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Context and Objectives: The Controlled Antenatal Thyroid Screening Study I (CATS-I) was a randomized controlled trial investigating the effects of levothyroxine therapy for suboptimal gestational thyroid function (SGTF), comparing outcomes in children of treated (SGTF-T) with untreated (SGTF-U) women during pregnancy. This follow-up study, CATS-II, reports the long-term effects on anthropometric, bone, and cardiometabolic outcomes in mothers and offspring and includes a group with normal gestational thyroid function (NGTF)., Design & Participants: 332 mothers (197 NGTF, 56 SGTF-U, 79 SGTF-T) aged 41.2±5.3 years (mean±SD) and 326 paired children assessed 9.3±1.0 years after birth for (i) body mass index (BMI); (ii) lean, fat, and bone mass by dual-energy X-ray absorptiometry; (iii) blood pressure, augmentation index, and aortic pulse-wave-velocity; and (iv) thyroid function, lipids, insulin, and adiponectin. The difference between group means was compared using linear regression., Results: Offspring's measurements were similar between groups. Although maternal BMI was similar between groups at CATS-I, after 9 years (at CATS-II) SGTF-U mothers showed higher BMI (median [interquartile ratio] 28.3 [24.6-32.6] kg/m2) compared with NGTF (25.8 [22.9-30.0] kg/m2; P = 0.029), driven by fat mass increase. At CATS-II SGTF-U mothers also had higher thyroid-stimulating hormone (TSH) values (2.45 [1.43-3.50] mU/L) than NGTF (1.54 [1.12-2.07] mU/L; P = 0.015), since 64% had never received levothyroxine. At CATS-II, SGTF-T mothers had BMI (25.8 [23.1-29.8] kg/m2, P = 0.672) and TSH (1.68 [0.89-2.96] mU/L; P = 0.474) values similar to NGTF mothers., Conclusions: Levothyroxine supplementation of women with SGTF did not affect long-term offspring anthropometric, bone, and cardiometabolic measurements. However, absence of treatment was associated with sustained long-term increase in BMI and fat mass in women with SGTF., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Thyroid hormones are essential for maintaining a pregnancy and optimal fetal neurological development. Pregnancy places additional demands on the thyroid axis and around 5% of women who have their thyroid function checked during gestation will have borderline low thyroid function (subclinical hypothyroidism or isolated hypothyroxinemia) identified. These borderline low thyroid states are associated with adverse obstetric and offspring outcomes. Whilst it is well established that overt hypothyroidism requires treatment with levothyroxine, it is less clear whether there is any benefit of treating borderline low thyroid states. This review summarizes the potential indications for treatment of subclinical hypothyroidism and isolated hypothyroxinemia., (Copyright © 2020. Published by Elsevier Ltd.)

Context & Objectives: The Controlled Antenatal Thyroid Screening (CATS) study was the first randomized controlled trial to investigate effects of treating suboptimal gestational thyroid function (SGTF) on child cognition. Since observational studies indicated that SGTF may also increase symptoms of autism and attention-deficit/hyperactivity disorder (ADHD), the CATS cohort was used to investigate whether treatment of mothers affected their children's behavior., Design & Participants: Mothers (N = 475) completed 3 questionnaires: the Strengths and Difficulties Questionnaire (SDQ), the Child ADHD Questionnaire, and the Social Communication Questionnaire (SCQ, used as a screen for autism spectrum disorder [ASD]), about their children (mean age 9.5 years). Group comparisons of total scores, numbers of children above clinical thresholds, and association between high maternal free thyroxine (FT4) (> 97.5th percentile of the UK cohort, "overtreated") and child neurodevelopment were reported., Results: There were no differences in total scores between normal gestational thyroid function (GTF) (n = 246), treated (n = 125), and untreated (n = 104) SGTF groups. More children of treated mothers scored above clinical thresholds, particularly the overtreated. Scores were above thresholds in SDQ conduct (22% vs 7%), SCQ total scores (7% vs 1%), and ADHD hyperactivity (17% vs 5%) when comparing overtreated (n = 40) and untreated (N = 100), respectively. We identified significantly higher mean scores for SDQ conduct (adjusted mean difference [AMD] 0.74; 95% confidence interval [CI], 0.021-1.431; P = 0.040, effect size 0.018) and ADHD hyperactivity (AMD 1.60, 95% CI, 0.361-2.633; P = 0.003, effect size 0.028) comparing overtreated with normal-GTF children., Conclusions: There was no overall association between SGTF and offspring ADHD, ASD, or behavior questionnaire scores. However, children of "overtreated" mothers displayed significantly more ADHD symptoms and behavioral difficulties than those of normal-GTF mothers. Thyroxine supplementation during pregnancy requires monitoring to avoid overtreatment., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context and Objective: The Controlled Antenatal Thyroid Screening (CATS) study investigated treatment of suboptimal gestational thyroid function (SGTF) on childhood cognition and found no difference in intelligence quotient (IQ) at 3 years between children of treated and untreated SGTF mothers. We have measured IQ in the same children at age 9.5 years and included children from normal gestational thyroid function (normal-GTF) mothers., Design, Setting, and Participants: One examiner, blinded to participant group, assessed children's IQ (Wechsler Intelligence Scale for Children, Fourth Edition UK), long-term memory, and motor function (Developmental Neuropsychological Assessment II) from children of 119 treated and 98 untreated SGTF mothers plus children of 232 mothers with normal-GTF. Logistic regression explored the odds and percentages of an IQ < 85 in the groups., Results: There was no difference in IQ < 85 between children of mothers with normal-GTF and combined SGTF, i.e., treated and untreated (fully adjusted odds ratio [OR] = 1.15 [95% confidence interval (CI) 0.52, 2.51]; P = 0.731). Furthermore, there was no significant effect of treatment [untreated OR = 1.33 (95% CI 0.53, 3.34); treated OR = 0.75 (95% CI 0.27, 2.06) P = 0.576]. IQ < 85 was 6.03% in normal-GTF, 7.56% in treated, and 11.22% in untreated groups. Analyses accounting for treated-SGTF women with free thyroxine > 97.5th percentile of the entire CATS-I cohort revealed no significant effect on a child's IQ < 85 in CATS-II. IQ at age 3 predicted IQ at age 9.5 (P < 0.0001) and accounted for 45% of the variation., Conclusions: Maternal thyroxine during pregnancy did not improve child cognition at age 9.5 years. Our findings confirmed CATS-I and suggest that the lack of treatment effect may be a result of the similar proportion of IQ < 85 in children of women with normal-GTF and SGTF.

