By Gary M. Pepper, M.D.
(This article is for educational purposes only and is not intended as medical advice or treatment)
During the Covid-19 pandemic my medical practice has been operating as normally as possible. The other day a young woman arrived wearing a surgical mask with a stack of medical records in hand, for a new patient appointment. Her difficulties began 6 weeks prior with intense tenderness in the right side of her neck just above the clavicle (collarbone) which varied in intensity over the course of about 10 days. Evaluation by her primary care physician uncovered newly elevated thyroid hormone levels. During our discussion she recalled a respiratory tract infection starting a week before the neck pain developed.Â Still complaining of lung congestion she denied fever or shortness of breath.Â Sitting comfortably, the thyroid was no longer tender but was slightly enlarged and unusually firm.Â Reading on it will become clear why my preliminary diagnosis is sub-acute thyroiditis, an inflammation of the thyroid following a viral respiratory tract infection, possibly Covid-19.
The nature of interaction between the thyroid and coronavirus is unknown but we are on the verge of finding out as we investigate cases like this. Until then, our understanding of how other viral infections affect the thyroid can provide grounds for speculation. A good place to start is with Hashimotoâ€™s thyroiditis, also known as chronic lymphocytic thyroiditis. This is a common thyroid disease most often diagnosed in middle-aged women although it can occur in both sexes and all ages. As an autoimmune disease Hashimoto’s results when immune cells and the antibodies they produce attack the thyroid gland. Normally immune cells, known as lymphocytes, with their antibodies are protective against viral and bacterial infection. In autoimmune thyroid disease a population of the affected individualâ€™s immune cells begin to destroy thyroid cells instead. Technically this is an inflammatory reaction but unlike many inflammations, Hashimotoâ€™s is generally painless. Being painless, Hashimotoâ€™s can exist for many years before it is detected by routine blood tests for thyroid levels or is discovered on physical exam presenting as an enlarged and lumpy (nodular) thyroid gland.
The development of Hashimotoâ€™s is thought to involve inherited (genetic) factors but also likely requires an environmental trigger such as a virus to initiate clinical disease. The genetic nature of Hashimotoâ€™s is manifest in the occurrence of the disease in multiple members within a family. The type of viral infection promoting this disease is unclear. Some studies point to Epstein Barr virus, commonly called EB virus as a potential trigger for Hashimotoâ€™s activation. EB virus is extremely wide spread found in over 95% of the worldâ€™s population. In humans, it generally exists in an asymptomatic state from childhood to old age. In certain individuals, EB virus can create serious illnesses such as mononucleosis or cancers of the lymphoma type. Evidence that EB virus plays a significant role in autoimmune thyroid disease includes finding of the EB viral genetic material (RNA) in the thyroid tissue of 80% of those with Hashimotoâ€™s and 62% of those with Graveâ€™s (hyperthyroidism). 90% of all lymphomas involving the thyroid occur in those with Hashimotoâ€™s, and as just mentioned lymphoma is a characteristic cancer related to EB viral infection.
Why do some people and not others develop the more severe form of EB disease such as lymphoma or autoimmune thyroid disease? The likely explanation is that as mentioned above, genetic factors result in susceptibility to more aggressive complications of the viral infection. Many infectious disease experts are speculating similar genetic factors account for the extreme variability between individuals of complications of Covid-19.
Another form of thyroid inflammation that unlike Hashimotoâ€™s is often painful, is sub-acute or DeQuervainâ€™s thyroiditis. This thyroid disorder tends to occur days to weeks after an upper respiratory illness. The onset is often accompanied by fatigue, generalized muscle pain, low-grade fever and throat pain, which can radiate upward to the ears. At the onset of this disorder thyroid hormone levels are elevated due to destruction of thyroid cells releasing hormone into the blood. Many of the presenting symptoms of sub-acute thyroiditis are those of elevated thyroid levels such as rapid heart rate, sweating, and weight loss. These symptoms usually resolve in a few weeks and in 15-30% of patients due to thyroid tissue destruction permanently under active thyroid function (hypothyroidism) results.
Substantial evidence exists for involvement of viral infection in the development of sub-acute thyroiditis. For example, the occurrence of sub-acute thyroiditis is more frequent in summer when Coxsackievirus infection is most common. Virus particles similar to mumps and flu have also been found in the thyroid of people with sub-acute thyroiditis and outbreaks of this thyroid disease have occurred during mumps epidemics. Some experts believe that sub-acute thyroiditis is a â€œpost-viralâ€ illness, meaning the bodyâ€™s immune response persists even after cleansing the body of the virus but in a misdirected manner, attacking molecular targets on the thyroid cells that bear similarities with the virus structure. Interestingly, the occurrence of sub-acute thyroiditis is more common in those with Hashimotoâ€™s.
The presence of HTLV-1 viruses has also been associated with development of autoimmune thyroid disease including both Hashimotoâ€™s thyroiditis and Graveâ€™s disease (hyperthyroidism). Evidence for this involves finding antibodies to HTLV-1 virus in Hashimotoâ€™s and Graveâ€™s patients. About 6% of those with Graveâ€™s and 7% of Hashimotoâ€™s having these antibodies. Since 95% of people with antibodies to HTLV-1 never develop any symptoms, screening people for this infection is currently not being done.
A common question in my medical practice is whether those with Hashimotoâ€™s have increased vulnerability to Covid-19 infection? There have been no formal studies of this as yet but in a poll of the 10 endocrinologists in my group none felt that Hashimotoâ€™s was a risk factor for suppression of the immune system which could result in more severe viral complications. Also, there is no compelling evidence that those with Hashimotoâ€™s have impaired ability to fight infections.
Studies indicate that low levels of thyroid hormone can result in impaired immune function without any link to underlying Hashimotoâ€™s. This relationship should motivate those with hypothyroidism to check that their thyroid hormone levels are optimized to help maintain immune function. There is disagreement in the medical community regarding what exactly constitutes best thyroid hormone levels and how to achieve those levels when medication is required. Concerned individuals should discuss this matter with a qualified health care provider and valuable information on this topic can be found at www.metabolism.com.
Another question in the wake of the coronavirus pandemic is whether the virus induces pathological changes in the thyroid such as seen with Hashimotoâ€™s thyroiditis or sub-acute thyroiditis. If infection by this virus does affect the thyroid the clinical signs and symptoms could take weeks after recovery from Covid-19 to become apparent. As detailed by the case reported at the beginning of this article, initial symptoms of sub-acute thyroiditis include pain in the throat often radiating upward to the ears, swelling in the lower neck, and tenderness in this area. During the early phase of sub-acute thyroiditis symptoms of elevated thyroid levels can also occur including excessive sweating, persistently feeling hot, rapid heartbeat, shakiness, and unexplained weight loss. If enough damage is done to the thyroid by the inflammation within a few more weeks symptoms of low (hypo) thyroid levels may develop such as feeling unusually cold, muscle cramps, unexplained weight gain, fatigue, constipation and facial puffiness. Individuals are encouraged to consult with their health care professional if experiencing these or other unusual symptoms to determine if they represent a medical disorder.
Whether the novel coronavirus plays a role in development of these or other thyroid diseases remains to be determined.