Keywords
Mutation
Thyroid Hormone Resistance Syndrome
Thyrotropin
Thyroxine
Triiodothyronine
DNA
Genetic Counseling
Thyroid hormone beta receptor
How to Cite
Abstract
Introduction: Variants in the beta thyroid hormone receptor gene are the main cause of thyroid hormone resistance syndrome. The inheritance is autosomal dominant and is characterized by decreased sensitivity of tissues to thyroid hormones. The clinical manifestations are variable with symptoms of hyperthyroidism or hypothyroidism.
Purpose: To document a potentially pathogenic genetic variant of the thyroid hormone receptor beta gene related to RHT syndrome not reported in the literature and provide information on the diagnostic approach.
Case presentation: A 43-year-old man presented with symptoms of hyperthyroidism and who was found to have persistently elevated free T4 levels with an inappropriately normal TSH. Simple and contrast-enhanced magnetic resonance imaging of the sella turca showed a pituitary gland without lesions. A TRH stimulation test was performed, obtaining an adequate response indicating a presumptive diagnosis of THR. The genetic study revealed a variant c.1046_1047insCCTGGT(p.Val349_Ser350insLeuVal) in the THRB gene, the bioinformatic analysis of the protein was carried out, indicating that it was pathogenic with a confidence of 89.4%.
Discussion: The diagnostic suspicion is given by the discrepancy in the values of thyrotropin, thyroxine and triiodothyronine. A complete diagnostic approach must be carried out, ruling out interference in the tests, abnormalities in the transport of thyroid hormones and thyrotropinoma; The TRH stimulus test guides the diagnosis and the genetic test its confirmation.
Conclusion: We report a new mutation related to the thyroid hormone resistance syndrome phenotype. This case demonstrates the importance of emphasizing genetic evaluation.
References
Gutiérrez Restrepo J, Montoya escobar JF. Síndrome de resistencia a las hormonas tiroideas: reporte de un caso. Med Lab. 2013;19:161-71.
Flórez Romero A, Hurtado Amézquita Y, León Muñoz L, Révérend Lizcano C. Resistencia a la hormona tiroidea: revisión de la literatura. Rev Colomb Endocrinol Diabet Metab. 2023;10(1):e741. https://doi.org/10.53853/encr.10.1.741
Pappa T, Refetoff S. Resistance to thyroid hormone beta: a focused review. Front Endocrinol (Lausanne). 2021;12:656551. https://doi.org/10.3389/fendo.2021.656551
Refetoff S, DeWind LT, DeGroot LJ. Familial syndrome combining deaf-mutism, stippled epiphyses, goiter and abnormally high PBI: possible target organ refractoriness to thyroid hormone. J Clin Endocrinol Metab. 1967;27(2):279-94. https://dx.doi.org/10.1210/jcem-27-2-279
Olateju TO, Vanderpump MPJ. Thyroid hormone resistance. Ann Clin Biochem. 2006;43(Pt 6):431-40. https://doi.org/10.1258/000456306778904678
Kiess W, Werther G. Best practice & research clinical endocrinology & metabolism. Hormone replacement strategies in paediatric and adolescent endocrine disorders. Preface. Best Pract Res Clin Endocrinol Metab. 2015 jun.;29(3):313-4. https://doi.org/10.1016/j.beem.2015.04.012
Persani L, Campi I. Syndromes of resistance to thyroid hormone action. Exp Suppl. 2019;111:55-84. https://doi.org/10.1007/978-3-030-25905-1_5
Refetoff S, Bassett JHD, Beck-Peccoz P, Bernal J, Brent G, Chatterjee K, et al. Classification and proposed nomenclature for inherited defects of thyroid hormone action, cell transport, and metabolism. J Clin Endocrinol Metab. 2014;99(3):768-70. https://doi.org/10.1210/jc.2013-3393
Mooradian AD. Age-related resistance to thyroid hormone action. Drugs Aging. 2019 nov. 1;36(11):1007-14. https://doi.org/10.1007/s40266-019-00711-7
Rivas AM, Lado-Abeal J. Thyroid hormone resistance and its management. Proc (Bayl Univ Med Cent). 2016 dic. 11;29(2):209-11. https://doi.org/10.1080/08998280.2016.11929421
Durán P, Mejía L, Lozano MC, Salguero F, Laverde G, Lattig MC. Resistencia a la hormona tiroidea en dos familias colombianas: identificación y caracterización de mutaciones en el receptor beta de la hormona tiroidea. Medicina. 2013;35(1):7-16. https://revistamedicina.net/index.php/Medicina/article/view/45
Censi S, Barollo S, Watutantrige-Fernando S, Manso J, Ferrara AM, Mian C. A novel thyroid hormone receptor beta mutation (G357R) in a family with resistance to thyroid hormone beta: extending the borders of the “hot” region in the THRB gene. Thyroid. 2019;29(3):449-51. https://doi.org/10.1089/thy.2018.0201
