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This version published online on December 11, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-1067
A more recent version of this article appeared on March 1, 2008
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Right arrow Thyroid

Submitted on May 14, 2007
Accepted on November 29, 2007

TYPE 2 DEIODINASE POLYMORPHISM (THR92ALA) PREDICTS L-THYROXINE DOSE TO ACHIEVE TARGET TSH LEVELS IN THYROIDECTOMIZED PATIENTS

Massimo Torlontano*, Cosimo Durante, Isabella Torrente, Umberto Crocetti, Giovanni Augello, Giuseppe Ronga, Teresa Montesano, Laura Travascio, Antonella Verrienti, Rocco Bruno, Stefano Santini, Palmina D'Arcangelo, Bruno Dallapiccola, Sebastiano Filetti, and Vincenzo Trischitta

Units of Endocrinology (M.T., U.C., G.A., V.T.) and Clinical Chemistry (S.S., P.D'A.), Scientific Institute Casa Sollievo della Sofferenza, 71013 S. Giovanni Rotondo, Italy; Departments of Clinical Sciences (C.D., G.R., T.M., L.T., A.V., S.F., V.T.) and Experimental Medicine and Pathology (B.D.), "Sapienza" University, 00161 Rome, Italy; Casa Sollievo della Sofferenza-Mendel Institute (I.T., B.D., V.T.), 00161 Rome, Italy; Unit of Endocrinology (R.B.), Tinchi-Pisticci Hospital, 75020 Matera, Italy

* To whom correspondence should be addressed. E-mail: m.torlontano{at}tin.it.

Context: Type 2 deiodinase (D2) converts T4 in T3 in several human tissues, including hypothalamus and pituitary and plays, therefore, a pivotal role on the negative feedback regulation of TSH secretion. A common variant of the gene, Thr92Ala, has been identified and associated with decreased D2 enzymatic activity.

Objective: To investigate whether this polymorphism predicts T4 dosage needed to obtain target TSH levels, in thyroidectomized patients.

Setting: Ambulatory patients.

Patients: One hundred ninety-one 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-Group, n= 117, <0.1 mU/L) or near-suppressed (near-supp-Group, n= 74, ≥0.1<0.5 mU/L) serum TSH levels.

Main outcome measures: DNA genotyping for D2 Thr92Ala variant and evaluation of T4 dose (mcg/kg) needed to obtain target TSH levels.

Results: Ala/Ala homozygous patients needed a higher T4 dose as compared to patients carrying the Thr92 variant (X/Thr patients) according to a recessive genetic model (2.08±0.43 vs 1.90±0.35 mcg/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 of 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.
Key words: Thr92Ala • thyroid cancer • L-thyroxine






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