Iranian Journal of Reproductive Medicine Vol.10. No.1.

pp: 47-52, January 2012

Comparison of serum levels of Tri‐iodothyronine (T3),

Thyroxine (T4), and Thyroid‐Stimulating Hormone
(TSH) in preeclampsia and normal pregnancy
Nayereh Khadem1 M.D., Hossein Ayatollahi2 M.D., Fatemeh Vahid Roodsari3 M.D., Sedigheh Ayati3
M.D., Ehsan Dalili4 M.D., Masoud Shahabian4 M.D., Taraneh Mohajeri3 M.D., Mohamad Taghi
Shakeri5 M.D.

1 Department of Obstetrics and Gynecology, Emam Reza Hospital, Women’s Health Research Center,
Mashhad University of Medical Sciences, Mashhad, Iran.
2 Department of Hematology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
3 Department of Obstetrics and Gynecology, Ghaem Hospital, Mashhad University of Medical Sciences,
Mashhad, Iran.
4 General Physician, Mashhad University of Medical Sciences, Mashhad, Iran.
5 Department of Medicosocial, Biostatics Unit, Ghaem Hospital, Mashhad University of Medical
Sciences, Mashhad, Iran.

Received: 27 October 2009; accepted: 30 April 2011

Abstract
Background: The physiological changes in thyroid gland during pregnancy have been
suggested as one of the pathophysiologic causes of preeclampsia.
Objective: The aim of this study was comparison of serum levels of Tri‐iodothyronine
(T3), Thyroxine (T4), and Thyroid‐Stimulating Hormone (TSH) in preeclampsia and
normal pregnancy.
Materials and Methods: In this case‐control study, 40 normal pregnant women and 40
cases of preeclampsia in third trimester of pregnancy were evaluated. They were
compared for serum levels of Free T3 (FT3), Free T4 (FT4) and TSH. The data was
analyzed by SPSS software with the use of t‐student, Chi‐square, Independent sample
T-test and Bivariate correlation test. p≤0.05 was considered statistically significant.
Results: The mean age was not statistically different between two groups (p=0.297). No
significant difference was observed in terms of parity between two groups (p=0.206).
Normal pregnant women were not significantly different from preeclampsia cases in the
view of FT3 level (1.38 pg/ml vs. 1.41 pg/ml, p=0.803), FT4 level (0.95 pg/ml vs. 0.96
pg/ml, p=0.834) and TSH level (3.51 μIU/ml vs. 3.10 μIU/ml, p=0.386).
Conclusion: The findings of the present study do not support the hypothesis that
changes in FT3, FT4 and TSH levels could be possible etiology of preeclampsia.

Key words: Tri‐iodothyronine (T3), Thyroxine (T4), Thyroid ‐Stimulating Hormone (TSH), Preeclampsia, Pregnancy,
Thyroid.
This article was extracted from G.P. thesis.

Introduction gestation (1). This disorder is unique to human

pregnancy in which numerous genetic immune-
The term preeclampsia describes the logical and environmental factors interact.
development of hypertension ≥140/90 mmHg with Therefore, it is a leading cause of maternal and
proteinuria ≥300mg/24h after 20th week of fetal morbidity and mortality throughout the world
and still is one of the most complex problems in
Corresponding Author: obstetrics (2). It has long been recognized that
Fatemeh Vahid Roodsari, Department of Obstetrics and maternal thyroid hormone excess or deficiency can
Gynecology, Ghaem Hospital, Mashhad University of influence maternal and fetal outcome at all stages
Medical Sciences, Mashhad, Iran. of pregnancy and can interfere with ovulation and
Email: [email protected]
 Khadem et al

