Prevalence of Thyroid Nodules and Thyroid Cancer in Individuals with a First-Degree Family History of Non-Medullary Thyroid Cancer: A Cross-Sectional Study Based on Sonographic Screening

Background: The actual rates of suspicious thyroid nodules (TNs) and confirmed thyroid cancer (TC) in putatively "at-risk" selected populations (e.g., individuals with family history of TC) are still uncertain. Methods: Our aim was to explore the prevalence of TC and TN in a cross-sectional study of a consenting population of unaffected individuals (10 years of age or older) with a first-degree relative known to have non-medullary TC (NMTC). Enrolled subjects underwent ultrasonographic studies of the neck between 2009 and 2018. Nodules considered suspicious according to current guidelines were subjected to fine-needle aspiration biopsy (FNAB) for cytology. Results: The screenee population comprised 1176 individuals (median age 42 [26–56] years, 650 females, 55.3%) from 473 kindreds (346 with 1 established NMTC diagnosis at entry, 103 with 2 established NMTC diagnoses, and 24 with 3 or more established NMTC diagnoses at entry). Screening revealed TNs in 500 screenees (42.5%; confidence interval [CI] 39.7–45.4%). Ninety-seven of these (19.4%; CI 16.2–23.1%) underwent FNAB. Only 11 cases of TC were diagnosed in the whole population (0.9%; CI 0.5–1.7%). The prevalence of TC in screenees from kindreds with ≥3 cases (3/24, 12.5%) was higher than that for kindreds with one affected member (6/346, 1.7%; p = 0.01, odds ratio [OR] 7.99; CI 1.21–40.75) and for those with two affected members (2/103, 1.9%; p = 0.05, OR 7.05; CI 0.76–89.44). The prevalence of TNs was 61.8% (CI 56.6–66.8%), 75.7% (CI 66.6–83%), and 66.7% (CI 46.7–82%) in the kindreds with 1, 2, and ≥3 cases, respectively (p = 0.03). Conclusions: On the whole, ultrasound-based screening of unaffected relatives of individuals with established diagnoses of NMTC is likely to reveal a high prevalence of TN and a low prevalence of TC. However, a significantly higher prevalence of TC may be found among screenees from kindreds with at least three established NMTC diagnoses before screening, suggesting that closer surveillance may be warranted in kindreds with this level of familiality.