|Year : 2015 | Volume
| Issue : 1 | Page : 3-7
Thyroid function in pregnant women with gestational diabetes: Is screening necessary?
Mahmoud Parham1, Firouzeh Asgarani1, Mohammad Bagherzadeh2, Gholamreaza Ebrahimi3, Jamshid Vafaeimanesh2
1 Endocrinologist, Clinical Research Development Center, Department of Internal Medicine, Qom University of Medical Sciences, Qom, Iran
2 Internist, Clinical Research Development Center, Department of Internal Medicine, Qom University of Medical Sciences, Qom, Iran
3 Researcher, Clinical Research Development Center, Department of Internal Medicine, Qom University of Medical Sciences, Qom, Iran
|Date of Web Publication||18-Dec-2014|
Dr. Jamshid Vafaeimanesh
Clinical Research Development Center, Department of Internal Medicine, Qom University of Medical Sciences, Shahid Beheshti Hospital, Shahid Beheshti Boulevard, Qom
Source of Support: None, Conflict of Interest: None
Background: The goal of prenatal care is mother's and baby's health. Pregnancy is the time of hormonal changes, which cause endocrine disorders in pregnant woman encountering risk to the mother and fetus. Two important and more common problems in pregnancy are gestational diabetes mellitus (GDM) and thyroid disorders. Approximately 1.1-14.3% of pregnant women suffer from GDM and hypothyroidism affects 2.5-6.47% of them. There are some recommendations for diagnosis and screening of GDM but there is no clear advice about the need for performing thyroid function tests during pregnancy. In this study, we aimed to evaluate the need for measurement of thyroid function tests in pregnant women with GDM. Materials and Methods: In this case-control study, 210 pregnant women (105 with and 105 without GDM) were enrolled during 2011-2012 and serum levels of free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were compared between two groups. Results: Mean TSH levels in case and control groups were 3.43 ± 2.06 and 1.74 ± 1.47 μIU/mL, respectively and was statistically higher in case group (P = 0.023). Mean FT4 levels in case and control groups were respectively 1.41 ± 0.69 and 1.5 ± 0.61 ng/dL, which were not statistically different in both groups (P = 0.67). Among patients with GDM, 18 (17.1%) had subclinical hypothyroidism and 11 (10.48%) had clinical hypothyroidism, while among non-GDM patients, 7 (6.66%) had subclinical hypothyroidism and 4 (3.81%) had clinical hypothyroidism. Conclusion: In patients with GDM, hypothyroidism (clinical and subclinical) was obviously higher, the mean serum TSH level was higher in these women, and it was within a range that required treatment. So, it is suggested considering screening and treatment of hypothyroidism in patients with gestational diabetes.
Keywords: Gestational diabetes, pregnancy, thyroid function
|How to cite this article:|
Parham M, Asgarani F, Bagherzadeh M, Ebrahimi G, Vafaeimanesh J. Thyroid function in pregnant women with gestational diabetes: Is screening necessary?. Thyroid Res Pract 2015;12:3-7
|How to cite this URL:|
Parham M, Asgarani F, Bagherzadeh M, Ebrahimi G, Vafaeimanesh J. Thyroid function in pregnant women with gestational diabetes: Is screening necessary?. Thyroid Res Pract [serial online] 2015 [cited 2019 Jun 15];12:3-7. Available from: http://www.thetrp.net/text.asp?2015/12/1/3/147271
| Introduction|| |
The goal of prenatal care is to ensure health of the mother and giving birth to a healthy baby.  Pregnancy is the time of complicated hormonal changes. The most common endocrine conditions encountered in pregnancy are gestational diabetes mellitus (GDM) and thyroid disease. Gestational diabetes is a condition, in which pregnant women without being previously diagnosed of diabetes, show onset of carbohydrate intolerance or being first diagnosed during pregnancy, especially during their third trimester.  In 1964, O'Sullivan and Mohan  published the criteria for GDM diagnosis by the use of 100 g oral glucose tolerance test (OGTT).
Prevalence of GDM is 1.1-14.3% based on the ethnic and clinical characteristics of the population and the type of diagnostic test.  Adverse outcomes of GDM in pregnancy include pre-eclampsia, increased cesarean rates, prenatal mortality and macrosomia, shoulder dystocia, birth defects, metabolic complications in neonate and morbidity due to subsequent childhood obesity.  The prevalence of hypothyroidism during pregnancy in the United States is estimated to be approximately 2-3% that most (2-2.5%) is subclinical. 
