Vol 70, No 1 (2019)
Case report
Published online: 2018-10-30

open access

Page views 2767
Article views/downloads 1385
Get Citation

Connect on Social Media

Connect on Social Media

Resistance to thyroid hormone with a mutation of the thyroid β receptor gene in an eight-month-old infant — a case report

Elżbieta A. Foryś-Dworniczak1, Carla Moran1, Barbara Kalina-Faska1, Ewa Małecka-Tendera1, Agnieszka Zachurzok1
Pubmed: 30450533
Endokrynol Pol 2019;70(1):124-130.

Abstract

Introduction: Resistance to thyroid hormone (RTHβ) is a rare syndrome of impaired tissue responsiveness to thyroid hormones (THs). The disorder has an autosomal dominant or recessive pattern of inheritance. Most of the reported mutations have been detected in the thyroid hormone receptor β gene (THRβ). Case report: Authors present an eight-month-old infant with poor linear growth, decreased body weight, tachycardia, positive family history, and neonatal features suggestive of RTHβ. Both our patient and his mother had elevated free thyroxine, free triiodothyronine, and non-suppressed thyrotropin (TSH) concentration. The fluorescent sequencing analysis showed a heterozygous mutation c.728G > A in TRβ gene. This pathogenic variant is known to be associated with THR. Conclusions: The clinical presentation of RTHb is variable, ranging from isolated biochemical abnormalities to symptoms of thyrotoxicosis or hypothyroidism. The syndrome should be suspected in patients with increased serum TH level, accompanied by a normal or elevated TSH concentration. The affected patients require individualised management.

Article available in PDF format

View PDF Download PDF file

References

  1. Refetoff S. Resistance to thyroid hormone with and without receptor gene mutations. Ann Endocrinol. (Paris). 2003; 64(1): 23–25.
  2. Agrawal NK, Goyal R, Rastogi A, et al. Thyroid hormone resistance. Postgrad Med J. 2008; 84(995): 473–477.
  3. Lafranchi SH, Snyder DB, Sesser DE, et al. Follow-up of newborns with elevated screening T4 concentrations. J Pediatr. 2003; 143(3): 296–301.
  4. Flamant F, Baxter JD, Forrest D. International Union of Pharmacology. LIX. The pharmacology and classification of the nuclear receptor superfamily: thyroid hormone receptors. Pharmacol Rev. 2006; 58(4): 705–711.
  5. 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.
  6. Pohlenz J, Weiss RE, Macchia PE. 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.
  7. 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.
  8. Refetoff S. Resistance to thyroid hormone. In: Braverman LE, Utiger RE. ed. Werner and Ingbar’s The thyroid: a fundamental and clinical text. 9th ed. Lippincott, Williams and Wilkins, Philadelphia 2005: 1109–1129.
  9. Beck-Peccoz P, Chatterjee VK. The variable clinical phenotype in thyroid hormone resistance syndrome. Thyroid. 1994; 4(2): 225–232.
  10. Weiss RE, Refetoff S. Treatment of resistance to thyroid hormone — primum non nocere. J Clin Endocrinol Metab. 1999; 84(2): 401–404.
  11. Niklasson A, Albertsson-Wikland K. Continuous growth reference from 24th week of gestation to 24 months by gender. BMC Pediatr. 2008; 8(8).
  12. Niedźwiecka Z, Palczewska I. Wskaźniki rozwoju fizycznego w pierwszych trzech latach życia dzieci urodzonych przedwcześnie. Medycyna Wieku Rozwojowego. 1997; 1(supl. 1): 3–71.
  13. Palczewska I, Nieźwiecka Z. Wskaźniki rozwoju somatycznego dzieci i młodzieży warszawskiej. Medycyna Wieku Rozwojowego, 2001; 5. ; 52(supl. 1): 113–114.
  14. Onigata K, Yagi H, Sakurai A, et al. A novel point mutation (R243Q) in exon 7 of the c-erbA beta thyroid hormone receptor gene in a family with resistance to thyroid hormone. Thyroid. 1995; 5(5): 355–358.
  15. Onigata K, Szinnai G. Resistance to thyroid hormone. Endocr Dev. 2014; 26: 118–129.
  16. Yen PM. Molecular basis of resistance to thyroid hormone. Trends Endocrinol Metab. 2003; 14(7): 327–333.
  17. Mixson AJ, Hauser P, Tennyson G, et al. Differential expression of mutant and normal beta T3 receptor alleles in kindreds with generalized resistance to thyroid hormone. J Clin Invest. 1993; 91(5): 2296–2300.
  18. Frank-Raue K, Lorenz A, Haag C, et al. Severe form of thyroid hormone resistance in a patient with homozygous/hemizygous mutation of T3 receptor gene. Eur J Endocrinol. 2004; 150(6): 819–823.
  19. Ferrara AM, Onigata K, Ercan O, et al. Homozygous thyroid hormone receptor β-gene mutations in resistance to thyroid hormone: three new cases and review of the literature. J Clin Endocrinol Metab. 2012; 97(4): 1328–1336.
  20. Canadas KT, Rivkees SA, Udelsman R, et al. Resistance to thyroid hormone associated with a novel mutation of the thyroid β receptor gene in a four-year-old female. Int J Pediatr Endocrinol. 2011; 2011(1): 3.
  21. Weiss RE. Management of patients with resistance to thyroid hormone. Thyroid Today. 1999; 12: 1–11.
  22. Yatsuga S, Hiromatsu Y, Sasaki S, et al. A two-day-old hyperthyroid neonate with thyroid hormone resistance born to a mother with well-controlled Graves' disease: a case report. J Med Case Rep. 2012; 6: 246.
  23. Weiss RE, Stein MA, Refetoff S. Behavioral effects of liothyronine (L-T3) in children with attention deficit hyperactivity disorder in the presence and absence of resistance to thyroid hormone. Thyroid. 1997; 7(3): 389–393.