title: Clinical phenotype of a new type of thyroid hormone resistance caused by a mutation of the TRα1 receptor: consequences of LT4 treatment.
abstract: BACKGROUND
  Recently the first patients with inactivating mutations in T₃ receptor (TR)-α1 have been identified. These patients have low free T₄, low T₄, high T₃, low rT₃, and normal TSH serum levels, in combination with growth retardation, delayed bone development, and constipation.
  
  
  OBJECTIVE
  The aim of the current study was to report the effects of levothyroxine (LT4) treatment on the clinical phenotype of 2 patients (father and daughter) with a heterozygous inactivating mutation in TRα1.
  
  
  METHODS
  Both patients were treated with LT4 for the last 5 years. To evaluate the effect of LT4 treatment, LT4 was withdrawn for 35 days and subsequently reinitiated. Data were collected from medical records, by reanalysis of serum collected over the last 6 years, and by a detailed clinical evaluation.
  
  
  RESULTS
  Treatment with LT4 resulted in a suppression of serum TSH and normalization of serum free T₄ and rT₃, whereas T₃ levels remained elevated in both patients. In addition, there was a normalization of the dyslipidemia as well as a response in serum IGF-I, SHBG, and creatine kinase in the index patient. All these parameters returned to pretreatment values when LT4 was briefly stopped. LT4 also resulted in an improvement of certain clinical features, such as constipation and nerve conductance. However, cognitive and fine motor skill defects remained.
  
  
  CONCLUSIONS
  This study reports the consequences of LT4 treatment over a prolonged period of time in 2 of the first patients with a heterozygous mutation in TRα1. LT4 therapy leads to an improvement of certain but not all features of the clinical phenotype.
authors: Departments of Internal Medicine, Erasmus University Medical Center, 3000 CA Rotterdam, The Netherlands.
authors: Alies A
authors: AA
authors: van Mullem
authors: Dionisios
authors: D
authors: Chrysis
authors: Alexandra
authors: A
authors: Eythimiadou
authors: Elizabeth
authors: E
authors: Chroni
authors: Agathocles
authors: A
authors: Tsatsoulis
authors: Yolanda B
authors: YB
authors: de Rijke
authors: W Edward
authors: WE
authors: Visser
authors: Theo J
authors: TJ
authors: Visser
authors: Robin P
authors: RP
authors: Peeters
mesh_terms: D002648:Child; D003248:Constipation / Q000209:etiology / Q000517:prevention & control; D004351:Drug Resistance; D050171:Dyslipidemias / Q000209:etiology / Q000517:prevention & control; D005260:Female; D016368:Frameshift Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction / Q000187:drug effects; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics* / Q000378:metabolism; D018382:Thyroid Hormone Resistance Syndrome / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D013963:Thyroid Hormones / Q000097:blood; D013974:Thyroxine / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D037021:Thyroid Hormone Receptors alpha; D013963:Thyroid Hormones; D013974:Thyroxine