GENETIC ASPECTS OF THE EFFECTIVENESS OF REPLACEMENT THERAPY AND THE SCOPE OF SURGICAL INTERVENTION IN PATIENTS WITH TOXIC GOITER

Objective. To investigate the frequency of Val174Ala polymorphism in SLCO1B1 gene in patients with toxic goiter (TG) and to evaluate the influence of the revealed mutations on the efficacy of substitutive hormonotherapy and adequacy of the choice of the extent of TG surgery. Methods. The study of Val174Ala polymorphism in 41 patients operated on TG was carried out. The mean age of patients was 48.2±13.0 years; 7 men and 34 women. Toxic diffuse goiter (TDG) was diagnosed in 19 patients, toxic multinodular goiter (TMG) – in 22; thus thyroidectomy (TE) was performed in 21 cases, subtotal thyroid resection (STR) – in 20 cases. Results. The study revealed polymorphism in 16 patients (39.02%): heterozygous (CT type) – in 15 patients (36.59%); normal homozygous / mutant type (CC type) – in 1 patient (2.44%). Normal homozygous / wild type (TT), indicating the absence of polymorphism, was detected in 25 patients (60.98%). When L-T4 was administered based on the dose specified in clinical recommendations, in 6 of 16 patients with polymorphism in the postoperative period subclinical thyrotoxicosis symptoms (TSH from 0.38 to 0.02 mMe/l) were observed, in 4 patients - partial return of thyrotoxicosis symptoms (TSH – 0.01 mMe/l). All these patients underwent TE. As a result, the Thyroxine dose of 125 mcg was reduced to 75 mcg in 6 patients, and in 4 patients – to 100 mcg per day. The remaining 6 patients with preoperative polymorphism underwent STR with Thyroxine administration considering this factor. Conclusion. Significant relationship between the daily dosage of L-T4 and the presence of SLCO1B1 polymorphism has been revealed in the study. When prescribing substitutive hormonotherapy, its necessary to consider the results of genetic testing of SLCO1B1 polymorphism, which was detected in 39% of patients. In case of polymorphism detection, the STR should be preferred in order to prevent adverse reactions of substitutive therapy and adequate dose selection.