15
views
0
recommends
+1 Recommend
2 collections
    0
    shares

          The flagship journal of the Society for Endocrinology. Learn more

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Autoimmune hypothyroidism and trastuzumab therapy: a rare association

      research-article

      Read this article at

      ScienceOpenPublisherPMC
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Summary

          We report a case of a woman with a diagnosis of breast cancer who unintentionally started gaining weight, feeling tired, and constipated 44 weeks after the initiation of trastuzumab. Hypothyroidism secondary to an autoimmune thyroiditis associated with trastuzumab was diagnosed, the first case described in Portugal and the fourth case described worldwide. Our intention regarding the publication of this case report is to alert the clinicians treating people with trastuzumab that they should ask the patients about symptoms of hypothyroidism and should screen the thyroid function of the patients before, during, and after the initiation of trastuzumab.

          Learning points
          • Trastuzumab is a humanized MAB used in HER2-positive breast and gastric cancer.

          • Trastuzumab-associated autoimmune thyroid disease (AITD) is rare (incidence rate in an RCT of 0.3%).

          • Manifestations of autoimmune thyroiditis associated with trastuzumab resemble those of hypothyroidism in other clinical contexts, but the presence of goiter is highlighted as a reason for medical evaluation. Biochemically, it is characterized by an increased thyroid-stimulating hormone (TSH) with or without a low FT4/FT3, and sonographically with a pattern of thyroiditis.

          • The treatment consists of levothyroxine, in a dose of 1.6–1.8 µg/kg/day, with re-evaluation of the thyroid function in 4–6 weeks.

          • We report the first case of autoimmune thyroiditis secondary to trastuzumab in Portugal.

          • It is important to evaluate the thyroid function before, during, and after the initiation of this therapeutic agent.

          Related collections

          Most cited references6

          • Record: found
          • Abstract: found
          • Article: not found

          HER2-targeted therapies — a role beyond breast cancer

          HER2 is an established therapeutic target in a large subset of women with breast cancer; a variety of agents including trastuzumab, pertuzumab, lapatinib, neratinib and trastuzumab emtansine (T-DM1) have been approved for the treatment of HER2-positive breast cancer. HER2 is also overexpressed in subsets of patients with other solid tumours. Notably, the addition of trastuzumab to first-line chemotherapy has improved the overall survival of patients with HER2-positive gastric cancer, and has become the standard-of-care treatment for this group of patients. However, trials involving pertuzumab, lapatinib and T-DM1 have failed to provide significant improvements in the outcomes of patients with HER2-positive gastric cancer. HER2-targeted therapies are also being tested in patients with other solid tumours harbouring HER2 overexpression, and/or amplifications or other mutations of the gene encoding HER2 (ERBB2), including biliary tract, colorectal, non-small-cell lung and bladder cancers. The experience with gastric cancer suggests that the successes observed in HER2-positive breast cancer might not be replicated in these other tumour types, owing to differences in the level of HER2 overexpression and other aspects of disease biology. In this Review, we describe the current role of HER2-targeted therapies beyond breast cancer and also highlight the potential of novel HER2-targeted agents that are currently in clinical development.
            • Record: found
            • Abstract: found
            • Article: not found

            Clinical Immunogenicity of rHuPH20, a Hyaluronidase Enabling Subcutaneous Drug Administration

            Recombinant human PH20 hyaluronidase (rHuPH20) is used to facilitate dispersion of subcutaneously delivered fluids and drugs. This report summarizes rHuPH20 immunogenicity findings from clinical trials where rHuPH20 was co-administered with SC human immunoglobulin, trastuzumab, rituximab, or insulin. Plasma samples were obtained from evaluable subjects participating in ten different clinical trials as well as from healthy plasma donors. A bridging immunoassay and a modified hyaluronidase activity assay were used to determine rHuPH20-reactive antibody titers and neutralizing antibodies, respectively. rHuPH20-binding antibody populations from selected subjects with positive titers were affinity-purified and subjected to further characterization such as cross-reactivity with endogenous PH20. Among individual trials, the prevalence of pre-existing rHuPH20-reactive antibodies varied between 3 and 12%, excepting the primary immunodeficiency (PID) studies. Incidence of treatment-induced rHuPH20 antibodies was 2 to 18%, with the highest titers (81,920) observed in PID. No neutralizing antibodies were observed. Within most trials, the kinetics of antibody responses were comparable between pre-existing and treatment-induced antibody responses, although responses classified as persistent were more common in subjects with pre-existing titers. There was no association between antibody positivity and either local or systemic adverse events. Pre-existing and treatment-induced antibody populations were of similar immunoglobulin isotypes and cross-reacted to endogenous PH20 to similar extents. No cross-reactivity to PH20 paralogs was detected. rHuPH20 induces only modest immunogenicity which has no association with adverse events. In addition, antibodies purified from baseline-positive individuals are qualitatively similar to those purified from individuals developing rHuPH20-reactive antibodies following exposure to the enzyme. Electronic supplementary material The online version of this article (doi:10.1208/s12248-015-9782-0) contains supplementary material, which is available to authorized users.
              • Record: found
              • Abstract: found
              • Article: not found

              Immune reconstitution syndrome and the thyroid.

              Reconstitution Graves' disease occurs in three settings. First, bone marrow transplantation from a donor with Graves' disease may cause this disease to appear in the recipient, as a result of adoptive immunity, although disordered immunoregulation secondary to graft-versus-host disease may also play a role. Second, alemtuzumab treatment for multiple sclerosis leads to the development of Graves' disease in up to a third of patients during the phase of naive T-cell expansion, which follows therapeutic lymphocyte depletion. Other reconstitution autoimmune phenomena, including immune thrombocytopaenic purpura, are also recognised after alemtuzumab administration. Finally, reconstitution Graves' disease may occur during a similar phase of CD4(+) T-cell expansion, which follows highly active antiretroviral therapy for human immunodeficiency virus infection. Again, this complication is part of a broader spectrum of immunoregulatory disturbances, which can arise after immune reconstitution. The mechanisms responsible for reconstitution Graves' disease are at present unclear, but may include a relative bias towards a Th2-mediated immune response and reduced competition for autoreactive lymphocytes to expand during the time when recovery from lymphopenia commences.

                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                27 March 2023
                2023
                : 2023
                : 2
                : 22-0412
                Affiliations
                [1 ]Hospital de Braga , EPE, Portugal
                [2 ]Faculdade de Medicina , Universidade de Coimbra, Portugal
                Author notes
                Correspondence should be addressed to V Lopes; Email: valentim.silva.lopes@ 123456hb.min-saude.pt
                Author information
                http://orcid.org/0000-0003-2835-7709
                http://orcid.org/0000-0003-0499-9790
                Article
                EDM220412
                10.1530/EDM-22-0412
                10241240
                37096975
                1e671e59-e566-463b-8b4c-73b9911f316a
                © the author(s)

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

                History
                : 20 December 2022
                : 27 March 2023
                Categories
                Adult
                Female
                White
                Portugal
                Thyroid
                Thyroid
                Unusual Effects of Medical Treatment
                Unusual Effects of Medical Treatment

                adult,female,white,portugal,thyroid,unusual effects of medical treatment,april,2023

                Comments

                Comment on this article

                Related Documents Log