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European Thyroid Journal Oct 2023With the widespread use of sensitive imaging techniques, which include neck visualization, a conspicuous number of thyroid nodules emerge and demand attention. Most...
With the widespread use of sensitive imaging techniques, which include neck visualization, a conspicuous number of thyroid nodules emerge and demand attention. Most lesions are benign, asymptomatic, and do not warrant treatment. In the case of cancer diagnosis, most are small, intrathyroidal and indolent neoplasms that can safely be managed conservatively. There is a pronounced need for more cost-effective, risk-adapted approaches to the management of this highly prevalent condition, taking the wishes of the patient into consideration. Thus, the present guidelines aim at providing a clinical practice guide for the initial workup and the subsequent management of adult individuals harboring thyroid nodules. Importantly, these guidelines are not intended to cover the management of thyroid malignancy. The manuscript and the specific recommendations were developed by reconciling the best available research evidence with the knowledge and clinical experience of the panelists and updating aspects of a number of previous European Thyroid Association guidelines.
Topics: Adult; Humans; Biopsy, Fine-Needle; Neck; Thyroid Neoplasms; Thyroid Nodule
PubMed: 37358008
DOI: 10.1530/ETJ-23-0067 -
JAMA Oct 2023Overt hyperthyroidism, defined as suppressed thyrotropin (previously thyroid-stimulating hormone) and high concentration of triiodothyronine (T3) and/or free thyroxine... (Review)
Review
IMPORTANCE
Overt hyperthyroidism, defined as suppressed thyrotropin (previously thyroid-stimulating hormone) and high concentration of triiodothyronine (T3) and/or free thyroxine (FT4), affects approximately 0.2% to 1.4% of people worldwide. Subclinical hyperthyroidism, defined as low concentrations of thyrotropin and normal concentrations of T3 and FT4, affects approximately 0.7% to 1.4% of people worldwide. Untreated hyperthyroidism can cause cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes. It may lead to unintentional weight loss and is associated with increased mortality.
OBSERVATIONS
The most common cause of hyperthyroidism is Graves disease, with a global prevalence of 2% in women and 0.5% in men. Other causes of hyperthyroidism and thyrotoxicosis include toxic nodules and the thyrotoxic phase of thyroiditis. Common symptoms of thyrotoxicosis include anxiety, insomnia, palpitations, unintentional weight loss, diarrhea, and heat intolerance. Patients with Graves disease may have a diffusely enlarged thyroid gland, stare, or exophthalmos on examination. Patients with toxic nodules (ie, in which thyroid nodules develop autonomous function) may have symptoms from local compression of structures in the neck by the thyroid gland, such as dysphagia, orthopnea, or voice changes. Etiology can typically be established based on clinical presentation, thyroid function tests, and thyrotropin-receptor antibody status. Thyroid scintigraphy is recommended if thyroid nodules are present or the etiology is unclear. Thyrotoxicosis from thyroiditis may be observed if symptomatic or treated with supportive care. Treatment options for overt hyperthyroidism from autonomous thyroid nodules or Graves disease include antithyroid drugs, radioactive iodine ablation, and surgery. Treatment for subclinical hyperthyroidism is recommended for patients at highest risk of osteoporosis and cardiovascular disease, such as those older than 65 years or with persistent serum thyrotropin level less than 0.1 mIU/L.
CONCLUSIONS AND RELEVANCE
Hyperthyroidism affects 2.5% of adults worldwide and is associated with osteoporosis, heart disease, and increased mortality. First-line treatments are antithyroid drugs, thyroid surgery, and radioactive iodine treatment. Treatment choices should be individualized and patient centered.
