Advertisement

Hormones

, Volume 15, Issue 4, pp 534–539 | Cite as

A new TRβ mutation in resistance to thyroid hormone syndrome

  • Corina Neamţu
  • Claudiu Ţupea
  • Diana Păun
  • Anca Hoisescu
  • Adina Ghemigian
  • Samuel Refetoff
  • Chutintorn Sriphrapradang
Case report
  • 3 Downloads

Abstract

Thyroid hormones (TH) exert their actions by binding nuclear receptors alpha (TRα1) and beta (TRβ1 and TRβ2). Resistance to thyroid hormone (RTH) is a clinical syndrome with various clinical manifestations, its hallmark being decreased tissue sensitivity to the action of thyroid hormones. We report the case of a family harbouring a novel TRβ mutation. Sequencing of the TRβ gene revealed a single nucleotide substitution-C to G in codon 340: glutamine was replaced by glutamic acid. The clinical picture and biochemical and hormonal panel showed significant differences within the family, despite their sharing the same mutation. We also present the result of low-dose antithyroid treatment in one member of the family diagnosed with this rare condition.

Key words

Mutation Resistance to thyroid hormone Single nucleotide substitution Thyroid hormone receptors 

References

  1. 1.
    Refetoff S, DeWind LT, DeGroot LJ, 1967 Familial Syndrome combining deaf-mutism, stippled epiphyses, goiter, and abnormally high PBI: possible target organ refractoriness to thyroid hormone. J Clin Endocrinol Metab 27: 279–294.CrossRefGoogle Scholar
  2. 2.
    Refetoff S, Weiss RE, Usala SJ, 1993 The syndromes of resistance to thyroid hormone. Endocr Rev 14: 348–399.PubMedGoogle Scholar
  3. 3.
    Dumitrescu AM, Refetoff S, 2015 Impaired Sensitivity to Thyroid Hormone: Defects of Transport, Metabolism and Action. Thyroid Manager (https://doi.org/thyroidmanager.org).
  4. 4.
    Amor AJ, Halperin I, Alfayate R, et al, 2014 Identification of four novel mutations in the thyroid hormone receptor-β gene in 164 Spanish and 2 Greek patients with resistance to thyroid hormone. Hormones (Athens) 13: 74–78.CrossRefGoogle Scholar
  5. 5.
    Vandalem JL, Pirens G, Hennen G, 1981 Familial inappropriate TSH secretion: evidence suggesting a dissociated pituitary resistance to T3 and T4. J Endocrinol Invest 4: 413–422.CrossRefGoogle Scholar
  6. 6.
    Barsano CP, Skosey C, DeGroot LJ, et al, 1982 Serum thyroglobulin in the management of patients with thyroid cancer. Arch Intern Med 142: 763–767.CrossRefGoogle Scholar
  7. 7.
    Adams M, Matthews C, Collingwood TN, Tone Y, Beck-Peccoz P, Chatterjee KK, 1994 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 94: 506–515.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Usala SJ, Menke JB, Watson TL, et al, 1991 A new point mutation in the 3,5,3′-triiodothyronine-binding domain of the c-erbAβ thyroid hormone receptor is tightly linked to generalized resistance to thyroid hormone. J Clin Endocrinol Metab 72: 32–38.CrossRefGoogle Scholar
  9. 9.
    Dumitrescu AM, Refetoff S, 2013 Reduced sensitivity to thyroid hormone: defects of transport, metabolism and action. In Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. Braverman, LE, Cooper DS (eds), Wolters Kluver/Lippincott, Williams & Wilkins Publications, Philadelphia, PA, pp; 845–873.Google Scholar
  10. 10.
    Boccone L, Mariotti S, Dessi V, Pruna D, Meloni A, Loudianos G, 2010 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 53: 392–395.CrossRefGoogle Scholar
  11. 11.
    Dumitrescu AM, Liao XH, Abdullah MS, et al, 2005 Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. Nat Genet 37: 1247–1252.CrossRefGoogle Scholar
  12. 12.
    Cartwright D, O’Shea P, Rajanayagam O, et al, 2009 Familial dysalbuminemic hyperthyroxinemia: a persistent diagnostic challenge. Clin Chem 55: 1044–1046.CrossRefGoogle Scholar
  13. 13.
    Kaplan MM, Swartz SL, Larsen PR, 1981 Partial peripheral resistance to thyroid hormone. Am J Med 70: 1115–1121.CrossRefGoogle Scholar
  14. 14.
    Usala SJ, 1991 Molecular diagnosis and characterization of resistance to thyroid hormone syndromes. Thyroid 1: 361–367.CrossRefGoogle Scholar
  15. 15.
    Bassett JH, Harvey CB, Williams GR, 2003 Mechanisms of thyroid hormone receptor-specific nuclear and extra nuclear actions. Mol Cell Endocrinol 213: 1–11.CrossRefGoogle Scholar
  16. 16.
    Takeda K, Sakurai A, DeGroot LJ, Refetoff S, 1992 Recessive inheritance of thyroid hormone resistance caused by complete deletion of the protein-coding region of the thyroid hormone receptor-β gene. J Clin Endocrinol Metab 74: 49–55.PubMedGoogle Scholar
  17. 17.
    Bochukova E, Schoenmakers N, Agostini M, et al, 2012 A Mutation in the Thyroid Hormone Receptor Alpha Gene. N Engl J Med 366: 243–249.CrossRefGoogle Scholar
  18. 18.
    Yoh SM, Chatterjee VKK, Privalsky ML, 1997 Resistance to thyroid hormone syndrome manifests as an aberrant interaction between mutant T3 receptor and transcriptional corepressor. Mol Endocrinol 11: 470–480.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Chatterjee VKK, Nagaya T, Madison LD, Datta S, Rantoumis A, Jameson JL, 1991 Thyroid hormone resistance syndrome. Inhibition of normal receptor function by mutant thyroid hormone receptors. J Clin Invest 87: 1977–1984.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Hayashi Y, Weiss RE, Same DH, et al, 1995 Do clinical manifestations of resistance to thyroid hormone correlate with the functional alteration of the corresponding mutant thyroid hormone-β receptors? J Clin Endocrinol Metab 80: 3246–3256.CrossRefGoogle Scholar
  21. 21.
    Bantle JP, Seeling S, Mariash CN, Ulstrom RA, Oppenheimer JH, 1982 Resistance to thyroid hormones: A disorder frequently confused with Graves’ disease. Arch Intern Med 142: 1867–1871.CrossRefGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2016

Authors and Affiliations

  • Corina Neamţu
    • 1
  • Claudiu Ţupea
    • 1
  • Diana Păun
    • 1
  • Anca Hoisescu
    • 1
  • Adina Ghemigian
    • 1
  • Samuel Refetoff
    • 2
  • Chutintorn Sriphrapradang
    • 2
  1. 1.National Institute of Endocrinology “C.I. Parhon”BucharestRomania
  2. 2.University of Chicago MedicineChicagoUSA

Personalised recommendations