**Author details**

Poondy Gopalratnam Raman Address all correspondence to: drpgraman@yahoo.com M.G.M. Medical College, DAVV, lndore, MP, India

#### **Chapter 2 Provisional chapter**

#### **Congenital Hypothyroidism Congenital Hypothyroidism**

#### Sanjay Saran Sanjay Saran

**5.** Increased urinary excretion of iodine in pregnancy impairs thyroid hormone production. This in turn leads to goiter, maternal, and fetal hypothyroidism. Maternal hypothyroidism

The current open access book on thyroid disorders covers many interesting topics. On the whole, various titles are interesting and provide additional information. I am sure this online

is seen in 2–3%. Thyroid hormone requirement increases by 25–50 μg/day.

book on thyroid disorders will be read by readers with great enthusiasm.

Address all correspondence to: drpgraman@yahoo.com

M.G.M. Medical College, DAVV, lndore, MP, India

**Author details**

4 Thyroid Disorders

Poondy Gopalratnam Raman

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.81129

#### **Abstract**

Congenital hypothyroidism is one of the commonest preventable causes of mental retardation is also the most common congenital endocrine disorder of childhood. The subtlety of clinical features and protective effect of the maternal hormone on fetal brain after crossing the placenta mask the clinical features. The incidence varies from 1 in 4000 to 1 in 1000 in newborn infants in various parts of world and is increasing worldwide. Thyroid agenesis remains the most common etiology of CH and other causes are dyshormonogenesis, defects in peripheral thyroid hormone transport, metabolism, or action. CH is usually diagnosed after neonatal screening tests and if treatment started with in few weeks of birth neurodevelopmental outcome is usually normal. Levothyroxine (T4) remains the treatment of choice as most brain T3 is derived from local monodeiodination of T4 and studies have shown normal serum level of T3 in infant treated with T4 alone.

DOI: 10.5772/intechopen.81129

**Keywords:** congenital, hypothyroidism, levothyroxine, TSH, thyroid

#### **1. Introduction**

Congenital hypothyroidism (CH), one of the commonest preventable causes of mental retar dation is also the most common congenital endocrine disorder of childhood [1]. Neurodevelopmental outcome is usually better if treatment is started within in few weeks of birth [2]. The subtlety of clinical features and the maternal hormone crossing the placenta provides a protective effect on the fetal brain masking the clinical signs [3]. In addition to this even the most severe forms of CH have some functioning residual thyroid tissue further making clinical diagnosis difficult [4]. As the age of the neonate progresses so does the hypothyroxinemia leading to progression of the clinical signs and symptoms which increases the risk for irreversible brain injury. To prevent this, treatment needs to be started as soon as possible after

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

birth. For all the above reasons, screening has evolved as the best way to detect infants with CH in developed countries. In North America, more than 1400 infants out of the 5 million newborns screened are diagnosed with CH annually.

transport (mutations in monocarboxylase transporter 8), metabolism (selenocysteine insertion sequencebinding protein 2), or resistance to action (mutations of thyroid hormone receptor) are some rare causes. Among the aforementioned defects, mutations of the thyroid peroxidase (TPO) gene form the most prevalent cause of inherited defects in CH [24]. The incidence of thyroid dyshormonogenesis has been increasing and now accounts for 30–40% case of CH

Congenital Hypothyroidism

7

http://dx.doi.org/10.5772/intechopen.81129

Maternal thyrotropin receptor–blocking antibodies, exposure to maternal antithyroid medications, iodine deficiency or iodine excess are the major causes of transient CH in children.

Central congenital hypothyroidism is rare and is usually associated with and is usually associated with developmental anomaly of the pituitary gland and is usually associated with other pituitary hormone deficiencies like adrenocorticotropin and gonadotropins [25]. If isolated, it usually results from a mutation in the thyroid stimulating hormone β TSHβ subunit gene or TRH receptor gene. Less often it is due to mutation in transcription factor gene regulating

In countries with newborn screening programs CH is diagnosed after neonatal screening tests. However, only 25% of the world wide birth population has the access and undergoes the said screening tests [26]. For the remaining 75% infants, particularly concentrated in develop-

48–72 h after birth is the ideal time for the newborn screening tests, the reason being that the physiological surge in TSH that occurs after the first hours after birth to a peak serum level of 80 mIU/L slowly starts to decrease over the next several days [27]. Sample taken within 48 h of birth may lead to false positive results whereas screening done in very sick newborn or

In case of a critically ill new born, preterm birth or in case of a home delivery sample should be collected by 7 days of age. Capillary blood samples taken by heel prick method are placed on circles of specialize filter paper, dried at room temperature, then sent to a centralized laboratory. Second blood sample taken at 2–4 week is a part of the protocol in some screening programs. The additional incidence of CH based on a second screening at 2 weeks of age is approximately 1 in 30,000 [28, 29]. Preterm and LBW infants, critically ill infants, samesex twins, and infants whose initial screen was performed in the first 24 h of life are some

Earlier the screening protocol for CH was T4 estimation followed by TSH only if t4 was low however with increasing accuracy of TSH assays on small volumes of blood, initial TSH testing has become the sine qua non of most screening protocols [31]. Both methods allow for the detection of most of the infants having CH but each method has its own merits and demerits. Measuring T4 first and then TSH detects some cases of secondary hypothyroidism and

pituitary development i.e. HESX1, LHX3, LHX4, OTX2, SOX3, PIT1 and PROP1 [1].

ing countries, clinical suspicion of hypothyroid leads to thyroid function evaluation.

but thyroid dysgenesis remains the most common cause of CH [12].

**4. Diagnostic evaluation**

**4.1. Newborn thyroid screening protocols**

following blood transfusion may lead to false negative result.

examples where a routine second screening must be performed [30].
