|Year : 2021 | Volume
| Issue : 5 | Page : 98-103
Prevalence of thyroid dysfunction and anti–thyroid peroxidase antibody in gestational diabetes mellitus
Arun Karat1, Chandni Radhakrishnan2, Nallaveetil K Thulaseedharan1, Suneetha Kalam3
1 Department of Medicine, Government Medical College, Kozhikode, Kerala, India
2 Department of Emergency Medicine, Government Medical College, Kozhikode, Kerala, India
3 Department of Obstetrics and Gynecology, Government Medical College, Kozhikode, Kerala, India
|Date of Submission||21-Mar-2021|
|Date of Acceptance||27-May-2021|
|Date of Web Publication||20-Jul-2021|
Dr. Arun Karat
PKDAS Institute of Medical Sciences, Palakkad 679522, Kerala.
Source of Support: None, Conflict of Interest: None
Background: Gestational diabetes mellitus (GDM) and thyroid dysfunction are the two common endocrine disorders affecting pregnancy. Some association was hypothesized between GDM and thyroid dysfunction in the literature. The main aim of this study was to unveil this metabolic interplay as better understanding may facilitate early diagnosis and intervention thereby limiting major fetal and maternal adverse events. Here we estimated the prevalence of abnormal thyroid function and anti–thyroid peroxidase (anti-TPO) antibody and also studied the risk factors for thyroid disorders in patients with GDM. Materials and Methods: This cross-sectional study was conducted between February 2014 and January 2015. A total of 100 consecutive pregnant women diagnosed to have GDM as per the American Diabetes Association 2013 recommendations were recruited and thyroid stimulating hormone, free triiodothyronine (T3), free thyroxine (T4), and anti-TPO antibody assays were done. Details regarding pregnancy outcome and any complications if present were also obtained and analyzed. The prevalence is expressed as proportions, and the statistical significance of risk factors was assessed using the chi-square test and independent t-test. Results: Abnormal thyroid function was detected in 31 (31%) patients, which includes 17 cases of subclinical hypothyroidism (54%), 10 hypothyroidism (32%), 2 (6%) subclinical hyperthyroidism, and one case each of isolated low T3 and isolated low T4. Anti-TPO antibody was positive in 35 patients (35%). History of GDM in previous pregnancy, family history of diabetes mellitus, presence of clinically detectable thyroid gland enlargement, and presence of anti-TPO antibody in serum were found to increase the risk of thyroid dysfunction. Majority of the subjects had uneventful delivery, and no significant increase in maternal or fetal complications was reported. Conclusions: This study showed a high prevalence of thyroid dysfunction and anti-TPO antibody in GDM patients. The significant thyroid abnormalities detected were subclinical hypothyroidism and hypothyroidism. The risk of thyroid dysfunction is elevated in patients with the presence of anti-TPO antibody. This scenario provides a strong ground to recommend meticulous assessment of thyroid function in GDM patients.
Keywords: Anti-TPO, free T3, free T4, gestational diabetes mellitus, hyperthyroidism, hypothyroidism, thyroid, TSH
|How to cite this article:|
Karat A, Radhakrishnan C, Thulaseedharan NK, Kalam S. Prevalence of thyroid dysfunction and anti–thyroid peroxidase antibody in gestational diabetes mellitus. J Diabetol 2021;12, Suppl S1:98-103
|How to cite this URL:|
Karat A, Radhakrishnan C, Thulaseedharan NK, Kalam S. Prevalence of thyroid dysfunction and anti–thyroid peroxidase antibody in gestational diabetes mellitus. J Diabetol [serial online] 2021 [cited 2021 Jul 30];12, Suppl S1:98-103. Available from: https://www.journalofdiabetology.org/text.asp?2021/12/5/98/321821
| Introduction|| |
Pregnancy brings about many physiological changes in the body as a result of interactions occurring at the fetomaternal interface. Alterations in the structure and functions of the endocrine system is one among them. These normal physiological adaptations can go unchecked in some individuals with either genetic predilections or due to environmental triggers which, lead to various metabolic and endocrine disorders in pregnancy.
