Differential diagnosis between autoimmune thyrotoxicosis and thyroid hormone resistance syndrome: clinical case report

Cover Page
Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access


We report a case of 50-year-old woman with thyroid hormone resistance syndrome. For 20 years this patient have been treated for autoimmune thyrotoxicosis: she underwent thyroid surgery and then was on thyroid-blocking therapy. Repeated laboratory tests demonstrated elevated serum thyroid hormones concentrations and elevated TSH concentration. Inappropriate TSH secretion became the reason for conducting further investigations. In those cases, the diagnostic approach is complicated and cases may be referred as a syndrome of thyroid hormones resistance or as a pituitary mass. Results of magnetic resonance imaging as well as results of octreotide test did not confirm TSH-producing pituitary adenoma. Lack of consistent thyrotoxicosis symptoms and normal level of biochemical markers that reflect peripheral tissue response to excessive thyroid hormones action were regarded as an evidence for thyroid hormones resistance syndrome. In cases of thyroid hormone resistance syndrome, there is no reduction in thyroid hormones after octreotide administration and we could observe it in our patient. Thereby clinical data and laboratory tests supported the diagnosis of thyroid hormone resistance syndrome. To establish definitive diagnosis and to verify genetic cause of the disease we performed direct sequencing of the THRB gene exons 9–10.

Full Text

Restricted Access

About the authors

Natalya V. Mazurina

Endocrinology Research Centre

Author for correspondence.
Email: natalyamazurina@mail.ru
ORCID iD: 0000-0001-8077-9381
SPIN-code: 9067-3062