In some studies, the prevalence is higher. For example, in one study among the 633 pregnant women of Indian origin, the prevalence of thyroid dysfunction was high in their second trimester and subclinical hypothyroidism was seen in 6.47% while overt hypothyroidism was detected in 4.58% of women.  These conditions should be treated; otherwise, they may affect mother and fetus adversely.  Because of these known complications, screening of pregnant women for these common endocrine disorders (gestational diabetes and thyroid dysfunction) is discussed by endocrinology societies and there are various and up-to-date recommendations in this regard. Advice about diabetes is more specific and clear.
Screening for GDM, for all pregnant women and high-risk patients who tested negative in early pregnancy, should be performed between 24 and 28 weeks of gestation by a 75 g of OGTT, with fasting plasma glucose measurement at 1 and 2 hours, in these not previously diagnosed with overt diabetes. It is better to perform OGTT in the morning after an overnight fast of at least 8 hours. GDM is diagnosis when any of the following plasma glucose values are exceeded: Fasting: ≥92 mg/dL (5.1 mmol/L);1 h: ≥180 mg/dL (10.0 mmol/L);2 h: ≥153 mg/dL (8.5 mmol/L). ,
Today, universal thyroid screening in pregnant women is controversial. Some associations divide pregnant women to low-risk and high-risk groups for thyroid disorders. They advice the control of thyroid disorders only in high-risk individuals; for example, the 2002 practice guidelines from the American College of Obstetricians and Gynecologists (ACOG) recommend thyroid testing only in symptomatic high-risk pregnant women who have a personal history of thyroid disorders, type 1 diabetes or other autoimmune disorders. 
On the contrary, others do not believe in this division. For instance, the American Association of Clinical Endocrinologists (AACE) recommends routine thyroid function screening before pregnancy for all patients intended to be pregnant or during their first trimester.  The point that has been raised recently is that following these recommendations for thyroid screening that defined high-risk groups, makes a significant percentage of women with high TSH levels not to be detected. 
The incidence of thyroid disorders in patients with gestational diabetes is controversial, as some studies have found no association between gestational diabetes and thyroid dysfunction. ,, Oppositely, the others stated that hypotyroxinemia is clearly more common among patients with GDM  and some believe that hypothyroid patients are at higher risk of GDM.  In this study, we aimed to compare the thyroid dysfunction in pregnant women with and without GDM and evaluate the need for thyroid screening in these patients.
| Materials and Methods|| |
In this case-control study, we enrolled 210 pregnant women (105 women with and 105 without GDM) with gestational age of 24-28 weeks referring to diabetes clinic of Shahid Beheshti Hospital during 2011-2012. They were enrolled by consecutive patient selection and if they had eligibility criteria, then demographic data and history were recorded. Blood pressure (BP) was measured in both arms using mercury sphygmomanometer (Yamasu, Japan). Patients were sitting at least for five minutes and it was measured twice at ten-minute intervals.  The mean of these two blood pressures was assumed as the patient's blood pressure.
Inclusion criteria were pregnancy at 24-28 weeks of gestation and consent for the study. Exclusion criteria were multiple pregnancies, family history of thyroid disease, a personal history of thyroid disorders, type 1 diabetes, recurrent miscarriages, infertility, previous head or neck irradiation and overt diabetes. A diagnosis of overt diabetes was made in women whose fasting blood sugar (FBS) was ≥126 mg/dL [7.0 mmol/L]. 
All individuals signed informed consent prior to their enrollment in the study. The study was planned according to the ethical guidelines following the Declaration of Helsinki. The Qom University of Medical Sciences' ethics committee approved our study protocol following local biomedical-research regulations.
For diagnosis of GDM, the American Diabetic Association's recommendation was used. Women used 75g glucose after 8 hours night fasting and then FBS, 1hpp and 2hpp were measured. The GDM diagnosis was made when any of the following plasma glucose values were exceeded: Fasting: ≥92mg/dL; 1 hpp: ≥180 mg/dL; 2 hpp: ≥153 mg/dL.  Plasma glucose was measured by the enzymatic method. Its intra- and inter-assay coefficient of variation (CV) was 1.5% and 0.91%, respectively. The fasting samples were stored at −70°C at the Shahid Beheshti Hospital laboratory for measurement of thyroid function tests if the patients were enrolled in the study. TSH was measured by IRMA (Pishtaz Teb kit, made in Iran). The intra-assay and inter-assay CV was 1.7 and 0.3%, respectively. Its normal range was 0.32-5.2 μIU/mL. Serum FT4 concentration was measured by EIA (enzymatic immunoassay) by means of DiaMetra kits, made in Iran. Its normal range was 0.76-2.24 ng/dL in pregnant women and 0.8-2 ng/dL in adults. Then the women were assigned in two groups (with and without GDM) and their serum levels of FT4 and TSH were compared.
