Authors

  • Solijonova Umida Ilhomjonovna
    4rd-year students of Tashkent International University of Kimyo, Faculty of General Medicine, Uzbekistan
  • Erdanova Nigina Doniyorovna
    4rd-year students of Tashkent International University of Kimyo, Faculty of General Medicine, Uzbekistan

DOI:

https://doi.org/10.37547/ijmscr/Volume05Issue07-05

Keywords:

Autoimmune thyroiditis anti-thyroid peroxidase antibodies (AT-TPO) hypothyroidism

Abstract

In recent years, the study of thyroid function during pregnancy, including the level of thyroid antibodies (anti-thyroglobulin antibodies, AT-TG) throughout pregnancy and their impact on pregnancy outcomes, has been the focus of endocrinologists, obstetricians-gynecologists, and pediatricians. In particular, hypothyroidism plays a key role in thyroid dysfunction and affects fetal development. This article examines the changes that may occur during pregnancy in patients with autoimmune thyroiditis.


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International Journal of Medical Sciences And Clinical Research

20

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VOLUME

Vol.05 Issue07 2025

PAGE NO.

20-23

DOI

10.37547/ijmscr/Volume05Issue07-05



Course of Autoimmune Thyroiditis During Pregnancy

Solijonova Umida Ilhomjonovna

4rd-year students of Tashkent International University of Kimyo, Faculty of General Medicine, Uzbekistan

Erdanova Nigina Doniyorovna

4rd-year students of Tashkent International University of Kimyo, Faculty of General Medicine, Uzbekistan

Received:

31 May 2025;

Accepted:

29 June 2025;

Published:

31 July 2025

Abstract:

In recent years, the study of thyroid function during pregnancy, including the level of thyroid antibodies

(anti-thyroglobulin antibodies, AT-TG) throughout pregnancy and their impact on pregnancy outcomes, has been
the focus of endocrinologists, obstetricians-gynecologists, and pediatricians. In particular, hypothyroidism plays a
key role in thyroid dysfunction and affects fetal development. This article examines the changes that may occur
during pregnancy in patients with autoimmune thyroiditis.

Keywords:

Autoimmune thyroiditis, anti-thyroid peroxidase antibodies (AT-TPO), fetus, hypothyroidism,

pregnancy, thyroid gland.

Introduction:

Autoimmune thyroiditis is more common

among women than men, affecting 5

20% of women of

reproductive age. Even if a mother does not have
thyroid dysfunction but has anti-thyroid peroxidase
antibodies, this can negatively impact pregnancy
outcomes, increasing the risk of early miscarriage,
preterm birth, intrauterine growth restriction, and fetal
neurodevelopmental disorders. The development of
these conditions is influenced both by hypothyroidism
caused by autoimmune thyroiditis and by the direct
effect

of

anti-thyroid

peroxidase

antibodies.

Hypothyroidism during pregnancy primarily poses a
significant risk to fetal development, particularly the
central nervous system.

Thyroid Gland and Pregnancy: During physiological
pregnancy, significant metabolic changes occur in a
woman's div, primarily due to the temporary
endocrine organ

the developing placenta. This leads

to alterations in the levels of proteins (placental
lactogenic hormone, chorionic hormone) and steroid
hormones (estriol, estrone, estradiol, progesterone) in
the mother's div. The daily production of placental
hormones gradually increases and reaches very high
levels in the third trimester of pregnancy:
approximately 300

400 mg of progesterone, around

200 mg of estradiol, and about 1.5

2 g of placental

lactogen.

During pregnancy, under the influence of placental
estrogens, the synthesis of thyroxine-binding globulin
(TBG) is enhanced, leading to an increase in the levels
of T3 and T4 bound to transport proteins in the blood.
This process involves the attachment of sialic acids to
TBG molecules, which significantly prolongs its half-life
and uptake by hepatocytes [8,20]. It has been shown
that absolute or relative hyperestrogenemia, which
underlies

various

hyperplastic

processes

in

reproductive organs (such as uterine fibroids,
endometrial hyperplasia and polyps, adenomyosis,
endometriosis, and fibrocystic mastopathy), is a direct
cause of thyroid enlargement. Thyroid gland
enlargement during pregnancy [4,24] is primarily
attributed to the effects of placental estrogens. The
structural similarity between human chorionic
gonadotropin (hCG) and thyroid-stimulating hormone
(TSH) explains the influence of hCG on thyroid growth
and function [6,13,21].

