Congenital and acquired goiter in children
- Stephen LaFranchi, MD
Stephen LaFranchi, MD
- Professor of Pediatrics
- Oregon Health & Sciences University
- Section Editors
- Douglas S Ross, MD
Douglas S Ross, MD
- Section Editor — Thyroid Disease
- Professor of Medicine
- Harvard Medical School
- Mitchell E Geffner, MD
Mitchell E Geffner, MD
- Section Editor — Pediatric Endocrinology
- Professor of Pediatrics
- Keck School of Medicine, University of Southern California
Children may have goiters that are diffuse or nodular, and the goiters may be associated with normal, decreased, or increased thyroid hormone production. The causes of goiter in children and adults are similar, but their relative frequency varies substantially. In the United States, for example, most children with a goiter have chronic autoimmune thyroiditis, whereas among adults, nontoxic nodular goiters predominate.
Goiter may be present at birth or detected at any age thereafter. The goiter may be caused by increased thyrotropin (TSH) secretion (acting as a thyroid growth factor) resulting from hypothyroidism; antibodies that activate TSH receptors (Graves' disease) with increased thyroid hormone secretion; or TSH-independent processes, such as inflammation associated with autoimmune thyroiditis, benign and malignant tumors, and infiltrative disease.
Once a goiter is detected, the appropriate diagnostic evaluation is aimed at identifying the underlying cause and assessing thyroid function. Both of these factors will determine management. This topic review will consider congenital and acquired goiters, independent of their function, in infants and children.
Thyroid nodules and cancers, and the causes of hypothyroidism and hyperthyroidism in children are discussed separately. (See "Thyroid nodules and cancer in children" and "Clinical manifestations and diagnosis of hyperthyroidism in children and adolescents" and "Acquired hypothyroidism in childhood and adolescence".)
THYROID SIZE IN INFANTS AND CHILDREN
The mean (±SD) thyroid volume, measured by ultrasonography, in 68 term neonates in Chicago was 0.9 ± 0.2 mL . In an extensive study of 7- to 14-year-old children from an iodine-sufficient area of Italy, the mean thyroid volume increased with age from 3.1 to 6.3 mL (table 1) . Thyroid size correlates with body surface area; among children 6 to 14 years of age, the upper 95th percentile was 6.2 mL per m2 in one series . In a report of 6- to 12-year old children from Japan, where intake of iodine is relatively high (median urinary iodine 281.6 mcg/L), thyroid volumes were smaller, increasing from 1.5 mL to 3.8 mL over this age period . Clinically, we use the "rule of thumb" to evaluate thyroid size in older children: each lobe of the normal thyroid gland is approximately the size of the terminal phalanx of the child's thumb.
- Vade A, Gottschalk ME, Yetter EM, Subbaiah P. Sonographic measurements of the neonatal thyroid gland. J Ultrasound Med 1997; 16:395.
- Aghini-Lombardi F, Antonangeli L, Pinchera A, et al. Effect of iodized salt on thyroid volume of children living in an area previously characterized by moderate iodine deficiency. J Clin Endocrinol Metab 1997; 82:1136.
- Lisböa HR, Gross JL, Orsolin A, Fuchs S. Clinical examination is not an accurate method of defining the presence of goitre in schoolchildren. Clin Endocrinol (Oxf) 1996; 45:471.
- Fuse Y, Saito N, Tsuchiya T, et al. Smaller thyroid gland volume with high urinary iodine excretion in Japanese schoolchildren: normative reference values in an iodine-sufficient area and comparison with the WHO/ICCIDD reference. Thyroid 2007; 17:145.
- Muir A, Daneman D, Daneman A, Ehrlich R. Thyroid scanning, ultrasound, and serum thyroglobulin in determining the origin of congenital hypothyroidism. Am J Dis Child 1988; 142:214.
- Pohlenz J, Rosenthal IM, Weiss RE, et al. Congenital hypothyroidism due to mutations in the sodium/iodide symporter. Identification of a nonsense mutation producing a downstream cryptic 3' splice site. J Clin Invest 1998; 101:1028.
- Nicola JP, Nazar M, Serrano-Nascimento C, et al. Iodide transport defect: functional characterization of a novel mutation in the Na+/I- symporter 5'-untranslated region in a patient with congenital hypothyroidism. J Clin Endocrinol Metab 2011; 96:E1100.
- Spitzweg C, Morris JC. Genetics and phenomics of hypothyroidism and goiter due to NIS mutations. Mol Cell Endocrinol 2010; 322:56.
- Ris-Stalpers C, Bikker H. Genetics and phenomics of hypothyroidism and goiter due to TPO mutations. Mol Cell Endocrinol 2010; 322:38.
- De Marco G, Agretti P, Montanelli L, et al. Identification and functional analysis of novel dual oxidase 2 (DUOX2) mutations in children with congenital or subclinical hypothyroidism. J Clin Endocrinol Metab 2011; 96:E1335.