Valdes Socin H, Chanson P, Delemer B, Tabarin A, Rohmer V, Mockel J, et al. The changing spectrum of TSH-secreting pituitary adenomas: diagnosis and management in 43 patients. Eur J Endocrinol. 2003;148(4):433-42. https://doi.org/10.1530/eje.0.1480433
Beck-Peccoz P, Persani L, Mannavola D, Campi I. Pituitary tumours: TSH-secreting adenomas. Best Pract Res Clin Endocrinol Metab. 2009;23(5):597-606. https://doi.org/10.1016/j.beem.2009.05.006
Gurnell M, Halsall DJ, Chatterjee VK. What should be done when thyroid function tests do not make sense? Clin Endocrinol (Oxf). 2011;74(6):673-8. https://doi.org/10.1111/j.1365-2265.2011.04023.x
Beck-Peccoz P, Persani L. Thyrotropinomas. Endocrinol Metab Clin North Am. 2008;37(1):123-34. https://doi.org/10.1016/j.ecl.2007.10.001
Beck-Peccoz P, Giavoli C, Lania A. A 2019 update on TSH-secreting pituitary adenomas. J Endocrinol Invest. 2019;42(12):1401-6. https://doi.org/10.1007/s40618-019-01066-x
Tjörnstrand A, Nyström HF. Diagnosis of endocrine disease: diagnostic approach to TSH-producing pituitary adenoma. Eur J Endocrinol. 2017;177(4):R183-97. https://doi.org/10.1530/eje-16-1029
Bourebaba N, Ngo TH, ?mieszek A, Bourebaba L, Marycz K. Sex hormone binding globulin as a potential drug candidate for liver-related metabolic disorders treatment. Biomed Pharmacother. 2022;153. https://doi.org/10.1016/j.biopha.2022.113261
Ohba K. An update on the pathophysiology and diagnosis of inappropriate secretion of thyroid-stimulating hormone. Int J Mol Sci. 2021;22(12). https://doi.org/10.3390/ijms22126611
Beck-Peccoz P, Brucker-Davis F, Persani L, Smallridge RC, Weintraub BD. Thyrotropin-secreting pituitary tumors. Endocr Rev. 1996;17(6):610-38. https://doi.org/10.1210/edrv-17-6-610
Macchia E, Lombardi M, Raffaelli V, Piaggi P, Macchia L, Scattina I, et al. Clinical and genetic characteristics of a large monocentric series of patients affected by thyroid hormone (Th) resistance and suggestions for differential diagnosis in patients without mutation of Th receptor ?. Clin Endocrinol (Oxf). 2014;81(6):921-8. https://doi.org/10.1111/cen.12556
Briet C, Suteau V, Illouz F, Rodien P. Thyrotropin-secreting tumor “TSH-PitNET”: From diagnosis to treatment. Ann Endocrinol (París). 2023;84(4). https://doi.org/10.1016/j.ando.2023.01.004
Mannavola D, Persani L, Vannucchi G, Zanardelli M, Fugazzola L, Verga U, et al. Different responses to chronic somatostatin analogues in patients with central hyperthyroidism. Clin Endocrinol (Oxf). 2005;62(2):176-81. https://doi.org/10.1111/j.1365-2265.2004.02192.x
Sun H, Cao L, Zheng R, Xie S, Liu C. Update on resistance to thyroid hormone syndrome?. Ital J Pediatr. 2020;46(1):1-5. https://doi.org/10.1186%2Fs13052-020-00929-x
Singh, B.K., Yen, P.M. A clinician’s guide to understanding resistance to thyroid hormone due to receptor mutations in the TR? and TR? isoforms. Clin Diabetes Endocrinol 3, 8 (2017). https://doi.org/10.1186/s40842-017-0046-z
Santos Mata MA, Ariza Jimenez AB, Macias Lopez F, de la Camara Moraño C. Thyroid hormone resistance: multicentrical case series study. Horm Metab Res. 2022;54(2):67-75. https://doi.org/10.1055/a-1725-8533
Moran C, Chatterjee K. Resistance to thyroid hormone due to defective thyroid receptor alpha. Best Pract Res Clin Endocrinol Metab. 2015;29(4):647-57. https://doi.org/10.1016/j.beem.2015.07.007
Bernal J. [Thyroid hormone resistance syndromes]. Endocrinol Nutr. 2011;58(4):185-96. https://doi.org/10.1016/j.endonu.2011.02.001
Concolino P, Costella A, Paragliola RM. Mutational landscape of resistance to thyroid hormone beta (RTH?). Mol Diagn Ther. 2019;23(3):353-68. https://doi.org/10.1007/s40291-019-00399-w
Ramos LS, Kizys MML, Kunii IS, Spinola-Castro AM, Nesi-França S, Guerra RA, et al. Assessing the clinical and molecular diagnosis of inherited forms of impaired sensitivity to thyroid hormone from a single tertiary center. Endocrine. 2018;62(3):628-38. https://doi.org/10.1007/s12020-018-1673-6
Dieu X, Sueur G, Moal V, Boux de Casson F, Bouzamondo N, Bouhours N, et al. Apparent resistance to thyroid hormones: from biological interference to genetics. Ann Endocrinol (París). 2019;80(5-6):280-5. https://doi.org/10.1016/j.ando.2019.06.005
Tagami T. An overview of thyroid function tests in subjects with resistance to thyroid hormone and related disorders. Endocr J. 2021;68(5):509-17. https://doi.org/10.1507/endocrj.ej21-0059
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