Type 2 deiodinase polymorphism (threonine 92 alanine) predicts L-thyroxine dose to achieve target thyrotropin levels in thyroidectomized patients.
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.
Torlontano
Massimo
M
Department of Endocrinology, Scientific Institute Casa Sollievo della Sofferenza, v.le Cappuccini, 71013 San Giovanni Rotondo, Italy. m.torlontano@tin.it
Durante
Cosimo
C
Torrente
Isabella
I
Crocetti
Umberto
U
Augello
Giovanni
G
Ronga
Giuseppe
G
Montesano
Teresa
T
Travascio
Laura
L
Verrienti
Antonella
A
Bruno
Rocco
R
Santini
Stefano
S
D'Arcangelo
Palmina
P
Dallapiccola
Bruno
B
Filetti
Sebastiano
S
Trischitta
Vincenzo
V
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
D007453:Iodide Peroxidase; D013972:Thyrotropin; D013974:Thyroxine; D000097564:Iodothyronine Deiodinase Type II