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.
Pregnancy; hypothyroidism; subclinical hypothyroidism; autoimmunity and India
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.
Pregnancy; Thyroid hypo function; Prediction; Screening; Logistic models
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.
Hypothyroidism; Pregnancy; Prevalence; Thyrotropin
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.
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.
recurrent miscarriage; thyroid peroxidase; hypothyroidism; preterm birth
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.
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.
: 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.
Hyperthyroidism; Hypothyroidism; Thyroid diseases in pregnancy; Goiter
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.
Anti-TPO positive; epidemiology; free T3; free T4; hypothyroidism; India; prevalence; subclinical hypothyroidism; undetected hypothyroidism
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.
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.
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.
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.
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.
To determine the importance of screening for Thyriod disorders in the first trimester of pregnancy.
Materials and Methods:
The Study was conducted on 305 patients which were were randomly selected and screened on OPD basis by TSH levels (cut off level 0.10-2.50 mIU/ml).
In the 305 women screened mean age was 24.46 years, mean gestational age was 9.09 weeks, 89.83% were euthyroid, 9.8%were hypothyroid, 0.32% were hyperthyroid. Incidence of hypothyroidism in high risk population was 20.58% and in normal population was 6.7%. There was significant association of thyroid disorders with high risk factors (P < 0.001). In hypothyroid women 46% had adverse perinatal outcomes and 53.33% had normal outcomes. This shows statistically significant association abnormal TSH values with adverse pregnancy outcomes (P < 0.001). In abnormal perinatal outcomes 6.2% women had Caesarean section out of them 73.68% were euthyroid, 26.31% were hypothyroid 1.9% had preterm labour, out of them 50% were euthyroid, 50% were hypothyroid. Out of 2.2% spontaneous abortions 28.5% were in euthyroid group while 71.4% were in hypothyroid group. There was 1 term stillbirth in hypothyroid group. This study showed significant association between abnormal thyroid stimulating hormone (TSH) values and adverse perinatal outcomes (P < 0.001).
There is significant correlation between risk factors and hypothyroidism. So high risk screening is mandatory in early pregnancy. But if we screen only high risk population we would miss 4.6% cases which could have been diagnosed and treated earlier. Therefore it is important to screen all pregnant women in the first trimester, it should be made mandatory.
Hypothyroidism in pregnancy; screening in first trimester; Universal screening
Mexican Americans are at an increased risk of both thyroid dysfunction and metabolic syndrome (MS). Thus it is conceivable that some components of the MS may be associated with the risk of thyroid dysfunction in these individuals. Our objective was to investigate and replicate the potential association of MS traits with thyroid dysfunction in Mexican Americans.
We conducted association testing for 18 MS traits in two large studies on Mexican Americans – the San Antonio Family Heart Study (SAFHS) and the National Health and Nutrition Examination Survey (NHANES) 2007–10. A total of 907 participants from 42 families in SAFHS and 1633 unrelated participants from NHANES 2007–10 were included in this study. The outcome measures were prevalence of clinical and subclinical hypothyroidism and thyroid function index (TFI) – a measure of thyroid function. For the SAFHS, we used polygenic regression analyses with multiple covariates to test associations in setting of family studies. For the NHANES 2007–10, we corrected for the survey design variables as needed for association analyses in survey data. In both datasets, we corrected for age, sex and their linear and quadratic interactions.
TFI was an accurate indicator of clinical thyroid status (area under the receiver-operating-characteristic curve to detect clinical hypothyroidism, 0.98) in both SAFHS and NHANES 2007–10. Of the 18 MS traits, waist circumference (WC) showed the most consistent association with TFI in both studies independently of age, sex and body mass index (BMI). In the SAFHS and NHANES 2007–10 datasets, each standard deviation increase in WC was associated with 0.13 (p < 0.001) and 0.11 (p < 0.001) unit increase in the TFI, respectively. In a series of polygenic and linear regression models, central obesity (defined as WC ≥ 102 cm in men and ≥88 cm in women) was associated with clinical and subclinical hypothyroidism independent of age, sex, BMI and type 2 diabetes in both datasets. Estimated prevalence of hypothyroidism was consistently high in those with central obesity, especially below 45y of age.
WC independently associates with increased risk of thyroid dysfunction. Use of WC to identify Mexican American subjects at high risk of thyroid dysfunction should be investigated in future studies.
