DIABETICMedicine DOI: 10.1111/dme.12580

Research: Epidemiology Evaluation of thyroid dysfunction and autoimmunity in gestational diabetes mellitus and its relationship with postpartum thyroiditis N. Maleki and Z. Tavosi Department of Internal Medicine, Shohadaye Khalije Fars Hospital, Bushehr University of Medical Sciences, Bushehr, Iran Accepted 22 August 2014

Abstract Aims To evaluate thyroid dysfunction and autoimmunity in women with gestational diabetes and to investigate the frequency of postpartum thyroiditis in women with gestational diabetes.

A total of 350 women with gestational diabetes and 350 healthy pregnant women were enrolled in the study. We studied the thyroid hormone profiles of the women in each group during pregnancy (at 24–28 weeks’ gestation) and after delivery (at 6 weeks, 3, 6 and 9 months, and 1 year postpartum).

Materials and methods

A total of 342 women with gestational diabetes and 313 healthy pregnant women completed the follow-up during pregnancy and 1 year after delivery. Of the women with gestational diabetes, 16.6% had thyroid dysfunction, while of the healthy pregnant women, 6.1% had thyroid dysfunction. The prevalence of postpartum thyroiditis was higher in the women with a history of gestational diabetes (19.6%) than in the healthy pregnant women (10.2%), and this difference was statistically significant.

Results

According to the results of the present study, the prevalence of postpartum thyroiditis was higher in women with a history of gestational diabetes than in healthy women. We recommend that all women with gestational diabetes and women who have previous thyroid dysfunction should be screened for thyroid hormonal abnormalities during pregnancy and for 1 year after pregnancy.

Conclusion

Diabet. Med. 00, 000–000 (2014)

Introduction Gestational diabetes mellitus is defined as any degree of glucose intolerance with onset or first recognition during pregnancy [1]. The main pathophysiological defects that occur in gestational diabetes are the same as those observed with Type 2 diabetes: marked insulin resistance and impairment of insulin secretion [2]. Gestational diabetes is associated with several adverse outcomes for both mother and child, including pre-eclampsia, macrosomia, and caesarean delivery, and their associated morbidities [3,4]. The benefits of screening are that identifying pregnant women with diabetes and providing the appropriate therapy can decrease fetal and maternal morbidity [5,6]. American Diabetes Association guidelines estimate that 7% of all pregnancies are affected by gestational diabetes [7]. The prevalence of gestational diabetes in Asian countries varies Correspondence to: Nasrollah Maleki. E-mail: [email protected]

ª 2014 The Authors. Diabetic Medicine ª 2014 Diabetes UK

substantially according to the screening strategy and diagnostic criteria applied, and ranges from 1 to 20%, with evidence of an increasing trend over recent years [8]. In European countries the prevalence of gestational diabetes has been reported to be 2–6% of pregnancies [9]. International Association of Diabetes and Pregnancy Study Group guidance recommends a 75-g oral glucose tolerance test at 24–28 weeks ‘ gestation for all women not previously diagnosed with overt diabetes [10]. Gestational diabetes is increasingly recognized as a general risk factor for the development of Type 2 diabetes. According to a systematic review, up to 60% of women with gestational diabetes had progressed to Type 2 diabetes during 10 years of post-pregnancy follow-up [11]. In one study, the majority of the patients with gestational diabetes did not show evidence of ongoing autoimmune destruction of b cells during the index pregnancy, but the women with islet cell antibody-positive gestational diabetes had a high risk of developing Type 1 diabetes later in life [12].

