Basics
Description
Goiter is enlargement of the thyroid gland.
Epidemiology
- The most common cause of pediatric goiter in the United States is chronic lymphocytic thyroiditis.
- The prevalence of goiter in the United States is 3-7%, although the incidence is much higher in regions of iodine deficiency.
- Thyroid cancers make up 0.5-1.5% of all malignancies in children and adolescents.
- Both thyroid tumors and autoimmune thyroid disease are more common in females than males.
Prevalence
World Health Organization (WHO) Global Database on Iodine Deficiency (1993-2003)
- Goiter prevalence globally is 15.8% of the general population.
- Insufficient iodine intake among school-aged children ranges from 10.1% in the Americas to 59.9% in Europe.
- 54 countries had iodine deficiency, 29 countries had excessive iodine intake, and 43 countries achieved optimal iodine intake.
Etiology
- Multinodular goiter (MNG) loci have been identified on chromosome 14q and on chromosome Xp22 and 3q26.
- Germline mutations in DICER1 (chromosome 14q31) have been found in familial MNG-1, with and without ovarian Sertoli-Leydig cell tumors.
- Germline mutation in thyroid transcription factor-1 (TITF-1/NKX2.1) has been found in patients with papillary thyroid carcinoma and a history of multinodular goiter.
- Other genes implicated in simple goiter formation: thyroglobulin, thyroid-stimulating hormone (TSH) receptor, and Na+/I- symporter
- Thyroid peroxidase mutations lead to iodide organification defects and goitrous congenital hypothyroidism.
- Twin and family studies show a modest to major effect of environmental factors, especially iodine deficiency and cigarette smoking.
- Excessive maternal ingestion of iodine during pregnancy can lead to congenital goiter with increased iodine uptake on scan and in some babies, a transient hypothyroidism.
- Autoimmune goiters, such as chronic lymphocytic thyroiditis, occur in children with a genetic predisposition.
- Thyroid cancers are usually sporadic. Medullary carcinoma can be familial (autosomal dominant), as part of multiple endocrine neoplasia (MEN) type 2A and 2B, or as isolated malignancy.
- Pendred syndrome (autosomal recessive) causes congenital sensorineural deafness and an iodine organification defect that leads to goiter.
Diagnosis
History
- Symptoms of hypothyroidism:
- Increase in sedentary behavior
- Lethargy
- Weight gain
- Constipation
- Cold intolerance
- Dry skin and/or hair
- Hair loss
- Symptoms of hyperthyroidism:
- Hyperactivity
- Irritability
- Difficulty concentrating or focusing in school
- Hyperphagia
- Weight loss
- Diarrhea
- Heat intolerance
- Careful dietary and medication history
- History of head, neck, or chest irradiation is associated with increased risk of carcinoma.
- Family history of thyroid carcinoma or MEN syndrome
Physical Exam
Inspect, palpate, and auscultate the neck:
- Neck extension aids inspection.
- Palpation is best performed standing behind the child:
- Determine if the thyroid is diffusely enlarged or asymmetric, evaluate gland firmness, and assess for any nodularity.
- Check for cervical lymphadenopathy.
- Pain on palpation suggests acute inflammation.
- Auscultate with the stethoscope diaphragm (while patient holds his or her breath) for a bruit, which indicates hyperthyroidism-associated hypervascularity.
- Careful examination for signs of hypothyroidism or hyperthyroidism
- Linear growth and weight pattern
- Pulse
- Sexual development
- Deep tendon reflexes
- Skin
- Have patient drink water during inspection of gland.
Diagnostic Tests & Interpretation
- Thyroid function tests: Total T4 and TSH are best screens for hypothyroidism or hyperthyroidism.
- T3 radioimmunoassay in cases of suspected hyperthyroidism (note: radioimmunoassay, which measures total T3, and not resin uptake, which indirectly assesses thyroid hormone-binding capacity)
- In cases of suspected chronic lymphocytic thyroiditis: antithyroglobulin and antimicrosomal (antiperoxidase) antibodies
- In cases of suspected Graves disease: thyroid-stimulating immunoglobulins (or TSH-receptor antibodies)
- Fine-needle aspiration biopsy in children should be considered only for evaluation of low-risk or purely cystic thyroid nodules. (A higher percentage of solitary thyroid nodules are malignant in children compared with adults.)
- Calcitonin levels: elevated in 75% of patients with medullary thyroid carcinoma
Lab
Urinary iodine (UI) concentration is the best measure of the adequacy of iodine intake.
Imaging
- Ultrasound to determine the number, size, and nature (cystic, solid, or mixed) of nodules
- 123I thyroid scans in cases of solitary nodules to establish whether the nodule concentrates iodide
- "Cold" nodules (no I uptake) suggest neoplasia and require immediate evaluation by a pediatric endocrinologist and surgeon.
