Abstract
The most common endocrine disorders during pregnancy are gestational diabetes mellitus (GDM) and thyroid disease. Individually, they have been shown to contribute to adverse obstetric outcomes. A case control study was conducted to evaluate and compare thyroid function in patients with and without gestational diabetes mellitus at Institute of Nuclear Medicine & Allied Sciences (INMAS), Cumilla in collaboration with the Department of Obstetrics & Gynaecology, Cumilla Medical College Hospital in between January to December 2021. According to inclusion and exclusion criteria, 148 pregnant women were included in the study, 74 patients with GDM (case) and 74 patients with non-GDM (control). The thyroid function was evaluated by serum TSH and FT4. Data analysis was done by chi-square test (categorical variables) and unpaired t- test (continuous variables).
In the study, mean age was relatively higher in GDM patients (28.84 ± 3.64 years) than non-GDM (27.12 ± 3.99years). Most of the patients 86 (58.1%) were in < 30 years age group. Majority was multigravida. TSH value was high in case group (4.68 ± 5.71 mIU/ml) in comparison to control (2.78 ± 3.74 mIU/ml) and statistically significant (P <0.05). In the study, 16.2% (24 of 148) patients had thyroid disorder. Thyroid disorder was more in GDM (21.6%) versus non-GDM (10.8%) patients. Association of thyroid disorder with GDM patients was higher than non-GDM group, but the result was not statistically significant [OR: 2.3 (CI: 1 to 5.7); p=0.074].
Thyroid disorder was more in gestational diabetes mellitus patients in comparison to patients without gestational diabetes mellitus. In the study the most common thyroid disorder was subclinical hypothyroidism in both case and control groups.
Introduction
The goal of antenatal care is to ensure the 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.1 The prevalence of GDM in pregnant women varies substantially, ranging from 1.7% to 11.6% in advanced economies.2 In Asian countries, the prevalence varies according to the screening strategy and diagnostic criteria and ranges from 1% to 20%, with an increasing trend in recent years.3 Higher levels of diabetogenic hormones, reduced physical activity, decreased energy expenditure, increased carbohydrate consumption, lack of adequate sleep and other stresses during gestation increase insulin requirements of pregnant women. Increased insulin requirement enhances development of GDM in susceptible pregnant women such as obese women and those with dysfunctional pancreatic β-cells or insulin resistance. GDM is associated with several adverse outcomes including miscarriage, excessive fetal growth, shoulder dystocia, birth injuries, nerve palsies and neonatal metabolic abnormalities. The risk of perinatal mortality is not increased but the risk of macrosomia is high. Gestational diabetes is a strong risk factor for diabetes in later life.4
The prevalence of thyroid dysfunctions in pregnancy is 6-7%. It was hypothesized that thyroid hormones gradually increase during the first trimester but decrease gradually over the rest of pregnancy.5 The steady rise of human chorionic gonadotropin (hCG) hormone during the first trimester was claimed to induce follicular thyroid cells to release triiodothyronine (T3) and thyroxine (T4), which reduced thyroid-stimulating hormone (TSH) via negative feedback mechanism. During the second and third trimesters, TSH increases while T3 and T4 decrease following hCG withdrawal. Lower levels of free T3 (FT3) and free T4 (FT4) over the last two thirds of pregnancy can also be explained by high thyroid hormones transport proteins concentrations induced by placental estrogens.
The overall prevalence of hypothyroidism in pregnancy varies from 0.3% -11.1% with subclinical hypothyroidism being commoner than overt hypothyroidism.6 Thyroid disorders are often overlooked in pregnancy because of their non-specific symptoms and the hyper-metabolic state of pregnancy. Hence, the laboratory measurements of thyroid function play an important role in the assessment of maternal thyroid health. The mainstay of thyroid function evaluation is serum Thyroid Stimulating Hormone (TSH) and free T4 (FT4) assessment.