Waist circumference; Central obesity; Thyroid dysfunction; Mexican Americans
Background and Objective
Hypothyroidism and autoimmune thyroiditis are more prevalent than previously considered in women during pregnancy and the postpartum, and are associated with adverse effects on the mother and her fetus. We determined the efficacy and accuracy of screening women for primary hypothyroidism and autoimmune thyroiditis by testing TSH and two thyroid antibodies (TAb): thyroperoxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb), in eluates of filter paper specimens collected during early pregnancy and the postpartum.
We enrolled 494 first-trimester pregnant women with no exclusion criteria into a prospective study to detect primary hypothyroidism and autoimmune thyroiditis. Finger stick blood was applied to filter paper, dried in room air, eluted, and promptly tested for TSH and TAb. A total of 178 of the pregnant women (36%) were tested in the early postpartum. Women with abnormal results had confirmatory serum tests.
It was found that 91 pregnant women (18.4%) and 43 postpartum women (24.2%) had abnormal TSH values (>4.0 mU/L) and/or positive TAb; 140 pregnant women (28.3%) had TSH values >2.5 mU/L. All subjects with TSH values >4.0 mU/L tested positive for TAb. Eighteen women (3.6%) who tested normal during pregnancy tested abnormal in the postpartum.
This study confirms that TSH and TPOAb measured in eluates of blood-spotted filter paper specimens are excellent screening tests to detect primary hypothyroidism and autoimmune thyroiditis in pregnant and postpartum women. Results are very comparable to serum data in this population published in the literature.
Hypothalamic-pituitary-thyroid axis dysfunction in the pathophysiology of bipolar disorder has received less attention as compared with that in depressive disorder.
To study the prevalence of hypothyroidism in patients diagnosed with bipolar disorder and compare it with a population norm.
Settings and Design:
The setting was the psychiatry inpatient unit of a tertiary care hospital. The design was retrospective and observational.
Subjects and Methods:
A retrospective observational study was performed, referring to the case records of 84 cases of bipolar disorder admitted to the Department of Psychiatry in a Tertiary Referral Center during the year 2010-2012. The prevalence of hypothyroidism both subclinical as demonstrated by elevated thyroid stimulating hormone (TSH) levels (cut-off value 4.2 μU/ml) and overt hypothyroidism (fasting T4 <0.92 ng/dl and TSH >4.2 μU/ml) was calculated. This was compared with the population prevalence of hypothyroidism as determined by an epidemiological study carried out in the year 2009, in the same region. The correlation between hypothyroidism, gender, lithium prophylaxis and family history of mood disorder was computed.
Percentage prevalence of hypothyroidism in the sample was calculated and compared to a population norm. The correlation between hypothyroidism, gender, lithium prophylaxis and family history of mood disorder was computed using the odds ratio (OR).
The total prevalence of hypothyroidism in both males and females in the bipolar group was comparable with that in the general population. There is a significant association between family history of mood disorder in first degree relatives and patients having hypothyroidism (OR 5.504 and P = 0.012). There were no statistically significant associations between thyroid abnormalities and age, duration of illness and lithium prophylaxis.
There is no significant association between hypothyroidism and bipolar disorder. Family history of mood disorder and hypothyroidism show significant association. (OR -5.504 AND P = 0.012).
Bipolar disorder; hypothalamic-pituitary-thyroid axis; hypothyroidism
Purpose of the Review:
Thyroid disturbances are common in women during their reproductive years. Thyroid dysfunction interferes with human reproductive physiology, reduces the likelihood of pregnancy and adversely affects pregnancy outcome, thus becoming relevant in the algorithm of reproductive dysfunction. This review highlights the gap in knowledge regarding the contribution of thyroid dysfunction in reproduction.
Following implantation, the maintenance of the pregnancy is dependent on a multitude of endocrinological events that will eventually aid in the successful growth and development of the fetus. It is estimated that approximately 8-12% of all pregnancy losses are the result of endocrine factors. Autoimmune thyroid disease is present in around 4% of young females and up to 15% are at risk because they are thyroid antibody-positive. There is a strong relationship between thyroid immunity on one hand and infertility, miscarriage, and thyroid disturbances in pregnancy and postpartum, on the other hand. Even minimal hypothyroidism can increase rates of miscarriage and fetal death and may also have adverse effects on later cognitive development of the offspring. Hyperthyroidism during pregnancy may also have adverse consequences.
