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https://www.readbyqxmd.com/read/27913646/critical-differences-between-induced-and-spontaneous-mouse-models-of-graves-disease-with-implications-for-antigen-specific-immunotherapy-in-humans
#1
Basil Rapoport, Bianca Banuelos, Holly A Aliesky, Nicole Hartwig Trier, Sandra M McLachlan
Graves' hyperthyroidism, a common autoimmune disease caused by pathogenic autoantibodies to the thyrotropin (TSH) receptor (TSHR), can be treated but not cured. This single autoantigenic target makes Graves' disease a prime candidate for Ag-specific immunotherapy. Previously, in an induced mouse model, injecting TSHR A-subunit protein attenuated hyperthyroidism by diverting pathogenic TSHR Abs to a nonfunctional variety. In this study, we explored the possibility of a similar diversion in a mouse model that spontaneously develops pathogenic TSHR autoantibodies, NOD...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27913611/silent-somatotroph-tumour-revisited-from-a-study-of-80-patients-with-and-without-acromegaly-and-a-review-of-the-literature
#2
Laura Chinezu, Alexandre Vasiljevic, Jacqueline Trouillas, Marion Lapoirie, Emmanuel Jouanneau, Gérald Raverot
BACKGROUND: Silent somatotroph tumours are growth hormone (GH) immunoreactive (IR) pituitary tumours without clinical and biological signs of acromegaly. Their better characterisation is required to improve the diagnosis. MATERIALS AND METHODS: Twenty-one silent somatotroph tumours were compared to 59 somatotroph tumours with acromegaly. Tumours in each group were classified into GH and plurihormonal (GH/prolactin (PRL)/±thyroid-stimulating hormone (TSH)) and into densely granulated (DG) and sparsely granulated (SG) types...
February 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27906859/recent-advances-in-nuclear-medicine-in-endocrine-oncology
#3
Markus Luster, Andreas Pfestroff, Frederik A Verburg
PURPOSE OF REVIEW: The purpose is to review recent advances concerning the role of nuclear medicine in endocrine oncology. RECENT FINDINGS: For I therapy of thyroid cancer a thyrotropin (TSH) more than 30 mU/l has for many years been deemed a condition sine qua non. However, new data show that patients with lower TSH levels at the time of ablation have the same rate of successful ablation as those with TSH more than 30 mU/l.I-124 combined integrated positron emission tomography and computed X-ray tomography was shown to be highly accurate in predicting findings on posttherapy radioiodine scanning and was shown to have a high prognostic power...
January 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27905199/high-prevalence-of-anti-tsh-receptor-antibody-in-fibromyalgia-syndrome
#4
Kenya Nishioka, Toyoyoshi Uchida, Chie Usui, Ryota Tanaka, Takashi Matsushima, Yoshifuji Matsumoto, Ikuro Nakamura, Kusuki Nishioka, Nobutaka Hattori
AIM: Fibromyalgia syndrome (FMS) is defined as chronic widespread pain that cannot be accounted for by any other medical disorder. Our aim was to explore the prevalence of thyroid autoimmunity in patients with FMS. METHODS: For determining thyroid function in 207 FMS patients, we tested for the titers of free tri-iodothyronine, free thyroxine, thyroid-stimulating hormone (TSH), anti-thyroid peroxidase antibody (TPOAb), anti-thyroglobulin antibody (TgAb) and anti-TSH receptor antibody (TRAb)...
November 30, 2016: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/27904073/a-case-of-familial-dysalbuminemic-hyperthyroxinemia-fdh-in-japan-fdh-as-a-possible-differential-diagnosis-of-syndrome-of-inappropriate-secretion-of-thyroid-stimulating-hormone-sitsh
#5
Sakiko Kobayashi, Jaeduk Yoshimura Noh, Taeko Shimizu, Tomoaki Sato, Isao Kurihara, Kiminori Sugino, Hiroshi Itoh, Koichi Ito
Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant condition and is the most commonly inherited euthyroid hyperthyroxinemia in Caucasians. However, it is extremely rare in Asian populations. A 30-year-old Japanese woman, who was incidentally found to have apparent thyroid dysfunction, was admitted to our hospital in 2004. She had extremely elevated serum free thyroxine (FT4), moderately elevated free triiodothyronine (FT3), and normal thyroid-stimulating hormone (TSH). Clinical thyroid examination revealed no abnormalities other than small goiter...
