Endocrine Abstracts

Introduction: Type 2 deiodinase (D2) catalyses intracellular T₃ production in several human tissues including pituitary gland, hence occupying an important role in the feedback regulation of TSH secretion. Although several previous researches have shown that Thr92Ala D2 polymorphism with decreased D2 enzymatic activity influences the levothyroxine dose requirement and the set point of the hypothalamus–pituitary–thyroid axis for postoperative TSH suppressive therapy in thyroid cancer patients, the clinical implications of D2 polymorphism and liothyronine replacement in thyroid cancer patients are still unknown.

Methods: The effect of liothyronine combination on TSH suppression according to Thr92Ala D2 polymorphism in 40 papillary thyroid cancer patients (20 males and 20 females; age 46.6±10.9 years, range 20–66) who were persistently unable to repress the serum TSH levels to less than 0.1 μIU/ml for at least 3 months despite the daily 2.0 μg/kg intake of levothyroxine were analysed. Total thyroidectomy with central compartment neck dissection and postoperative radioactive iodine ablation was performed in all patients at least a mean of 48.8±35.8 months before this study.

Results: In these patients, a decreased of mean TSH level was observed in all patients after 3 months of 12.5 μg liothyronine add on with 50 μg reduction of levothyroxine (3.18 vs 0.28 μIU/ml, P=0.002). After liothyronine combination, serum T₃ and free T₄ levels became more comparable to preoperative levels. Of the 40 patients, Ala/Ala homozygous genotype was observed in eight patients (20%), while WT and heterozygous type were observed in 15 (37.5%) and 17 (42.5%) patients, respectively. Preoperative serum free T₄ level was lower in Ala/Ala homozygous patients (0.98 vs 1.28 ng/dl, P=0.006). Ala/Ala homozygous patients displayed higher ratio of TSH level before and after liothyronine combination compared with patients carrying the Thr92 variant (X/Thr patients) (133.9±178.6 vs 25.5±41.5, P=0.003).

Conclusion: Thr92Ala D2 polymorphism is associated with liothyronine-dependent TSH suppressive intensity in athyreotic individuals. Thr92Ala D2 polymorphism analysis will be beneficial in predicting the effect of T₃ combination in thyroid cancer patients that are unable to achieve a full TSH suppression from levothyroxine mono-therapy.