المؤلفون: Helen Budge, James Law, José Joaquín Muros, Ellie Finn, David E. Morris, Lindsay Robinson, Louise Denvir, Valerie Astle, Michael E. Symonds, Tabitha Randell

المصدر: Journal of the Endocrine Society
Digibug. Repositorio Institucional de la Universidad de Granada
instname

مصطلحات موضوعية: 0301 basic medicine, Autoimmune hypothyroidism, medicine.medical_specialty, Cold stimulation, endocrine system, endocrine system diseases, Thyroid hormones, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Stimulation, Brown adipose tissue, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Euthyroid, Clinical Research Articles, Increased TSH, thyroid hormones, Obesity and Adipocyte Biology, business.industry, Thyroid, autoimmune, brown adipose tissue, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Cold-induced thermogenesis, infrared thermography, Infrared thermography, hypothyroidism, BAT activity, business, Autoimmune, cold-induced thermogenesis

الوصف: The interaction between thyroid status and brown adipose tissue (BAT) activation is complex. We assessed the effect of autoimmune hypothyroidism (ATD) in female children on BAT activation, measured using infrared thermography. Participants with ATD had lower resting (hypothyroid, 34.9 +- 0.7°C; control, 35.4 +- 0.5°C; P = 0.03) and stimulated (hypothyroid, 35.0 +- 0.6°C; control, 35.5 +- 0.5°C; P = 0.04) supraclavicular temperatures compared with controls, but there was no difference between groups in the temperature increase with stimulation. BAT activation, calculated as the relative temperature change comparing the supraclavicular temperature to a sternal reference region, was reduced in participants with ATD (hypothyroid, 0.1 +- 0.1°C; control, 0.2 +- 0.2°C; P = 0.04). Children with ATD were frequently biochemically euthyroid due to replacement therapy, but, despite this, increased relative supraclavicular temperature was closely associated with increased TSH (r = 0.7, P = 0.01) concentrations. Girls with ATD had an attenuated thermogenic response to cold stimulation compared with healthy controls, but, contrary to expectation, those with suboptimal biochemical control (with higher TSH) showed increased BAT activation. This suggests that the underlying disease process may have a negative effect on BAT response, but high levels of TSH can mitigate, and even stimulate, BAT activity. In summary, thyroid status is a complex determinant of BAT activity in girls with ATD.
This work was supported by a pump-priming grant from Nottingham University Hospitals Charity (Grant PP-Law-Nov12).

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d552c1b383e3270f1d6183968a88f0eTest
http://europepmc.org/articles/PMC6872489Test

المؤلفون: Carlos Eduardo Bernal Barquero, Victoria Peyret, Juan Pablo Nicola, Ana María Masini-Repiso, Romina Celeste Geysels, Mariano Martín

المصدر: Journal of the Endocrine Society
CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET

مصطلحات موضوعية: 0301 basic medicine, Thyroid nodules, endocrine system, endocrine system diseases, Endocrinology, Diabetes and Metabolism, differentiated thyroid cancer, 030209 endocrinology & metabolism, DIFFERENTIATED THYROID CANCER, Follicular cell, purl.org/becyt/ford/1 [https], Thyroid carcinoma, 03 medical and health sciences, 0302 clinical medicine, I2 DEFICIENCY DISORDERS, NA+/I2 SYMPORTER, medicine, purl.org/becyt/ford/1.6 [https], Thyroid cancer, health care economics and organizations, Thyroid, I2 TRANSPORT DEFECT, Chemistry, congenital hypothyroidism, radioiodine therapy, Mini-Review, RADIOIODINE THERAPY, medicine.disease, I− deficiency disorders, CONGENITAL HYPOTHYROIDISM, Congenital hypothyroidism, 030104 developmental biology, medicine.anatomical_structure, Symporter, I− transport defect, Cancer research, Immunohistochemistry, Na+/I− symporter

