Refetoff syndrome (GTHR) – 6 Symptoms and Signs

What is Refetoff syndrome (GTHR)

This congenital genetic disorder is an autosomal recessive form of thyroid hormone resistance

This condition is caused by mutation in the thyroid hormone receptor gene, as is selective pituitary resistance to thyroid hormone 


  1. Deafness-thyroid hormone resistance syndrome
  2. Generalized resistance to thyroid hormone
  3. GTHR
  4. Thyroid Hormone Unresponsiveness


40 cases of this condition have been reported worldwide

Age of onset

  1. Childhood
  2. Infancy
  3. Neonatal

What are the Symptoms and Signs?

  1. Ears– Congenital deafness
  2. Low birth weight for dates
  3. EyesExophthalmos
  4. Skeleton– Stippled epiphyses
  5. NeckGoiter
  6. Endocrine– End organ unresponsiveness to thyroid hormone
    – Thyroid hormone receptor-beta gene (THR1) deletion
    – Clinical euthyroidism


  • Abnormally high PBI
  • – Elevated blood thyroid hormones
  • – Elevated thyrotropin
  • – Normal response to thyrotropin-releasing hormone

Research Reports of Refetoff syndrome

A case of refetoff syndrome

  • A 22-year old man with a goiter and clinical manifestations of mild thyrotoxicosis (finger tremor, palpitation, tachycardia) was diagnosed as a syndrome of inappropriate secretion of TSH.
  • Serum concentrations of T4, free T4, T3 and TSH were 24.1 micrograms/100 ml, 4.07 ng/100 ml, 261 ng/100 ml and 1.72 microU/ml, respectively.
  • Thyroidal 131I uptake at 24 hr was 80%.
  • The BMR was within the normal range. He had a normal TSH response to TRH (500 micrograms) with a peak level of 23.8 microU/ml.
  • The basal level of alpha-subunit of TSH was not elevated (0.35 ng/ml).
  • Oral 1-T3 administration (75 and 150 micrograms daily) raised serum T3 concentration, reduced basal TSH and blunted TSH response to TRH.
  • The diurnal variation of TSH was maintained.
  • There was no evidence of abnormalities in the secretion of other pituitary hormones.
  • These findings were compatible with thyroid hormone resistance.
  • However, the presence of a microadenoma in the pituitary gland was suspected with CT scan.
  • Bilateral and simultaneous venous sampling for TSH from inferior petrosal sinus showed no gradient in TSH concentration indicating that a TSH secreting pituitary tumor was unlikely.
  • These data suggest that inappropriate TSH secretion in the present patient is resulted from resistance to thyroid hormone.
  • In the present study selective venous sampling is useful to differentiate the thyroid hormone resistance from a TSH secreting tumor.


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