Reference Intervals of Thyroid Function Tests Assessed by Immunoassay and Mass Spectrometry in Healthy Pregnant Women Living in Catalonia

Background: Recent guidelines recommend establishing a local reference interval (RI) for thyroid function. We aimed to establish trimester-specific RIs for thyrotropin (TSH) and free thyroxine (FT4) in a cohort of healthy pregnant women in Catalonia (Spain). Methods: A prospective observational study was conducted with 332 healthy pregnant women, from the first trimester (1T) to delivery. TSH was measured using an Architect® immunoassay (Abbott) and FT4 by two immunoassays, Architect® (Abbott) and Cobas® (Roche), in the three trimesters. FT4 was also measured by liquid chromatography mass spectrometry (LC/MS/MS) in the 1T. Results: TSH (µUI/mL) increased throughout pregnancy (1T: 0.03–3.78; 2T: 0.51–3.53; 3T: 0.50–4.32; p < 0.0001) and FT4 (pmol/L) progressively decreased (Architect® 1T: 10.42–15.96; 2T: 8.37–12.74; 3T: 8.24–12.49; p < 0.0001; and Cobas®: 1T: 11.46–19.05; 2T: 9.65–14.67; 3T: 8.88–14.54; p < 0.0067). The FT4 RI during 1T determined LC/MS/MS was 8.75–18.27. Despite the 1T FT4 results measured by LC/MS/MS and with the two immunoassays being significantly correlated, the results obtained by the three methods were found to be non-interchangeable. Conclusions: We established trimester-specific RIs for TSH and for FT4 with immunoassays in our population. We also validated the 1T FT4 using LC/MS/MS to confirm the results of FT4 lower than the 2.5th percentile or higher than the 97.5th percentile.

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Gestation specific reference intervals for thyroid function tests in pregnancy

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2015-0569 ◽

2016 ◽

Vol 54 (8) ◽

Cited By ~ 6

Author(s):

Süleyman Akarsu ◽

Filiz Akbiyik ◽

Eda Karaismailoglu ◽

Zeliha Gunnur Dikmen

Keyword(s):

Pregnant Women ◽

Thyroid Function ◽

First Trimester ◽

Reference Intervals ◽

Specific Reference ◽

Thyroid Function Tests ◽

Second Trimester ◽

Third Trimester ◽

The Third ◽

Function Tests

AbstractThyroid function tests are frequently assessed during pregnancy to evaluate thyroid dysfunction or to monitor pre-existing thyroid disease. However, using non-pregnant reference intervals can lead to misclassification. International guidelines recommended that institutions should calculate their own pregnancy-specific reference intervals for free thyroxine (FT4), free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH). The objective of this study is to establish gestation-specific reference intervals (GRIs) for thyroid function tests in pregnant Turkish women and to compare these with the age-matched non-pregnant women.Serum samples were collected from 220 non-pregnant women (age: 18–48), and 2460 pregnant women (age: 18–45) with 945 (39%) in the first trimester, 1120 (45%) in the second trimester, and 395 (16%) in the third trimester. TSH, FT4 and FT3 were measured using the Abbott Architect i2000SR analyzer.GRIs of TSH, FT4 and FT3 for first trimester pregnancies were 0.49–2.33 mIU/L, 10.30–18.11 pmol/L and 3.80–5.81 pmol/L, respectively. GRIs for second trimester pregnancies were 0.51–3.44 mIU/L, 10.30–18.15 pmol/L and 3.69–5.90 pmol/L. GRIs for third trimester pregnancies were 0.58–4.31 mIU/L, 10.30–17.89 pmol/L and 3.67–5.81 pmol/L. GRIs for TSH, FT4 and FT3 were different from non-pregnant normal reference intervals.TSH levels showed an increasing trend from the first trimester to the third trimester, whereas both FT4 and FT3 levels were uniform throughout gestation. GRIs may help in the diagnosis and appropriate management of thyroid dysfunction during pregnancy which will prevent both maternal and fetal complications.

