{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T10:29:58Z","timestamp":1753439398194},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T00:00:00Z","timestamp":1629331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Endocr Disord"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Thyroid stimulating hormone (TSH) receptor and local infiltrate lymphocytes have been considered as major pathological factors for developing thyroid-related ophthalmopathy. Overexpression of insulin-like growth factor-I (IGF-I) receptor has emerged as a promising therapeutic target for refractory patients. However, the relationship between activation of growth hormone (GH)\/IGF-I receptor signaling and development or exacerbation of thyroid ophthalmopathy has not been elucidated. Herein we describe a case that provides further clarification into the association between thyroid-related ophthalmopathy and GH\/IGF-I receptor signaling.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>A 62-year-old Japanese female diagnosed with thyroid-related ophthalmopathy was admitted to Kurume University Hospital. She had received daily administration of GH subcutaneously for severe GH deficiency; however, serum IGF-I levels were greater than +\u20092 standard deviation based on her age and sex. She exhibited mild thyrotoxicosis and elevation in levels of TSH-stimulating antibody. Discontinuation of GH administration attenuated the clinical activity scores of her thyroid-related ophthalmopathy. Additionally, concomitant use of glucocorticoid and radiation therapies resulted in further improvement of thyroid-related ophthalmopathy. The glucocorticoid administration was reduced sequentially, followed by successful termination. Thereafter, the patient did not undergo recurrence of thyroid-related ophthalmopathy and maintained serum IGF-I levels within normal physiological levels.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>We describe here a case in which development of thyroid-related ophthalmopathy occurred upon initiation of GH administration. GH\/IGF-I signaling was highlighted as a risk factor of developing thyroid-related ophthalmopathy. Additionally, aberrant TSH receptor expression was suggested to be a primary pathophysiological mechanism within the development of thyroid-related ophthalmopathy. Physicians should be aware of the risks incurred via GH administration, especially for patients of advanced age, for induction of thyroid-related ophthalmopathy.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12902-021-00834-2","type":"journal-article","created":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T09:06:23Z","timestamp":1629363983000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Thyroid-related ophthalmopathy development in concurrence with growth hormone administration"],"prefix":"10.1186","volume":"21","author":[{"given":"Shimpei","family":"Iwata","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Tsumura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Ashida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ichiro","family":"Tokubuchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mutsuyuki","family":"Demiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miyuki","family":"Kitamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Ohshima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamiko","family":"Yano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayako","family":"Nagayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junichi","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Munehisa","family":"Tsuruta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiichi","family":"Motomura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeo","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masatoshi","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"834_CR1","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1056\/NEJMra0905750","volume":"362","author":"RS Bahn","year":"2010","unstructured":"Bahn RS. Graves\u2019 ophthalmopathy. N Engl J Med. 2010;362:726\u201338.","journal-title":"N Engl J Med"},{"key":"834_CR2","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1159\/000443828","volume":"5","author":"L Bartalena","year":"2016","unstructured":"Bartalena L, Baldeschi L, Boboridis K, Eckstein A, Kahaly GJ, Marcocci C, et al. The 2016 European Thyroid association\/European group on graves\u2019 orbitopathy guidelines for the management of Graves\u2019 orbitopathy. Eur Thyroid J. 2016;5:9\u201326.","journal-title":"Eur Thyroid J"},{"key":"834_CR3","first-page":"3045","volume":"81","author":"EA Otto","year":"1996","unstructured":"Otto EA, Ochs C, Hansen C, Wall JR, Kahaly GJ. Orbital tissue-derived t lymphocytes from patients with Graves\u2019 ophthalmopathy recognize autologous orbital antigens. J Clin Endocrinol Metab. 