Diverse Abnormalities of the c-erbAβ Thyroid Hormone Receptor Gene in Generalized Thyroid Hormone Resistance

  • Stephen J. Usala
  • Barry B. Bercu
  • Samuel Refetoff
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 299)


The syndrome of generalized thyroid hormone resistance (GTHR) was first described in 1967 in a kindred, G, with elevated free thyroid hormones and absence of the typical clinical features of hyperthyroidism (1). The proband, a 6-year-old girl, demonstrated stippled epiphyses, dysmorphic features (bird-like facies, pigeon breast, and winged scapulae) and deaf-mutism. The syndrome was transmitted as a recessive trait and affected members were the product of a consanguineous union. As children, affected members had intelligence quotients within the ranges normally seen in hearingimpaired individuals (1,2). Although minimal delay of bone age was observed in affected members, final adult height was above the parental mean. Interestingly, affected members showed a paradoxical increase of serum TSH in response to the administration of suppressive doses of T3 (3) and no significant effect of antithyroid drugs on the level of TSH (2). This constellation of clinical findings in the original kindred--stippled epiphyses, somatic abnormalities, and deafmutism--has never been reported in other kindreds with GTHR. However, less severe hearing defects, learning disabilities and growth retardation are not uncommon.


Thyroid Hormone Thyroid Hormone Receptor Thyroid Hormone Level Affected Member Thyroid Hormone Action 
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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Stephen J. Usala
    • 1
  • Barry B. Bercu
    • 2
  • Samuel Refetoff
    • 3
  1. 1.Department of MedicineEast Carolina University School of MedicineGreenvilleUSA
  2. 2.Department of PediatricsUniversity of South Florida College of MedicineTampaUSA
  3. 3.Thyroid Study Unit Departments of Medicine and PediatricsUniversity of ChicagoChicagoUSA

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