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Reference Intervals of Thyroid Function Tests in First Trimester Vietnamese Pregnant Women

Clinical Laboratory ◽

10.7754/clin.lab.2020.200415 ◽

2020 ◽

Vol 66 (12/2020) ◽

Author(s):

Luong Ly ◽

Nhu Vuong ◽

Minh Chau ◽

Hanh Phan ◽

Quan Pham ◽

...

Keyword(s):

Pregnant Women ◽

Thyroid Function ◽

First Trimester ◽

Reference Intervals ◽

Thyroid Function Tests ◽

Function Tests

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Evaluation of Thyroid Function in Pregnant Women Using Automated Immunoassays

Clinical Chemistry ◽

10.1093/clinchem/hvab009 ◽

2021 ◽

Author(s):

K Aaron Geno ◽

Matthew S Reed ◽

Mark A Cervinski ◽

Robert D Nerenz

Keyword(s):

Pregnant Women ◽

Equilibrium Dialysis ◽

Reference Interval ◽

First Trimester ◽

Reference Intervals ◽

Free Thyroxine ◽

Specific Reference ◽

Childbearing Age ◽

Thyroid Autoantibody ◽

The Impact

Abstract Introduction Automated free thyroxine (FT4) immunoassays are widely available, but professional guidelines discourage their use in pregnant women due to theoretical under-recoveries attributed to increased thyroid hormone binding capacity and instead advocate the use of total T4 (TT4) or free thyroxine index (FTI). The impact of this recommendation on the classification of thyroid status in apparently euthyroid pregnant patients was evaluated. Methods After excluding specimens with thyroid autoantibody concentrations above reference limits, thyroid-stimulating hormone (TSH), FT4, TT4, and T-uptake were measured on the Roche Cobas® platform in remnant clinical specimens from at least 147 nonpregnant women of childbearing age and pregnant women at each trimester. Split-sample comparisons of FT4 as measured by the Cobas and equilibrium dialysis were performed. Results FT4 decreased with advancing gestational age by both immunoassay and equilibrium dialysis. TSH declined during the first trimester, remained constant in the second, and increased throughout the third, peaking just before delivery. Interpretation of TT4 concentrations using 1.5-times the nonpregnant reference interval classified 13.6% of first trimester specimens below the lower reference limit despite TSH concentrations within trimester-specific reference intervals. Five FTI results from 480 pregnant individuals (about 1.0%) fell outside the manufacturer’s reference interval. Conclusions Indirect FT4 immunoassay results interpreted in the context of trimester-specific reference intervals provide a practical and viable alternative to TT4 or FTI. Declining FT4 and increasing TSH concentrations near term suggest that declining FT4 is not an analytical artifact but represents a true physiological change in preparation for labor and delivery.

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Moderate Iodine Deficiency Is Common in Pregnancy but Does Not Alter Maternal and Neonatal Thyroid Function Tests

Frontiers in Endocrinology ◽

10.3389/fendo.2020.523319 ◽

2020 ◽

Vol 11 ◽

Author(s):

Tal Schiller ◽

Arnon Agmon ◽

Viviana Ostrovsky ◽

Gabi Shefer ◽

Hilla Knobler ◽

...

Keyword(s):