- Barium swallow studies can reveal a fistulous tract between the left piriform sinus and the left thyroid lobe in children with recurrent acute suppurative thyroiditis. Such fistulas are amenable to surgical resection.
Differential Diagnosis
- Fat neck
- Adipose tissue
- Large sternocleidomastoid muscles
- Thyroglossal duct cysts
- Nonthyroidal neoplasms: lymphoma, teratoma, hygroma, ganglioneuroma
- Immunologic
- Chronic lymphocytic thyroiditis (often referred to as Hashimoto thyroiditis)
- Graves disease
- Amyloid deposition (familial Mediterranean fever, juvenile rheumatoid arthritis)
- Infectious
- Acute suppurative thyroiditis (most often Streptococcus pyogenes, Staphylococcus aureus, and Streptococcus pneumoniae)
- Subacute thyroiditis (often viral)
- Environmental
- Goitrogens: iodide, lithium, amiodarone, oral contraceptives, perchlorate, cabbage, soybeans, cassava, thiocyanate in tobacco smoke (smoking is especially goitrogenic in iodine-deficient areas)
- Iodine deficiency (exacerbated by pregnancy)
- Neoplastic
- Thyroid adenoma/carcinoma
- Follicular adenoma: benign
- Follicular, papillary, or mixed carcinoma: well-differentiated; follicular 90%
- Medullary carcinoma: 4-10% as part of the MEN type 2 syndrome
- TSH-secreting adenoma
- Lymphoma
- Congenital
- Ectopic gland
- Unilateral agenesis of gland
- Dyshormonogenesis
- T4 resistance
- Miscellaneous:
- Simple colloid goiter
- Multinodular goiter
Treatment
Alert
Possible conflicts: In manic depressive patients on lithium and cardiac patients on amiodarone, medication-induced thyroid abnormalities can be a significant problem that should be addressed by the endocrinologist and appropriate subspecialist.
Medication
- Goiters with hypothyroidism: l-thyroxine
- Goiter with hyperthyroidism: Treatment consists of antithyroid drugs (methimazole); if remission is not achieved after 1 or 2 years, radioactive iodine ablation (131I) or surgery (near-total or total thyroidectomy) may be considered.
- Duration depends on the cause of the goiter.
Alert
FDA issued a black box warning (6/4/2009) against propylthiouracil (PTU) use in treating Graves disease owing to risk of severe liver injury including life-threatening acute liver failure.
Additional Therapies
Additional Therapies
Intraamniotic injections of l-thyroxine may treat fetal goitrous hypothyroidism. Large fetal goiters pose a risk of airway compromise at birth.
Surgery/Other Procedures
- Surgery solely to decrease size of goiter indicated only if adjacent structures are compressed.
- Rates of complications after pediatric total thyroidectomy are similar for benign and malignant thyroid diseases; most common is transient hypocalcemia.
- Cancer
- Surgery is recommended for a nonfunctioning nodule if there is:
- A history of radiation
- Rapid growth of a firm nodule
- Evidence of satellite lymph nodes
- Evidence of impingement on other neck structures
- Evidence of distant metastases
- Following surgery, radioiodide therapy is administered if a follow-up iodine scan reveals any residual tissue or metastases.
- Suppressive doses of exogenous thyroid hormone are then given to maintain TSH levels <0.2 mIU/L.
- Thyroglobulin levels are useful as markers of thyroid tissue; calcitonin level serves as tumor marker for medullary carcinoma.
Ongoing Care
Follow-up Recommendations
- Potential for goiter regression depends on its cause. Goiters associated with chronic lymphocytic thyroiditis and Graves disease may or may not decrease in size with treatment.
- A goiter patient who is clinically and biochemically euthyroid still requires careful follow-up for the detection of the early signs of developing thyroid dysfunction.
- Potential complications of thyroid surgery include laryngeal nerve damage and hypoparathyroidism. Complication rates are lower in high-volume centers.
- Long-term follow-up of patients with thyroid cancer is recommended, as disease can recur decades after initial diagnosis and therapy.
Alert
- Work up solitary thyroid nodules aggressively. Remember: Incidence of malignancy in these nodules in children is 15-40% (less in adults).
- Malignancy is more likely in euthyroid pediatric patients with nodules that have palpable lymph nodes, compressive signs, microcalcifications, intranodular vascularization, and lymph node alterations.
- Differentiated thyroid carcinoma in prepubertal children, compared to pubertal adolescents, has a more aggressive presentation and more frequently a family history of thyroid carcinoma.
Diet
- Depends on the cause of the goiter
- Incidence of iodine deficiency (endemic) goiter has greatly declined since the addition of potassium iodide to table salt.
