replacement of thyroid hormones before anesthesia. Impairment of thermoregulatory responses requires proper care to minimize heat loss intraoperatively.