Endocrine Abstracts

Background: The familial predisposition to the development of autoimmune thyroiditis disease (AITD), including both Graves’ and Hashimoto’s diseases, is well known. This evidence could be related to both common genetic susceptibility and environmental factors. Genetic anticipation has been reported in some Mendelian diseases, including non-thyroidal autoimmune diseases, as a phenomenon for which an accumulation of alterations in susceptibility genes, generation after generation, could lead to an early disease onset in younger generations. However, to date data concerning the anticipation in AITD’s onset are few and controversial, and we thus aimed to investigate the occurrence of this phenomenon in a large series of AITD families.

Methods: This is a cross-sectional observational study, performed in a single reference center for thyroid diseases from September 2023 to February 2024. We evaluated age of onset of AITD in sixty-one families affected with AITD (9 with Graves’ disease e 52 with autoimmune hypothyroidism). We excluded from the analysis subjects belonging to the same generation (e.g. sisters and brothers). We divided patients and their relatives into two generational (Gen) groups based on relationship (Gen1 n = 52, range 18-81 years; Gen2 n = 54, range 13-74 years).

Results: Among the 125 familial members affected with AITD (17 males and 108 females; 119 Caucasian e 6 non-Caucasian), 15 (12%) were affected with Graves’ disease (GD) and 110 (88%) with Hashimoto’s thyroiditis (HT). In addition, 116 familial members had the same disease (3/116 GD and 113/116 HT), while nine patients had a discordant disease compared to family members. We observed a significant difference between the mean age of AITD onset in Gen1 compared to Gen2 (50±13.58 vs 37±14.3 years, P < 0.001).

Conclusions: Our preliminary data indicate an intergenerational anticipation of AITD in familial settings and may suggest the need for an earlier screening of AITD in young family members. Several factors may contribute this phenomenon, including the diffusion of thyroid screening in conditions at risk, but these data prompt further studies involving larger cohorts and including families with more than two generations.