- Wang F, Lu K, Yang Z, et al. Genotypes and phenotypes of congenital goitre and hypothyroidism caused by mutations in dual oxidase 2 genes. Clin Endocrinol (Oxf) 2014; 81:452.
- Kopp P, Bizhanova A. Clinical and molecular characteristics of Pendred syndrome. Ann Endocrinol (Paris) 2011; 72:88.
- Everett LA, Morsli H, Wu DK, Green ED. Expression pattern of the mouse ortholog of the Pendred's syndrome gene (Pds) suggests a key role for pendrin in the inner ear. Proc Natl Acad Sci U S A 1999; 96:9727.
- Scott DA, Wang R, Kreman TM, et al. The Pendred syndrome gene encodes a chloride-iodide transport protein. Nat Genet 1999; 21:440.
- Soh LM, Druce M, Grossman AB, et al. Evaluation of genotype-phenotype relationships in patients referred for endocrine assessment in suspected Pendred syndrome. Eur J Endocrinol 2015; 172:217.
- Citterio CE, Machiavelli GA, Miras MB, et al. New insights into thyroglobulin gene: molecular analysis of seven novel mutations associated with goiter and hypothyroidism. Mol Cell Endocrinol 2013; 365:277.
- van de Graaf SA, Ris-Stalpers C, Veenboer GJ, et al. A premature stopcodon in thyroglobulin messenger RNA results in familial goiter and moderate hypothyroidism. J Clin Endocrinol Metab 1999; 84:2537.
- Peteiro-Gonzalez D, Lee J, Rodriguez-Fontan J, et al. New insights into thyroglobulin pathophysiology revealed by the study of a family with congenital goiter. J Clin Endocrinol Metab 2010; 95:3522.
- Moreno JC, Klootwijk W, van Toor H, et al. Mutations in the iodotyrosine deiodinase gene and hypothyroidism. N Engl J Med 2008; 358:1811.
- Ribault V, Castanet M, Bertrand AM, et al. Experience with intraamniotic thyroxine treatment in nonimmune fetal goitrous hypothyroidism in 12 cases. J Clin Endocrinol Metab 2009; 94:3731.
- Brown RS, Bellisario RL, Mitchell E, et al. Detection of thyrotropin binding inhibitory activity in neonatal blood spots. J Clin Endocrinol Metab 1993; 77:1005.
- Thomas Jde V, Collett-Solberg PF. Perinatal goiter with increased iodine uptake and hypothyroidism due to excess maternal iodine ingestion. Horm Res 2009; 72:344.
- Paschke R, Ludgate M. The thyrotropin receptor in thyroid diseases. N Engl J Med 1997; 337:1675.
- Nishihara E, Fukata S, Hishinuma A, et al. Prevalence of thyrotropin receptor germline mutations and clinical courses in 89 hyperthyroid patients with diffuse goiter and negative anti-thyrotropin receptor antibodies. Thyroid 2014; 24:789.
- Ringel MD, Schwindinger WF, Levine MA. Clinical implications of genetic defects in G proteins. The molecular basis of McCune-Albright syndrome and Albright hereditary osteodystrophy. Medicine (Baltimore) 1996; 75:171.
- Mastorakos G, Mitsiades NS, Doufas AG, Koutras DA. Hyperthyroidism in McCune-Albright syndrome with a review of thyroid abnormalities sixty years after the first report. Thyroid 1997; 7:433.
- Maiorana R, Carta A, Floriddia G, et al. Thyroid hemiagenesis: prevalence in normal children and effect on thyroid function. J Clin Endocrinol Metab 2003; 88:1534.
- Rallison ML, Dobyns BM, Keating FR, et al. Occurrence and natural history of chronic lymphocytic thyroiditis in childhood. J Pediatr 1975; 86:675.
- Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002; 87:489.
- Popova G, Paterson WF, Brown A, Donaldson MD. Hashimoto's thyroiditis in Down's syndrome: clinical presentation and evolution. Horm Res 2008; 70:278.
- de Vries L, Bulvik S, Phillip M. Chronic autoimmune thyroiditis in children and adolescents: at presentation and during long-term follow-up. Arch Dis Child 2009; 94:33.
- Fava A, Oliverio R, Giuliano S, et al. Clinical evolution of autoimmune thyroiditis in children and adolescents. Thyroid 2009; 19:361.
- Feingold SB, Smith J, Houtz J, et al. Prevalence and functional significance of thyrotropin receptor blocking antibodies in children and adolescents with chronic lymphocytic thyroiditis. J Clin Endocrinol Metab 2009; 94:4742.
- Kambalapalli M, Gupta A, Prasad UR, Francis GL. Ultrasound characteristics of the thyroid in children and adolescents with goiter: a single center experience. Thyroid 2015; 25:176.
- Vlachopapadopoulou E, Thomas D, Karachaliou F, et al. Evolution of sonographic appearance of the thyroid gland in children with Hashimoto's thyroiditis. J Pediatr Endocrinol Metab 2009; 22:339.
