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Indications for treatment of subclinical hypothyroidism and isolated hypothyroxinaemia in pregnancy.Best Practice & Research. Clinical... Jul 2020Thyroid hormones are essential for maintaining a pregnancy and optimal fetal neurological development. Pregnancy places additional demands on the thyroid axis and around... (Review)
Review
Thyroid hormones are essential for maintaining a pregnancy and optimal fetal neurological development. Pregnancy places additional demands on the thyroid axis and around 5% of women who have their thyroid function checked during gestation will have borderline low thyroid function (subclinical hypothyroidism or isolated hypothyroxinemia) identified. These borderline low thyroid states are associated with adverse obstetric and offspring outcomes. Whilst it is well established that overt hypothyroidism requires treatment with levothyroxine, it is less clear whether there is any benefit of treating borderline low thyroid states. This review summarizes the potential indications for treatment of subclinical hypothyroidism and isolated hypothyroxinemia.
Topics: Asymptomatic Diseases; Female; Humans; Hypothyroidism; Pregnancy; Pregnancy Complications; Prenatal Care; Thyroid Hormones; Thyroxine
PubMed: 32828674
DOI: 10.1016/j.beem.2020.101436 -
Frontiers in Endocrinology 2024Non-scarring alopecia is typically represented by two main types: alopecia areata (AA) and androgenetic alopecia (AGA). While previous observational studies have...
BACKGROUND
Non-scarring alopecia is typically represented by two main types: alopecia areata (AA) and androgenetic alopecia (AGA). While previous observational studies have indicated a link between non-scarring alopecia and hypothyroidism, the precise causal relationship remains uncertain. To determine the potential links between non-scarring alopecia and hypothyroidism, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis.
METHODS
We used independent genetic instruments from the FinnGen consortium for AA (682 cases, 361,140 controls) and AGA (195 cases, 201,019 controls) to investigate the association with hypothyroidism in the UK Biobank study (22,687 cases, 440,246 controls). The primary analysis was performed using the inverse variance-weighted method. Complementary approaches were employed to evaluate the pleiotropy and heterogeneity.
RESULTS
Genetically predicted AA exhibited a positive causal effect on hypothyroidism (odds ratio [OR], 1.0017; 95% confidence interval [CI], 1.0004-1.0029; = 0.0101). Additionally, hypothyroidism was found to be strongly correlated with an increase in the risk of AA (OR, 45.6839; 95% CI, 1.8446-1131.4271, = 0.0196). However, no causal relationship was demonstrated between AGA and hypothyroidism. A sensitivity analysis validated the integrity of these causal relationships.
CONCLUSION
This MR study supports a bidirectional causal link between AA and hypothyroidism. Nevertheless, additional research is needed to gain a more thorough comprehension of the causal relationship between non-scarring alopecia and hypothyroidism.
Topics: Humans; Mendelian Randomization Analysis; Alopecia Areata; Hypothyroidism; Odds Ratio
PubMed: 38562416
DOI: 10.3389/fendo.2024.1356832 -
Frontiers in Endocrinology 2022Immunotherapy has revolutionized the treatment of solid malignancies, but is associated with endocrine-related adverse events. This study aims to dissect the natural...
BACKGROUND
Immunotherapy has revolutionized the treatment of solid malignancies, but is associated with endocrine-related adverse events. This study aims to dissect the natural course of immunotherapy-induced hypothyroidism and provide guidance regarding diagnosis and management in patients with and without pre-existing hypothyroidism.
METHODS
A retrospective analysis was conducted using patients who received immunotherapy between 2010-2019 within a multicenter hospital system. Participants were separated in three groups-those with pre-existing hypothyroidism, those who developed primary hypothyroidism and those with hypophysitis within a year of their first immunotherapy. Serial effects of immunotherapy on thyroid function tests (TFTs) and levothyroxine dosing were evaluated.