The thyrotropic activity of hCG is approximately 100
times lower than that of TSH. By the end of the first
trimester, hCG is responsible for thyroid enlargement
and hyperthyroidism in pregnant women [2,18,14].
Increased hCG production leads to transient
gestational thyrotoxicosis in 1

2% of pregnant women,

often accompanied by hyperemesis gravidarum
[15,24].


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The causes of thyrotoxicosis during pregnancy may be

linked to enhanced expression of the β

-subunit of the

hCG gene [13] and structural changes in hCG, which
prolong its half-life or increase the mass of the
syncytiotrophoblast. Other factors contributing to
thyroid enlargement include developing iodine
deficiency during pregnancy, particularly in the
northwestern regions of Uzbekistan. Iodine deficiency
occurs due to its transfer to the fetus via the placenta
and increased renal iodine clearance as a result of
enhanced glomerular filtration [11].

Of course, iodine deficiency is not the only cause of
thyroid enlargement during pregnancy, as an average
increase in thyroid size by 10

15% is observed even in

regions with adequate iodine intake and iodine
prophylaxis [21,23].

Thus, thyroid enlargement during pregnancy is
associated with placental hormonal function, iodine
intake, and urinary iodine levels. Increased metabolism
of TBG in the liver leads to elevated total T3 and T4
levels in the blood. Consequently, the levels of free
thyroid hormone fractions slightly decrease by the end
of pregnancy [9,16]. In iodine-deficient regions,
pregnant women often experience hypothyroxinemia,
which manifests in a more pronounced form [3,19].

TSH levels in pregnant women typically remain within
the physiological range observed in non-pregnant
women. The exception is patients with gestational
hyperthyroidism, in whom hCG causes TSH levels to
drop below 0.2 mIU/L.

Fetal Thyroid Development: The fetal thyroid gland
develops from the primitive gut. Its formation begins in
the 4th week of pregnancy. By the end of the first
trimester, the fetal thyroid is capable of accumulating
iodine, synthesizing thyroid hormones, and releasing
them into the bloodstream. As pregnancy progresses,
total and free T4 levels in fetal blood increase, reaching
adult levels by the 36th week. Total and free T3 levels
rise to a lesser extent.

By the second trimester, the negative feedback
mechanism within the fetal hypothalamic-pituitary-
thyroid system is established. At birth, fetal TSH levels
are significantly higher than those seen in adults. In the
mature maternal placenta, thyroid hormones undergo
deiodination and barely reach the fetal circulation. TSH
also cannot cross the placental barrier. Thus, the fetal
hypothalamic-pituitary-thyroid

system

functions

autonomously, independently of the maternal system.

During the first trimester of fetal development, even
before the fetal thyroid gland becomes functional, the
fetus remains under the control of maternal thyroid
hormones.

By the end of the third trimester, placental
permeability to maternal thyroid hormones slightly
increases. Thyroid hormones are essential for the
normal growth and development of the fetus, the
differentiation of its organs and tissues

primarily the

morphological and functional development of the
central nervous system

the regulation of metabolic

processes, and the formation of adaptive responses.
This importance is explained by the fact that, unlike T3
and T4, thyroid hormones barely cross the blood-brain
barrier.

The levels of total and free thyroxine (T4),
triiodothyronine (T3), thyroid-stimulating hormone
(TSH), and thyrotropin-releasing hormone (TRH)
gradually increase from the 17th

20th week to the

34th

37th week of pregnancy as gestation progresses.

The established direct correlation between thyroxine
and TSH levels at these stages of development indicates
that the negative feedback mechanism within the fetal
hypothalamic-pituitary-thyroid system is not yet fully
developed.

However, there is reliable evidence supporting the
existence of a functional negative feedback mechanism
between the thyroid gland and the pituitary gland
during the antenatal period. This is confirmed by the
increased thyroid volume and TSH levels in fetuses and
newborns with primary hypothyroidism, as well as the
reduction of these parameters following the
administration of thyroxine into the amniotic cavity.

Autoimmune thyroiditis (AIT) is a chronic autoimmune
disease of the thyroid gland and is one of the most
common causes of primary hypothyroidism. It occurs 5
to 10 times more frequently in women than in men.
Anti-thyroid autoantibodies, one of the hallmarks of
the disease, are found in 5

26% of women of

reproductive age. According to a study by Wigghem,
the annual risk of developing hypothyroidism in women
with high levels of anti-thyroid peroxidase (TPO)
antibodies is 2.1%. Anti-thyroid antibodies are
detected in 13

20% of pregnant women.

