A paper published in The Journal of Clinical Endocrinology & Metabolism sounds an alarm for clinicians treating COVID-19 patients to be on the lookout for possible cases of subacute thyroiditis post-infection.
COVID-19 upended the world as we knew it in 2020, and its effects are continuing to be felt. New clinical sequelae are also emerging, not surprisingly, including subacute thyroiditis (SAT).
Researchers in Italy, the second country after China to be involved in the pandemic and, as some have speculated, possibly home to a particularly virulent strain of the coronavirus, were the first to report on post-COVID-19 SAT and published their findings in The Journal of Clinical Endocrinology & Metabolism online ahead of print in May.
In “Subacute Thyroiditis After Sars-COV-2 Infection,” Francesco Latrofa, MD, of the Endocrinology Unit I, Department of Clinical and Experimental Medicine at the University Hospital of Pisa in Italy, and team describe an 18-year-old female patient who tested positive for COVID-19 via oropharyngeal swab on February 28, 2020 after her father (also her housemate) had been hospitalized for the virus. By March 14, 2020, she was no longer ill and twice tested negative for the virus. Suddenly, three days later, the patient experienced fever, fatigue, palpitations, and neck pain radiating to her jaw. On March 19, 2020, with the neck pain worsening, she was referred to Latrofa and team.
To backtrack a bit, the patient had previously experienced transient hyperthyrotropinemia, but imaging and testing on February 21, 2020, just before the onset of her viral illness, demonstrated that she was euthyroid, including a negative result for antibodies to thyroglobulin (TgAb), thus ruling out thyroid disease. Explains Latrofa, “The patient was asymptomatic, and measurement of thyroid-stimulating hormone (TSH) was part of the routine labs suggested by her family doctor. Hyperthyrotropinemia, when isolated (i.e., with no evidence of autoimmune thyroid disease) cannot be considered as an evidence of disease by itself but prompts re-evaluation of thyroid function. Indeed, thyroid function was normal a few months later, shortly before the onset of SAT.”
On examination on March 19, her heartrate was rapid and her thyroid tender to palpation. Given the association of SAT with thyroid dysfunction, which this patient had a history of, the team suspected SAT. Laboratory tests (thyroid hormone function tests) and ultrasound provided further evidence, and the patient was started on prednisone on March 20 while still in the acute phase of SAT to combat her symptoms as well reduce the risk of recurrence. Within one week the patient was no longer symptomatic, and within two weeks, clinical, biochemical, and imaging signs were back to normal.
Importantly, although the pathogenesis of SAT is not completely understood, it is thought to have a viral or postviral (inflammatory) origin in genetically predisposed individuals. SAT is often preceded by an upper respiratory tract infection or symptoms like malaise, fatigue, and low-grade fever. It can occur seasonally, in the summer period, when the peak of infection by enterovirus occurs and has been also correlated with viral epidemics of mumps. The most relevant evidence for its viral origin is the detection of rising level of antibodies to viruses in convalescent patients.
However, the virus has been isolated from the thyroid of subjects with SAT in only a very few cases. Studies based on fine-needle aspiration of the thyroid from patients with SAT failed to isolate the virus. Although possibly associated with the de novo appearance of thyroglobulin autoantibodies TgAb-IgG to Tg as well as to the other thyroid autoantigens, SAT usually recovers without autoimmune sequelae.
In a study published in the June issue of The Journal of Clinical Endocrinology & Metabolism, Latrofa and team showed that Tg leak associated with thyroid injury induces the production of specific TgAb-IgM, which, in turn, increases the clearance of Tg and might prevent the establishment of a persistent thyroid autoimmune response.
In the case in “Subacute Thyroiditis After Sars-COV-2 Infection,” the confirmed prior thyroid disease-free status of the patient combined with the emergence of SAT 15 days after recovery from COVID-19 suggest that COVID-19 is likely the cause of her bout of SAT. Furthermore, “a second and a third case of SAT post-COVID-19 have now been published in the Journal of Endocrinological Investigation by a group of endocrinologists at the University of Insubria (in Varese, Italy) and a group of internal medicine doctors at the Ankara Hospital (in Turkey),” Latrofa says.
Although this patient completely recovered, “a common lasting sequelae of SAT is hypothyroidism, due to the damage of the gland,” Latrofa says. Notably, autopsy of patients who have died after the 2002 SARS-CoV outbreak showed thyroid gland damage. “However, hypothyroidism is treated with levothyroxine, usually with no troubles, as the majority of cases of permanent hypothyroidism,” he continues.
“We alert clinicians to look for this additional clinical manifestation related to SARS-CoV-2 infection. In some cases, the symptoms of SAT are mild and therefore SAT could remain undiagnosed in patients with relevant symptoms of SARS-CoV-2 infection involving other organs.” – Francesco Latrofa, MD, Endocrinology Unit I, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy
As for other postviral diseases that clinicians should look out for, Latrofa cites recently reported cases of Guillain-Barré syndrome (a neurological disorder that has been associated with infectious agents) related to COVID-19.
With COVID-19 infection continuing to spread worldwide, with more than 18 million cases reported at the time of this writing, Latrofa and team have an urgent message for endocrinologists. “We alert clinicians to look for this additional clinical manifestation related to SARS-CoV-2 infection. In some cases, the symptoms of SAT are mild and therefore SAT could remain undiagnosed in patients with relevant symptoms of SARS-CoV-2 infection involving other organs.”
With the ability of this coronavirus to trigger SAT, the probability is high that it can cause other postviral syndromes and damage other body systems. This case study has unveiled more of COVID-19’s potential to do harm in unexpected ways.
Horvath is a freelance writer based in Baltimore, Md. In the August issue, she wrote the CEU preview article that detailed investigating thyroid “imposters.”