Thyroid nodules and cancer 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 Geffner, MD
Mitchell Geffner, MD
- Section Editor — Pediatric Endocrinology
- Professor of Pediatrics
- Keck School of Medicine, University of Southern California
About 2 percent of children have palpable thyroid nodules. Most of these are benign, including inflammatory lesions or follicular adenomas, but a few are malignant.
The thyroid gland in children is particularly susceptible to irradiation and carcinogenesis. This may be one reason that children with thyroid cancer tend to present with advanced disease. As compared with adults, children with thyroid cancer display a greater frequency of lymph node metastases and distant metastases at the time of diagnosis and higher rates of recurrence during the first decade after diagnosis. Despite these characteristics, children with thyroid cancer generally have a good prognosis.
The evaluation of a child presenting with a thyroid nodule, and an overview of the treatment of thyroid carcinoma is discussed in this topic review. Congenital and acquired goiter and thyroid cysts are discussed separately. (See "Congenital and acquired goiter in children".)
In a study conducted in the southwestern United States, thyroid nodules detectable by palpation were present in 1.8 percent of school children between the ages of 11 and 18 years . In a follow-up study 20 years later, nodules were present in only 0.45 percent of the same subjects, showing that nodules disappeared in 75 percent of subjects . In a group of children without suspected thyroid disease who underwent contrast-enhanced computed tomography (CT) of the chest, thyroid nodules were detected in 1.4 percent, which is much lower than the rate of unsuspected thyroid nodules detected on CT in adults .
Most thyroid nodules in children are benign, but the percentage of nodules harboring cancer in children is probably higher than the commonly quoted figure of 5 percent in adults. Estimates of the rate of malignancy in published case series vary widely, ranging from 10 to 50 percent [4,5]. However, it may be that the 10 to 50 percent rate of cancer in childhood nodules reported in the past is higher than would be found in more recent series, particularly in "incidentally discovered" nodules. Indeed, malignancy was discovered in 5.7 percent of the nodules incidentally detected by contrast-enhanced CT in the study cited above, which is similar to the reported malignancy rate for thyroid nodules in adults, and substantially lower than the previously reported malignancy rates for children . The following calculations also would support a lower estimate of the malignancy rate in children: The Surveillance, Epidemiology and End Results (SEER) registry from 1973 through 2004 reported a total of 1753 pediatric patients with thyroid cancer, with an annual incidence of 0.54 cases per 100,000 population . An annual incidence of 0.54 per 100,000 is equivalent to a prevalence of 10 per 100,000 children aged 1 to 18 years. If 1.8 per 100 children have solitary nodules, but only 10 per 100,000 children develop cancer, approximately only 1 in 180 solitary nodules represents thyroid cancer (0.5 percent). Thus, the higher percentages noted above likely represent "referral bias" of children with increased risk factors for thyroid cancer .
- Rallison ML, Dobyns BM, Keating FR Jr, et al. Thyroid nodularity in children. JAMA 1975; 233:1069.
- Rallison ML, Dobyns BM, Meikle AW, et al. Natural history of thyroid abnormalities: prevalence, incidence, and regression of thyroid diseases in adolescents and young adults. Am J Med 1991; 91:363.
- Baez JC, Zurakowski D, Vargas SO, Lee EY. Incidental Thyroid Nodules Detected on Thoracic Contrast-Enhanced CT in the Pediatric Population: Prevalence and Outcomes. AJR Am J Roentgenol 2015; 205:W360.
- Kirkland RT, Kirkland JL, Rosenberg HS, et al. Solitary thyroid nodules in 30 children and report of a child with a thyroid abscess. Pediatrics 1973; 51:85.
- Hung W. Solitary thyroid nodules in 93 children and adolescents. a 35-years experience. Horm Res 1999; 52:15.
- Hogan AR, Zhuge Y, Perez EA, et al. Pediatric thyroid carcinoma: incidence and outcomes in 1753 patients. J Surg Res 2009; 156:167.
- Niedziela M. Pathogenesis, diagnosis and management of thyroid nodules in children. Endocr Relat Cancer 2006; 13:427.