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Association of postpartum thyroiditis with thyroid dysfunction/autoimmunity  N. Maleki and Z. Tavosi

Thyroid disorders are the second most common endocrine disorder found in pregnancy. Overt hypothyroidism is estimated to occur in 0.3–0.5% of pregnancies. Subclinical hypothyroidism appears to occur in 2–3% of pregnancies and hyperthyroidism is present in 0.1–0.4% [13]. Postpartum thyroiditis is defined as transient or permanent thyroid dysfunction occurring in the first year after delivery and is based on an autoimmune inflammation of the thyroid. Typically, patients have a brief phase of thyrotoxicosis lasting 2–4 weeks, followed by hypothyroidism for 4–12 weeks, and then resolution; often, however, only one phase is apparent [14]. The condition is associated with the presence of thyroid peroxidase antibodies antepartum, and is three times more common in women with Type 1 diabetes. As in subacute thyroiditis, the radioactive iodine uptake is initially suppressed. In addition to painless goitre, silent thyroiditis can be distinguished from subacute thyroiditis by a normal erythrocyte sedimentation rate and the presence of thyroid peroxidase antibodies. Glucocorticoid treatment is not indicated for postpartum thyroiditis. Severe thyrotoxic symptoms can be managed with a brief course of propranolol. Thyroxine replacement may be needed for the hypothyroid phase but should be withdrawn after 6–9 months, as recovery is the rule. Annual follow-up thereafter is recommended, because a proportion of these individuals develop permanent hypothyroidism. The condition may recur in subsequent pregnancies [15]. Screening for thyroid disease in pregnancy remains a contentious issue. To date, few studies have been conducted on the relationship between gestational diabetes and postpartum thyroiditis. The aim of the present study was to evaluate thyroid dysfunction and autoimmunity in women with gestational diabetes. In addition, we investigated the frequency of postpartum thyroiditis in women with gestational diabetes.

Subjects and methods Study population

This was a prospective cross-sectional study carried out in the Department of Endocrinology, in collaboration with the Department of Obstetrics and Gynaecology at a medical college hospital, which is the largest public sector hospital in Bushehr City, Iran. The study was conducted over 2 years from April 2011 to October 2013. A total of 350 pregnant women with gestational diabetes (study group) and 350 healthy pregnant women (control group) were enrolled in the study. The two groups were matched for age. The inclusion criterion was pregnancy at 24–28 weeks’ gestation. Women with a history of gestational diabetes in the previous pregnancy, those known to have pre-existing diabetes, systemic hypertension, history of thyroid disease or a history of drug use that might affect thyroid function (glucocorticoids, lithium, amiodarone, iodide, aminoglutethimide and

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octreotide)[16] and those who did not provide consent were excluded from the study. We studied the thyroid hormone levels and antithyroid antibodies in both groups during pregnancy (at 24–28 weeks’ gestation) and after delivery (6 weeks, 3, 6 and 9 months, and 1 year postpartum). A standardized questionnaire was used and details pertaining to family history, medical and obstetric history were collected. BMI and blood pressure were also recorded. Written informed consent was obtained from all participants.

Diagnosis of gestational diabetes

All the selected participants underwent a 50-g glucose challenge test, without considering the timing of the last meal. Women with blood sugar levels ≥ 7.8 mmol/l (140 mg/dl) after 1 h proceeded to a 75-g 2-h oral glucose tolerance test. A 75-g oral glucose tolerance test was performed in the morning after an overnight fast of at least 8 h, with plasma glucose measurement after fasting and at 1 and 2 h. A diagnosis of gestational diabetes was made when the results showed any of the following plasma glucose values [17]: fasting ≥ 5.1 mmol/l (92 mg/dl); 1-h ≥ 10.0 mmol/l (180 mg/dl); or 2-h ≥ 8.5 mmol/l (153 mg/dl). Women with gestational diabetes received individualized diet and/or insulin treatment.

