Prevalence of DICER1 variants in large multinodular goiter: thyroid function, clinical and imaging characteristics.

Objective: Mutations in DICER1 are found in differentiated thyroid carcinoma (DTC) and in multinodular goiter (MNG) at a younger age with other tumors, which characterizes DICER1 syndrome. DICER1 is one driver to DTC; however, it is also found in benign nodules. We speculated that patients with mutations in DICER1 may present long-lasting MNG. Our aim was to investigate the frequency of DICER1 variants in patients with MNG.

Subjects and methods: Patients who submitted to total thyroidectomy due to large MNG with symptoms were evaluated. DICER1 hotspots were sequenced from thyroid nodule samples. To confirm somatic mutation, DNA from peripheral blood was also analyzed.

Results: Among 715 patients, 154 were evaluated with 56.2 ± 12.3 years old (28-79) and the thyroid volume was 115.7 ± 108 mL (16.2-730). We found 11% with six DICER1 variations in a homo or heterozygous state. Only rs12018992 was a somatic DICER1 variant. All remaining variants were synonymous and likely benign, according to the ClinVar database. The rs12018992 was previously described in an adolescent with DTC, measuring 13 mm. There were no significant differences according to gender, familial history of goiter, age, thyroid volume, TSH and TI-RADS classification between DICER1 carriers. Free T4 were lower in patients with DICER1 polymorphisms (13.77 ± 1.8 vs. 15.44 ± 2.4 pmol/L, p = 0.008), regardless of TSH levels.

Conclusion: We conclude that germline DICER1 variants can be found in 11% of large goiters but no second-hit somatic mutation was found. DICER1 is one driver to thyroid lesion and a second-hit event seems unnecessary in the MNG development.