Solitary Thyroid Nodule Clinical Presentation
- Author: Andre Hebra, MD; Chief Editor: Stephen Kemp, MD, PhD more...
Most patients with a thyroid nodule have an asymptomatic neck mass, usually discovered by a parent or a pediatrician on routine examination. Upon evaluation, close attention should be paid to the presence of symptoms, the course of development of the mass, family history, and exposure to x-rays.
A history of head and neck irradiation increases the risk of nodularity and malignancy. This correlation is well-documented. Although the use of head and neck irradiation for benign conditions has decreased, this factor remains important, especially in patients with prior malignancies.
A family history of thyroid disease, benign or malignant, can be found in a significant number of patients with thyroid cancer and may help determine which patients have an increased risk. However, family history of thyroid disease also increases risk for autoimmune thyroiditis, and malignancy should not be assumed automatically.
Characteristics of the nodule
The history of the mass should be reviewed carefully. Time of initial appearance, rate of growth, and any associated symptoms especially can assist the clinician in determining the malignancy potential of the mass.
Rapid growth is an indicator of malignancy. Therefore, further diagnostic tests should be expediently obtained.
Transient tenderness within the mass at any time may signify an inflammatory process. However, this same symptom may also be caused by tumor hemorrhage, necrosis, or cyst formation. This information can be used to assist the clinician in determining malignancy of the mass.
Although most patients are asymptomatic, some exhibit evidence of altered levels of thyroid hormones or nerve involvement.
Symptoms of hyperthyroidism include nervousness, heat intolerance, diarrhea, muscle weakness, and loss of weight and appetite.
Hypothyroidism may result in cold intolerance, constipation, fatigue, and weight gain, which, in children, is primarily caused by the accumulation of myxedematous fluid.
Signs and symptoms of local nerve involvement should trigger rapid investigation because it may be indicative of local invasiveness from malignancy. The most important of these signs are dysphagia and hoarseness.
Obtaining a thorough history can be helpful for assessing malignancy and determining the need for surgery and/or medical therapy.
In patients with a thyroid mass, careful physical examination is a key step in evaluating malignancy. Most patients are asymptomatic, but exophthalmos rarely may be present in a person with a hyperfunctioning nodule. In one study, 55% of pediatric patients with thyroid cancer had no other symptoms than a neck mass, whereas 23% had only neck and cervical masses. Therefore, the lack of symptoms should not preclude thorough evaluation.
Careful examination of the neck reveals the nature, location, and tenderness of the mass; fixation of the thyroid to surrounding tissue; and the presence of other cervical masses, which can be metastases or lymphadenopathy.
Benign masses are usually movable, soft, and nontender. Malignancy is associated with a hard nodule, fixation to surrounding tissue, and regional lymphadenopathy. See the image below.
Suspicions of cancer rise in incidents of a true solitary thyroid nodule, especially if designated as cold on scintigraphy. Reported rapid growth or recurrent laryngeal nerve dysfunction found on examination may indicate malignancy and local infiltration.
Finally, if medullary carcinoma is suspected in conjunction with multiple endocrine neoplasia (MEN) 2B, multiple mucosal neuromas, marfanoid body habitus, and skeletal defects may also be evident.
Many risk factors are associated with the development of thyroid nodules and cancer. A family history of thyroid disease, benign or malignant, significantly increases risk. Fowler et al found that a family history of thyroid disease was present in 41% of their patients with thyroid nodules. A family history of endocrine tumors also has been shown to increase risk, especially in persons with MEN. Increased risk has been found in some endemic areas, although environmental reasons have not been elucidated fully. In the pediatric population, pubertal girls are more likely to develop a thyroid nodule, although the risk of malignancy in these individuals is lower than that in boys. Thyroid disease has also been associated with familial polyposis syndrome.
Exposure to certain carcinogens predisposes patients to the development of thyroid disease. Previous head and neck irradiation is the most obvious and well-known risk factor.
In the first half of the 20th century, head and neck irradiation was used widely for treating a number of benign conditions, including acne, tonsillar enlargement, thymic enlargement, and tinea capitis. During this period, the incidence of thyroid nodules in children and the risk of malignancy in the nodules were much higher.