Assessment of thyroid function during pregnancy

Free triiodothyronine, free thyroxine, thyroxine-binding globulin, thyroid-stimulating hormone, anti-thyroid peroxidase and anti-thyroglobulin levels were measured in all women with gestational diabetes and in the healthy pregnant women in the control group. Thyroid-stimulating hormone levels were determined using an immunoradiometric assay (Spectra, Fenzia, Finland). As the trimester-specific reference ranges for thyroid-stimulating hormone were not available in our laboratory, the following reference ranges were recommended: first trimester, 0.1–2.5 mIU/l; second trimester, 0.2–3.0 mIU/l; and third trimester, 0.3–3.0 mIU/l [18]. Serum free thyroxine and free triiodothyronine levels were measured by a radioimmunoassay method (Vitros Immunodiagnostic Products, Ortho-Clinical Diagnostics Inc., Rochester, NY, USA). The reference ranges for free thyroxine were: 3.7– 23.4 pmol/l (0.26–1.92 ng/dl) for the first trimester; 7.4– 18.9 pmol/l (0.59–1.56 ng/dl) for the second trimester; and 8.3–15.6 pmol/l (0.65–1.25 ng/dl) for the third trimester. The 1-year postpartum free thyroxine reference range for the same population was 9.9–28.4 pmol/l (0.77–2.26 ng/dl) [19]. Reference ranges for free thyroxine index during pregnancy were as follows: first trimester, 8.5–19 mIU/l; second trimester, 9.7–21 mIU/l; and third trimester, 8.7–20.4 mIU/l [20]. Anti-thyroid peroxidase and anti-thyroglobulin were measured using an enzyme-linked immunosorbent assay (Radim, Rome, Italy). Antibody activity was considered to be positive

ª 2014 The Authors. Diabetic Medicine ª 2014 Diabetes UK

DIABETICMedicine

Association of postpartum thyroiditis with thyroid dysfunction/autoimmunity  N. Maleki and Z. Tavosi

Table 1 Thyroid hormone profiles in the control group (healthy pregnant women) and in the study group (women with gestational diabetes) during pregnancy

Variable Normal range Control group (n = 313), mean  SD Study group (n = 342), mean  SD

Free triiodothyronine, pmol/l

Free thyroxine, pmol/l

TSH, mU/l

TBG, mg/ml

Anti-thyroid peroxidase, IU/ml

Anti-thyroglobulin, IU/ml

4.2–7.7 5.8  0.9

8.0–19.0 9.9  1.8

0.3–4.5 2.1  0.8

15–32 47  6

Up to 100 74  48

Up to 150 128  64

3.9  0.8

6.4  1.2

3.5  1.2

43  8

95  53

176  88

TBG, thyroxine binding-globulin; TSH, thyroid-stimulating hormone.

Table 2 Rates of postpartum thyroiditis in the study groups

Study group Women with thyroid dysfunction and gestational diabetes (N = 57) Women who were euthyroid with gestational diabetes (N = 285) Women with thyroid dysfunction without gestational diabetes (N = 19) Women who were euthyroid without gestational diabetes (N = 294)

Rate of postpartum thyroiditis, n (%) 38 (66.7) 29 (10.2) 9 (47.4) 23 (7.8)

difference was significant (P = 0.005). Pregnant women with underlying thyroid dysfunction were therefore at higher risk of postpartum thyroiditis than pregnant women with gestational diabetes; underlying thyroid dysfunction during pregnancy compared with gestational diabetes was more associated with postpartum thyroiditis . The prevalence of postpartum thyroiditis was higher in women with gestational diabetes and without thyroid dysfunction (10.2%) than in women without gestational diabetes and without thyroid dysfunction (7.8%), and this difference was significant (P = 0.038); women who had previous gestational diabetes compared with women without gestational diabetes were at higher risk of postpartum thyroiditis. Overall, postpartum thyroiditis was observed in 67 (19.6%) women with a history of gestational diabetes in the first postpartum year. All patients were diagnosed in the first 9 months after delivery and there were no new cases thereafter. Of these 67 patients with postpartum thyroiditis, 45 (67.2%) presented only with hypothyroidism, 14 (20.9%) presented with transient hyperthyroidism and eight (11.9%) presented with transient hyperthyroidism followed by hypothyroidism. Among patients with hypothyroidism, 53 (58.5%) had signs and symptoms of hypothyroidism and required treatment with levothyroxine. After 9 months of treatment, levothyroxine was discontinued for 6 weeks and the thyroid-function tests re-evaluated: three patients (5.7%) had permanent hypothyroidism. All of the untreated women with hypothyroidism had become euthyroid by 1 year

