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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 -
Lancet (London, England) Feb 2024Thyrotoxicosis causes a variety of symptoms and adverse health outcomes. Hyperthyroidism refers to increased thyroid hormone synthesis and secretion, most commonly from... (Review)
Review
Thyrotoxicosis causes a variety of symptoms and adverse health outcomes. Hyperthyroidism refers to increased thyroid hormone synthesis and secretion, most commonly from Graves' disease or toxic nodular goitre, whereas thyroiditis (typically autoimmune, viral, or drug induced) causes thyrotoxicosis without hyperthyroidism. The diagnosis is based on suppressed serum concentrations of thyroid-stimulating hormone (TSH), accompanied by free thyroxine and total or free tri-iodothyronine concentrations, which are raised (overt hyperthyroidism) or within range (subclinical hyperthyroidism). The underlying cause is determined by clinical assessment, detection of TSH-receptor antibodies and, if necessary, radionuclide thyroid scintigraphy. Treatment options for hyperthyroidism include antithyroid drugs, radioactive iodine, and thyroidectomy, whereas thyroiditis is managed symptomatically or with glucocorticoid therapy. In Graves' disease, first-line treatment is a 12-18-month course of antithyroid drugs, whereas for goitre, radioactive iodine or surgery are preferred for toxic nodules or goitres. Evidence also supports long-term treatment with antithyroid drugs as an option for patients with Graves' disease and toxic nodular goitre.
Topics: Humans; Antithyroid Agents; Goiter, Nodular; Iodine Radioisotopes; Thyroid Neoplasms; Hyperthyroidism; Graves Disease; Thyrotoxicosis; Thyroiditis
PubMed: 38278171
DOI: 10.1016/S0140-6736(23)02016-0 -
Frontiers in Cellular and Infection... 2023Recently the role of gut microbial dysbiosis in many ocular disorders, including but not limited to uveitis, age-related macular degeneration (AMD), diabetic retinopathy...
INTRODUCTION
Recently the role of gut microbial dysbiosis in many ocular disorders, including but not limited to uveitis, age-related macular degeneration (AMD), diabetic retinopathy (DR), dry eye, keratitis and orbitopathy is a hot research topic in the field. Targeting gut microbiota to treat these diseases has become an unstoppable trend. Bibliometric study and visualization analysis have become essential methods for literature analysis in the medical research field. We aim to depict this area's research hotspots and future directions by bibliometric software and methods.
METHODS
We search all the related publications from the Web of Science Core Collection. Then, CiteSpace was applied to analyze and visualize the country distributions, dual-map overlay of journals, keyword bursts, and co-cited references. VOSviewer was employed to identify authors, co-cited authors, journals and co-cited journals and display the keyword co-occurrence networks.
RESULTS
A total of 284 relevant publications were identified from 2009 to 2023. The number of studies has been small in the first five years and has grown steadily since 2016. These studies were completed by 1,376 authors from 41 countries worldwide, with the United States in the lead. Lin P has published the most papers while Horai R is the most co-cited author. The top journal and co-cited journal are both Investigative Ophthalmology & Visual Science. In the keyword co-occurrence network, except gut microbiota, inflammation becomes the keyword with the highest frequency. Co-citation analyses reveal that gut dysbiosis is involved in common immune- and inflammation-mediated eye diseases, including uveitis, diabetic retinopathy, age-related macular degeneration, dry eye, and Graves' orbitopathy, and the study of microbiomes is no longer limited to the bacterial populations. Therapeutic strategies that target the gut microbiota, such as probiotics, healthy diet patterns, and fecal microbial transplantation, are effective and critical to future research.
CONCLUSIONS
In conclusion, the bibliometric analysis displays the research hotspots and developmental directions of the involvement of gut microbiota in the pathogenesis and treatment of some ocular diseases. It provides an overview of this field's dynamic evolution and structural relationships.