- Corrias A, Cassio A, Weber G, et al. Thyroid nodules and cancer in children and adolescents affected by autoimmune thyroiditis. Arch Pediatr Adolesc Med 2008; 162:526.
- Goldfarb M, Gondek SS, Sanchez Y, Lew JI. Clinic-based ultrasound can predict malignancy in pediatric thyroid nodules. Thyroid 2012; 22:827.
- Svensson J, Ericsson UB, Nilsson P, et al. Levothyroxine treatment reduces thyroid size in children and adolescents with chronic autoimmune thyroiditis. J Clin Endocrinol Metab 2006; 91:1729.
- Scarpa V, Kousta E, Tertipi A, et al. Treatment with thyroxine reduces thyroid volume in euthyroid children and adolescents with chronic autoimmune thyroiditis. Horm Res Paediatr 2010; 73:61.
- Brix TH, Kyvik KO, Hegedüs L. Major role of genes in the etiology of simple goiter in females: a population-based twin study. J Clin Endocrinol Metab 1999; 84:3071.
- Hollowell JG, Staehling NW, Hannon WH, et al. Iodine nutrition in the United States. Trends and public health implications: iodine excretion data from National Health and Nutrition Examination Surveys I and III (1971-1974 and 1988-1994). J Clin Endocrinol Metab 1998; 83:3401.
- Caldwell KL, Jones R, Hollowell JG. Urinary iodine concentration: United States National Health And Nutrition Examination Survey 2001-2002. Thyroid 2005; 15:692.
- Cheetham T, Plumb E, Callaghan J, et al. Dietary restriction causing iodine-deficient goitre. Arch Dis Child 2015; 100:784.
- Zimmermann MB, Wegmüller R, Zeder C, et al. The effects of vitamin A deficiency and vitamin A supplementation on thyroid function in goitrous children. J Clin Endocrinol Metab 2004; 89:5441.
- Erdoğan MF, Demir O, Emral R, et al. More than a decade of iodine prophylaxis is needed to eradicate goiter among school age children in a moderately iodine-deficient region. Thyroid 2009; 19:265.
- Boyages SC, Halpern JP, Maberly GF, et al. A comparative study of neurological and myxedematous endemic cretinism in western China. J Clin Endocrinol Metab 1988; 67:1262.
- Friedrich-Rust M, Theobald J, Zeuzem S, Bojunga J. Thyroid function and changes in ultrasound morphology during antiviral therapy with pegylated interferon and ribavirin in patients with chronic hepatitis C. J Viral Hepat 2009; 16:168.
- Shies A, Nemet D, Rathaus V, Eliakim A. Transient hyperthyroidism due to acute suppurative thyroiditis in an adolescent female. J Pediatr Endocrinol Metab 2011; 24:205.
- Xia CX, Li R, Wang ZH, et al. A rare cause of goiter: Langerhans cell histiocytosis of the thyroid. Endocr J 2012; 59:47.
- Nordyke RA, Gilbert FI Jr, Harada AS. Graves' disease. Influence of age on clinical findings. Arch Intern Med 1988; 148:626.
- Schwab KO, Pfarr N, van der Werf-Grohmann N, et al. Autonomous thyroid adenoma: only an adulthood disease? J Pediatr 2009; 154:931.
- Josephson GD, Spencer WR, Josephson JS. Thyroglossal duct cyst: the New York Eye and Ear Infirmary experience and a literature review. Ear Nose Throat J 1998; 77:642.
- Ewing CA, Kornblut A, Greeley C, Manz H. Presentations of thyroglossal duct cysts in adults. Eur Arch Otorhinolaryngol 1999; 256:136.
- Heshmati HM, Fatourechi V, van Heerden JA, et al. Thyroglossal duct carcinoma: report of 12 cases. Mayo Clin Proc 1997; 72:315.
- Rath SR, Bartley A, Charles A, et al. Multinodular Goiter in children: an important pointer to a germline DICER1 mutation. J Clin Endocrinol Metab 2014; 99:1947.
- THYROID SIZE IN INFANTS AND CHILDREN
- CONGENITAL GOITER
- Inborn errors of thyroid hormone production
- Transplacental passage of maternal thyroid-reactive antibodies
- Maternal ingestion of antithyroid drugs and other goitrogens
- Activating mutations of the TSH-receptor (congenital nonimmune hyperthyroidism)
- Activating mutations of the G-protein alpha subunit (McCune-Albright syndrome)
- Thyroid hemiagenesis
- ACQUIRED GOITER
- Chronic autoimmune (Hashimoto's) thyroiditis
- - Associations
- - Clinical presentation
- - Evaluation
- - Treatment
- Colloid goiter
- Iodine-deficiency goiter
- Ingestion of goitrogens
- Subacute granulomatous thyroiditis
- Acute suppurative thyroiditis
- Thyroid infiltrative disease
- Goiter with hyperthyroidism
- - Graves' disease
- - Toxic adenoma
- Thyroid cysts
- Thyroglossal duct cysts
- Thyroid adenomas or carcinomas
- SUMMARY AND RECOMMENDATIONS