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1.  Maternal Subclinical Hypothyroidism, Thyroid Autoimmunity, and the Risk of Miscarriage: A Prospective Cohort Study 
Thyroid  2014;24(11):1642-1649.
Background: Increasing data suggest that subclinical hypothyroidism (SCH) and thyroid autoimmunity (TAI) are associated with adverse pregnancy outcomes, but there are limited data on the association of these conditions in early pregnancy with subsequent miscarriage.
Methods: In this prospective cohort study, we screened 3315 women at low risk for thyroid dysfunction at four to eight weeks' gestation from iodine-sufficient areas of China between January 2012 and September 2012. Thyrotropin (TSH), free thyroxine (fT4), and the autoantibodies thyroid-peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) were measured. Based on these results, women were divided into four groups for comparison: euthyroidism (ET), isolated SCH, isolated TAI (positive TPOAb or/and TgAb), and SCH with TAI (SCH+TAI). The SCH group was stratified into two subgroups (SCH 1 and SCH 2) on the basis of the level of TSH (2.5≤TSH<5.22 or 5.22≤TSH<10 respectively). Accordingly, the SCH+TAI group was also stratified into two subgroups (SCH+TAI 1 and SCH+TAI 2). The outcome of interest was miscarriage, defined as spontaneous pregnancy loss prior to 20 weeks.
Results: Compared to women with ET, the risk of miscarriage was significantly higher among women with SCH 2 (7.1% vs. 2.2%, aOR 3.40 [CI 1.62–7.15]; p=0.002), isolated TAI (5.7% vs. 2.2%, aOR 2.71 [CI 1.43–5.12]; p=0.003), SCH+TAI 1 (10.0% vs. 2.2%, aOR 4.96 [CI 2.76–8.90]; p=0.000), and SCH+TAI 2 (15.2% vs. 2.2%, aOR 9.56 [CI 3.76–24.28]; p=0.000). The gestational ages of 110 women at miscarriage were lower among women with subclinical thyroid abnormalities compared to ET (11.13±3.21 weeks with subclinical thyroid abnormalities vs. 9.33±1.71 weeks with ET; p=0.024). In parallel with the higher TSH levels, there were earlier gestation ages at miscarriage between subgroups of SCH and SCH+TAI (SCH 1 vs. SCH 2: 10.79±1.77 vs. 9.70±1.47 weeks, p=0.039; SCH+TAI 1 vs. SCH+TAI 2: 9.59±1.97 vs. 8.88±1.24 weeks, p=0.031).
Conclusions: Women with SCH and TAI are at an increased risk of miscarriage between four and eight gestational weeks. Women with a combination of SCH and TAI were found to have the highest risk and earlier gestational ages of miscarriage.
PMCID: PMC4229690  PMID: 25087688
2.  High prevalence of subclinical hypothyroidism during first trimester of pregnancy in North India 
Thyroid dysfunction is a common occurrence in pregnancy and affects both maternal and fetal outcomes. There are limited data on prevalence of hypothyroidism during pregnancy from India. Therefore, this study was designed to evaluate the prevalence of thyroid dysfunction especially hypothyroidism during first trimester in a large public hospital in North India.
Materials and Methods:
All the consecutive first trimester pregnant women attending Lok Nayak and Kasturba Hospitals were enrolled in the study after institutional ethics approval and consent from the study subjects. The pregnant women with diagnosed thyroid disease and on thyroid medications were excluded from the study. Morning samples of study participants were analyzed for thyroid hormone profile which included free T3, free T4, TSH, and TPO Ab. In addition, all study participants were tested for CBC, LFT, KFT, and lipid profile.
A total of 1000 women were enrolled for this prospective observational study. The mean (SD) age of study subjects was 25.6 (11.1) years, and mean (SD) gestational age was 10.3 (3.4) weeks. One hundred and forty-three (14.3%) subjects had TSH values more than 4.5 mIU/L above the cutoff used for definition of hypothyroidism. Out of these, 135 had normal free T4 and therefore labeled as subclinical hypothyroidism and 7 had low free T4 suggestive of overt hypothyroidism. TPO Ab was positive in 68 (6.82%) of total, 25 (18.5%) of subclinical and 5 (71%) of overt hypothyroid patients.
Hypothyroidism, especially subclinical, is common in North Indian women during first trimester. Further countrywide studies are needed to evaluate the prevalence and etiology of hypothyroidism to prevent maternal and fetal adverse effects of hypothyroidism in India.
PMCID: PMC3683205  PMID: 23776903
Pregnancy; hypothyroidism; subclinical hypothyroidism; autoimmunity and India
3.  Prevalence of thyroid dysfunction among women during the first trimester of pregnancy at a tertiary care hospital in Haryana 
Undetected and untreated thyroid disorders are associated with adverse maternal and fetal outcomes. There are limited data on the prevalence of newly diagnosed thyroid disease during pregnancy from India. Therefore, this study was designed to evaluate the prevalence of thyroid dysfunction, especially hypothyroidism during the first trimester of pregnancy.
Materials and Methods:
The present cross-sectional study was conducted at Department of endocrinology and antenatal clinic in the Obstetrics and Gynecology Pt. B.D. Sharma PGIMS, Rohtak over a period of 1-year. The total sample population comprised of 461 pregnant women with uncomplicated intrauterine singleton pregnancies in the first trimester of gestation without any history of thyroid disease or intake of any thyroid medication. Morning blood samples from the participants were analyzed for thyroid function tests, which included FT3, FT4, thyroid-stimulating hormone (TSH) and anti-thyroid peroxidase antibodies (TPO).
A total of 461 women were enrolled for this study. Mean maternal age was 23.79 ± 3.47 years. Median gestational age was 8 weeks 5 days. The median FT3, FT4 and TSH were 3.3 pg/mL, 1.25 ng/dL, and 1.40 mIU/L, respectively. Anti-TPO was elevated in 128 (27.8%) pregnant women. 99 (21.5%) women had sub-clinical hypothyroidism and 39 (39.4%) among them were positive for anti-TPO (P ≤ 0.001). 2 (0.4%) of women had overt hyperthyroidism, whereas 15 (3.3%) of the women had sub-clinical hyperthyroidism.
