10-Year-Old Girl With Abnormal Thyroid Indices

Question

A 10-year- old girl presented, complaining of fatigue. Her lab results showed T₄ 1.8 mcg/dL and thyroid stimulating hormone (TSH) > 400 mIU/L. What would you recommend for the initial work-up of this patient? What would be used for the initial thyroid replacement?

Response from Alan M. Schindler, MD

Most 10-year-old children have more energy than their parents can easily contend with, so a continuing complaint or observation of "fatigue" is disturbing and should prompt an investigation of physical and/or psychosocial problems that might manifest as fatigue. A history of the child's general health, behavior, and social interactions (both within and outside the home) can give important clues. The physical examination and the pattern of the child's growth and development complement the history and may yield a specific diagnosis.

Some children complaining of fatigue will be hypothyroid. Hypothyroidism tends to develop insidiously. A gradual loss of energy or interest in previous activities, slowing rate of growth/sexual development with continuing weight gain, changes in facial and other somatic features including a goiter, or constitutional symptoms of cold intolerance, constipation, or dry skin may go unnoticed by a family for some time. These typical signs and symptoms of hypothyroidism may be subtle or absent, so it makes sense to evaluate thyroid function in the child who complains of fatigue.

Almost all children with acquired hypothyroidism have autoimmune lymphocytic (Hashimoto) thyroiditis. Lymphocytic infiltration of the thyroid gland slowly destroys the gland's ability to produce thyroid hormone. Blood levels of total thyroxine (T₄) and free-T₄ gradually decrease. In response, hypothalamic thyrotropin-releasing hormone and pituitary thyrotropin (ie, thyroid stimulating hormone, or TSH) increase to try to stimulate the impaired thyroid gland. Eventually, there is enough destruction of the gland that the person becomes clinically hypothyroid with low T₄, low free-T₄, and high TSH, as in the case presented.

To investigate and manage the child with low T₄ and high TSH, one should assess, record, and follow physical findings related to hypothyroidism, including the size and texture of the thyroid gland, which can span the gamut from practically nonpalpable, to uniformly enlarged, to nodular. Imaging studies and/or biopsy are usually not necessary unless a single nodule is palpable on physical examination. About 90% of children with lymphocytic thyroiditis have thyroid antiperoxidase or anti-thyroglobulin antibodies in their blood. The presence of these antibodies, which are believed to contribute to the destruction of the thyroid gland, essentially confirm the diagnosis. Less commonly, TSH-receptor blocking antibodies may inhibit the effect of TSH; these are not routinely measured.

Lymphocytic thyroiditis is very common, with a female:male ratio of 2:1 in children and 10:1 in adults. Approximately 1.0%-1.5% of children under age 18 years are affected. The prevalence increases with age. Children with Down syndrome, Turner syndrome, or autoimmune diseases such as type 1 diabetes mellitus have a much higher prevalence of lymphocytic thyroiditis and should be tested annually. Initially, most individuals with lymphocytic thyroiditis are asymptomatic or may have a small goiter. Many become hypothyroid over time, with the incidence increasing with age. The earliest indicator of developing hypothyroidism is an increase in TSH with normal T₄ (ie, subclinical hypothyroidism).

Other, much less common causes of acquired hypothyroidism include systemic conditions such as cystinosis and histiocytosis, or therapies such as irradiation and certain medications. The child's history should reveal these conditions.

Treatment of acquired hypothyroidism is straightforward: thyroid hormone replacement with synthetic levothyroxine. The dose is weight/size related, about 100 mcg/m²/day, or 3-4 mcg/kg/day for children and 2 mcg/kg/day for adults. (Start with the lower dose if a child has been hypothyroid for a long time to avoid rapid advance in skeletal maturation.) The medication is available in many dosages as tablets that can be crushed and given with food. Adequacy of therapy is demonstrated by resolution of constitutional symptoms and return of thyroid hormone levels (T₄, free-T₄, TSH) to normal. Thyroid hormone levels should be checked about 4-6 weeks after starting treatment, then every 6-12 months until growth is completed, and then once a year, with the medication dose being adjusted as necessary. One should be aware that a goiter may not completely resolve and that antibodies in the blood will persist.