The frequent occurrence of AIT in certain family
members, as well as the presence of specific HLA
system antigens (HLA-DR3 and HLA-DR5), suggests a
genetic predisposition to the disease. These antigens
are also associated with an increased susceptibility to
other systemic and organ-specific autoimmune
diseases, such as rheumatism, rheumatoid arthritis,

systemic lupus erythematosus, Graves’ disease, type 1

diabetes,

autoimmune

adrenal

insufficiency,

autoimmune oophoritis, diffuse alopecia, and others.
The onset of AIT is often preceded by infectious
diseases, excessive sun exposure, or an excessive
intake of iodine.


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AIT can develop either with thyroid gland enlargement
(Hashimot

o’s goiter) or without an increase in gland

volume (atrophic thyroiditis). In both cases, histological
examination reveals lymphoid and plasmacytic
infiltration in thyroid tissue, destruction of the follicular
apparatus, and fibrosis.

In the 1950s, thyroid autoantigens (thyroglobulin and
the microsomal antigen

thyroid peroxidase) were

identified, and the first experimental model of
autoimmune thyroiditis was developed by immunizing
rabbits with homologous thyroid extracts. Under the
influence of T-helper cells, B-lymphocytes transform
into plasma cells and produce autoantibodies against
thyroglobulin and thyroid peroxidase. Anti-thyroid
autoantibodies interact with T-killer cells in the
follicular epithelium. Additionally, TPO autoantibodies
bind to the C1/C3 fraction of the complement system,
forming cytotoxic pathogenic immune complexes that
act on thyrocytes.

Intensive destruction of thyroid epithelial cells can lead
to a significant increase in T3 and T4 levels in the blood
and a decrease in TSH levels, resulting in destructive
thyrotoxicosis. As the volume of functioning thyroid
tissue decreases, a temporary or permanent decline in
thyroid function occurs, leading to transient or
permanent hypothyroidism.

In 5.9% of women, remission of autoimmune thyroiditis
(AIT) by the end of pregnancy is followed by an
exacerbation in the postpartum period, known as
postpartum thyroiditis. This condition develops in one-
third of women who had detectable thyroid peroxidase
(TPO) autoantibodies in their blood at the beginning of
pregnancy. The disease may initially present with signs
of thyrotoxicosis due to the destruction of thyroid
parenchyma (occurring 2

4 months after childbirth),

followed by a phase of transient hypothyroidism (6

8

months postpartum). In 19.2% of women with
significant primary hypothyroidism, the first symptoms
of the disease appear 1

2 years after childbirth.

Clinical manifestations of AIT without changes in
thyroid function are rare. In the hypertrophic form of
the disease, patients may experience an increase in
neck volume and complain of pressure in the anterior
neck region. On palpation, the thyroid gland appears
enlarged and firm. If the goiter reaches a significant
size, it may compress adjacent organs. In the focal form
of thyroiditis, localized thyroid induration may be
perceived as a nodular goiter, sometimes requiring
fine-needle aspiration biopsy (FNAB) to differentiate it
from thyroid tumors. A characteristic ultrasound sign of
the disease is a diffuse decrease in thyroid tissue
echogenicity.

The diagnosis of AIT is based on a combination of

findings: in some cases, a "wooden" gland density on
palpation, a distinct echographic thyroid structure, and
elevated levels of anti-thyroid autoantibodies in the
blood. The functional state of the thyroid gland
depends on the amount of preserved parenchyma and
the intensity of destructive processes.

There are reports suggesting that AIT may be
associated with infertility, particularly in women with
external genital endometriosis or polycystic ovary
syndrome (PCOS). Some studies indicate that most
women with hyperplastic processes in the reproductive
system show decreased thyroid function, and in rare
cases, thyroid enlargement.

REFERENCES

Allan W.C, Haddow J.E, Palomaki G.E, Williams J.R,
Mitchell M.L, Hermos R.J, et al. Maternal thyroid
deficiency and pregnancy complications: implications
for population screening. J Med Screen. 2000.7(3):127-
30.