الوصف: Iodine is a crucial component of thyroid hormones; therefore, a key requirement for thyroid hormone biosynthesis is that iodide (I2) be actively accumulated in the thyroid follicular cell. The ability of the thyroid epithelia to concentrate I2 is ultimately dependent on functional Na+/ I2 symporter (NIS) expression at the plasma membrane. Underscoring the significance of NIS for thyroid physiology, loss-of-function mutations in the NIS-coding SLC5A5 gene cause an I2 transport defect, resulting in dyshormonogenic congenital hypothyroidism. Moreover, I2 accumulation in the thyroid cell constitutes the cornerstone for radioiodide ablation therapy for differentiated thyroid carcinoma. However, differentiated thyroid tumors often exhibit reduced (or even undetectable) I2 transport compared with normal thyroid tissue, and they are diagnosed as cold nodules on thyroid scintigraphy. Paradoxically, immunohistochemistry analysis revealed that cold thyroid nodules do not express NIS or express normal, or even higher NIS levels compared with adjacent normal tissue, but NIS is frequently intracellularly retained, suggesting the presence of posttranslational abnormalities in the transport of the protein to the plasma membrane. Ultimately, a thorough comprehension of the mechanisms that regulate NIS transport to the plasma membrane would have multiple implications for radioiodide therapy, opening the possibility to identify new molecular targets to treat radioiodide-refractory thyroid tumors. Therefore, in this review, we discuss the current knowledge regarding posttranslational mechanisms that regulate NIS transport to the plasma membrane under physiological and pathological conditions affecting the thyroid follicular cell, a topic of great interest in the thyroid cancer field. Fil: Martín, Mariano. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina Fil: Geysels, Romina Celeste. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina Fil: Peyret, Victoria. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Bernal Barquero, Carlos Eduardo. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas; Argentina Fil: Masini-Repiso, Ana María. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Bioquímica Clínica; Argentina Fil: Nicola, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8864927304aeda83eaf48e872e3ab39cTest
http://europepmc.org/articles/PMC6316985Test

المؤلفون: Masayo Kagami, Keisuke Nagasaki, Akie Nakamura, Tsutomu Ogata, Keiko Matsubara, Maki Fukami, Shinichiro Sano

المصدر: Journal of the Endocrine Society

مصطلحات موضوعية: 0301 basic medicine, musculoskeletal diseases, medicine.medical_specialty, Parathyroid, Bone, and Mineral Metabolism, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, GNAS complex locus, Missense mutation, Allele, Pseudohypoparathyroidism, Clinical Research Articles, biology, molecular classification, business.industry, Brachydactyly, pseudohypoparathyroidism, congenital hypothyroidism, medicine.disease, Congenital hypothyroidism, 030104 developmental biology, Endocrinology, Differentially methylated regions, biology.protein, (epi)genotype-phenotype analysis, STX16, business

الوصف: Context: Pseudohypoparathyroidism type I (PHP-I) is divided into PHP-Ia with Albright hereditary osteodystrophy and PHP-Ib, which usually shows no Albright hereditary osteodystrophy features. Although PHP-Ia and PHP-Ib are typically caused by genetic defects involving α subunit of the stimulatory G protein (Gsα)–coding GNAS exons and methylation defects of the GNAS differentially methylated regions (DMRs) on the maternal allele, respectively, detailed phenotypic characteristics still remains to be examined. Objective: To clarify phenotypic characteristics according to underlying (epi)genetic causes. Patients and Methods: We performed (epi)genotype-phenotype analysis in 69 Japanese patients with PHP-I; that is, 28 patients with genetic defects involving Gsα-coding GNAS exons (group 1) consisting of 12 patients with missense variants (subgroup A) and 16 patients with null variants (subgroup B), as well as 41 patients with methylation defects (group 2) consisting of 21 patients with broad methylation defects of the GNAS-DMRs (subgroup C) and 20 patients with an isolated A/B-DMR methylation defect accompanied by the common STX16 microdeletion (subgroup D). Results: Although (epi)genotype-phenotype findings were grossly similar to those reported previously, several important findings were identified, including younger age at hypocalcemic symptoms and higher frequencies of hyperphosphatemia in subgroup C than in subgroup D, development of brachydactyly in four patients of subgroup C, predominant manifestation of subcutaneous ossification in subgroup B, higher frequency of thyrotropin resistance in group 1 than in group 2, and relatively low thyrotropin values in four patients with low T4 values and relatively low luteinizing hormone/follicle-stimulating hormone values in five adult females with ovarian dysfunction. Conclusion: The results imply the presence of clinical findings characteristic of each underlying cause and provide useful information on the imprinting status of Gsα.
(Epi)genotype-phenotype analysis in 69 Japanese patients with pseudohypoparathyroidism type I indicates the presence of clinical findings characteristic of each underlying cause.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::223e4a45a744e846c6014a7986952b75Test
http://europepmc.org/articles/PMC5779104Test

