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Thyroid Disorders in Children and Adolescents A Review ONLINE FIRST

Patrick Hanley, MD1,2; Katherine Lord, MD1,2; Andrew J. Bauer, MD1,2
[+] Author Affiliations
1The Thyroid Center, Division of Endocrinology and Diabetes, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
2Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia
JAMA Pediatr. Published online August 29, 2016. doi:10.1001/jamapediatrics.2016.0486
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Importance  Normal thyroid gland function is critical for early neurocognitive development, as well as for growth and development throughout childhood and adolescence. Thyroid disorders are common, and attention to physical examination findings, combined with selected laboratory and radiologic tools, aids in the early diagnosis and treatment.

Objective  To provide a practical review of the presentation, evaluation, and treatment of thyroid disorders commonly encountered in a primary care practice.

Evidence Review  We performed a literature review using the PubMed database. Results focused on reviews and articles published from January 1, 2010, through December 31, 2015. Articles published earlier than 2010 were included when appropriate for historical perspective. Our review emphasized evidence-based management practices for the clinician, as well as consensus statements and guidelines. A total of 479 articles for critical review were selected based on their relevance to the incidence, pathophysiology, laboratory evaluation, radiological assessment, and treatment of hypothyroidism, hyperthyroidism, thyroid nodules, and thyroid cancer in children and adolescents. Eighty-three publications were selected for inclusion in this article based on their relevance to these topics.

Findings  The primary care physician is often the first health care professional responsible for initiating the evaluation of a thyroid disorder in children and adolescents. Patients may be referred secondary to an abnormal newborn screening, self-referred after a caregiver raises concern, or identified to be at risk of a thyroid disorder based on findings from a routine well-child visit. Irrespective of the path of referral, knowledge of the signs and symptoms of hypothyroidism, hyperthyroidism, and thyroid nodules, as well as the general approach to evaluation and management, will help the primary care physician complete an initial assessment and determine which patients would benefit from referral to a pediatric endocrinologist.

Conclusions and Relevance  Early identification and treatment of thyroid disease in children and adolescents is critical to optimize growth and development. The primary care physician plays a critical role in identifying patients at risk. An understanding of risk factors, clinical signs and symptoms, and interpretation of screening laboratories ensures an efficient and accurate diagnosis of these common disorders. Regular communication between the primary care physician and the subspecialist is critical to optimize outcome because the majority of patients with thyroid disorders will require long-term to lifelong medical therapy and/or surveillance.

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Figure 1.
Diagram Summarizing the Biosynthesis of Thyroid Hormone and Correlations With Thyroid Disorders

Thyroid hormone synthesis begins with iodide uptake by thyroid follicular cells via the sodium-iodide symporter (NIS), a protein that is regulated by thyrotropin (thyroid stimulating hormone; [TSH]) as well as iodine status. Iodide is transported across the apical membrane via pendrin and subsequently oxidized by thyroid peroxidase (TPO) using endogenously generated H2O2. The TPO-mediated iodination of tyrosine residues on thyroglobulin (Tg) forms mono- and diiodotyrosines (MIT and DIT), which then couple to form T3 (1 MIT plus 1 DIT) or T4 (2 DITs). T3 and T4 attached to Tg are stored as colloid in the follicular lumen. T3 and T4 are released from the thyroid follicular cell after endocytosis and proteolysis of the Tg-bound T3 and T4. Congenital hypothyroidism may be secondary to mutations in multiple genes associated with thyroid hormone biosynthesis. Autoimmune hypothyroidism (Hashimoto thyroiditis) is usually associated with antibodies against TPO and/or TG. These autoantibodies indicate immune activation against the thyroid gland and damage to thyroid follicular cells. In autoimmune hyperthyroidism (Graves disease), thyroid-stimulating immunoglobulins (TSIs) bind to the TSH receptor resulting in dysregulated overproduction of T3 and T4.

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Figure 2.
Path of Embryologic Descent of the Thyroid Gland and Postembryonic Neck Anatomy

The thyroid gland develops in the pharyngeal floor, the lateral portion from neural crest cells and the larger median portion from the primitive pharynx. It migrates from the foramen cecum through the thyroglossal duct along a path anterior to the hyoid bone, reaching its mature shape and location inferior to the cricoid cartilage by the seventh week of gestation. Failure to complete migration may be secondary to mutations in several genes (Table 1). Aberrant ectopic thyroid tissue may be found anywhere along the path of descent, including within the tongue (lingual thyroid). Persistence of the inferior portion of the thyroglossal duct results in the formation of the pyramidal lobe of the thyroid. Failure of the thyroglossal duct to involute may be associated with formation of a thyroglossal duct cyst, a structure that may harbor aberrant, and even the only, thyroid tissue.

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Figure 3.
Examination of the Thyroid Gland in Pediatric Patients

Examination of the thyroid gland is an important and readily accomplished aspect of a complete pediatric physical examination. The examination follows the important steps of any examination; look (A) and feel and listen (B and C). An enlarged thyroid (goiter) is defined by the ability to visualize the shape of the thyroid gland during physical examination (A and Table 3). Auscultation may be restricted to patients with suspected hyperthyroidism, in which a bruit, a continuous “murmur-like” sound from increased blood flow in the gland, may be appreciated using the bell of the stethoscope. A complete examination of the lateral neck lymph nodes (C) is an important addition to the examination of patients with thyroid nodules because differentiated thyroid cancer frequently metastasizes to lymph nodes in the neck. Palpable symmetric level IIA and IIB lymph nodes are a common finding in pediatric patients but thyroid cancer should be in the differential diagnosis for patients found to have persistent, large, firm lymph nodes in levels III, IV, and V.

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