Trimester-specific Reference Intervals Research Articles

The American Thyroid Association and American Association of Clinical Endocrinologists Hyperthyroidism and Other Causes of Thyrotoxicosis Guidelines: Viewpoints from Japan and Korea

ThyroidVol. 21, No. 6 EditorialsThe American Thyroid Association and American Association of Clinical Endocrinologists Hyperthyroidism and Other Causes of Thyrotoxicosis Guidelines: Viewpoints from Japan and KoreaShunichi Yamashita, Nobuyuki Amino, and Young Kee ShongShunichi YamashitaMember of the council of the Asia & Oceania Thyroid Association (AOTA).Director, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.Search for more papers by this author, Nobuyuki AminoAOTA advisory member to the World Thyroid Foundation.Kuma Hospital, Kobe, Japan.Search for more papers by this author, and Young Kee ShongMember of the council of the Asia & Oceania Thyroid Association (AOTA).Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.Search for more papers by this authorPublished Online:10 Jun 2011https://doi.org/10.1089/thy.2011.2106.ed1AboutSectionsView articleView Full TextPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited ByEvaluation of analytic and clinical performance of two immunoassays for detecting thyroid‐stimulating receptor antibody in the diagnosis of Graves’ disease9 November 2021 | Journal of Clinical Laboratory Analysis, Vol. 35, No. 12Aeromedical Decision Making for Military Aircrew with Graves’ DiseaseAerospace Medicine and Human Performance, Vol. 92, No. 12Graves’ Disease4 May 2021Hyperthyreose8 December 2021Safety of long-term antithyroid drug treatment? A systematic review27 May 2019 | Journal of Endocrinological Investigation, Vol. 42, No. 11Is Hyperthyroidism Diagnosed and Treated Appropriately in the United States?Advances in Surgery, Vol. 53When should antithyroid drug therapy to reduce the relapse rate of hyperthyroidism in Graves’ disease be discontinued?24 June 2019 | Endocrine, Vol. 65, No. 2Change of surgical strategy for Graves’ disease from subtotal thyroidectomy to total thyroidectomy: a single institutional experienceEndocrine Journal, Vol. 66, No. 2Determining patient selection tool and response predictor for outpatient 30 mCi radioiodine ablation dose in non-metastatic differentiated thyroid carcinoma: a Japanese perspectiveEndocrine Journal, Vol. 65, No. 3Long-Term Antithyroid Drug Treatment: A Systematic Review and Meta-Analysis Fereidoun Azizi and Ramin Malboosbaf1 October 2017 | Thyroid, Vol. 27, No. 10Emphasis on the early diagnosis of antithyroid drug-induced agranulocytosis: retrospective analysis over 16 years at one Chinese center24 February 2017 | Journal of Endocrinological Investigation, Vol. 40, No. 7Comparative Effectiveness of Treatment Choices for Graves' Hyperthyroidism: A Historical Cohort Study Vishnu Sundaresh, Juan P. Brito, Prabin Thapa, Rebecca S. Bahn, and Marius N. Stan1 April 2017 | Thyroid, Vol. 27, No. 4A SURVEY OF CLINICAL PRACTICE PATTERNS IN MANAGEMENT OF GRAVES DISEASE IN THE MIDDLE EAST AND NORTH AFRICAEndocrine Practice, Vol. 23, No. 3HyperthyroidismThe Lancet, Vol. 388, No. 10047Punica granatum (pomegranate) peel extract exerts potent antitumor and anti-metastasis activity in thyroid cancer1 January 2016 | RSC Advances, Vol. 6, No. 87A 2013 European survey of clinical practice patterns in the management of Graves' disease9 January 2015 | Clinical Endocrinology, Vol. 84, No. 1Antithyroid Arthritis Syndrome: A Case Report and Review of the LiteratureInternal Medicine, Vol. 55, No. 24Thyroidectomy in Patients with Graves’ DiseaseEstablishment of Trimester-Specific Reference Intervals for Thyroid Hormones in Korean Pregnant WomenAnnals of Laboratory Medicine, Vol. 35, No. 2A Case of Marine-Lenhart Syndrome with a Negative TSH Receptor Antibody Titer Successfully Treated with a Fixed, Low Dose of I 131Case Reports in Endocrinology, Vol. 2014Diagnosis and management of Graves disease: a global overview15 October 2013 | Nature Reviews Endocrinology, Vol. 9, No. 12Dual Thyroid Ectopia with Graves’ Disease: a Case Report and a Review of the Literature9 August 2012 | Nuclear Medicine and Molecular Imaging, Vol. 46, No. 4Subclinical Thyroid Disease: Time to Enter the Age of Evidence-Based Medicine Bernard Goichot and Simon H. Pearce1 August 2012 | Thyroid, Vol. 22, No. 8Changes in the thyroid function of Graves^|^rsquo; disease patients treated by subtotal thyroidectomyEndocrine Journal, Vol. 59, No. 12 Volume 21Issue 6Jun 2011 InformationCopyright 2011, Mary Ann Liebert, Inc.To cite this article:Shunichi Yamashita, Nobuyuki Amino, and Young Kee Shong.The American Thyroid Association and American Association of Clinical Endocrinologists Hyperthyroidism and Other Causes of Thyrotoxicosis Guidelines: Viewpoints from Japan and Korea.Thyroid.Jun 2011.577-580.http://doi.org/10.1089/thy.2011.2106.ed1Published in Volume: 21 Issue 6: June 10, 2011PDF download

