What symptoms and treatment options are associated with thyroid nodules?

Thyroid Nodules: Causes, Symptoms, and Treatment

Causes and Prevalence

Thyroid nodules are extremely common, detected in up to 65% of the general population, with approximately 50% of people having at least one nodule by age 60. 1 The increased detection is largely due to widespread use of diagnostic imaging performed for unrelated purposes. 1

• Most thyroid nodules (85-93%) are benign, with only 7-15% harboring malignancy. 2, 3
• Nodules are more prevalent in women (5% palpable) compared to men (1% palpable) in iodine-sufficient regions. 3
• The exact etiology varies, but nodules can represent colloid nodules, adenomas, cysts, or thyroid cancer. 4

Clinical Symptoms

The majority of thyroid nodules are asymptomatic and discovered incidentally. 2 When symptoms do occur, they include:

Compressive Symptoms (approximately 5% of nodules)

• Dysphagia (difficulty swallowing) 5
• Dyspnea (shortness of breath) 5
• Orthopnea and obstructive sleep apnea 5
• Dysphonia (voice changes) 5
• Neck discomfort or pressure sensation 6

Cosmetic Concerns

• Visible neck enlargement causing patient distress 7
• Palpable neck mass 5

Functional Symptoms (approximately 5% progress to functional disease)

• Signs of hyperthyroidism if the nodule is autonomously functioning 7, 1
• Subclinical hyperthyroidism may be present even in "euthyroid" hot nodules 4

Diagnostic Evaluation

Initial Assessment

Measurement of thyroid-stimulating hormone (TSH) is the first-line test to identify hyperfunctioning nodules. 3, 6

• If TSH is subnormal, the patient has thyrotoxicosis and requires radionuclide scanning. 5
• For euthyroid patients, ultrasound is the gold standard for characterization. 5, 2

Ultrasound Features

Ultrasound provides high-resolution imaging to characterize nodules for malignancy risk. 5

Suspicious features warranting biopsy include: 1

• Solid composition
• Hypoechogenicity
• Irregular margins
• Microcalcifications

Benign features include: 1

• Cystic or spongiform appearance
• No suspicious characteristics

Fine-Needle Aspiration (FNA)

Lesions larger than 1 cm should be biopsied, and smaller lesions with suspicious features or risk factors should also undergo FNA regardless of size. 6, 1

• FNA is the standard method for determining whether a nodule is benign. 2
• Indeterminate cytology (20-30% of biopsies) may require molecular testing. 1

Additional Testing

• Serum calcitonin measurement if medullary thyroid carcinoma is suspected 3
• Radionuclide scanning is first-line for hyperfunctioning nodules but not helpful for determining malignancy in euthyroid patients 5, 4
• CT or MRI may be indicated for substernal extension or suspected invasive cancer 5

Treatment Options

Observation and Surveillance

Most benign thyroid nodules can be safely managed with observation. 2, 1

• Asymptomatic benign nodules <2 cm: surveillance ultrasound at 12-24 month intervals 7
• Smaller lesions with benign histology can be followed and reevaluated if they grow 6
• Small (<1.5 cm) occult nodules can be observed 4

Surgical Management

Surgery is warranted for nodules causing compressive symptoms, those with malignant cytology, or nodules demonstrating significant growth. 8, 6

Specific indications include: 5, 8

• Nodules increasing by ≥2 mm within 1 year or volume increase ≥50%
• Symptomatic compression or cosmetic concerns
• Malignant or suspicious cytology (Bethesda V-VI)
• Clinical risk factors for malignancy

Surgical approach: 8

• Partial thyroidectomy (hemithyroidectomy) for unilateral nodules preserves thyroid function
• Provides definitive diagnosis and treatment in a single procedure

Thermal Ablation Techniques

Thermal ablation (radiofrequency, microwave, or laser ablation) is an optional treatment for benign nodules that are enlarging, symptomatic, or cosmetically concerning. 5

Indications for thermal ablation: 5

• Benign nodules ≥2 cm causing symptoms
• Autonomously functioning adenomas
• Recurrent nodules after chemical ablation
• Patients who refuse or cannot tolerate surgery

Thermal ablation is NOT appropriate when there is uncertainty about malignancy potential. 8

For select malignant nodules (T1aN0M0 papillary thyroid cancer ≤1 cm), thermal ablation may be considered in specialized centers. 5

Medical Management

Levothyroxine suppression therapy is NOT indicated for benign thyroid nodules in iodine-sufficient patients, as there are no clinical benefits and overtreatment may induce hyperthyroidism. 9

• Recent evidence casts doubt on the efficacy of suppressive therapy for benign nodules 4
• Suppressive therapy carries risks of bone loss and cardiac side effects, especially in elderly and postmenopausal women 4

Treatment of Autonomously Functioning Nodules

Hot nodules can be treated with: 4

• Radioiodine therapy
• Surgery
• Ethanol injection

Treatment is warranted if subclinical hyperthyroidism is present with significant osteoporosis risk. 4

Follow-Up Protocol

Post-Surgical Follow-Up

Initial follow-up at 1 month post-procedure, then at 3,6, and 12 months during the first year. 8

• TSH and thyroid function testing 8
• Ultrasound surveillance of remaining thyroid tissue 8

Surveillance for Benign Nodules

• Serial ultrasound monitoring for documented growth 8
• Reassessment for new suspicious features, growth patterns, or symptoms 7

Common Pitfalls to Avoid

• Do not routinely use CT, MRI, or PET/CT for initial evaluation of thyroid nodules unless there is concern for substernal extension or invasive cancer. 5
• Do not biopsy all nodules—use risk stratification systems based on ultrasound features to reduce unnecessary biopsies. 2
• Do not prescribe levothyroxine suppression therapy for benign nodules as routine treatment. 9, 4
• Do not assume all cold nodules are malignant—most are benign despite being non-functioning on scan. 4
• In children, maintain higher suspicion as the malignancy rate is much higher than in adults, and FNA is less accurate. 6