Aetiology

The aetiology is presumed to be viral.[4]​[6]​​​​ An overlapping seasonal distribution of subacute thyroiditis and enterovirus infections has been reported.[1][7][8]

The disease is thought to occur after an upper respiratory tract infection.[4]​ It has been hypothesised that subacute thyroiditis occurs as a response to a variety of viral infections in a genetically predisposed person.[9]​ However, it is not clear whether this represents a host response to the viral infection or a viral infection of the thyroid.[10]

Post-convalescent viral titres of many common viruses (e.g., influenza, adenovirus, mumps,coxsackie, echo, H1N1) are raised, and then decrease, in patients after the diagnosis of subacute thyroiditis.[11][12]​​ A patient may show multiple viral antibodies that rise and fall in this pattern, suggesting this may be an anamnestic response to the inflammatory thyroid condition rather than the cause.[10]

Data from a German national registry (2015-2022) indicate that the seasonal pattern of subacute thyroiditis remained unchanged in 2020, despite the decreased incidence of enteroviruses and other pathogens (except SARS-CoV-2) attributable to enhanced pandemic-related hygiene measures.[8]​ No other analysed virus, including SARS-CoV-2, was associated with subacute thyroiditis.

Evidence regarding the association between subacute thyroiditis and COVID-19 infection, or COVID-19 vaccination, is equivocal.[13][14][15][16][17]​​

​Histocompatibility studies show a predominance of certain human leucocyte antigen (HLA) alleles in patients with subacute thyroiditis.[6][18][19][20] The HLA-B*35 allele is present in approximately 81% of patients with subacute thyroiditis.[20]​ Familial cases of subacute thyroiditis associated with HLA-B*35 have been observed.[21]​​

Subacute thyroiditis has also been associated with HLA-B*18:01, -DRB1*01, and -C*04:01.[3][19][20]

Pathophysiology

Subacute thyroiditis is a destructive thyroiditis that results in the release of preformed thyroid hormones (triiodothyronine [T3] and thyroxine [T4]) into the circulation. The thyroid is often enlarged and firm to palpation.[4]​

The elevated thyroid hormone levels in the blood can result in the symptoms of thyrotoxicosis (e.g., palpitations, tremor, heat intolerance) and suppress the pituitary secretion of thyroid-stimulating hormone (TSH). The thyroid destruction, combined with the TSH suppression, results in low iodine uptake by the entire thyroid gland, even if the inflammation is focal within one part of the thyroid. Because the thyrotoxicosis is caused by release of preformed hormone, antithyroid drugs are ineffective in reducing thyroid hormone levels and should not be used in the thyrotoxic phase of subacute thyroiditis.[4][22]​ During the thyrotoxic phase, thyroid histology (although not typically recommended for diagnosis) shows thyroid follicle destruction, infiltrates of mononuclear cells, and characteristic multinucleated giant cell granulomas.[23]​[24][25][26]

Depletion of thyroid hormone stores from the thyroid gland accounts for the hypothyroid phase that follows the thyrotoxic phase of subacute thyroiditis.[23]​ This form of primary hypothyroidism typically self-resolves upon thyroid response to increased pituitary TSH secretion; normal thyroid hormone function is restored during the final euthyroid phase.

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