European Thyroid Journal hyperthyroidism special collection

 

Hyperthyroidism presents a fascinating and occasionally challenging clinical problem. This special topic collection brings together the best of the recently published papers on this subject, including the new causes of thyrotoxicosis following SARS-CoV2 infection or vaccination, as well as a focus on Graves' disease in younger patients.

If you are interested in contributing an original research article to this collection, please submit your article proposal to etj@bioscientifica.com.

 

Hyperthyroidism

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Ringo Manta Department of Nuclear Medicine, CHU Saint Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium

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Charlotte Martin Department of Infectious Diseases, CHU Saint Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium

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Vinciane Muls Department of Gastroenterology and Endoscopy, CHU Saint-Pierre, University Libre de Bruxelles (ULB), Brussels, Belgium

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Kris G Poppe Department of Endocrinology, CHU Saint Pierre, Université Libre de Bruxelles (ULB), Brussels, Belgium

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A 22-year-old male with a history of ulcerative colitis and nephrotic syndrome treated with immunomodulatory agents including vedolizumab and mycophenolic acid developed hyperthyroidism 2 weeks following the first administration of BNT162b2 vaccine (Pfizer-BioNTech COVID-19 vaccine). Graves’ disease (GD) was diagnosed based on the elevated thyrotropin-receptor antibody, thyroid scintigraphy and ultrasound. To this day, four cases of new-onset GD following SARS-CoV-2 vaccine were reported in patients with no previous history of thyroid disease. Two cases of recurrence of GD following SARS-CoV-2 vaccine were also reported. Although the underlying mechanisms of vaccine-induced autoimmunity remain to be clarified, there is a rationale for the association between SARS-CoV-2 vaccination and the development of Th1-mediated diseases, at least in predisposed individuals. The BNT162b2 vaccine could be a trigger for GD in some patients. However, the benefit/risk ratio remains by far in favour of SARS-CoV-2 vaccination considering the potentially higher risk of severe infection in these patients.

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Sébastien Verdickt Department of Endocrinology, University Hospitals of Leuven, Leuven, Belgium

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Falco Van Nes Department of Endocrinology, University Hospitals of Leuven, Leuven, Belgium

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Carolien Moyson Department of Endocrinology, University Hospitals of Leuven, Leuven, Belgium

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Toon Maes Department of Endocrinology, Imeldaziekenhuis Bonheiden, Bonheiden, Belgium

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Paul Van Crombrugge Department of Endocrinology, OLV Ziekenhuis Aalst-Asse-Ninove, Aalst, Belgium

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Annick Van den Bruel Department of Endocrinology, AZ Sint Jan Brugge, Brugge, Belgium

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Brigitte Decallonne Department of Endocrinology, University Hospitals of Leuven, Leuven, Belgium

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Objective

We investigated whether a positive thyroid peroxidase antibody (TPO Ab) status before radioactive iodine (RAI) therapy in patients with Graves’ hyperthyroidism is a predictive factor for developing hypothyroidism post RAI.

Methods

We performed a retrospective study of patients with Graves’ hyperthyroidism with known TPO Ab status, receiving the first administration of RAI. Patients from four thyroid outpatient centres in Belgium receiving their first RAI therapy between the years 2011 and 2019 were studied. Clinical, laboratory, imaging, and treatment data were recorded from medical charts. Hypothyroidism and cure (defined as combined hypo- and euthyroidism) were evaluated in period 1 (≥2 and ≤9 months, closest to 6 months post RAI) and period 2 (>9 months and ≤24 months post RAI, closest to 12 months post RAI).

Results

A total of 152 patients were included of which 105 (69%) were TPO Ab-positive. Compared to TPO Ab-negative patients, TPO Ab-positive patients were younger, had a larger thyroid gland, and had more previous episodes of hyperthyroidism. In period 1, 89% of the TPO Ab-positive group developed hypothyroidism and 72% in the TPO Ab-negative group (P = 0.007). In period 2, the observation was similar: 88% vs 72% (P = 0.019). In the multivariate logistic regression analysis, a positive TPO Ab status was associated with hypothyroidism in period 2 (adjusted OR: 4.78; 95% CI: 1.27–20.18; P = 0.024). In period 1, the aOR was 4.16 (95% CI: 1.0–18.83; P = 0.052).

