J Korean Med Sci.  2010 Sep;25(9):1368-1371. 10.3346/jkms.2010.25.9.1368.

A Case of Resistance to Thyroid Hormone with Thyroid Cancer

• Kim HK
• Kim D
• Yoo EH
• Lee JI
• Jang HW
• Tan AH
• Hur KY
• Kim JH
• Kim KW
• Chung JH
• Kim SW

• KMID: 1785919
• DOI: http://doi.org/10.3346/jkms.2010.25.9.1368

Abstract

Resistance to thyroid hormone (RTH) is an autosomal dominant hereditary disorder that is difficult to diagnose because of its rarity and variable clinical features. The magnitude of RTH is caused by mutations in the thyroid hormone receptor beta (TRbeta) gene. We recently treated a 38-yr-old woman with RTH who had incidental papillary thyroid carcinoma. She presented with goiter and displayed elevated thyroid hormone levels with an unsuppressed TSH. She was determined to harbor a missense mutation of M310T in exon 9 of the TRbeta gene, and diagnosed with generalized RTH. This mutation has not yet been reported in Korea. RTH is very rare and easily overlooked, but should be considered in patients who present with goiter and elevated thyroid hormone levels with an unsuppressed TSH. The association between thyroid cancer and RTH needs further study.

Keyword

Thyroid Hormone Resistance Syndrom; Thyroid Hormone Receptor; Thyroid Hormone Receptors beta; Mutation; Thyroid Neoplasms

MeSH Terms

Adult
Diagnosis, Differential
Exons
Female
Humans
Mutation, Missense
Thyroid Gland/radionuclide imaging
Thyroid Hormone Receptors beta/genetics
Thyroid Hormone Resistance Syndrome/complications/*diagnosis
Thyroid Hormones/blood
Thyroid Neoplasms/*complications/genetics/ultrasonography

Figure

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  Fig. 1 The ultrasonography of thyroid showed 0.6 cm hypoechoic nodule in the right lobe with taller-than-wide appearance, which was suspicious for malignancy.

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  Fig. 2 The 99mTechnetium thyroid scan showed diffuse enlargement of both lobes of the thyroid with homogenously increased uptake (10.1%).

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  Fig. 3 Exaggerated response of TSH to TRH stimulation was observed in the patient with resistance to thyroid hormone.

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  Fig. 4 The DNA sequence analysis of the TRβ gene showed a substitution of threonine (ACG) for methionine (ATG) at codon 310 (M310T) of exon 9.

Reference

1. Refetoff S. The Thyroid. 2005. 9th ed. Philadelphila: Lippincott Williams & Wilkins;1109–1129.

2. Yun YS, Hong SK, Ahn CW, Nam JH, Park SW, Cha BS, Song YD, Lee EJ, Lim SK, Kim KR, Lee HC, Huh KB. Mutations in thyroid hormone receptor-beta with patients with generalized resistance and pituitary resistance to thyroid hormone. J Korean Soc Endocrinol. 2000. 15:113–120.

3. Hwang JK, Kim KW, Kim TY, Kim SW, Park YJ, Park DJ, Kim SY, Lee HK, Cho BY. A case of syndrome of resistance to thyroid hormone associated with mutation (M313T) in thyroid hormone receptor beta gene. J Korean Soc Endocrinol. 2003. 18:206–213.

4. Seo JY, Yoon IS, Yoo JH, Ahn SY, Jeong HL, Shin CH, Yang SW. A case of thyroid hormone resistance (RTH). J Korean Soc Pediatr Endocrinol. 2005. 10:100–104.

5. Park TJ, Kang JK, Seo KW, Kim HJ, Chung YS, Lee KW, Jeong SY, Kim HJ, Kim DJ. A case of resistance syndrome to thyroid hormone associated with mutation (G345D) in the thyroid hormone receptor beta gene. J Korean Soc Endocrinol. 2007. 22:277–281.

6. Shin JY, Ki CS, Kim JK. Identification of a de novo mutation (H435Y) in the THRB gene in a Korean patient with resistance to thyroid hormone. Korean J Pediatr. 2007. 50:576–579.

7. Kim JH, Park TS, Baek HS, Kim GH, Yoo HW, Park JH. A newly identified insertion mutation in the thyroid hormone receptor-beta gene in a Korean family with generalized thyroid hormone resistance. J Korean Med Sci. 2007. 22:560–563.

8. Kim DY, Kim YM, Choi HH, Lee JY, Han JP, Lee SJ, Choi MG. A case of pituitary resistance to thyroid hormone with nonfunctioning pituitary microadenoma. Korean J Med. 2008. 74:94–99.

9. Kim JY, Choi ES, Lee JC, Lee KU, Kim YJ, Kim SJ, Lee YW. Resistance to thyroid hormone with missense mutation (V349M) in the thyroid hormone receptor beta gene. Korean J Intern Med. 2008. 23:45–48.

10. Cho BY. Clinical thyroidology. 2005. 2nd ed. Seoul: Korea Medical Book.

11. Usala SJ, Bale AE, Gesundheit N, Weinberger C, Lash RW, Wondisford FE, McBride OW, Weintraub BD. Tight linkage between the syndrome of generalized thyroid hormone resistance and the human c-erbA beta gene. Mol Endocrinol. 1988. 2:1217–1220.

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

13. Taniyama M, Ishikawa N, Momotani N, Ito K, Ban Y. Toxic multinodular goitre in a patient with generalized resistance to thyroid hormone who harbours the R429Q mutation in the thyroid hormone receptor beta gene. Clin Endocrinol (Oxf). 2001. 54:121–124.

14. Berker D, Aydin Y, Tutuncu YA, Isik S, Delibasi T, Berker M, Guler S, Kamel N. Somatotropin adenoma and resistance to thyroid hormone. J Endocrinol Invest. 2009. 32:284–286.

15. Lin KH, Shieh HY, Chen SL, Hsu HC. Expression of mutant thyroid hormone nuclear receptors in human hepatocellular carcinoma cells. Mol Carcinog. 1999. 26:53–61.

16. Puzianowska-Kuznicka M, Krystyniak A, Madej A, Cheng SY, Nauman J. Functionally impaired TR mutants are present in thyroid papillary cancer. J Clin Endocrinol Metab. 2002. 87:1120–1128.

17. Puzianowska-Kuznicka M, Nauman A, Madej A, Tanski Z, Cheng S, Nauman J. Expression of thyroid hormone receptors is disturbed in human renal clear cell carcinoma. Cancer Lett. 2000. 155:145–152.

18. Li Z, Meng ZH, Chandrasekaran R, Kuo WL, Collins CC, Gray JW, Dairkee SH. Biallelic inactivation of the thyroid hormone receptor beta1 gene in early stage breast cancer. Cancer Res. 2002. 62:1939–1943.

19. Horkko TT, Tuppurainen K, George SM, Jernvall P, Karttunen TJ, Makinen MJ. Thyroid hormone receptor beta1 in normal colon and colorectal cancer-association with differentiation, polypoid growth type and K-ras mutations. Int J Cancer. 2006. 118:1653–1659.

20. Suzuki H, Willingham MC, Cheng SY. Mice with a mutation in the thyroid hormone receptor beta gene spontaneously develop thyroid carcinoma: a mouse model of thyroid carcinogenesis. Thyroid. 2002. 12:963–969.