Background: Thyroid autoimmunity, especially Graves' disease or hypothyroidism with positive autoantibodies (TRAb) to the thyrotropin receptor (TSHR), occurs in 30–40% of patients with relapsing multiple sclerosis following treatment with alemtuzumab (ALTZ). ALTZ therapy therefore provides a unique opportunity to study the evolution of TRAb prior to clinical presentation. TRAb can stimulate (TSAb), block (TBAb), or not affect ("neutral") the TSHR function, causing hyperthyroidism, hypothyroidism, or euthyroidism, respectively. Methods: A longitudinal retrospective analysis was conducted of TRAb bioactivity over a period of nine years in 45 multiple sclerosis patients receiving ALTZ using available stored serum. Of these 45 patients, 31 developed thyroid dysfunction (TD) and 14 remained euthyroid despite being followed for a minimum of five years (NO-TD). The presence of TRAb was evaluated at standardized time points: (i) before ALTZ, (ii) latest time available following ALTZ and before TD onset, and (iii) following ALTZ during/after TD onset. Serum TRAb were detected by published in-house assays (ihTRAb): flow cytometry detecting any TSHR-binding TRAb, and luciferase bioassays detecting TSAb/TBAb bioactivity. Purified immunoglobulin G was used to verify TSAb/TBAb in selected hypothyroid cases. Standard clinical automated measurements of TRAb, antithyroid peroxidase autoantibodies (TPOAb), thyrotropin, free thyroxine, and free triiodothyronine were also collected. Results: Before ALTZ, combined ihTRAb (positive with flow cytometry and/or luciferase bioassay) but not automated TRAb were present in 5/16 (31.2%) TD versus 0/14 (0%) NO-TD (p = 0.017). Detectable ihTRAb preceded TD development in 9/28 (32.1%) and by a median of 1.2 years (range 28 days–7.3 years). Combination testing of ihTRAb and TPOAb at baseline predicted 20% of subsequent cases of hyperthyroidism and 83% of hypothyroidism. Conclusions: Evidence is presented that TRAb measured with custom-made assays can be detected prior to any change in thyroid function in up to a third of cases of ALTZ-related TD. Furthermore, the presence of ihTRAb prior to ALTZ treatment was strongly predictive of subsequent TD. The findings suggest that a period of affinity maturation of TRAb may precede clinical disease onset in some cases. Combined testing of TPOAb and ihTRAb may increase the ability to predict those who will develop TD following ALTZ. [ABSTRACT FROM AUTHOR]

Background Children whose mothers had low thyroid hormone levels during pregnancy have been reported to have decreased cognitive function. The reported research is part of the follow-on study of the Controlled Antenatal Thyroid Screening Study (CATS I), a randomised controlled trial which investigated the impact of treated vs. untreated low thyroid hormone level in women during pregnancy with the primary outcome being the child's IQ at age 3. No significant differences in IQ were found between the treated and untreated groups. These children are now aged between 7 and 10 years and aspects of their cognitive functioning including their IQ are being reassessed as part of CATS II. Methods/Design Cognitive assessments generate an IQ score and further tests administered will investigate long term memory function and motor coordination. The aim is to complete the assessments with 40% of the children born to mothers either in the treated or untreated low thyroid hormone groups (n = 120 per group). Also children born to mothers who had normal thyroid functioning during CATS I are being assessed for the first time (n = 240) to provide a comparison. Assessments are conducted either in the research facility or the participant's home. Discussion The study is designed to assess the cognitive functioning of children born to mothers with low thyroid hormone levels and normal thyroid functioning during pregnancy. This is the largest study of its type and also is distinguishable in its longitudinal design. The research has the potential to have a significant impact on public health policy in the UK; universal screening of thyroid hormone levels in pregnancy may be the recommendation. [ABSTRACT FROM AUTHOR]