المؤلفون: Cari M. Kitahara, Dóra Kӧrmendiné Farkas, Jens Otto Lunde Jørgensen, Henrik Toft Sørensen, Deirdre Cronin-Fenton

المصدر: Kitahara, C M, Komendiné Farkas, D, Jørgensen, J O L, Cronin-Fenton, D & Sørensen, H T 2018, ' Benign Thyroid Diseases and Risk of Thyroid Cancer : A Nationwide Cohort Study ', Journal of Clinical Endocrinology and Metabolism, vol. 103, no. 6, pp. 2216-2224 . https://doi.org/10.1210/jc.2017-02599Test

مصطلحات موضوعية: Male, Thyroiditis, Goiter, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Denmark, Clinical Biochemistry, Hypothyroidism/complications, Biochemistry, Gastroenterology, Hyperthyroidism, Hyperthyroidism/complications, Cohort Studies, 0302 clinical medicine, Endocrinology, Registries, Thyroid cancer, Thyroid disease, Incidence, Thyroid, Middle Aged, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, Thyroid nodules, Adult, Risk, medicine.medical_specialty, endocrine system, Adenoma, 030209 endocrinology & metabolism, Thyroid Neoplasms/epidemiology, 03 medical and health sciences, Sex Factors, Hypothyroidism, Internal medicine, medicine, Humans, Thyroid Neoplasms, Clinical Research Articles, Aged, business.industry, Biochemistry (medical), medicine.disease, Denmark/epidemiology, Cancer registry, Thyroiditis/complications, business

الوصف: Context: Thyroid nodules, adenomas, and goiter have consistently been associated with thyroid cancer risk. Few studies have assessed whether thyroid dysfunction and thyroid autoimmunity influence this risk.Objective: To examine thyroid cancer risk after diagnoses of a wide range of benign thyroid conditions.Design: Hospital and cancer registry linkage cohort study for the years 1978 to 2013.Setting: Nationwide (Denmark).Participants: Patients diagnosed with hyperthyroidism (n = 85,169), hypothyroidism (n = 63,143), thyroiditis (n = 12,532), nontoxic nodular goiter (n = 65,782), simple goiter (n = 11,582), other/unspecified goiter (n = 21,953), or adenoma (n = 6,481) among 8,258,807 residents of Denmark during the study period.Main Outcome Measures: We computed standardized incidence ratios (SIRs) for differentiated thyroid cancer, excluding the first 12 months of follow-up after benign thyroid disease diagnosis.Results: SIRs were significantly elevated for all benign thyroid diseases apart from hypothyroidism. SIRs were higher for men than women and in the earlier follow-up periods. Elevated SIRs were observed for localized and regional/distant thyroid cancer. After excluding the first 10 years of follow-up, hyperthyroidism [n = 27 thyroid cancer cases; SIR = 2.00; 95% confidence interval (CI): 1.32 to 2.92], nontoxic nodular goiter (n = 83; SIR = 4.91; 95% CI: 3.91 to 6.09), simple goiter (n = 8; SIR = 4.33; 95% CI: 1.87 to 8.53), other/unspecified goiter (n = 20; SIR = 3.94; 95% CI: 2.40 to 6.08), and adenoma (n = 9; SIR = 6.02; 95% CI: 2.76 to 11.5) remained positively associated with thyroid cancer risk.Conclusions: We found an unexpected increased risk of differentiated thyroid cancer, including regional/distant disease, following diagnosis of hyperthyroidism and thyroiditis that could not be solely attributed to increased medical surveillance. Hypothyroidism was less clearly associated with thyroid cancer risk.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c58eb996cc6123af4fd68f396d866375Test
https://europepmc.org/articles/PMC6276704Test/

