This indicates that perhaps patients’ preference for one therapy form over the other may be explained by local intracerebral factors, again perhaps influenced by different gene expressions of DIO2 and/or the thyroid hormone transporters. However, the serum T3 and T4 levels did not differ between WT and CC polymorphism patients in that study.
showed that hypothyroid patients harbouring the CC genotype of the type II iodothyronine deiodinases ( DIO2) rs225014 polymorphism, seen in 16% in a population-based study from the UK, had worse baseline general health scores and did also benefit more on L-T3 + L-T4 combination therapy compared to patients harbouring the wild type (WT) alleles. ĭifferential local expression and activity of iodothyronine deoidinases and thyroid hormone transmembrane transporters may be an explanation. standard L-T4 monotherapy) was shown to be only very modest. Weight loss may also be part of the explanation, but although statistically significant, the weight loss in L-T3 + L-T4-treated patients (vs.
A different co-morbidity status could perhaps explain some of the difference. also studied hypothyroid patients with biochemically restored euthyroidism due to L-T4 substitution and found that the group of patients dissatisfied with their treatment had the same serum TSH, T3, and T4 concentrations as the patients having no complaints.
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On the other hand, no differences in hypothyroid symptoms, quality of life, or cognitive function were seen in a double-blind, randomized, clinical trial with cross-over design on 52, L-T4-treated, hypothyroid patients receiving 3 L-T4 doses in random order for 8 weeks: usual dose, 25 μg less, or 25 μg more resulting in serum TSH values of 2.8 ± 0.4, 1.1 ± 0.2, and 0.3 ± 0.1 mU/L, respectively ( p < 0.001). Several other studies, in which patients were treated with a high dose of thyroid hormone with subsequently low serum TSH values, support these findings. However, they had all serum TSH values of <0.2 mU/L, and were thus slightly overtreated. reported better well-being in patients treated with a supra-optimal dose of 50 μg L-T4. , no difference was observed in symptom scores or various serum lipid profiles in those treated with L-T3 + L-T4 versus those treated with L-T4 alone. In the meta-analysis by Grozinsky-Glasberg et al. No study has ever explained why so many patients prefer L-T3. reviewed 5 cross-over studies and showed that 48% of all hypothyroid patients preferred the L-T3 + L-T4 combination therapy, 27% preferred L-T4 monotherapy, and 25% had no preference. In the 2012 European Thyroid Association guidelines for the use of L-T4 and L-T3 in the treatment of hypothyroidism, Wiersinga et al. Many patients do not feel well on standard levo-thyroxine (L-T4) treatment, and many patients may benefit from experimental treatment with combined levo-triiodothyronine (L-T3) + L-T4 preparations. Hypothyroidism is very common and affects up to 10% of the female population. In the future, combination therapy may be restricted or may be even recommended to individuals harbouring certain polymorphisms.
Conclusion: The present study indicates that the combination of polymorphisms in DIO2 (rs225014) and MCT10 (rs17606253) enhances hypothyroid patients’ preference for L-T4 + L-T3 replacement therapy. 100% of our patients in the 3 groups preferred the combined treatment (Jongheere-Terpstra trend test, p = 0.009). Two polymorphisms (rs225014 ( DIO2, Thr92Ala) and rs17606253 ( MCT10)) were combined yielding 3 groups: none vs. Results: 27 out of 45 patients (60%) preferred the combination therapy. We investigated 3 single nucleotide polymorphisms (SNPs) on the type II iodothyronine deiodinase ( DIO2) gene (rs225014 (Thr92Ala), rs225015, and rs12885300 (ORFa-Gl圓Asp)) and 1 SNP on the cellular membrane transport-facilitating monocarboxylate transporter ( MCT10) gene (rs17606253), and asked in which of the 2 treatment periods patients felt better (i.e., which treatment was preferred). L-T4 was hereafter adjusted to obtain normal serum TSH values. In all periods, 50 μg L-T4 was blindly replaced by either (identical) 50 μg L-T4 or by 20 μg T3. The patients were randomized into 2 groups of either 3 continuous months’ L-T4 therapy followed by 3 months’ combination therapy or vice versa. Methods: A total of 45 overtly autoimmune, hypothyroid patients – now euthyroid on ≥6 months’ L-T4 therapy – participated in a prospective, double-blind, cross-over study. The reason for this is yet to be explored.
Objectives: In previous studies, around half of all hypothyroid patients preferred levo-thyroxine (L-T4) + levo-triiodothyronine (L-T3) combination therapy, 25% preferred T4, and 25% had no preference.
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