fertility (3, 4). During the first trimester, the fetus and 40 normal pregnant women who had referred
is reliant on transplacental passage of maternal to Ghaem Hospital related to Mashhad University
thyroxine, as the fetal thyroid is not fully of Medical Sciences in 2007. The inclusion criteria
functional until about 16th weeks of gestation, were all consecutively diagnosed cases of
whereas thyroid hormone receptors in fetal tissues preeclampsia (blood pressure ≥140/90mmHg and
are functional much earlier (5). proteinuria≥300mg/24h after 20th week of
Although, pregnancy is usually associated with gestation) with gestational age>34 weeks and
very mild hyperthyroxinemia, women complicated singleton pregnancy and no history of thyroid
with preeclampsia have high incidence of disease before and through pregnancy.
hypothyroidism that might correlate with the The patients with the history of hypertension,
severity of preeclampsia (6). The mechanism of renal disorders, cardio vascular diseases, any
hypothyroidism in preeclampsia has not been metabolic disorder before or during the pregnancy,
identified, but the changes in thyroid function and history of intake of any medication such as
during pregnancy are accounted for by high levothyroxine that may affect on thyroid function
circulating estrogens (7). There are controversies were excluded from the study.
about the mechanism and clinical significance of Written informed consent was obtained from all
low concentration of thyroid hormones in patients participating in the study and they were
preeclampsia which is related to decreased plasma assured about the privacy of the data. The study
protein concentrations and increased endothelin was approved by the Human Research Ethics
level (7). Committee of Mashhad University of Medical
Maternal hypothyroidism is the most common Sciences. Preeclampsia was defined as mild when
disorder of thyroid function in pregnant women blood pressure (BP) exceeded 140/90 mmHg on
and is associated with pregnancy‐induced two more occasions at least 6-h apart and
hypertension, fetal mortality, placental abruption, proteinuria exceeded 300 mg/24-h, and as severe
preterm delivery, and reduced intellectual function when BP was at least 160/110 mmHg and
in the offspring (8). These outcomes have been proteinuria exceeded 5 g/24-h (21).
associated with both overt hypothyroidism After hospitalization, 3 CC of venous brachial
(elevated serum TSH concentration and reduced blood samples were obtained from each woman
free T4 concentration), that is found in about 0.2% (cases and controls), after the diagnosis was made
of pregnant women, as well as subclinical before the initiation of the antihypertensive
hypothyroidism (elevated serum TSH and free T4 treatment, and before delivery (26). Blood pressure
concentration) that is found in about 2.3% of values were recorded in a semireclining position
pregnant women (9-11). by the researcher every 6 h.
Maternal overt hyperthyroidism (suppressed The right arm was used in a roughly horizontal
serum TSH and elevated serum free T3 and T4 position at heart level. For diastolic blood pressure
concentration) is less common that affects measurements, both phases (muffling sound and
approximately two of 1000 pregnant women (2). disappearance sound) were recorded. This is very
Kumar and coworkers in 2003 reported that the important, since the level measured at phase IV is
level of TSH was increased during first, second about 5 to 10 mmHg higher than that measured at
and third trimester in all normal pregnant women phase V. Blood pressure measurements were
(12). Larijani et al in 2004 reported that serum obtained with random-zero sphygmoma-nometers
levels of free T4 and TSH were higher in women and were recorded in sitting position (15).
with severe preeclampsia compared with mild Thyrotropin (TSH) concentration was measured
preeclampsia and normal pregnancy (13). by a sensitive immunoradiometric (IRMA) method
The severity and duration of maternal thyroid (Kavoshyar, Tehran, Iran), and concentration of
disease necessary to produce these abnormalities free T3 and free T4 by (Immunotech, Marseille,
value and timing of therapeutic intervention remain France). All biochemical measurements were
controversial (14, 15). The aim of this study is performed by RIA. Normal levels of thyroid
comparison of serum levels of T3, T4 and TSH in hormones were as follows: TSH 0.4-4.5 µU/mL,
preeclampsia and normal pregnancy. free T4 0.8-2.3ng/dL, free T3 0.13-0.55 ng/dL
(25).
Materials and methods All women were followed up through their
antenatal, intrapartum and postpartum period. They
This case‐control, analytic‐descriptive study were especially observed for the development of
was performed on 40 women with preeclampsia the symptoms and signs of hypothyroidism.

