Clin Chem Lab Med 2014; 52(9): 1305–1311
Frank A. Quinn, Miguel A. Reyes-Mendez, Lisa Nicholson, Lourdes Puerto Compean and Miriam Lugo Tavera*
Thyroid function and thyroid autoimmunity in apparently healthy pregnant and non-pregnant Mexican women Abstract Background: Thyroid disorders are common in women of reproductive age, and thyroid dysfunction during pregnancy has been associated with adverse outcomes for mother and child. Thyroid function and thyroid function tests (TFTs) can be influenced by a variety of factors, such as ethnicity, the presence of autoimmune thyroid disease (AITD), dietary iodine intake, pregnancy, and methodological differences. However, no large-scale studies have been published which examine TFTs and prevalence of AITD in Mexican pregnant women and women of reproductive age. Methods: TFTs and thyroid autoantibody testing were performed on 660 pregnant and 104 non-pregnant women from Mérida, Yucatán, Mexico. After removal of thyroid autoantibody positive individuals and women with thyroid stimulating hormone (TSH) > 4.94 mIU/L, reference intervals were calculated for TFT for non-pregnant women and pregnant women by trimester. Results: Anti-thyroidperoxidase antibodies (TPO-Ab) and/or anti-thyroglobulin antibodies (Tg-Ab) were positive in 14.4% and 13.5% of non-pregnant and pregnant women, respectively. TSH values were significantly higher in women who were positive for TPO-Ab and co-positive for TPO-Ab and Tg-Ab. TSH values were also significantly higher in Tg-Ab positive pregnant women. Other TFTs were not significantly different based on antibody status. Using antibody negative women, reference intervals were determined for TFTs in pregnant (gestational age-specific) and non-pregnant women. *Corresponding author: Miriam Lugo Tavera, Clínica de Mérida S.A. de C.V., Mérida, Mexico, E-mail: [email protected] Frank A. Quinn: Abbott Diagnostics, Abbott Laboratories, Abbott Park, IL, USA Miguel A. Reyes-Mendez: Abbott Diagnostics, Abbott Laboratories de México, México D. F., México Lisa Nicholson: Health Policy Center, School of Public Health, University of Illinois at Chicago, Chicago, IL, USA Lourdes Puerto Compean: Clínica de Mérida S.A. de C.V., Mérida, Mexico
Conclusions: Laboratory evidence of AITD is common in this population of Mexican pregnant and non-pregnant women. TFT results and reference intervals are influenced by pregnancy and thyroid autoimmunity. For optimal interpretation of TFT results, gestational age-specific reference intervals established using a local patient population should be used. Keywords: autoimmune thyroid disease; Mexico; pre gnancy; thyroid function. DOI 10.1515/cclm-2014-0350 Received February 18, 2014; accepted April 1, 2014; previously published online April 29, 2014
Introduction Thyroid disorders are common in pregnant women, however, they often go unrecognized and undertreated [1–3]. During pregnancy, at least 2%–3% of women are affected by thyroid dysfunction, and approximately 10% have laboratory evidence of thyroid autoimmunity (TAI), despite being clinically and biochemically euthyroid [4]. Proper thyroid function during pregnancy is critical because maternal thyroid dysfunction, including the presence of thyroid autoantibodies, has been associated with numerous adverse outcomes (e.g., increased risk of miscarriage, preterm birth, impaired neurological development of the child, maternal postpartum thyroid disease, etc.) for both the mother and developing child [1, 2]. Thyroid hormones play an important role in fetal development, particularly during the first trimester, when the fetus is entirely dependent on the mother for thyroid hormones [1]. Pregnancy places increased demands on the maternal thyroid, and if the mother has occult or undertreated thyroid disease, TAI, or sub-optimal iodine nutrition, maternal thyroid function during pregnancy can be compromised [1, 2]. For these reasons, it is important to understand maternal thyroid status either pre-conception, or early during the pregnancy, especially in women
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1306 Quinn et al.: Thyroid function in Mexican women already being treated for thyroid disease or those with known risk factors, such as a personal or family history of thyroid disease, presence of thyroid autoantibodies or other autoimmune disease, a history of head or neck irradiation, and age > 30 years old [2, 4]. Clinical diagnosis of thyroid disease during pregnancy presents special challenges, as many of the signs and symptoms of thyroid dysfunction are non-specific, may not be present at all until disease is well advanced, or may be attributed to the pregnancy itself [5]. In this context, laboratory testing assumes even greater importance in assessing maternal thyroid function [5, 6]. However, physiological changes associated with pregnancy can complicate the interpretation of maternal thyroid function tests (TFT) [1, 6]. It is well established in the literature that gestational age-specific reference intervals are needed to allow proper interpretation of TFT results during pregnancy [6–10]. It is also known that thyroid function and TAI can be influenced by genetic and dietary factors and that TFT results can be method-specific [6–10]. Due to these variables, population and method-specific TFT reference intervals can aide interpretation of TFT results [6–10]. Optimally, reference intervals for laboratory tests are best established using patient specimens representative of the population served by the laboratory [11]. However, it is often not practical for clinical laboratories to establish local reference intervals for all tests they perform, and many clinical laboratories use reference intervals reported in the literature or provided by the assay manufacturer, which may or may not be appropriate for the local patient population. There are very little published data on thyroid function, prevalence of autoimmune thyroid disease (AITD), and population-specific reference intervals in Mexican women. The objectives of our study were to determine the prevalence of laboratory evidence for AITD in pregnant and non-pregnant Mexican women, determine TFT reference intervals in thyroid autoantibody negative non-pregnant women, determine gestational age-specific reference intervals for TFT in thyroid autoantibody negative women, and compare the prevalence of TAI and TFT reference intervals in pregnant and non-pregnant women.