The widely studied and the most common endocrine abnormality in pregnancy is progressive increase in insulin resistance with advancing gestation. Gestational diabetes mellitus (GDM) is defined as any degree of carbohydrate intolerance with onset or first detection during pregnancy. The expanding population of metabolic syndrome in the general community exhibits least tolerance to the diabetogenic state of pregnancy and contributes maximum to the explosive increase in the prevalence of GDM. GDM is associated with various maternal and perinatal adverse outcomes. In the long run, such mothers are at high risk of developing diabetes mellitus and metabolic syndrome. Similarly, children born to GDM mothers also carry elevated risk of glucose intolerance, obesity, and metabolic syndrome in the future., Based on data from different population, the prevalence of GDM varies between 1% and 14%.
To handle the excessive metabolic demands in pregnancy, the thyroid gland adapts to its full functional capacity, and thyroid abnormalities occur as the second commonest endocrine disorder. Thyroid hormone profile shows dynamic changes as a result of changes in the level of binding proteins, changes in the iodine requirement in pregnancy, increased urinary loss of iodine, and due to the effect of beta human chorionic gonadotrophin. The thyroid autoantibodies are detectable in approximately 10% of pregnant ladies at 16 weeks. Their presence in pregnancy complicated by thyroid dysfunction and GDM is important as it holds the speculation of an autoimmune etiology responsible for these disorders.
The adverse maternal and fetal outcomes that result from diabetes mellitus or thyroid dysfunction are well studied, and the timely intervention to correct these abnormalities had met with good results. When insulin resistance and thyroid dysfunction go closely related in the general population, there is strong biological plausibility of their simultaneous occurrence and additive effects during gestation. The co-occurrence of diabetes mellitus and thyroid disorders has already been demonstrated in experimental rats. Some possible interactions between these two endocrinopathies have been speculated though the definite evidence is still lacking.
The prevalence of thyroid dysfunction in gestational diabetes mellitus patients if properly identified could help for screening and early intervention in such high-risk individuals. Timely recognition and appropriate management will reduce the chance of bad pregnancy outcome like miscarriage and premature delivery and adverse fetal outcomes. The present study was planned with the objectives to study the prevalence and risk factors of abnormal thyroid function and anti–thyroid peroxidase (anti-TPO) antibody in patients with GDM. As a secondary objective, the data regarding pregnancy outcome were also collected and analyzed.
| Materials and Methods|| |
This is a cross-sectional hospital-based study conducted in the Internal Medicine and Obstetrics Department of Government Medical College, Calicut, Kerala, which is a tertiary care hospital in South India. The research protocol was approved by the Institutional Research Committee and the Institutional Ethics Committee. Sample size calculation was done using the formula ZPQ/d2 using prevalence from the literature and an allowable error of 20% of the prevalence. One hundred consecutive pregnant women with GDM diagnosed according to American Diabetes Association recommendations 2013 at 24–28 weeks of gestation were enrolled into the study after getting their informed consent. Oral glucose tolerance test (OGTT) was performed with 75 g glucose in the morning after an overnight fast of at least 8h. The diagnosis of GDM is made when any of the following plasma glucose values are exceeded: fasting: ≥92 mg/dL, 1 h: ≥180 mg/dL, 2 h: ≥153 mg/dL.
The exclusion criteria were
- Patients on any medication that may alter normal thyroid function
- Pregnant patients with overt diabetes mellitus
- Patients already diagnosed to have some thyroid disease or with a history of thyroid disease
- Patients with any other medical or pregnancy related comorbidities
- Patients with a history of any other autoimmune diseases
Subjects were evaluated by detailed history and physical examination. Blood samples were collected for thyroid function test [thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4)] and anti-TPO antibody assay between 24–28 weeks of gestation. Subjects with hypothyroidism or subclinical hypothyroidism received treatment with a target TSH of 3 mIU/L. They were followed up till the time of delivery to study the fetal and maternal outcomes.
Hypothyroidism is defined as low FT3 and FT4 with elevated TSH. Subclinical hypothyroidism is defined as elevated TSH with normal FT3 and FT4 levels. Subclinical hyperthyroidism is diagnosed when TSH is low with normal thyroid hormone levels. Isolated low triiodothyronine (T3) and low thyroxine (T4) are diagnosed as isolated reduction of FT3 and FT4 below normal, respectively, with normal TSH. The normal values of thyroid function test in pregnancy are given in [Table 1].