Pregnant women with subclinical hypothyroidism or thyroid antibodies have an increased risk of complications, especially pre-eclampsia, perinatal mortality, and miscarriage. Universal screening for thyroid hormone abnormalities is not routinely recommended at present, but thyroid function must be examined in female with fetal loss or menstrual disturbances. Practitioners providing health care for women should be alert to thyroid disorders as an underlying etiology for recurrent pregnancy loss.
Recurrent pregnancy; thyroid autoimmunity; thyroid disorder
Objective To determine if pre-eclampsia is associated with reduced thyroid function during and after pregnancy.
Design Nested case-control study during pregnancy and population based follow-up study after pregnancy.
Setting Calcium for Pre-eclampsia Prevention trial of healthy pregnant nulliparous women in the United States during 1992-5, and a Norwegian population based study (Nord-Trondelag Health Study or HUNT-2) during 1995-7 with linkage to the medical birth registry of Norway.
Participants All 141 women (cases) in the Calcium for Pre-eclampsia Prevention trial with serum measurements before 21 weeks’ gestation (baseline) and after onset of pre-eclampsia (before delivery), 141 normotensive controls with serum measurements at similar gestational ages, and 7121 women in the Nord-Trondelag Health Study whose first birth had occurred in 1967 or later and in whom serum levels of thyroid stimulating hormone had been subsequently measured.
Main outcome measures Thyroid function tests and human chorionic gonadotrophin and soluble fms-like tyrosine kinase 1 concentrations in the Calcium for Pre-eclampsia Prevention cohort and odds ratios for levels of thyroid stimulating hormone above the reference range, according to pre-eclampsia status in singleton pregnancies before the Nord-Trondelag Health Study.
Results In predelivery specimens of the Calcium for Pre-eclampsia Prevention cohort after the onset of pre-eclampsia, thyroid stimulating hormone levels increased 2.42 times above baseline compared with a 1.48 times increase in controls. The ratio of the predelivery to baseline ratio of cases to that of the controls was 1.64 (95% confidence interval 1.29 to 2.08). Free triiodothyronine decreased more in the women with pre-eclampsia than in the controls (case ratio to control ratio 0.96, 95% confidence interval 0.92 to 0.99). The predelivery specimens but not baseline samples from women with pre-eclampsia were significantly more likely than those from controls to have concentrations of thyroid stimulating hormone above the reference range (adjusted odds ratio 2.2, 95% confidence interval 1.1 to 4.4). Both in women who developed pre-eclampsia and in normotensive controls the increase in thyroid stimulating hormone concentration between baseline and predelivery specimens was strongly associated with increasing quarters of predelivery soluble fms-like tyrosine kinase 1 (P for trend 0.002 and <0.001, respectively). In the Nord-Trondelag Health Study, women with a history of pre-eclampsia in their first pregnancy were more likely than other women (adjusted odds ratio 1.7, 95% confidence interval 1.1 to 2.5) to have concentrations of thyroid stimulating hormone above the reference range (>3.5 mIU/l). In particular, they were more likely to have high concentrations of thyroid stimulating hormone without thyroid peroxidase antibodies (adjusted odds ratio 2.6, 95% confidence interval 1.3 to 5.0), suggesting hypothyroid function in the absence of an autoimmune process. This association was especially strong (5.8, 1.3 to 25.5) if pre-eclampsia had occurred in both the first and the second pregnancies.
Conclusion Increased serum concentration of soluble fms-like tyrosine kinase 1 during pre-eclampsia is associated with subclinical hypothyroidism during pregnancy. Pre-eclampsia may also predispose to reduced thyroid function in later years.
To evaluate clinical value of a new self-sequential longitudinal reference intervals of thyroid function during pregnancy.
Material and methods
We established two different series of reference intervals: self-sequential longitudinal reference intervals (SLRI) and general gestation-specific reference intervals (GSRI). For SLRI, the serum of 301 cases were collected five times in every case throughout the gestation. For GSRI, A total of 1455 subjects included in the study. We collected the serum respectively at various trimesters. We used TSH of both reference intervals to screen 1744 pregnant women, and compared the percentage of potential misclassification.