المؤلفون: Krishnaji R. Kulkarni, Michael Cobble, Paulo H Harada, Julie E. Buring, Nancy R. Cook, Samia Mora

المصدر: Journal of the Endocrine Society

مصطلحات موضوعية: medicine.medical_specialty, Very low-density lipoprotein, endocrine system diseases, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Context (language use), 030204 cardiovascular system & hematology, Thyroid function tests, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Internal medicine, insulin resistance, Medicine, Euthyroid, coagulation, Clinical Research Articles, Subclinical infection, Thyroid, medicine.diagnostic_test, business.industry, medicine.disease, metabolomics, 3. Good health, subclinical hypothyroidism, lipoproteins, Endocrinology, inflammation, Thyroid function, business, Lipoprotein

الوصف: Context: Whether subclinical hypothyroidism (SCH) is associated with cardiometabolic abnormalities is uncertain. Objective: To examine diverse cardiometabolic biomarkers across euthyroid, SCH, and overt hypothyroidism (HT) in women free of cardiovascular disease. Design: Cross-sectional adjusted associations for lipids, lipoprotein subclasses, lipoprotein insulin resistance score, inflammatory, coagulation, and glycemic biomarkers by analysis of covariance for thyroid categories or thyroid stimulating hormone (TSH) quintiles on a Women’s Health Study subcohort. Setting: Outpatient. Patients or Other Participants: Randomly sampled 3914 middle-aged and older women for thyroid function analysis (TSH, free T4), of whom 3321 were not on lipid-lowering therapy. Intervention: None. Main Outcome Measure: Associations of SCH and HT with cardiometabolic markers. Results: Going from euthyroid to HT, the lipoprotein subclass profiles were indicative of insulin resistance (respective values and P for trend): larger very-low-density lipoprotein size (nm) (51.5 [95% confidence interval (CI), 51.2, 51.8] to 52.9 [51.8, 54.1], P = 0.001); higher low-density lipoprotein (LDL) particle concentration (nmol/L) [1283 (95% CI, 1267, 1299) to 1358 (1298, 1418), P = 0.004], and smaller LDL size. There was worsening lipoprotein insulin resistance score from euthyroid (49.2; 95% CI, 48.3, 50.2) to SCH (52.1; 95% CI, 50.1, 54.0) and HT (52.1; 95% CI, 48.6, 55.6); P for trend of 0.008. Of the other biomarkers, SCH and HT were associated with higher high-sensitivity C-reactive protein and hemoglobin A1c. For increasing TSH quintiles, results were overall similar. Conclusions: In apparently healthy women, SCH cardiometabolic profiles indicated worsening insulin resistance and higher cardiovascular disease risk markers compared with euthyroid individuals, despite similar LDL and total cholesterol. These findings suggest that cardiometabolic risk may increase early in the progression toward SCH and overt HT.
In otherwise healthy middle-aged and older women, subclinical hypothyroidism is independently associated with cardiometabolic profile indicating worsening insulin resistance and higher cardiovascular disease risk.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4a6aaae57b23e99145e70179a2c817d1Test
http://europepmc.org/articles/PMC5453652Test

