Graves’ Disease Following SARS-CoV-2 Infection Presenting as Acute Flaccid Quadriparesis
Year: 2025
Type: article
Abstract: Sir, Coronavirus disease 2019 (COVID-19) or its vaccination can lead to flare up or initiation of autoimmune diseases.[1] Graves’ disease is one of the endocrinological autoimmune complications that can occur after a COVID-19 infection.[2] Thyrotoxic periodic paralysis (TPP) is a rare manifestation of it which may mimic other neurologic manifestations of COVID-19 such as demyelinating disorders.[3] The exact mechanism for thyroid dysfunction in COVID-19 patients is not clear, but cells in the thyroid gland are known to express both angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) receptors. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses these receptors to enter cells and triggers an immunological response.[4] There is only one case report of TPP occurring in patients who recently suffered from COVID-19, presenting with quadriparesis.[5] A young adult male presented with sudden onset of inability to lift all limbs. Initially, weakness started on the lower limbs which gradually progressed to the upper limbs. On the previous night, he had taken a carbohydrate-rich diet. He had no associated symptoms of numbness, facial weakness, slurred speech, blurred vision, urinary retention, or incontinence. He had a similar episode 1 week back which lasted for 30 min and recovered spontaneously. One month back, he suffered from mild COVID-19. Over the past few weeks, he noticed a weight loss of around 7 kg and occasionally having palpitation. He did not have any similar illness in the past and was not on any long-term medications. There was no significant family history. Thyroid function tests before the diagnosis of COVID-19 were normal. On examination, blood pressure was 140/80 mmHg with a pulse rate of 92 beats/min. He had a small diffuse goiter, nontender, with no bruit and fine tremors in both hands. There were no signs of thyroid eye disease. Neurological examination revealed reduced tone in all the limbs and with absent deep tendon reflexes. The weakness was more in the lower limbs (power ⅖) when compared with the upper limbs (power ⅗). There was no involvement of the sensory system with intact cranial nerves. Subsequent investigations revealed hypokalemia [Table 1]. He was diagnosed to have hypokalemic periodic paralysis (HPP). He was initiated on intravenous (IV) potassium chloride (KCl) replacement, then put on oral KCl. Hypokalemia resolved the next day (potassium: 5 mmol/L) and weakness improved dramatically with normal muscle power in all the limbs.Table 1: Baseline investigationsBaseline routine investigations are shown in Table 1. Laboratory findings were consistent with hyperthyroidism [Table 2]. Thyrotropin receptor antibody (TRAb) and anti-thyroid peroxidase (anti-TPO) were positive at 37.5 IU/L (reference range ≤1.75 IU/L) and 66 IU/L (0–34 IU/L), respectively. Radioactive iodine uptake (RAIU) showed diffuse markedly increased uptake over both lobes of the thyroid. Hence, the diagnosis of Graves’ disease was made. He was started on carbimazole 10 mg daily and propranolol 40 mg once a day. After starting carbimazole treatment the patient has improved clinically.Table 2: Serial thyroid profileAutoimmune hyperthyroidism or Graves’ disease is one of the complications of COVID-19.[6] It is well established that viral infections can contribute to the pathogenesis of autoimmune thyroid disorders.[7] Graves’ disease can rarely present as TPP which is commonly reported in Asian males between 20 and 40 years of age.[8] Moreover, any infection can precipitate TPP. Various neurological complications have been reported with COVID-19 including rare complications like Guillian–Barré (GBS).[9] In this index patient, GBS was unlikely due to the episodic nature of the presentation and a relatively fast recovery. The clinical features favor more toward electrolyte imbalances like hypokalemia. Tan et al.[5] first reported a similar case of a 32 years old Chinese male presenting as TPP. Risk factors for hypokalemia in patients with COVID-19 include gastrointestinal loss, urinary loss, and diuretic use. Persistent hypokalemia had been reported in patients who recovered from COVID-19.[10] SARS-CoV-2 binds to ACE2 receptors and hampers the ability of ACE2 to regulate RAS. This RAS upregulation leads to increase delivery of sodium and water in the renal collection tubule and subsequent potassium excretion, resulting in hypokalemia.[10] Furthermore, in TPP hypokalemia occurs due to the intracellular shift of potassium induced by the thyroid hormone sensitization of Na+/K+–ATPase. This leads to hyperpolarization of cell membrane potential, and resultant flaccid paralysis and areflexia.[11] The pathophysiology of HPP and TPP appears to be similar making it a close differential. TPP is more commonly associated with Graves’ disease but rarely autoimmune thyroiditis can be a cause. TRAb and anti-TPO are both positive in the index case and the RAIU showed diffuse increase uptake which confirmed the diagnosis of Graves’ disease. The patient’s gender, age, and ethnicity made him particularly susceptible to developing TPP.[12] Molecular mimicry is the main mechanism behind various autoimmune and inflammatory diseases associated with COVID-19.[13] Thyroid diseases like Graves’ disease and thyroiditis following COVID-19 have been reported.[1] It has been postulated that both ACE2 and TMPRSS2 receptors are responsible for the cellular entry of SARS-CoV-2 into the thyroid follicular cells.[4] Moreover, COVID-19 may trigger Graves’ disease by altering the immune system in susceptible individuals. Cytokines like interleukin (IL)-1β, IL-6, tumor necrosing factor-α and interferon-γ are elevated in the SARS-CoV-2 induced hyperinflammatory state. Croce et al.[14] pointed out that these cytokines exert a multitude of effects on the hypothalamic–pituitary–thyroid axis, on circulating thyroid hormone binding proteins, and the thyroid hormones metabolism. The cytokine storm associated with SARS-CoV-2 may promote the hyperactivity of the Th1/Th17 immune response.[15] On the contrary, few systematically performed studies including a review on thyroid dysfunction in COVID-19 showed that pre and post-COVID-19 thyroid function tests remained unchanged. Rarely, abnormalities observed were temporarily associated and maximum recovered within 3 months. Therefore, it is very likely that there may not be any causal relationship between Graves’ disease and COVID-19.[16,17] TPP is a rare complication after Graves’ disease with an incidence of 0.1% in Western population.[18] But, the incidence rises up to 2% in Asian population, as they are genetically predisposed.[19] Treatment of TPP consists of potassium correction and antithyroid drugs. Potassium replacement can be done with either intravenous or oral KCl.[12] Beta-blockers can also be given to further prevent the intracellular shift of potassium. Electrolyte imbalances like hypokalemia need to be considered as one of the causes of acute flaccid quadriparesis following SARS-CoV-2 infection. Though TPP is considered an uncommon presentation, thyroid function should be done in all the patients with hypokalemia who recently had COVID-19. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal.The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Source: Neurology India
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4407798560