Evaluating the use of a two-step age-based cutoff for the UICC/AJCC TNM staging system in patients with papillary or follicular thyroid cancer.

Background: The joint Union International Contre le Cancer and American Joint Committee on Cancer (UICC/AJCC) Tumor, Node, Metastasis (TNM) staging system for differentiated thyroid cancer (DTC) involves a single age cutoff as a prognostic criterion. Because a single cutoff is a dichotomization of what might be a sliding scale, using multiple age cutoffs might result into a better stage definition. The aim of our study was to investigate if using a two-step age-based cutoff would improve the TNM staging system regarding disease-specific survival (DSS).

Impact of Thyroglobulin and Thyroglobulin Antibody Assay Performance on the Differential Classification of DTC Patients.

Context: Measurements of thyroglobulin (Tg) and Tg antibodies are crucial in the follow-up of treated differentiated thyroid cancer (DTC) patients. Interassay differences may significantly impact follow-up.

Objective: The aim of this multicenter study was to explore the impact of Tg and Tg antibody assay performance on the differential classification of DTC patients, as described in national and international guidelines.

Iodine supplementation: compliance and association with adverse obstetric and neonatal outcomes.

Objectives: Over 1.9 billion people worldwide are living in areas estimated to be iodine insufficient. Strategies for iodine supplementation include campaigns targeting vulnerable groups, such as women in pre-conception, pregnancy and lactation.

Association of Maternal Thyroid Function with Gestational Hypercholanemia.

High bile acid concentration is associated with adverse perinatal outcomes (i.e., stillbirth and preterm birth) and experimental studies indicate that thyroid hormone regulates bile acid metabolism, but this has not yet been translated to clinical data in pregnant women.

Functional Characterization of the Novel and Specific Thyroid Hormone Transporter SLC17A4.

A recent genome-wide association study identified the locus associated with circulating free thyroxine (T4) concentrations. Human SLC17A4, being widely expressed in the gastrointestinal tract, was characterized as a novel triiodothyronine (T3) and T4 transporter. However, apart from the cellular uptake of T3 and T4, transporter characteristics are currently unknown.

Structure-Guided Approach to Relieving Transcriptional Repression in Resistance to Thyroid Hormone α.

Mutations in thyroid hormone receptor α (TRα), a ligand-inducible transcription factor, cause resistance to thyroid hormone α (RTHα). This disorder is characterized by tissue-specific hormone refractoriness and hypothyroidism due to the inhibition of target gene expression by mutant TRα-corepressor complexes. Using biophysical approaches, we show that RTHα-associated TRα mutants devoid of ligand-dependent transcription activation function unexpectedly retain the ability to bind thyroid hormone.

Thyroid Function and the Risk of Alzheimer's Disease: A Mendelian Randomization Study.

Observational studies suggest an association between thyroid function and risk of dementia, but the causality and direction of these effects are unclear. We aim to test whether genetically predicted variation within the normal range of thyroid function and hypothyroidism is causally associated with the risk of Alzheimer's disease (AD). Mendelian randomization (MR) analyses using genetic instruments are associated with normal range thyrotropin (TSH) and free thyroxine (fT4) levels.

Change in Thyroid Hormone Metabolite Concentrations Across Different Thyroid States.

In contrast to the thyroid hormones (TH) 3,3',5-triiodothyronine (T3) and thyroxine (T4), current literature on thyroid hormone metabolite concentrations in the hypothyroid and hyperthyroid states is inconclusive. It is unknown how thyroidectomy affects thyroid hormone metabolite concentrations and if levothyroxine (LT4) replacement therapy after thyroidectomy restores thyroid hormone metabolite concentrations in those without a thyroid gland. The treatment of patients with differentiated thyroid cancer (DTC) covers the euthyroid, hypothyroid, and (subclinical) hyperthyroid states and therefore provides a unique model to answer this.

Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling.

Background: Observational studies suggest interconnections between thyroid status, metabolism, and risk of coronary artery disease (CAD), but causality remains to be proven. The present study aimed to investigate the potential causal relationship between thyroid status and cardiovascular disease and to characterize the metabolomic profile associated with thyroid status.

Methods: Multi-cohort two-sample Mendelian randomization (MR) was performed utilizing genome-wide significant variants as instruments for standardized thyrotropin (TSH) and free thyroxine (fT4) within the reference range.

Relationship between Blood Trihalomethane Concentrations and Serum Thyroid Function Measures in U.S. Adults.

Toxicological studies show that exposure to disinfection byproducts, including trihalomethanes (THMs), negatively affects thyroid function; however, few epidemiological studies have explored this link. This study included 2233 adults (ages ≥20 years) from the 2007-2008 National Health and Nutrition Examination Survey (NHANES) who were measured for blood THM concentrations [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), or bromoform (TBM)] and serum thyroid function biomarkers [thyroid-stimulating hormone, free thyroxine (FT4), total thyroxine (TT4), free triiodothyronine (FT3), total triiodothyronine (TT3), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb)]. Multivariable linear regression models showed positive associations between blood TCM, BDCM, and total THMs (the sum of all four THMs) concentrations and serum FT4, whereas inverse associations were found between blood DBCM and total brominated THM (Br-THM; the sum of BDCM, DBCM, and TBM) concentrations and serum TT3 (all < 0.

Thyroid Function in Adults with Prader-Willi Syndrome; a Cohort Study and Literature Review.

