Skip to main content
Journal cover image

Extreme thyroid hormone resistance in a patient with a novel truncated TR mutant.

Publication ,  Journal Article
Phillips, SA; Rotman-Pikielny, P; Lazar, J; Ando, S; Hauser, P; Skarulis, MC; Brucker-Davis, F; Yen, PM
Published in: J Clin Endocrinol Metab
November 2001

Resistance to thyroid hormone (RTH) is a syndrome in which patients have elevated thyroid hormone (TH) levels and decreased sensitivity to its action. We describe a child with extreme RTH and a severe phenotype. A 22-month-old female presented to the NIH with goiter, growth retardation, short stature, and deafness. Additionally, the patient had hypotonia, mental retardation, visual impairment, and a history of seizures. Brain magnetic resonance imaging showed evidence of demyelination and bilateral ventricular enlargement. The patient had markedly elevated free T3 and free T4 levels of more than 2000 pg/dl (normal, 230-420 pg/dl) and more than 64 pmol/liter (normal, 10.3-20.6 pmol/liter), respectively, and TSH of 6.88 mU/liter (normal, 0.6-6.3 mU/liter). These are the highest TH levels reported for a heterozygous RTH patient. A T3 stimulation test confirmed the diagnosis of RTH in the pituitary and peripheral tissues. Molecular analyses of the patient's genomic DNA by PCR identified a single base deletion in exon 10 of her TRbeta gene that resulted in a frameshift and early stop codon. This, in turn, encoded a truncated receptor that lacked the last 20 amino acids. Cotransfection studies showed that the mutant TR was transcriptionally inactive even in the presence of 10(-6) M T3 and had strong dominant negative activity over the wild-type receptor. It is likely that the severely defective TRbeta mutant contributed to the extreme RTH phenotype and resistance in our patient.

Duke Scholars

Published In

J Clin Endocrinol Metab

DOI

ISSN

0021-972X

Publication Date

November 2001

Volume

86

Issue

11

Start / End Page

5142 / 5147

Location

United States

Related Subject Headings

  • Triiodothyronine
  • Transfection
  • Transcription, Genetic
  • Thyroxine
  • Thyroid Hormone Resistance Syndrome
  • Phenotype
  • Magnetic Resonance Imaging
  • Infant
  • Humans
  • Gene Deletion
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Phillips, S. A., Rotman-Pikielny, P., Lazar, J., Ando, S., Hauser, P., Skarulis, M. C., … Yen, P. M. (2001). Extreme thyroid hormone resistance in a patient with a novel truncated TR mutant. J Clin Endocrinol Metab, 86(11), 5142–5147. https://doi.org/10.1210/jcem.86.11.8051
Phillips, S. A., P. Rotman-Pikielny, J. Lazar, S. Ando, P. Hauser, M. C. Skarulis, F. Brucker-Davis, and P. M. Yen. “Extreme thyroid hormone resistance in a patient with a novel truncated TR mutant.J Clin Endocrinol Metab 86, no. 11 (November 2001): 5142–47. https://doi.org/10.1210/jcem.86.11.8051.
Phillips SA, Rotman-Pikielny P, Lazar J, Ando S, Hauser P, Skarulis MC, et al. Extreme thyroid hormone resistance in a patient with a novel truncated TR mutant. J Clin Endocrinol Metab. 2001 Nov;86(11):5142–7.
Phillips, S. A., et al. “Extreme thyroid hormone resistance in a patient with a novel truncated TR mutant.J Clin Endocrinol Metab, vol. 86, no. 11, Nov. 2001, pp. 5142–47. Pubmed, doi:10.1210/jcem.86.11.8051.
Phillips SA, Rotman-Pikielny P, Lazar J, Ando S, Hauser P, Skarulis MC, Brucker-Davis F, Yen PM. Extreme thyroid hormone resistance in a patient with a novel truncated TR mutant. J Clin Endocrinol Metab. 2001 Nov;86(11):5142–5147.
Journal cover image

Published In

J Clin Endocrinol Metab

DOI

ISSN

0021-972X

Publication Date

November 2001

Volume

86

Issue

11

Start / End Page

5142 / 5147

Location

United States

Related Subject Headings

  • Triiodothyronine
  • Transfection
  • Transcription, Genetic
  • Thyroxine
  • Thyroid Hormone Resistance Syndrome
  • Phenotype
  • Magnetic Resonance Imaging
  • Infant
  • Humans
  • Gene Deletion