In the 1950s, 70% of thyroid nodules in children harbored malignancy. Fortunately, widespread misuse of irradiation has ceased, and malignancy rates have fallen.
Irradiation is still a factor in children who have received therapeutic radiation for Hodgkin lymphoma, bone marrow transplants, or other malignancies or in those who have been exposed to unusual environmental radiation, such as the Chernobyl accident.
Thyroid tumors may occur as early as 5 years to as late as 40 years after radiation exposure, with a peak at 10-20 years after treatment. Radiation levels as low as 0.1 Gy have been demonstrated to increase the risk of cancer. Nuclear fallout exposure, such as that which occurred at Nagasaki, Hiroshima, and Chernobyl, also significantly increases risk. Children near Chernobyl were 62 times more likely to develop thyroid cancer after the Chernobyl incident than before it occurred. These tumors were especially aggressive, often occurring 4-6 years after exposure.
A history of other malignancy may also increase risk for thyroid cancer. Alkylating agents have been associated with the development of thyroid nodules and malignancy. In addition, thyroid cancer comprises 9% of all second malignancies, most often associated with Hodgkin lymphoma. The mean age at incidence of second malignancies is 20 years.
Several genetic markers are under investigation for their association with thyroid tumors. Papillary tumors are more likely to demonstrate abnormalities on chromosome arm 10q, whereas follicular tumors more often involve chromosome 3.
The ras proto-oncogene is present in 80% of follicular tumors and often is present in follicular adenomas. It is also found in 20% of papillary tumors, and the presence of p21 ras is considered a prognostic indicator.
The ret proto-oncogene is associated with papillary tumors and medullary cancer, both familial and nonfamilial. It may be induced directly by radiation exposure. The presence of ret mutations in patients with family histories of MEN 2 is an indication for prophylactic thyroidectomy.
Finally, mutations in the thyroid-stimulating hormone (TSH)-receptor gene have been associated with the development of papillary tumors. As genetic research continues, the actual cause of thyroid tumors may become more evident.
Kihara M, Hirokawa M, Masuoka H, Yabuta T, Shindo H, Higashiyama T, et al. Evaluation of cytologically benign solitary thyroid nodules by ultrasonography: A retrospective analysis of 1877 cases. Auris Nasus Larynx. 2012 Oct 23. [Medline].
Raval MV, Browne M, Chin AC, et al. Total thyroidectomy for benign disease in the pediatric patient--feasible and safe. J Pediatr Surg. 2009 Aug. 44(8):1529-33. [Medline].
Desjardins JG, Khan AH, Montupet P, et al. Management of thyroid nodules in children: a 20-year experience. J Pediatr Surg. 1987 Aug. 22(8):736-9. [Medline].
Hung W, Anderson KD, Chandra RS, et al. Solitary thyroid nodules in 71 children and adolescents. J Pediatr Surg. 1992 Nov. 27(11):1407-9. [Medline].
Hung W. Solitary thyroid nodules in 93 children and adolescents. a 35-years experience. Horm Res. 1999. 52(1):15-8. [Medline].
Chiesa F. Thyroid disease in northern Italian children born around the time of the Chernobyl nuclear accident. Annals of Oncology. 2004. 15:1842-6. [Medline].
Newman KD, Black T, Heller G, Azizkhan RG, Holcomb GW 3rd, Sklar C, et al. Differentiated thyroid cancer: determinants of disease progression in patients 1111111111111111Ann Surg</i>. 1998 Apr. 227(4):533-41. [Medline].
Bouhabel S, Payne RJ, Mlynarek A, Hier M, Caglar D, Tamilia M. Are solitary thyroid nodules more likely to be malignant?. J Otolaryngol Head Neck Surg. 2012 Apr. 41(2):119-23. [Medline].
Fowler CL, Pokorny WJ, Harberg FJ. Thyroid nodules in children: current profile of a changing disease. South Med J. 1989 Dec. 82(12):1472-8. [Medline].
Al-Shaikh A, Ngan B, Daneman A, Daneman D. Fine-needle aspiration biopsy in the management of thyroid nodules in children and adolescents. J Pediatr. 2001 Jan. 138(1):140-2. [Medline].