Conclusion

A positive TPO Ab status in patients with Graves’ hyperthyroidism receiving the first administration of RAI is associated with a higher risk of early hypothyroidism.

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Hippolyte Dupuis Department of Endocrinology, Diabetology and Metabolism, Huriez Hospital, Lille University Hospital, Lille, France
University of Lille, Lille, France

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Emilie Merlen Department of Endocrinology, Diabetology and Metabolism, Huriez Hospital, Lille University Hospital, Lille, France

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Arnaud Jannin Department of Endocrinology, Diabetology and Metabolism, Huriez Hospital, Lille University Hospital, Lille, France
University of Lille, Lille, France

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Philippe Jamme University of Lille, Lille, France
Department of Dermatology, Lille University Hospital, Lille, France

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Alexandre Fagart Department of Nuclear Medicine, Valenciennes Hospital Center, Valenciennes, France

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Marie-Christine Vantyghem Department of Endocrinology, Diabetology and Metabolism, Huriez Hospital, Lille University Hospital, Lille, France
University of Lille, Lille, France

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Miriam Ladsous Department of Endocrinology, Diabetology and Metabolism, Huriez Hospital, Lille University Hospital, Lille, France

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Introduction

Immune checkpoint inhibitors (ICI) are used to treat cancers including metastatic melanomas and can induce endocrine side effects. The thyroid is frequently affected with classically transient thyrotoxicosis followed by hypothyroidism. The evolution of thyroid nodules and goiters under ICI therapy is poorly described.

Case presentation

A 72-year-old male presenting with hyperthyroidism due to a toxic nodule in a multinodular goiter (MNG) started ICI therapy combining ipilimumab and nivolumab to treat metastatic melanoma. After an initial worsening of thyrotoxicosis, treated with carbimazole, he developed profound hypothyroidism, persisting after carbimazole discontinuation, needing a long-term levothyroxine supplementation. Ultrasound control performed 6 months after ICIs treatment initiation revealed diffuse thyroid atrophy with involution of all nodules. 123I-scintigraphy confirmed a destructive mechanism.

Discussion

The evolution of MNG and toxic nodules is poorly described in patients treated with ICI since systematic US evaluations are lacking. We describe for the first time a toxic nodule cured by ICI therapy inducing destructive thyroiditis.

Conclusion

Pre-existing nodules and MNG, even if toxic, are not a contraindication for ICI treatment provided the patients are carefully monitored.

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Hiroyuki Iwaki Division of Endocrinology, Department of Internal Medicine, Seirei Hamamatsu General Hospital, Hamamatsu, Japan

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Kenji Ohba Medical Education Center, Hamamatsu University School of Medicine, Hamamatsu, Japan

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Eisaku Okada Department of Community Health and Preventive Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

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Takeshi Murakoshi Obstetrics and Gynecology, Maternal and Perinatal Care Center, Seirei Hamamatsu General Hospital, Hamamatsu, Japan

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Yumiko Kashiwabara Division of Endocrinology, Department of Internal Medicine, Seirei Hamamatsu General Hospital, Hamamatsu, Japan

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Chiga Hayashi Division of Endocrinology, Department of Internal Medicine, Seirei Hamamatsu General Hospital, Hamamatsu, Japan

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Akio Matsushita Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

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Shigekazu Sasaki Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

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Takafumi Suda Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan

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Yutaka Oki Department of Metabolism and Endocrinology, Hamamatsu-Kita Hospital, Hamamatsu, Japan

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Rieko Gemma Division of Endocrinology, Department of Internal Medicine, Seirei Hamamatsu General Hospital, Hamamatsu, Japan