RESULTS
822 patients were screened, with 85 determined to have pre-existing hypothyroidism, 48 primary hypothyroidism and 12 hypophysitis. All groups displayed fluctuations in TFTs around weeks 6-8 of treatment. In the pre-existing hypothyroidism group, the levothyroxine dose was higher at 54 weeks than at baseline with the difference showing a trend towards statistical significance (p=0.06). The observed mean levothyroxine dose was significantly lower than the mean calculated weight-based dose for all groups. This finding was most clinically significant for the hypophysitis group (mean difference: -58.3 mcg, p<0.0001). The mean 0.9 mcg/kg levothyroxine dose at week 54 for the hypophysitis group was statistically lower than the other groups (p=0.009).
CONCLUSION
It is reasonable to screen with TFTs every 4 weeks, and space out TFTs surveillance to every 12 weeks after week 20. Our findings suggest a more conservative approach for levothyroxine dosing in those developing hypothyroidism, especially hypophysitis, such as initiating at 0.9-1.2 mcg/kg.
Topics: Humans; Hypothyroidism; Immunotherapy; Retrospective Studies; Thyroid Function Tests; Thyroxine
PubMed: 35360059
DOI: 10.3389/fendo.2022.798253 -
Frontiers in Endocrinology 2022Primary hypothyroidism severely impacts the quality of life of patients through a decrease in the production of the thyroid hormones T3 and T4, leading to symptoms... (Review)
Review
Primary hypothyroidism severely impacts the quality of life of patients through a decrease in the production of the thyroid hormones T3 and T4, leading to symptoms affecting cardiovascular, neurological, cognitive, and metabolic function. The incidence rate of primary hypothyroidism is expected to increase in the near future, partially due to increasing survival of patients that have undergone radiotherapy for head and neck cancer, which induces this disease in over half of those treated. The current standard of care encompasses thyroid hormone replacement therapy, traditionally in the form of synthetic T4. However, there is mounting evidence that this is unable to restore thyroid hormone signaling in all tissues due to often persistent symptoms. Additional complications are also present in the form of dosage difficulties, extensive drug interactions and poor patience compliance. The alternative therapeutic approach employed in the past is combination therapy, which consists of administration of both T3 and T4, either synthetic or in the form of desiccated thyroid extract. Here, issues are present regarding the lack of regulation concerning formulation and lack of data regarding safety and efficacy of these treatment methods. Tissue engineering and regenerative medicine have been applied in conjunction with each other to restore function of various tissues. Recently, these techniques have been adapted for thyroid tissue, primarily through the fabrication of regenerative scaffolds. Those currently under investigation are composed of either biopolymers or native decellularized extracellular matrix (dECM) in conjunction with either primary thyrocytes or stem cells which have undergone directed thyroid differentiation. Multiple of these scaffolds have successfully restored an athyroid phenotype . However, further work is needed until clinical translation can be achieved. This is proposed in the form of exploration and combination of materials used to fabricate these scaffolds, the addition of peptides which can aid restoration of tissue homeostasis and additional experimentation providing data on safety and efficacy of these implants.
Topics: Humans; Thyroxine; Hypothyroidism; Thyroid (USP); Quality of Life; Hormone Replacement Therapy; Thyroid Hormones
PubMed: 36277721
DOI: 10.3389/fendo.2022.997288 -
Journal of Veterinary Internal Medicine 2016Primary hypothyroidism is a common endocrinopathy in dogs. In contrast, central hypothyroidism is rare in this species.
BACKGROUND
Primary hypothyroidism is a common endocrinopathy in dogs. In contrast, central hypothyroidism is rare in this species.
OBJECTIVES
The objective of this article is to describe the occurrence and clinical presentation of central hypothyroidism in Miniature Schnauzers. Additionally, the possible role of the thyroid-stimulating hormone (TSH)-releasing hormone receptor (TRHR) gene and the TSHβ (TSHB) gene was investigated.