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postpartum. Among patients with postpartum thyroiditis, 71.2 and 64.7% were positive for anti-thyroid peroxidase and anti-thyroglobulin antibodies, respectively, in the first 9 months after delivery. Of the 313 healthy women, postpartum thyroiditis was observed in 32 (10.2%) in the first year after delivery. Of these 32 patients with postpartum thyroiditis, 18 (56.2%) presented only with hypothyroidism, nine (28.1%) presented with transient hyperthyroidism and five (15.6%) presented with transient hyperthyroidism followed by hypothyroidism. Among patients with hypothyroidism, 4.9% had permanent hypothyroidism. Of the 32 healthy women with postpartum thyroiditis, 65.3 and 61.9% were positive for anti-thyroid peroxidase and anti-thyroglobulin antibodies, respectively, in the first 9 months after delivery. Visible goitre was found in 17.6% of the women with a history of gestational diabetes and in 5.4% of the healthy women (P = 0.001). Based on these results, the prevalence of postpartum thyroiditis was higher in women with a history of gestational diabetes (19.6%; 95% CI 12.9–26.3%) than in healthy women (10.2%; 95% CI 7.8–12.6%), and this difference was significant (P = 0.005). Women who were positive for thyroid autoantibodies during pregnancy had a greater risk of maintaining a positive titre in the postpartum period (relative risk 3.77; CI 95% 3.08–4.46). Prevalence of postpartum thyroiditis in women with a history of thyroid autoantibodies positive during pregnancy was higher (relative risk 4.55; CI 95% 3.18–5.92).

Discussion Thyroid dysfunction is the second most common endocrine disorder, after diabetes mellitus. The diagnosis of thyroid disease during pregnancy requires an understanding of the changes in thyroid physiology and thyroid function tests that accompany normal pregnancy. Five factors alter thyroid function in pregnancy: (1) the transient increase in human chorionic gonadotropin during the first trimester, which stimulates the thyroid-stimulating hormone-receptor; (2) the oestrogen-induced rise in thyroxine-binding globulin during the first trimester, which is sustained during pregnancy; (3) alterations in the immune system, leading to the onset,

ª 2014 The Authors. Diabetic Medicine ª 2014 Diabetes UK

DIABETICMedicine

Association of postpartum thyroiditis with thyroid dysfunction/autoimmunity  N. Maleki and Z. Tavosi

Table 1 Thyroid hormone profiles in the control group (healthy pregnant women) and in the study group (women with gestational diabetes) during pregnancy

Variable Normal range Control group (n = 313), mean  SD Study group (n = 342), mean  SD

Free triiodothyronine, pmol/l

Free thyroxine, pmol/l

TSH, mU/l

TBG, mg/ml

Anti-thyroid peroxidase, IU/ml

Anti-thyroglobulin, IU/ml

4.2–7.7 5.8  0.9

8.0–19.0 9.9  1.8

0.3–4.5 2.1  0.8

15–32 47  6

Up to 100 74  48

Up to 150 128  64

3.9  0.8

6.4  1.2

3.5  1.2

43  8

95  53

176  88

TBG, thyroxine binding-globulin; TSH, thyroid-stimulating hormone.

Table 2 Rates of postpartum thyroiditis in the study groups

Study group Women with thyroid dysfunction and gestational diabetes (N = 57) Women who were euthyroid with gestational diabetes (N = 285) Women with thyroid dysfunction without gestational diabetes (N = 19) Women who were euthyroid without gestational diabetes (N = 294)

Rate of postpartum thyroiditis, n (%) 38 (66.7) 29 (10.2) 9 (47.4) 23 (7.8)