Abalovich M, Gutierrez S, Alcaraz G, Maccallini G,
Garcia

A,

Levalle

O.Overt

and

subclinical

hypothyroidism complicating pregnancy.Thyroid. 2002
J.12 (1):63-8.

Bernal J. Thyroid hormone receptors in brain
development and function. Nat Clin Pract 4. Endocrinol
Metabol 2007;3:3:249

Blumenthal NJ, Byth K, Eastman CJ. Prevalence of
thyroid dysfunction and thyroid antibodies in a private
obstetrical practice in Sydney. Aust N Z J Obstet
Gynaecol. 2016 Jun. 56 (3):307-11.

Glinoer D. Regulation of thyroid function in pregnancy:
pathways of endocrine adaptation from physiology to
pathology.

Endocr

Rev

(1997)

18:404

33.10.1210/edrv.18.3.0300

Glinoer D.,Riahi M., Griien J.P., Kinthaert J.//Ibid.- 1994.
Vol. 79. -P.197-204. 7. 18:404 Klein R.Z., Haddow J.E.,
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vol.35.-P41-46.

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vol.35.-P41-46.

Kamijo k., Saito T., Sato M. et al \\Endoccrinol. Jap.-
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Vol.37,N3.

P 397-403.

Leung AS, Millar LK, Koonings PP, Montoro M,
Mestman JH. Perinatal outcome in hypothyroid
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McLeod DS, Cooper DS. The incidence and prevalence
of thyroid autoimmunity. Endocrine 2012;42:252-65.

Porterfield S.P., Hendrich C.E.// Endicr. Rev. -1993 .

vol.14

P.94-106.

Strango-Green A., Roman S.H., Cobin R .H. et
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background image

International Journal of Medical Sciences And Clinical Research

23

https://theusajournals.com/index.php/ijmscr

International Journal of Medical Sciences And Clinical Research (ISSN: 2771-2265)

Vanderpump MP. The epidemiology of thyroid disease.
Br Med Bull 2011;99:39-51.

Wilson KL, Casey BM, McIntire DD, Halvorson LM,
Cunningham FG. Subclinical thyroid disease and the
incidence of hypertension in pregnancy. Obstet
Gynecol. 2012 Feb. 119 (2 Pt 1):315-20.

Stagnaro-Green A.Abalovich M.Alexander E.et al.
Guidelines of the American Thyroid Association for the
diagnosis and management of thyroid disease during
pregnancy and postpartum. Thyroid. 2011; 21: 1081-
1125.

Krassas G.E. Poppe K.Glinoer D.Thyroid function and
human reproductive health. Endocr Rev. 2010; 31:
702-755

Mannisto T.Mendola P.Grewal J.Xie Y.Chen Z.Laughon
S.K.Thyroid diseases and adverse pregnancy outcomes
in a contemporary US cohort.J Clin Endocrinol Metab.
2013; 98: 2725-2733

Bucci I, Giuliani C, Napolitano G. Thyroid-Stimulating
Hormone Receptor Antibodies in Pregnancy: Clinical
Relevance. Front Endocrinol (Lausanne). 2017 Jun
30;8:137. doi: 10.3389/fendo.2017.00137.

Alexander EK ,Pearce EN ,Brent G et al. Guidelines of
the American Thyroid Association for the diagnosis and
management of thyroid disease during pregnancy and
the postpartum. Thyroid. 2017; 27: 315-389

Barbesino G, Tomer Y. Clinical review: Clinical utility of
TSH receptor antibodies. Clin Endocrinol Metab. 2013
Jun;98(6):2247-55. doi: 10.1210/jc.2012-4309.

Glinoer D ,Riahi M ,Grün JP ,Kinthaert J. Risk of
subclinical hypothyroidism in pregnant women with
asymptomatic autoimmune thyroid disorders. J Clin
Endocrinol Metab. 1994; 79: 197-204.

Pearce EN, Oken E, Gillman MW, Lee SL, Magnani B,
Platek D, Braverman LE. Association of first-trimester
thyroid function test values with thyroperoxidase
antidiv status, smoking, and multivitamin use. Endocr
Pract.

2008

Jan-Feb;14(1):33-9.

doi:10.4158/EP.14.1.33.

Moreno-Reyes R ,Glinoer D ,Van Oyen H ,Vandevijvere
S. High prevalence of thyroid disorders in pregnant
women in a mildly iodine-deficient country: a
population-based study. J Clin Endocrinol Metab. 2013;
98: 3694-3701

References

Allan W.C, Haddow J.E, Palomaki G.E, Williams J.R, Mitchell M.L, Hermos R.J, et al. Maternal thyroid deficiency and pregnancy complications: implications for population screening. J Med Screen. 2000.7(3):127-30.

