|Year : 2021 | Volume
| Issue : 2 | Page : 41-45
Thyroid function tests in euthyroid pregnant and non-pregnant women
Arya Padmakumar, Lucetta Amelia Dias, Nidhi Sharma
Department of Obstetrics and Gynaecology, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
|Date of Submission||05-May-2021|
|Date of Acceptance||29-Oct-2021|
|Date of Web Publication||28-Feb-2022|
No. 5 Jayanthi Street, Dr Seethapathi Nagar, Velachery 600042, Chennai.
Source of Support: None, Conflict of Interest: None
Background: Pregnancy is associated with significant but reversible changes in thyroid functions, which may exacerbate thyroid disorders or improve thyroid disorders. Objectives: The present study was done to find out changes in thyroid function tests in each trimester in normal pregnant women when compared with non-pregnant women in a tertiary healthcare center. Materials and Methods: A cross-sectional study of 80 euthyroid women in the age group of 16–40 years was done. Twenty were non-pregnant and 20 were from first, second, and third trimesters each. Serum level measurement of T3, T4, and TSH was done with chemiluminescence technique. Results: The results of the study showed a progressive decrease in the mean values of FT3 and FT4, with a significant decrease in FT3 (P-value < 0.0001) and FT4 (P-value =0.0129) only in the third trimester. There was a progressive increase in the mean TSH levels through the pregnancy; however, there was no significant increase when compared with the non-pregnant women. Conclusion: There is a significant increase in serum T3 and T4 in pregnancy. Specific reference intervals should be used to identify the patients at risk and to take early interventions of treatment.
Keywords: Pregnancy, thyroid function tests, thyroid-stimulating hormone
|How to cite this article:|
Padmakumar A, Dias LA, Sharma N. Thyroid function tests in euthyroid pregnant and non-pregnant women. J Cardio Diabetes Metab Disord 2021;1:41-5
| Introduction|| |
Thyroid disorders are the commonest endocrine disorders in women of child-bearing age group and pregnancy. The thyroid function during pregnancy has been found to be of utmost importance to determine maternal wellbeing and fetal growth and development. Thyroid function tests most commonly include free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH), and their levels are used for diagnosing thyroid disorders [Figure 1]. Previous studies have demonstrated that during pregnancy, maternal thyroid hormones are essential for fetal growth and development, and their deficiency can affect the pregnancy outcome and the developing fetus. However, the interpretation of thyroid function tests can be challenging due to some physiologic changes that occur during pregnancy.,
Physiological changes in pregnancy are: (A) low levels of TSH during the first trimester due to stimulatory effect of human chorionic gonadotropin (hCG) which has a structure similar to TSH, (B) increase in thyroid-binding globulin (TBG) due to estradiol and altered hepatic glycosylation, which decreases its clearance, (C) increase in the urinary iodide excretion which can lead to impaired thyroid hormone production, and (D) changes in the immune system, leading to the occurrence or exacerbation of any underlying autoimmune thyroid disease.
The commonest cause of maternal hypothyroidism worldwide is iodine deficiency. Autoimmune thyroiditis can be caused due to Hashimoto’s thyroiditis (chronic) and de Quervain’s thyroiditis (subacute/transient). Iatrogenic causes include previous thyroidectomy, previous radio-iodine or iodide treatment, drug therapy by lithium, amiodarone, etc. Congenital hypothyroidism can be caused by thyroid gland dysgenesis, thyroid dyshormonogenesis, or genetic mutations of thyroid receptors. Rarely, hypothyroidism may be a result of infiltrative disorders such as sarcoidosis.
During pregnancy, the body automatically regulates and equalizes the thyroid hormone concentration changes by increasing iodide absorption from food., This equilibrium is difficult to achieve when there is a deficiency in iodine supplementation. Gestational thyroid dysfunction is common and, if left untreated, is usually associated with risk of miscarriage, hypertension, growth restriction, and placental abruption.,
Previous studies recommended the use of pregnancy-specific reference intervals to evaluate maternal thyroid function, which can prevent the misinterpretation of thyroid function in pregnancy. If a non-pregnant reference range is used, many maternal thyroid diseases could be potentially misclassified. Therefore, maternal thyroid hormone assessment should be done using pregnancy-specific reference ranges which are based on local pregnant women data. Hence, this study was undertaken to analyze the gestational age-dependent reference intervals for thyroid hormone levels for the local population.
| Materials and Methods|| |
This cross-sectional case–control matched study was conducted in the Outpatient Department of Obstetrics and Gynecology at Saveetha Medical College and Hospital, Chennai. The study consisted of a total of 80 women, among which 20 were non-pregnant and 20 were selected each from first, second, and third trimesters. The study was carried out by consecutive enumerative sampling in February 2020 after getting written informed consent from participants in local language. A single interviewer filled the questionnaire. Data were stored in a password-protected computer.
