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Type 2 Deiodinase Polymorphism (Threonine 92 Alanine) Predicts L-Thyroxine Dose to Achieve Target Thyrotropin Levels in Thyroidectomized Patients

Units of Endocrinology (M.T., U.C., G.A., V.T.) and Clinical Chemistry (S.S., P.D.), 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.), "La Sapienza" University, 00161 Rome, Italy; Casa Sollievo della Sofferenza-Mendel Institute (I.T., B.D., V.T.), 00161 Rome, Italy; and Unit of Endocrinology (R.B.), Tinchi-Pisticci Hospital, 75020 Matera, Italy

Address all correspondence and requests for reprints to: Massimo Torlontano, M.D., Department of Endocrinology, Scientific Institute Casa Sollievo della Sofferenza, v.le Cappuccini, 71013 San Giovanni Rotondo, Italy. 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, 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.

Setting: Ambulatory patients were included in the study.

Patients: 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, 0.1 < 0.5 mU/liter) serum TSH levels.

Main Outcome Measures: DNA genotyping for D2 Thr92Ala variant and evaluation of T₄ dose (µg/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 µg/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.