Topics: Adult; Female; Humans; Male; Pregnancy; Antithyroid Agents; Graves Disease; Hyperthyroidism; Iodine; Iodine Radioisotopes; Osteoporosis; Thyroid Neoplasms; Thyroid Nodule; Thyroiditis; Thyrotoxicosis; Thyrotropin; Thyroxine; Weight Loss
PubMed: 37847271
DOI: 10.1001/jama.2023.19052 -
International Journal of Molecular... Jun 2023Thyroid function affects multiple sites of the female hypothalamic-pituitary gonadal (HPG) axis. Disruption of thyroid function has been linked to reproductive... (Review)
Review
Thyroid function affects multiple sites of the female hypothalamic-pituitary gonadal (HPG) axis. Disruption of thyroid function has been linked to reproductive dysfunction in women and is associated with menstrual irregularity, infertility, poor pregnancy outcomes, and gynecological conditions such as premature ovarian insufficiency and polycystic ovarian syndrome. Thus, the complex molecular interplay between hormones involved in thyroid and reproductive functions is further compounded by the association of certain common autoimmune states with disorders of the thyroid and the HPG axes. Furthermore, in prepartum and intrapartum states, even relatively minor disruptions have been shown to adversely impact maternal and fetal outcomes, with some differences of opinion in the management of these conditions. In this review, we provide readers with a foundational understanding of the physiology and pathophysiology of thyroid hormone interactions with the female HPG axis. We also share clinical insights into the management of thyroid dysfunction in reproductive-aged women.
Topics: Pregnancy; Female; Humans; Adult; Reproduction; Thyroid Hormones; Thyroid Diseases; Polycystic Ovary Syndrome
PubMed: 37372963
DOI: 10.3390/ijms24129815 -
Frontiers in Endocrinology 2023Thyroid hormones and essential elements iodine (I), selenium (Se), iron (Fe), copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), etc. play an important role in the... (Review)
Review
Thyroid hormones and essential elements iodine (I), selenium (Se), iron (Fe), copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), etc. play an important role in the work of many organs and systems of the body, including the immune system and the thyroid gland, and a violation of their supply can be the cause of pathological changes in them. In pathology, the interaction between thyroid hormones (TG), minerals and the immune system is disturbed. The review of the literature examines the immunomodulatory role of TG, minerals, their properties, and their participation in the pathogenesis of autoimmune thyroid diseases (AITD). The study of the relationship between the excess or deficiency of minerals and AITD is described. The basis of the development of AITD - Hashimoto's thyroiditis (HT), Graves' disease (GD), Graves' ophthalmopathy (GO) is the loss of immune tolerance to thyroid antigens - thyroid peroxidase (TPO), thyroglobulin (Tg) and thyroid-stimulating hormone receptor (TSH-R). Immune-mediated mechanisms - production of autoantibodies to thyroid antigens and lymphocytic thyroid infiltration - are involved in the pathogenesis of AITD. Insufficiency of regulatory T cells (Treg) and regulatory B cells (Breg), imbalance between Th17-lymphocytes and Treg-lymphocytes, abnormal production of pro-inflammatory cytokines has a significant influence on the progression of AITD. With AITD, the balance between oxidants and antioxidants is disturbed and oxidative stress (OS) occurs. The lack of modern effective pharmacological therapy of AITD prompted us to consider the mechanisms of influence, possibilities of immunocorrection of pathogenetic factors using TG, micro/macronutrients. In order to develop a more effective treatment strategy, as well as approaches to prevention, a critical analysis of the ways of immunotherapeutic use of dietary supplements of I, Se, Zn, Mg and other minerals in AITD was carried out.
Topics: Humans; Thyroid Hormones; Hashimoto Disease; Zinc; Selenium; Magnesium
PubMed: 37711890
DOI: 10.3389/fendo.2023.1225494 -
Journal of Veterinary Internal Medicine 2023Erroneous thyroid function test results can occur because of drugs that alter thyroid hormone physiology in one or more aspects, including synthesis, secretion,... (Review)
Review
Erroneous thyroid function test results can occur because of drugs that alter thyroid hormone physiology in one or more aspects, including synthesis, secretion, distribution, and metabolism. Research since publication of the last review in the Journal of Veterinary Internal Medicine (JVIM) 20 years ago has evaluated the effects of amiodarone, zonisamide, inhalant anesthetics, clomipramine, trilostane, and toceranib on thyroid function tests in the dog. In addition, recent work on the effects of glucocorticoids, sulfonamides, phenobarbital, and nonsteroidal anti-inflammatory drugs will be reviewed. Awareness of these effects is necessary to avoid misdiagnosis of hypothyroidism and unnecessary treatment.