difference was significant (P = 0.005). Pregnant women with underlying thyroid dysfunction were therefore at higher risk of postpartum thyroiditis than pregnant women with gestational diabetes; underlying thyroid dysfunction during pregnancy compared with gestational diabetes was more associated with postpartum thyroiditis . The prevalence of postpartum thyroiditis was higher in women with gestational diabetes and without thyroid dysfunction (10.2%) than in women without gestational diabetes and without thyroid dysfunction (7.8%), and this difference was significant (P = 0.038); women who had previous gestational diabetes compared with women without gestational diabetes were at higher risk of postpartum thyroiditis. Overall, postpartum thyroiditis was observed in 67 (19.6%) women with a history of gestational diabetes in the first postpartum year. All patients were diagnosed in the first 9 months after delivery and there were no new cases thereafter. Of these 67 patients with postpartum thyroiditis, 45 (67.2%) presented only with hypothyroidism, 14 (20.9%) presented with transient hyperthyroidism and eight (11.9%) presented with transient hyperthyroidism followed by hypothyroidism. Among patients with hypothyroidism, 53 (58.5%) had signs and symptoms of hypothyroidism and required treatment with levothyroxine. After 9 months of treatment, levothyroxine was discontinued for 6 weeks and the thyroid-function tests re-evaluated: three patients (5.7%) had permanent hypothyroidism. All of the untreated women with hypothyroidism had become euthyroid by 1 year

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postpartum. Among patients with postpartum thyroiditis, 71.2 and 64.7% were positive for anti-thyroid peroxidase and anti-thyroglobulin antibodies, respectively, in the first 9 months after delivery. Of the 313 healthy women, postpartum thyroiditis was observed in 32 (10.2%) in the first year after delivery. Of these 32 patients with postpartum thyroiditis, 18 (56.2%) presented only with hypothyroidism, nine (28.1%) presented with transient hyperthyroidism and five (15.6%) presented with transient hyperthyroidism followed by hypothyroidism. Among patients with hypothyroidism, 4.9% had permanent hypothyroidism. Of the 32 healthy women with postpartum thyroiditis, 65.3 and 61.9% were positive for anti-thyroid peroxidase and anti-thyroglobulin antibodies, respectively, in the first 9 months after delivery. Visible goitre was found in 17.6% of the women with a history of gestational diabetes and in 5.4% of the healthy women (P = 0.001). Based on these results, the prevalence of postpartum thyroiditis was higher in women with a history of gestational diabetes (19.6%; 95% CI 12.9–26.3%) than in healthy women (10.2%; 95% CI 7.8–12.6%), and this difference was significant (P = 0.005). Women who were positive for thyroid autoantibodies during pregnancy had a greater risk of maintaining a positive titre in the postpartum period (relative risk 3.77; CI 95% 3.08–4.46). Prevalence of postpartum thyroiditis in women with a history of thyroid autoantibodies positive during pregnancy was higher (relative risk 4.55; CI 95% 3.18–5.92).

Discussion Thyroid dysfunction is the second most common endocrine disorder, after diabetes mellitus. The diagnosis of thyroid disease during pregnancy requires an understanding of the changes in thyroid physiology and thyroid function tests that accompany normal pregnancy. Five factors alter thyroid function in pregnancy: (1) the transient increase in human chorionic gonadotropin during the first trimester, which stimulates the thyroid-stimulating hormone-receptor; (2) the oestrogen-induced rise in thyroxine-binding globulin during the first trimester, which is sustained during pregnancy; (3) alterations in the immune system, leading to the onset,

