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Introduction: Cognitive impairment and reduced well-being are common manifestations of Graves' disease (GD). These symptoms are not only prevalent during the active phase of the disease but also often prevail for a long time after hyperthyroidism is considered cured. The pathogenic mechanisms involved in these brain-derived symptoms are currently unknown. The overall aim of the CogThy study is to identify the mechanism behind cognitive impairment to be able to recognise GD patients at risk., Methods and Analysis: The study is a longitudinal, single-centre, case-controlled study conducted in Göteborg, Sweden on premenopausal women with newly diagnosed GD. The subjects are examined: at referral, at inclusion and then every 3.25 months until 15 months. Examinations include: laboratory measurements; eye evaluation; neuropsychiatric and neuropsychological testing; structural MRI of the whole brain, orbits and medial temporal lobe structures; functional near-infrared spectroscopy of the cerebral prefrontal cortex and self-assessed quality of life questionnaires. The primary outcome measure is the change in medial temporal lobe structure volume. Secondary outcome measures include neuropsychological, neuropsychiatric, hormonal and autoantibody variables. The study opened for inclusion in September 2012 and close for inclusion in October 2019. It will provide novel information on the effect of GD on medial temporal lobe structures and cerebral cortex functionality as well as whether these changes are associated with cognitive and affective impairment, hormonal levels and/or autoantibody levels. It should lead to a broader understanding of the underlying pathogenesis and future treatment perspectives., Ethics and Dissemination: The study has been reviewed and approved by the Regional Ethical Review Board in Göteborg, Sweden. The results will be actively disseminated through peer-reviewed journals, national and international conference presentations and among patient organisations after an appropriate embargo time., Trial Registration Number: 44321 at the public project database for research and development in Västra Götaland County, Sweden (https://www.researchweb.org/is/vgr/project/44321)., Competing Interests: Competing interests: HNF has received lecture fees from Siemens Inc., AstraZeneca and Bristol-Myers Squibb., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Iodine is essential for normal brain development. Moderate and severe fetal iodine deficiency results in substantial to serious developmental delay in children. Mild iodine deficiency in pregnancy is associated with neurodevelopmental deficits in the offspring, but evidence from randomised trials is lacking. The aim of the Swedish Iodine in Pregnancy and Development in Children study is to determine the effect of daily supplementation with 150 µg iodine during pregnancy on the offspring's neuropsychological development up to 14 years of age., Methods and Analysis: Thyroid healthy pregnant women (n=1275: age range 18-40 years) at ≤12 weeks gestation will be randomly assigned to receive multivitamin supplements containing 150 µg iodine or non-iodine-containing multivitamin daily throughout pregnancy. As a primary outcome, IQ will be measured in the offspring at 7 years (Wechsler Intelligence Scale for Children-V). As secondary outcomes, IQ will be measured at 3.5 and 14 years, psychomotor development at 18 months and 7 years, and behaviour at 3.5, 7 and 14 years. Iodine status (urinary iodine concentration) will be measured during pregnancy and in the offspring at 3.5, 7 and 14 years. Thyroid function (thyroid hormones, thyroglobulin), and deiodinase type 2 polymorphisms will be measured during pregnancy and in the offspring at 7 and 14 years. Structural MRI or other relevant structural or functional brain imaging procedures will be performed in a subgroup of children at 7 and 14 years. Background and socioeconomic information will be collected at all follow-up times., Ethics and Dissemination: This study is approved by the Ethics Committee in Göteborg, Sweden (Diary numbers: 431-12 approved 18 June 2012 (pregnancy part) and 1089-16 approved 8 February 2017 (children follow-up)). According to Swedish regulations, dietary supplements are governed by the National Food Agency and not by the Medical Product Agency. Therefore, there is no requirement for a monitoring committee and the National Food Agency does not perform any audits of trial conduct. The trial will be conducted in accordance with the Declaration of Helsinki. The participating sites will be contacted regarding important protocol changes, both orally and in writing, and the trial registry database will be updated accordingly. Study results will be presented at relevant conferences, and submitted to peer-reviewed journals with open access in the fields of endocrinology, paediatrics and nutrition. After the appropriate embargo period, the results will be communicated to participants, healthcare professionals at the maternal healthcare centres, the public and other relevant groups, such as the national guideline group for thyroid and pregnancy and the National Food Agency., Trial Registration Number: NCT02378246; Pre-results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)