Lugo-Vicente H, Ortiz VN, Irizarry H, et al. Pediatric thyroid nodules: management in the era of fine needle aspiration. J Pediatr Surg. 1998 Aug. 33(8):1302-5. [Medline].
Millman B, Pellitteri PK. Nodular thyroid disease in children and adolescents. Otolaryngol Head Neck Surg. 1997 Jun. 116(6 Pt 1):604-9. [Medline].
Bentley AA, Gillespie C, Malis D. Evaluation and management of a solitary thyroid nodule in a child. Otolaryngol Clin North Am. 2003 Feb. 36(1):117-28. [Medline].
Bukhari MH. An updated audit of fine needle aspiration cytology procedure of solitary thyroid nodule. Diagn Cytopathol. 2008. 36:104-12. [Medline].
Canadian Pediatric Thyroid Nodule (CaPTN) Study Group. The Canadian Pediatric Thyroid Nodule Study: an evaluation of current management practices. J Pediatr Surg. 2008. 43:826-30. [Medline].
Cotran RS, Kumar V, Robbins SL. The thyroid. Robbins Pathologic Basis of Disease. 5th ed. 1994. 1121-42.
Dreimane D, Varma SK. Common childhood thyroid disorders. Indian J Pediatr. 1997 Jan-Feb. 64(1):3-10. [Medline].
Fisher DA. The thyroid gland. Clinical Paediatric Endocrinology. 1989. 309-37.
Flannery TK, Kirkland JL, Copeland KC, et al. Papillary thyroid cancer: a pediatric perspective. Pediatrics. 1996 Sep. 98(3 Pt 1):464-6. [Medline].
Herrmann MA, Hay ID, Bartelt DH Jr, et al. Cytogenetic and molecular genetic studies of follicular and papillary thyroid cancers. J Clin Invest. 1991 Nov. 88(5):1596-604. [Medline].
[Guideline] Iqbal CW, Wahoff DC. Diagnosis and management of pediatric endocrine neoplasms. Curr Opin Pediatr. 2009 Jun. 21(3):379-85. [Medline].
Loh KC, Greenspan FS, Gee L, et al. Pathological tumor-node-metastasis (pTNM) staging for papillary and follicular thyroid carcinomas: a retrospective analysis of 700 patients. J Clin Endocrinol Metab. 1997 Nov. 82(11):3553-62. [Medline].
Lugo-Vicente H, Ortiz VN. Pediatric thyroid nodules: insights in management. Bol Asoc Med P R. 1998 Apr-Jun. 90(4-6):74-8. [Medline].
Niedziela M. Pathogenesis, diagnosis and management of thyroid nodules in children. Endocr Relat Cancer. 2006. 13:427-53. [Medline].
Sclafani AP, Valdes M, Cho H. Hashimoto's thyroiditis and carcinoma of the thyroid: optimal management. Laryngoscope. 1993 Aug. 103(8):845-9. [Medline].
Stevens C, Lee JK, Sadatsafavi M, Blair GK. Pediatric thyroid fine-needle aspiration cytology: a meta-analysis. J Pediatr Surg. 2009. 44:2184-91.
Stezhko VA, Buglova EE, Danilova LI. A cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: objectives, design and methods. Radiat Res. 2004 Apr. 161(4):481-92. [Medline].
Takahashi T, Fujimori K, Simon SL. Thyroid nodules, thyroid function and dietary iodine in the Marshall islands. Int J Epidemiol. 1999 Aug. 28(4):742-9. [Medline].
Tucker ME. Radiofrequency Bests Laser for Ablation of Thyroid Nodules. Medscape Medical News. May 8, 2013. Available at http://www.medscape.com/viewarticle/803790. Accessed: May 15, 2013.
Walfish PG, Tseng KH. Thyroid physiology and pathology. Pediatric Endocrinology. 1989. 367-448.
Yip FW, Reeve TS, Poole AG. Thyroid nodules in childhood and adolescence. Aust N Z J Surg. 1994 Oct. 64(10):676-8. [Medline].