Management of hyperthyroidism during pregnancy and lactation

Poorly treated or untreated maternal overt hyperthyroidism may affect pregnancy outcome. Fetal and neonatal hypo- or hyper-thyroidism and neonatal central hypothyroidism may complicate health issues during intrauterine and neonatal periods. To review articles related to appropriate management of hyperthyroidism during pregnancy and lactation. A literature review was performed using MEDLINE with the terms 'hyperthyroidism and pregnancy', 'antithyroid drugs and pregnancy', 'radioiodine and pregnancy', 'hyperthyroidism and lactation', and 'antithyroid drugs and lactation', both separately and in conjunction with the terms 'fetus' and 'maternal.' Antithyroid drugs are the main therapy for maternal hyperthyroidism. Both methimazole (MMI) and propylthiouracil (PTU) may be used during pregnancy; however, PTU is preferred in the first trimester and should be replaced by MMI after this trimester. Choanal and esophageal atresia of fetus in MMI-treated and maternal hepatotoxicity in PTU-treated pregnancies are of utmost concern. Maintaining free thyroxine concentration in the upper one-third of each trimester-specific reference interval denotes success of therapy. MMI is the mainstay of the treatment of post partum hyperthyroidism, in particular during lactation. Management of hyperthyroidism during pregnancy and lactation requires special considerations and should be carefully implemented to avoid any adverse effects on the mother, fetus, and neonate.

An effective analysis of screening strategies for thyroid disorders during early pregnancy

Objective To use the first trimester-specific reference intervals of thyroid-related hormones to explore the prevalence of thyroid dysfunction during early pregnancy and to analyze effectiveness of different screening strategies. Methods In this study 2 899 pregnant women were enrolled during the first trimester of gestation. TSH, FT4, FT3, and thyroid peroxidase antibody （TPOAb） were measured and thyroid disorders of pregnant women were diagnosed based on the first trimester-specific reference intervals. Results The prevalence of hypothyroidism was significantly higher in the high-risk group than in the non-high risk group （ 16.3% vs 5.3%,RR = 3.1,95% CI 2.4-4.0, P〈0.01 ）. TPOAb （ RR = 4.7, 95 % CI 3.6-6.0, P〈0.01 ）, and personal history of thyroid diseases （ RR=3.2, 95% CI 1.9-5.4, P〈0.01 ） increased the risk of hypothyroidism. The prevalence of hyperthyroidism was higher in the high-risk group （3.1% vs 1.4%, P = 0. 006, RR = 2.2, 95% CI 1.2-3.9, P=0.006）. TPOAb （RR=2.6, 95%CI 1.3-5.0, P=0.007）, and presence of personal history of thyroid diseases（ RR=4.7, 95% CI 1.7-12.5, P=0.006） also increased the risk of hyperthyroidism. 56.7% women with hypothyroidism and 64. 7% women with hyperthyroidism were in the non-high risk group. Conclusion We recommend that screening all pregnant women for thyroid disorders in the first trimester with TSH, FT4, and TPOAb is more effective than the case-finding approach. Key words: First trimester pregnancy ; Screening; Thyroid dysfunction ; Risk factors

The prevalence of thyroid disorders during early pregnancy in China: the benefits of universal screening in the first trimester of pregnancy