48 Iranian Journal of Reproductive Medicine Vol.10. No.1. pp: 47-52, January 2012
 Levels of T3, T4, and TSH in preeclampsia

Statistical analysis The mean parity in case group was 1.87±1.45

Frequency tables were used for description of and in control group was 1.48±1.07. There was no
data, Chi‐square, t‐student test and Bivariate significant difference between two groups in the
correlation test for analyzing data and logistic view of mean of parity (p=0.206) (Table I). In case
regression for controlling the intervention group the mean T3 level was 1.38±0.74 pg/ml, and
variables. For evaluating two groups, Pearson in control group it was 1.41±0.39 pg/ml. No
correlation coefficient test and Independent sample significant difference was observed between two
‘t-test’ were used. p≤0.05 was considered groups in the view of T3 level (p=0.803) (Table I).
statistically significant. The mean T4 level was 0.95±0.27 pg/ml in case
group and 0.96±0.16 pg/ml in control group.
Results There was no significant difference between
two groups in the view of T4 level (p=0.834)
A total of 80 women were enrolled in this (Table I). The mean TSH level was 3.51±1.84
study. Among them, 40 women with preeclampsia μIU/ml in case group and 3.10±2.01 μIU/ml in
were in case group and 40 healthy pregnant women control group. No significant difference was
were in control group. In case group, the mean age observed between two groups regarding TSH level
of the women was 28±6 yrs and in control group (p=0.386) (Table I). In both groups, there was no
the mean age was 26±5 yrs. No significant significant difference between T3 level and mean
difference was observed in the view of mean age, of parity and age, between T4 level and mean of
proteinuria and systolic and diastolic blood parity and age, between TSH level and mean of
pressure between two groups (p=0.297) (Table I, parity and age.
Table II).

Table I. Demographic characteristics of the women in both groups.

Statistical index Mean±SD
p-value
Parameters Case Control
Age (year) 28±6 26±5 0.297
Parity 1.87±1.45 1.4±1.07 0.206
FT3 level(pg/ml) 1.38±0.74 1.41±0.39 0.803
FT4 level(pg/ml) 0.95±0.27 0.96±0.16 0.834
TSH level(μIU/ml) 3.51±1.84 3.10±2.01 0.386

Table II. Demographic characteristics of the women in both groups.

groups N Mean Std. Deviation Std. Error mean
Gestational
Case 33 35.5758 3.68299 0.64113
Control 2 38.5000 0.70711 0.50000
High sys- before
Case 29 157.5862 20.29341 3.76869
Control 2 1800000 0.00000 0.00000
High dia- before
Case 29 101.8966 13.12126 2.43656
Control 2 150.0000 7.07107 5.00000
High sys- after
Case 29 140.1724 19.47905 3.61717
Control 2 147.5000 17.67767 12.50000
High dia- after
Case 26 89.8077 10.62834 2.08439
Control 2 82.5000 3.53553 2.50000
24 hours urine protein
Case 24 0.9942 -
1.73162
Control 1 0.0400 -
Total 25 0.9560 1.70586 -
High dia: high diastolic blood pressure. High sys: high systolic blood pressure.

Iranian Journal of Reproductive Medicine Vol.10. No.1. pp: 47-52, January 2012 49
 Khadem et al

