COVID-19 Vaccine Linked to Exacerbation of Graves Disease

graves disease
graves disease
Investigators report on a case series of patients who experienced new onset or relapsed Graves disease-related hyperthyroidism following undergoing vaccination for COVID-19.

Clinicians should be aware of the potential development or exacerbation of autoimmune thyroid disorders in predisposed individuals after exposure to the COVID-19 vaccination, researchers reported in the Journal of Clinical Endocrinology and Metabolism.

The investigators presented their findings from a case series of 12 patients who presented with new-onset or relapse of Graves disease-related hyperthyroidism to a tertiary endocrinology clinic in Singapore from January to December 2021. All patients had received SARS-CoV-2 mRNA vaccines; 6 patients had new-onset symptoms and 6 experienced relapse of a previously well-controlled condition.

The median age of participants was 35.5 years (range, 22-74), and 11 were women. The overall median time to onset of hyperthyroid symptoms was 17 days (interquartile range [IQR], 8-27) after receiving the COVID-19 vaccine.

Among the group, 5 patients developed clinical and/or biochemical hyperthyroidism after the first dose of the SARS-CoV-2 mRNA vaccine, with a median symptom onset time of 7 days (IQR, 5-21). The remaining 7 patients developed hyperthyroidism after the second dose of the SARS-CoV-2 vaccine, with a median symptom onset of 21 days (IQR, 11-31).

The participants had a median free thyroxine (FT4) level of 49.5 pmol/L (IQR, 24.5-69) at initial diagnosis of Graves disease. Free triiodothyronine levels were measured in 4 patients, with concentrations ranging from 6.3 pmol/L to more than 40 pmol/L. Thyroid-stimulating hormone (TSH) levels were less than 0.01 mIU/L in 6 patients and close to 0.01 mIU/L in the remaining 6 patients.

The median TSH receptor antibody concentration was 6.2 IU/L (range, 2.4-32) at diagnosis of Graves disease. A majority of patients who experienced relapse had an increase in FT4 level and a decrease in TSH level shortly after receiving the vaccine, and 9 patients had a normal FT4 level within a median of 42 days (IQR, 31-58).

“In our case series, we observed that the exacerbation of hyperthyroidism can occur after the first or subsequent doses of the vaccine,” stated the researchers. “Importantly, all the patients were able to tolerate a subsequent booster dose of SARS-CoV-2 mRNA vaccine without further exacerbation of hyperthyroidism.”

The temporal sequence in these patients indicates that thyrotoxicosis may be related to the COVID-19 vaccination, although there is no evidence to prove a causal relationship, noted the investigators.

“We believe that the SARS-CoV-2 vaccinations or boosters should not be delayed given the clear protection against severe disease conferred by the vaccine,” the study authors advised. “Increased awareness among endocrinologists and primary care physicians and patients is required for early identification of a relapse or new-onset Graves disease.”


Chee YJ, Liew H, Hoi WH, et al. SARS-CoV-2 mRNA vaccination and Graves’ disease: a report of 12 cases and review of the literature. J Clin Endocrinol Metab. Published online March 2, 2022. doi:10.1210/clinem/dgac119