Residency · Residency · Medicine Pediatrics
Thyroid Nodules and Differentiated Thyroid Cancer in Children vs. Adults
Introduction
Thyroid nodules are common in adults, found in up to 50% of the population by ultrasound, but rare in children. However, when a thyroid nodule is identified in a child, the risk of malignancy is 2-3 times higher than in adults. Differentiated thyroid cancer (DTC) -- encompassing papillary and follicular thyroid cancer -- behaves differently in pediatric and adult populations, with children presenting with more advanced disease but paradoxically having excellent long-term survival. Med-peds physicians must understand the age-specific evaluation, surgical management, and long-term surveillance of thyroid nodules and DTC.
Epidemiology
Thyroid Nodules
Adults: Prevalence of palpable nodules ~5%; ultrasound-detected nodules ~50%; 5-15% are malignant. Children: Prevalence of palpable nodules ~1-2%; 20-25% of pediatric thyroid nodules are malignant. Risk factors for thyroid cancer include prior radiation exposure (therapeutic or environmental), family history of thyroid cancer, and genetic syndromes.
Thyroid Cancer
Adults: Most common endocrine malignancy; ~44,000 new cases annually in the U.S.; papillary thyroid cancer (PTC) accounts for 85%. Children: ~2,000 cases annually in the U.S.; PTC accounts for >90%. Female predominance in both populations, more pronounced in adults (3-4:1) than children (2:1) Pediatric thyroid cancer incidence has been increasing, partly due to increased detection.
Presentation and Evaluation
Clinical Assessment
Palpable thyroid nodule: Most common presentation in both ages. Cervical lymphadenopathy: More common in pediatric DTC at diagnosis (~60-80% vs ~20-30% in adults) TSH measurement: First-line laboratory test; suppressed TSH suggests autonomous nodule (rare in children) Thyroid ultrasound: Essential for characterizing nodule features and evaluating cervical lymph nodes.
Ultrasound Risk Stratification
Suspicious features: Solid hypoechoic composition, irregular margins, microcalcifications, taller-than-wide shape, extrathyroidal extension. ATA adult guidelines: TI-RADS classification guides FNA thresholds based on pattern and size. ATA pediatric guidelines: Lower size thresholds for FNA in children given higher malignancy risk; FNA recommended for nodules >=1 cm with suspicious features (some recommend lower thresholds) Evaluate lateral and central cervical lymph nodes in both populations.
Fine Needle Aspiration (FNA)
Bethesda System for Reporting Thyroid Cytopathology applies to both children and adults. Categories I-VI: Non-diagnostic, benign, atypia of undetermined significance (AUS), follicular neoplasm, suspicious for malignancy, malignant. Pediatric consideration: Higher malignancy rates across all Bethesda categories compared to adults. AUS/FLUS (Bethesda III) in children: 28% malignancy rate vs ~10-15% in adults; lower threshold for surgical intervention. Molecular testing (e.g., Afirma, ThyroSeq): Widely used in adults to guide management of indeterminate cytology; less validated in pediatric populations.
Differences in Disease Behavior
| Feature | Pediatric DTC | Adult DTC |
|---|---|---|
| Malignancy rate of nodules | 20-25% | 5-15% |
| Lymph node metastases at diagnosis | 60-80% | 20-30% |
| Pulmonary metastases at diagnosis | 15-25% | <5% |
| BRAF V600E mutation | ~30% | ~60% |
| RET/PTC fusions | Common | Uncommon |
| Disease-specific mortality | <2% (30+ years) | <5% overall; higher if age >55 |
| Recurrence rate | 20-30% | 5-15% |
| Recommended surgery | Total thyroidectomy | Lobectomy may suffice for low-risk |
Pediatric DTC
Presents with more advanced locoregional disease: higher rates of bilateral thyroid involvement, extrathyroidal extension, and lymph node metastases. Pulmonary metastases at diagnosis in 15-25% of pediatric DTC vs. <5% of adults. Despite advanced presentation, disease-specific mortality is <2% over 30+ years. Recurrence rates are higher (20-30%) but respond well to additional treatment. BRAF V600E mutation: Less common in children (~30%) than adults (~60%); RET/PTC fusions more prevalent in pediatric PTC.
