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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: +998911329697
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.
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
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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 was noted when switching to
combination therapy.
Practical significance
1. It has been demonstrated that despite the simplicity and convenience of L-T4 replacement
monotherapy, many patients continue to have decompensated hypothyroidism, and in some
patients, despite adequately
selected L-T4 monotherapy, a number of manifestations of hypothyroidism, such as
atherogenic dyslipidemia, persist.
2. The feasibility of monitoring such peripheral markers of the effects of thyroid hormones
as lipid spectrum indicators for a comprehensive assessment of the adequacy of replacement
therapy for
hypothyroidism has been shown. 3. A group of patients with hypothyroidism for whom
switching to LT4+L-T3 combination therapy would be most appropriate has been identified.
4. The safety of physiological doses of L-T3 in terms of their effect on the cardiovascular
system in young patients has been demonstrated.
5. In the presence of osteoporosis risk factors in patients, the need to assess bone mineral
density before prescribing the L-T4+L-T3 combination has been substantiated.
6. A scheme for selecting replacement therapy for primary hypothyroidism has been
proposed, taking into account the assessment of peripheral markers of thyroid hormone
effects.
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
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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
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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