Considering the immense impact that maternal thyroid dysfunction has on maternal and fetal outcomes, prompt identification of thyroid dysfunction and its timely treatment is essential. Thus, universal screening of pregnant women for thyroid dysfunction should be considered especially in a country like India due to the high prevalence of thyroid dysfunction.
PMCID: PMC4366784  PMID: 25932401
First trimester; pregnancy; thyroid dysfunction
4.  Thyroid dysfunction and pregnancy outcomes 
Pregnancy has a huge impact on the thyroid function in both healthy women and those that have thyroid dysfunction. The prevalence of thyroid dysfunction in pregnant women is relatively high.
The objective of this review was to increase awareness and to provide a review on adverse effect of thyroid dysfunction including hyperthyroidism, hypothyroidism and thyroid autoimmune positivity on pregnancy outcomes.
Materials and Methods:
In this review, Medline, Embase and the Cochrane Library were searched with appropriate keywords for relevant English manuscript. We used a variety of studies, including randomized clinical trials, cohort (prospective and retrospective), case-control and case reports. Those studies on thyroid disorders among non-pregnant women and articles without adequate quality were excluded.
Overt hyperthyroidism and hypothyroidism has several adverse effects on pregnancy outcomes. Overt hyperthyroidism was associated with miscarriage, stillbirth, preterm delivery, intrauterine growth retardation, low birth weight, preeclampsia and fetal thyroid dysfunction. Overt hypothyroidism was associated with abortion, anemia, pregnancy-induced hypertension, preeclampsia, placental abruption, postpartum hemorrhage, premature birth, low birth weight, intrauterine fetal death, increased neonatal respiratory distress and infant neuro developmental dysfunction. However the adverse effect of subclinical hypothyroidism, and thyroid antibody positivity on pregnancy outcomes was not clear. While some studies demonstrated higher chance of placental abruption, preterm birth, miscarriage, gestational hypertension, fetal distress, severe preeclampsia and neonatal distress and diabetes in pregnant women with subclinical hypothyroidism or thyroid autoimmunity; the other ones have not reported these adverse effects.
While the impacts of overt thyroid dysfunction on feto-maternal morbidities have been clearly identified and its long term impact on childhood development is well known, data on the early and late complications of subclinical thyroid dysfunction during pregnancy or thyroid autoimmunity are controversial. Further studies on maternal and neonatal outcomes of subclinical thyroid dysfunction maternal are needed.
PMCID: PMC4609317  PMID: 26494985
Thyroid disease; Pregnancy outcome; Hypothyroidism; Hyperthyroidism
5.  Two logistic models for the prediction of hypothyroidism in pregnancy 
BMC Research Notes  2011;4:205.
The mounting evidence linking hypothyroidism during pregnancy with poor pregnancy outcome underscores the need for screening and, therefore, a search for more reliable and cheaper screening methods.
The study was conducted in two phases. The phase one study comprised of healthy women in different stages of pregnancy who attended routine antenatal clinic at St Theresa's Maternity Hospital, Enugu, Nigeria from September 6 to October 18 1994. In this study the variables compared between the hypothyroid and non-hypothyroid pregnant women were maternal age, the number of the pregnancy or gravidity, gestational age, social class, body weight, height, the clinically assessed size of the thyroid gland, serum free thyroxin (FT4) and serum thyrotrophin (TSH). Based on the parameter differences between the two comparison groups of pregnant women two Logistic models, Model I and Model 11, were derived to differentiate the hypothyroid group from their non-hypothyroid counterparts. The two logistic models were then applied in a prospective validation study involving 197 pregnant women seen at presentation in Mother of Christ Specialist Hospital and Maternity, Ogui Road, Enugu from March 2002 to November 2007
The findings were that 82 (50.3%) of the 163 pregnant women had thyroid gland enlargement while 60 (36.8%) had hypothyroidism as defined by FT4 values below and/or TSH above their laboratory reference ranges. The pregnant subjects with hypothyroidism, compared with their non-hypothyroid counterparts, were characterized by a higher gravidity (p < 0.01), a higher body weight (p < 0.01), a higher goiter prevalence rate (p < 0.01) and a more advanced gestational age (p < 0.0001). A significant, positive correlation was also found between body weight and gestational age (r = 0.5; p < 0.01) At the cut-off point for Model l (fitted with gravidity, thyroid size and gestational age) it had a sensitivity of 100%, a specificity of 72.8% and an overall predictive accuracy of 82.9%; whereas for Model II (fitted with gravidity, thyroid size and body weight) the sensitivity was 100%, the specificity was 59.2% and the overall accuracy of discrimination was 74.8%. In the prospective validation study both models showed a sensitivity of 100% each with specificities of 85.5% for Model I and 76.2% for Model II.
It is concluded that logistic models fitting gravidity, thyroid gland size and gestational age or body weight are useful alternatives in screening for hypothyroidism during pregnancy. There is, however, a need for further independent confirmation of these findings.
PMCID: PMC3148985  PMID: 21682920
Pregnancy; Thyroid hypo function; Prediction; Screening; Logistic models
6.  Prevalence of Subclinical Hypothyroidism in Pregnant Women in Tehran-Iran 
Maternal subclinical hypothyroidism during pregnancy is associated with various adverse outcomes. Recent consensus guidelines advocate universal thyroid function screening during pregnancy. There are no data from Iran about the prevalence of thyroid hypofunction in pregnancy. This study aims to find the prevalence of thyroid dysfunction.
Materials and Methods
In this descriptive cross sectional study, thyrotropin (TSH) was measured in 3158 pregnant women irrespective of gestational age from October 2008-March 2012. If TSH was more than 2.5 mIU/L in the first trimester or more than 3 mIU/L in the second or third trimester, free T4 was measured to diagnose subclinical/ overt hypothyroidism. If serum free T4 was in the normal range (0.7-1.8 ng/dl) the diagnosis was subclinical hypothyroidism and if below the normal range, overt hypothyroidism was diagnosed.