Optimal maternal thyroid function during pregnancy is important for both the mother and the fetus. Maternal hypothyroidism has been associated with adverse pregnancy complications as well as detrimental effects upon fetal neurocognitive development. This is especially true during the first trimester, when the developing fetus is completely dependent on the mother for thyroid hormone that is critical for its growth and development. Specific adverse maternal outcomes include anaemia, abortion, preterm labour, gestational hypertension, preeclampsia, and placental abruption. Fetal complications include prematurity, Intrauterine Growth Restriction (IUGR), Intrapartum Fetal Distress (FD) and Intrauterine Fetal Demise (IUFD). These complications are more frequent with overt hypothyroidism than with subclinical hypothyroidism and adequate thyroxine treatment reduces the risk of poor obstetrical outcome.7
The prevalence of hyperthyroidism in pregnancy varies from 0.2%–3% and subclinical hyperthyroidism is upto 1.7%. Severe maternal hyperthyroidism is associated with increased risk of stillbirth, preterm delivery, IUGR, preeclampsia, and heart failure. Also, thyrotoxicosis at conception increases the risk for spontaneous abortion. Subclinical hyperthyroidism in pregnancy has not been found to be associated with adverse outcomes.1
The prevalence 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 hypothyroidism either overt or subclinical is clearly more common among patients with GDM.8
Materials & Methods
A case control study was conducted to evaluate and compare thyroid function in patients with and without GDM at Institute of Nuclear Medicine & Allied Sciences (INMAS), Cumilla in collaboration with the Department of Obstetrics & Gynaecology, Cumilla Medical College Hospital in between January to December 2021. According to inclusion and exclusion criteria, 148 pregnant women were included in the study, 74 patients with GDM (case) and 74 patients with non-GDM (control). Inclusion criteria included- patients with confirmed GDM, healthy pregnant women (control), 2nd and 3rd trimester of pregnancy (above 12 weeks of gestation), patients who were willing to be included in the study. Exclusion criteria included- known case or history of thyroid disorders or GDM, multiple pregnancies, history of pregnancy loss, preterm delivery, or infertility, pregnancy with known complications (excluding GDM), serious concomitant medical illness including severe cardiac disease, uncontrolled diabetes mellitus, hypertension, or renal diseases. The thyroid function was evaluated by serum TSH and FT4. Data analysis was done by chi-square test (categorical variables) and unpaired t- test (continuous variables).
Result & Discussion
Mean age in the study was 28 ± 3.9 years (M ± SD). Mean age was relatively higher in GDM patients (28.84 ± 3.64; range: 21 to 35 years) than non-GDM (27.12 ± 3.99; range: 20 to 34 years) and when means were compared, it was statistically significant (<0.05). Majority patients were Muslim and educated and 102 (68.9%) patients had different levels of education. The maximum patients in the study belonged to lower economic status, came from rural area and were home makers. No statistically significant differences were found in religion, residence, occupation, educational and economic status among the groups. Most of the patients were multigravida in both arms, in GDM group 44 (59.5%) patients and in non-GDM group 38 (51.4%) [Table-1]. The demographic characteristics were more or less similar with other studies. Parham et al. in 2015 found that mean age of GDM and non-GDM were 30.7 ± 4.7 and 29.7 ± 6.0 years respectively.9
Thyroid disorder, particularly subclinical hypothyroidism is a common endocrine disorder in pregnant women. In the study, TSH value was high in case group (GDM) 4.68 ± 5.71 mIU/ml (M ± SD) in comparison to control 2.78 ± 3.74 and statistically significant (P <0.05). Considering FT4 value, it was higher in control group (11.53 ± 2.88 pmol/ml) in comparison to case group (10.47 ± 2.19) and statistically significant (P <0.05) [Table-02].
In the study, 16.2% (24 of 148) patients had thyroid disorder. Thyroid disorder was more in case group; 21.6% (16 of 74) in GDM and 10.8% (8 of 74) in non-GDM patients. Association of thyroid disorder with GDM was higher than non-GDM patients, but the result was not statistically significant [OR: 2.3 (CI: 1 to 5.7); p=0.074]. The majority of the patients (83.8%, 124 of 148) had normal thyroid function in the study, in both cases (78.4%, 58 of 74) and control (89.2%, 66 of 74) group [Table-03].
