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Updated: Jul 4, 2025
Author Spotlight: Integrating Ultrasound Imaging with Biochemical Markers for Thyroid Disease Diagnosis
Published on: February 9, 2024
Prevalence of DICER1 variants in large multinodular goiter: thyroid function, clinical and imaging characteristics
Lara Judith Cabral Miranda1, Débora L S Danilovic2, Felipe Augusto Brasileiro Vanderlei3
1Laboratório de Endocrinologia Celular e Molecular (LIM25), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.
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.
Insights
Germline DICER1 variants are present in 11% of patients with large multinodular goiter (MNG). A second-hit somatic mutation was not found, suggesting it may not be necessary for MNG development.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- DICER1 gene mutations are implicated in differentiated thyroid carcinoma (DTC) and DICER1 syndrome.
- DICER1 is a known driver in DTC but also found in benign thyroid nodules.
- The role of DICER1 in benign multinodular goiter (MNG) development is not fully understood.
Purpose of the Study:
- To investigate the frequency of DICER1 variants in patients with MNG.
- To explore the potential association between DICER1 variants and long-lasting MNG.
- To determine if a second-hit somatic mutation is required for MNG development.
Main Methods:
- Sequencing of DICER1 hotspots in thyroid nodule samples from patients undergoing thyroidectomy for large MNG.
- Analysis of peripheral blood DNA to confirm somatic mutations.
- Evaluation of clinical and biochemical data, including thyroid volume, TSH, and TI-RADS classification.
Main Results:
- 11% of evaluated patients (154 out of 715) carried DICER1 variations (homozygous or heterozygous).
- Only one somatic DICER1 variant (rs12018992) was identified; other variants were synonymous and likely benign.
- Lower Free T4 levels were observed in patients with DICER1 polymorphisms, irrespective of TSH levels.
Conclusions:
- Germline DICER1 variants are detectable in a significant proportion (11%) of individuals with large MNG.
- The absence of a second-hit somatic mutation suggests it may not be essential for the development of MNG.
- DICER1 acts as a driver in thyroid lesions, but its role in MNG pathogenesis may differ from DTC.