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Background: Several guidelines have recommended that the use of the lowest effective dose of antithyroid drugs (ATDs) that maintains maternal serum free thyroxine (FT4) levels at or moderately above the upper limit of the reference range is appropriate for fetal euthyroid status. However, little is known about whether ATD dosage affects the difference in serum FT4 levels between the mother and neonate. We conducted a retrospective study at a tertiary hospital in Japan to investigate the dose-dependent influence of ATDs on both maternal and fetal thyroid hormone status. Materials and Methods: We retrospectively examined 62 pregnant women who delivered between 2007 and 2016 and were treated for Graves’ hyperthyroidism with ATD at any stage during pregnancy. We selected individuals whose data on maternal FT4 level within 4 weeks of their deliveries and cord FT4 level of their infants at the time of delivery were available. Those with multiple pregnancies, iodine or glucocorticoid treatment, and fetal goiter detected by ultrasonography were excluded. Results: After the exclusion criteria were applied, we recruited 40 individuals. The cord FT4 levels were significantly lower than the maternal FT4 levels in patients treated with high-dosage ATDs (methimazole >5 mg daily or propylthiouracil >100 mg daily). However, there were no significant differences between maternal and cord FT4 levels in patients treated with low-dosage ATDs (methimazole ≤5 mg daily or propylthiouracil ≤100 mg daily). We selected 35 individuals whose data on maternal thyrotropin receptor-binding inhibitory immunoglobulin (TBII) level were available. Multiple linear regression analysis adjusted for ATD dosage, maternal TBII level, and gestational period found that ATD dosage was a significant predictor of the difference in serum FT4 levels between the mother and neonate. In terms of maternal complications, multiple logistic regression analysis identified maternal free triiodothyronine (FT3) level as a significant predictor of the incidence of preterm delivery. Conclusions: We found a dose-dependent influence of ATDs on the difference in serum FT4 levels between mothers with Graves’ hyperthyroidism and their neonates. Further studies to evaluate the optimal target FT4 and FT3 levels for the mother and neonate during pregnancy may improve the outcome of pregnant women with Graves’ hyperthyroidism.

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Sarah L. Lutterman Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Nitash Zwaveling-Soonawala Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Hein J. Verberne Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Frederik A. Verburg Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands

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A.S. Paul van Trotsenburg Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Christiaan F. Mooij Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Background: Graves’s disease (GD) is the most common cause of hyperthyroidism. Maximal 30% of pediatric GD patients achieve remission with antithyroid drugs. The majority of patients therefore require definitive treatment. Both thyroidectomy and radioactive iodine (RAI) are often used as definitive treatment for GD. However, data on efficacy and short- and long-term side effects of RAI treatment for pediatric GD are relatively scarce. Methods: A systematic review of the literature (PubMed and Embase) was performed to identify studies reporting the efficacy or short- and long-term side effects of RAI treatment in pediatric GD. Results: Twenty-three studies evaluating 1,283 children and adolescents treated with RAI for GD were included. The treatment goal of RAI treatment changed over time, from trying to achieve euthyroidism in the past to aiming at complete thyroid destruction and subsequent hypothyroidism in the last 3 decades. The reported efficacy of a first RAI treatment when aiming at hypothyroidism ranged from 42.8 to 97.5%, depending on the activity administered. The efficacy seems to increase with higher RAI activities. When aiming at hypothyroidism, both short- and long-term side effects of treatment are very rare. Long-term side effects were mainly seen in patients in whom treatment aimed at achieving euthyroidism. Conclusion: RAI is a safe definitive treatment option for pediatric GD when aiming at complete thyroid destruction. When aiming at hypothyroidism, the efficacy of treatment seems to increase with a higher RAI activity. Prospective studies are needed to determine the optimal RAI dosing regimen in pediatric GD.

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Lucia Russo Department of Medicine, DIMED, Internal Medicine 3, University of Padua, Padova, Italy
Department of Endocrinology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium

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Thi Ngoc Huyen Nguyen Department of Endocrinology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium

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Aglaia Kyrilli Department of Endocrinology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium

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Martin Robin Department of Nuclear Medicine, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium

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Pierre Bel Lassen Department of Urology, Hôpital Universitaire des Enfants Reine Fabiola, Université Libre de Bruxelles, Brussels, Belgium

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Rodrigo Moreno-Reyes UMRS 1166 (Inserm), Paris, France

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Bernard Corvilain Department of Endocrinology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium

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Objective: Endogenous subclinical hyperthyroidism (eSCH) is defined by subnormal serum thyroid-stimulating hormone (TSH) level. There is limited evidence of metabolic changes induced by eSCH. The aim of our work was to evaluate changes in BMI and lipid parameters after radioiodine treatment in patients with grade 1 (TSH: 0.1–0.39 mlU/L) and 2 (TSH <0.1 mlU/L) eSCH. Design: A retrospective study was performed on 74 patients with eSCH caused by benign autonomous nodular goiter which was treated with radioiodine. Methods: We assessed BMI, lipids parameters, and TSH after radioiodine therapy. The 12-month follow-up time point was used to compare the primary outcome variables. TSH was measured by the electrochemiluminescence method. Results: After radioiodine therapy, the absolute and relative increases in BMI at 12 months were significantly higher in the grade 2 group than in the grade 1 group (1.07 ± 0.27 kg/m<sup>2</sup> vs. 0.26 ± 0.15 kg/m<sup>2</sup>, respectively; p = 0.023 and 4.01 ± 0.98% vs. 1.01 ± 0.56%, respectively; p = 0.026). Compared to baseline, significant increases in the levels of total cholesterol and LDL were observed after treatment in the grade 2 eSCH group (16.7 ± 4.5 mg/dL p < 0.01 and 14.3 ± 4.1 mg/dL p < 0.01, respectively) but not in the grade 1 group. In a multivariate model, a negative correlation was observed between pretreatment TSH levels and absolute BMI gain (p < 0.01). Conclusions: After correction of eSCH, increases in BMI and LDL levels were observed only in patients with grade 2 eSCH. Pretreatment serum TSH was the main independent factor associated with BMI changes after radioiodine treatment.

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Katarzyna Pelewicz Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland

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Rafał Wolny Department of Interventional Cardiology and Angiology, National Institute of Cardiology, Warsaw, Poland

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Tomasz Bednarczuk Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland

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Piotr Miśkiewicz Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland

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Introduction: Iodinated contrast media (ICM)-induced hyperthyroidism is an underestimated, potentially severe condition; however, its prevention has not been sufficiently investigated. The aim of this study was to evaluate the influence of ICM on thyroid status, the advantages of prophylactic therapy for iodine-induced hyperthyroidism (IIH) in patients with euthyroid goiter and cardiovascular comorbidities, and the association between the incidence of IIH and thyroid volume. Methods: Thirty-six euthyroid patients undergoing procedures involving ICM administration were divided into 2 groups: the first group (n = 13) received prophylactic treatment with thiamazole or thiamazole combined with sodium perchlorate during ICM exposure; the second group (n = 23) did not receive prophylaxis. Thyroid-stimulating hormone levels were evaluated before and after ICM, and thyroid hormone levels were assessed after ICM at different points in time. The morphology of the thyroid was evaluated by ultrasonography. Results: Twenty-one patients (58%) developed hyperthyroidism after ICM. Hyperthyroidism was observed more frequently in the group without prophylactic treatment than in the group with prophylaxis (65 vs. 15%, respectively; p = 0.006). No cases of overt hyperthyroidism were observed in the group receiving thiamazole with sodium perchlorate. IIH persisted for a median time of 52.5 days. Larger thyroid volume was associated with a significantly higher occurrence of ICM-induced hyperthyroidism (p = 0.04). Conclusions: Patients with euthyroid goiter receiving ICM are at risk of developing hyperthyroidism. The occurrence of hyperthyroidism after ICM in euthyroid patients with goiter is higher in those with larger thyroid volume. The frequency of ICM-induced hyperthyroidism in euthyroid patients with goiter is lower in those receiving prophylactic therapy with thiamazole in monotherapy or in combination with sodium perchlorate than in those not receiving prophylactic treatment.

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Clotilde Saïe Thyroid and Endocrine Tumors Unit, Pitié-Salpêtrière Hospital APHP, Sorbonne University, Paris, France

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Cécile Ghander Thyroid and Endocrine Tumors Unit, Pitié-Salpêtrière Hospital APHP, Sorbonne University, Paris, France

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Samir Saheb Apheresis Unit, Pitié-Salpêtrière Hospital, AP-HP, Sorbonne University, Paris, France

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Christel Jublanc Department of Endocrinology, Pitié-Salpêtrière Hospital APHP, Sorbonne University, Paris, France

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Denis Lemesle Department of Anaesthesia, Pitié-Salpêtrière Hospital APHP, Sorbonne University, Paris, France