A total of 80 women, who are euthyroid, healthy, and consuming iodine fortified salt, in the age group of 16–40 years were included in the study. Women with multiple pregnancies, pre-existing thyroid disease, hyperemesis gravidarum, molar pregnancy, pre-eclampsia, and those who did not consume iodine fortified salt were excluded. Women who did not consume iodinated salt were not included because dietary requirements of iodine are increased in pregnancy due to increased transplacental uptake of iodide and increased maternal renal clearance of iodide. Furthermore, trophoblast also contains abundance of Type 3 deiodinase (DI). Type 3 DI converts T4 to reverse T3 and T3 to di-idothyronine (T2), both of which are inactive metabolites., This results in high levels of rT3 in fetus, the significance of which is not yet understood. Hence, multiple pregnancies, molar pregnancy, and preeclampsia pregnancy were also excluded to remove any bias due to trophoblastic disorders. Those with previous history of thyroid diseases and consanguineous marriages were excluded from the study. The study was approved by Ethical and Review board of the institution (SMC/IEC/2019/003).
All pregnant women were asked to fill a questionnaire (13 multiple choice questions and 1 open-ended question) in local language about age, parity, consanguineous marriage, and previous history of any hypo/hyperthyroidism and intake of iodinated salt in the pre-conception period and during pregnancy. An open-ended question was asked about the sea food diet preferences in pregnancy and any food fads.
Cronbach’s alpha was used to validate the questionnaire and it ranged from 0.81 to 0.86 for all questions. Pre-pregnancy weight and height were also recorded. A first trimester scan was done to measure crown rump length (CRL) to confirm the gestational age of pregnancy and to exclude molar pregnancy and twins in all cases.
Blood samples were collected between 8 am and 10 am in the early morning fasting state from both the groups. Then, thyroid function tests were done in biochemistry laboratory by measuring serum levels of TSH, free thyroxine (FT4), and free triiodothyronine (FT3) using commercially available chemiluminescence technique.
Data were entered in Microsoft Excel sheet in password-protected computer. Descriptive and inferential statistics were used to analyze the data. A comparison of the thyroid hormone levels was done between the non-pregnant women and pregnant women in each trimester. The data were expressed in the form of mean±SD. A P-value of 0.01 was taken as statistically significant.
| Results|| |
Data were analyzed for 60 pregnant and 20 non-pregnant women. This is a cross-sectional study so there was no attrition.
The mean age of pregnant women population studied was 29.17 ± 3.15. The mean parity of the study population was 1.62 ± 0.52. [Table 1] is the comparison of TFT levels between non-pregnant women and pregnant women in each trimester. It shows that the mean FT3 and FT4 values progressively decreased through the pregnancy but the mean TSH value increased progressively through the pregnancy.
|Table 1: Trend in the free T3, free T4, and TSH values in pregnant and non-pregnant women in first, second, and third trimesters (n = number of pregnant women, SD= standard deviation)|
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[Table 2] is the comparison of serum FT3 between the groups done by calculation of P-value. It showed decline in the mean FT3 values in the first and second trimesters and a significant decrease in the third trimester (P < 0.01) when compared with the non-pregnant group [Table 2]. [Table 2] also shows the comparison of P-values of FT4 between the groups. It showed a decline in the mean FT4 values in the first and second trimesters and a significant decline in the third trimester (P < 0.01), with relation to the non-pregnant group. [Table 2] also reveals the P-values of TSH between the two groups. It showed a progressive increase in the mean TSH value in the first, second, and third trimesters but without any significance (P < 0.01), with relation to the non-pregnant group.
|Table 2: Changes in FT3, FT4, and TSH of pregnant women in first, second, and third trimesters when compared with non-pregnant status (P-value<0.01 was considered statistically significant*)|
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| Discussion|| |
Pregnancy is a state of increased iodine requirement due to enhanced transplacental transfer of iodide to fetus and increased maternal renal clearance due to increased renal blood flow. Additionally placenta has abundant type 3 DI that inactivates T4 and T3. As a result, compensatory mechanisms get activated and the thyroid gland enlarges by an average of 10–20% and there is increased thyroid glandular iodine uptake and synthesis of thyroid hormones. In iodine-deficient areas, there may be an obvious thyroid gland enlargement in pregnancy.
Hyperestrogenemic state of pregnancy starting from the first trimester induces a marked and early rise in serum TBG concentrations resulting in increased total T3 and T4., However, the circulating levels of free T3 and free T4 remain near normal if the thyroid is able to secrete more hormones in response to the increased requirements of pregnancy.