Anti-TPO assay was done by Enzyme Immuno Assay. Anti-TPO estimation has a sensitivity of 2 IU/mL with a coefficient of variation of 6.4%–7.1% without significant cross reactivity. Titre above 30 IU was taken as significant. Thyroid function test was done by electrochemiluminescence method. It has a sensitivity of 0.005 mIU/L, 0.3 pmol/L, 0.4 pg/mL for TSH, FT4, and FT3, respectively. Coefficients of variation for the above tests are 1.1%–3.2%, 1.7%–2.3%, and 4.3%–7.8%, respectively. All samples were processed and analyzed in the same laboratory on the same day of sample collection.
Initially, baseline, clinical, and laboratory data were analyzed, and their means were calculated as a measure of central tendency. The prevalence of thyroid dysfunction and anti-TPO positivity was expressed as proportions. Differences between groups were compared with Student’s t-test for parametric continuous variables and with chi-square test for categorical variables. A P value <0.05 was used as the threshold for statistical significance. Data analysis was performed with the SPSS V 16.0 software.
| Results|| |
The mean age of the population was 28.13 years, with a range of 19–39 years. The baseline variables are summarized in [Table 2].
Abnormal thyroid function test was observed in 31% (31/100) of the patients. The most common abnormality was subclinical hypothyroidism (17%, 17/100) followed by hypothyroidism (10%, 10/100). The frequency distribution of different patterns of abnormal thyroid function test is depicted in [Graph 1].
|Graph 1: Numbers on the bars represent the total number of patients. x axis = thyroid dysfunction, y axis = frequency|
Click here to view
Anti-TPO titre was highly variable in the subjects ranging from 4 to 984 IU/mL. (mean = 83, SD = 148.5). Any value above 30 was considered as elevated, and value >100 IU/mL was taken as strongly positive.
Thirty-five percent (35/100) of the patients had elevated titre of anti-TPO (>30 IU/mL). The distribution of patients is as given in the pie diagram [Graph 2]. Fifty-eight percent (18/31) of the patients with abnormal thyroid function were found to have elevated anti-TPO titre. The prevalence of anti-TPO in various subgroups of thyroid dysfunction is given in [Table 3].
|Graph 2: Distribution of anti–thyroid peroxidase antibody. Numbers on the pie diagram represent the total number of cases in the respective category|
Click here to view
|Table 3: Prevalence of anti-TPO antibody in patients with thyroid dysfunction|
Click here to view
Analysis of risk factors
Multiple risk factors for thyroid dysfunction and thyroid autoimmunity were analyzed separately using chi square, independent Student’s t-test, or Mann–Whitney U test, and the results are as summarized in [Table 4] and [Table 5].
|Table 4: Analysis of quantitative variables as risk factors for thyroid dysfunction and anti-TPO positivity|
Click here to view
|Table 5: Association of risk factors with thyroid dysfunction and anti-TPO positivity|
Click here to view
Statistically significant risk factors for thyroid dysfunction in GDM patients are
- i) History of GDM in previous pregnancies.
- ii) Family history of type 2 diabetes mellitus in first-degree relatives.
- iii) Presence of goitre.
- iv) Positive anti-TPO antibody in serum (directly related to titre).
Various risk factors for anti-TPO positivity were analyzed, and we found that these subjects were likely to be older, multiparous, and have a family history of diabetes mellitus.
Pregnancy outcome details were available for 92 patients. Details of eight patients could not be collected as they shifted to other centers for delivery and further treatment. Because our study protocol did not include the effect of intervention, follow-up values of thyroid function tests or blood glucose were not collected. Gestational age at delivery varied from 36 to 40 weeks with a mean of 37.27 weeks. Sixty-three patients had normal delivery, and remaining 29 underwent caesarean section. There was no increase in the number of caesarean deliveries. The mean birth weight was 3.39 ± 0.539kg (range = 1.85–4.6kg). Maternal complications reported include one case of postpartum hemorrhage and one case of postoperative wound infection. Fetal complications reported include neonatal jaundice, hypoglycemia, meconium aspiration, and one baby with congenital talipes equinovarus. Neonatal screening showed normal TSH in all the babies. None of the fetal or maternal complications were found to be more common in our study group than in the general population. Similarly, none of them showed a significant association with abnormal thyroid function or anti-TPO antibodies.
| Discussion|| |
The association between hypothyroidism and metabolic syndrome including diabetes mellitus and insulin resistance in general population is a subject of extensive studies. It is estimated that among diabetic patients, 2.7% had overt hypothyroidism, while the prevalence of subclinical hypothyroidism reached up to 30% in these patients. Pregnancy associated with both diabetes mellitus and hypothyroidism possesses elevated risk of preterm delivery, and these patients are more likely to receive infertility treatment and have multiple abortions. Our study reports high prevalence of thyroid dysfunction among GDM patients, majority of which is subclinical hypothyroidism. In addition, a good number of cases were found to have anti-TPO antibodies in the serum.