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Charlotte Lussey-Lepoutre Nuclear Medicine Department, Pitié-Salpêtrière Hospital APHP, Sorbonne Université, Inserm U970, Paris, France

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Laurence Leenhardt Thyroid and Endocrine Tumors Unit, Pitié-Salpêtrière Hospital APHP, Sorbonne University, Paris, France

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Fabrice Menegaux Department of Surgery, Pitié-Salpêtrière Hospital APHP, Sorbonne University, Paris, France

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Christophe Tresallet Department of Surgery, Avicennes Hospital, Paris, France

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Camille Buffet Thyroid and Endocrine Tumors Unit, Pitié-Salpêtrière Hospital APHP, Sorbonne University, Paris, France

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Introduction: Hyperthyroid patients who are unresponsive to medical treatment remain a challenging clinical problem. Objective: The goal of our study was to evaluate the use of therapeutic plasma exchange (TPE) in hyperthyroid patients and their outcome after TPE. Method: We retrospectively reviewed 22 patients who underwent TPE for refractory thyrotoxicosis in our institution: 13 with Graves’ disease, 7 with amiodarone-induced thyrotoxicosis (AIT), 1 with toxic goiter, and 1 pregnant patient with familial nonautoimmune thyrotoxicosis. Results: Before TPE, all patients had severe hyperthyroidism, and antithyroid drugs were either contraindicated or not sufficiently effective to restore euthyroidism promptly. After all the TPEs, free T<sub>4</sub> (fT4) decreased significantly by 48% (p = 0.001) and fT3 by 52% (p = 0.0001). The median number of TPE sessions per patient was 4 (range: 1–10). There were no complications during the 91 TPE sessions. Total thyroidectomy with no severe side effects was performed on 16/22 patients and 1 other patient was treated with radioactive iodine. One patient died from severe thyrotoxicosis during medical care. The remaining 4 patients were followed up without any radical treatment. For all 7 patients with AIT, iterative TPE led to a significant clinical improvement, and amiodarone was continued for 1 patient. Available treatments were continued between TPE sessions (cholestyramine for 13 patients [60%] and glucocorticoids for 16 patients [73%]). Conclusion: TPE allowed a safe decrease of 50% in thyroid hormone levels, and it should be considered for refractory hyperthyroid patients when medical treatments are contraindicated or have failed to restore euthyroidism, irrespective of the etiology of the thyrotoxicosis.

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Saeed Sohrabpour Otorhinolaryngology Research Center, Amir-Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran

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Farrokh Heidari Otorhinolaryngology Research Center, Amir-Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran

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Ebrahim Karimi Otorhinolaryngology Research Center, Amir-Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran

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Reza Ansari Otorhinolaryngology Research Center, Amir-Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran

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Ardavan Tajdini Otorhinolaryngology Research Center, Amir-Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran

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Firouzeh Heidari Otorhinolaryngology Research Center, Amir-Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran

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Introduction: Since December 2019, novel coronavirus (COVID-19) infection has been identified as the cause of an outbreak of respiratory illness in Wuhan, China. The classic presentation of COVID-19 infection was described as fever, myalgia, cough, and fatigue. Whether coronavirus can directly attack the endocrine glands is unclear. Objective: Post-viral subacute thyroiditis (SAT, de Quervain thyroiditis) has been reported following other viral infection. A limited number of SAT after COVID-19 infection have been reported up to now. Methods: Here, we reported 6 patients with SAT and positive COVID-19 serology tests. Demographic, clinical, biochemical, and imaging data were presented. Results: In this study, 6 patients (4 women and 2 men) with clinician manifestations and physical examination in favor of SAT were described. Cervical ultrasonography showed bilateral hypoechoic areas in the thyroid gland which was suggestive of SAT. Elevated C-reactive protein, erythrocyte sedimentation rate, free thyroxine, free tri-iodothyronine, and undetectable thyrotropin were found in laboratory evaluations. Both IgM and IgG were positive for COVID-19 infection, but the PCR tests were negative in all patients. Patients had history of working in a COVID center and/or family member hospitalized due to COVID-19 pneumonia. Patients were followed up for 1 month and were treated effectively with steroids. Conclusion: This report may help physicians to identify lesser-known manifestations and complications of COVID-19. Early diagnosis of COVID-19 infection results in the prevention of further transmission.

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