Association of Maternal Iodine Status With Child IQ: A Meta-Analysis of Individual Participant Data.

Context: Although the consequences of severe iodine deficiency are beyond doubt, the effects of mild to moderate iodine deficiency in pregnancy on child neurodevelopment are less well established.

Objective: To study the association between maternal iodine status during pregnancy and child IQ and identify vulnerable time windows of exposure to suboptimal iodine availability.

Design: Meta-analysis of individual participant data from three prospective population-based birth cohorts: Generation R (Netherlands), INMA (Spain), and ALSPAC (United Kingdom); pregnant women were enrolled between 2002 and 2006, 2003 and 2008, and 1990 and 1992, respectively.

Human chorionic gonadotropin and risk of pre-eclampsia: prospective population-based cohort study.

Objectives: Abnormal placentation in early pregnancy may play a role in the pathogenesis of pre-eclampsia. Human chorionic gonadotropin (hCG) regulates placental development and angiogenesis and may affect the ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) in the serum. The aims of this study were to investigate the association of total hCG with the risk of pre-eclampsia and to examine the potential effect of pro- and anti-angiogenic factors on this association.

Insight Into Molecular Determinants of T3 vs T4 Recognition From Mutations in Thyroid Hormone Receptor α and β.

Context: The two major forms of circulating thyroid hormones (THs) are T3 and T4. T3 is regarded as the biologically active hormone because it binds to TH receptors (TRs) with greater affinity than T4. However, it is currently unclear what structural mechanisms underlie this difference in affinity.

Association of Maternal Thyroid Function and Thyroidal Response to Human Chorionic Gonadotropin with Early Fetal Growth.

Background: Early pregnancy fetal growth is a relevant determinant of pregnancy outcome and child health during later life. During the first trimester, fetal growth depends on the transfer of maternal thyroid hormone, and optimal thyroid hormone availability is ensured via stimulation of the maternal thyroid by human chorionic gonadotropin (hCG). The potent stimulatory effects of hCG on gestational thyroid function and its clinical relevance with early fetal growth remain unknown and need to be examined.

Basic Fibroblast Growth Factor Induces Adipogenesis in Orbital Fibroblasts: Implications for the Pathogenesis of Graves' Orbitopathy.

Background: Basic fibroblast growth factor (bFGF) has been implicated in the pathogenesis of Graves' orbitopathy (GO). It stimulates several processes, including hyaluronan synthesis, involved in orbital tissue volume expansion and may act synergistically with platelet-derived growth factor (PDGF)-BB. PDGF-BB is known to stimulate adipogenesis in orbital fibroblasts, but the effect of bFGF on adipogenesis in orbital fibroblasts is so far unknown.

Functional Analysis of Genetic Variation in the SECIS Element of Thyroid Hormone Activating Type 2 Deiodinase.

Context: Thyroid hormone is important for normal brain development. The type 2 deiodinase (D2) controls thyroid hormone action in the brain by activating T4 to T3. The enzymatic activity of D2 depends on the incorporation of selenocysteine for which the selenocysteine-insertion sequence (SECIS) element located in the 3' untranslated region is indispensable.

Role of Leucine 341 in Thyroid Hormone Receptor Beta Revealed by a Novel Mutation Causing Thyroid Hormone Resistance.

Leucine 341 has been predicted from crystal structure as an important residue for thyroid hormone receptor beta (TRβ) function, but this has never been confirmed in functional studies. Here, a novel p.L341V mutation as a cause of resistance to TRβ is described, suggesting an important role for L341 in TRβ function.

Mutated Thyroid Hormone Transporter OATP1C1 Associates with Severe Brain Hypometabolism and Juvenile Neurodegeneration.

Background: Thyroid hormones (TH) are essential for brain development and function. The TH transporters monocarboxylate transporter 8 (MCT8) and organic anion transporter1 C1 (OATP1C1) facilitate the transport of TH across the blood-brain barrier and into glia and neuronal cells in the brain. Loss of MCT8 function causes Allan-Herndon-Dudley syndrome (AHDS, OMIM 300523) characterized by severe intellectual and motor disability due to cerebral hypothyroidism.

Iodine Intake is Associated with Thyroid Function in Mild to Moderately Iodine Deficient Pregnant Women.

Background: Studies indicate that mild to moderate iodine deficiency in pregnancy may have a long-term negative impact on child neurodevelopment. These effects are likely mediated via changes in maternal thyroid function, since iodine is essential for the production of thyroid hormones. However, the impact of iodine availability on thyroid function during pregnancy and on thyroid function reference ranges are understudied.

The Association of Thyroid Function With Bone Density During Childhood.

Context: Although the skeleton is a well-known thyroid hormone target organ, very little data are available on the association of thyroid function with bone outcomes during childhood.

Objective: To study the association of thyroid function with bone mass during childhood.