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036


Ekaterina A. Troshina

Endocrinology Research Centre

Email: troshina@inbox.ru
ORCID iD: 0000-0002-8520-8702
SPIN-code: 8821-8990

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036

MD, PhD, professor

Olga S. Chukhacheva

Endocrinology Research Centre

Email: ochukhacheva@gmail.com
ORCID iD: 0000-0001-5675-5419
SPIN-code: 3484-6222

Russian Federation, 11, Dm. Ulyanova street, Moscow, 117036



  1. Ross DS, Burch HB, Cooper DS, et al. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016;26(10):1343-1421. doi: https://doi.org/10.1089/thy.2016.0229
  2. Tjornstrand A, Nystrom HF. Diagnosis of endocrine disease: Diagnostic approach to TSH-producing pituitary adenoma. Eur J Endocrinol. 2017;177(4):R183-R197. doi: https://doi.org/10.1530/EJE-16-1029
  3. Dumitrescu AM, Refetoff S. The syndromes of reduced sensitivity to thyroid hormone. Biochim Biophys Acta. 2013;1830(7):3987-4003. doi: https://doi.org/10.1016/j.bbagen.2012.08.005
  4. Ortiga-Carvalho TM, Sidhaye AR, Wondisford FE. Thyroid hormone receptors and resistance to thyroid hormone disorders. Nat Rev Endocrinol. 2014;10(10):582-591. doi: https://doi.org/10.1038/nrendo.2014.143
  5. Cheng SY, Leonard JL, Davis PJ. Molecular aspects of thyroid hormone actions. Endocr Rev. 2010;31(2):139-170. doi: https://doi.org/10.1210/er.2009-0007
  6. Brent GA. Mechanisms of thyroid hormone action. J Clin Invest. 2012;122(9):3035-3043. doi: https://doi.org/10.1172/JCI60047
  7. Refetoff S, Dumitrescu AM. Syndromes of reduced sensitivity to thyroid hormone: genetic defects in hormone receptors, cell transporters and deiodination. Best Pract Res Clin Endocrinol Metab. 2007;21(2):277-305. doi: https://doi.org/10.1016/j.beem.2007.03.005
  8. Adams M, Matthews C, Collingwood TN, et al. Genetic analysis of 29 kindreds with generalized and pituitary resistance to thyroid hormone. Identification of thirteen novel mutations in the thyroid hormone receptor beta gene. J Clin Invest. 1994;94(2):506-515. doi: https://doi.org/10.1172/JCI117362
  9. Bochukova E, Schoenmakers N, Agostini M, et al. A mutation in the thyroid hormone receptor alpha gene. N Engl J Med. 2012; 366(3):243-249. doi: https://doi.org/10.1056/NEJMoa1110296
  10. Mannavola D, Persani L, Vannucchi G, et al. Different responses to chronic somatostatin analogues in patients with central hyperthyroidism. Clin Endocrinol (Oxf). 2005;62(2):176-181. doi: https://doi.org/10.1111/j.1365-2265.2004.02192.x
  11. Osuna PM, Udovcic M, Sharma MD. Hyperthyroidism and the Heart. Methodist Debakey Cardiovasc J. 2017;13(2):60-63. doi: https://doi.org/10.14797/mdcj-13-2-60
  12. Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007;116(15):1725-1735. doi: https://doi.org/10.1161/CIRCULATIONAHA.106.678326
  13. Hampl R, Kancheva R, Hill M, et al. Interpretation of sex hormone-binding globulin levels in thyroid disorders. Thyroid. 2003; 13(8):755-760. doi: https://doi.org/10.1089/105072503768499644
  14. Selva DM, Hammond GL. Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4alpha. J Mol Endocrinol. 2009;43(1):19-27. doi: https://doi.org/10.1677/JME-09-0025
  15. Nielsen J, Jensen RB, Juul A. Increased sex hormone-binding globulin levels in children and adolescents with thyrotoxicosis. Horm Res Paediatr. 2013;79:157-161. doi: https://doi.org/10.1159/000348837
  16. Nicholls JJ, Brassill MJ, Williams GR, Bassett JH. The skeletal consequences of thyrotoxicosis. J Endocrinol. 2012;213(3):209-221. doi: https://doi.org/10.1530/JOE-12-0059
  17. Williams GR, Bassett JHD. Thyroid diseases and bone health. J Endocrinol Invest. 2018;41(1):99-109. doi: https://doi.org/10.1007/s40618-017-0753-4
  18. Sadow PM, Reutrakul S, Weiss RE, Refetoff S. Resistance to thyroid hormone in the absence of mutations in the thyroid hormone receptor genes. Curr Opin Endocrinol Diabetes. 2000;7(5):253-259. doi: https://doi.org/10.1097/00060793-200010000-00008
  19. Weiss RE, Hayashi Y, Nagaya T, et al. Dominant inheritance of resistance to thyroid hormone not linked to defects in the thyroid hormone receptor alpha or beta genes may be due to a defective cofactor. J Clin Endocrinol Metab. 1996;81(12):4196-4203. doi: https://doi.org/10.1210/jcem.81.12.8954015
  20. Hennemann G, Docter R, Friesema EC, et al. Plasma membrane transport of thyroid hormones and its role in thyroid hormone metabolism and bioavailability. Endocr Rev. 2001;22(4):451-476. doi: https://doi.org/10.1210/edrv.22.4.0435
  21. Friesema EC, Ganguly S, Abdalla A, et al. Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem. 2003;278(41):40128-40135. doi: https://doi.org/10.1074/jbc.M300909200
  22. Boccone L, Mariotti S, Dessi V, et al. Allan-Herndon-Dudley syndrome (AHDS) caused by a novel SLC16A2 gene mutation showing severe neurologic features and unexpectedly low TRH-stimulated serum TSH. Eur J Med Genet. 2010;53(6):392-395. doi: https://doi.org/10.1016/j.ejmg.2010.08.001
  23. Visser WE, Friesema EC, Visser TJ. Minireview: thyroid hormone transporters: the knowns and the unknowns. Mol Endocrinol. 2011;25(1):1-14. doi: https://doi.org/10.1210/me.2010-0095
  24. Biebermann H, Ambrugger P, Tarnow P, et al. Extended clinical phenotype, endocrine investigations and functional studies of a loss-of-function mutation A150V in the thyroid hormone specific transporter MCT8. Eur J Endocrinol. 2005;153(3):359-366. doi: https://doi.org/10.1530/eje.1.01980
  25. Dumitrescu AM, Liao XH, Abdullah MS, et al. Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. Nat Genet. 2005;37(11):1247-1252. doi: https://doi.org/10.1038/ng1654
  26. Koenig RJ. Regulation of type 1 iodothyronine deiodinase in health and disease. Thyroid. 2005;15(8):835-840. doi: https://doi.org/10.1089/thy.2005.15.835
  27. Di Cosmo C, McLellan N, Liao XH, et al. Clinical and molecular characterization of a novel selenocysteine insertion sequence-binding protein 2 (SBP2) gene mutation (R128X). J Clin Endocrinol Metab. 2009;94(10):4003-4009. doi: https://doi.org/10.1210/jc.2009-0686
  28. Anselmo J, Refetoff S. Regression of a large goiter in a patient with resistance to thyroid hormone by every other day treatment with triiodothyronine. Thyroid. 2004;14(1):71-74. doi: https://doi.org/10.1089/105072504322783876
  29. Iglesias P, José Díez J. Posibilidades terapéuticas en la resistencia hipofisaria selectiva a las hormonas tiroideas. Med Clin. 2008;130(9):345-350. doi: https://doi.org/10.1157/13117351



Abstract - 1067

PDF (Russian) - 18

Remote (Russian) - 110




Copyright (c) 2019 Mazurina N.V., Troshina E.A., Chukhacheva O.S.

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

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies