**7. Management**

CH remains the most common preventable cause of mental retardation. Studies have shown that timing and dosing of thyroid hormone replacement are both crucial for neurological outcome. The infant must be rendered euthyroid as early as possible by starting the treatment promptly and at sufficient dose, as there is an inverse relationship between intelligence quotient (IQ) and the age of diagnosis. Despite early diagnosis the neurological outcome may be poor due to delay in starting treatment, lower starting thyroid hormone dosing and severity of the hypothyroidism, which itself correlates with the underlying etiology [39].

#### **7.1. Formulation**

Levothyroxine (lthyroxine) remain the treatment of choice. Although biologically active form is triiodothyronine (T3) but most brain T3 is derived from local monodeiodination of T4. As studies have shown normal serum level of T3 in infant treated with T4 alone, so treatment with T3 is not essential for normal neurological outcome/brain development [40]. Currently, only tablets form of lthyroxine are approved for use owing to inconsistent delivery of liquid formulations. However, in some countries in Europe, lthyroxine suspension is also available and is used to normalize thyroid function.

#### **7.2. Administration**

Crushed levothyroxine (lthyroxine) tablet is mixed with 1–2 ml of breast milk, formula or water and resultant suspension is squirted into cheek pad or put on open nipple for infant to feed. Various substances like such as calcium and iron preparation, soy protein formula, sucralfate, aluminum hydroxide and cholestyramine interfere levothyroxine (lthyroxine) absorption through gut and thus should not be given together [41, 42]. Although, recommendation is to take levothyroxine (lthyroxine) empty stomach but for infant it may not be feasible.

#### **7.3. Dosages**

**6.4. Thyroid receptor antibody**

10 Thyroid Disorders

**6.5. Urinary iodine estimation**

**7. Management**

**7.1. Formulation**

**7.2. Administration**

tion regarding iodine deficiency or excess.

and is used to normalize thyroid function.

Transient CH in children can also be caused by maternal thyroid receptor blocking antibodies TRBAb. Absent radionuclide uptake with small or normal sized eutopic gland suggests transient congenital hypothyroidism as a result of transplacental passage of the antibody from the mother to the child. For confirmation the measurement of serum TRB-Ab in mother and/or

24 h urinary iodine excretion approximates the iodine ingestion. For neonates the normal range is approximately 50–100 mg/24 h. Urinary iodine measurement may provide confirma-

CH remains the most common preventable cause of mental retardation. Studies have shown that timing and dosing of thyroid hormone replacement are both crucial for neurological outcome. The infant must be rendered euthyroid as early as possible by starting the treatment promptly and at sufficient dose, as there is an inverse relationship between intelligence quotient (IQ) and the age of diagnosis. Despite early diagnosis the neurological outcome may be poor due to delay in starting treatment, lower starting thyroid hormone dosing and severity

Levothyroxine (lthyroxine) remain the treatment of choice. Although biologically active form is triiodothyronine (T3) but most brain T3 is derived from local monodeiodination of T4. As studies have shown normal serum level of T3 in infant treated with T4 alone, so treatment with T3 is not essential for normal neurological outcome/brain development [40]. Currently, only tablets form of lthyroxine are approved for use owing to inconsistent delivery of liquid formulations. However, in some countries in Europe, lthyroxine suspension is also available

Crushed levothyroxine (lthyroxine) tablet is mixed with 1–2 ml of breast milk, formula or water and resultant suspension is squirted into cheek pad or put on open nipple for infant to feed. Various substances like such as calcium and iron preparation, soy protein formula, sucralfate, aluminum hydroxide and cholestyramine interfere levothyroxine (lthyroxine) absorption through gut and thus should not be given together [41, 42]. Although, recommendation is to take levothyroxine (lthyroxine) empty stomach but for infant it may not be feasible.

of the hypothyroidism, which itself correlates with the underlying etiology [39].

infant may be done by a thyrotropinbinding inhibitor immunoglobulin (TBII) assay.

For the optimal neurodevelopmental outcome, the treatment goal is to normalize T4 and TSH within 2 and 4 weeks respectively [33, 43, 44]. In a study infants had significant lower cognitive, attention and achievement scores who took more than 2 weeks to normalize thyroid function compared to infants who attained normal thyroid function at 1 or 2 weeks of treatment [45]. Adequacy and the timing of treatment determines optimal neurodevelopmental outcome and thus American academy of pediatrics and European society of pediatric endocrinology recommend 10–15 μgm/kg/day as initial dose [46]. Studies show that this dose normalizes serum T4 within 3 days and TSH within 2–4 weeks. To achieve these goals, it is important to start higher initial dose of the recommended range in case of severe CH. In a study infants who were started on higher initial doses of 50 μgm had fullscale IQ scores 11 points higher than those started on lower initial doses of 37.5 μgm [45].

#### **7.4. Target concentrations**

The target T4 concentrations lies in the upper half of reference range according to the Guidelines issued by the American academy of pediatrics and European society for pediatric endocrinology [30, 47–49]. Target values for T4 being 10–16 μgm/dl; FT4 1.4–2.3 ng/dl and TSH <5 μU/dl (optimally 0.5–2.0 μU/dl) for initial 3 years of life following this T4 should be kept in the upper half of normal range. Low IQ in infants with T4 concentration below 10 μgm/dl and TSH above 15 μU/dl was seen during the first year of life compared to those had serum T4 more than 10 μgm/dl [50]. Better intellectual outcome in children with CH was seen with higher doses of levothyroxine (lthyroxine) [51]. Contrary to this other studies have shown behavior problems like increased anxiety, social withdrawal and poor concentration with higher doses in children at age of 8 years. Thus demonstrating potential dangers of overtreatment with levothyroxine in CH children [52].
