COVID-19

This Thyroid Disorder May Be A Marker For Covid-19 Infection

By now, many people may be familiar with loss of smell or taste or ”Covid toes” (red and sore toes) as markers of Covid-19 infection. But there is now another possible clinical condition to consider, based on a new case report out of Italy published in the Journal of Clinical Endocrinology and Metabolism.

While this case represents the first report of the condition known as subacute thyroiditis (SAT) as a possible marker of Covid-19 infection, the association of this particular illness in relation to SARS-CoV-2, the virus that causes Covid-19, makes clinical sense. Certainly more study and evaluation of past and future cases will be necessary in order to verify the new linkage to Covid-19. That said, SAT has been associated with a number of viral infections as causative in origin.

SAT typically develops after an upper respiratory tract viral infection leading to neck pain, swelling of the thyroid gland (small butterfly-shaped gland in the front of your neck), along with systemic symptoms such as fever, fatigue, loss of appetite and muscle aches. SAT is characterized by 3 phases: thyrotoxicosis (increased thyroid function), hypothyroidism (reduced thyroid function), with a return to normal thyroid function in about 3 months. While we often see evidence of thyrotoxicosis with this condition, hypothyroidism is less common clinically.

While we typically diagnose SAT clinically, blood tests and imaging of the neck (ultrasound or radionuclide scanning) are also helpful. Thyroid function tests (TFTs) such as free T4, T3, TSH (Thyroid Stimulating Hormone) and inflammatory markers known as ESR (erythrocyte sedimentation rate) and CRP (C-Reactive Protein) are important in the evaluation of this condition. (ESR and CRP are quite elevated in the initial stages of SAT). Steroids are often helpful in the first several weeks of the illness and can be tapered over 4-6 weeks. However, a trial of non-steroidal anti-imflammatory medication for several days can also be started prior to initiation of steroids in many cases. Medication to lower the heart rate (beta-blockers) during the initial phases in also typically prescribed. Some patients require supplementation with the thyroid hormone, levothyroxine, if they develop hypothyroidism during or after treatment.

In the acute phase of the illness, ultrasound of the thyroid demonstrates low density regions of both lobes of the thyroid associated with reduced vascularization (evidence of blood vessels), while radionuclide scanning shows reduced or even absent uptake of a “tracer” given intravenously.

In the case described by the authors, a 18 year old woman developed fever, neck pain radiating to the jaw, and palpitations 15 days after she tested positive for SARS-CoV-2, the virus that causes Covid-19.

But what’s interesting about the case is the timing of onset of her symptoms, along with the results of her oropharygeal swabs. The case report explains that the woman was swabbed while she was asymptomatic because her father, who lived with her, has been hospitalized 2 days earlier for Covid-19. She ended up testing positive. In the next several days, she developed a cough and runny nose, never received treatment, and clinically recovered in 4 days. Two additional swabs, on days 14 and 15, after her initial swab (when she was asymptomatic) were both negative. But on day 18, things changed.

The authors explain that she developed tenderness and swelling of the thyroid gland, along with an elevated heart rate (tachycardia). Her level of free T4 and free T3 markedly increased, TSH was undetectable, along with an elevated CRP and ESR. Her neck ultrasound demonstrated bilateral low density areas within her thyroid gland indicating inflammation.

Meanwhile, it was also noted by the authors that just a month earlier, labs tests for the patient’s thyroid gland and ultrasound were normal, when she was asymptomatic and sought medical evaluation for abnormal elevation of thyroid function tests. After she was started on a steroid (prednisone), her neck pain and fever resolved within 2 days, with the remainder of her systemic symptoms gone in 7 days. After 40 days, her thyroid lab tests all returned to normal levels.

In reporting the first case of SAT after a SARS-CoV-2 infection, the authors’ goal is to “alert clinicians to additional and unreported clinical manifestation associated with Covid-19.”

“It’s a classic presentation of post-viral thyroiditis which is characterized by the onset of neck pain, fever and high thyroid hormone levels due to transient destruction of thyroid cells related to inflammation which occurs about 2-8 weeks after the onset of a viral infection,” said Dr. Minisha Sood, an endocrinologist with Lenox Hill Hospital in New York City referring to the patient described in the case report. “Subacute thyroiditis generally has multiple phases including an initial phase of high thyroid hormone levels (about 2-8 weeks), followed by a period of low thyroid hormone levels (about 2-8 weeks) and then restoration of normal thyroid function.”

“In this case example, it is quite clear that the onset of thyroiditis was due to Covid-19 and the course was typical of subacute thyroiditis as described in the setting of other common viral infections like coxsackievirus and adenovirus,” added Sood. “This patient was treated with steroids early in her course likely due to the degree of neck discomfort though an alternative commonly used approach is to give a trial of non-steroidal anti-inflammatory drugs (i.e. moderate to high dose ibuprofen) for 2-3 days to control pain and inflammation prior to advancing therapy by using glucocorticoids (steroids).”

As worldwide cases of Covid-19 continue to grow, Sood explained that “it is important to highlight complications of viral infections such as subacute thyroiditis, as this case “importantly reminds clinicians of the symptoms due to thyroiditis which can include anorexia/weight loss, fatigue, muscle aches, neck pain (which may radiate to the jaw or ears), neck swelling, palpitations, tremor and anxiety.”

“The possibility of thyroiditis when one experiences these symptoms post-Covid-19 infection should be kept in mind so that the proper diagnosis can be made,” emphasized Sood. And, as an increasing number of post-viral symptoms are being attributed to Covid-19 or complications of Covid-19 such as thrombotic events, “the potential of subacute thyroiditis should not be overlooked.” she added.

It’s commonly believed that SAT is due to the viral infection itself or a post-viral inflammatory reaction in people who are genetically pre-disposed to the disease. Specific HLA (Human Leukocyte Antigen) variants (HLA-bw35, HLA-B67, HLA-B15/62 and HLA-Drw8) have been reported to place people at higher risk for SAT.

SAT has also been linked to a higher incidence during the summer during outbreaks of coxsackievirus or echovirus. But other viruses including mumps, adenovirus, Epstein-Barr virus, hepatitis E, HIV, CMV, dengue fever, and rubella have also been linked to SAT. Of note, thyroid dysfunction and destruction was described by Wei et al., in the SARS outbreak in 2002. Thus far, Covid-19 has not been linked to the clinical presentation of SAT.

While other clinical findings such as pink eye (conjunctivitis) have been linked to a small percentage of people with Covid-19 (approximately 1-3%), this common inflammatory eye condition is not pathognomonic for Covid-19. It may be possible for Covid-19 to cause conjunctivitis, but this is rare according to the American Academy of Ophthalmology’s website.

Such is the case with SAT—we will have to see more data and more case presentations before we can make any firm conclusions about its occurrence in patients with Covid-19, especially regarding the timing and course of the disease.

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