November 30, 2016: Endocrine Journal
https://www.readbyqxmd.com/read/27903512/thyroid-hormone-stimulated-increases-in-pgc-1%C3%AE-and-ucp2-promote-life-history-specific-endocrine-changes-and-maintain-a-lipid-based-metabolism
#6
Bridget Martinez, José G Soñanez-Organis, Jose A Godoy-Lugo, Lillian Horin, Daniel E Crocker, Rudy M Ortiz
Thyroid hormones (TH) regulate metabolism, but are typically suppressed during times of stressful physiological conditions, including fasting. Interestingly, prolonged fasting in northern elephant seal pups is associated with reliance on a lipid-based metabolism and increased levels of circulating thyroid hormones that are partially attributed to active secretion as opposed to reduced clearance. This apparent paradox is coupled with complementary increases in cellular TH-mediated activity suggesting that in mammals naturally adapted to prolonged fasting TH are necessary to support metabolism...
November 30, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27895620/excessive-cytosolic-dna-fragments-as-a-potential-trigger-of-graves-disease-an-encrypted-message-sent-by-animal-models
#7
REVIEW
Yuqian Luo, Aya Yoshihara, Kenzaburo Oda, Yuko Ishido, Koichi Suzuki
Graves' hyperthyroidism is caused by autoantibodies directed against the thyroid-stimulating hormone receptor (TSHR) that mimic the action of TSH. The establishment of Graves' hyperthyroidism in experimental animals has proven to be an important approach to dissect the mechanisms of self-tolerance breakdown that lead to the production of thyroid-stimulating TSHR autoantibodies (TSAbs). "Shimojo's model" was the first successful Graves' animal model, wherein immunization with fibroblasts cells expressing TSHR and a major histocompatibility complex (MHC) class II molecule, but not either alone, induced TSAb production in AKR/N (H-2(k)) mice...
2016: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/27889471/functional-characterization-of-two-naturally-occurring-mutations-v-221-g-and-t-449-n-in-the-follicle-stimulating-hormone-receptor
#8
Antara A Banerjee, Swati K Achrekar, Shaini Joseph, Bhakti R Pathak, Smita D Mahale
Naturally occurring mutations in follicle stimulating hormone receptor (FSHR) affect the receptor function. Here, we characterized two such previously reported mutations, V(221)G and T(449)N, in the extracellular domain and transmembrane helix 3, of FSHR, respectively. Functional studies with the V(221)G mutant demonstrated an impairment in FSH binding and signaling. Validation of X-ray crystallography data indicating the contribution of FSHR specific residues in the vicinity of V(221) to contribute to FSH-FSHR interaction was carried out...
November 23, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27875255/glycosylation-pattern-analysis-of-glycoprotein-hormones-and-their-receptors
#9
Ricardo Núñez Miguel, Jane Sanders, Jadwiga Furmaniak, Bernard Rees Smith
We have studied glycosylation patterns in glycoprotein hormones (GPHs) and glycoprotein hormone receptor (GPHR) extracellular domains (ECD) from different species to identify areas not glycosylated that could be involved in inter- or intra-molecular interactions. Comparative models of the structure of the TSHR ECD in complex with TSH and in complex with TSHR autoantibodies (M22, stimulating and K1-70, blocking) were obtained based on the crystal structures of the FSH-FSHR ECD, M22-TSHR leucine-rich repeat domain (LRD) and K1-70-TSHR LRD complexes...
November 14, 2016: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/27864993/thyrotropin-alters-t-cell-development-in-the-thymus-in-subclinical-hypothyroidism-mouse-model
#10
Kunpeng Wu, Meng Zhao, Chunyan Ma, Haiqing Zhang, Xiaojing Liu, Lingyan Zhou, Jiajun Zhao, Ling Gao, Dan Wang
Subclinical hypothyroidism (SCH) is highly prevalent in the general population and is associated with potential deleterious effects. Although developing T cells express thyroid stimulating hormone receptor (TSH-R), the changes of T cell development in thymus in SCH have not been fully clarified. SCH mouse model, which is characterized by elevated serum TSH but similar thyroid hormone levels, were used to study the role of TSH in T cell development. Thymus weight of SCH mice increased 18% compared with controls...