Adult DTC
Typically presents as localized disease; advanced stage at diagnosis is less common but carries worse prognosis in older adults. Outcomes are generally excellent for DTC: 5-year survival >98% overall. Age >55 years is an adverse prognostic factor in the AJCC staging system. BRAF V600E-mutated tumors are associated with more aggressive behavior in adults.
Surgical Management
Extent of Surgery
Pediatric DTC: Total thyroidectomy is generally recommended given high rates of bilateral disease, lymph node metastases, and need for RAI therapy. Central neck dissection: Therapeutic (for clinically involved nodes) is recommended; prophylactic central dissection is debated. Lateral neck dissection: For FNA-confirmed lateral lymph node metastases. Adult DTC: Lobectomy may be appropriate for low-risk, small (<4 cm) unilateral tumors without extrathyroidal extension or lymph node involvement; total thyroidectomy for higher-risk features.
Surgical Risks
Recurrent laryngeal nerve injury: Risk 1-2% with experienced surgeon. Hypoparathyroidism: Transient in 10-20%, permanent in 1-3%; higher risk with bilateral surgery and central dissection. Pediatric considerations: Smaller anatomy increases technical difficulty; referral to high-volume pediatric thyroid surgeons (>=30 thyroidectomies/year) is strongly recommended by ATA guidelines.
Radioactive Iodine (RAI) Therapy
Pediatric patients: RAI is used more frequently due to advanced disease at presentation. RAI is indicated for residual or metastatic disease; empiric or dosimetry-based dosing. Pulmonary metastases in children often concentrate RAI and respond well to therapy. Adult patients: RAI for intermediate and high-risk DTC; low-risk patients may not need RAI after lobectomy or total thyroidectomy. Rheumatic TSH stimulation: Thyroid hormone withdrawal or recombinant TSH (Thyrogen) to raise TSH before RAI. Long-term risks of RAI: Salivary gland dysfunction, lacrimal duct obstruction, secondary malignancies (dose-dependent); fertility counseling especially important in pediatric patients.
Long-Term Surveillance
Thyroglobulin (Tg): Tumor marker for DTC after total thyroidectomy; should trend toward undetectable. Anti-thyroglobulin antibodies: Interfere with Tg measurement; monitor separately. Neck ultrasound: Regular surveillance for structural recurrence; every 6-12 months initially, then annually. TSH suppression: Degree of suppression based on risk stratification (low-risk: TSH 0.5-2.0; high-risk: TSH <0.1) Pediatric patients require decades of surveillance given long life expectancy and recurrence risk.
Clinical Pearls
Thyroid nodules in children have a 2-3x higher malignancy rate than in adults; all pediatric thyroid nodules warrant thorough evaluation. Pediatric DTC presents with more advanced disease but has excellent long-term survival (<2% mortality) Total thyroidectomy by a high-volume surgeon is recommended for pediatric DTC due to high rates of bilateral and multifocal disease. Molecular testing for indeterminate cytology is well-validated in adults but has limited pediatric data; higher Bethesda III malignancy rates in children may favor surgical excision. Lifelong thyroglobulin monitoring and surveillance imaging are essential given the prolonged recurrence risk.
References
- Francis GL, Waguespack SG, Bauer AJ, et al. Management guidelines for children with thyroid nodules and differentiated thyroid cancer: ATA guidelines. Thyroid. 2015;25(7):716-759.
- Haugen BR, Alexander EK, Bible KC, et al. 2015 ATA management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26(1):1-133.
- Bauer AJ. Thyroid nodules and differentiated thyroid cancer in the pediatric population. Endocrinol Metab Clin North Am. 2019;48(1):261-279.
- Clement SC, Kremer LCM, Links TP, et al. Thyroid cancer in children and adolescents: A systematic review of outcomes. Thyroid. 2018;28(9):1157-1168.