Most common thyroid disorder in both case and control group was subclinical hypothyroidism followed by primary hypothyroidism. One case of subclinical hyperthyroid was detected in control group and no primary hyperthyroidism was found in the study [Figure-01].
Several studies have reported prevalence of hypothyroidism in patients with diabetes ranging from 2.7 to 30% .10 Parham et al. in 2015 found that, in GDM 29 (27.6%) patients had thyroid dysfunction; 18 (17.1%) had subclinical hypothyroidism and 11 (10.48%) had clinical hypothyroidism. In non-GDM, 11 (10.5%) patients had thyroid dysfunctions; 7 (6.66%) had subclinical hypothyroidism and 4 (3.81%) had clinical hypothyroidism9 Izzo et al. in 2013 conducted a retrospective study on 112 patients with GDM and found association between thyroid disease and gestational diabetes, 18 (16.1%) had subclinical hypothyroidism; 12 (10.7%) had primary hypothyroidism and 5 patients (4.4%) had subclinical hyperthyroidism.11
Table 01: Summary of baseline characteristics in case and control (N= 148)
| Baseline characteristics | Case | Control | P-valuea | |||
| N=74 | % | N=74 | % | |||
| Age (years) | Mean ± SD | 28.84 ± 3.64 | 27.12 ± 3.99 | 0.007b | ||
| Range | 21-35 | 20-34 | ||||
| Religion | Muslim | 65 | 87.8% | 67 | 90.5% | 0.792 |
| Hindu | 09 | 12.2% | 07 | 09.5% | ||
| Residence | Rural | 48 | 64.9% | 46 | 62.2% | 0.865 |
| Urban | 26 | 35.1% | 28 | 37.8% | ||
| Education | Illiterate | 24 | 32.4% | 22 | 29.7% | 0.833 |
| Primary | 23 | 31.1% | 28 | 37.8% | ||
| SSC | 17 | 23.0% | 14 | 18.9% | ||
| HSC | 10 | 13.5% | 10 | 13.5% | ||
| Economic status | Lower class | 28 | 37.8% | 34 | 45.9% | 0.605 |
| Middle class | 28 | 37.8% | 24 | 32.4% | ||
| Upper class | 18 | 24.3% | 16 | 21.6% | ||
| Occupation | Housewife | 60 | 81.1% | 61 | 82.4% | 1.00 |
| Working | 14 | 18.9% | 13 | 17.6% | ||
| Gravida | Primigravida | 30 | 40.5% | 36 | 48.6% | 0.408 |
| Multigravida | 44 | 59.5% | 38 | 51.4% | ||
Case: Patients with GDM; Control: Patients without GDM.
P value reached from Chi square test a; P value reached from unpaired t-test b
Table 02: Comparison of FT4 & TSH levels in the study (n= 148)
| Investigations | Case | Control | P-value |
| Mean ± SD | Mean ± SD | ||
| TSH (mIU/ml) | 4.68 ± 5.71 | 2.78 ± 3.74 | 0.018 |
| FT4 (fmol/ml) | 10.47 ± 2.19 | 11.53 ± 2.88 | 0.013 |
Case: Patients with GDM; Control: Patients without GDM. Data were analyzed using Unpaired T-test
Table 03: Association of thyroid function with GDM in comparison to non-GDM patients in the study (n= 148)
| Thyroid function | Total | Case | Control | OR (95%CI) | P-value | |||
| n=148 | % | n=74 | % | n=74 | % | |||
| Thyroid disorder | 24 | 16.2% | 16 | 21.6% | 08 | 10.8% | 2.3 (1-5.7) | 0.074 |
| Euthyroid | 124 | 83.8% | 58 | 78.4% | 66 | 89.2% | ||
Case: Patients with GDM; Control: Patients without GDM. OR: Odds Ratio; CI: Confidence Interval P-value reached from Chi square test.