المؤلفون: Ronak Ghiya, Shema Ahmad

المصدر: Journal of the Endocrine Society

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, Anemia, Endocrinology, Diabetes and Metabolism, Levothyroxine, 030209 endocrinology & metabolism, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Thyroid peroxidase, Internal medicine, medicine, Thyroid Case Reports: Hypothyroidism and Hyperthyroidism II, Thyroid, biology, business.industry, Thyroid disease, medicine.disease, Ferritin, 030104 developmental biology, medicine.anatomical_structure, Iron-deficiency anemia, biology.protein, Thyroid function, business, medicine.drug

الوصف: Background Patients with thyroid disease have a high prevalence of iron-deficiency, but this is often times overlooked in the medical community. Treating a patient’s iron levels may be all that is needed to reverse his or her thyroid condition. Iodine is one of the main components of thyroid hormones; however, iodine requires iron in order for it to be fully utilized. Iron is an element that is essential for the human body to synthesize and metabolize the thyroid hormones. The body is dependent upon iron to convert thyroxine (T4) into the active hormone triiodothyronine (T3) via thyroid peroxidase (TPO). As such, low iron levels can impede thyroid function and patients can present with hypothyroid-like symptoms. Clinical Case A 50-year old female with no significant past medical history presented to our facility with chief complaints of fatigue and dizziness. She was referred by her PCP to our ED for anemia after her labs drawn the day prior were remarkable for a hemoglobin of 4.5 g/dL (n=12-16 g/dL). In the ED, her workup was remarkable for a hemoglobin of 4.9 g/dL and a TSH of 870.44 mIU/L and 719.84 mIU/L on re-check (n=0.36-3.74 mIU/L). Therefore, she was admitted for iron-deficiency anemia (IDA) and hypothyroidism. Her free T4 was undetectable at

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7ebe4ec5c35b357768fecc6ade8f8029Test
http://europepmc.org/articles/PMC6552785Test

المؤلفون: Elizabeth A. McAninch, Antonio C. Bianco, Kumar B. Rajan, Corinne H. Miller

مصطلحات موضوعية: medicine.medical_specialty, endocrine system, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Levothyroxine, 030209 endocrinology & metabolism, Context (language use), 030204 cardiovascular system & hematology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Sex hormone-binding globulin, Internal medicine, medicine, biology, business.industry, Biochemistry (medical), Thyroid, Primary hypothyroidism, medicine.anatomical_structure, biology.protein, Creatine kinase, business, hormones, hormone substitutes, and hormone antagonists, Lipoprotein, medicine.drug, Hormone, Meta-Analysis

الوصف: Context The standard of care for overt hypothyroidism is levothyroxine at doses that normalize serum TSH levels. Whether this approach universally restores thyroid hormone signaling is unknown. Objective To review studies of overt hypothyroidism in which participants were treated with levothyroxine to normalize serum TSH levels and measured other objective markers of thyroid hormone signaling. Design Databases were searched for studies that reported objective markers of thyroid hormone signaling (serum low-density lipoprotein (LDL), total cholesterol (TC), sex hormone-binding globulin (SHBG), creatine kinase and/or ferritin levels; cognition, energy expenditure, and/or renal function) in levothyroxine monotherapy for overt, primary hypothyroidism among nonpregnant adults with normal serum TSH levels. For studies with LDL, TC and SHBG outcomes, data were pooled using random effects meta-analysis. Results A total of 99 studies met inclusion criteria, including 65 that reported serum cholesterol data. Meta-analysis showed that levothyroxine-treated hypothyroid participants with normal serum TSH levels had 3.31 ± 1.64 mg/dL higher serum LDL levels (p=0.044) and 9.60 ± 3.55 mg/dL higher serum TC levels (p=0.007) compared to controls. In studies that did not concomitantly assess healthy controls, serum LDL levels were 138.3 ± 4.6 mg/dL (p

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a02751cd94abe774eadf9266ed300a3cTest
https://europepmc.org/articles/PMC6226605Test/

