# 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.

![Thyroid nodule evaluation algorithm for pediatric and adult patients](illustration-thyroid-nodule-evaluation.jpg)

## 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.

![Comparison of DTC staging and treatment approach in children vs adults](illustration-dtc-treatment-comparison.jpg)

## 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.

![Long-term surveillance timeline for differentiated thyroid cancer](illustration-dtc-surveillance-timeline.jpg)

## 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

1. 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.
2. 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.
3. Bauer AJ. Thyroid nodules and differentiated thyroid cancer in the pediatric population. *Endocrinol Metab Clin North Am*. 2019;48(1):261-279.
4. 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.