Materials and methods The study was performed on 660 de-identified surplus fresh serum samples from ambulatory pregnant women at local outpatient clinics (Mérida, Yucatán) who had laboratory testing performed as part of their routine antenatal care, and 104 samples from ambulatory nonpregnant women of approximately the same age at outpatient clinics who were having laboratory testing as part of routine care. Sample
collection and testing for the study took place from August 2010 to July 2011. All women had no personal or family history of thyroid disease, no other endocrine disorders, no history of goiter or neck irradiation, and were not using any medications except nutritional supplements. For pregnant women, patients with known fetal genetic abnormality or multiple gestations were excluded, and gestational age was calculated using the last menstrual period (LMP). Smoking status was not assessed. Each sample was tested once for thyroid stimulating hormone (TSH), free thyroxine (FT4), total thyroxine (TT4), free tri- iodothyronine (FT3), total tri-iodothyronine (TT3), anti-thyroidperoxidase antibodies (TPO-Ab), and anti-thyroglobulin antibodies (Tg-Ab). Assay testing was performed by chemiluminescent immunoassay on the Abbott ARCHITECT analyzer (Abbott Laboratories, Abbott Park, IL, USA) according to manufacturer’s instructions. The principles of this instrument system and performance characteristics for these assays have been previously described [12–15]. Manufacturer’s cut-off values for Anti-TPO (
Frank A. Quinn, Miguel A. Reyes-Mendez, Lisa Nicholson, Lourdes Puerto Compean and Miriam Lugo Tavera*
Thyroid function and thyroid autoimmunity in apparently healthy pregnant and non-pregnant Mexican women Abstract Background: Thyroid disorders are common in women of reproductive age, and thyroid dysfunction during pregnancy has been associated with adverse outcomes for mother and child. Thyroid function and thyroid function tests (TFTs) can be influenced by a variety of factors, such as ethnicity, the presence of autoimmune thyroid disease (AITD), dietary iodine intake, pregnancy, and methodological differences. However, no large-scale studies have been published which examine TFTs and prevalence of AITD in Mexican pregnant women and women of reproductive age. Methods: TFTs and thyroid autoantibody testing were performed on 660 pregnant and 104 non-pregnant women from Mérida, Yucatán, Mexico. After removal of thyroid autoantibody positive individuals and women with thyroid stimulating hormone (TSH) > 4.94 mIU/L, reference intervals were calculated for TFT for non-pregnant women and pregnant women by trimester. Results: Anti-thyroidperoxidase antibodies (TPO-Ab) and/or anti-thyroglobulin antibodies (Tg-Ab) were positive in 14.4% and 13.5% of non-pregnant and pregnant women, respectively. TSH values were significantly higher in women who were positive for TPO-Ab and co-positive for TPO-Ab and Tg-Ab. TSH values were also significantly higher in Tg-Ab positive pregnant women. Other TFTs were not significantly different based on antibody status. Using antibody negative women, reference intervals were determined for TFTs in pregnant (gestational age-specific) and non-pregnant women. *Corresponding author: Miriam Lugo Tavera, Clínica de Mérida S.A. de C.V., Mérida, Mexico, E-mail: [email protected] Frank A. Quinn: Abbott Diagnostics, Abbott Laboratories, Abbott Park, IL, USA Miguel A. Reyes-Mendez: Abbott Diagnostics, Abbott Laboratories de México, México D. F., México Lisa Nicholson: Health Policy Center, School of Public Health, University of Illinois at Chicago, Chicago, IL, USA Lourdes Puerto Compean: Clínica de Mérida S.A. de C.V., Mérida, Mexico
Conclusions: Laboratory evidence of AITD is common in this population of Mexican pregnant and non-pregnant women. TFT results and reference intervals are influenced by pregnancy and thyroid autoimmunity. For optimal interpretation of TFT results, gestational age-specific reference intervals established using a local patient population should be used. Keywords: autoimmune thyroid disease; Mexico; pre gnancy; thyroid function. DOI 10.1515/cclm-2014-0350 Received February 18, 2014; accepted April 1, 2014; previously published online April 29, 2014