Topics: Dogs; Animals; Thyroid Function Tests; Hypothyroidism; Thyroid Hormones; Amiodarone; Anti-Arrhythmia Agents; Dog Diseases
PubMed: 37498128
DOI: 10.1111/jvim.16823 -
Thyroid : Official Journal of the... Dec 2023Increased height has been associated with increased risk of hypothyroidism or thyroid cancer in epidemiological studies. However, the potential causal association... (Meta-Analysis)
Meta-Analysis
Increased height has been associated with increased risk of hypothyroidism or thyroid cancer in epidemiological studies. However, the potential causal association between height and hypothyroidism or thyroid cancer has not been thoroughly explored. Autoimmune thyroid disease (AITD) mainly presents as hypothyroidism, thus we aim to evaluate the causal relationship between height as exposure and its association with AITD or thyroid cancer. Mendelian randomization (MR) analyses were performed by using genetic instruments associated with height, which were selected from the largest genome-wide association meta-analysis for height in up to 5.4 million individuals. Summary-level data for AITD and thyroid cancer (including 30,234 and 3001 cases, respectively) were collected from the large number of available genome-wide association studies. Bidirectional MR was performed to test for reverse causal association between AITD and adult height. MR analyses showed that increased genetically predicted height was associated with a 4% increased risk of AITD ([CI 1.02 to 1.07], -value = 1.99E-03) per 1-standard deviation (SD) increase in genetically predicted height. The bidirectional MR did not show any causal association between AITD and adult height. Additionally, increased genetically predicted height was associated with 15% increased risk of thyroid cancer ([CI 1.07 to 1.23], -value = 2.32E-04) per 1-SD increase in height. Sensitivity analysis confirmed the main results. This MR study showed that 1-SD increase in genetically predicted height was associated with increased risk of AITD and thyroid cancer. In contrast, there was no evidence of a causal association of genetically predicted AITD with height. These results could further aid in investigation of height-related pathways as a means of gaining new mechanistic insights into AITD and thyroid cancer.
Topics: Adult; Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Hashimoto Disease; Hypothyroidism; Thyroid Neoplasms; Polymorphism, Single Nucleotide
PubMed: 37772697
DOI: 10.1089/thy.2023.0272 -
Frontiers in Endocrinology 2023Published data on the relationship between polycystic ovary syndrome (PCOS) and thyroid dysfunction are sparse and confusing. (Review)
Review
BACKGROUND
Published data on the relationship between polycystic ovary syndrome (PCOS) and thyroid dysfunction are sparse and confusing.
OBJECTIVE
To comprehensively review data available in the literature regarding the relationship between PCOS and the thyroid function, and its abnormalities.
METHODS
Nine main areas of interest were identified and analyzed according to the available evidence: 1) Evaluation of thyroid function for PCOS diagnosis; 2) Epidemiology data on thyroid function/disorders in patients with PCOS, and vice versa; 3) Experimental data supporting the relationship between thyroid function/disorders and PCOS; 4) Effects of thyroid function/disorders on PCOS features, and vice versa; 5) Effect of thyroid alterations on the cardiometabolic risk in women with PCOS; 6) Effect of thyroid abnormalities on reproductive outcomes in women with PCOS; 7) Relationship between thyroid function/abnormalities in patients with PCOS who are undergoing fertility treatment; 8) Effect of treatments for thyroid diseases on PCOS; and 9) Effect of treatments for PCOS on thyroid function. An extensive literature search for specific keywords was performed for articles published from 1970 to March 2023 using PubMed and Web of Science. Data were reported in a narrative fashion.