In the first trimester, furthermore, hCG is secreted from placenta that peaks in the end of first trimester.,, hCG is a bipeptide and has an identical TSH alpha subunit and a l-beta subunit with a limited sequence homology to TSH. hCG has a weak TSH-like activity and stimulates maternal T4 secretion. The transient hCG-induced rise in serum-free T4 inhibits maternal secretion of TSH from pituitary in the first trimester. In the first trimester, therefore, there is a mild increase in free T4 and a slight decrease in serum TSH., In our study, there is a marginal increase in serum TSH in the first trimester, although this is not statistically significant.
It is believed that there is a temporary resetting of hypothalamo-pituitary thyroid negative feedback system in early pregnancy that aims to increase T4 supply to fetus. Maternal supply of T4 to fetus is critical to fetal development in the first trimester as the fetal thyroid has not yet formed. T3 may also have a role to stimulate epidermal growth factor and 17-beta estradiol production by trophoblast that help in trophoblast invasion and syncytiotrophoblast differentiation.
This study compared the thyroid hormone levels of a total of 80 women in the pregnant and non-pregnant state, who were all aged between 16 and 40 years.
Results of this study showed that FT3 declined in the first trimester. FT4 also declined during the first trimester. TSH progressively rose in the first trimesters of pregnancy, but these changes were not found to be significant when compared with non-pregnant women. A study by Zarghami et al. showed that the FT4 values decreased progressively through the pregnancy with a significant decrease in the third trimester (P < 0.01), which was similar to our study. The TSH values also showed a trend similar to their study, where it increased progressively through the pregnancy but without any significance (P > 0.01) when compared with the non-pregnant group.
After the first trimester, the hCG levels in maternal blood drop and maternal serum TSH and FT4 return to a near normal in the second trimester as evidenced by other studies. In our study also, there was no statistically significant difference in the second trimester. However, the FT3 values in our study showed a progressive decline, with a significant decrease only in the third trimester (P < 0.01) when compared with the study by Zarghami et al., in which it showed a significant decrease in the second and third trimesters. Similar results are achieved by various other studies on serum thyroid hormone levels in pregnancy. The decline in serum levels of hormones can be explained by progressive hemodilution in second trimester pregnancy.,
In the third trimester, the decline of serum T3 and T4 was significant statistically. In the third trimester, the apparent mild hypothyroidism can be explained by a dilutional effect as there is a 50% increase in maternal blood volume. This alone cannot be only explanation as most of the increase in blood volume happens by the second trimester. Mild hypothyroidism in the third trimester could also be a physiological adaptation to try to conserve energy for parturition. It could also reflect the inability to compensate for the increased fetal demands of iodide with a more active fetal thyroid hormone synthesis, increased breakdown of maternal thyroid hormones by a larger placenta, and transfer of maternal T4 to fetus. The corresponding rise in TSH is the evidence of normal pituitary sensitivity to thyroid hormones. There was a rise of TSH in the third trimester in this study, although it was not statistically significant when compared with non-pregnant woman.
The American Thyroid Association (ATA) guidelines recommended that the interpretation of thyroid levels in pregnancy are based on trimester-specific reference ranges as defined in populations with adequate intake of iodine.,, The guidelines stated that the default TSH values should be 0.1–2.5 mIU/L for the first trimester, 0.2–3.0 mIU/L for the second trimester, and 0.3–3.5 mIU/L for the third trimester.
| Conclusion|| |
All pregnant women should undergo thyroid screening in pregnancy, and pregnancy-specific reference intervals should be used to identify patients at risk and to take early interventions of treatment.
Thyroid function tests in pregnancy should be interpreted against the gestational-age reference intervals and not against the normal non-pregnant reference intervals as it can lead to misclassification of the patients. There is a resetting of normal levels of free T3, T4, and TSH during pregnancy. The changes are reflective of the development of placenta and fetus. Maternal hypothyroidism is the only preventable cause of new born mental retardation, and thyroxine supplementation during pregnancy can prevent it.
The thyroid function testing of antenatal women was funded by grants from Saveetha University. This center provides free care to pregnant women who come for institutional care. The authors also thank the staff of Outpatient Department of Obstetrics and Gynecology and Department of Biochemistry, Saveetha Medical College and Hospital for the care given to research participants.
Financial support and sponsorship
Conflict of interest
The authors declare that there is no conflict of interest. We do not have any commercial association that might pose a conflict of interest in connection with the manuscript. We certify that neither this manuscript nor the one with substantially similar content under our authorship has been published or is being considered for publication elsewhere.
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[Table 1], [Table 2]