Thyroid Nodules Thyroid nodules are a common finding on physical examination and are demonstrated by high frequency ultrasonography in over two-thirds of patients (432). Occasionally such nodules are functional, and clinical and laboratory evaluation should be applied to distinguish these nodules from nonfunctional nodules, which are occasionally malignant. For nonfunctional “cold” nodules, fine-needle biopsy and aspiration are required to rule out malignancy. In the case of indeterminate aspirates, 2% to 20% are malignant; therefore, surgical biopsy often is indicated (433). Molecular diagnosis screening of the BRAF mutation improves the diagnosis of cancer on fine-needle aspiration (434).
Patients with Turner syndrome (and other forms of hypergonadotropic hypogonadism associated with abnormalities of the second sex chromosome) exhibit a high prevalence of autoimmune thyroid disorders. Approximately 50% of adult patients with Turner syndrome have antithyroid peroxidase (anti-TPO) and antithyroglobulin (anti-TG) autoantibodies. Of these patients, approximately 30% will develop subclinical or clinical hypothyroidism. The disorder is indistinguishable from Hashimoto thyroiditis. A susceptibility locus for Graves disease is noted on chromosome X (435). Because of the increased risk of autoimmune thyroid disease, it is recommended that women with Turner syndrome be screened with yearly TSH testing starting at the age of 4 (436).
Down syndrome, caused by an extra chromosome 21, is characterized by an atypical body habitus, mental retardation, cardiac malformations, an increased risk of leukemia, and a reduced life expectancy. The extra chromosome is almost always of maternal origin. Autoimmune thyroid disorders are more common in patients with Down syndrome than in the general population. The gene for autoimmune polyglandular syndrome I (APECED) was mapped to chromosome 21 and is thought to be a transcription factor involved in immune regulation (AIRE). This gene may play a role in the development of autoimmune thyroid disease in these patients (437). Hashimoto thyroiditis is the most common type of thyroid disease in individuals with Down syndrome. Hypothyroidism develops in as many as 50% of patients older than age 40 with Down syndrome. These clinical syndromes and other evidence suggest part of the genetic susceptibility to Hashimoto thyroiditis may reside on chromosomes X and 21. Because of the increased frequency of hypothyroidism associated with Down syndrome, it is recommended to screen individuals at 6 months, 12 months, and then annually thereafter (372).
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