Discussion the study on 82 pregnant women consecutively

admitted with the diagnosis of preeclampsia in the
Preeclampsia is a serious complication of third trimester. Only mean TSH was significantly
pregnancy with unknown etiology that may occur increased in preeclampsia cases as compared to
at any stage of second or third trimester (16, 17). control subjects (26).
Although it is defined in terms of hypertension and Their findings suggested that preeclamptic
proteinuria, it can affect other maternal systems, so women had higher incidence of biochemical
the presentation and progression of this disease are hypothyroidism compared with normotensive
variable (18, 19). Furthermore, the treatment of pregnant women. This difference in the results may
this disorder has not significantly changed from 50 be due to the fact that the time of blood sample
years ago so far (20). However, the cause of was different in the studies; lower levels of T3, T4
preeclampsia has remained unknown, but the along with high level of TSH would be observed at
condition has been reported to be correlated with a later stage of preeclampsia.
deficient intravascular production of prostacyclin, Some studies reported that serum TT3 and TT4
a vasodilator, and excessive production of were significantly decreased and TSH was
thromboxane, a platelet‐derived vasoconstrictor significantly increased in preeclampsia at third
and stimulant of platelet aggregation (13-15). trimester (27). High levels of FT4 and TT4 and
The endothelial cell dysfunction plays an low levels of TT3 and FT3 was observed in
important role in the pathogenesis of preeclampsia. toxemic patients compared to normal pregnant
Modest decreases in thyroid hormones along with women (23).
increased TSH level in maternal serum are Khandakar and colleagues in 2002 found TT4
level was significantly increased in pregnant
correlated with severity of preeclampsia and high
women at third trimester of pregnancy, but it was
levels of endothelin (21). Reduced serum
normal in non pregnant women. TT3 and TSH
concentration of T3 and T4 may also be explained
levels didn't increase (28). Moreover, Gulaboglu et
by the faulty estrogen production due to placental
al. reported that no difference was observed in
dysfunction in preeclampsia. FT4 concentration is
levels of TSH and FT4 between preeclamptic cases
not associated with plasma albumin (22).
and normal pregnant women, but FT3 level was
Higher levels of FT4 and total T4 (TT4) with
different between two groups (19). Lao et al
lower levels of FT3 and total T3 (TT3) are reported decreased levels of FT4 and increased
reported in preeclamptic patients compared to levels of TSH in preeclampsia (22).
normal pregnant women (23). The titers of FT3 are Vojvodic and associates reviewed medical
significantly related to the decreased plasma records of 183 preeclamptic patients; they found a
albumin concentration in preeclampsia (24). It has significantly higher incidence of preeclampsia in
been suggested that reduced concentration of pregnant women with hyperthyroidism and
thyroid hormones in preeclampsia may be due to hypothyroidism (29). The cause of the different
the loss of protein and protein‐bound hormones in results may be difference in study population.
the urine (6). Bankowska et al reported that thyroid dysfunction
The results of the present study suggest that the was concluded in 78.2% of pregnant women with
levels of T3, T4 and TSH were not significantly preeclampsia. They concluded that the thyroid
different between preeclampsia and normal function tests should be performed in all pregnant
pregnancy. A study from Qublan et al. performed women with preeclampsia (30).
on 27 severe preeclampsia cases reported that no The difference in the results of their study with
significant difference was observed in levels of the results of the present study could be various
FT4, FT3, and TSH between preeclamptic cases geographical areas, different races, and different
and normal pregnant group with various diets. Moreover, an abnormally functioning
gestational age subgroups (24). placenta is associated with decreased TBG and
Their finding is in accordance with the current higher rates of abortion. Abnormalities in placental
study. Kumar and coworkers in 2005 performed function can interfere with oestrogen production

50 Iranian Journal of Reproductive Medicine Vol.10. No.1. pp: 47-52, January 2012
 Levels of T3, T4, and TSH in preeclampsia

that leads to decreased levels of TBG, T3 and T4 10. Negro R, Formoso G, Mangieri T, Pezzarossa A, Dazzi D,
Hassan H. Levothyroid treatment in euthyroid pregnant
(31). Further studies with large population are
women with autoimmune thyroid disease: effects on
needed to certainly support the hypothesis that obstetrical complications. J Clin Endocrinol Metab 2006;
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with preeclampsia. 11. Haddow JE, Palomaki GE, Allan WC, Williams JR,
Knight GJ, Gagnon J, et al. Maternal thyroid deficiency
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present study, the measurement of serum levels of development of the child. N Engl J Med 1999; 341: 549-
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12. Kumar A, Gupta N, Nath T, Sharma JB, Sharma S.
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13. Larijani B, Marsoosi V, Aghakhani S, Moradi A,
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Hashemipour S. Thyroid hormone alteration in
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