Design, Setting, And Participants: Population-based prospective cohort including 4204 children with TSH and free T4 (FT4) measured at the age of 6 years.

The Association of Maternal Thyroid Autoimmunity During Pregnancy With Child IQ.

Context: Thyroperoxidase antibody (TPOAb) positivity is a major risk factor for gestational thyroid dysfunction. During the first 18 to 20 weeks of pregnancy, high concentrations of human chorionic gonadotropin (hCG) stimulate the thyroid to ensure adequate thyroid hormone availability for the developing fetus. However, TPOAb-positive women have an impaired thyroidal response to hCG stimulation.

Reference Ranges and Determinants of Thyroid Function During Early Pregnancy: The SELMA Study.

Context: Establishing reference ranges as well as identifying and quantifying the determinants of thyroid function during pregnancy is important for proper clinical interpretation and optimizing research efforts. However, such data are sparse, specifically for triiodothyronine measurements, and most studies do not take into account thyroid antibodies or human chorionic gonadotropin.

Objective: To determine reference ranges and to identify/quantify determinants of TSH, free T4 (FT4), free triiodothyronine (FT3), total T4 (TT4), and total triiodothyronine (TT3).

Comparing the Prognostic Value of the Eighth Edition of the American Joint Committee on Cancer/Tumor Node Metastasis Staging System Between Papillary and Follicular Thyroid Cancer.

Background: Recently, the eighth edition of the American Joint Committee on Cancer (AJCC)/tumor node metastasis (TNM) staging system for differentiated thyroid cancer (DTC) was published. Studies evaluating this new edition have so far only comprised patients with papillary thyroid cancer (PTC) or made no distinction between PTC and follicular thyroid cancer (FTC). Therefore, this study evaluated the prognostic value of the eighth edition of the AJCC/TNM staging system in a European population with DTC, focusing on potential differences between PTC and FTC.

Thyroid Function in Early Pregnancy, Child IQ, and Autistic Traits: A Meta-Analysis of Individual Participant Data.

Context: Low maternal free T4 (FT4) has been associated with poor child neurodevelopment in some single-center studies. Evidence remains scarce for the potential adverse effects of high FT4 and whether associations differ in countries with different iodine status.

Objective: To assess the association of maternal thyroid function in early pregnancy with child neurodevelopment in countries with a different iodine status.

Thyroid Hormones and Cardiovascular Function and Diseases.

Thyroid hormone (TH) receptors are present in the myocardium and vascular tissue, and minor alterations in TH concentration can affect cardiovascular (CV) physiology. The potential mechanisms that link CV disease with thyroid dysfunction are endothelial dysfunction, changes in blood pressure, myocardial systolic and diastolic dysfunction, and dyslipidemia. In addition, cardiac disease itself may lead to alterations in TH concentrations (notably, low triiodothyronine syndrome) that are associated with higher morbidity and mortality.

Serum microRNA profiles in athyroid patients on and off levothyroxine therapy.

Background: Levothyroxine replacement treatment in hypothyroidism is unable to restore physiological thyroxine and triiodothyronine concentrations in serum and tissues completely. Normal serum thyroid stimulating hormone (TSH) concentrations reflect only pituitary euthyroidism and, therefore, novel biomarkers representing tissue-specific thyroid state are needed. MicroRNAs (miRNAs), small non-coding regulatory RNAs, exhibit tissue-specific expression patterns and can be detectable in serum.

Thyroid function and atrial fibrillation: Is there a mediating role for epicardial adipose tissue?

Background: The underlying mechanism of the association between thyroid function and atrial fibrillation (AF) is poorly understood, but epicardial adipose tissue (EAT) could be a promising mediator.

Methods: In the 1995 participants (mean age 64.5 years) from the population-based Rotterdam Study, we measured thyroid function (thyroid-stimulating hormone, free thyroxine [FT4]) and performed computed tomography to quantify EAT volumes.

Effects of Thyrotropin on Peripheral Thyroid Hormone Metabolism and Serum Lipids.

Background: Subclinical hypothyroidism is associated with dyslipidemia and atherosclerosis. Whether these effects are in part mediated via direct effects of thyrotropin (TSH) on peripheral thyroid hormone (TH) metabolism and/or concentrations of serum lipids is not clear.

Objective: This study examined whether TSH has direct effects on peripheral TH metabolism and serum lipids.

Genetic screening of regulatory regions of pituitary transcription factors in patients with idiopathic pituitary hormone deficiencies.

Purpose: Mutation frequencies of PROP1, POU1F1 and HESX1 in patients with combined pituitary hormone deficiencies (CPHD) vary substantially between populations. They are low in sporadic CPHD patients in Western Europe. However, most clinicians still routinely send DNA of their CPHD patients for genetic screening of these pituitary transcription factors.