A total of 3158 pregnant women were evaluated. One hundred forty seven of them were diagnosed as hypothyroidism. Subclinical hypothyroidism and overt hypothyroidism were present in 131 (89.1%) and 16 (10.9%) women respectively. Prevalence of subclinical hypothyroidism was 4.15%. Most of the subclinical and overt hypothyroidism cases were diagnosed in the first trimester.
It appears logical to check TSH during pregnancy due to the observed prevalence of subclinical hypothyroidism.
PMCID: PMC4107690  PMID: 25083181
Hypothyroidism; Pregnancy; Prevalence; Thyrotropin
7.  Screening Strategies for Thyroid Disorders in the First and Second Trimester of Pregnancy in China 
PLoS ONE  2014;9(6):e99611.
Thyroid dysfunction during pregnancy is associated with multiple adverse outcomes, but whether all women should be screened for thyroid disorders during pregnancy remains controversial.
To evaluate the effectiveness of the targeted high risk case-finding approach for identifying women with thyroid dysfunction during the first and second trimesters of pregnancy.
Levels of thyroid stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibodies (TPOAb) were measured in 3882 Chinese women during the first and second trimester of pregnancy. All tested women were divided into the high risk or non-high risk groups, based on their history, findings from physical examination, or other clinical features suggestive of a thyroid disorder. Diagnosis of thyroid disorders was made according to the standard trimester-specific reference intervals. The prevalence of thyroid disorders in each group was determined, and the feasibility of a screening approach focusing exclusively on high risk women was evaluated to estimate the ability of finding women with thyroid dysfunction.
The prevalence of overt hypothyroidism or hyperthyroidism in the high risk group was higher than in the non-high risk group during the first trimester (0.8% vs 0, χ2 = 7.10, p = 0.008; 1.6% vs 0.2%, χ2 = 7.02, p = 0.008, respectively). The prevalence of hypothyroxinemia or TPOAb positivity was significantly higher in the high risk group than in the non-high risk group during the second trimester (1.3% vs 0.5%, χ2 = 4.49, p = 0.034; 11.6% vs 8.4%, χ2 = 6.396, p = 0.011, respectively). The total prevalence of hypothyroidism or hyperthyroidism and the prevalence of subclinical hypothyroidism or hyperthyroidism were not statistically different between the high risk and non-high risk groups, for either the first or second trimester.
The high risk screening strategy failed to detect the majority of pregnant women with thyroid disorders. Therefore, we recommend universal screening of sTSH, FT4, and TPOAb during the first trimester and second trimester of pregnancy.
PMCID: PMC4055732  PMID: 24925135
8.  Thyroid autoimmunity and obstetric outcomes in women with recurrent miscarriage: a case–control study 
Endocrine Connections  2013;2(2):118-124.
Thyroid antibody positivity during pregnancy has been associated with adverse outcomes including miscarriage and preterm delivery. The aim of the study is to evaluate the obstetric outcome in pregnant women with recurrent miscarriage and their response to levothyroxine (l-T4) therapy.
Study design and methods
All pregnant and non-pregnant women between 21 and 35 years of age with a history of two or more consecutive miscarriages were included in the study. A third group comprising 100 pregnant women without a history of miscarriage were taken as healthy controls. Thyroid autoimmunity, prevalence of subclinical hypothyroidism and maternal and foetal complications were analysed in all the groups with appropriate statistical methods.
The mean age of the patients included in the study was 27.0±3.1 years. Of 100 pregnant patients with previous recurrent miscarriage, thyroid autoimmunity (thyroid peroxidase antibody (TPOAb+) >34 U/ml) was found in 31% of the cases. The incidence of subclinical hypothyroidism was higher in TPOAb+ group than in TPOAb− group (52 vs 16%; P=0.0002). There was no difference in the prevalence of miscarriage or obstetric outcomes between recurrent miscarriage and healthy pregnant women group irrespective of TPO status.
The prevalence of thyroid autoimmunity was higher in pregnant women with a history of recurrent abortion compared with healthy pregnant control population. Following l-T4 treatment, there was no difference in prevalence of miscarriage between hypothyroid and euthyroid individuals in TPOAb+ women.
PMCID: PMC3691574  PMID: 23802061
recurrent miscarriage; thyroid peroxidase; hypothyroidism; preterm birth
9.  Subclinical hypothyroidism in pregnancy: An emerging problem in Southern West Bengal: A cross-sectional study 
Prevalence of subclinical hypothyroidism (SCH) in pregnancy varies widely in different parts of our country, but it has multiple adverse outcomes in both the mother and fetus.
This study was conducted to evaluate the prevalence of SCH in pregnant women during the first trimester and to identify the prevalence of thyroid autoimmunity in pregnant women.
Materials and Methods:
This cross-sectional study (March 2014 to February 2015) was conducted among the pregnant women attending antenatal clinic in their first trimester at a tertiary care center. Morning samples of study participants were analyzed for free thyroxin (FT4), thyroid stimulating hormone (TSH), and thyroid peroxidase antibody (TPO Ab). Data expressed as mean ± standard deviation and percentage (%) as applicable.
Of the 510 subjects, 168 had TSH value >2.5 μIU/ml (32.94%) with normal FT4 and they were diagnosed as SCH. TSH level >4.5 μIU/ml was estimated in 13.92% (71) of the subjects. TPO Ab was positive in 57 (33.93%) of subclinical hypothyroid and 5 (1.47%) of normal subjects. 70.42% (50) of the subjects with TSH >4.5 μIU/ml had positive TPO Ab.
Prevalence of SCH is high in South Bengal and routine thyroid screening at the first antenatal visit should be done to reduce the social and financial burden caused by SCH.
PMCID: PMC4780174  PMID: 27003976
Autoimmunity; first trimester; pregnancy; subclinical hypothyroidism
10.  Smoking and Early Pregnancy Thyroid Hormone and Anti-Thyroid Antibody Levels in Euthyroid Mothers of the Northern Finland Birth Cohort 1986 
Thyroid  2012;22(9):944-950.