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Research article

exacerbation or amelioration of an underlying autoimmune thyroid disease; (4) increased thyroid hormone metabolism by the placenta; and (5) increased urinary iodide excretion, which can cause impaired thyroid hormone production in areas of marginal iodine sufficiency [21–23]. During the first trimester, human chorionic gonadotropin induces a transient increase in free thyroxine levels, which is mirrored by a lowering of thyroid-stimulating hormone concentrations. After this period, serum free thyroxine concentrations decrease by ~10–15%, and serum thyroid-stimulating hormone values steadily return to normal. In addition, from early gestation, there is a marked increase in serum thyroxine-binding globulin concentrations, which peak around mid-gestation and are maintained thereafter. This event, in turn, is responsible for a significant rise in total thyroxine and triiodothyronine levels [23]. Anti-thyroid peroxidase antibodies are the most common anti-thyroid autoantibody, present in ~90% of Hashimoto’s thyroiditis, 75% of Graves’ disease and 10–20% of nodular goitre or thyroid carcinoma [24]. About 10% of the general population with normal thyroid function can have high-level anti-thyroid peroxidase antibody titres, although this may reach 30% in the elderly [24]. The relationship of autoimmune thyroid disease to pregnancy has been the subject of considerable interest, with the recognition of postpartum thyroid disease syndromes [25]. Anti-thyroid peroxidase antibodies are evident in most cases of postpartum thyroiditis and it has been found that the presence of these autoantibodies in early pregnancy was associated with a high risk of asymptomatic postpartum hypothyroidism [26]. The presence of anti-thyroid antibodies is associated with an increased risk of unexplained subfertility, miscarriage, recurrent miscarriage, preterm birth and maternal postpartum thyroiditis [27]. Postpartum thyroiditis is an autoimmune thyroid disease that occurs during the first year after delivery. The reported prevalence of postpartum thyroiditis varies globally and ranges from 1 to 17% [15,28]. In systematic reviews of prospective studies, the mean prevalence in the general population of women was ~7–8% [15,28]. Higher rates, up to 25%, have been reported in women with Type 1 diabetes, and the highest rates occur among women with a history of postpartum thyroiditis (pooled prevalence 42%) and in women with positive anti-thyroid peroxidase antibodies who had normal thyroid function during pregnancy (40–60% compared with 0–5% of women without antibodies) [15]. In Iran, the prevalence of postpartum thyroiditis has been reported to be 11.4% [29]. The frequency of postpartum thyroiditis raises the question of whether screening is indicated [30]. This could be carried out by periodic clinical evaluation or serum thyroidstimulating hormone assay after delivery. Alternatively, serum anti-thyroid peroxidase antibodies could be measured, either early in pregnancy or soon after delivery. High antibody concentrations at these times predict (but not with

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certainty) the later development of postpartum thyroiditis, and low concentrations make it very unlikely [31]. There is insufficient evidence to support a recommendation for screening all pregnant women for postpartum thyroiditis [15]. In 1993, Gerstein [32] performed a prospective cohort study of 51 pregnant women with Type 1 diabetes who were not taking thyroid medication. Of these, 40 women completed follow-up. Postpartum thyroid dysfunction occurred in 10 of the 40 women (25%; 95% CI 12.7–41.2%); postpartum thyroiditis developed in nine women and postpartum Graves’ disease developed in one woman during the first 6 months after delivery. Glycaemic control was not affected by thyroid dysfunction. Gerstein concluded that women with Type 1 diabetes were at a high risk of symptomatic postpartum thyroid dysfunction and therefore could benefit from routine thyroid function screening at postpartum visits [32]. One year later, Alvarez-Marfany et al. [33] performed a long-term prospective study of postpartum thyroid dysfunction in 41 pregnant women with insulin-dependent diabetes mellitus. A total of 28 women completed follow-up at 31 months postpartum: seven women developed thyroiditis, therefore, the incidence of postpartum thyroiditis in women with insulin-dependent diabetes was 25%. In that study, long-term follow-up did not find an increased incidence of hypothyroidism in women who did not require treatment in the first postpartum year. The authors recommended that all women with insulin-dependent diabetes be screened for thyroid hormonal abnormalities during pregnancy and at 3 months postpartum for postpartum thyroid dysfunction [33]. In 2002, Gallas et al. [34] performed a prospective cohort study of 126 pregnant women with Type 1 diabetes from eight Dutch clinics. Of these, 82 women completed the study. Thyroid dysfunction during pregnancy was observed in 22.5% (first trimester) and 18.4% (third trimester) of the women, and mostly consisted of subclinical hypothyroidism. Overt postpartum thyroiditis was found in 15.9% of the women and the incidence of postpartum thyroiditis was 10%. The women with postpartum thyroiditis were slightly older than those without postpartum thyroiditis and the prevalence of anti-thyroid peroxidase antibodies was higher in these women. The authors of that study suggested that pregnant women with Type 1 diabetes need to be screened for thyroid-stimulating hormone and anti-thyroid peroxidase antibodies [34]; however, women at highest risk of developing postpartum thyroiditis (e.g. those positive for antithyroid peroxidase antibodies, with Type 1 diabetes or with a previous episode of postpartum thyroiditis) should have a serum thyroid-stimulating hormone measurement at 3 and 6 months postpartum [15]. To date, few studies have been conducted on the prevalence of postpartum thyroiditis in pregnant women with gestational diabetes. According to the results of the present study, the prevalence of postpartum thyroiditis was higher in women