Kolmogorov-Smirnov test was performed to assess the variables normality. All data in this study were normally distributed, and presented as mean ± SD. Data between two groups were compared using student's t test. We used Chi-square test to compare qualitative variables between the two groups. P values less than 0.05 were considered statistically significant. We analyzed the data by Statistics Package for Social Science (SPSS version 16.0, SPSS Inc., Chicago, IL, USA). Pearson test was used to evaluate the association of parameters.
| Results|| |
In this study, 105 pregnant women with GDM (case) and 105 without GDM (control) were evaluated. Mean age of case and control groups were respectively 30.7 ± 4.7 and 29.7 ± 6.0 years and age was not statistically different in both groups (P = 0.2). Pregnancy at high risk ages (less than 18 years and above 35 years) was not statistically different in both groups (P = 0.370).
The pregnancy rate (gravidity) had no statistically significant difference in both groups (P = 0.36) [Table 1]. [Table 2] shows the mean GTT in both groups.
The mean serum level of TSH in patients with GDM and control groups were 3.43 ± 2.06 and 1.74 ± 1.47 μIU/mL, respectively and it was statistically higher in case group (P = 0.023). [Figure 1] shows the mean and confidence interval of TSH in both groups.
Among patients with GDM, 18 (17.1%) had subclinical hypothyroidism (TSH > 3 μIU/mL and normal FT4) and 11 (10.48%) had clinical hypothyroidism (TSH > 3 μIU/mL and FT4 < 0.76 ng/dL), while among non-GDM patients, 7 (6.66%) had subclinical hypothyroidism and 4 (3.81%) had clinical hypothyroidism. There was a statistically significant difference between both groups, clinical and subclinical hypothyroidism (P = 0.021 and P = 0.0193, respectively).
Mean serum level of FT4 in patients with GDM and control groups were respectively 1.41 ± 0.69 and 1.5 ± 0.61ng/dL and it was not statistically higher in case group (P = 0.760). There was a very weak positive correlation (R: 0.006) between FBS and TSH levels, which according to Pearson correlation test was not statistically significant (P = 0.96). Also, there was a weak correlation (R: 0.08) between TSH hormone level and age but no significant correlation was found between FBS and age (P = 0.51). Pregnancy rate (gravidity) and TSH level had a correlation of 0.12 but Spearman test showed no statistically significant relationship between them (P = 0.32).
| Discussion|| |
According to recent guidelines of American Thyroid Association (ATA), in the absence of laboratory-dependent, trimester-specific ranges for TSH, the recommended reference ranges are 0.1-2.5 mIU/L in the first trimester, 0.2-3.0 mIU/L in the second trimester, and 0.3-3.0 mIU/L in the third trimester.  During pregnancy, treatment of overt and subclinical hypothyroidism irrespective of thyroid peroxidase antibody (TPOAb) positivity is necessary for all women. Treatment is with levothyroxine (LFT 4 ) to maintain serum TSH in the trimester-specific goal range.  Although gestational hyperthyroidism is uncommon (0.2%), 2.5% of women experience hypothyroidism (autoimmune disease or suboptimal iodine intake), which predicts reduced neonatal and child neuropsychological development and maternal obstetric complications.  In one study, among 633 pregnant women of Indian origin, prevalence of thyroid dysfunction was high, in their second trimester; and subclinical hypothyroidism and overt hypothyroidism were seen in 6.47% and 4.58% of women, respectively.  In the United States, the prevalence of hypothyroidism during pregnancy is approximately 2-3%, of which most (2-2.5%) are subclinical.  In a study by Springer et al., elevated concentrations of TSH were found in 5.1%, suppression was found in 2.9% and TPOAb positivity in 11.5% women. 
In our study, the prevalence of hypothyroidism was higher so that of the whole patients, 7.1% had clinical and 11.9% had subclinical hypothyroidism.
It is now believed that in addition to overt thyroid dysfunction, subclinical dysfunction has adverse effects on maternal and fetal outcomes. Adverse outcomes of maternal hypothyroidism include increased risk of spontaneous abortion, premature delivery, gestational-induced hypertension, placental abortion, low-birth weight, fetal distress in labor, and impaired neuropsychological development.  Haddow and colleagues found that children 7-9 years old born to untreated hypothyroid women compared with age-matched children born to euthyroid women of less than 85, has a 7-point IQ deficit compared with 5% of controls.  The links between such obstetrical complications and subclinical hypothyroidism are less evident. 
