Successful management of congenital hypothyroidism requires timely confirmation of the diagnosis, accurate interpretation of thyroid function testing, effective treatment and consistent follow-up.

“Severe intellectual impairment typically does not occur in patients who receive the diagnosis and are treated early and adequately,” said Kupper A. Wintergerst, M.D., chief, pediatric endocrinology and director of the Wendy Novak Diabetes Institute, part of Norton Children’s Endocrinology, affiliated with the UofL School of Medicine.

Dr. Wintergerst is the Wendy L. Novak chair of pediatric diabetes care and clinical research.

Levothyroxine therapy (L-T4) should begin promptly with a diagnosis of congenital hypothyroidism to prevent severe intellectual disability, psychomotor dysfunction and impaired growth. If the newborn screen shows thyroid-stimulating hormone greater than 40 mIU/L, treatment should begin before waiting for the results of the confirmatory serum sample.

The infant also should be evaluated without delay by a primary care physician or pediatric endocrinologist to obtain a complete history and physical, and to assess the risk of thyroid-stimulating hormone receptor-blocking antibodies-mediated hypothyroidism.

Dr. Wintergerst is a co-author of “Congenital Hypothyroidism: Screening and Management,” published late last year in Pediatrics, an official peer-reviewed journal of the American Academy of Pediatrics.

“The goal of L-T4 treatment is to support normal neurocognitive development,” Dr. Wintergerst said. “The more quickly we are able to begin successful ongoing treatment of a patient with congenital hypothyroidism, the better the long-term outcome will be.”

Imaging should be performed only if the results will influence clinical management and should never delay treatment. In many cases, imaging does not alter clinical management of patients younger than age 3.

Accurate scintigraphy can be performed only when thyroid-stimulating hormone is elevated, either before L-T4 treatment or within two to three days after initiating treatment. It also can be performed in children older than 3 during a trial off L-T4 therapy.

With isolated primary congenital hypothyroidism, genetic testing is an option when a genetic diagnosis would alter clinical management.

The starting dose of L-T4 is 10 to 15 mcg/kg/day administered once daily. Optimally, this should begin by two weeks of age. Enteral administration of L-T4 tablets, crushed and suspended in human milk, non-soy-containing formula, or water is the treatment of choice, with approximately two to five milliliters per ounce of fluid.

L-T4 can be administered at any time of day in infants as long as the timing is consistent. If enteral administration is not possible, L-T4 can be administered intravenously. Soy, iron, calcium and/or fiber can interfere with L-T4 absorption.

The goal is to normalize serum free thyroxine and thyroid-stimulating hormone within two to four weeks of treatment. A downward adjustment of the dose may be needed after laboratory evaluation to prevent overtreatment.

After initial normalization, serum thyroid-stimulating hormone should be maintained in the age-specific reference range, while free thyroxine should be maintained in the upper half of the age-specific reference range — unless that would adversely affect thyroid-stimulating hormone levels.

Adherence, follow-up and parental education

An important aspect of managing congenital hypothyroidism is parental education on the importance of adherence to the treatment plan, including regular follow-up care.

“Many children with congenital hypothyroidism are lost to follow-up, which has negative consequences for their development,” Dr. Wintergerst said.

Patients should be evaluated every two weeks after the initiation of L-T4 treatment until serum thyroid-stimulating hormone levels are normal. Subsequently, they should be evaluated every one to two months until they are 6 months old and then every two to three months until age 1. From age 1 to age 3, they should be seen every three to four months.

After age 3, they should be evaluated every six to 12 months until they are adults. Monitoring thyroid-stimulating hormone is sufficient. Free thyroxine can be measured if medication adherence is a concern. They should be seen within four to six weeks of any change in L-T4 dosage.

At age 3, permanent congenital hypothyroidism can be confirmed by discontinuing L-T4 for four weeks, then measuring serum thyroid-stimulating hormone and free thyroxine levels.

Patients with permanent congenital hypothyroidism should remain on lifelong L-T4 therapy.