RESULTS
PCOS is a diagnosis of exclusion for which diagnosis is possible only after excluding disorders that mimic the PCOS phenotype, including thyroid dysfunctions. However, the tests and the cutoff values used for this are not specified. Many experimental and clinical data suggest a relationship between perturbations of the thyroid function and PCOS. Direct and unequivocal evidence on the effects of thyroid function/disorders on PCOS features are lacking. High thyroid-stimulating hormone levels and subclinical hypothyroidism may be associated with significant worsening of several intermediate endpoints of cardiometabolic risk in women with PCOS. Thyroid abnormalities may worsen reproductive outcomes, especially in patients undergoing fertility treatment. To date, there are no data demonstrating the efficacy of thyroid medications on fertility and cardiometabolic risk in women with PCOS. Lifestyle modification changes, metformin, and vitamin D seem to improve thyroid function in the general population.
CONCLUSION
PCOS and thyroid disorders are closely related, and their coexistence may identify patients with a higher reproductive and metabolic risk. Regular screening for thyroid function and thyroid-specific autoantibodies in women with PCOS, particularly before and during pregnancy, is highly recommended.
Topics: Female; Humans; Pregnancy; Polycystic Ovary Syndrome; Thyroid Diseases; Hypothyroidism; Thyroid Dysgenesis; Antibodies; Cardiovascular Diseases
PubMed: 37635968
DOI: 10.3389/fendo.2023.1251866 -
Biochimica Et Biophysica Acta. Reviews... Jul 2023Thyroid cancer (TC) is the most prevalent endocrine malignant tumor. Surgery, chemotherapy, radiotherapy, and radioactive iodine (RAI) therapy are the standard TC... (Review)
Review
Thyroid cancer (TC) is the most prevalent endocrine malignant tumor. Surgery, chemotherapy, radiotherapy, and radioactive iodine (RAI) therapy are the standard TC treatment modalities. However, recurrence or tumor metastasis remains the main challenge in the management of anaplastic thyroid cancer (ATC) and radioiodine (RAI) radioactive iodine-refractory differentiated thyroid cancer (RR-DTC). Several multi-tyrosine kinase inhibitors (MKIs), or immune checkpoint inhibitors in combination with MKIs, have emerged as novel therapies for controlling the progression of DTC, medullary thyroid cancer (MTC), and ATC. Here, we discuss and summarize the molecular basis of TC, review molecularly targeted therapeutic drugs in clinical research, and explore potentially novel molecular therapeutic targets. We focused on the evaluation of current and recently emerging tyrosine kinase inhibitors approved for systemic therapy for TC, including lenvatinib, sorafenib and cabozantinib in DTC, vandetanib, cabozantinib, and RET-specific inhibitor (selpercatinib and pralsetinib) in MTC, combination dabrafenib with trametinib in ATC. In addition, we also discuss promising treatments that are in clinical trials and may be incorporated into clinical practice in the future, briefly describe the resistance mechanisms of targeted therapies, emphasizing that personalized medicine is critical to the design of second-line therapies.
Topics: Humans; Thyroid Neoplasms; Iodine Radioisotopes; Anilides; Thyroid Carcinoma, Anaplastic; Protein Kinase Inhibitors
PubMed: 37257629
DOI: 10.1016/j.bbcan.2023.188928 -
Frontiers in Endocrinology 2023Breast and thyroid cancer are increasingly prevalent, but it remains unclear whether the observed associations are due to heightened medical surveillance or intrinsic...
BACKGROUND
Breast and thyroid cancer are increasingly prevalent, but it remains unclear whether the observed associations are due to heightened medical surveillance or intrinsic etiological factors. Observational studies are vulnerable to residual confounding, reverse causality, and bias, which can compromise causal inference. In this study, we employed a two-sample Mendelian randomization (MR) analysis to establish a causal link between breast cancer and heightened thyroid cancer risk.