ANIMALS
Miniature Schnauzers with proven central hypothyroidism, based on scintigraphy, and the results of a 3-day-TSH-stimulation test, or a TSH-releasing hormone (TRH)-stimulation test or both, presented to the Department of Clinical Sciences of Companion Animals at Utrecht University or the Department of Medicine and Clinical Biology of Small Animals at Ghent University from 2008 to 2012.
METHODS
Retrospective study. Pituitary function tests, thyroid scintigraphy, and computed tomography (CT) of the pituitary area were performed. Gene fragments of affected dogs and controls were amplified by polymerase chain reaction (PCR). Subsequently, the deoxyribonucleic acid (DNA) sequences of the products were analyzed.
RESULTS
Central hypothyroidism was diagnosed in 7 Miniature Schnauzers. Three dogs had disproportionate dwarfism and at least one of them had a combined deficiency of TSH and prolactin. No disease-causing mutations were found in the TSHB gene and the exons of the TRHR gene of these Schnauzers.
CONCLUSIONS AND CLINICAL IMPORTANCE
Central hypothyroidism could be underdiagnosed in Miniature Schnauzers with hypothyroidism, especially in those of normal stature. The fact that this rare disorder occurred in 7 dogs from the same breed suggests that central hypothyroidism could have a genetic background in Miniature Schnauzers.
Topics: Animals; Base Sequence; Case-Control Studies; DNA; Dog Diseases; Dogs; Dwarfism; Female; Genetic Predisposition to Disease; Humans; Hypothyroidism; Male; Pedigree; Recombinant Proteins; Thyroid Gland; Thyrotropin; Thyrotropin, beta Subunit; Thyroxine
PubMed: 26696394
DOI: 10.1111/jvim.13818 -
Problemy Endokrinologii May 2023Searching for aging key points is one of the main problems in geriatrics. More and more research in recent years has been devoted to the study of geroprotective... (Review)
Review
Searching for aging key points is one of the main problems in geriatrics. More and more research in recent years has been devoted to the study of geroprotective mechanisms, the impact of various conditions and diseases on aging in general. Of particular importance is the determination of age-related involutive processes in the human body, whether they are part of normal aging or a condition that needs to be corrected to improve the functioning of organs and systems. An important mechanism of aging starts is a change in hormonal activity of endocrine glands, in particular in hormonal activity of thyroid. Frequency of hypothyroidism in advanced age explains relevance of the chosen topic. The aim of the review was to find out the role hypothyroidism in aging. The main task was to define, whether thyroid hormones decrease in older age was a protective factor or pathological process. A review of the literature over the past 10 years on subclinical treatment was carried out and we identified the most pressing issues associated with hypothyroidism and aging. We studied data on the relationship between hypothyroidism and major geriatric syndromes, with special attention paid to cognitive diseases and emotional disorders.
Topics: Humans; Aged; Protective Factors; Hypothyroidism; Aging; Thyroid Hormones
PubMed: 37448266
DOI: 10.14341/probl13156 -
Endocrine Regulations Jan 2021Thyroid hormones play an important role in the development and maturation of the central nervous symptom and their failure in the prenatal period leading to an...
Thyroid hormones play an important role in the development and maturation of the central nervous symptom and their failure in the prenatal period leading to an irreversible brain damage. Their effect on the brain of adult, however, has not been fully studied. With the discovery of neurogenesis in the adult brain, many recent studies have been focused on the understanding the basic mechanisms controlling this process. Many neurogenesis regulatory genes are not only transcribed but also translated into the blood cells. The goal of our study was to analyze the transcriptional activity of neurogenesis regulatory genes in peripheral blood cells in patients with thyroid pathology. The pathway-specific PCR array (Neurotrophins and Receptors RT2 Profiler PCR Array, QIAGEN, Germany) was used to identify and validate the neurogenesis regulatory genes expression in patients with thyroid pathology and control group. The results showed that GFRA3, NGFR, NRG1, NTF3, NTRK1, and NTRK2 significantly decreased their expression in patients with autoimmune thyroiditis with rising serum of autoantibodies. The patients with primary hypothyroidism, as a result of autoimmune thyroiditis and postoperative hypothyroidism, had significantly lower expression of FGF2, NGFR, NRG1, and NTF3. The mRNA level of CNTFR was markedly decreased in the group of patients with postoperative hypothyroidism. No change in the ARTN, PSPN, TFG, MT3, and NELL1 expression was observed in any group of patients. The finding indicates that a decrease in thyroid hormones and a high level of autoantibodies, such as anti-thyroglobulin antibody and anti-thyroid peroxidase antibody, affect the expression of mRNA neurogenesis-regulated genes in patients with thyroid pathology.