- Iodide can also be added to communal drinking water or administered as iodized oil in isolated rural areas.
Prognosis
- Depends on the cause of the goiter
- Thyroid cancers usually follow an indolent course with excellent prognosis, especially the well-differentiated follicular cell carcinoma. Mortality is most common in medullary and undifferentiated carcinomas, which are relatively rare in children.
Complications
- Depending on gland size, goiters can produce a mass effect on midline neck structures. If the goiter is intrathoracic, it may cause pleural effusions or chylothorax.
- Typically, the child is euthyroid, but clinical hypothyroidism or hyperthyroidism may result from certain types of goiters.
- Therapy for thyroid cancer may induce permanent hypothyroidism.
Additional Reading
- Aghini Lombardi F, Fiore E, Tonacchera M, et al. The effect of voluntary iodine prophylaxis in a small rural community: the Pescopagano survey 15 years later. J Clin Endocrinol Metab. 2013;98(3):1031-1039. [View Abstract]
- Corrias A, Mussa A, Baronio F, et al. Diagnostic features of thyroid nodules in pediatrics. Arch Pediatr Adolesc Med. 2010;164(8):714-719. [View Abstract]
- Hashimoto H, Hashimoto K, Suehara N. Successful in utero treatment of fetal goitrous hypothyroidism: case report and review of the literature. Fetal Diagn Ther. 2006;21(4):360-365. [View Abstract]
- 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(5):708-714. [View Abstract]
- Raval MV, Browne M, Chin AC, et al. Total thyroidectomy for benign disease in the pediatric patient-feasible and safe. J Pediatr Surg. 2009;44(8):1529-1533. [View Abstract]
- Rivkees SA. Pediatric Graves' disease: controversies in management. Horm Res Paediatr. 2010;74(5):305-311. [View Abstract]
- 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(6):798-826. [View Abstract]
- Stevens C, Lee JK, Sadatsafavi M, et al. Pediatric thyroid fine-needle aspiration cytology: a meta-analysis. J Pediatr Surg. 2009;44(11):2184-2191. [View Abstract]
- Zimmermann MB, Hess SY, Molinari L, et al. New reference values for thyroid volume by ultrasound in iodine-sufficient schoolchildren: a World Health Organization/Nutrition for Health and Development Iodine Deficiency Study Group report. Am J Clin Nutr. 2004;79(2):231-237. [View Abstract]
Codes
ICD09
- 240.9 Goiter, unspecified
- 241.1 Nontoxic multinodular goiter
- 245.2 Chronic lymphocytic thyroiditis
- 246.1 Dyshormonogenic goiter
- 242.00 Toxic diffuse goiter without mention of thyrotoxic crisis or storm
ICD10
- E04.9 Nontoxic goiter, unspecified
- E04.2 Nontoxic multinodular goiter
- E06.3 Autoimmune thyroiditis
- E03.0 Congenital hypothyroidism with diffuse goiter
- E05.00 Thyrotoxicosis w diffuse goiter w/o thyrotoxic crisis
SNOMED
- 3716002 Goiter (disorder)
- 237570007 multinodular goiter (disorder)
- 21983002 Hashimoto thyroiditis (disorder)
- 217710005 Congenital iodine deficiency syndrome (disorder)
- 237536006 Lymphocytic thyroiditis - autoimmune (disorder)
- 353295004 Graves' disease (disorder)
FAQ
- Q: Does a bigger thyroid gland mean increased thyroid functioning?
- A: Goiters can be euthyroid, hypothyroid, or hyperthyroid, depending on cause.
- Q: Will the goiter decrease in size with treatment?
- A: This depends on the cause of the goiter.
- Q: Does a bigger thyroid gland mean cancer?
- A: Most pediatric goiters are benign, and thyroid cancers often are detected as solitary nodules within an otherwise normal gland (in children with solitary nodules, up to 40% are carcinomas). Patients with a history of goiter or benign nodules/adenomas have an increased risk of developing thyroid cancer.
- Q: Does thyroid cancer usually present with hyperthyroidism?
- A: No. The usual chief complaint is a solitary, hard, painless nodule in an euthyroid patient.
- Q: Is there an increased risk of thyroid cancer from diagnostic radiographs (chest radiographs, lateral neck films)?
- A: Routine diagnostic radiographs should fall well below the levels of radiation thought to increase risk of thyroid neoplasia. During more prolonged radiologic procedures that might expose the thyroid to higher doses of radiation, a lead neck shield is used.
- Q: Should prophylactic thyroidectomy be performed in children identified genetically as having familial medullary carcinoma?
- A: Yes. Because of the poorer prognosis associated with development of this cancer