Pathophysiology
Clinical meaning
Thyroid nodules are discrete lesions within the thyroid gland that are radiologically distinct from the surrounding parenchyma. They are extremely common, found in 4-7% of adults by palpation and 19-67% by high-resolution ultrasound. The vast majority (90-95%) are benign, including colloid nodules (most common, representing hyperplastic thyroid tissue), follicular adenomas (encapsulated benign neoplasms), thyroid cysts, and inflammatory nodules from Hashimoto thyroiditis. Nodule formation results from a combination of TSH stimulation, growth factors (IGF-1, EGF), iodine deficiency, genetic predisposition, and somatic mutations in thyroid cells. Autonomously functioning (hot) nodules contain activating mutations in the TSH receptor or Gs-alpha protein, causing constitutive cAMP signaling and independent thyroid hormone production. Malignant nodules (5-15%) arise from mutations in follicular cells (papillary, follicular, anaplastic carcinoma) or parafollicular C-cells (medullary carcinoma). The ACR Thyroid Imaging Reporting and Data System (TI-RADS) uses ultrasound features to risk-stratify nodules and determine FNA thresholds: suspicious features include hypoechogenicity, irregular margins, microcalcifications, taller-than-wide shape, and extrathyroidal extension.