New onset or deterioration of thyroid eye disease after mRNA SARS-CoV-2 vaccines:report of 2 cases and literature review.

CONTEXT: Occurrence of Graves' disease (GD) has been reported following SARS-CoV-2 vaccine administration, but little is known about thyroid eye disease (TED) after SARS-CoV-2 vaccination. METHODS: We report two cases of TED activation following SARS-CoV-2 vaccination: one case of TED worsening in a patient with GD, and one of de novo active TED progressing to dysthyroid optic neuropathy in a patient with a history of Hashimoto's hypothyroidism. Our literature search revealed 8 additional reported TED cases associated with SARS-CoV-2 vaccination until June 2022. We review the characteristics, duration and management of TED following SARS-CoV-2 vaccination in these cases. RESULTS: Of all 10 reported TED cases following SARS-CoV-2 vaccination, four cases developed new onset TED and 6 cases with prior stable TED experienced significant deterioration. Six patients had known Graves' disease and 2 patients had Hashimoto's thyroiditis. Two cases progressed to dysthyroid optic neuropathy, 6 had moderate/severe active disease and 2 cases had mild disease that did not require treatment. Seven TED cases received teprotumumab and had a favorable response, two of which had prior limited response to initial prednisone or methylprednisolone and tocilizumab therapy. CONCLUSIONS: New diagnosis or deterioration of TED after mRNA SARS-CoV-2 vaccination can occur, with most cases described in patients with underlying autoimmune thyroid disease. Our report raises awareness to this potential complication to promote early recognition and prompt management of TED associated with mRNA SARS-CoV-2 vaccines. Further studies are needed to explore the mechanism of TED following mRNA SARS-CoV-2 vaccination, risk factors, prevention and treatment.

Graves' orbitopathy post-SARS-CoV-2 vaccines: report on six patients.

CONTEXT: Autoimmune and inflammatory thyroid diseases (Graves' disease, subacute thyroiditis, chronic autoimmune thyroiditis) have been reported following SARS-CoV-2 vaccines but Graves' orbitopathy (GO) post-COVID-19 vaccination is uncommon. METHODS: We describe six new patients seen in Endocrinology Departments with Outpatient Clinics for GO following SARS-CoV-2 vaccines in France. RESULTS: After COVID-19 vaccination, GO was observed in six patients (three men, three women, mean age 53 ± 6 years) with a personal past history of Graves' disease (5/6) or orbitopathy (4/6). New-onset (n = 2) or recurrence (n = 4) of GO was observed following mRNA vaccines after the first (3/6) or second (3/6) dose, with the mean time from vaccination to GO at 23.8 ± 10.4 days. In one patient, thyrotoxicosis was confirmed by increased free T4 and low TSH concentrations while others had normal TSH levels, during chronic levothyroxine treatment in three patients. Four patients had significant anti-TSH receptor antibodies levels. According to the severity and activity of GO, the patients were treated using selenium (n = 2), intravenous glucocorticoids (n = 2), teprotumumab (n = 1), tocilizumab (n = 2) and orbital decompression (n = 1) with a significant improvement in GO signs and symptoms observed by most patients. CONCLUSION: In this study, we report the main data from six new patients with GO following SARS-CoV-2 vaccines. Clinicians need to be aware of the risk of new-onset or recurrent GO in predisposed patients with autoimmune thyroid diseases after COVID-19 vaccination. This study should not raise any concerns regarding SARS-CoV-2 vaccination since the risk of COVID-19 undoubtedly outweighs the incidence of uncommon GO after SARS-CoV-2 vaccination.

Nonsurgical treatment for upper eyelid retraction in patients with inactive Graves' orbitopathy.

PURPOSE: To evaluate the effectiveness of incobotulinumtoxinA (Xeomin®) in treating upper eyelid retraction in patients with Graves orbitopathy (GO) initially scheduled for surgery via two different application sites. METHODS: This is a comparative, prospective study, conducted at the Department of Ophthalmology, Medical School, University Hospital Centre Zagreb, EUGOGO site (EUropean Group On Graves' Orbitopathy) in Croatia from January 2020 till January of 2021 in accordance with national health headquarter recommendations. All patients were classified as inactive with marked eyelid retraction and randomly divided into groups according to application sites. Group A underwent transconjunctival application (18 eyes) and group B transcutaneous application (20 eyes) of incobotulinumtoxinA. The primary end point of this study was lowering the eyelid, to alleviate anterior eye segment symptoms and achieve acceptable aesthetic appearance until surgery becomes available. RESULTS: There were no nonresponders and we found no statistically significant difference in the degree of lowering the eyelid between the two application sites. Following rules for avoiding spread of SARS-CoV-19, none of the patients included in this study were infected. Moreover, participants reported diminishing of anterior eye segment irritation and improved aesthetics. CONCLUSION: Treatment of inactive GO patients with incobotulinumtoxinA for upper eyelid retraction is efficient and safe and can be used as an adjuvant treatment while patients wait for surgery, by alleviating symptoms and improving the level of aesthetic satisfaction without causing a threat to anterior eye segment and visual function. The study showed that effect of treatment was the same, whether we applied the toxin transconjunctivaly or transcutaneously.

Decrease in Bone Formation and Bone Resorption during Intravenous Methylprednisolone Pulse Therapy in Patients with Graves' Orbitopathy.

