title: Type 2 deiodinase polymorphism (threonine 92 alanine) predicts L-thyroxine dose to achieve target thyrotropin levels in thyroidectomized patients.
abstract: BACKGROUND
  Type 2 deiodinase (D2) converts T4 in T3 in several human tissues, including hypothalamus and pituitary, and, therefore, plays a pivotal role in the negative feedback regulation of TSH secretion. A common variant of the gene, threonine (Thr) 92 alanine (Ala), has been identified and associated with decreased D2 enzymatic activity.
  
  
  OBJECTIVE
  Our objective was to investigate whether this polymorphism predicts the T4 dosage needed to obtain target TSH levels in thyroidectomized patients.
  
  
  METHODS
  Ambulatory patients were included in the study.
  
  
  METHODS
  A total of 191 consecutive thyroid cancer patients, previously treated by near total thyroidectomy and radioiodine ablation, were studied. They were on stable T4 dose treatment aimed at obtaining either suppressed (supp) (n=117, <0.1 mU/liter) or near-supp (n=74, >or=0.1<0.5 mU/liter) serum TSH levels.
  
  
  METHODS
  DNA genotyping for D2 Thr92Ala variant and evaluation of T4 dose (microg/kg) needed to obtain target TSH levels were determined.
  
  
  RESULTS
  Ala/Ala homozygous patients needed a higher T4 dose as compared with patients carrying the Thr92 variant (X/Thr patients) according to a recessive genetic model (2.08+/-0.43 vs. 1.90+/-0.35 microg/kg; P<0.05). This difference was observable in the near-supp group (P=0.002), but not in the supp group (P=0.4).
  
  
  CONCLUSIONS
  D2 Thr92Ala polymorphism seems to predict the need for higher T4 intake in thyroidectomized patients. If this finding is confirmed in additional studies, it may predict the T4 requirement to suppress TSH on the basis of the individual genetic background.
authors: Department of Endocrinology, Scientific Institute Casa Sollievo della Sofferenza, v.le Cappuccini, 71013 San Giovanni Rotondo, Italy. m.torlontano@tin.it
authors: Massimo
authors: M
authors: Torlontano
authors: Cosimo
authors: C
authors: Durante
authors: Isabella
authors: I
authors: Torrente
authors: Umberto
authors: U
authors: Crocetti
authors: Giovanni
authors: G
authors: Augello
authors: Giuseppe
authors: G
authors: Ronga
authors: Teresa
authors: T
authors: Montesano
authors: Laura
authors: L
authors: Travascio
authors: Antonella
authors: A
authors: Verrienti
authors: Rocco
authors: R
authors: Bruno
authors: Stefano
authors: S
authors: Santini
authors: Palmina
authors: P
authors: D'Arcangelo
authors: Bruno
authors: B
authors: Dallapiccola
authors: Sebastiano
authors: S
authors: Filetti
authors: Vincenzo
authors: V
authors: Trischitta
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000627:therapeutic use*; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007453:Iodide Peroxidase; D013972:Thyrotropin; D013974:Thyroxine; D000097564:Iodothyronine Deiodinase Type II