Smokers in the general population have lower thyrotropin (TSH) and higher free triiodothyronine (fT3) and free thyroxine (fT4) concentrations, but the results in pregnant population vary from no effect to a decrease in TSH and fT4 concentrations and an increase in fT3 levels. Our objective was to further evaluate the question of whether there is an association between smoking, before and during pregnancy, with maternal thyroid function during pregnancy and with the risk for subsequent hypothyroidism.
Our study population was a prospective population-based cohort (N=9362), the Northern Finland Birth Cohort 1986, with extensive data throughout gestation. The mothers underwent serum sampling in early pregnancy. The samples were assayed for TSH, fT3, fT4, thyroid-peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (TG-Abs) (n=5805). Mothers with thyroid dysfunction diagnosed before or during pregnancy were excluded, leaving 4837 euthyroid mothers. The smoking status of mothers and fathers were requested by questionnaires during pregnancy. Subsequent maternal morbidity relating to hypothyroidism 20 years after the index pregnancy was evaluated using national registers.
Euthyroid mothers who smoked before, or continued smoking during first trimester of pregnancy, had higher serum fT3 (p<0.001) and lower fT4 (p=0.023) concentrations than nonsmokers. Smoking in the second trimester was associated with higher fT3 (p<0.001) concentrations, but no difference in fT4 concentrations compared with nonsmokers. TG-Abs were less common among smoking than nonsmoking mothers (2.5% vs. 4.7%, p<0.001), but the prevalence of TPO-Ab was similar. Paternal smoking had no independent effect on maternal early pregnancy thyroid hormone or antibody concentrations. The risk of subsequent maternal hypothyroidism after follow-up of 20 years was similar among prepregnancy smokers and nonsmokers.
In euthyroid women, smoking during pregnancy was associated with higher fT3 levels and lower fT4 levels; possibly reflecting smoking-induced changes in peripheral metabolism of thyroid hormones. No differences were found in TSH concentrations between smokers and nonsmokers. Our results differ from those of the general population, which usually have shown smoking-induced thyroidal stimulation. This is possibly due to pregnancy-induced changes in thyroid function. Decreases in fT4 levels among smokers might predispose to hypothyroidism or hypothyroxinemia during pregnancy. Despite these changes in thyroid function, smoking did not increase the woman's risk of subsequent hypothyroidism.
PMCID: PMC3429279  PMID: 22873201
11.  Trimester specific reference intervals for thyroid function tests in normal Indian pregnant women 
Accurate assessment of thyroid function during pregnancy is critical, for initiation of thyroid hormone therapy, as well as for adjustment of thyroid hormone dose in hypothyroid cases.
We evaluated pregnant women who had no past history of thyroid disorders and studied their thyroid function in each trimester.
Settings and Design:
86 normal pregnant women in the first trimester of pregnancy were selected for setting reference intervals. All were healthy, euthyroid and negative for thyroid peroxidase antibody (TPOAb). These women were serially followed throughout pregnancy. 124 normal nonpregnant subjects were selected for comparison. Material and methods: Thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and anti-TPO were measured using Roche Elecsys 1010 analyzer. Urinary iodine content was determined by simple microplate method. The 2.5th and 97.5th percentiles were calculated as the reference intervals for thyroid hormone levels during each trimester.
Statistical Analysis:
SPSS (version 14.0, SPSS Inc., Chicago, IL, USA) was used for data processing and analysis.
The reference intervals for the first, second and third trimesters for the following parameters: TSH 0.09-6.65, 0.51-6.66, 0.91-4.86 µIU/mL, FT4 9.81-18.53, 8.52-19.43, 7.39-18.28 pM/L and FT3 3.1-6.35, 2.39-5.12, 2.57-5.68 pM/L respectively. Thyroid hormone concentrations significantly differed during pregnancy at different stages of gestation. The pregnant women in the study had median urinary iodine concentration of 150-200 µg/l during each trimester.
The trimester-specific reference intervals for thyroid tests during pregnancy have been established for pregnant Indian women serially followed during pregnancy using 2.5th and 97.5th percentiles.
PMCID: PMC4743369  PMID: 26904477
Anti-thyroid peroxidase; pregnant women; reference intervals; thyroid function tests; trimester
12.  Thyroid diseases in pregnancy: The importance of anamnesis 
Pakistan Journal of Medical Sciences  2013;29(5):1187-1192.
Objective: Primary objective of our study was to evaluate the efficiency of detailed medical history and thyroid examination of the pregnant women presenting to our clinic from Rize province and nearby which was an endemic goiter region. It was aimed to investigate the frequency of thyroid diseases, pregnancy outcomes and the efficiency of screening with thyroid function tests during the first trimester of pregnancy as secondary endpoint.
Methodology : A prospective clinical study was conducted with 998 pregnant women between the ages of 17-48 years. In the first step of our study, a detailed medical history was obtained and a detailed thyroid gland examination was performed in all the patients (n=998). In the patients diagnosed with thyroid disease or considered to have thyroid disease with these results (n=107), thyroid diseases were evaluated with thyroid function tests and imagining methods. Analyses of socio-demographic data and nutrition were also made. In the second step, thyroid stimulating hormone (TSH), free T3 and free T4 tests were performed in the first antenatal examination of the pregnant cases considered not to have thyroid disease after medical history and examination (n=891). Parameters of thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb) and TSH receptor auto antibodies (TRAb) were investigated in the cases whose TSH, sT3 and sT4 levels were different than the reference values after examination of the endocrinologist. Thyroid ultrasonography was performed. Urinary iodine levels in 24 hour urine were investigated.
Results: During pregnancy, the incidence of hyperthyroidism and hypothyroidism in the whole study group were 2.8% (28/998) and 4.3% (43/998), respectively, 6.7% of the patients (67/998) had a diagnosis of thyroid disease before pregnancy. Hyperthyroidism and hypothyroidism depending on the TSH screening results were 1.9% (17/891) and 1.1% (10/891) respectively and the incidence of overt hyperthyroidism and overt hypothyroidism were 0.2% (2/891) and 0.2% (2/891) in the pregnant cases considered not to have thyroid disease with medical history and examination.