METHODS
We obtained the single nucleotide polymorphisms (SNPs) associated with breast cancer from a genome-wide association study (GWAS) conducted by the Breast Cancer Association Consortium (BCAC). The FinnGen consortium's latest and largest accessible GWAS thyroid cancer data at the summary level. We performed four MR analyses, including the inverse-variance-weighted (IVW), weighted median, MR-Egger regression, and weighted mode, to evaluate the potential causal connection between genetically predicted breast cancer and higher risk for thyroid cancer. Sensitivity analysis, heterogeneity and pleiotropy tests were used to ensure the reliability of our findings.
RESULTS
Our study revealed causal relationship between genetically predicted breast cancer and thyroid cancer (IVW method, odds ratio (OR) = 1.135, 95% confidence interval (CI): 1.006 to 1.279, = 0.038). However, there was no causal association between genetically predicted triple-negative breast cancer and thyroid cancer (OR = 0.817, 95% CI: 0.610 to 1.095, = 0.177). There was no directional pleiotropy or horizontal pleiotropy in the present study.
CONCLUSION
This two-sample MR study supports a causal link between ER-positive breast cancer and heightened the risk of thyroid cancer. Our analysis did not reveal a direct correlation between triple-negative breast cancer and thyroid cancer.
Topics: Humans; Triple Negative Breast Neoplasms; Genome-Wide Association Study; Mendelian Randomization Analysis; Reproducibility of Results; Thyroid Neoplasms
PubMed: 37288296
DOI: 10.3389/fendo.2023.1138149 -
Frontiers in Endocrinology 2023Human blood metabolites have demonstrated close associations with thyroid disorders in observational studies. However, it's essential to determine whether these...
BACKGROUND
Human blood metabolites have demonstrated close associations with thyroid disorders in observational studies. However, it's essential to determine whether these correlations imply causation. Mendelian Randomization (MR) offers a promising approach to investigate these patterns.
AIMS
The primary aim of our investigation is to establish causality between blood metabolites and three thyroid disorders: TC, GD, and HT.
METHODS
We employed a two-sample bidirectional MR analysis approach to assess the relationships between 452 blood metabolites and the three aforementioned thyroid disorders. Causal links were estimated using the IVW method, with sensitivity analyses conducted via MR-Egger, Weighted Median, and MR-PRESSO. We assessed potential heterogeneity and pleiotropy using MR-Egger intercept and Cochran's Q statistic. Additionally, we conducted pathway analysis to identify potential metabolic pathways.
RESULTS
We found 46 metabolites that showed suggestive associations with thyroid disease risk, especially Aspartate (OR=7.41; 95%CI: 1.51-36.27; P=0.013) and C-glycosyltryptophan (OR=0.04; 95%CI: 0.00-0.29; P=0.001) impacted TC, Kynurenine (OR=2.69; 95%CI: 1.08-6.66; P=0.032) and 4-androsten-3beta,17beta-diol disulfate 2 (OR=0.78; 95%CI: 0.48-0.91; P=0.024) significantly impacted GD, and Alpha-ketoglutarate (OR=46.89; 95%CI: 4.65-473.28; P=0.001) and X-14189-leucylalanine (OR=0.31; 95%CI: 0.15-0.64 P=0.001) significantly impacted HT. We also detected 23 metabolites influenced by TC and GD. Multiple metabolic pathways have been found to be involved in thyroid disease.
CONCLUSION
Our MR findings suggest that the identified metabolites and pathways can serve as biomarkers for clinical thyroid disorder screening and prevention, while also providing new insights for future mechanistic exploration and drug target selection.
Topics: Humans; Mendelian Randomization Analysis; Thyroid Diseases; Aspartic Acid
PubMed: 37876541
DOI: 10.3389/fendo.2023.1270336