Maternal thyroid disorders during early pregnancy can influence pregnancy outcome and fetal development. The recent Endocrine Society Clinical Practice Guideline recommends a case-finding approach in which pregnant women who are at high risk for developing thyroid disease are tested. The purpose of this study was to use the first trimester-specific reference intervals of thyroid-related hormones to explore the prevalence of thyroid dysfunction during early pregnancy and to analyze effectiveness of different screening strategies. A multicenter cohort study. A total of 2899 pregnant women were enrolled in this study during their first trimester of gestation. Levels of TSH, free thyroxine, free triiodothyronine, and thyroid peroxidase antibodies (TPOAb) were measured and thyroid disorders of pregnant women were diagnosed based on the first trimester-specific reference intervals. The prevalence of hypothyroidism was significantly higher in the high-risk group than in the non-high-risk group (10.9 vs 7.0%, χ²=7.1, P = 0.008). The prevalence of hyperthyroidism was not significantly different between the high-risk group and the non-high-risk group (2.7 vs 1.6%, χ²=2.27, P=0.13). Elevated levels of TPOAb and a personal history of thyroid disease increased the risk of thyroid dysfunction. A case-finding strategy for screening thyroid function in the high-risk group would miss about 81.6% pregnant women with hypothyroidism and 80.4% pregnant women with hyperthyroidism.

Valoración de la función tiroidea durante la gestación: intervalos de referencia de tirotropina y tiroxina no unida a proteína durante el primer trimestre

Background and objectives The physiological changes that occur during pregnancy affect the physiology of the thyroid gland. Consequently, interpretation of thyroid function markers during pregnancy requires trimester-specific reference intervals. The aims of our study were to: 1) establish first-trimester reference intervals for biochemical markers of thyroid function [thyroid-stimulating hormone (TSH) and free thyroxine (T4)] and 2) to establish the prevalence of autoimmune thyroid disease in pregnant women resident in Cartagena (Murcia, Spain). Patients and method A total of 441 women between weeks 11 and 13 of pregnancy were included in this study. A blood sample was extracted from all women to measure TSH, free T4 and antithyroid antibodies. Reference intervals for TSH and free T4 were determined in 400 pregnant women without autoimmune thyroid disease or known thyroid disease. Results Autoimmune thyroid disease was detected in 23 pregnant women (5.2%) who showed TSH levels higher than those in pregnant women without thyroid autoimmunity. First-trimester reference intervals were as follows: TSH: 0.130–3.710 mUI/L; free T4: 0.89–1.50 ng/dL. These reference intervals differed from the non-pregnant reference intervals used in our laboratory. Conclusions The reference intervals established are useful to evaluate thyroid function in women between 11 and 13 weeks of pregnancy. Interpretation of thyroid function requires intervals established in a reference population without autoimmune thyroid disease and with the methodology usually used to analyze these markers.

Therapeutic Drug Monitoring During Pregnancy and Lactation: Thyroid Function Assessment in Pregnancy—Challenges and Solutions

The diagnosis and monitoring of thyroid disease necessitates the knowledge of thyroid pathophysiology and of the technical limitations of current thyroid-related biochemical tests. Thyroid disease diagnosis and monitoring are further complicated during pregnancy and lactation, due to pregnancy-related changes in thyroid hormone metabolism. Dramatic changes that occur in thyroxine and triiodothyronine ranges during pregnancy pose challenges for hypothyroid gravidas. Very early in pregnancy, levothyroxine replacement needs to be increased. Moreover, increases in thyroid hormone replacement need to be conducted individually and on a timely basis. For reasons that are still not entirely clear, although dependent in part on changes in thyroxine binding, free thyroxine (FT4) levels decrease as pregnancy progresses necessitating the use of trimester-specific reference intervals for appropriate replacement. Thyroxine binding protein levels vary by hormonal status, inheritance, and disease states and are higher in pregnancy; hence, FT4 assays became popular because they measure the unbound hormone. However, current FT4 immunoassays are estimate tests that do not reliably measure FT4 and are known to be sensitive to alterations in binding proteins and therefore are method-specific. The need to reliably identify hypothyroxinemic pregnant patients, especially in the first trimester, is of prime importance for early fetal brain development before the fetal thyroid functions. This article addresses 1) the current limitations of laboratory-free thyroxine immunoassay methodologies and especially during pregnancy; 2) trimester-specific reference intervals for thyroid function tests; and 3) the study of levothyroxine pharmacokinetics in pregnant and nonpregnant women.