Topics: Humans; Gastrointestinal Microbiome; Graves Ophthalmopathy; Diabetic Retinopathy; Dysbiosis; Inflammation; Bibliometrics; Macular Degeneration
PubMed: 37621873
DOI: 10.3389/fcimb.2023.1225859 -
The Journal of Clinical Endocrinology... Nov 2023Inhibition of the neonatal fragment crystallizable receptor (FcRn) reduces pathogenic thyrotropin receptor antibodies (TSH-R-Ab) that drive pathology in thyroid eye... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Inhibition of the neonatal fragment crystallizable receptor (FcRn) reduces pathogenic thyrotropin receptor antibodies (TSH-R-Ab) that drive pathology in thyroid eye disease (TED).
OBJECTIVE
We report the first clinical studies of an FcRn inhibitor, batoclimab, in TED.
DESIGN
Proof-of-concept (POC) and randomized, double-blind placebo-controlled trials.
SETTING
Multicenter.
PARTICIPANTS
Patients with moderate-to-severe, active TED.
INTERVENTION
In the POC trial, patients received weekly subcutaneous injections of batoclimab 680 mg for 2 weeks, followed by 340 mg for 4 weeks. In the double-blind trial, patients were randomized 2:2:1:2 to weekly batoclimab (680 mg, 340 mg, 255 mg) or placebo for 12 weeks.
MAIN OUTCOME
Change from baseline in serum anti-TSH-R-Ab and total IgG (POC); 12-week proptosis response (randomized trial).
RESULTS
The randomized trial was terminated because of an unanticipated increase in serum cholesterol; therefore, data from 65 of the planned 77 patients were analyzed. Both trials showed marked decreases in pathogenic anti-TSH-R-Ab and total IgG serum levels (P < .001) with batoclimab. In the randomized trial, there was no statistically significant difference with batoclimab vs placebo in proptosis response at 12 weeks, although significant differences were observed at several earlier timepoints. In addition, orbital muscle volume decreased (P < .03) at 12 weeks, whereas quality of life (appearance subscale) improved (P < .03) at 19 weeks in the 680-mg group. Batoclimab was generally well tolerated, with albumin reductions and increases in lipids that reversed upon discontinuation.
CONCLUSIONS
These results provide insight into the efficacy and safety of batoclimab and support its further investigation as a potential therapy for TED.
Topics: Infant, Newborn; Humans; Graves Ophthalmopathy; Quality of Life; Antibodies, Monoclonal; Exophthalmos; Immunoglobulin G; Double-Blind Method; Treatment Outcome
PubMed: 37390454
DOI: 10.1210/clinem/dgad381 -
International Journal of Molecular... Aug 2023Secondary diabetes mellitus is frequently ignored in specialized literature. In this narrative review, the main endocrinopathies accompanied by increased glycemic values... (Review)
Review
Secondary diabetes mellitus is frequently ignored in specialized literature. In this narrative review, the main endocrinopathies accompanied by increased glycemic values are identified, as well as the mechanisms by which the excess or deficiency of certain hormones impact beta cell function or insulin resistance. The main endocrinopathies (acromegaly, Cushing's syndrome, Basedow-Graves' disease, pheochromocytoma, somatostatinoma and glucagonoma) and their characteristics are described along with the impact of hormone changes on blood sugar, body mass index and other parameters associated with diabetes. The overall information regarding the complex molecular mechanisms that cause the risk of secondary diabetes and metabolic syndrome is of crucial importance in order to prevent the development of the disease and its complications and particularly to reduce the cardiovascular risk of these patients. The purpose of this study is to highlight the particular features of endocrine pathologies accompanied by an increased risk of developing diabetes, in the context of personalized therapeutic decision making. The epidemiological, physiopathological, clinical and therapeutic approaches are presented along with the importance of screening for diabetes in endocrine diseases.