Pregnant Women ◽

Thyroid Function ◽

Iodine Deficiency ◽

Urinary Iodine ◽

Iodine Content ◽

First Trimester ◽

Thyroid Function Tests ◽

Neonatal Thyroid Function ◽

Iodine Deficiency In Pregnancy ◽

In Pregnancy

IntroductionAn Israeli national survey found that 85% of pregnant women had urinary iodine content (UIC) levels below the adequacy range (<150 µg/L). Widespread desalinated water usage and no national fortification plan are possible causes. Studies assessing relationships between iodine status and maternal and neonatal thyroid function provided varying results. Our aims were to determine whether iodine deficiency was associated with altered maternal or neonatal thyroid function and the factors leading to iodine deficiency.MethodsA cross-sectional study including 100 healthy women without prior thyroid disease, in their first trimester of a singleton pregnancy were recruited from an HMO clinic in central Israel. The women were followed from their first trimester. All women completed a 24-h dietary recall and life habits questionnaires. We tested for UIC, maternal and neonatal thyroid function, maternal autoantibodies, and neonatal outcomes.ResultsMedian UIC in our cohort was 49 µg/L [25%–75% interquartile range (IQR) 16-91.5 µg/L], with 84% below adequacy range. No correlation was found between iodine deficiency and maternal or neonatal thyroid function which remained within normal ranges. Antibody status did not differ, but thyroglobulin levels were significantly higher in iodine insufficient subjects. UIC was higher in women consuming an iodine containing supplement. There was no association between UIC and dietary iodine content or water source.ConclusionsModerate iodine deficiency is common in our healthy pregnant women population. Our data imply that moderate iodine deficiency in pregnancy seem sufficient to maintain normal maternal and neonatal thyroid function.

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Evaluation of maternal thyroid function during pregnancy: the importance of using gestational age-specific reference intervals

Acta Endocrinologica ◽

10.1530/eje-07-0249 ◽

2007 ◽

Vol 157 (4) ◽

pp. 509-514 ◽

Cited By ~ 152

Author(s):

Rt Stricker ◽

M Echenard ◽

R Eberhart ◽

M-C Chevailler ◽

V Perez ◽

...

Keyword(s):

Pregnant Women ◽

Thyroid Function ◽

Gestational Age ◽

Thyroid Disease ◽

Thyroid Dysfunction ◽

Reference Intervals ◽

Specific Reference ◽

Thyroid Function Tests ◽

Laboratory Evidence ◽

Maternal Thyroid

Background: Maternal thyroid dysfunction has been associated with a variety of adverse pregnancy outcomes. Laboratory measurement of thyroid function plays an important role in the assessment of maternal thyroid health. However, occult thyroid disease and physiologic changes associated with pregnancy can complicate interpretation of maternal thyroid function tests (TFTs). Objective and methods: To 1) establish the prevalence of laboratory evidence for autoimmune thyroid disease (AITD) in pregnant women; 2) establish gestational age-specific reference intervals for TFTs in women without AITD; and 3) examine the influence of reference intervals on the interpretation of TFT in pregnant women. Serum samples were collected from 2272 pregnant women, and TFT performed. Gestational age-specific reference intervals were determined in women without AITD, and then compared with the non-pregnant assay-specific reference intervals for interpretation of testing results. Results: Thyroid peroxidase antibodies (TPO-Ab) and thyroglobulin antibodies (Tg-Ab) were positive in 10.4 and 15.7% of women respectively. TPO-Ab level was related to maternal age, but TPO-Ab status, Tg-Ab status, and Tg-Ab level were not. Women with TSH > 3.0 mIU/l were significantly more likely to be TPO-Ab positive. Gestational age-specific reference intervals for TFT were significantly different from non-pregnant normal reference intervals. Interpretation of TFT in pregnant women using non-pregnant reference intervals could potentially result in misclassification of a significant percentage of results (range: 5.6–18.3%). Conclusion: Laboratory evidence for thyroid dysfunction was common in this population of pregnant women. Accurate classification of TFT in pregnant women requires the use of gestational age-specific reference intervals.