Both SLRI and GSRI differed substantially from that for non-pregnant women (p < 0.05). There are similar fluctuations of serum TSH, FT4 and TPO-Ab during normal pregnancy. Although there were no significant differences in most reference intervals between SLRI and GSRI. But the IQR of SLRI were usually smaller than GSRI , especially in 1st trimester. Two hundred and fifty two women (14.4%) at various trimesters whose serum TSH concentration was within SLRI would be misclassified, while 23 women (1.3%) with a TSH concentration outside limit would not be identified. 0.11-3.84% women would got thyroid diseases during pregnancy. Subclinical hypothyroidism is most common maternal thyroid disorders.
The SLRI can reflected the changes of thyroid function realistically, and can be used to decrease the percentage of potential misclassification of thyroid dysfunction during pregnancy. Screening for thyroid dysfunction of pregnant women is recommended and important.
pregnancy; thyroid hormones; reference intervals; self-sequential; outcome
Aim. To investigate obstetric features of pregnant women with thyroid disorders and thyroid function tests of their newborn infants. Methods. Women with hypothyroidism and having anti-thyroglobulin (ATG) and anti-thyroid peroxidase (anti-TPO) antibodies were assigned as group I, women with hypothyroidism who did not have autoantibodies were assigned as group II, and women without thyroid problems were assigned as group III. Results. Pregnant women with autoimmune hypothyroidism (group I) had more preterm delivery and their babies needed more frequent neonatal intensive care unit (NICU) admission. In group I, one infant was diagnosed with compensated hypothyroidism and one infant had transient hyperthyrotropinemia. Five infants (23.8%) in group II had thyroid-stimulating hormone (TSH) levels >20 mIU/mL. Only two of them had TSH level >7 mIU/L at the 3rd postnatal week, and all had normal free T4 (FT4). Median maternal TSH level of these five infants with TSH >20 mIU/mL was 6.6 mIU/mL. In group III, six infants (6.5%) had TSH levels above >20 mIU/mL at the 1st postnatal week. Conclusion. Infants of mothers with thyroid problems are more likely to have elevated TSH and higher recall rate on neonatal thyroid screening. Women with thyroid disorders and their newborn infants should be followed closely for both obstetrical problems and for thyroid dysfunction.
To know the status of thyroid disorder in population of far western region of Nepal.
A total of 808 cases (133 men and 675 non pregnant women) were included and study was carried out using data retrieved from the register maintained in the Department of Biochemistry of the Nepalgunj Teaching Hospital between 1st January, 2011 and 28th February, 2012. The variables collected were age, sex, and thyroid function profile including free T3, free T4 and TSH.
The percentage of thyroid disorders was 33.66% in far western region of Nepal. The people were highly affected by overt hyperthyroidism (14.9%) followed by subclinical hyperthyroidism (9.9%). The subclinical hypothyroidism was 7.9% while 1% overt hypothyroidism only in a far western region of Nepal. Females were highly affected by overt hyperthyroidism (17.8%), followed by subclinical hyperthyroidism (11.9%). A total of 5.9% females were affected by subclinical hypothyroidism while only 1.2% by overt hypothyroidism. Males were affected only by subclinical hypothyroidism (18.0%) in this present study. High number of total thyroid dysfunction was observed in 21 to 40 years of age groups, followed by 41 to 60 years of age groups. Less than 40 years people were having 1.03, 0.99, 2.51 and 1.15 times risk of developing overt hyperthyroidism, subclinical hyperthyroidism, overt hypothyroidism and subclinical hyperthyroidism respectively compared to greater than 40. Female were having 0.29 times risk of developing subclinical hyperthyroidism compared to male. But overt hyperthyroidism, subclinical hyperthyroidism and overt hypothyroidism female were having more risk of developing compared to male.
The thyroid disorder, especially overt hyperthyroidism (14.9%) and subclinical hyperthyroidism (9.9%) was high. Further studies are required to characterize the reasons for this high prevalence.
Risk assessment; Thyroid function; Nepal
Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10−8) were detected at TPO-rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO-rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and combined effects (genetic risk scores) of these variants on (subclinical) hypo- and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a high genetic risk score had, besides an increased risk of TPOAb-positivity (OR: 2.18, 95% CI 1.68–2.81, P = 8.1×10−8), a higher risk of increased thyroid-stimulating hormone levels (OR: 1.51, 95% CI 1.26–1.82, P = 2.9×10−6), as well as a decreased risk of goiter (OR: 0.77, 95% CI 0.66–0.89, P = 6.5×10−4). The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, which was replicated in an independent cohort of patients with Graves' disease (OR: 1.37, 95% CI 1.22–1.54, P = 1.2×10−7 and OR: 1.25, 95% CI 1.12–1.39, P = 6.2×10−5). The MAGI3 variant was also associated with an increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18–2.10, P = 1.9×10−3). This first GWAS meta-analysis for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. The results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which TPOAb-positives are particularly at risk of developing clinical thyroid dysfunction.