Introduction Thyroid disorders are common in pregnant women, however, they often go unrecognized and undertreated [1–3]. During pregnancy, at least 2%–3% of women are affected by thyroid dysfunction, and approximately 10% have laboratory evidence of thyroid autoimmunity (TAI), despite being clinically and biochemically euthyroid [4]. Proper thyroid function during pregnancy is critical because maternal thyroid dysfunction, including the presence of thyroid autoantibodies, has been associated with numerous adverse outcomes (e.g., increased risk of miscarriage, preterm birth, impaired neurological development of the child, maternal postpartum thyroid disease, etc.) for both the mother and developing child [1, 2]. Thyroid hormones play an important role in fetal development, particularly during the first trimester, when the fetus is entirely dependent on the mother for thyroid hormones [1]. Pregnancy places increased demands on the maternal thyroid, and if the mother has occult or undertreated thyroid disease, TAI, or sub-optimal iodine nutrition, maternal thyroid function during pregnancy can be compromised [1, 2]. For these reasons, it is important to understand maternal thyroid status either pre-conception, or early during the pregnancy, especially in women
Brought to you by | Karolinska Institute Authenticated Download Date | 5/30/15 9:32 AM
1306 Quinn et al.: Thyroid function in Mexican women already being treated for thyroid disease or those with known risk factors, such as a personal or family history of thyroid disease, presence of thyroid autoantibodies or other autoimmune disease, a history of head or neck irradiation, and age > 30 years old [2, 4]. Clinical diagnosis of thyroid disease during pregnancy presents special challenges, as many of the signs and symptoms of thyroid dysfunction are non-specific, may not be present at all until disease is well advanced, or may be attributed to the pregnancy itself [5]. In this context, laboratory testing assumes even greater importance in assessing maternal thyroid function [5, 6]. However, physiological changes associated with pregnancy can complicate the interpretation of maternal thyroid function tests (TFT) [1, 6]. It is well established in the literature that gestational age-specific reference intervals are needed to allow proper interpretation of TFT results during pregnancy [6–10]. It is also known that thyroid function and TAI can be influenced by genetic and dietary factors and that TFT results can be method-specific [6–10]. Due to these variables, population and method-specific TFT reference intervals can aide interpretation of TFT results [6–10]. Optimally, reference intervals for laboratory tests are best established using patient specimens representative of the population served by the laboratory [11]. However, it is often not practical for clinical laboratories to establish local reference intervals for all tests they perform, and many clinical laboratories use reference intervals reported in the literature or provided by the assay manufacturer, which may or may not be appropriate for the local patient population. There are very little published data on thyroid function, prevalence of autoimmune thyroid disease (AITD), and population-specific reference intervals in Mexican women. The objectives of our study were to determine the prevalence of laboratory evidence for AITD in pregnant and non-pregnant Mexican women, determine TFT reference intervals in thyroid autoantibody negative non-pregnant women, determine gestational age-specific reference intervals for TFT in thyroid autoantibody negative women, and compare the prevalence of TAI and TFT reference intervals in pregnant and non-pregnant women.
Materials and methods The study was performed on 660 de-identified surplus fresh serum samples from ambulatory pregnant women at local outpatient clinics (Mérida, Yucatán) who had laboratory testing performed as part of their routine antenatal care, and 104 samples from ambulatory nonpregnant women of approximately the same age at outpatient clinics who were having laboratory testing as part of routine care. Sample
collection and testing for the study took place from August 2010 to July 2011. All women had no personal or family history of thyroid disease, no other endocrine disorders, no history of goiter or neck irradiation, and were not using any medications except nutritional supplements. For pregnant women, patients with known fetal genetic abnormality or multiple gestations were excluded, and gestational age was calculated using the last menstrual period (LMP). Smoking status was not assessed. Each sample was tested once for thyroid stimulating hormone (TSH), free thyroxine (FT4), total thyroxine (TT4), free tri- iodothyronine (FT3), total tri-iodothyronine (TT3), anti-thyroidperoxidase antibodies (TPO-Ab), and anti-thyroglobulin antibodies (Tg-Ab). Assay testing was performed by chemiluminescent immunoassay on the Abbott ARCHITECT analyzer (Abbott Laboratories, Abbott Park, IL, USA) according to manufacturer’s instructions. The principles of this instrument system and performance characteristics for these assays have been previously described [12–15]. Manufacturer’s cut-off values for Anti-TPO (