Free thyroxine reference interval in each trimester of pregnancy determined with the Roche Modular E-170 electrochemiluminescent immunoassay

Objective To determine using a simplified study design trimester-specific FT4 reference intervals in pregnancy with the Roche Modular immunoassay in routine use. Design and methods Surplus blood from 300 women in each trimester, drawn at documented times in the gestation, and from 40 age-matched nonpregnant women were assayed for FT4, thyroid stimulating hormone (TSH) and antithyroid peroxidase autoantibody (anti-TPO). Results After excluding women positive for anti-TPO and with abnormal TSH, reference intervals were calculated as 12.5–19.1 pmol/L (nonpregnant group), 11–19 pmol/L (first trimester), 9.7–17.5 pmol/L (second trimester) and 8.1–15.3 pmol/L (third trimester). 3rd trimester FT4 was significantly lower than that of the second trimester ( p < 0.001) which, in turn, was lower than that of the first trimester ( p < 0.001). FT4 reference intervals in pregnancy were significantly lower than in the nonpregnant women ( p < 0.002). Conclusions The observed trimester-specific FT4 reference intervals progressively decline with advancing gestation and differ significantly from one another.

Gestation-Specific Thyroxine and Thyroid Stimulating Hormone Levels in the United States and Worldwide

Euthyroid women experience dramatic changes in the demand for thyroid hormone production as early as the first trimester of pregnancy. These changes are important for fetal neurodevelopment and organ development as well as maternal health and succesful full term pregnancy. Therefore, gestation-specific reference intervals assist in appropriate clinical management of thyroid disease in pregnancy to ensure maternal and fetal health. To determine trimester-specific levels of serum thyroxine (T4) and thyroid stimulating hormone (TSH) in the U.S. population based on the National Health and Nutrition Survey III and compare these with published trimester-specific T4 and TSH means and medians obtained in other countries worldwide. Trimester-specific means and medians for T4 and TSH were determined for the U.S. population based on the National Health and Nutrition Survey III database (1988-1994). These were compared with trimester-specific means and medians of other countries in the published literature. Mean serum T4 levels for the U.S. population were 141.35, 152.95, and 142.65 nmol/L in the three trimesters, respectively, whereas mean serum TSH levels were 0.91, 1.03, and 1.32 mIU/L. Gestation-specific mean T4 and TSH levels for the representative U.S. population are well within the trimester-specific reference intervals. T4 and TSH measured during pregnancy in longitudinal and cross-sectional studies of populations worldwide demonstrate that, in some populations, T4 and TSH levels are outside the normal trimester-specific reference intervals.

Tandem Mass Spectrometry Improves the Accuracy of Free Thyroxine Measurements During Pregnancy

Pregnancy is a time of rapidly changing demands on the thyroid axis, and knowledge of thyroid hormone levels, especially during the first trimester, is important for ensuring maternal and fetal health. The thyroid hormone assays currently in use become more inaccurate at extremes of binding protein concentrations and when heterophilic antibodies are present. Pregnancy is characterized by both these conditions, making accurate determination of free thyroid hormone levels by conventional direct analog immunoassay methods difficult. The objective of this study was to characterize the performance of a novel tandem mass spectrometric assay for free thyroxine during the physiologic conditions of pregnancy. Healthy women without a history of thyroid abnormalities were recruited from the obstetrics and gynecology and endocrinology clinics of a university medical center and their thyroid status was monitored. Free thyroxine levels were assessed by both immunoassay and tandem mass spectrometry during the course of their pregnancy. Serum thyrotropin levels were also measured. The distributions of free thyroid concentrations obtained by the two assays were compared. The tandem mass spectrometry and immunoassay values did not correlate well with each other. However, tandem mass spectrometry values correlated well with the current gold standard equilibrium dialysis values. Moreover, the good agreement between equilibrium dialysis and tandem mass spectrometry was maintained across all weeks of gestation. We conclude that tandem mass spectrometry has a superior performance to immunoassay for the measurement of free thyroxine during pregnancy. Furthermore, it is ideally suited to generating trimester-specific reference intervals for free thyroxine levels. Future studies will determine if it is a better assay to use in most clinical circumstances.

