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Treatment and prognosis of congenital hypothyroidism

INTRODUCTION

Congenital hypothyroidism is one of the most common treatable causes of intellectual disability (mental retardation). Screening programs have been established in most developed countries to detect and treat this disorder, which affects approximately 1 in 3000 newborns [1]. (See "Clinical features and detection of congenital hypothyroidism".)

Delays in diagnosis and treatment of congenital hypothyroidism will result in impaired neurocognitive outcome (as measured by intelligence quotient [IQ]). Even after diagnosis, IQ and neurologic development may suffer if the infant has hypothyroidism during the first two to three years of life, a time of critical brain dependence on thyroid hormone. Hypothyroidism in such infants may result from delayed detection and initiation of treatment after birth or from inadequate treatment during the first two to three years of life. Thus, appropriate initial therapy and follow-up are essential.

TREATMENT

The overall goals of treatment are to assure normal growth and development and psychometric outcome similar to genetic potential, by restoring the serum T4 concentration rapidly to the normal range followed by continued clinical and biochemical euthyroidism.

Oral T4 is the treatment of choice. Although triiodothyronine (T3) is the more biologically active hormone, the majority of brain T3 is derived from local deiodination of T4; thus, it is not necessary to use T3. To correct hypothyroxinemia as rapidly as possible, treatment should be initiated in an infant with a clearly positive screening test as soon as confirmatory blood samples have been drawn; treatment should not be delayed by waiting for the results of the confirmatory tests [2]. (See "Clinical features and detection of congenital hypothyroidism", section on 'Newborn screening programs'.)

Dose of T4 — Both the timing and dose of thyroid hormone replacement are important [3-5]. The initial goal of treatment should be to restore the serum T4 concentration to >10 mcg/dL (>129 nmol/L) as rapidly as possible. In one small study, patients who took longer than two weeks to normalize their thyroid function had lower cognitive, attention, and achievement scores than those who achieved normal function within two weeks after therapy was started [3]. In a literature review identifying 11 studies evaluating the age of onset of thyroid hormone treatment, infants started "early" (12 to 30 days of age) had a mean IQ 15.7 points higher than infants started "later" (>30 days of age) [4].
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