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Differential Growth Rates of Benign vs. Malignant Thyroid Nodules

Context
Thyroid nodule growth was once considered concerning for malignancy, but data showing that benign nodules grow questioned the use of this paradigm. To date, however, no studies have adequately evaluated whether growth rates differ in malignant vs. benign nodules.


Objective
To sonographically evaluate growth rates in benign and malignant thyroid nodules ≥1 cm.


Design
Prospective, cohort study of patients with tissue diagnosis of benign or malignant disease, with repeated ultrasound evaluation six or more months apart.


Main Outcomes
Growth rate in largest dimension of malignant compared with benign thyroid nodules. Regression models were used to evaluate predictors of growth.


Results
Malignant nodules (126) met inclusion criteria (≥6-month nonoperative followup) and were compared with 1363 benign nodules. Malignant nodules were not found to be uniquely selected or prospectively observed solely for low-risk phenotype. Median ultrasound intervals were similar (21.8 months for benign nodules; 20.9 months for malignant nodules). Malignant nodules were more likely to grow >2 mm/y compared with benign nodules [relative risk (RR) = 2.5, 95% confidence interval (CI), 1.6 to 3.1; P < 0.001], which remained true after adjustment for clinical factors. The RR of a nodule being malignant increased with faster growth rates. Malignant nodules growing >2 mm/y had greater odds of being more aggressive cancers [intermediate risk: odds ratio (OR) = 2.99; 95% CI, 1.20 to 7.47; P = 0.03; higher risk: OR = 8.69; 95% CI, 1.78 to 42.34; P = 0.02].


Conclusions
Malignant nodules, especially higher-risk phenotypes, grow faster than benign nodules. As growth >2 mm/y predicts malignant compared with benign disease, this clinical parameter can contribute to the assessment of thyroid cancer risk.