The Pediatric Page
Thyroid Disorders in Children: A Brief Synopsis - January 2005
Congenital hypothyroidism is an important cause of preventable mental retardation. Most newborn screening programs measure thyroid-stimulating hormone (TSH) and the preferred sampling time is at age 3-5 days. Earlier sampling increases the rate of false-positive results. The prevalence of congenital hypothyroidism is approximately 1 in 4,000 births. Etiologies include thyroid dysgenesis (75%), thyroid dyshormonogenesis (10%), TSH deficiency (5%) and transient hypothyroidism (10%, usually iodine, drug or maternal antibody induced).
Confirmatory diagnosis is based on measurement of T4 (low) and TSH (high). Optional studies include ultrasound and radionucleotide scan. Fewer than 5% of infants are diagnosed on clinical grounds before the screening report. Subtle manifestations of hypothyroidism include a large posterior fontanelle, prolonged jaundice, macroglossia, hoarse cry, distended abdomen, umbilical hernia, hypotonia or goiter. Treatment with L-thyroxine (75-100-mcg/m2/d) must be initiated as soon as the diagnosis is suspected. Delayed treatment is associated with a diminished mean IQ.
Hashimoto thyroiditis (autoimmune hypothyroidism, chronic lymphocytic thyroiditis) is an autoimmune, inflammatory process causing 55-65% of all euthyroid goiters and nearly all cases of hypothyroidism in childhood and adolescence. Prevalence studies have found that as many as 1.2% of school-aged children have chronic lymphocytic thyroiditis as defined by an enlarged thyroid gland and detectable thyroid antibodies in the serum. Females predominate at a ratio of 2:1 with a peak age of onset in mid-puberty. There is a high familial incidence. Hashimoto thyroiditis is rare in children under 4 years. Antibody markers include anti-thyroglobulin and anti-thyroperoxidase antibodies. One or both are present in virtually all patients with Hashimoto’s, but they are not specific for this disorder and may be found in other autoimmune diseases such as Graves’, Addison’s and Type 1 diabetes.
Hashimoto thyroiditis presents in one of three ways: thyromegaly with euthyroidism, toxic thyroiditis, or hypothyroidism with or without thyromegaly. Most patients are asymptomatic and present with a goiter. The gland may be symmetrically or asymmetrically enlarged with a bosselated (cobblestone) texture. Toxic thyroiditis (Hashitoxicosis) is a transient, self-limited form of hyperthyroidism occurring in less than 5% of patients. If hypothyroidism is present, there may be a history of poor growth, fatigue, constipation, mild weight gain, dry skin and cold intolerance.
The initial workup should include measurement of serum free T4, TSH and anti-thyroid antibodies. The incidence of hypothyroidism is 3-13%, but compensated hypothyroidism (normal T4 and high TSH, signifying possible impending hypothyroidism) occurs in up to 35%.
In addition, serum T3 concentration should be determined if the patient appears to have hyperthyroidism.
Treatment for Hashimoto thyroiditis involves L-thyroxine (50-100 mcg/m2/d) to normalize TSH and T4. Long-term follow-up studies indicated that chronic lymphocytic thyroiditis resolves in 50% of children. Replacement therapy should continue until the patient has achieved final adult height. At that time, a trial without medication may be considered. If a child has positive antibodies but is euthyroid, replacement therapy is not necessary; however, thyroid function should be monitored regularly.
Graves’ disease (autoimmune hyperthyroidism) is the autonomous production of excessive thyroid hormones by an usually enlarged thyroid gland. It is the most common cause of hyperthyroidism in children. There is a high familial incidence and females predominate in a 3:1 ratio. The peak incidence occurs during adolescence.
Thyroid-stimulating immunoglobulins (TSI) are present in most patients. These antibodies activate the TSH receptors to stimulate thyroid hormone production and secretion, and cause thyromegaly. Anti-thyroglobulin and anti-thyroperoxidase antibodies are also found in many patients, but in lower levels than in Hashimoto thyroiditis. Graves’ disease and Hashimoto thyroiditis may in fact be a part of a spectrum of the same disease process.
Clinical features include nervousness, irritability, palpitations, tachycardia, tremor, increased appetite with weight loss, diarrhea, difficulty sleeping, heat intolerance, poor school performance, irregular periods and rapid height velocity. Most patients have a goiter. Up to 50% of children with Graves’ disease manifest ophthalmopathy, with lid retraction and stare being the most common signs. Graves dermopathy (pretibial myxedema) in children is rare.
The mainstay of medical management is antithyroid medications with methimazole or propylthiouracil. Both are equally effective at decreasing production of T4 and T3, but propylthiouracil also blocks peripheral conversion of T4 to T3. Side effects are infrequent, but include skin rashes, arthritis, hepatitis and agranulocytosis. Remission of Graves’ disease occurs in 25% of cases over 2 years. If medical treatment must be discontinued because of side effects, relapses, or non-compliance, thyroid ablative therapy or thyroidectomy should be implemented.
Thyroid cancer in children. There is about a 30% chance that a nodule found in a child will be malignant. In children who have had other forms of cancer, there is a 50-fold increased risk of thyroid cancer secondary to the use of radiation therapy. Basic thyroid function tests are usually normal. Fine needle aspiration is the simplest and most direct method to determine the architecture of a thyroid nodule. Thyroid scans can also be helpful in the evaluation of a thyroid nodule. A “cold” area (hypofunctioning) on scan increases the suspicion of malignancy while “hot” (hyperfunctioning) nodules are almost invariably benign.
Papillary cancer is the most common malignant thyroid tumor in children (60-80% of all cases). Pure follicular and medullary carcinomas comprise the remainder of cases. Medullary carcinomas may be sporadic, familial (autosomal dominant), or part of one of the multiple endocrine neoplasia syndromes. Malignant or suspicious lesions require surgical intervention and post-operative ablation with 131I followed by appropriate surveillance.
This information provided by California Pacific Medical Center’s Division of Pediatric Endocrinology.
Saleh Adi, M.D.
Tel. (415) 600-1793
Pager (415) 809-0034