1996;81:3045\u201350.","journal-title":"J Clin Endocrinol Metab"},{"key":"834_CR4","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1507\/endocrj.EJ16-0038","volume":"63","author":"Y Ueda-Sakane","year":"2016","unstructured":"Ueda-Sakane Y, Kanamoto N, Fushimi Y, Tanaka-Mizuno S, Yasuno S, Miura M, et al. Overall safety and efficacy of high-dose and low-dose intravenous glucocorticoid therapy in patients with moderate-to-severe active Graves\u2019 ophthalmopathy. Endocr J. 2016;63:703\u201314.","journal-title":"Endocr J"},{"key":"834_CR5","doi-asserted-by":"publisher","first-page":"521","DOI":"10.3389\/fimmu.2017.00521","volume":"8","author":"E Fr\u00f6hlich","year":"2017","unstructured":"Fr\u00f6hlich E, Wahl R. Thyroid autoimmunity: role of anti-thyroid antibodies in thyroid and extra-thyroidal diseases. Front Immunol. 2017;8:521.","journal-title":"Front Immunol"},{"key":"834_CR6","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1056\/NEJMoa1910434","volume":"382","author":"RS Douglas","year":"2020","unstructured":"Douglas RS, Kahaly GJ, Patel A, Sile S, Thompson EHZ, Perdok R, et al. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020;382:341\u201352.","journal-title":"N Engl J Med"},{"key":"834_CR7","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1159\/000452913","volume":"48","author":"G Bodart","year":"2017","unstructured":"Bodart G, Farhat K, Charlet-Renard C, Salvatori R, Geenen V, Martens H. The somatotrope growth hormone-releasing hormone\/growth hormone\/insulin-like growth factor-1 axis in immunoregulation and immunosenescence. Front Horm Res. 2017;48:147\u201359.","journal-title":"Front Horm Res"},{"key":"834_CR8","doi-asserted-by":"publisher","first-page":"893","DOI":"10.3390\/ijms19030893","volume":"19","author":"JJ D\u00edez","year":"2018","unstructured":"D\u00edez JJ, Sangiao-Alvarellos S, Cordido F. Treatment with growth hormone for adults with growth hormone deficiency syndrome: benefits and risks. Int J Mol Sci. 2018;19:893.","journal-title":"Int J Mol Sci"},{"key":"834_CR9","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1089\/thy.2011.0056","volume":"21","author":"K Kamijo","year":"2011","unstructured":"Kamijo K, Murayama H, Uzu T, Togashi K, Olivo PD, Kahaly GJ. Similar clinical performance of a novel chimeric thyroid-stimulating hormone receptor bioassay and an automated thyroid-stimulating hormone receptor binding assay in Graves\u2019 disease. Thyroid. 2011;21:1295\u20139.","journal-title":"Thyroid"},{"key":"834_CR10","doi-asserted-by":"publisher","first-page":"3888","DOI":"10.1210\/jc.2016-2118","volume":"101","author":"M Fleseriu","year":"2016","unstructured":"Fleseriu M, Hashim IA, Karavitaki N, Melmed S, Murad MH, Salvatori R, et al. Hormonal replacement in hypopituitarism in adults: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101:3888\u2013921.","journal-title":"J Clin Endocrinol Metab"},{"key":"834_CR11","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1089\/thy.1999.9.791","volume":"9","author":"K Kasagi","year":"1999","unstructured":"Kasagi K, Shimatsu A, Miyamoto S, Misaki T, Sakahara H, Konishi J. Goiter associated with acromegaly: sonographic and scintigraphic findings of the thyroid gland. Thyroid. 1999;9:791\u20136.","journal-title":"Thyroid"},{"key":"834_CR12","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1507\/endocrj.EJ12-0110","volume":"59","author":"T Isojima","year":"2012","unstructured":"Isojima T, Shimatsu A, Yokoya S, Chihara K, Tanaka T, Hizuka N, et al. Standardized centile curves and reference intervals of Serum Insulin-Like Growth factor-I (IGF-I) levels in a normal Japanese population using the LMS method. Endocr J. 2012;59:771\u201380.","journal-title":"Endocr J"},{"key":"834_CR13","doi-asserted-by":"publisher","first-page":"353","DOI":"10.2169\/internalmedicine.53.1518","volume":"53","author":"Y Hiromatsu","year":"2014","unstructured":"Hiromatsu Y, Eguchi H, Tani J, Kasaoka M, Teshima Y. Graves\u2019 ophthalmopathy: epidemiology and natural history. Intern Med. 2014;53:353\u201360.","journal-title":"Intern Med"},{"key":"834_CR14","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1210\/jc.2009-2470","volume":"95","author":"SD Lytton","year":"2010","unstructured":"Lytton SD, Ponto KA, Kanitz M, Matheis N, Kohn LD, Kahaly GJ. A novel thyroid stimulating immunoglobulin bioassay is a functional indicator of activity and severity of Graves\u2019 orbitopathy. J Clin Endocrinol Metab. 