Individuals with thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune thyroid diseases (AITD), which are common in the general population and associated with increased cardiovascular, metabolic and psychiatric morbidity and mortality. As the causative genes of TPOAbs and AITD remain largely unknown, we performed a genome-wide scan for TPOAbs in 18,297 individuals, with replication in 8,990 individuals. Significant associations were detected with variants at TPO, ATXN2, BACH2, MAGI3, and KALRN. Individuals carrying multiple risk variants also had a higher risk of increased thyroid-stimulating hormone levels (including subclinical and overt hypothyroidism), and a decreased risk of goiter. The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, and the MAGI3 variant was also associated with an increased risk of hypothyroidism. This first genome-wide scan for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. These results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which individuals are particularly at risk of developing clinical thyroid dysfunction.
A high prevalence of postpartum thyroid dysfunction has been reported in several countries, but there have been no systematic studies of its prevalence in Britain. Among a group of 901 consecutive, unselected pregnant women thyroid autoantibodies were detected in 117 (13%) at booking. The clinical course of postpartum thyroid dysfunction, factors associated with its development, and its likely prevalence were defined in 100 of these women with thyroid antibodies and 120 women with no such antibodies who were matched for age. None of the women had a history of autoimmune thyroid disease. Normal reference ranges for thyroid function during pregnancy and post partum were established in the 120 women negative for thyroid antibodies. On the basis of these observations postpartum thyroid dysfunction was observed in 49 (22%) of the 220 women studied, and the prevalence in the total group of 901 women was estimated to be 16·7%. Thyroid dysfunction, mainly occurring in the first six months post partum, was usually transient and included both destruction induced hyperthyroidism and hypothyroidism. The development of the syndrome was significantly related to smoking more than 20 cigarettes a day and the presence of thyroid microsomal autoantibodies at booking. Of the 16 women with a family history of thyroid disease in whom thyroid microsomal autoantibody activity was detectable at booking, 11 developed thyroid dysfunction. Age, parity, presence of goitre at presentation, duration of breast feeding, and the sex and birth weight of the infant were not associated with the development of postpartum thyroid dysfunction.
The mood changes experienced by women post partum may in part be associated with altered thyroid function during this time.
To determine the role of peak systolic velocity, end-diastolic velocity and resistance indices of both the right and left inferior thyroid arteries measured by color-flow Doppler ultrasonography for a differential diagnosis between gestational transient thyrotoxicosis and Graves' disease during pregnancy.
The right and left inferior thyroid artery-peak systolic velocity, end-diastolic velocity and resistance indices of 96 patients with thyrotoxicosis (41 with gestational transient thyrotoxicosis, 31 age-matched pregnant patients with Graves' disease and 24 age- and sex-matched non-pregnant patients with Graves' disease) and 25 age- and sex-matched healthy euthyroid subjects were assessed with color-flow Doppler ultrasonography.
The right and left inferior thyroid artery-peak systolic and end-diastolic velocities in patients with gestational transient thyrotoxicosis were found to be significantly lower than those of pregnant patients with Graves' disease and higher than those of healthy euthyroid subjects. However, the right and left inferior thyroid artery peak systolic and end-diastolic velocities in pregnant patients with Graves' disease were significantly lower than those of non-pregnant patients with Graves' disease. The right and left inferior thyroid artery peak systolic and end-diastolic velocities were positively correlated with TSH-receptor antibody levels. We found an overlap between the inferior thyroid artery-blood flow velocities in a considerable number of patients with gestational transient thyrotoxicosis and pregnant patients with Graves' disease.
This study suggests that the measurement of inferior thyroid artery-blood flow velocities with color-flow Doppler ultrasonography does not have sufficient sensitivity and specificity to be recommended as an initial diagnostic test for a differential diagnosis between gestational transient thyrotoxicosis and Graves' disease during pregnancy.
Gestational transient thyrotoxicosis; Graves' disease; Inferior thyroid artery; Color-flow Doppler ultrasonography; Pregnancy