- Vergamini LB, Frazier AL, Abrantes FL, et al. Increase in the incidence of differentiated thyroid carcinoma in children, adolescents, and young adults: a population-based study. J Pediatr 2014; 164:1481.
- Davies SM. Subsequent malignant neoplasms in survivors of childhood cancer: Childhood Cancer Survivor Study (CCSS) studies. Pediatr Blood Cancer 2007; 48:727.
- Taylor AJ, Croft AP, Palace AM, et al. Risk of thyroid cancer in survivors of childhood cancer: results from the British Childhood Cancer Survivor Study. Int J Cancer 2009; 125:2400.
- Sassolas G, Hafdi-Nejjari Z, Casagranda L, et al. Thyroid cancers in children, adolescents, and young adults with and without a history of childhood exposure to therapeutic radiation for other cancers. Thyroid 2013; 23:805.
- Imaizumi M, Ohishi W, Nakashima E, et al. Association of radiation dose with prevalence of thyroid nodules among atomic bomb survivors exposed in childhood (2007-2011). JAMA Intern Med 2015; 175:228.
- Feng X, Milas M, O'Malley M, et al. Characteristics of benign and malignant thyroid disease in familial adenomatous polyposis patients and recommendations for disease surveillance. Thyroid 2015; 25:325.
- Tan MH, Mester J, Peterson C, et al. A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands. Am J Hum Genet 2011; 88:42.
- Bonora E, Tallini G, Romeo G. Genetic Predisposition to Familial Nonmedullary Thyroid Cancer: An Update of Molecular Findings and State-of-the-Art Studies. J Oncol 2010; 2010:385206.
- Gara SK, Jia L, Merino MJ, et al. Germline HABP2 Mutation Causing Familial Nonmedullary Thyroid Cancer. N Engl J Med 2015; 373:448.
- Pellegriti G, Lumera G, Malandrino P, et al. Thyroid cancer in thyroglossal duct cysts requires a specific approach due to its unpredictable extension. J Clin Endocrinol Metab 2013; 98:458.
- Alzahrani AS, Baitei EY, Zou M, Shi Y. Clinical case seminar: metastatic follicular thyroid carcinoma arising from congenital goiter as a result of a novel splice donor site mutation in the thyroglobulin gene. J Clin Endocrinol Metab 2006; 91:740.
- 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.
- Berker D, Isik S, Ozuguz U, et al. Prevalence of incidental thyroid cancer and its ultrasonographic features in subcentimeter thyroid nodules of patients with hyperthyroidism. Endocrine 2011; 39:13.
- Kovatch KJ, Bauer AJ, Isaacoff EJ, et al. Pediatric Thyroid Carcinoma in Patients with Graves' Disease: The Role of Ultrasound in Selecting Patients for Definitive Therapy. Horm Res Paediatr 2015.
- Lazar L, Lebenthal Y, Steinmetz A, et al. Differentiated thyroid carcinoma in pediatric patients: comparison of presentation and course between pre-pubertal children and adolescents. J Pediatr 2009; 154:708.
- Feinmesser R, Lubin E, Segal K, Noyek A. Carcinoma of the thyroid in children--a review. J Pediatr Endocrinol Metab 1997; 10:561.
- Gupta A, Ly S, Castroneves LA, et al. A standardized assessment of thyroid nodules in children confirms higher cancer prevalence than in adults. J Clin Endocrinol Metab 2013; 98:3238.
- Niedziela M, Breborowicz D, Trejster E, Korman E. Hot nodules in children and adolescents in western Poland from 1996 to 2000: clinical analysis of 31 patients. J Pediatr Endocrinol Metab 2002; 15:823.
- Francis GL, Waguespack SG, Bauer AJ, et al. Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid 2015; 25:716.
- Horvath E, Majlis S, Rossi R, et al. An ultrasonogram reporting system for thyroid nodules stratifying cancer risk for clinical management. J Clin Endocrinol Metab 2009; 94:1748.
- Mussa A, De Andrea M, Motta M, et al. Predictors of Malignancy in Children with Thyroid Nodules. J Pediatr 2015; 167:886.
