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      Unexpected cure of a toxic nodule in a multinodular goiter induced by immune checkpoint inhibitors: a case report

      case-report

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          Abstract

          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.

          Related collections

          Most cited references14

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          Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma

          Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma.
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            Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights Into Underlying Involved Mechanisms.

            Thyroid immune-related adverse events (irAEs) in patients treated with programmed death receptor-1 (PD-1) blockade are increasingly recognized as one of the most common adverse effects. Our aim was to determine the incidence and examine the potential mechanisms of anti-PD-1-induced thyroid irAEs.
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              Is Open Access

              Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study

              Abstract Context Immune checkpoint inhibitors, including anti–programmed cell death-1 (PD-1) antibodies, have become promising treatments for a variety of advanced malignancies. However, these medicines can cause immune-related adverse events (irAEs), including endocrinopathies. Objective This study examined the incidence of endocrine irAEs induced by nivolumab. Patients and Main Outcome Measured Sixty-six patients treated with nivolumab at Nagoya University Hospital were prospectively evaluated for pituitary hormones, thyroid function, antithyroid antibodies (Abs), and glucose levels every 6 weeks after the initiation of nivolumab for 24 weeks. Results Four out of 66 patients developed destructive thyroiditis, and three patients developed hypothyroidism requiring levothyroxine replacement. The prevalence of positive anti-thyroglobulin Abs (TgAbs) and/or anti–thyroid peroxidase Abs (TPOAbs) at baseline was significantly higher in the group that developed destructive thyroiditis (3/4) compared with the group that did not develop thyroiditis (3/62; P = 0.002). There were no significant differences in other clinical variables between the groups. There were no endocrine irAEs other than destructive thyroiditis during the 24 weeks. The prevalence of TgAbs and/or TPOAbs at baseline was not associated with the development of other irAEs, including pneumonitis, colitis, or skin reactions. Conclusions Our real-world data showed that destructive thyroiditis was an endocrine irAE that was frequently induced by nivolumab and was significantly associated with positive TgAbs and/or TPOAbs before treatment. Our findings indicate that evaluating these Abs before treatment may help identify patients with a high risk of thyroidal irAEs and may have important clinical benefit.

                Author and article information

                Journal
                Eur Thyroid J
                Eur Thyroid J
                ETJ
                European Thyroid Journal
                Bioscientifica Ltd (Bristol )
                2235-0640
                2235-0802
                26 May 2022
                01 August 2022
                : 11
                : 4
                : e220024
                Affiliations
                [1 ]Department of Endocrinology , Diabetology and Metabolism, Huriez Hospital, Lille University Hospital, Lille, France
                [2 ]University of Lille , Lille, France
                [3 ]Department of Dermatology , Lille University Hospital, Lille, France
                [4 ]Department of Nuclear Medicine , Valenciennes Hospital Center, Valenciennes, France
                Author notes
                Correspondence should be addressed to H Dupuis: hippolyte.dupuis.etu@ 123456univ-lille.fr
                Author information
                http://orcid.org/0000-0003-0052-4675
                Article
                ETJ-22-0024
                10.1530/ETJ-22-0024
                9254277
                35621352
                566cb84c-1ec8-4966-b8f7-1f2863097543
                © The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 29 April 2022
                : 26 May 2022
                Categories
                Case Report

                thyroid atrophy,immune checkpoint inhibitors,toxic nodule,multinodular goiter,destructive thyroiditis

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