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Association of postpartum thyroiditis with thyroid dysfunction/autoimmunity  N. Maleki and Z. Tavosi

with a history of gestational diabetes (19.6%) than in healthy women (10.2%), and this difference was significant. In 2006, Agarwal et al. [35] performed a study to determine the prevalence of abnormal thyroid function and anti-thyroid antibodies during early pregnancy in 301 pregnant women at high risk of gestational diabetes. No significant difference was found between the 80 women (26.6%) with gestational diabetes and the 221 (73.4%) women without gestational diabetes for any of the thyroid function tests. In the cohort tested for anti-thyroid peroxidase antibodies, the 51 women (20.0%) who were positive for anti-thyroid peroxidase antibodies had a higher mean thyroid-stimulating hormone level than the women negative for anti-thyroid peroxidase antibodies. They concluded that routine screening for thyroid abnormalities, which can be effectively and easily incorporated into screening practices already in place for gestational diabetes, would result in improved obstetric care [35]. In 2008, Azriel et al. [36] performed a cohort study of 1700 pregnant women with gestational diabetes to estimate thyroid peroxidase frequency during gestation and its relationship with postpartum thyroiditis. In 1053 women (60.3%) a follow-up assessment of thyroid function after delivery was performed. In all, 22.7% of the women were thyroid peroxidase-positive. A clear association between the presence of thyroid peroxidase and recurrent pregnancy loss (≥ 3 miscarriages) was found. The prevalence of hypothyroxinaemia in the cohort was 5.1%, regardless of autoantibody levels. The frequency of the presence of thyroid peroxidase postpartum was 39.9%. Women positive for thyroid peroxidase during pregnancy had a greater risk of maintaining a positive titre postpartum. The prevalence of postpartum thyroiditis in women positive for thyroid peroxidase during gestation was higher. They recommended that women with gestational diabetes be screened for thyroid function during pregnancy and during the postpartum period [36]. There are no established therapies to prevent the occurrence of postpartum thyroiditis in patients with anti-thyroid peroxidase antibodies. Administration of thyroxine or iodine to pregnant women with high serum anti-thyroid antibody concentrations did not prevent postpartum thyroiditis [37]. By contrast, selenium supplementation may decrease inflammatory activity in pregnant women with autoimmune hypothyroidism [38], and may reduce the risk of postpartum thyroiditis in women who are positive for thyroid peroxidase antibodies. This was shown in a trial of 151 thyroid peroxidase-positive women randomly assigned to receive selenium (200 lg daily) or placebo (beginning at ~12 weeks’ gestation). The prevalence of postpartum thyroiditis was significantly lower in the selenium group (29 vs 49%) [39]. The routine clinical application of this supplementation requires further study. In conclusion, thyroid dysfunction is common during pregnancy and adequate diagnosis and treatment is

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important to prevent adverse maternal and fetal outcomes. According to the results of the present study, the prevalence of postpartum thyroiditis was higher in women with a history of gestational diabetes than in healthy women. In addition, pregnant women with underlying thyroid dysfunction were at higher risk of postpartum thyroiditis than pregnant women with gestational diabetes. We recommend that all pregnant women with gestational diabetes, or women who have previous thyroid dysfunction, be screened for thyroid hormonal abnormalities during pregnancy and for 1 year after pregnancy.

Funding sources

None.

Competing interests

None declared.

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Evaluation of thyroid dysfunction and autoimmunity in gestational diabetes mellitus and its relationship with postpartum thyroiditis.

To evaluate thyroid dysfunction and autoimmunity in women with gestational diabetes and to investigate the frequency of postpartum thyroiditis in wome...
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