Conclusion: Detailed medical history and family history obtained during the first trimester of pregnancy helped us to identify 6.7% of thyroid diseases among the pregnant women. This result effectively emphasizes the importance of detailed first prenatal examination regarding the thyroid.
PMCID: PMC3858910  PMID: 24353717
Hyperthyroidism; Hypothyroidism; Thyroid diseases in pregnancy; Goiter
13.  Prevalence of hypothyroidism in adults: An epidemiological study in eight cities of India 
Hypothyroidism is believed to be a common health issue in India, as it is worldwide. However, there is a paucity of data on the prevalence of hypothyroidism in adult population of India.
Materials and Methods:
A cross-sectional, multi-centre, epidemiological study was conducted in eight major cities (Bangalore, Chennai, Delhi, Goa, Mumbai, Hyderabad, Ahmedabad and Kolkata) of India to study the prevalence of hypothyroidism among adult population. Thyroid abnormalities were diagnosed on the basis of laboratory results (serum FT3, FT4 and Thyroid Stimulating Hormone [TSH]). Patients with history of hypothyroidism and receiving levothyroxine therapy or those with serum free T4 <0.89 ng/dl and TSH >5.50 μU/ml, were categorized as hypothyroid. The prevalence of self reported and undetected hypothyroidism, and anti-thyroid peroxidase (anti-TPO) antibody positivity was assessed.
A total of 5376 adult male or non-pregnant female participants ≥18 years of age were enrolled, of which 5360 (mean age: 46 ± 14.68 years; 53.70% females) were evaluated. The overall prevalence of hypothyroidism was 10.95% (n = 587, 95% CI, 10.11-11.78) of which 7.48% (n = 401) patients self reported the condition, whereas 3.47% (n = 186) were previously undetected. Inland cities showed a higher prevalence of hypothyroidism as compared to coastal cities. A significantly higher (P < 0.05) proportion of females vs. males (15.86% vs 5.02%) and older vs. younger (13.11% vs 7.53%), adults were diagnosed with hypothyroidism. Additionally, 8.02% (n = 430) patients were diagnosed to have subclinical hypothyroidism (normal serum free T4 and TSH >5.50 μIU/ml). Anti – TPO antibodies suggesting autoimmunity were detected in 21.85% (n = 1171) patients.
The prevalence of hypothyroidism was high, affecting approximately one in 10 adults in the study population. Female gender and older age were found to have significant association with hypothyroidism. Subclinical hypothyroidism and anti-TPO antibody positivity were the other common observations.
PMCID: PMC3743364  PMID: 23961480
Anti-TPO positive; epidemiology; free T3; free T4; hypothyroidism; India; prevalence; subclinical hypothyroidism; undetected hypothyroidism
14.  Thyroid Autoimmunity is Associated with Decreased Cytotoxicity T Cells in Women with Repeated Implantation Failure 
Thyroid autoimmunity (TAI), which is defined as the presence of autoantibodies against thyroid peroxidase (TPO) and/or thyroglobulin (TG), is related to repeated implantation failure (RIF). It is reported that TAI was involved in reproductive failure not only through leading thyroid function abnormality, but it can also be accompanied with immune imbalance. Therefore, this study was designed to investigate the association of thyroid function, immune status and TAI in women with RIF. Blood samples were drawn from 72 women with RIF to evaluate the prevalence of TAI, the thyroid function, the absolute numbers and percentages of lymphocytes. The prevalence of thyroid function abnormality in RIF women with TAI was not significantly different from that in RIF women without TAI (χ2 = 0.484, p > 0.05). The absolute number and percentage of T cells, T helper (Th) cells, B cells and natural killer (NK) cells were not significantly different in RIF women with TAI compared to those without TAI (all p > 0.05). The percentage of T cytotoxicity (Tc) cells was significantly decreased in RIF women with TAI compared to those without TAI (p < 0.05). Meanwhile, Th/Tc ratio was significantly increased (p < 0.05). These results indicated that the decreased Tc percentage and increased Th/Tc ratio may be another influential factor of adverse pregnancy outcomes in RIF women with TAI.
PMCID: PMC4586615  PMID: 26308040
infertility; repeated implantation failure; thyroid autoimmunity; lymphocytes
15.  Thyroglobulin Autoantibodies: Is There Any Added Value in the Detection of Thyroid Autoimmunity in Women Consulting for Fertility Treatment? 
Thyroid  2013;23(8):1022-1028.
Thyroid autoimmunity (TAI) is frequent in infertile women, but to what extent thyroglobulin autoantibodies (Tg-Abs) contribute to TAI is unclear in the literature. The aims of the present study were to determine the prevalence of TAI in women consulting for fertility problems and to investigate the impact of isolated Tg-Abs, isolated thyroid peroxidase autoantibodies (TPO-Abs), and the presence of both autoantibody types on thyroid function. Furthermore, thyroid function was compared between women with and without TAI and between infertile and fertile women.
A cross-sectional data analysis nested within an ongoing prospective cohort study was performed in order to determine the prevalence of TAI in unselected women consulting our tertiary referral center for reproductive medicine (CRM). The women underwent a determination of serum thyrotropin (TSH), free thyroxine (FT4), TPO-Abs, and Tg-Abs. The cause of infertility, age, body-mass index (BMI), and smoking habits were recorded.
The prevalence of TAI was 16% (163/992). In 8% of cases, both types of autoantibodies were present, in 5% isolated positive Tg-Abs were found, and 4% had isolated positive TPO-Abs (p=0.025 and p=0.003 respectively). The prevalence of TAI was significantly higher in infertile women as compared to that in fertile controls (19% vs. 13%; p=0.047). The median serum TSH level was significantly higher in the women with TAI and with isolated positive Tg-Abs compared to that in women without TAI (1.83 [1.44] and 1.90 [0.85] vs. 1.47 [0.94] mIU/L; p<0.001 respectively). The median FT4, age, BMI, and smoking habits were comparable between the study groups.
The prevalence of TAI was higher in infertile women as compared to fertile women consulting our CRM. Five percent of the women had isolated positive Tg-Abs and a significantly higher serum TSH compared to that in women without TAI.