BACKGROUND: Treatment with glucocorticoids (GCs) is associated with side effects. In contrast to the well-known negative impact on bone tissue exerted by oral GCs, few data are available regarding intravenous GCs. We investigated the influence of intravenous methylprednisolone (IVMP) on bone turnover markers (BTM): amino-terminal propeptide of type I procollagen (P1NP) and the C-terminal telopeptide of type I collagen (CTX), and on calcium metabolism parameters: 1,25-dihydroxyvitamin D (1,25(OH)2D), 25-hydroxyvitamin D (25(OH)D), calcium (Ca), phosphate (P), and intact parathormone (iPTH). METHODS: In a prospective study, 23 consecutive subjects with Graves' orbitopathy were included and treated with IVMP according to the European Group on Graves' Orbitopathy recommendations. We evaluated effects on BTM occurring during the first 7 days after 0.5 g IVMP, and after the therapy with 12 IVMP pulses with a cumulative dose of 4.5 g. RESULTS: We observed prompt but transient decrease of P1NP (p < 0.001) and the reduction of CTX (p = 0.02) after the first IVMP pulse. Following the full course of IVMP therapy, both P1NP and CTX were found decreased (p < 0.05 and p < 0.01, respectively). CONCLUSIONS: A single pulse of 0.5 g IVMP already decreases bone formation and resorption; however, this change is transient. The full therapy is associated with suppression of bone turnover.

Guideline interpretation: The 2021 European Group on Graves′ Orbitopathy Clinical Practice Guidelines for the Medical Management of Graves′ Orbitopathy

The 2021 European Group on Graves′ Orbitopathy (EUGOGO) Clinical Practice Guidelines for the Medical Management of Graves′ Orbitopathy was released in July, 2021. Based on the 2016 version, the new guidelines updated the first-line management algorithm for patients with Graves′ orbitopathy in moderate-to-severe and active period, provided multiple second-line treatment pathways and made detailed recommendations from aspects of clinical assessment, general measures, and management of specific conditions, etc. At the same time, efficacy evaluation and management during COVID-19 period were explained in detail. The new guidelines also mentioned some novel treatment strategies of GO which still need further efficacy and safety verification. © 2022 Center for Ancient Philosophy and the Classical Tradition. All rights reserved.

Orbital inflammatory disease following mRNA SARS-CoV-2 vaccine.

A 65-year-old woman reported orbital symptoms two days after her first dose and presented exacerbation of signs after the second dose of BNT162b2 mRNA vaccine. The temporal relationship between the COVID-19 vaccination and orbital symptoms suggests a probable link between SARS-CoV-2 mRNA vaccine and this orbital inflammatory disease.

Disulfiram Exerts Antifibrotic and Anti-Inflammatory Therapeutic Effects on Perimysial Orbital Fibroblasts in Graves' Orbitopathy.

Fibrosis of extraocular muscles (EOMs) is a marker of end-stage in Graves' orbitopathy (GO). To determine the antifibrotic and anti-inflammatory therapeutic effects and the underlying molecular mechanisms of disulfiram (DSF) on perimysial orbital fibroblasts (pOFs) in a GO model in vitro, primary cultures of pOFs from eight patients with GO and six subjects without GO (NG) were established. CCK-8 and EdU assays, IF, qPCR, WB, three-dimensional collagen gel contraction assays, cell scratch experiments, and ELISAs were performed. After TGF-ß1 stimulation of pOFs, the proliferation rate of the GO group but not the NG group increased significantly. DSF dose-dependently inhibited the proliferation, contraction, and migration of pOFs in the GO group. Additionally, DSF dose-dependently inhibited fibrosis and extracellular matrix production markers (FN1, COL1A1, α-SMA, CTGF) at the mRNA and protein levels. Furthermore, DSF mediates antifibrotic effects on GO pOFs partially through the ERK-Snail signaling pathway. In addition, DSF attenuated HA production and suppressed inflammatory chemokine molecule expression induced by TGF-ß1 in GO pOFs. In this in vitro study, we demonstrate the inhibitory effect of DSF on pOFs fibrosis in GO, HA production, and inflammation. DSF may be a potential drug candidate for preventing and treating tissue fibrosis in GO.

Selected thyreology problems during the COVID-19 pandemic. Hypothyroidism and hyperthyroidism - did anything change?

On March 11, 2020, the World Health Organisation (WHO) observed the scale of epidemic risk and declared the state of the COVID-19 pandemic. Most countries, including Poland, implemented national and local emergency management plans to deal with the imminent threat of SARS-CoV-2 infection, one of the most serious in this century, according to many experts. In the era of pandemic, during which an epidemiological regime and social distancing are constantly recommended, and routine medical care and planned surgical procedures have been postponed or significantly reduced, patients and their physicians have to struggle on a daily basis with difficult access to diagnostic and therapeutic procedures. This is a great challenge for both groups. The aim of this study is to assess the current state of knowledge about thyreological diseases during the COVID-19 pandemic and to provide indications for the introduced therapeutic changes on the basis of recent scientific literature published up to December 2020 and searches of the PubMed, Google Scholar, EMBASE, and Web of Science databases, which searched for keywords related to SARS-CoV-2 and its influence on thyreology problems. The main focus was on diagnostic and therapeutic differences in the era of the COVID-19 pandemic, bearing in mind the most common endocrinopathies, i.e. hypothyroidism and hyperthyroidism, as well as advantages and disadvantages and possibilities of using telemedicine in the common practice of a specialist physician.

Thyroid disorders and SARS-CoV-2 infection: From pathophysiological mechanism to patient management.

The World Health Organization (WHO) declared the COVID-19 epidemic to be a global pandemic in March 2020. COVID-19 is an infection caused by SARS-CoV-2, a coronavirus that utilizes the angiotensin-2 converting enzyme to penetrate thyroid and pituitary cells, and may result in a "cytokine storm". Based on the pathophysiological involvement of the pituitary-thyroid axis, the current review discusses the diagnosis of abnormal thyroid function test, and the management of patients presenting with thyrotoxicosis, thyroid-associated orbitopathy and hypothyroidism in the context of SARS-CoV-2 infection.