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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Case Report

A Novel TSH Receptor Gene Variant Associated with Non-Autoimmune Hyperthyrotropinemia: A Case Report

Author(s): Ilaria Piva, Simona Censi, Jacopo Manso, Susi Barollo, Loris Bertazza, Carla Scaroni, Caterina Mian and Mattia Barbot*

Volume 24, Issue 2, 2024

Published on: 31 August, 2023

Page: [273 - 276] Pages: 4

DOI: 10.2174/1871530323666230824153915

Price: $65

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Abstract

Background: Resistance to TSH is defined as reduced sensitivity to normal, biologicallyactive TSH, and abnormally high levels of TSH are needed to achieve normal levels of thyroid hormones.

Case Presentation: A 15-year-old female patient, having been treated since childhood with levothyroxine for hyperthyrotropinemia was referred to our institution complaining of tachycardia after the levothyroxine therapy had been increased. Thyroid ultrasound features were normal, and thyroid antibodies were negative. The therapy was gradually tapered in light of the symptoms, although subclinical hypothyroidism was evident at thyroid function tests. First-degree relatives were tested for thyroid function, and the father was also found to have a previously-unknown subclinical hypothyroidism. The patient underwent genetic testing for TSH receptor (TSHR) gene mutations, which revealed a gene variant hitherto not described: p.C598R (c.1792T>C). The father was also tested and was found to carry the same mutation, while other first-degree relatives were wild-type for the TSHR gene. An in-silico analysis was performed, which revealed a loss-of-function phenotype corresponding to the described variant, suggesting a novel loss-of-function TSH receptor gene mutation.

Conclusion: In this case report, we present a novel loss-of-function gene mutation in the TSH receptor gene associated with a TSH resistance phenotype.

Keywords: Non-autoimmune hyperthyrotropinemia, novel tsh receptor gene mutation, tsh receptor, thyroid, hyperthyrotropinemia, familial hyperthyrotropinemia.

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Graphical Abstract
[1]
Kleinau, G.; Worth, C.L.; Kreuchwig, A.; Biebermann, H.; Marcinkowski, P.; Scheerer, P.; Krause, G. Structural-functional features of the thyrotropin receptor: A class A G-protein-coupled receptor at work. Front. Endocrinol., 2017, 8, 86.
[http://dx.doi.org/10.3389/fendo.2017.00086] [PMID: 28484426]
[2]
Miguel, R.N.; Sanders, J.; Jeffreys, J.; Depraetere, H.; Evans, M.; Richards, T.; Blundell, T.L.; Rees Smith, B.; Furmaniak, J. Analysis of the thyrotropin receptor-thyrotropin interaction by comparative modeling. Thyroid, 2004, 14(12), 991-1011.
[http://dx.doi.org/10.1089/thy.2004.14.991] [PMID: 15650352]
[3]
Narumi, S.; Hasegawa, T. TSH resistance revisited. Endocr. J., 2015, 62(5), 393-398.
[http://dx.doi.org/10.1507/endocrj.EJ15-0131] [PMID: 25797365]
[4]
Stephenson, A.; Lau, L.; Eszlinger, M.; Paschke, R. The thyrotropin receptor mutation database update. Thyroid, 2020, 30(6), 931-935.
[http://dx.doi.org/10.1089/thy.2019.0807] [PMID: 32111150]
[5]
Alberti, L.; Proverbio, M.C.; Costagliola, S.; Romoli, R.; Boldrighini, B.; Vigone, M.C.; Weber, G.; Chiumello, G.; Beck-Peccoz, P.; Persani, L. Germline mutations of TSH receptor gene as cause of nonautoimmune subclinical hypothyroidism. J. Clin. Endocrinol. Metab., 2002, 87(6), 2549-2555.
[http://dx.doi.org/10.1210/jcem.87.6.8536] [PMID: 12050212]
[6]
Refetoff, S. Resistance to thyrotropin. J. Endocrinol. Invest., 2003, 26(8), 770-779.
[http://dx.doi.org/10.1007/BF03347364] [PMID: 14669836]
[7]
Grasberger, H.; Refetoff, S. Resistance to thyrotropin. Best Pract. Res. Clin. Endocrinol. Metab., 2017, 31(2), 183-194.
[http://dx.doi.org/10.1016/j.beem.2017.03.004] [PMID: 28648507]
[8]
Tenenbaum-Rakover, Y.; Almashanu, S.; Hess, O.; Admoni, O.; Hag-Dahood Mahameed, A.; Schwartz, N.; Allon-Shalev, S.; Bercovich, D.; Refetoff, S. Long-term outcome of loss-of-function mutations in thyrotropin receptor gene. Thyroid, 2015, 25(3), 292-299.
[http://dx.doi.org/10.1089/thy.2014.0311] [PMID: 25557138]
[9]
Barollo, S.; Pezzani, R.; Cristiani, A.; Redaelli, M.; Zambonin, L.; Rubin, B.; Bertazza, L.; Zane, M.; Mucignat-Caretta, C.; Bulfone, A.; Pennelli, G.; Casal Ide, E.; Pelizzo, M.R.; Mantero, F.; Moro, S.; Mian, C. Prevalence, tumorigenic role, and biochemical implications of rare BRAF alterations. Thyroid, 2014, 24(5), 809-819.
[http://dx.doi.org/10.1089/thy.2013.0403] [PMID: 24295088]
[10]
Sunthornthepvarakul, T.; Gottschalk, M.E.; Hayashi, Y.; Refetoff, S. Brief report: Resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene. N. Engl. J. Med., 1995, 332(3), 155-160.
[http://dx.doi.org/10.1056/NEJM199501193320305] [PMID: 7528344]
[11]
Fricke-Otto, S.; Pfarr, N.; Mühlenberg, R.; Pohlenz, J. Mild congenital primary hypothyroidism in a Turkish family caused by a homozygous missense thyrotropin receptor (TSHR) gene mutation (A593 V). Exp. Clin. Endocrinol. Diabetes, 2005, 113(10), 582-585.
[http://dx.doi.org/10.1055/s-2005-865914] [PMID: 16320156]
[12]
Calebiro, D.; Gelmini, G.; Cordella, D.; Bonomi, M.; Winkler, F.; Biebermann, H.; de Marco, A.; Marelli, F.; Libri, D.V.; Antonica, F.; Vigone, M.C.; Cappa, M.; Mian, C.; Sartorio, A.; Beck-Peccoz, P.; Radetti, G.; Weber, G.; Persani, L. Frequent TSH receptor genetic alterations with variable signaling impairment in a large series of children with nonautoimmune isolated hyperthyrotropinemia. J. Clin. Endocrinol. Metab., 2012, 97(1), E156-E160.
[http://dx.doi.org/10.1210/jc.2011-1938] [PMID: 22049173]
[13]
Russo, D.; Betterle, C.; Arturi, F.; Chiefari, E.; Girelli, M.E.; Filetti, S. A novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH. J. Clin. Endocrinol. Metab., 2000, 85(11), 4238-4242.
[http://dx.doi.org/10.1210/jc.85.11.4238] [PMID: 11095460]
[14]
Tonacchera, M.; Agretti, P.; De Marco, G.; Perri, A.; Pinchera, A.; Vitti, P.; Chiovato, L. Thyroid resistance to TSH complicated by autoimmune thyroiditis. J. Clin. Endocrinol. Metab., 2001, 86(9), 4543-4546.
[http://dx.doi.org/10.1210/jcem.86.9.7791] [PMID: 11549705]

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