PMCID: PMC3752510  PMID: 23405888
16.  Five-Year Follow-Up for Women With Subclinical Hypothyroidism in Pregnancy 
Increasing numbers of women are being treated with l-thyroxine in pregnancy for mild thyroid dysfunction because of its association with impaired neuropsychological development in their offspring and other adverse obstetric outcomes. However, there are limited data to indicate whether treatment should be continued outside of pregnancy.
We aimed to determine whether subclinical hypothyroidism and maternal hypothyroxinemia resolve postdelivery.
Design, Setting, and Participants:
A total of 523 pregnant healthy women with no known thyroid disorders were recruited during routine antenatal care and provided blood samples at 28 weeks of pregnancy and at a mean of 4.9 years postpregnancy.
Main Outcome Measures:
TSH, free T4, free T3, and thyroid peroxidase antibody levels were measured in serum taken in pregnancy and at follow-up.
Subclinical hypothyroidism in pregnancy (TSH >3 mIU/L) was present in 65 of 523 (12.4%) women. Of these, 49 (75.4%) women had normal thyroid function postpregnancy; 16 of 65 (24.6%) had persistent high TSH (TSH >4.5 mIU/L postpregnancy) with 3 women receiving l-thyroxine treatment. A total of 44 of 523 (8.4%) women had isolated maternal hypothyroxinemia in pregnancy (free T4 <10th centile and TSH ≤3 mIU/L). Only 2 of 44 (4.5%) had TSH >4.5 mIU/L outside pregnancy. Of the women with subclinical hypothyroidism in pregnancy with antibody measurements available, those with thyroid peroxidase antibodies in pregnancy were more likely to have persistently elevated TSH or be receiving l-thyroxine replacement after pregnancy (6 of 7 [86%] vs 10 of 57 [18%], P < .001).
The majority of cases of subclinical hypothyroidism in pregnancy are transient, so treatment with l-thyroxine in these patients should be reviewed because it may not be warranted after pregnancy.
PMCID: PMC4207946  PMID: 24217906
17.  Prevalence of hypothyroidism in pregnancy: An epidemiological study from 11 cities in 9 states of India 
A previous hospital based study from Delhi revealed a high prevalence of hypothyroidism in pregnant women. Several other studies with small sample size also indicate a rising trend of prevalence of hypothyroidism during pregnancy in India.
To assess prevalence of hypothyroidism in pregnant women from various states/cities across India.
Materials and Methods:
This was a cross-sectional multicenter study conducted at Allahabad (Uttar Pradesh), Bengaluru (Karnataka), Chennai (Tamil Nadu), Kolkata (West Bengal), Hyderabad (Telangana), Nasik (Maharashtra), Rohtak (Haryana), Pune (Maharashtra), New Delhi (Delhi), Srinagar (Kashmir), and Vizag (Andhra Pradesh) enrolling 2599 pregnant women. Estimation of thyroid stimulating hormone (TSH), free T4, and antithyroid peroxidase (TPO) antibodies was carried out using Roche modular kit using ECLIA technology in a central laboratory.
We found in our study population that 13.13% of pregnant women have hypothyroidism (n = 388), using a cutoff TSH level of 4.5 μIU/ml. This prevalence was much higher using the American Thyroid Association criteria. Anti-TPO antibodies were positive in 20.74% of all pregnant women (n = 613), whereas 40% (n = 155) of hypothyroid pregnant women were positive for anti-TPO antibodies.
This study concludes that there is a high prevalence of hypothyroidism (13.13%), majority being subclinical in pregnant women during the first trimester from India and universal screening of hypothyroidism may be desirable in our country.
PMCID: PMC4855970  PMID: 27186559
Epidemiology; hypothyroidism; pregnancy
18.  The Effect of Anti-Thyroid Peroxidase Antibodies on Pregnancy Outcomes in Euthyroid Women 
Thyroid autoimmunity can have an adverse impact on the outcome of the pregnancy. Although the adverse effects of antithyroid antibodies have been well studied in hypothyroid women, their effects in euthyroid women are not well evaluated.
The study was conducted to assess the overall prevalence of anti-Thyroid Peroxidase (anti-TPO) antibodies in pregnant women and the effect of anti-TPO positivity on the outcome of pregnancy in euthyroid women.
Materials and Methods
One thousand Indian women, in their first trimester were screened for anti-TPO antibodies to know the prevalence. Of this, euthyroid women who were positive for the presence of anti-TPO antibody were selected and their obstetric history was recorded. These women were followed up and the incidences of maternal and foetal complications were recorded. The complications were compared with the past obstetric history and outcomes in parity and gestation matched controls (anti-TPO negative).
The prevalence of anti-TPO positivity was 11% (n=110). Out of the positives, those with elevated Thyroid Stimulating Hormone (TSH) were 6.5%. The prevalence of euthyroid women who were anti-TPO positive was 4% (n=40). Anti-TPO positive, euthyroid females had a higher prevalence of infertility, anaemia and preterm delivery as compared to the controls (p<0.0001). No differences were observed between the two groups in terms of history of abruption recurrent abortions, intrauterine growth restriction, postpartum haemorrhage, symptomatic hypothyroidism, hypertensive disorders of pregnancy and foetal complications.
Anti-TPO positivity is common in pregnant women. Anti-TPO positive euthyroid females had a higher prevalence of infertility, anaemia as well as preterm delivery. Our results indicate that anti-TPO screening in pregnancy, may aid in early identification of the women at risk.
PMCID: PMC5072023  PMID: 27790523
Autoimmunity; Endocrine disorder; Thyroid autoimmunity
19.  Thyroid Function in Pregnancy and Its Influences on Maternal and Fetal Outcomes 
Maternal thyroid function alters during pregnancy. Inadequate adaptation to these changes results in thyroid dysfunction and pregnancy complications.
This prospective study aimed to evaluate the prevalence of thyroid diseases in pregnancy and its outcomes in south of Iran.