November 16, 2016: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/27848228/high-levels-of-dna-polymerase-%C3%AE-mrna-corresponding-with-the-high-activity-in-graves-thyroid-tissue
#11
N Hayakawa, Y Sato, A Nagasaka, Y Mano, T Nagasaka, A Nakai, K Iwase, S Yoshida
INTRODUCTION: High DNA polymerase β activity has been observed in the thyroid tissue of patients with Graves' disease (Nagasaka et al. in Metabolism 37:1051-1054, 1988). This fact aroused our interest in whether the alteration of DNA polymerase β activity depends on DNA polymerase β (DNA poly β) mRNA levels, which may be modulated by thyroid-stimulating hormone (TSH) or thyroid-stimulating substances, i.e. TSH receptor antibody (TRAb). RESULT: Addition of TSH or TRAb to primary cultures of Graves' disease thyroid cells for 4 h led to no increase in DNA poly β mRNA levels...
November 15, 2016: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/27826021/effects-of-exposure-to-microcystin-lr-at-environmentally-relevant-concentrations-on-the-metabolism-of-thyroid-hormones-in-adult-zebrafish-danio-rerio
#12
Zidong Liu, Dapeng Li, Qing Hu, Rong Tang, Li Li
Microcystin-LR (MC-LR) has the potential to disturb thyroid hormone homeostasis. However, the effects of MC-LR at environmentally relevant concentrations on the thyroid system in adult fish are still unclear. In this study, adult zebrafish were exposed to 0, 1, 5, and 25 μg/L MC-LR for 7, 14, 21, and 28 days. Whole-body thyroid hormones (THs) levels and thyroid follicle histology were used to assess thyroid function. The transcription of corticotropin-releasing hormone (crh), thyroid-stimulating hormone (tsh), transthyretin (ttr), thyroid hormone receptors (trs) genes, and the activities of iodothyronine deiodinases (IDs) were investigated to study the process of TH metabolism disruption...
December 15, 2016: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/27821020/duox2-gene-mutation-manifesting-as-resistance-to-thyrotropin-rtsh-phenotype
#13
Panudda Srichomkwun, Junta Takamatsu, Deborah A Nickerson, Michael J Bamshad, Jessica X Chong, Samuel Refetoff
Resistance to TSH (RTSH; defined by an elevated TSH and a normal or hypoplastic thyroid gland) can be caused by mutations in genes encoding the TSH receptor and PAX8, and it has been linked to a locus on chromosome 15. In two non-consanguineous families with non-goitrous euthyroid hyperthyrotropinemia, typical of the RTSH phenotype, exome analysis identified five rare DUOX2 gene variants (p.A649E, p.P1391A, p.R885L, p.G488R and p.SF965-6SfsX29) found to be pathogenic. This form of non-goitrous dyshormonogenesis masquerades both clinically and biochemically as RTSH...
November 7, 2016: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/27813690/fetal-neonatal-thyrotoxicosis-in-a-newborn-from-a-hypothyroid-woman-with-hashimoto-s-thyroiditis
#14
Florian W Kiefer, Katrin Klebermass-Schrehof, Manuel Steiner, Christof Worda, Gregor Kasprian, Tanja Diana, George J Kahaly, Alois Gessl
CONTEXT: Fetal/neonatal thyrotoxicosis is a rare but potentially life-threatening condition. It is most commonly observed in poorly controlled Graves' disease during pregnancy. CASE DESCRIPTION: Here we describe the first reported case of thyrotoxicosis in a fetus/newborn from a woman with Hashimoto's thyroiditis and levothyroxine-treated hypothyroidism. Transplacental passage of stimulating TSH-receptor antibodies, measured by a cell-based bioassay, was the underlying mechanism of fetal/neonatal thyrotoxicosis even though the mother had no history of hyperthyroidism...
November 4, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27809680/in-vivo-functional-consequences-of-human-thra-variants-expressed-in-the-zebrafish
#15
Federica Marelli, Silvia Carra, Giuditta Rurale, Franco Cotelli, Luca Persani
Heterozygous mutations in the thyroid hormone receptor alpha (THRA) gene cause Resistance to Thyroid Hormone alpha (RTHα), a disease characterized by variable manifestations reminiscent of untreated congenital hypothyroidism but a raised T3/T4 ratio and normal TSH levels. We recently described that zebrafish embryos expressing a dominant negative (DN) form of thraa recapitulate the key features of RTHα, and that zebrafish and human receptors are functionally interchangeable. In this study we expressed several human TRα variants in zebrafish embryos and analyzed the resulting phenotypes...