Topics: Humans; Diabetes Mellitus; Metabolic Syndrome; Insulin Resistance; Acromegaly; Graves Disease; Adrenal Gland Neoplasms
PubMed: 37628857
DOI: 10.3390/ijms241612676 -
Seminars in Nuclear Medicine Mar 2024Autoimmune thyroid diseases (AITDs) include a wide spectrum of thyroid diseases affecting more commonly women than men. The most frequent forms are Graves' Disease (GD)... (Review)
Review
Autoimmune thyroid diseases (AITDs) include a wide spectrum of thyroid diseases affecting more commonly women than men. The most frequent forms are Graves' Disease (GD) and Hashimoto's thyroiditis / Autoimmune Thyroiditis (AIT), but there are also other immunogenic destructive forms of thyroiditis, that is, silent and postpartum thyroiditis. In the last decade, AITDs and other inflammatory thyroid diseases related to anti-tumor molecular drugs are more frequently seen due to the widespread use of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICPIs). Autoimmune thyroiditis related to SARS-CoV-2 infection has been a novel entity in recent years. Graves' Disease and AIT may shift from hyperthyroidism to hypothyroidism, which may complicate the differential diagnosis and further treatment strategy. Moreover, all AITDs may manifest with thyrotoxicosis (a clinical condition marked with high serum levels of thyroid hormones) which has to be distinguished from hyperthyroidism (increased thyroid hormone production and secretion as a result of hyperfunctioning thyroid gland) due to different therapeutic approaches. Nuclear medicine techniques, such as radioiodine uptake (RAIU) and thyroid scintigraphy, using Tc- pertechnetate (Na[Tc]TcO) or 123-Iodine (Na[I]I), have a crucial role in the differential diagnosis. Measurement of thyroid antibodies, e.g. thyroid peroxidase antibodies (TPO) and thyrotropin receptor antibodies (TRAb), as well as thyroid ultrasound, are complementary methods in the evaluation of thyroid disorders.
Topics: Male; Female; Humans; Iodine Radioisotopes; Graves Disease; Hyperthyroidism; Thyroiditis, Autoimmune; Thyroiditis; Thyroid Diseases
PubMed: 38044176
DOI: 10.1053/j.semnuclmed.2023.11.002 -
Reviews in Endocrine & Metabolic... Feb 2024Graves' disease (GD) is the commonest cause of hyperthyroidism and has a strong female preponderance. Everyday clinical practice suggests strong aggregation within... (Review)
Review
Graves' disease (GD) is the commonest cause of hyperthyroidism and has a strong female preponderance. Everyday clinical practice suggests strong aggregation within families and twin studies demonstrate that genetic factors account for 60-80% of risk of developing GD. In this review, we collate numerous genetic studies and outline the discoveries over the years, starting with historic candidate gene studies and then exploring more recent genome-wide linkage and association studies, which have involved substantial cohorts of East Asian patients as well as those of European descent. Variants in genes including HLA, CTLA4, and PTPN22 have been shown to have substantial individual effects on disease susceptibility. In addition, we examine emerging evidence concerning the possibility that genetic variants may correlate with relevant clinical phenotypes including age of onset of GD, severity of thyrotoxicosis, goitre size and relapse of hyperthyroidism following antithyroid drug therapy, as well as thyroid eye disease. This review supports the inheritance of GD as a complex genetic trait, with a growing number of more than 80 susceptibility loci identified so far. Future implementation of more targeted clinical therapies requires larger studies investigating the influence of these genetic variants on the various phenotypes and different outcomes of conventional treatments.
