Endocrine Abstracts

Objectives: During the Covid-19 pandemic caused by the severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2), vaccination has been widely adopted. Both SARS-CoV-2 infection and Covid-19 vaccines have been associated with several thyroid disorders. We studied the risk of Thyroid Eye Disease (TED) following Covid-19 vaccination.

Methods: This self-controlled-case-series study, validated model in assessing vaccine safety, included 98 consecutive patients (71 females and 27 males, mean-age 50 years) who attended our tertiary referral centre for new-onset (n =90) or reactivated (n =8) TED occurred in the period Jan 2021–Aug 2022, during the Covid-19 vaccination campaign launched in late 2020. Ninety-one (93%) patients had Graves’ disease, 5 (5%) euthyroid TED and 2 (2%) Hashimoto’s thyroiditis; 54/98 (55%) had a positive family history for thyroid/autoimmune disorders. For each vaccinated patient, we calculated person-days in time-windows after each dose, defined as ‘exposed’ if TED onset/reactivation occurred 1-28 days after vaccination and ‘unexposed’ if occurring outside such time-window. Poisson regression models were fitted to calculate incidence rate ratio (IRR) and 95% confidence-intervals (CI) of exposed vs unexposed. Sensitivity analyses were conducted considering only new-onset TED, gender, age, smoking, Covid-19 vaccine doses type and number and different exposed periods (29-56 and 57-84 days).

Results: Covid-19 vaccines were administered in 81 (83%) and never in 13 (13%) patients; data were missing in 4 patients. Of the 81 vaccinated subjects, 25 (31%) developed TED 1-28 days after vaccination (exposed) and 56 (69%) outside such time-window (unexposed). The IRR for TED was 3.24 (CI 2.01-5.20) overall and 5.29 (CI 2.71-10.3) in patients below 50 years of age. Gender and smoking did not modify the association between TED and vaccination, also when considering cases of disease new onset only. The TED risk seemed unrelated to the type or number of doses administered and progressively reduced over time following vaccination (P-trend 0.01). The TED severity was similar across the study subgroups. SARS-CoV-2 infection occurred in 23/98 (23%) patients during the study period and seemed not associated with TED.

Conclusions: The risk of TED development or reactivation is significantly increased shortly after Covid-19 vaccination, especially in subjects of less than 50 years of age. Possible mechanisms include spike protein interaction with the widely expressed ACE-II receptor or its cross-reactivity with thyroid self-proteins, and immune reactions induced by adjuvants. Until more safety data about Covid-19 vaccines will be available, caution and strict monitoring of individuals undergoing vaccination is suggested, especially if young and at risk of developing thyroid autoimmunity.