Materials and Methods:
This prospective study was conducted on 600 healthy singleton pregnant women who aged 18 to 35 years old at 15 to 28 weeks of gestation. We investigated the prevalence of thyroid dysfunctions in women. Multivariate analysis was performed to determine the effect thyroid dysfunction on obstetric and neonatal outcome.
Thyroid stimulating hormone (TSH) levels of 0.51, 1.18, 1.68, 2.4, and 4.9 mIU/L were at 2.5th, 25th, 50th, 75th, and 97.5th percentile in our population. The prevalence of clinical hypothyroidism, subclinical hypothyroidism, overt hyperthyroidism, and subclinical hyperthyroidism in all pregnant women was 2.4%, 11.3%, 1.2%, and 0.3%, respectively. In addition, 1.4% of patients had isolated hypothyroxinemia. Clinical hypothyroidism was associated with increased risk of preterm delivery (P = 0.045). Subclinical hypothyroidism had a significant association with intrauterine growth restriction (IUGR) (P = 0.028) as well as low Apgar score at first minute (P = 0.022). Maternal hyperthyroidism was associated with IUGR (P = 0.048).
We revealed that thyroid dysfunction during pregnancy was associated with IUGR and low Apgar score even in subclinical forms. Further studies are required to determine whether early diagnosis and treatment of thyroid diseases, even in subclinical form, can prevent their adverse effect on fetus.
PMCID: PMC4338651  PMID: 25745488
UGR; Fetal Growth Retardation; Thyroid Dysfunction; Thyroid Disease
20.  Prevalence of Overt and Subclinical Thyroid Dysfunction Among Pregnant Women and Its Effect on Maternal and Fetal Outcome 
To determine the current prevalence of thyroid dysfunction in normal pregnant women and to study the impact of thyroid dysfunction on maternal and fetal outcome.
400 pregnant women between 13 and 26 weeks of gestation were registered for the study. Apart from routine obstetrical investigations, TSH tests were done. Free T4 and anti-TPO antibody tests were done in patients with deranged TSH. Patients were followed up till delivery. Their obstetrical and perinatal outcomes were noted.
The prevalence of hypothyroidism and hyperthyroidism was 12 and 1.25 %, respectively. Adverse maternal effects in overt hypothyroidism included preeclampsia (16.6 vs. 7.8 %) and placental abruption (16.6 vs. 0.8 %). Subclinical hypothyroidism was associated with preeclampsia (22.3 vs. 7.8 %) as compared to the euthyroid patients. Adverse fetal outcomes in overt hypothyroidism included spontaneous abortion (16.6 vs. 2.39 %), preterm birth (33.3 vs. 5.8 %), low birth weight (50 vs. 12.11 %), intrauterine growth retardation (25 vs. 4.9 %), and fetal death (16.6 vs. 1.7 %) as compared to the euthyroid women. Adverse fetal outcomes in subclinical hypothyroidism included spontaneous abortion (5.5 vs. 2.39 %), preterm delivery (11.2 vs. 5.8 %), low birth weight (25 vs. 12.11 %), and intrauterine growth retardation (8.4 vs. 4.9 %) as compared to the euthyroid women.
The prevalence of thyroid disorders was high in our study with associated adverse maternal and fetal outcomes. Routine screening of thyroid dysfunction is recommended to prevent adverse fetal and maternal outcome.
PMCID: PMC3984645  PMID: 24757337
Thyroid dysfunction; Prevalence; Maternal outcome; Fetal outcome
21.  Further Evidence on the Role of Thyroid Autoimmunity in Women with Recurrent Miscarriage 
It has been twenty years since the first paper reporting the association between thyroid antibodies (TAIs) and spontaneous miscarriage was published. Following this observation, several studies have clearly demonstrated an increased prevalence of TAI in patients with recurrent miscarriage (RM). However, the exact mechanism underlying this association remains a matter of debate. The aim of the present study was to evaluate the thyroid function, throughout a specific test, in patient with RM and TAI focusing on the hypothesis that TAI should be an indirect sign of a mild thyroid dysfunction. 46 patients with RM and TAI were included in the study. All patients underwent short TRH stimulation test showing an abnormal response in the vast majority of cases (65%). Normal FT4 and FT3 mean values were found whereas TSH values were in the upper normal range (2.64 ± 1.3 mUI/L). Our data support the hypothesis that in patients with RM the presence of TAI is an indirect sign of a subtle thyroid dysfunction detectable by a specific test. This test give the possibility to identify women with RM in which specific therapeutic approaches could effectively improve the possibility for a successful pregnancy.
PMCID: PMC3272809  PMID: 22319528
22.  The spectrum of thyroid dysfunction in an Australian hepatitis C population treated with combination Interferon-α2β and Ribavirin 
The study aims to assess the pattern of thyroid response to combination Interferon-α2β (IFN-α) and Ribavirin (RBV) anti-viral therapy in an Australian hepatitis C cohort. These include the prevalence of thyroid dysfunction (TD) including hyperthyroidism and hypothyroidism and their possible predictors, the common overall pattern of thyroid function tests whilst receiving therapy and TD outcomes, and the correlation with HCV status outcome.
A retrospective analysis of all medical records was performed to assess thyroid function in Hepatitis C Virus (HCV) patients who were treated at the Hunter Area hepatitis C treatment center between 1995 and March 2004. The centre is part of the John Hunter hospital, a major tertiary referral centre in New South Wales, Australia.
There were 272 cases available for review. The prevalence of TD is 6.7 percent and is made up predominantly of females (80 percent). There were 3 (1.1 percent) cases of hyperthyroidism with 2 (67 percent) females. Thirteen out of fifteen (80 percent) cases of hypothyroidism were females with the overall prevalence of 5.5 percent. The majority of hypothyroid patients still required Thyroxine supplement at the end of follow up.
Ninety three percent of HCV treated patients have intact thyroid function at the end of treatment. The predominant TD is hypothyroidism. The predominant pattern of thyrotoxicosis (TTX) is that of thyroiditis although the number is small. Graves' like disease was not observed. People with pre-existing thyroid auto-antibodies should be closely monitored for thyroid dysfunction, particularly hypothyroidism.