Topics: Humans; Female; Genotype; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Graves Disease; Graves Ophthalmopathy; Protein Tyrosine Phosphatase, Non-Receptor Type 22
PubMed: 38108994
DOI: 10.1007/s11154-023-09848-8 -
Journal of Medical Virology Aug 2023Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) damages multiple organs, including the thyroid, by direct invasion and cell entry via angiotensin-converting... (Review)
Review
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) damages multiple organs, including the thyroid, by direct invasion and cell entry via angiotensin-converting enzyme 2 or indirectly by promoting excessive inflammation in the body. The immune system is a critical factor in antiviral immunity and disease progression. In the context of SARS-CoV-2 infection, the immune system may become overly activated, resulting in a shift from regulatory to effector responses, which may subsequently promote the development and progression of autoimmune diseases. The incidence of autoimmune thyroid diseases, such as subacute thyroiditis, Graves' disease, and Hashimoto's thyroiditis, increases in individuals with COVID-19 infection. This phenomenon may be attributed to aberrant responses of T-cell subtypes, the presence of autoantibodies, impaired regulatory cell function, and excessive production of inflammatory cytokines, namely interleukin (IL)-6, IL-1β, interferon-γ, and tumor necrosis factor-α. Therefore, insights into the immune responses involved in the development of autoimmune thyroid disease according to COVID-19 can help identify potential therapeutic approaches and guide the development of effective interventions to alleviate patients' symptoms.
Topics: Humans; Thyroiditis, Autoimmune; COVID-19; SARS-CoV-2; Thyroiditis; Graves Disease
PubMed: 37515444
DOI: 10.1002/jmv.29001 -
European Journal of Nuclear Medicine... Sep 2023This document provides the new EANM guideline on radioiodine therapy of benign thyroid disease. Its aim is to guide nuclear medicine physicians, endocrinologists, and...
This document provides the new EANM guideline on radioiodine therapy of benign thyroid disease. Its aim is to guide nuclear medicine physicians, endocrinologists, and practitioners in the selection of patients for radioiodine therapy. Its recommendations on patients' preparation, empiric and dosimetric therapeutic approaches, applied radioiodine activity, radiation protection requirements, and patients follow-up after administration of radioiodine therapy are extensively discussed.
Topics: Humans; Iodine Radioisotopes; Graves Disease; Thyroid Diseases; Radiometry; Radiation Protection
PubMed: 37395802
DOI: 10.1007/s00259-023-06274-5 -
Ophthalmic Plastic and Reconstructive... Dec 2023Dysthyroid optic neuropathy (DON) is a sight-threatening complication of thyroid eye disease (TED). This review provides an overview of the epidemiology, pathogenesis,... (Review)
Review
PURPOSE
Dysthyroid optic neuropathy (DON) is a sight-threatening complication of thyroid eye disease (TED). This review provides an overview of the epidemiology, pathogenesis, diagnosis, and current therapeutic options for DON.
METHODS
A literature review.
RESULTS
DON occurs in about 5% to 8% of TED patients. Compression of the optic nerve at the apex is the most widely accepted pathogenic mechanism. Excessive stretching of the nerve might play a role in a minority of cases. Increasing age, male gender, smoking, and diabetes mellitus have been identified as risk factors. Diagnosis of DON is based on a combination of ≥2 clinical findings, including decreased visual acuity, decreased color vision, relative afferent pupillary defect, visual field defects, or optic disc edema. Orbital imaging supports the diagnosis by confirming apical crowding or optic nerve stretching. DON should be promptly treated with high-dose intravenous glucocorticoids. Decompression surgery should be performed, but the response is incomplete. Radiotherapy might play a role in the prevention of DON development and may delay or avoid the need for surgery. The advent of new biologic-targeted agents provides an exciting new array of therapeutic options, though more research is needed to clarify the role of these medications in the management of DON.
CONCLUSIONS
Even with appropriate management, DON can result in irreversible loss of visual function. Prompt diagnosis and management are pivotal and require a multidisciplinary approach. Methylprednisolone infusions still represent first-line therapy, and surgical decompression is performed in cases of treatment failure. Biologics may play a role in the future.
Topics: Humans; Male; Glucocorticoids; Graves Ophthalmopathy; Methylprednisolone; Optic Nerve; Papilledema
PubMed: 38054987
DOI: 10.1097/IOP.0000000000002555