Figure 01: Comparison of patients according to thyroid function in the study (n= 148)
Conclusion
Thyroid disorder was more in gestational diabetes mellitus patients in comparison to patients without gestational diabetes mellitus. In the study the most common thyroid disorder was subclinical hypothyroidism in both case and control groups.
Authors of This Article
- Dr. M M Arif Hosen, Associate Professor, Institute of Nuclear Medicine & Allied Sciences (INMAS), Cumilla, E-mail: dr.arif43@gmail.com
- Dr. Md. Nazmul Islam, Assistant Professor, Institute of Nuclear Medicine & Allied Sciences (INMAS), Cumilla.
- Dr. Shartaz Begum, Professor and Head, Department of Obstetrics & Gynaecology, Cumilla Medical College Hospital, Cumilla.
- Dr. Fahema Farjana Shimu, Assistant Registrar, Department of Obstetrics & Gynaecology, Cumilla Medical College Hospital, Cumilla.
- Dr. Shibli Nishad Alam, Medical Officer, Institute of Nuclear Medicine & Allied Sciences (INMAS), Rajshahi.
References
- Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, Peeters RP, Sullivan S. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid. 2017 Mar;27(3):315-389. doi: 10.1089/thy.2016.0457. Erratum in: Thyroid. 2017 Sep;27(9):1212. doi: 10.1089/thy.2016.0457.correx. PMID: 28056690.
- Schneider S, Bock C, Wetzel M, Maul H, Loerbroks A. The prevalence of gestational diabetes in advanced economies. J Perinat Med. 2012 Sep;40(5):511-20. doi: 10.1515/jpm-2012-0015. PMID: 23120759.
- Tutino GE, Tam WH, Yang X, Chan JC, Lao TT, Ma RC. Diabetes and pregnancy: perspectives from Asia. Diabet Med. 2014 Mar;31(3):302-18. doi: 10.1111/dme.12396. PMID: 24417604.
- Philips JC, Emonts P, Pintiaux A, Kirkpatrick C, Scheen AJ. Prise en charge du diabète gestationnel [Management of gestational diabetes]. Rev Med Liege. 2013 Sep;68(9):489-96. French. PMID: 24180206.
- Moon HW, Chung HJ, Park CM, Hur M, Yun YM. Establishment of trimester-specific reference intervals for thyroid hormones in Korean pregnant women. Ann Lab Med. 2015 Mar;35(2):198-204. doi: 10.3343/alm.2015.35.2.198. Epub 2015 Feb 12. PMID: 25729721; PMCID: PMC4330169.
- Nambiar V, Jagtap VS, Sarathi V, Lila AR, Kamalanathan S, Bandgar TR, Menon PS, Shah NS. Prevalence and impact of thyroid disorders on maternal outcome in asian-Indian pregnant women. J Thyroid Res. 2011;2011:429097. doi: 10.4061/2011/429097. Epub 2011 Jul 17. PMID: 21789274; PMCID: PMC3140706.
- Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, Nixon A, Pearce EN, Soldin OP, Sullivan S, Wiersinga W; 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 Oct;21(10):1081-125. doi: 10.1089/thy.2011.0087. Epub 2011 Jul 25. PMID: 21787128; PMCID: PMC3472679.
- 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(2):51-9. PMID: 21258277.
- Parham Mahmoud, Asgarani Firouzeh, Bagherzadeh Mohammad, Ebrahimi Gholamreaza, Vafaeimanesh Jamshid. Thyroid function in pregnant women with gestational diabetes: Is screening necessary?. Thyroid Research and Practice 12(1):p 3-7, Jan–Apr 2015. DOI: 10.4103/0973-0354.147271.
- Hage M, Zantout MS, Azar ST. Thyroid disorders and diabetes mellitus. J Thyroid Res. 2011;2011:439463. doi: 10.4061/2011/439463. Epub 2011 Jul 12. PMID: 21785689; PMCID: PMC3139205.
- Izzo, Tiziana and Lo Dico, G. and Richiusa, Pierina. Pregnancy, gestational diabetes, thyroid function: our experience.Giornale italiano di ostetricia e ginecologia, 2013; 35(3). pp. 466-470. ISSN 1971-1433.