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REPLACEMENT THERAPY OF PRIMARY HYPOTHYROIDISM:
MONOTHERAPY WITH L-THYROXINE AND COMBINATION THERAPY OF L-
THYROXINE AND TRIIODOTHYRONINE
Lutfullaev Oltin Oybekovich
Asian International University
Tel: +998934500601
oltinlutfullayev @ gmail . com
ABSTRACT:
The prevalence of overt hypothyroidism in the general population is 0.2 - 2%,
but in certain groups of the population, in particular, among the elderly, it reaches 15%, so
hypothyroidism is one of the most common endocrine diseases. Overt hypothyroidism is an
absolute indication for replacement therapy with thyroid hormones. Currently, L-thyroxine
monotherapy is mainly used for replacement therapy of hypothyroidism, although studies
that would directly compare it with L-T4 + LТЗ combination therapy have been virtually
non-existent to date. In recent years, reports have begun to appear in the literature on some
advantages of L-T3 + L-T4 combination therapy for hypothyroidism. A number of studies
indicate positive dynamics of psychological indicators against the background of L-T4 + L-
T3 combination therapy compared to L-T4 monotherapy. On the other hand, some studies
have not confirmed the advantages of combination therapy compared to L-T4 monotherapy.
Thus, to date, there is no clear data on the possible advantages and disadvantages of
combination therapy L-T4 + L-T3 compared to L-T4 monotherapy. It should be noted that,
despite the simplicity and convenience of L-T4 monotherapy, some patients, for various
reasons, are in a state of chronic decompensation of hypothyroidism, or, despite maintaining
a normal TSH level, present complaints characteristic of hypothyroidism, which to some
extent may be evidence of the imperfection of this replacement therapy.
Objective and tasks
The aim of the work was to evaluate the characteristics of L-T4 replacement monotherapy
compared to combination therapy with L-T4 and L-T3 in patients with primary overt
hypothyroidism. To achieve this goal, the following tasks were put forward:
1. To evaluate the quality of hypothyroidism compensation in patients receiving L-T4
monotherapy and to compare the levels of TSH and thyroid hormones during L-T4
replacement monotherapy and L-T4+L-T3 combination therapy.
2. To evaluate the dynamics of lipid spectrum parameters during two replacement therapy
options.
3. To evaluate and compare bone metabolism parameters and their dynamics during
two replacement therapy options.
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4. To evaluate the safety of using physiological doses of L-T3 from the standpoint of the
possible impact on cardiovascular system performance.
Scientific novelty
1. For the first time, a comparative study of two options of replacement therapy for primary
hypothyroidism was conducted: L-T4 monotherapy and L-T4+L-T3 combination therapy
using physiological doses of L-T3 using a crossover design and randomization when
forming groups.
2. It was shown that despite adequate L-T4 therapy, atherogenic dyslipidemia often persists
in patients and positive dynamics of the lipid spectrum was demonstrated when patients
were transferred to L-T4+L-T3 combination therapy.
3. The feasibility of assessing peripheral markers of thyroid hormone effects, in particular,
lipid spectrum parameters for a comprehensive assessment of hypothyroidism compensation
was demonstrated.
4. When assessing the dynamics of bone metabolism markers against the background of
combination therapy for hypothyroidism, a more pronounced activation of bone resorption
was revealed compared to bone formation.
5. The absence of a negative effect of physiological doses of L-T3 preparations on the state
of the cardiovascular system during combined replacement therapy for hypothyroidism has
been proven.
6. In some patients with persistent symptoms against the background of adequate L-T4
monotherapy, positive dynamics of the psychoemotional state were noted when transferred
to combination therapy
CONCLUSIONS
1. L-T4 replacement monotherapy, which achieves normalization of TSH levels, is
accompanied by the circulation of a non-physiologically high fT4 level, while an increase in
the L-T4 dose, leading to a decrease in TSH levels to a low-normal level, does not ensure
the maintenance of a GGZ level similar to that in healthy people.
2. A single dose of L-T3 preparations in the morning does not allow adequately modeling
the production of triiodothyronine by the thyroid gland due to the short half-life of L-T3
preparations.
3. Against the background of L-T4 replacement monotherapy, atherogenic dyslipidemia
persists in some patients with hypothyroidism, which is eliminated by prescribing
combination therapy with L-T4 and L-T3 preparations. 4. Prescribing combination therapy
L-T4+L-T3 is accompanied by a somewhat greater activation of bone resorption compared
to L-T4 monotherapy, which may be accompanied by a decrease in bone mineral density. 5.
In some patients with hypothyroidism, despite adequate L-T4 monotherapy according to
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hormonal study data, a number of symptoms persist that can be relieved by switching to
combination therapy L-T4+L-T3.
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