Topics: Adult; Autoantibodies; Gene Expression Regulation; Humans; Hypothyroidism; Iodide Peroxidase; Middle Aged; Nerve Growth Factors; Neurogenesis; RNA, Messenger; Thyroid Hormones; Thyroiditis, Autoimmune
PubMed: 33600668
DOI: 10.2478/enr-2021-0002 -
Endocrine Reviews Feb 2016Thyroglobulin (Tg) is a vertebrate secretory protein synthesized in the thyrocyte endoplasmic reticulum (ER), where it acquires N-linked glycosylation and conformational... (Review)
Review
Thyroglobulin (Tg) is a vertebrate secretory protein synthesized in the thyrocyte endoplasmic reticulum (ER), where it acquires N-linked glycosylation and conformational maturation (including formation of many disulfide bonds), leading to homodimerization. Its primary functions include iodide storage and thyroid hormonogenesis. Tg consists largely of repeating domains, and many tyrosyl residues in these domains become iodinated to form monoiodo- and diiodotyrosine, whereas only a small portion of Tg structure is dedicated to hormone formation. Interestingly, evolutionary ancestors, dependent upon thyroid hormone for development, synthesize thyroid hormones without the complete Tg protein architecture. Nevertheless, in all vertebrates, Tg follows a strict pattern of region I, II-III, and the cholinesterase-like (ChEL) domain. In vertebrates, Tg first undergoes intracellular transport through the secretory pathway, which requires the assistance of thyrocyte ER chaperones and oxidoreductases, as well as coordination of distinct regions of Tg, to achieve a native conformation. Curiously, regions II-III and ChEL behave as fully independent folding units that could function as successful secretory proteins by themselves. However, the large Tg region I (bearing the primary T4-forming site) is incompetent by itself for intracellular transport, requiring the downstream regions II-III and ChEL to complete its folding. A combination of nonsense mutations, frameshift mutations, splice site mutations, and missense mutations in Tg occurs spontaneously to cause congenital hypothyroidism and thyroidal ER stress. These Tg mutants are unable to achieve a native conformation within the ER, interfering with the efficiency of Tg maturation and export to the thyroid follicle lumen for iodide storage and hormonogenesis.
Topics: Animals; Congenital Hypothyroidism; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Genetic Predisposition to Disease; Halogenation; Humans; Models, Biological; Models, Molecular; Mutation; Protein Conformation; Thyroglobulin; Thyroid Gland
PubMed: 26595189
DOI: 10.1210/er.2015-1090 -
Journal of Endocrinological... May 2024Hypothyroidism is prevalent at all ages and represents a non-communicable disease with preventable consequences. (Review)
Review
BACKGROUND
Hypothyroidism is prevalent at all ages and represents a non-communicable disease with preventable consequences.
METHOD
Narrative review.
