Skip to main content
SpringerLink
Log in

A case of resistance to thyroid hormone without mutation in the thyroid hormone receptor beta

  • Case Report
  • Published:
Irish Journal of Medical Science Aims and scope Submit manuscript

Abstract

Background

Resistance to Thyroid Hormone (RTH) is a condition caused by tissue hyposensitivity to the effects of circulating thyroid hormone, and may be misdiagnosed as hyperthyroidism.

Aims

We report the first case of RTH in an Irish patient highlighting the clinical features and the pathophysiological mechanism underlying the characteristic laboratory abnormalities found in the condition.

Methods

We describe an isolated case of RTH initially misdiagnosed as hyperthyroidism, and detail the investigations which ultimately led to the correct diagnosis. Genetic screening of the thyroid hormone receptor beta gene was performed.

Results

Thyroid function tests including T3 suppression test and TRH-stimulation test suggested a diagnosis of RTH. Genetic testing failed to demonstrate a mutation in the thyroid hormone receptor.

Conclusion

RTH is a rare inherited condition that may be misdiagnosed as hyperthyroidism. The case we describe most likely results from a de novo mutation in an as yet undiscovered gene. RTH should be considered in patients with elevated thyroid hormone levels and normal TSH so that unnecessary and potentially harmful treatment can be avoided.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Snyder D, Sesser D, Skeels M. Thyroid disorders in newborn infants with elevated screening T4. Thyroid 1997; 7 (Suppl 1): S1–29(abst)

    Google Scholar 

  2. Refetoff S, Weiss RE, Usala SJ. The syndromes of resistance to thyroid hormone.Endocr Rev 1993; 14: 348–399

    CAS  PubMed  Google Scholar 

  3. Yen PM. Molecular basis of resistance to thyroid hormone.Trends Endocrinol Metab 2003; 14(7): 327–333

    Article  CAS  PubMed  Google Scholar 

  4. Takeda K, Sakurai A, De Groot U, Refetoff S. Recessive inheritance of thyroid hormone resistance caused by complete deletion of the protein-coding region of the thyroid hormone receptor-gene.J Clin Endocrinol Metab 1992; 74: 49–55

    Article  CAS  PubMed  Google Scholar 

  5. Beck-Peccoz P, Chatterjee VKK. The variable clinical phenotype in thyroid hormone resistance syndrome.Thyroid 1994; 4(2): 225–32

    Article  CAS  PubMed  Google Scholar 

  6. Brucker-Davis F, Skarulis MC, Grace MB et al. Genetic and clinical features of 42 kindreds with resistance to thyroid hormone. The National Institutes of Health prospective study.Ann Int Med 1995; 123(8): 572–583

    CAS  PubMed  Google Scholar 

  7. Weiss RE, Macocci C, Bruno-Bossio G, Refetoff S. Multiple genetic factors in the heterogeneity of Thyroid Hormone Resistance.J Clin Endocrinol Metab 1993; 76(1): 257–259

    Article  CAS  PubMed  Google Scholar 

  8. Pohlenz J, Weiss RE, Macchia PE et al. Five new families with Resistance to Thyroid Hormone not caused by mutations in the thyroid hormone receptor gene.J Clin Endocrinol Metab 1999; 84(11): 3919–3928

    Article  CAS  PubMed  Google Scholar 

  9. Weiss RE, Hayashi Y, Nagaya T et al. Dominant inheritance of Resistance to Thyroid Hormone not linked to defects in the thyroid hormone receptor or genes may be due to a defective cofactor.J Clin Endocrinol Metab 1996; 81(12): 4196–4203

    Article  CAS  PubMed  Google Scholar 

  10. Gauthier K, Chassande O, Platerotti M et al. Different functions for the thyroid hormone receptors TRα and TRβ in the control of thyroid hormone production and post-natal development.EMBO J 1999; 18: 623–631

    Article  CAS  PubMed  Google Scholar 

  11. Kaneshige M, Suzuki H, Kaneshige K et al. A targeted dominant negative mutation of the thyroid hormone alpha 1 receptor causes increased mortality, infertility, and dwarfism in mice.Proc. Natl.Acad. Sci. (USA) 2001; 98: 15095–15100

    Article  CAS  Google Scholar 

  12. Liu YY, Schultz JJ, Brent GA. A thyroid hormone receptor alpha gene mutation (P398H) is associated with visceral adiposity and impaired catecholamine-stimulated lipolysis in mice.J. Biol. Chem. 2003; 278: 38913–38920

    Article  CAS  PubMed  Google Scholar 

  13. Weiss RE, Xu J, Ning G, Pohlenz J, O’Malley BW, Refetoff S. Mice deficient in the steroid receptor coactivator-1 (SRC-1) are resistant to thyroid hormone.EMBO J 1999; 18: 1900–1904

    Article  CAS  PubMed  Google Scholar 

  14. Brown NS, Smart A, Sharma V et al. Thyroid hormone resistance and increased metabolic rate in the RXR-gamma-deficient mice.J Clin Invest 2000; 106: 73–79

    Article  CAS  PubMed  Google Scholar 

  15. Reutrakul S, Sadow PM, Pannain S et al. Search for Abnormalities of Nuclear Corepressors, Coactivators, and a Coregulator in Families without Mutations in Thyroid Hormone Receptor β or α Genes.J Clin Endocrinol Metab 2000; 85(10): 3609–17

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept of Endocrinology, Royal College of Surgeons, Connolly Hospital Blanchardstown, Dublin 15

    J. H. McDermott, A. Agha, M. McMahon & S. Sreenan

  2. Dept of Endocrinology, Trinity College Dublin, St James’s Hospital, Dublin, Ireland

    D. Gasparro

  3. Depts of Medicine, University of Chicago, Chicago, Illinois, USA

    L. Moeller & S. Refetoff

  4. Depts of Pediatrics and the Committee on Genetics, University of Chicago, Chicago, Illinois, USA

    S. Refetoff

  5. Depts of Human Genetics, University of Chicago, Chicago, Illinois, USA

    A. M. Dumitrescu

Authors
  1. J. H. McDermott
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Agha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. McMahon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Gasparro
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L. Moeller
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. M. Dumitrescu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S. Refetoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. S. Sreenan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Sreenan.

Additional information

Supported in part by grants DK15070 and RR00055 from the National Institutes of Health, USA

Rights and permissions

Reprints and permissions

About this article

Cite this article

McDermott, J.H., Agha, A., McMahon, M. et al. A case of resistance to thyroid hormone without mutation in the thyroid hormone receptor beta. Ir J Med Sci 174, 60–64 (2005). https://doi.org/10.1007/BF03168985

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03168985

Keywords

Search

Navigation