- Corrias A, Einaudi S, Chiorboli E, et al. Accuracy of fine needle aspiration biopsy of thyroid nodules in detecting malignancy in childhood: comparison with conventional clinical, laboratory, and imaging approaches. J Clin Endocrinol Metab 2001; 86:4644.
- Arda IS, Yildirim S, Demirhan B, Firat S. Fine needle aspiration biopsy of thyroid nodules. Arch Dis Child 2001; 85:313.
- Izquierdo R, Shankar R, Kort K, Khurana K. Ultrasound-guided fine-needle aspiration in the management of thyroid nodules in children and adolescents. Thyroid 2009; 19:703.
- Al Nofal A, Gionfriddo MR, Javed A, et al. Accuracy of thyroid nodule sonography for the detection of thyroid cancer in children: systematic review and meta-analysis. Clin Endocrinol (Oxf) 2015.
- Wells SA Jr, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 2015; 25:567.
- Alexander EK, Kennedy GC, Baloch ZW, et al. Preoperative diagnosis of benign thyroid nodules with indeterminate cytology. N Engl J Med 2012; 367:705.
- Nikiforov YE, Ohori NP, Hodak SP, et al. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. J Clin Endocrinol Metab 2011; 96:3390.
- American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009; 19:1167.
- Rachmiel M, Charron M, Gupta A, et al. Evidence-based review of treatment and follow up of pediatric patients with differentiated thyroid carcinoma. J Pediatr Endocrinol Metab 2006; 19:1377.
- Sosa JA, Tuggle CT, Wang TS, et al. Clinical and economic outcomes of thyroid and parathyroid surgery in children. J Clin Endocrinol Metab 2008; 93:3058.
- Rivkees SA, Mazzaferri EL, Verburg FA, et al. The treatment of differentiated thyroid cancer in children: emphasis on surgical approach and radioactive iodine therapy. Endocr Rev 2011; 32:798.
- Hay ID, Gonzalez-Losada T, Reinalda MS, et al. Long-term outcome in 215 children and adolescents with papillary thyroid cancer treated during 1940 through 2008. World J Surg 2010; 34:1192.
- Marti JL, Jain KS, Morris LG. Increased risk of second primary malignancy in pediatric and young adult patients treated with radioactive iodine for differentiated thyroid cancer. Thyroid 2015; 25:681.
- Hung W, Sarlis NJ. Current controversies in the management of pediatric patients with well-differentiated nonmedullary thyroid cancer: a review. Thyroid 2002; 12:683.
- Handkiewicz-Junak D, Wloch J, Roskosz J, et al. Total thyroidectomy and adjuvant radioiodine treatment independently decrease locoregional recurrence risk in childhood and adolescent differentiated thyroid cancer. J Nucl Med 2007; 48:879.
- Luster M, Handkiewicz-Junak D, Grossi A, et al. Recombinant thyrotropin use in children and adolescents with differentiated thyroid cancer: a multicenter retrospective study. J Clin Endocrinol Metab 2009; 94:3948.
- Kuijt WJ, Huang SA. Children with differentiated thyroid cancer achieve adequate hyperthyrotropinemia within 14 days of levothyroxine withdrawal. J Clin Endocrinol Metab 2005; 90:6123.
- Kirk JM, Mort C, Grant DB, et al. The usefulness of serum thyroglobulin in the follow-up of differentiated thyroid carcinoma in children. Med Pediatr Oncol 1992; 20:201.
- American Thyroid Association Guidelines Task Force, Kloos RT, Eng C, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 2009; 19:565.
- Palmer BA, Zarroug AE, Poley RN, et al. Papillary thyroid carcinoma in children: risk factors and complications of disease recurrence. J Pediatr Surg 2005; 40:1284.
- CLINICAL PRESENTATION
- Thyroid function tests
- Thyroid scintigraphy
- Neck ultrasound
- Fine-needle aspiration
- Genetic testing
- Benign thyroid nodules
- Differentiated thyroid cancer (DTC)
- Medullary thyroid carcinoma
- SUMMARY AND RECOMMENDATIONS