In normal pregnancy, the prevalence of hypothyroidism shows great geographical variation. In iodine sufficient and developed countries, the reported prevalence is as low as 0.5%. At the same time, studies from India report a prevalence of 4.5%–4.8%. Researches conducted across different parts of Kerala and other states consistently show a lower prevalence rate of thyroid dysfunction and anti-TPO antibody in pregnancy in comparison to our cohort of GDM patients.,,,,
Hypothyroidism in pregnancy can cause a number of adverse events that include first-trimester abortions, anemia, postpartum hemorrhage, gestational hypertension, and placental abruption., Fetal complications like multinodular goiter, small or large-for-gestational-age babies, abnormal neurological development, psychological disorders, and poor intelligence quotient are also well described.
Multiple similar studies conducted across the world reported a higher prevalence of thyroid dysfunction in GDM patients.,,,, A hypothesis of thyroid autoimmunity triggered by hyperglycemia is also proposed by some investigators.,, A Chinese study also came supporting this view and has shown that the serum levels of T3, FT3, T4, FT4 were significantly lower in GDM patients. Recent studies have reported increased incidence of thyroid autoimmunity in type 2 diabetes mellitus, thus implying that diabetes mellitus can trigger the onset of thyroid autoimmunity. Although in these patients GDM usually resolves after delivery, up to 70% of them develop overt type 2 diabetes mellitus within 10 years.
In our study, among these 100 patients, 10% had hypothyroidism, 17% subclinical hypothyroidism, 2% subclinical hyperthyroidism, and one case each of isolated FT3 and FT4. Subclinical hypothyroidism—the most frequent thyroid abnormality in our study—has gained significant clinical importance recently. The adverse effects of untreated subclinical hypothyroidism have been reported in both mother and the fetus, and in many centers, pharmacologic therapy is practiced for this entity. One study from the Indian state of Haryana reported a high prevalence of 21% from a cross-sectional study of 461 pregnant patients. A meta-analysis involving six cohort studies with 35,530 patients showed increased risk of GDM in subclinical hypothyroidism with an odds ratio of 1.35. Subclinical hypothyroidism is a strong risk factor for subsequent development of GDM, and the risk increases with increasing value of TSH. The other subgroups of thyroid function abnormalities found in our study (subclinical hyperthyroidism, isolated low FT3 and FT4) were not found to have any statistical or clinical significance. Isolated fall in FT3 or FT4 can be explained by the changes in the blood level of thyroid binding globulin occurring during pregnancy. Some studies report a nonsignificant difference in the prevalence of thyroid dysfunction between those with and without GDM. This could be due to the regional difference, racial difference, or due to difference in the rate of iodine consumption. Higher rate of iodine consumption is known to be a triggering factor for thyroid autoimmunity.
The prevalence of anti-TPO in normal pregnancy varies between 10% and 20%. In GDM patients, maximum prevalence was reported as 27%. Among the 35 patients in our study who were anti-TPO positive, 3 patients had titre more than 500 IU/mL, 18 had values between 100 and 500, and 14 had values between 30 and 100. Among 31 patients with thyroid dysfunction, 58% were thyroid antibody positive. In the hypothyroidism and subclinical hypothyroidism groups, 90% and 41% patients were positive. The prevalence of antibody shows an increasing trend with higher maternal age, multiparity, and family history of diabetes mellitus. This tendency was already demonstrated in a study published in 2012. The presence of thyroid autoantibodies indicates diminished functional reserve of thyroid gland, which may fail to adapt to the full potential as the pregnancy advances. Many such women were found to have subclinical hypothyroidism in the first trimester but subsequently progress to frank hypothyroidism in the later pregnancy. There is association between pregnancy loss and thyroid antibodies.,,
Maternal complications observed were one case of postpartum hemorrhage and one case of postepisiotomy wound infection. Among newborns, there were 12 cases of neonatal jaundice, 4 neonatal hypoglycemia, and 1 baby had meconium aspiration syndrome. There was one baby with congenital talipes equinovarus. None of these events were directly related to thyroid dysfunction or autoantibodies and were not statistically significant. Probably because of the proper treatment they received, no significant complications in mother or baby could be demonstrated.