المؤلفون: Leonardo Pardo, Jesús González de Buitrago, José Moreno, Patricia M. Hinkle, Mireia Jiménez-Rosés, Marta Cerezo García

المصدر: Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid
Consejería de Sanidad de la Comunidad de Madrid

مصطلحات موضوعية: 0301 basic medicine, Male, Transcriptional Activation, medicine.medical_specialty, endocrine system, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Mutation, Missense, Thyrotropin, 030209 endocrinology & metabolism, Context (language use), Biology, Thyroid Function Tests, Biochemistry, Thyroid function tests, Short stature, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Rare Diseases, Internal medicine, medicine, Central hypothyroidism, Congenital Hypothyroidism, Missense mutation, Humans, Computer Simulation, Genetic Predisposition to Disease, Child, Clinical Research Articles, medicine.diagnostic_test, Receptors, Thyrotropin-Releasing Hormone, Biochemistry (medical), Thyroid, medicine.disease, Congenital hypothyroidism, Pedigree, IGSF1, 030104 developmental biology, medicine.anatomical_structure, GTP-Binding Protein alpha Subunits, Gq-G11, medicine.symptom, hormones, hormone substitutes, and hormone antagonists

الوصف: Context:Central congenital hypothyroidism (CCH) is an underdiagnosed disorder characterized by deficient production and bioactivity of thyroid-stimulating hormone (TSH) leading to low thyroid hormone synthesis. Thyrotropin-releasing hormone (TRH) receptor (TRHR) defects are rare recessive disorders usually associated with incidentally identified CCH and short stature in childhood.Objectives:Clinical and genetic characterization of a consanguineous family of Roma origin with central hypothyroidism and identification of underlying molecular mechanisms.Design:All family members were phenotyped with thyroid hormone profiles, pituitary magnetic resonance imaging, TRH tests, and dynamic tests for other pituitary hormones. Candidate TRH, TRHR, TSHB, and IGSF1 genes were screened for mutations. A mutant TRHR was characterized in vitro and by molecular modeling.Results:A homozygous missense mutation in TRHR (c.392T > C; p.I131T) was identified in an 8-year-old boy with moderate hypothyroidism (TSH: 2.61 mIU/L, Normal: 0.27 to 4.2; free thyroxine: 9.52 pmol/L, Normal: 10.9 to 25.7) who was overweight (body mass index: 20.4 kg/m2, p91) but had normal stature (122 cm; –0.58 standard deviation). His mother, two brothers, and grandmother were heterozygous for the mutation with isolated hyperthyrotropinemia (TSH: 4.3 to 8 mIU/L). The I131T mutation, in TRHR intracellular loop 2, decreases TRH affinity and increases the half-maximal effective concentration for signaling. Modeling of TRHR-Gq complexes predicts that the mutation disrupts the interaction between receptor and a hydrophobic pocket formed by Gq.Conclusions:A unique missense TRHR defect identified in a consanguineous family is associated with central hypothyroidism in homozygotes and hyperthyrotropinemia in heterozygotes, suggesting compensatory elevation of TSH with reduced biopotency. The I131T mutation decreases TRH binding and TRHR-Gq coupling and signaling.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fdadc8b022faeb2e5c84045ca2fc84ecTest
https://europepmc.org/articles/PMC5505191Test/

المؤلفون: Jayne A. Franklyn, W. T. Longstreth, Jacobijn Gussekloo, Tinh-Hai Collet, Misa Imaizumi, Robert Luben, Christine Baumgartner, Bruce M. Psaty, John P. Walsh, Kay-Tee Khaw, Anne B. Newman, Layal Chaker, Luigi Ferrucci, J. Wouter Jukema, Rui M. B. Maciel, Christoph Wanner, Marcus Dörr, Christiane Drechsler, Giorgio Iervasi, Alexandra Bremner, Graziano Ceresini, Manuel R. Blum, Ian Ford, Salman Razvi, Nicolas Rodondi, Wendy P. J. den Elzen, Stephan J. L. Bakker, M. Arfan Ikram, Rudi G. J. Westendorp, David J. Stott, Robin P. Peeters, Henry Völzke, José Augusto Sgarbi, Douglas C. Bauer, Anne R. Cappola, Oscar H. Franco, Marileen L.P. Portegies, Albert Hofman, Abbas Dehghan, Robin P. F. Dullaart, Marco Medici

