Congenital hypothyroidism

Congenital hypothyroidism (CH) is defined as thyroid hormone deficiency present at birth. Babies with CH who are not identified and treated promptly develop severe mental retardation. Most of the babies with CH do not manifest the typical known signs and symptoms of hypothyroidism, and this is most likely due to transplacental passage of some maternal thyroid hormone in addition to some residual neonatal thyroid function, as might be seen with thyroid hypoplasia, an ectopic gland, or mild dyshormonogenesis. Screening for CH has enabled the virtual eradication of the devastating effects of mental retardation due to sporadic CH in most developed countries of the world. CH is classified into permanent and transient forms, which in turn can be divided into primary, secondary, or peripheral etiologies. Permanent CH refers to a persistent deficiency of thyroid hormone that requires life-long treatment. Transient CH refers to a temporary deficiency of thyroid hormone that is discovered at birth but recovers to normal in the first few months or years of life. In the last several decades, there have been exciting advances in our understanding of fetal and neonatal thyroid physiology. In addition, advances in molecular biology have helped in understanding the early events in thyroid gland embryogenesis, mechanisms of thyroid action in the brain, the molecular basis for many of the inborn errors of thyroid hormonogenesis, and thyroid hormone action. However, many questions and challenges are still not answered. For example, the increasing numbers of surviving small and premature neonates with abnormalities in thyroid function need definite diagnostic criteria and whether they require medical therapy. Another challenge is the dilemma of finding the best screening methodology that is sensitive and cost effective.     

Congenital hypothyroidism

Congenital Hypothyroidism (CH) is one of the most common preventable causes of mental retardation with a worldwide incidence of 1:4000 live births. Ideally universal screening at 3–4 days of age should be done for detecting CH. Abnormal values on screening (T4 < 6.5 ug/dL, TSH > 20mu/L) should be confirmed by a venous sample (using age appropriate cutoffs) before initiating treatment. Term as well as preterm infants with low T4 and elevated TSH should be started on L-thyroxine at a dose of 10–15μg/ kg/ day as soon as the diagnosis is made. Regular monitoring should be done to ensure that T4 is in the upper half of normal range. The outcome of CH depends on the time of initiation of therapy and the dose of L-thyroxine used with the best outcome in infants started on treatment before 2 weeks of age with a dose > 9.5μg/ kg/ day.     

Congenital hypothyroidism

Congenital hypothyroidism is one of the most common diseases in paediatric endocrinology. Thyroid hormones are essential in brain development, which takes place during foetal life and early postnatal life up to the 2nd year of age. The main etiologic factors of congenital hypothyroidism are anomalies of development, function and regulation of the thyroid gland. Clinical signs of thyroid hormone deficiency in infants are non-specific. Early diagnosis is based on newborn screening for congenital hypothyroidism, which was started in Poland in 1977. Treatment within the first days of life with appropriate dosage of thyroxine prevents mental retardation. This paper summarises current knowledge on congenital hypothyroidism in children.     

Congenital hypothyroidism

The 1980s have seen widespread growth in the screening of newborn infants for congenital hypothyroidism (CH). By 1982 it was estimated that 7-9 million infants were screened annually.¹ There has been further expansion since 1982, not only in communities with highly developed public health programmes, but also in less developed centres.² Experience from Hong Kong is reported in a previous issue of this journal.³     

Congenital hypothyroidism.

Because of the lack of signs and symptoms in the first weeks of life, the most important tool for the early diagnosis of congenital hypothyroidism is a newborn screening program.     

Congenital hypothyroidism and development

The authors present the developmental outcome of 16 children with congenital hypothyroidism diagnosed by screening in the neonatal period, using the Brazelton and the Dubowitz scales in the newborn and the Griffiths scale subsequently. Results are compared with those of a control group assessed at 6 and 18 months using the Griffiths scale.     

Congenital familial hypertonia

1. This complex of symptoms appears to be congenital, familial, and hereditary. It is apparently transmitted by a dominant gene, probably on chromosome 5. 2. Hypertonicity with rigidity of all voluntary muscles usually presents at birth. 3. Feeding problems are due to dysphagia or laryngospasm associated with aspiration and dyspnea. 4. Respiratory problems are characterized by apneic episodes due to muscle spasm. 5. Prolonged episodes of muscular rigidity secondary to sudden stimuli result in frequent falls, characteristically en bloc, like a statue. 6. Continuous electromyographic activity even at rest (with absence of fasciculations) improves after intravenous diazepam.     

Contribution of genetic factors to neonatal transient hypothyroidism

BACKGROUND: The causes of neonatal transient hypothyroidism (NTH) remain incompletely understood. Whether it is influenced by genetic background is rarely discussed and remains unproven. A defect in thyroid peroxidase is a common cause of dyshormonogenesis of the thyroid gland in Taiwanese, with a novel mutation (2268insT) present in nearly 90% of alleles studied. OBJECTIVE: To determine if the presence of this common mutation is associated with NTH in Taiwan. METHODS: A mismatched primer was designed and used for this specific 2268insT mutation to screen 1000 normal babies and 260 babies with confirmed NTH. RESULTS: The carrier rate for 2268insT in normal babies (1/200) was significantly lower than in babies with NTH (1/13; p<0.0001). CONCLUSIONS: The results strongly suggest that the presence of this thyroid peroxidase mutation contributes to the development of NTH. Likely pathogenetic explanations include the effect of the stress of extrauterine adaptation during labour on an immature pituitary-thyroid axis in genetically predisposed individuals, combined with environmental triggers such as iodine deficiency, perinatal iodine exposure, and/or goitrogen contamination.     

Congenital hypothyroidism with Prader-Willi syndrome

We report a 1 year-old female patient with severe hypotonia who has congenital hypothyroidism and Prader-Willi syndrome (PWS). At birth she was found to have congenital hypothyroidism caused by an ectopic sublingual thyroid gland and was commenced on thyroid replacement therapy. She continued to have severe motor delay and therefore further diagnostic evaluation was performed. PWS was confirmed by DNA and fluorescence in situ hybridization (FISH) analysis. This report emphasizes the need to further investigate patients who are found to have congenital hypothyroidism and do not improve adequately on treatment.     

Congenital angiosarcoma with transient response to paclitaxel

Angiosarcoma is a rare diagnosis with a poor prognosis. We report the first known case of congenital angiosarcoma. We also report a transient response with paclitaxel, an agent that may have a role in unresectable angiosarcoma.