November 3, 2016: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/27802347/ret-ptc-rearrangements-are-associated-with-elevated-postoperative-tsh-levels-and-multifocal-lesions-in-papillary-thyroid-cancer-without-concomitant-thyroid-benign-disease
#16
Xuan Su, Caiyun He, Jiangjun Ma, Tao Tang, Xiao Zhang, Zulu Ye, Yakang Long, Qiong Shao, Jianyong Shao, Ankui Yang
RET/PTC rearrangements, resulting in aberrant activity of the RET protein tyrosine kinase receptor, occur exclusively in papillary thyroid cancer (PTC). In this study, we examined the association between RET/PTC rearrangements and thyroid hormone homeostasis, and explored whether concomitant diseases such as nodular goiter and Hashimoto's thyroiditis influenced this association. A total of 114 patients diagnosed with PTC were enrolled in this study. Thyroid hormone levels, clinicopathological parameters and lifestyle were obtained through medical records and surgical pathology reports...
2016: PloS One
https://www.readbyqxmd.com/read/27793633/use-of-177-lu-dotatate-in-the-treatment-of-iodine-refractory-thyroid-carcinomas
#17
P Oliván-Sasot, M Falgás-Lacueva, J García-Sánchez, V Vera-Pinto, C Olivas-Arroyo, P Bello-Arques
In a patient with a differentiated thyroid cancer the standard treatment protocol to be followed is surgery, ablation of thyroid remnants with (131)Iodine ((131)I), and TSH suppression. However, the treatment with (131)I is not effective in some cases, and it no longer becomes a therapeutic option due to cell de-differentiation with loss of (131)I uptake. Systemic treatment can be used as other options, although patients are not always responsive; thus, the disease may progress and therapeutic options may run out...
October 25, 2016: Revista Española de Medicina Nuclear e Imagen Molecular
https://www.readbyqxmd.com/read/27785976/anti-tsh-autoantibodies-in-patients-with-macro-tsh-and-long-term-changes-in-macro-tsh-and-serum-tsh-levels
#18
Naoki Hattori, Takashi Ishihara, Naoki Matsuoka, Takanori Saito, Akira Shimatsu
<b><i>Background:</i></b> Macro-TSH is a high-molecular-weight form of TSH. Most cases of macro-TSH are TSH complexed with immunoglobulin G. This study was undertaken to characterize macro-TSH. <b><i>Methods:</i></b> Blood samples taken from patients with subclinical hypothyroidism were screened for the presence of macro-TSH with the polyethylene glycol method and confirmed with gel filtration chromatography. The TSH receptor antibody (TRAb) was quantified with an electrochemiluminescence immunoassay...
October 27, 2016: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/27781146/prevalence-and-impact-of-autoimmune-thyroid-disease-on-myasthenia-gravis-course
#19
Justyna Kubiszewska, Beata Szyluk, Piotr Szczudlik, Zbigniew Bartoszewicz, Małgorzata Dutkiewicz, Maksymilian Bielecki, Tomasz Bednarczuk, Anna Kostera-Pruszczyk
OBJECTIVES: Autoimmune thyroid diseases (ATDs) frequently accompany myasthenia gravis (MG) and may influence its course. We aimed to determine the association and impact of ATD with early- (<50 years), late-onset MG, or thymoma-MG. MATERIALS AND METHODS: Prevalence of ATD was measured in a cross-sectional study of 343 consecutive patients with MG (236 F, 107 M) aged 4-89 years; 83.8% were seropositive, in 2.9%, anti-MuSK antibodies were detected. Concentrations of antithyroid peroxidase antibodies, antithyroglobulin antibodies, antithyrotropin receptor antibodies, and TSH level were measured in all patients...
October 2016: Brain and Behavior
https://www.readbyqxmd.com/read/27774323/syndrome-of-reduced-sensitivity-to-thyroid-hormones-two-case-reports-and-a-literature-review
#20
Anastasios Anyfantakis, Dimitrios Anyfantakis, Irene Vourliotaki
Resistance to thyroid hormone (RTH) is an extremely rare dominantly inherited condition of impaired tissue responsiveness to thyroid hormone (TH). Most patients with RTH have mutations in the gene that encodes the β isoform of the receptor of thyroid hormone (THR-β gene). Mutant receptors are unable to activate or repress target genes. The majority of them are asymptomatic or rarely have hypo- or hyperthyroidism. RTH is suspected by the finding of persistent elevation of serum levels of free T3 (FT3) and free T4 (FT4) and nonsuppressed TSH...
2016: Case Reports in Endocrinology
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