The striking prevalence of thyroid autoantibody especially in the hypothyroid group points toward an autoimmune etiology as the major pathogenic mechanism. The hyperglycemia of GDM along with the altered immunological mileu of pregnancy could be the triggering event. The role of known and unknown shared risk factors, both genetic and environmental, needs consideration in the future studies.
Our study had few limitations as well. As the sample size was small and follow-up was short, the study might have missed many adverse effects of abnormal thyroid function. The adverse effects that may occur in the early gestations may be missed as the study was conducted toward the later stages of gestation. Even though small and negligible, there is a possibility of accidental inclusion of type 1 and new-onset type 2 diabetes mellitus patients as study subjects as we did not do a follow-up OGTT after delivery. Though the neonatal screening for thyroid dysfunction was normal in all the babies, a long-term follow-up would be ideal to look for evolution of any thyroid dysfunction or autoimmunity or any long-term complication of GDM. Lack of a control group is another limitation as we had to depend on literature data to get the prevalence of thyroid dysfunction in pregnancy without GDM. A matched control group from the same population could have been an ideal method for comparison.
According to our observations, thyroid dysfunction and thyroid autoantibody were noted in a sizeable number of cases with gestational diabetes mellitus. Their combined effect on the pregnancy could be synergistic though we could not demonstrate it here. We suggest extensive research on this area to fill the knowledge gap regarding the pathogenesis, risk factors, and the effect of interventions on this combined disorder.
Ethical approval and patient consent
The study was approved by the Institutional Ethics Committee. Written informed consent was obtained from each subject before enrollment.
Financial support and sponsorship
This study received research grant from Research Society for Study of Diabetes in India Kerala chapter.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Feldt-Rasmussen U, Mathiesen ER. Endocrine disorders in pregnancy: Physiological and hormonal aspects of pregnancy. Best Pract Res Clin Endocrinol Metab 2011;25:875-84.
Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997;20:1183-97.
Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, et al
. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991-2002.
Landon MB, Mele L, Spong CY, Carpenter MW, Ramin SM, Casey B, et al
; Eunice Kennedy Shriver National Institute of Child Health, and Human Development (NICHD) Maternal–Fetal Medicine Units (MFMU) Network. The relationship between maternal glycemia and perinatal outcome. Obstet Gynecol 2011;117:218-24.
Olivieri A, Valensise H, Magnani F, Medda E, De Angelis S, D’Archivio M, et al
. High frequency of antithyroid autoantibodies in pregnant women at increased risk of gestational diabetes mellitus. Eur J Endocrinol 2000;143:741-7.
Standards of Medical Care in Diabetes—2013. American Diabetes Association Diabetes Care 2013 Jan; 36(Suppl 1):S11-S66.
Calvo R, Morreale de Escobar G, Escobar del Rey F, Obregón MJ. Maternal nonthyroidal illness and fetal thyroid hormone status, as studied in the streptozotocin-induced diabetes mellitus rat model. Endocrinology 1997;138:1159-69.
Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al
; American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and Postpartum. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid 2011;21:1081-125.
Feely J, Isles TE. Screening for thyroid dysfunction in diabetics. Br Med J 1979;1:1678.
Tirosh D, Benshalom-Tirosh N, Novack L, Press F, Beer-Weisel R, Wiznitzer A, et al
. Hypothyroidism and diabetes mellitus - A risky dual gestational endocrinopathy. PeerJ 2013;1:e52.
Nambiar V, Jagtap VS, Sarathi V, Lila AR, Kamalanathan S, Bandgar TR. Prevalence and impact of thyroid disorders on maternal outcome in Asian-Indian pregnant women. J Thyroid Res 2011;2011:6 p. Article ID: 429097.
Seena KB, Ajithkumar VR. Screening of thyroid dysfunction in pregnancy. J Evolut Med Dental Sci 2017;6:1505+.
Fathima Thasneem EA, Shahnas M, Abdul Vahab KP. Obstetric and neonatal outcome of thyroid dysfunction in pregnancy. Int J Clin Obstet Gynaecol 2019;3:232-4.