Abalovich M, Gutierrez S, Alcaraz G, Maccallini G, Garcia A, Levalle O.Overt and subclinical hypothyroidism complicating pregnancy.Thyroid. 2002 J.12 (1):63-8.

Bernal J. Thyroid hormone receptors in brain development and function. Nat Clin Pract 4. Endocrinol Metabol 2007;3:3:249

Blumenthal NJ, Byth K, Eastman CJ. Prevalence of thyroid dysfunction and thyroid antibodies in a private obstetrical practice in Sydney. Aust N Z J Obstet Gynaecol. 2016 Jun. 56 (3):307-11.

Glinoer D. Regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev (1997) 18:404– 33.10.1210/edrv.18.3.0300

Glinoer D.,Riahi M., Griien J.P., Kinthaert J.//Ibid.- 1994. Vol. 79. -P.197-204. 7. 18:404 Klein R.Z., Haddow J.E., Faix J.D.et al.//clin.Endocri nol-1991.–vol.35.-P41-46.

Klein R.Z., Haddow J.E., Faix J.D.et al.//clin.Endocri nol-1991.–vol.35.-P41-46.

Kamijo k., Saito T., Sato M. et al Endoccrinol. Jap.-1990–Vol.37,N3.– P 397-403.

Leung AS, Millar LK, Koonings PP, Montoro M, Mestman JH. Perinatal outcome in hypothyroid pregnancies. Obstet Gynecol. 1993 Mar. 81 (3):349-53. McLeod DS, Cooper DS. The incidence and prevalence of thyroid autoimmunity. Endocrine 2012;42:252-65.

Porterfield S.P., Hendrich C.E.// Endicr. Rev. -1993 . – vol.14 – P.94-106.

Strango-Green A., Roman S.H., Cobin R .H. et al.//J.A.M.A-1990-Vol.264,N11.-P1422 1425

Vanderpump MP. The epidemiology of thyroid disease. Br Med Bull 2011;99:39-51.

Wilson KL, Casey BM, McIntire DD, Halvorson LM, Cunningham FG. Subclinical thyroid disease and the incidence of hypertension in pregnancy. Obstet Gynecol. 2012 Feb. 119 (2 Pt 1):315-20.

Stagnaro-Green A.Abalovich M.Alexander E.et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011; 21: 1081-1125.

Krassas G.E. Poppe K.Glinoer D.Thyroid function and human reproductive health. Endocr Rev. 2010; 31: 702-755

Mannisto T.Mendola P.Grewal J.Xie Y.Chen Z.Laughon S.K.Thyroid diseases and adverse pregnancy outcomes in a contemporary US cohort.J Clin Endocrinol Metab. 2013; 98: 2725-2733

Bucci I, Giuliani C, Napolitano G. Thyroid-Stimulating Hormone Receptor Antibodies in Pregnancy: Clinical Relevance. Front Endocrinol (Lausanne). 2017 Jun 30;8:137. doi: 10.3389/fendo.2017.00137.

Alexander EK ,Pearce EN ,Brent G et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017; 27: 315-389

Barbesino G, Tomer Y. Clinical review: Clinical utility of TSH receptor antibodies. Clin Endocrinol Metab. 2013 Jun;98(6):2247-55. doi: 10.1210/jc.2012-4309.

Glinoer D ,Riahi M ,Grün JP ,Kinthaert J. Risk of subclinical hypothyroidism in pregnant women with asymptomatic autoimmune thyroid disorders. J Clin Endocrinol Metab. 1994; 79: 197-204.

Pearce EN, Oken E, Gillman MW, Lee SL, Magnani B, Platek D, Braverman LE. Association of first-trimester thyroid function test values with thyroperoxidase antibody status, smoking, and multivitamin use. Endocr Pract. 2008 Jan-Feb;14(1):33-9. doi:10.4158/EP.14.1.33.

Moreno-Reyes R ,Glinoer D ,Van Oyen H ,Vandevijvere S. High prevalence of thyroid disorders in pregnant women in a mildly iodine-deficient country: a population-based study. J Clin Endocrinol Metab. 2013; 98: 3694-3701