PMCID: PMC1266361  PMID: 16219106
23.  Hyperthyroid and Hypothyroid Status Was Strongly Associated with Gout and Weakly Associated with Hyperuricaemia 
PLoS ONE  2014;9(12):e114579.
The aim of this study was to estimate the risk of hyperuricaemia and gout in people with hypothyroid or hyperthyroid status.
This study analyzed data from individuals who participated in health screening programs at Chang Gung Memorial Hospital in northern Taiwan (2000–2010). Participants were categorized as having euthyroid, hypothyroid, or hyperthyroid status according to their thyroid-stimulating hormone (TSH) levels. Multinomial logistic regression models were used to calculate the odds ratios (95% CI) for hyperuricaemia and gout in participants with thyroid dysfunction compared to euthyroid participants.
A total of 87,813 (euthyroid, 83,502; hypothyroid, 1,460; hyperthyroid, 2,851) participants were included. The prevalence of hyperuricaemia was higher in hyperthyroid subjects (19.4%) than in euthyroid subjects (17.8%) but not in hypothyroid subjects (19.3%). The prevalence of gout was significantly higher in both hypothyroid (6.0%) and hyperthyroid (5.3%) subjects than in euthyroid subjects (4.3%). In men, hypothyroid or hyperthyroid status was not associated with hyperuricaemia. However, hypothyroid or hyperthyroid status was associated with ORs (95% CI) of 1.47 (1.10–1.97) and 1.37 (1.10–1.69), respectively, for gout. In women, hypothyroid status was not associated with hyperuricaemia or gout. However, hyperthyroid status was associated with ORs (95% CI) of 1.42 (1.24–1.62) for hyperuricaemia and 2.13 (1.58–2.87) for gout.
Both hyperthyroid and hypothyroid status were significantly associated with gout and weakly associated with hyperuricaemia. A thyroid function test for gout patients may by warranted.
PMCID: PMC4259336  PMID: 25486420
24.  Prevalence of Thyroid Disorders in Children at a Tertiary Care Hospital in Western India 
Thyroid hormone abnormalities are the commonest endocrine disorder in India and also the commonest preventable cause of mental retardation. In the absence of neonatal screening, thyroid disorders remain largely unrecognized in Indian children.
To determine the prevalence, clinical profile, aetiology and associated co-morbidities of thyroid dysfunction in children.
Materials and Methods
A prospective, hospital based, observational study was conducted at a tertiary care hospital in Western India. Children below 12 years of age visiting the Pediatric out-patient department (OPD) and in-patient department (IPD) were included if they had clinical suspicion of thyroid dysfunction. Demographic data and clinical features of the recruited children were noted along with family history of thyroid disorders and use of iodized salt. Thyroid profile consisting of Tri-iodothyronin (T3), Thyroxin (T4) and Thyroid stimulating hormone (TSH) levels were tested in all. Investigations were also carried out to look for the cause and complications of hypothyroidism. These children were also followed up with appropriate therapy to look for response of therapy and complications to the same.
Sixty five children were found to have thyroid function abnormalities, 61 having hypothyroidism and 4 having hyperthyroidism. There was a low prevalence of goiter. The clinical feature of patients with hypo and hyperthyroidism was similar to other reported studies. The commonest aetiology of hypothyroidism was found to be dyshormonogenesis. A host of co-morbidities was observed along with thyroid dysfunction. On follow up with appropriate therapy, most of the children became euthyroid and complications were observed in only a minority.
There is a high prevalence of thyroid dysfunction in children in western India and need for similar studies from different regions of the country covering larger population are well appreciated.
PMCID: PMC4800610  PMID: 27042544
Goiter; Growth retardation; Hypothyroidism; Thyroid dysfunction
25.  High Prevalence of Thyroid Dysfunction Among Pregnant Women in Lubumbashi, Democratic Republic of Congo 
Thyroid  2014;24(3):568-575.
Background: Despite notable progress in the fight against iodine deficiency disorders in the Democratic Republic of Congo, a recent study has shown that pregnant women in Lubumbashi were still iodine deficient. Our objective was to assess thyroid function in this population.
Methods: In a cross-sectional study conducted in maternity units from three different socioeconomic areas in Lubumbashi, serum thyrotropin, free thyroxine, thyroglobulin, and thyroperoxidase antibodies were measured in 225 pregnant women attending antenatal visits, in 75 women who recently delivered, and in 75 nonpregnant controls. The outcome was the prevalence of thyroid dysfunction.
Results: Median values in pregnant women, women who recently delivered, and nonpregnant women were 1.80, 2.80, and 1.54 mIU/L for thyrotropin (p<0.001); 0.85, 1.11, and 1.16 ng/dL for free thyroxine (p<0.001); and 13.3, 9.5, and 10.4 ng/mL for thyroglobulin (p=0.01), respectively. The prevalence of thyroid dysfunction in pregnant women, in women who recently delivered, and in nonpregnant women was 31%, 8%, and 20% for isolated hypothyroxinemia (p<0.001); 12%, 24%, and 5% for subclinical hypothyroidism (p=0.002); 8%, 3%, and 3%, for overt hypothyroidism (p=0.09); and 5%, 13%, and 4%, for positive thyroperoxidase antibodies (p=0.03), respectively. In multiple logistic regression, women who were pregnant or who recently delivered, who lived in a poor socioeconomic area, and who had low urinary iodine concentration were more likely to have an increased serum thyrotropin: odds ratio (OR)=3.43 (95% confidence interval [CI] 1.23–9.53) for pregnancy, OR=4.49 [CI 1.66–15.01] for postpartum period, OR=3.68 [CI 1.85–7.35] for semiurban area, and OR=0.44 [CI 0.19–0.96] for urinary iodine concentration ≥250 μg/L.
Conclusions: Our results show that there is a high prevalence of thyroid dysfunction in pregnant women of Lubumbashi, and this high prevalence is associated with iodine deficiency. To prevent obstetrical adverse outcomes and neurological damage in children, iodine supplementation is needed before conception or in early pregnancy in Lubumbashi.
PMCID: PMC3949433  PMID: 23957235

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