Dhanwal DK, Bajaj S, Rajput R, Subramaniam KA, Chowdhury S, Bhandari R, et al
. Prevalence of hypothyroidism in pregnancy: An epidemiological study from 11 cities in 9 states of India. Indian J Endocrinol Metab 2016;20:387-90.
Garg R, Agrawal P, Agrawal V, Urvashi , Singh S. Prevalence of thyroid dysfunction in pregnancy. Indian J Clin Pract2019;30.
Saraladevi R, Nirmala Kumari T, Shreen B, Usha Rani V. Prevalence of thyroid disorder in pregnancy and pregnancy outcome. IAIM 2016;3:1-11.
Hallengren B, Lantz M, Andreasson B, Grennert L. Pregnant women on thyroxine substitution are often dysregulated in early pregnancy. Thyroid 2009;19:391-4.
Poppe K, Glinoer D. Thyroid autoimmunity and hypothyroidism before and during pregnancy. Hum Reprod Update 2003;9:149-61.
Betti M, Ceccatelli G, Belcari F, Moscuzza F, Cuttano A, Vuerich M, et al
. Neonatal outcome in newborns from mothers with endocrinopathies. Gynecol Endocrinol 2011;27:248-50.
Tizzo G, Di loco P, Richiusa . Pregnancy, gestational diabetes, thyroid function. Our experience. Giornale italiano di ostetricia e ginecologia 2013;35:466-70.
Ohashi M, Furukawa S, Michikata K, Kai K, Sameshima H, Ikenoue T. Risk-based screening for thyroid dysfunction during pregnancy. J Pregnancy 2013;2013:619718.
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. [Full text]
Velkoska Nakova V, Krstevska B, Dimitrovski Ch, Simeonova S, Hadzi-Lega M, Serafimoski V. Prevalence of thyroid dysfunction and autoimmunity in pregnant women with gestational diabetes and diabetes type 1. Prilozi 2010;31:51-9.
Vitacolonna E, Lapolla A, Di Nenno B, Passante A, Bucci I, Giuliani C, et al
. Gestational diabetes and thyroid autoimmunity. Int J Endocrinol 2012;2012: 6 p. Article ID 867415.
Chubb SA, Davist WA, Inman Z, Davis TME. Prevalence and progression of subclinical hypothyroidism in women with type 2 diabetes: The fremantle diabetes study. Clin Endocrinol 2005;62:480-6,200.
Safian S, Esna-Ashari F, Borzouei S. Thyroid dysfunction in pregnant women with gestational diabetes mellitus. Curr Diabetes Rev 2020;16:895-9.
Rajesh R, Goel V, Nanda S, Rajput M, Seth S. Prevalence of thyroid dysfunction among women during the first trimester of pregnancy at a tertiary care hospital in Haryana. Indian J of Endocrinol Metab 2015;19:416-9.
Toulis KA, Stagnaro-Green A, Negro R. Maternal subclinical hypothyroidsm and gestational diabetes mellitus: A meta-analysis. Endocr Pract 2014;20:703-14.
Tudela CM, Casey BM, McIntire DD, Cunningham FG. Relationship of subclinical thyroid disease to the incidence of gestational diabetes. Obstet Gynecol 2012;119:983-8.
Hajieh S, Shahbazian N, Baniani MR, Yazdanpanah L, Latifi SM. Evaluation of thyroid dysfunction in pregnant women with gestational and pre-gestational diabetes. Pak J Med Sci 2013;29:638-41.
Polyxeni K, Dimitris A, Vaggelis G, Theano R, Eleni F, Maria V, et al
. Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes. J Clin Endocrinol Metab 2012;97: 4464-72.
Glinoer D, Rihai M, Grün JP, Kinthaert J. Risk of subclinical hypothyroidism in pregnant woman with autoimmune thyroid disorders. J Clin Endocrinol Metab 1994;79:197.
Stagnaro-Green A, Roman SH, Cobin RH, el-Harazy E, Alvarez-Marfany M, Davies TF. Detection of at-risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA 1990;264:1422-5.
Iijima T, Tada H, Hidaka Y, Mitsuda N, Murata Y, Amino N. Effects of autoantibodies on the course of pregnancy and fetal growth. Obstet Gynecol 1997;90:364-9.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]