المساهمون: Internal Medicine, Neurology, Radiology & Nuclear Medicine, Epidemiology, Lifestyle Medicine (LM), Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Thyroid Studies Collaboration

المصدر: The Journal of Clinical Endocrinology & Metabolism
Journal of Clinical Endocrinology and Metabolism, 101(11), 4270-4282. Endocrine Society
Journal of Clinical Endocrinology and Metabolism, 101(11), 4270-4282. ENDOCRINE SOC
Journal of Clinical Endocrinology and Metabolism, 101(11), 4270-4282
The Journal of clinical endocrinology and metabolism, vol. 101, no. 11, pp. 4270-4282

مصطلحات موضوعية: medicine.medical_specialty, endocrine system, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, BLOOD-PRESSURE, 030209 endocrinology & metabolism, Reference range, Context (language use), ISCHEMIC-HEART-DISEASE, ALL-CAUSE, 030204 cardiovascular system & hematology, Biochemistry, 03 medical and health sciences, SUBCLINICAL HYPOTHYROIDISM, 0302 clinical medicine, Endocrinology, Interquartile range, Internal medicine, medicine, OLDER-ADULTS, Prospective cohort study, Stroke, business.industry, CARDIOVASCULAR RISK, Biochemistry (medical), Thyroid, Original Articles, medicine.disease, DYSFUNCTION, 3. Good health, SERVICES TASK-FORCE, medicine.anatomical_structure, SERUM THYROTROPIN, MYOCARDIAL-INFARCTION, Meta-analysis, Thyroid function, business, hormones, hormone substitutes, and hormone antagonists

الوصف: Context: The currently applied reference ranges for thyroid function are under debate. Despite evidence that thyroid function within the reference range is related with several cardiovascular disorders, its association with the risk of stroke has not been evaluated previously.Design and Setting: We identified studies through a systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline TSH, free T-4, and stroke outcomes were included, and we collected individual participant data from each study, including thyroid function measurements and incident all stroke (combined fatal and nonfatal) and fatal stroke. The applied reference range for TSH levels was between 0.45 and 4.49 mIU/L.Results: We collected individual participant data on 43 598 adults with TSH within the reference range from 17 cohorts, with a median follow-up of 11.6 years (interquartile range 5.1-13.9), including 449 908 person-years. Age- and sex-adjusted pooled hazard ratio for TSH was 0.78 (95% confidence interval [CI] 0.65-0.95 across the reference range of TSH) for all stroke and 0.83 (95% CI 0.62-1.09) for fatal stroke. For the free T4 analyses, the hazard ratio was 1.08 (95% CI 0.99-1.15 per SD increase) for all stroke and 1.10 (95% CI 1.04-1.19) for fatal stroke. This was independent of cardiovascular risk factors including systolic blood pressure, total cholesterol, smoking, and prevalent diabetes.Conclusion: Higher levels of TSH within the reference range may decrease the risk of stroke, highlighting the need for further research focusing on the clinical consequences associated with differences within the reference range of thyroid function.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e29ceab826f765bd6b624e7ed8131ecTest
https://pure.eur.nl/en/publications/22e23fe6-b574-40c6-95ed-2f3be5a49d48Test

المؤلفون: Sabrina Corbetta, Patrizia Porazzi, Mariacarolina Salerno, Paolo Prontera, Gabriella Nebbia, Natascia Tiso, Mohamad Maghnie, Roberto Gastaldi, Giovanna Weber, Daniela Frizziero, Laura Fugazzola, Luana Mandarà, Roberta Biffanti, Federica Marelli, Giorgio Radetti, Maria Cristina Vigone, Luca Persani, Tiziana de Filippis