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Maternal thyroid function test level during the first trimester of pregnancy at a center Yazd, Iran: A cross-sectional study

International Journal of Reproductive BioMedicine ◽

10.18502/ijrm.v19i3.8573 ◽

2021 ◽

Author(s):

Farahnaz Farzaneh ◽

Farzaneh Khastehfekr

Keyword(s):

Thyroid Hormones ◽

Thyroid Function ◽

First Trimester ◽

Cross Sectional Study ◽

Reference Intervals ◽

Reference Ranges ◽

Thyroid Function Tests ◽

Sectional Study ◽

Cross Sectional ◽

First Trimester Of Pregnancy

Background: Thyroid dysfunction is associated with negative pregnancy outcomes. There is a lack of reliable information on thyroid hormones in Iranian pregnant women, especially in Yazd. Objective: To determine the safe thyroid hormone levels in women of Yazd and also the first trimester-specific reference ranges for serum thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3). Materials and Methods: In this cross-sectional study, the serum of 1,148 women in the first trimester of pregnancy was analyzed. Thyroid function tests (TSH, T4, T3) were measured through radioimmunoassay (RIA) [immunoradiometric (IRMA) for TSH]. The study was conducted in Yazd, from September 2018 to November 2019. Reference intervals were defined as the 5th, 50th, and 95th percentiles. Results: The mean age of the participants was 28.78 (± 5.86 yr) (range: 15-45 yr). The thyroid hormones reference intervals in the first trimester were TSH (0.2-3.8 mIU/l), T4 (7.45-12.75, μg/dl), and T3 (100-217 ng/dl). Conclusion: The results of the present study determined a local thyroid function measurement in the first trimester of pregnancy at a center of Yazd, Iran. This could facilitate the decision-making of maternal TSH level during the first trimester of pregnancy. Key words: First pregnancy trimester, Thyrotropin, Thyroxine, Triiodothyronine.

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Trimester- and Assay-Specific Thyroid Reference Intervals for Pregnant Women in China

International Journal of Endocrinology ◽

10.1155/2016/3754213 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 7

Author(s):

Jinfang Xing ◽

Enwu Yuan ◽

Jing Li ◽

Yuchao Zhang ◽

Xiangying Meng ◽

...

Keyword(s):

Thyroid Function ◽

Chinese Women ◽

Reference Interval ◽

First Trimester ◽

Cross Sectional Study ◽

Reference Intervals ◽

Thyroid Stimulating Hormone ◽

Thyroid Peroxidase ◽

American Thyroid Association ◽

Cross Sectional

Objective. The guidelines of the American Thyroid Association (ATA) recommend an upper limit reference interval (RI) of thyroid stimulating hormone (TSH) of 2.5 mIU/L in the first trimester of pregnancy and 3.0 mIU/L in subsequent trimesters, but some reported ranges in China are significantly higher. Our study aimed to establish trimester- and assay-specific RIs for thyroid hormones in normal pregnant Chinese women. Methods. In this cross-sectional study, 2540 women with normal pregnancies (first trimester, n=398; second trimester, n=797; third trimester, n=1345) and 237 healthy nonpregnant control subjects were recruited. Serum TSH, free thyroxin (FT4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) levels were determined by automated chemiluminescence with an Immulite 2000 system (Siemens, Erlangen, Germany). After outliers were excluded, the 2.5–97.5th percentiles were used to define the RIs. Results. The RIs of thyroid function in the first, second, and third trimesters of pregnancy and in nonpregnant controls were 0.07–3.96, 0.27–4.53, 0.48–5.40, and 0.69–5.78 mIU/L for TSH and 9.16–18.12, 8.67–16.21, 7.80–13.90, and 8.24–16.61 pmol/L for FT4, respectively. Conclusion. The trimester- and assay-specific RIs of thyroid function during pregnancy differed between trimesters, which suggests that it is advisable to detect and avoid misclassification of thyroid dysfunction during pregnancy for women in Henan, China.

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Trimester-Specific Reference Ranges for Thyroid Hormones in Iranian Pregnant Women

Journal of Thyroid Research ◽

10.1155/2013/651517 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 11

Author(s):

Ladan Mehran ◽

Atieh Amouzegar ◽

Hossein Delshad ◽

Sahar Askari ◽

Mehdi Hedayati ◽

...