REVIEW
In children and adolescents, the most devastating consequences of undertreatment with levothyroxine (LT4) are poor growth and development. Delayed treatment in congenital hypothyroidism can lead to permanent brain damage. In young to middle-aged adults, symptoms are often overlooked, and treatment delayed by many years. The resulting consequences are also at this age group compromised brain and physical function but less severe and partly reversible with treatment. The under-treated condition often results in a higher risk of, e.g., increased cardiovascular disease burden, obesity, hypertension, poor physical capacity, and poor quality of life. Excessive replacement is at all adult age groups associated with increased risk of cardiac death, osteoporosis, loss of muscle function, psychological instability and poor quality of life. In young fertile women, the consequences of undertreatment with LT4 are subnormal fertility, recurrent pregnancy loss, compromised fetal growth, and neurocognitive development. On the other hand, excessive LT4 treatment has been related to gestational hypertension, preeclampsia and preterm birth. In the elderly, care must be given to avoid confusing a slightly high age-related serum TSH with requirement for LT4 treatment in a truly hypothyroid patient. Excessive LT4 treatment in patients of high age is associated with an increased mortality.
CONCLUSION
Suboptimal and excessive LT4 replacement of the preventable non-communicable disease hypothyroidism requires more focus from the healthcare system and from the global political systems to prevent the personally devastating and socioeconomically challenging consequences.
Topics: Humans; Hormone Replacement Therapy; Hypothyroidism; Thyroid Hormones; Female; Thyroxine; Quality of Life
PubMed: 38015369
DOI: 10.1007/s40618-023-02229-7 -
Frontiers in Immunology 2024Hypothyroidism, a prevalent endocrine disorder, carries significant implications for maternal and infant health, especially in the context of maternal hypothyroidism.... (Review)
Review
BACKGROUND
Hypothyroidism, a prevalent endocrine disorder, carries significant implications for maternal and infant health, especially in the context of maternal hypothyroidism. Despite a gradual surge in recent research, achieving a comprehensive understanding of the current state, focal points, and developmental trends in this field remains challenging. Clarifying these aspects and advancing research could notably enhance maternal-infant health outcomes. Therefore, this study employs bibliometric methods to systematically scrutinize maternal hypothyroidism research, serving as a reference for further investigations.
OBJECTIVE
Through bibliometric analysis, this study seeks to unveil key research focus areas, developmental trends, and primary contributors in Maternal Hypothyroidism. The findings offer insights and recommendations to inform future research endeavors in this domain.
METHODS
Literature metrics analysis was performed on data retrieved and extracted from the Web of Science Core Collection database. The analysis examined the evolution and thematic trends of literature related to Maternal Hypothyroidism. Data were collected on October 28, 2023, and bibliometric analysis was performed using VOSviewer, CiteSpace, and the Bibliometrix software package, considering specific characteristics such as publication year, country/region, institution, authorship, journals, references, and keywords.
RESULTS
Retrieved from 1,078 journals, 4,184 articles were authored by 18,037 contributors in 4,580 institutions across 113 countries/regions on six continents. Maternal Hypothyroidism research publications surged from 44 to 310 annually, a 604.54% growth from 1991 to 2022. The USA (940 articles, 45,233 citations), China Medical University (82 articles, 2,176 citations), and Teng, Weiping (52 articles, 1,347 citations) emerged as the most productive country, institution, and author, respectively. "Thyroid" topped with 233 publications, followed by "Journal of Clinical Endocrinology & Metabolism" (202) with the most citations (18,513). "Pregnancy" was the most cited keyword, with recent high-frequency keywords such as "outcome," "gestational diabetes," "iodine intake," "preterm birth," "guideline," and "diagnosis" signaling emerging themes in Maternal Hypothyroidism.
CONCLUSIONS
This study unveils developmental trends, global collaboration patterns, foundational knowledge, and emerging frontiers in Maternal Hypothyroidism. Over 30 years, research has predominantly focused on aspects like diagnosis, treatment guidelines, thyroid function during pregnancy, and postpartum outcomes, with a central emphasis on the correlation between maternal and fetal health.
Topics: Infant, Newborn; Infant; Female; Pregnancy; Humans; Premature Birth; Hypothyroidism; Authorship; Bibliometrics
PubMed: 38596686
DOI: 10.3389/fimmu.2024.1370707