المساهمون: De Filippis, Tiziana, Marelli, Federica, Nebbia, Gabriella, Porazzi, Patrizia, Corbetta, Sabrina, Fugazzola, Laura, Gastaldi, Roberto, Vigone, Maria Cristina, Biffanti, Roberta, Frizziero, Daniela, Mandarà, Luana, Prontera, Paolo, Salerno, Mariacarolina, Maghnie, Mohamad, Tiso, Natascia, Radetti, Giorgio, Weber, Giovanna, Persani, Luca, de Filippis, T, Marelli, F, Nebbia, G, Porazzi, P, Corbetta, S, Fugazzola, L, Gastaldi, R, Vigone, Mc, Biffanti, R, Frizziero, D, Mandarà, L, Prontera, P, Salerno, M, Maghnie, M, Tiso, N, Radetti, G, Persani, L.

المصدر: Europe PubMed Central

مصطلحات موضوعية: 0301 basic medicine, Male, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Fluorescent Antibody Technique, Biochemistry, Pathogenesis, 0302 clinical medicine, Endocrinology, Alagille syndrome, Serrate-Jagged Proteins, Child, Zebrafish, Thyroid, Penetrance, Congenital hypothyroidism, Alagille Syndrome, Diabetes and Metabolism, medicine.anatomical_structure, Adult, Animals, Calcium-Binding Proteins, Child, Preschool, Computational Biology, Female, Humans, Intercellular Signaling Peptides and Proteins, Jagged-1 Protein, Membrane Proteins, Thyroid Dysgenesis, Zebrafish Proteins, Biochemistry (medical), endocrine system, JAG1, medicine.medical_specialty, JAG1 Loss-Of-Function Variations, Novel Predisposing Event, Pathogenesis of Congenital Thyroid Defects, congenital hypothyroidism, 030209 endocrinology & metabolism, Context (language use), Biology, Thyroid dysgenesis, 03 medical and health sciences, Internal medicine, medicine, Preschool, medicine.disease, 030104 developmental biology

الوصف: CONTEXT: The pathogenesis of congenital hypothyroidism (CH) is still largely unexplained. We previously reported that perturbations of the Notch pathway and knockdown of the ligand jagged1 cause a hypothyroid phenotype in the zebrafish. Heterozygous JAG1 variants are known to account for Alagille syndrome type 1 (ALGS1), a rare multisystemic developmental disorder characterized by variable expressivity and penetrance. OBJECTIVE: Verify the involvement of JAG1 variants in the pathogenesis of congenital thyroid defects and the frequency of unexplained hypothyroidism in a series of ALGS1 patients. DESIGN, SETTINGS, AND PATIENTS: A total of 21 young ALGS1 and 100 CH unrelated patients were recruited in academic and public hospitals. The JAG1 variants were studied in vitro and in the zebrafish. RESULTS: We report a previously unknown nonautoimmune hypothyroidism in 6/21 ALGS1 patients, 2 of them with thyroid hypoplasia. We found 2 JAG1 variants in the heterozygous state in 4/100 CH cases (3 with thyroid dysgenesis, 2 with cardiac malformations). Five out 7 JAG1 variants are new. Different bioassays demonstrate that the identified variants exhibit a variable loss of function. In zebrafish, the knock-down of jag1a/b expression causes a primary thyroid defect, and rescue experiments of the hypothyroid phenotype with wild-type or variant JAG1 transcripts support a role for JAG1 variations in the pathogenesis of the hypothyroid phenotype seen in CH and ALGS1 patients. CONCLUSIONS: clinical and experimental data indicate that ALGS1 patients have an increased risk of nonautoimmune hypothyroidism, and that variations in JAG1 gene can contribute to the pathogenesis of variable congenital thyroid defects, including CH.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c503b84fc2252c736abc88a8c8b591cdTest
http://hdl.handle.net/11567/876561Test