Keyword(s):

Thyroid Hormones ◽

Pregnant Women ◽

Thyroid Function ◽

Final Analysis ◽

Reference Intervals ◽

Specific Reference ◽

Reference Ranges ◽

Thyroid Function Tests ◽

Thyroid Disorder ◽

Function Tests

Background. Due to many physiological changes during pregnancy, interpretation of thyroid function tests needs trimester-specific reference intervals for a specific population. There is no normative data documented for thyroid hormones on healthy pregnant women in Iran. The present survey was conducted to determine trimester-specific reference ranges for serum TSH, thyroxine (TT4), and triiodothyronine (TT3).Methods. The serum of 215 cases was analyzed for measurement of thyroid function tests by immunoassay method of which 152 iodine-sufficient pregnant women without thyroid autoantibodies and history of thyroid disorder or goiter were selected for final analysis. Reference intervals were defined as 5th and 95th percentiles.Results. Reference intervals in the first, second, and third trimesters were as follows: TSH (0.2–3.9, 0.5–4.1, and 0.6–4.1 mIU/l), TT4 (8.2–18.5, 10.1–20.6, and 9–19.4 μg/dl), and TT3 (137.8–278.3, 154.8–327.6, and 137–323.6 ng/dl), respectively. No correlation was found between TSH and TT4 or TT3. Significant correlation was found between TT4 and TT3 in all trimesters (r=0.35,P<0.001).Conclusion. The reference intervals of thyroid function tests in pregnant women differ among trimesters. Applying trimester-specific reference ranges of thyroid hormones is warranted in order to avoid misclassification of thyroid dysfunction during pregnancy.

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Reference Intervals for Thyroid Hormones During the First Trimester of Gestation: A Report from an Area with a Sufficient Iodine Level

Hormone and Metabolic Research ◽

10.1055/a-0855-7128 ◽

2019 ◽

Vol 51 (03) ◽

pp. 165-171

Author(s):

Maryam Kianpour ◽

Ashraf Aminorroaya ◽

Massoud Amini ◽

Awat Feizi ◽

Mohsen Janghorbani ◽

...

Keyword(s):

Pregnant Women ◽

First Trimester ◽

Reference Intervals ◽

Specific Reference ◽

Thyroid Peroxidase ◽

Urinary Iodine Concentration ◽

Reference Ranges ◽

Thyroid Function Tests ◽

Iodine Level ◽

First Trimester Of Pregnancy

AbstractThe physiological changes during pregnancy modulate the endocrine system. Therefore, both the American and the European thyroid associations recommend the use of local trimester-specific reference intervals. The purpose of this study was to establish the first trimester reference intervals for thyroid function tests in the central area of Iran. We examined 436 pregnant women in their first trimester of pregnancy, and 444 non-pregnant women in a cross sectional study. Serum levels of thyroid stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), thyroid peroxidase antibody, urinary iodine concentration (UIC), and thyroid volume were measured for all subjects. The first trimester-specific reference intervals (2.5th–97.5th percentile) were determined for 185 pregnant women and 256 non-pregnant women with negative TPOAb, adequate iodine level (UIC≥150 μg/l in pregnant and UIC≥100 μg/l in non-pregnant women), and normal thyroid examination. We calculated multiples of the median (MoM) for TFTs to normalize the obtained data. The first trimester-specific reference intervals of serum TSH, FT4, and FT3 for pregnant women were 0.20–4.60 mIU/l, 9.0–18.02 pmol/l, and 3.40–5.64 pmol/l, respectively, while the corresponding figures for non-pregnant women were 0.59–5.60 mIU/l, 9.52–19.30 pmol/l, and 3.70–5.55 pmol/l, respectively. The first and 99th percentile MoM of TSH in pregnant women in their first-trimester was 0.06–4.62. The local normal reference ranges for the first trimester of pregnancy in central region of Iran were different from the ranges suggested by the ATA.

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