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      Growth hormone and insulin-like growth factor 1 affect the severity of Graves’ disease

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          Abstract

          Graves’ disease, the most common form of hyperthyroidism in iodine-replete countries, is associated with the presence of immunoglobulins G (IgGs) that are responsible for thyroid growth and hyperfunction. In this article, we report the unusual case of a patient with acromegaly and a severe form of Graves’ disease. Here, we address the issue concerning the role of growth hormone (GH) and insulin-like growth factor 1 (IGF1) in influencing thyroid function. Severity of Graves’ disease is exacerbated by coexistent acromegaly and both activity indexes and symptoms and signs of Graves’ disease improve after the surgical remission of acromegaly. We also discuss by which signaling pathways GH and IGF1 may play an integrating role in regulating the function of the immune system in Graves’ disease and synergize the stimulatory activity of Graves’ IgGs.

          Learning points:
          • Clinical observations have demonstrated an increased prevalence of euthyroid and hyperthyroid goiters in patients with acromegaly.

          • The coexistence of acromegaly and Graves’ disease is a very unusual event, the prevalence being <1%.

          • Previous in vitro studies have showed that IGF1 synergizes the TSH-induced thyroid cell growth-activating pathways independent of TSH/cAMP/PKA cascade.

          • We report the first case of a severe form of Graves’ disease associated with acromegaly and show that surgical remission of acromegaly leads to a better control of symptoms of Graves’ disease.

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          Most cited references53

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          Immune-neuro-endocrine interactions: facts and hypotheses.

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            Insulin-like growth factor-I regulation of immune function: a potential therapeutic target in autoimmune diseases?

            This topically limited review explores the relationship between the immune system and insulin-like growth factors (IGF-I and IGF-II) and the proteins through which they act, including IGF-I receptor (IGF-IR) and the IGF-I binding proteins. The IGF/IGF-IR pathway plays important and diverse roles in tissue development and function. It regulates cell cycle progression, apoptosis, and the translation of proteins. Many of the consequences ascribed to IGF-IR activation result from its association with several accessory proteins that are either identical or closely related to those involved in insulin receptor signaling. Relatively recent awareness that IGF-I and IGF-IR regulate immune function has cast this pathway in an unexpected light; it may represent an important switch governing the quality and amplitude of immune responses. IGF-I/IGF-IR signaling may also participate in the pathogenesis of autoimmune diseases, although its relationship with these processes seems complex and relatively unexplored. On the one hand, IGF-I seems to protect experimental animals from developing insulin-deficient diabetes mellitus. In contrast, activating antibodies directed at IGF-IR have been detected in patients with Graves' disease, where the receptor is overexpressed by multiple cell types. The frequency of IGF-IR+ B and T cells is substantially increased in patients with that disease. Potential involvement of IGF-I and IGF-IR in the pathogenesis of autoimmune diseases suggests that this pathway might constitute an attractive therapeutic target. IGF-IR has been targeted in efforts directed toward drug development for cancer, employing both small-molecule and monoclonal antibody approaches. These have been generally well-tolerated. Recognizing the broader role of IGF-IR in regulating both normal and pathological immune responses may offer important opportunities for therapeutic intervention in several allied diseases that have proven particularly difficult to treat.
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              Physiological and pathological regulation of thyroid cell proliferation and differentiation by thyrotropin and other factors.

                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
                07 June 2017
                2017
                : 2017
                : 17-0061
                Affiliations
                [1 ]Endocrinology , ‘Casa Sollievo della Sofferenza’, IRCCS, San Giovanni Rotondo, FoggiaItaly
                [2 ]Department of Medical , Oral and Biotechnological Sciences, Dental School, University ‘G. d’Annunzio’ of Chieti-Pescara, ChietiItaly
                Author notes
                Correspondence should be addressed to A Di Cerbo; Email: Alessandro811@ 123456hotmail.it
                Article
                EDM170061
                10.1530/EDM-17-0061
                5467652
                28620496
                c367682b-55d7-47d2-8a44-1c89abf5199f
                © 2017 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

                History
                : 3 May 2017
                : 10 May 2017
                Categories
                Unique/Unexpected Symptoms or Presentations of a Disease

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