Endocrine Abstracts

Objectives: The risk of multinodular goiter (MNG) and cancer in tumor-predisposition syndromes, is not well established in both, children and adults. MNG is a common clinical feature of DICER1 syndrome in children and adults. DICER1 syndrome is caused by germline pathogenic mutations in the DICER1 gene. The spectrum of ultrasonographic findings of MNG in DICER1mut+ patients is characteristic and largely distinct from typical features of thyroid malignancy and therefore should inform physicians performing thyroid US of the possible presence of underlying DICER1 syndrome (Sci Rep. 2022 Sep 23;12(1):15888). The aim of this study was to determine the incidence of MNG in patients with DICER1 syndrome.

Methods: This retrospective study evaluated patients with MNG diagnosed between 2009 and 2023 at a single center by the same pediatric endocrinologist. Based on ultrasonographic features, 40 patients (25 children <18y and 15 adults) from 22 families were initially enrolled for DICER1 gene analysis. In 13 families (59.1%) pathogenic variant of DICER1 gene was found. All pathogenic variants in DICER1 (referred to hereon as DICER1 mut+) were identified in a single research university laboratory. DICER1mut+ was found in 29/40 patients with MNG (72.5%), 16 children and 13 adults. The number of studied subjects for DICER1 mutation was enlarged by 5 family members of affected patients who had no MNG. In all DICER1 mutation was also confirmed. Analysis of all DICER1mut+ patients (n = 34, 13 adults and 21 children) showed that MNG was present in 29 patients, 16 children and 13 adults (85.3%). 3 children with MNG and DICER1mut+ have not been operated yet. Thyroid cancer was found in two (1 mPTCvF and 1 FTC) among 13 operated children (15.4%). In a group of 5 children who have normal thyroid on ultrasound, 1 had pleuropulmonary blastoma (PPB) and cystic nephroma (mother with MNG), 1 had PPB alone (mother with MNG) and the 3 remaining are asymptomatic to date (one parent of each has MNG). MNG was present in all families who carry the mutation however, in two families PPB was the primary reason for endocrine consultation and further genetic testing.

Conclusions: This study showed that MNG is present in the vast majority of patients with DICER1mut+ and the risk of cancer is not low. Further genotype-phenotype relationship may shed a new light on the risk of multinodular goiter and thyroid cancer in these patients and also in asymptomatic to date carriers.