In Sahu et al.'s study, overt hypothyroids were prone to have pregnancy-induced hypertension, intrauterine growth retardation and intrauterine fetal death. Cesarean section rate due to fetal distress was significantly higher among pregnant subclinical hypothyroid women. Neonatal complications and gestational diabetes were significantly higher in overt hyperthyroidism group.  Therefore, thyroid dysfunction screening in pregnancy should be considered. Today, the need for universal thyroid screening in pregnant women is controversial. Some associations divide people to low-risk and high-risk groups of thyroid disorders and advice the control of thyroid disorders in high-risk individuals. For example, the 2002 practice guidelines from ACOG recommend thyroid testing only in symptomatic high-risk pregnant women or women with a personal history of thyroid disorders or type 1 diabetes, or other autoimmune disorders. 
The remarkable thing is that the ACOG guidelines do not recommend testing in asymptomatic women or women with small goiters. The Endocrine society recommends screening of pregnant women or those who wish to become pregnant in case of having symptoms or physical exam findings suggestive of a goiter or hypothyroidism, a personal or family history of thyroid disease, a personal history of autoimmune disorder or type 1 diabetes, recurrent miscarriages or infertility, or previous head or neck irradiation. 
On the other hand, some others recommend the thyroid function tests as a necessary screening in all pregnant women. For example, AACE recommends routine thyroid function screening before pregnancy for all patients who wish to become pregnant or during their first trimester (13). The point that has been raised recently is that following these recommendations for thyroid screening that defined high-risk groups, makes a significant percentage of women with high TSH levels not to be detected.  For instance, in a study by Chang et al., 2.6% of women had a TSH above 4.2 mIU/L, and the prevalence was higher in the high-risk group in comparison with low-risk group. However, 30% of the women with an elevated TSH were in the low-risk population, suggesting that current screening guidelines would miss about one-third of pregnant women with hypothyroidism. 
In another study, based on trimester-specific reference ranges, 5.7% of the women had an elevated TSH in pregnancy. Of the 56 women with a high TSH, 9 had a history of thyroid disease, 1 had a history of type 1 diabetes, and one had a history of dyschromia. Based on current Endocrine Society case-finding guidelines, only these women with an elevated TSH would have undergone thyroid testing in pregnancy. The others would not have been tested, assuming they were asymptomatic and did not have a palpable goiter. 
Given these findings, it seems that we should increase the screening range for thyroid disorders. Patients with gestational diabetes are one of the groups that thyroid disorders are discussed. The increased prevalence of thyroid dysfunction in these patients is controversial. For example, in a pilot study in 1997, in Germany, 50 pregnant women were investigated for a possible correlation between thyroid function abnormalities and gestational diabetes. No significant association was found between diabetes and thyroid function abnormalities. 
In another study, in 2006, in Emirates, 301 pregnant women were enrolled and no statistically significant difference was found between the 80 (26.6%) women with GDM and the 221 (73.4%) women without GDM for any of the thyroid function tests.  In our study, we found opposite findings and among GDM patients, 18 (17.1%) had subclinical hypothyroidism and 11 (10.48%) had clinical hypothyroidism, while among non-GDM patients, 7 (6.66%) had subclinical hypothyroidism and 4 (3.81%) had clinical hypothyroidism. Also, TSH serum level was statistically and obviously higher in GDM patients and is within a range that needs treatment. Although the prevalence of hypothyroidism was statistically different in both groups, it was not statistically different in FT4 levels of both groups, which was according to findings of Velkoska Nakova's study.  It seems that the difference of findings of our study with Agarwal et al.'s study is due to not matching both groups in Agarwal's study for GDM (16). Of course, in Karakosta's study that evaluated pregnant women with thyroid dysfunction for GDM, found that the combination of high TSH and thyroid autoimmunity in early pregnancy was associated with a 4-fold increased risk for gestational diabetes. 
| Conclusion|| |
Thyroid dysfunction, particularly hypothyroidism and more commonly subclinical hypothyroidism is a common endocrine disorder in pregnant women. It seems that high-risk groups are more than the group assigned for screening. One such group is people with GDM. So, it is recommended that in these people, thyroid function evaluation and, if necessary, treatment should be performed.
| Acknowledgments|| |
Initial data of this paper was based on the General Physician's thesis that is completed and was funded by Deputy of Research and Education of Qom University of Medical Sciences. The authors would like to thank all participants who cooperated during the study. The authors would like to thank Mrs. Fatemeh Hosseinzadeh (staff of Clinical Research Development Center) for translating the paper
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[Table 1], [Table 2]