Thyrotrophin and free thyroxine trimester-specific reference intervals in a mixed ethnic pregnant population in the United Arab Emirates

Background Physiological alterations in the homeostatic control of thyroid hormones cause changes in thyroid function tests in pregnant women. A lack of method, trimester and population-specific reference intervals for free thyroxine (FT4) and thyrotrophin (TSH) makes interpretation of FT4 and TSH levels in pregnancy difficult. We established trimester-specific reference intervals for TSH and FT4 in a mixed ethnic population of pregnant women attending two antenatal clinics in the United Arab Emirates. Methods TSH and FT4 result from 1140 women with uncomplicated singleton pregnancy were available. The 95% reference intervals were determined for TSH and FT4 for each trimester for Arab women from the United Arab Emirates and other Arab countries and Asian women. Results Suppressed TSH levels in the first trimester recovered to non-pregnant levels in the third trimester. There was a significant difference in TSH levels between trimesters 1 and 2, and 2 and 3 ( p < 0.0005). There was no significant difference in the TSH levels between the various ethnic groups. Mean FT4 levels decreased with each progressive trimester in all groups. There were significant differences in FT4 levels between all three trimesters ( p < 0.005), especially between the first and second trimesters. FT4 differed significantly between UAE nationals and Asians in the first and second trimesters ( p < 0.005). Conclusions In general, the findings were in keeping with earlier reports. Use of trimester-specific reference intervals should help in the appropriate interpretation of thyroid hormone results in the mixed UAE population.

Steroid hormone levels in pregnancy and 1 year postpartum using isotope dilution tandem mass spectrometry

To establish normal, trimester-specific reference intervals for serum 17beta-estradiol, progesterone (P), 17alpha-hydroxyprogesterone, cortisol, 11-deoxycortisol, androstenedione, DHEA, and DHEAS, measured simultaneously using isotope dilution tandem mass spectrometry. Sequential cohort study. Healthy women undergoing a normal pregnancy (age, 25-38 years; mean, 30 years) attending a prenatal well clinic at gestation weeks 12, 22, and 32 and approximately 1 year postpartum. Trimester-specific reference intervals of endogenous steroid hormones analyzed using an isotope dilution tandem mass spectrometer equipped with an atmospheric pressure photoionization source with deuterium-labeled internal standards. Serum estradiol, P, 17alpha-hydroxyprogesterone, and 11-deoxycortisol increased throughout pregnancy; cortisol increased up to the second trimester and then remained steady, while androstenedione increased by 80 percent by gestation week 12, then remained constant. Serum DHEA-S decreased by 50% by the third trimester. Trimester-specific reference intervals are reported for eight serum steroids. The ratios of individual serum hormone concentrations during pregnancy relative to their 1-year postpartum concentrations illustrate the expected normal trends of changes in hormone concentrations during pregnancy.

Trimester-specific reference intervals for thyroxine and triiodothyronine in pregnancy in iodine-sufficient women using isotope dilution tandem mass spectrometry and immunoassays

Background Accurate assessment of the pregnant woman's thyroid status is critical, for both the initiation of thyroid hormone therapy and for the adjustment of thyroid hormone dose in those already receiving thyroid hormone. Trimester-specific intervals are especially important during pregnancy when thyroid insufficiency may be associated with adverse obstetric outcome and fetal neurodevelopmental deficits. We defined pregnancy-specific reference intervals for thyroxine (T4) and 3,5,3'-triiodothyronine (T3). We used a novel isotope dilution tandem mass spectrometry (LC/MS/MS) method, and compare these to reference intervals obtained by immunoassays (IAs) performed on the same samples. Methods Concentrations of circulating T4 and T3 were measured simultaneously during first, second and third trimesters and postpartum in iodine-sufficient, healthy, singleton pregnancies using API-3000 LC/MS/MS with deuterium-labeled internal standard ( l-thyroxine-d 2). Immunoassays were conducted on the same samples (T4 Dade Behring RxL, T3 DPC-Immunolite). Results Linear regression is reported for method comparisons; for T4, the slope decreased from r=0.900 in nonpregnant women to 0.802–0.820 during pregnancy. For T3, correlations between LC/MS/MS and immunoassays were weaker in all cases ( r=0.407–0.574). Conclusion In this longitudinal study, we established trimester-specific reference intervals for T4 and T3 by LC/MS/MS and compare these to intervals obtained by immunoassays.