Prader-Willi syndrome (PWS) is a complex genetic syndrome combining hypotonia, hyperphagia, a PWS-specific neurocognitive phenotype, and pituitary hormone deficiencies, including hypothyroidism. The low muscle mass associated with PWS causes a low energy expenditure due to a low basal metabolic rate. Combined with increased energy intake due to hyperphagia, this results in a high risk of obesity and associated cardiovascular disease.

Association of Thyroid Dysfunction With Cognitive Function: An Individual Participant Data Analysis.

Importance: In clinical guidelines, overt and subclinical thyroid dysfunction are mentioned as causal and treatable factors for cognitive decline. However, the scientific literature on these associations shows inconsistent findings.

Objective: To assess cross-sectional and longitudinal associations of baseline thyroid dysfunction with cognitive function and dementia.

Association of phthalate exposure with thyroid function during pregnancy.

Background: The extent of thyroid disruptive effects of phthalates during pregnancy remains unclear.

Aim: To investigate the association of maternal urinary phthalates with markers of the thyroid system during early pregnancy.

Methods: Urinary concentrations of phthalate metabolites and serum concentrations of thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4) and free and total triiodothyronine (FT3 and TT3) were measured in pregnant women in early pregnancy in the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (2007-ongoing), a population-based prospective cohort.

Effects of Thyroid Function on Hemostasis, Coagulation, and Fibrinolysis: A Mendelian Randomization Study.

Untreated hypothyroidism is associated with acquired von Willebrand syndrome, and hyperthyroidism is associated with increased thrombosis risk. However, the causal effects of thyroid function on hemostasis, coagulation, and fibrinolysis are unknown. In a two-sample Mendelian randomization (MR) study with genome-wide association variants, we assessed causality of genetically predicted hypothyroidism ( = 134,641), normal-range thyrotropin (TSH;  = 54,288) and free thyroxine (fT4) ( = 49,269), hyperthyroidism ( = 51,823), and thyroid peroxidase antibody positivity ( = 25,821) on coagulation (activated partial thromboplastin time, von Willebrand factor [VWF], factor VIII [FVIII], prothrombin time, factor VII, fibrinogen) and fibrinolysis (D-dimer, tissue plasminogen activator [TPA], plasminogen activator inhibitor-1) from the CHARGE Hemostasis Consortium ( = 2583-120,246).

Virtual Reality Tailored to the Needs of Post-ICU Patients: A Safety and Immersiveness Study in Healthy Volunteers.

Objectives: ICU treatments frequently result in long-term psychologic impairments, negatively affecting quality of life. An effective treatment strategy is still lacking. The aim of this study was to describe and evaluate the safety and immersiveness of a newly designed ICU-specific virtual reality module.

Thyroid Function and Mood Disorders: A Mendelian Randomization Study.

Observational studies suggest that even minor variations in thyroid function are associated with the risk of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD). However, it is unknown whether these associations are causal or not. We used a Mendelian randomization (MR) approach to investigate causal effects of minor variations in thyrotropin (TSH) and free thyroxine (fT4) levels on MDD and BD risk.

Preferences of patients and clinicians for treatment of Graves' disease: a discrete choice experiment.

Objective: Treatment options for Graves' disease (GD) consist of antithyroid drugs (ATD), radioactive iodine (RAI) and total thyroidectomy (TT). Guidelines recommend to discuss these options with patients, taking into account patients' preferences. This study aims to evaluate and compare patients' and clinicians' preferences and the trade-offs made in choosing treatment.

Adaptive Thermogenesis Driving Catch-Up Fat Is Associated With Increased Muscle Type 3 and Decreased Hepatic Type 1 Iodothyronine Deiodinase Activities: A Functional and Proteomic Study.

Refeeding after caloric restriction induces weight regain and a disproportionate recovering of fat mass rather than lean mass (catch-up fat) that, in humans, associates with higher risks to develop chronic dysmetabolism. Studies in a well-established rat model of semistarvation-refeeding have reported that catch-up fat associates with hyperinsulinemia, glucose redistribution from skeletal muscle to white adipose tissue and suppressed adaptive thermogenesis sustaining a high efficiency for fat deposition. The skeletal muscle of catch-up fat animals exhibits reduced insulin-stimulated glucose utilization, mitochondrial dysfunction, delayed contraction-relaxation kinetics, increased proportion of slow fibers and altered local thyroid hormone metabolism, with suggestions of a role for iodothyronine deiodinases.

The Association of TSH and Thyroid Hormones With Lymphopenia in Bacterial Sepsis and COVID-19.

Context: Lymphopenia is a key feature of immune dysfunction in patients with bacterial sepsis and coronavirus disease 2019 (COVID-19) and is associated with poor clinical outcomes, but the cause is largely unknown. Severely ill patients may present with thyroid function abnormalities, so-called nonthyroidal illness syndrome, and several studies have linked thyrotropin (thyroid stimulating hormone, TSH) and the thyroid hormones thyroxine (T4) and 3,5,3'-triiodothyronine (T3) to homeostatic regulation and function of lymphocyte populations.

Objective: This work aimed to test the hypothesis that abnormal thyroid function correlates with lymphopenia in patients with severe infections.

Associations between Human Chorionic Gonadotropin, Maternal Free Thyroxine, and Gestational Diabetes Mellitus.

Human chorionic gonadotropin (hCG) is a marker of placental function, which also stimulates the maternal thyroid gland. Maternal thyroid function can be associated with the pathophysiology of gestational diabetes mellitus (GDM). We aimed to study whether there is an association of hCG concentrations in early pregnancy with GDM and whether it is mediated through maternal thyroid hormones.