2010;95:2123\u201331.","journal-title":"J Clin Endocrinol Metab"},{"key":"834_CR15","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1210\/er.2018-00066","volume":"40","author":"TJ Smith","year":"2019","unstructured":"Smith TJ, Janssen JAMJL. Insulin-like Growth Factor-I receptor and thyroid-associated ophthalmopathy. Endocr Rev. 2019;40:236\u201367.","journal-title":"Endocr Rev"},{"key":"834_CR16","doi-asserted-by":"publisher","first-page":"4397","DOI":"10.4049\/jimmunol.181.6.4397","volume":"181","author":"S Tsui","year":"2008","unstructured":"Tsui S, Naik V, Hoa N, Hwang CJ, Afifiyan NF, Sinha Hikim A, et al. Evidence for an association between thyroid-stimulating hormone and insulin-like growth factor 1 receptors: a tale of two antigens implicated in Graves\u2019 disease. J Immunol. 2008;181:4397\u2013405.","journal-title":"J Immunol"},{"key":"834_CR17","doi-asserted-by":"publisher","first-page":"T29","DOI":"10.1530\/JME-17-0276","volume":"61","author":"M Mohyi","year":"2018","unstructured":"Mohyi M, Smith TJ. IGF1 receptor and thyroid-associated ophthalmopathy. J Mol Endocrinol. 2018;61:T29\u201343.","journal-title":"J Mol Endocrinol"},{"key":"834_CR18","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.coemr.2018.01.007","volume":"2","author":"CC Krieger","year":"2018","unstructured":"Krieger CC, Morgan SJ, Neumann S, Gershengorn MC. Thyroid Stimulating Hormone (TSH)\/Insulin-like Growth Factor 1 (IGF1) receptor cross-talk in human cells. Curr Opin Endocr Metab Res. 2018;2:29\u201333.","journal-title":"Curr Opin Endocr Metab Res"},{"key":"834_CR19","doi-asserted-by":"publisher","first-page":"1748","DOI":"10.1056\/NEJMoa1614949","volume":"376","author":"TJ Smith","year":"2017","unstructured":"Smith TJ, Kahaly GJ, Ezra DG, Fleming JC, Dailey RA, Tang RA, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376:1748\u201361.","journal-title":"N Engl J Med"},{"key":"834_CR20","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.1210\/jc.2014-3913","volume":"100","author":"FH Duarte","year":"2015","unstructured":"Duarte FH, Jallad RS, Bronstein MD. Clomiphene citrate for treatment of acromegaly not controlled by conventional therapies. J Clin Endocrinol Metab. 2015;100:1863\u20139.","journal-title":"J Clin Endocrinol Metab"},{"key":"834_CR21","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1515\/jpem-2016-0122","volume":"29","author":"J Szczapa-Jagustyn","year":"2016","unstructured":"Szczapa-Jagustyn J, Gotz-Wi\u0119ckowska A, Koci\u0119cki J. An update on thyroid-associated ophthalmopathy in children and adolescents. J Pediatr Endocrinol Metab. 2016;29:1115\u201322.","journal-title":"J Pediatr Endocrinol Metab"},{"key":"834_CR22","doi-asserted-by":"publisher","first-page":"5455","DOI":"10.1210\/en.2005-0714","volume":"146","author":"WT Oliver","year":"2005","unstructured":"Oliver WT, Rosenberger J, Lopez R, Gomez A, Cummings KK, Fiorotto ML. The local expression and abundance of Insulin-Like Growth Factor (IGF) binding proteins in skeletal muscle are regulated by age and gender but not local IGF-I in vivo. Endocrinology. 2005;146:5455\u201362.","journal-title":"Endocrinology"}],"container-title":["BMC Endocrine Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12902-021-00834-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12902-021-00834-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12902-021-00834-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,19]],"date-time":"2021-08-19T09:08:25Z","timestamp":1629364105000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcendocrdisord.biomedcentral.com\/articles\/10.1186\/s12902-021-00834-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,19]]},"references-count":22,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["834"],"URL":"https:\/\/doi.org\/10.1186\/s12902-021-00834-2","relation":{},"ISSN":["1472-6823"],"issn-type":[{"value":"1472-6823","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,19]]},"assertion":[{"value":"21 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures performed in this study were in accordance with the ethical standards of the Institutional Review Board of Kurume University Hospital and with the principles of the Declaration of Helsinki 2013. Written informed consent to participate in this study was obtained from the patients. The Institutional Review Board of Kurume University Hospital (2020-045) approved this report.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent for publication of the clinical details was obtained from the patients.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors have no conflicts of interest to declare.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"168"}}