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Fulltext Orbital Signaling in Graves' Orbitopathy

Draman MS, Zhang L, Dayan C, Ludgate M

Front Endocrinol (Lausanne), 2021;12:739994.
PMID: 34899596 DOI: 10.3389/fendo.2021.739994

Graves' orbitopathy (GO) is a complex and poorly understood disease in which extensive remodeling of orbital tissue is dominated by adipogenesis and hyaluronan production. The resulting proptosis is disfiguring and underpins the majority of GO signs and symptoms. While there is strong evidence for the thyrotropin receptor (TSHR) being a thyroid/orbit shared autoantigen, the insulin-like growth factor 1 receptor (IGF1R) is also likely to play a key role in the disease. The pathogenesis of GO has been investigated extensively in the last decade with further understanding of some aspects of the disease. This is mainly derived by using in vitro and ex vivo analysis of the orbital tissues. Here, we have summarized the features of GO pathogenesis involving target autoantigens and their signaling pathways.

Matched MeSH terms: Receptors, Thyrotropin/metabolism*
Pseudohypoparathyroidism: A case of hypocalcemia and hypothyroidism diagnosed during the postpartum period

Lim KP, Yong SL

Malays Fam Physician, 2019;14(1):31-34.
PMID: 31289630

We describe a 29-year-old Para 1 post-Emergency Lower Segment Caesarean Section (EMLSCS) for fetal distress and Preterm Rupture of the Membrane (PROM) referred by the Obstetric team for persistent bradycardia. She had the typical features of Albright's Hereditary Osteodystrophy (AHO). The laboratory investigation revealed hypocalcemia, hyperphosphatemia with a high Parathyroid hormone (PTH) level and low free Thyroxine 4 (fT4) with high Thyroid Stimulating Hormone (TSH). The patient was diagnosed with Pseudohypoparathyroidism (PHP) Type 1A associated with TSH resistance based on the somatic features of AHO present as well as biochemical and radiological abnormalities.

Matched MeSH terms: Receptors, Thyrotropin
Fulltext Clinical value of a rapid fully automated thyroid autoantibody assay in the diagnosis and management of graves disease

Hanita, O., Azura, N.R., Faizal, M.M.Z.

Medicine & Health, 2012;7(1):24-31.
MyJurnal

The most common cause of hyperthyroidism is Graves disease (GD) which is characterised by the presence of autoantibodies which binds to the TSH receptor (TRAb). Recently, a rapid, fully automated electrochemiluminescent immunoassay ElecsysAnti-TSHR for detection of autoantibodies to TSH receptor was made available for routine clinical use. The objective of this study is to evaluate this assay and to determine the sensitivity, specificity and cut-off value. Interassay and total imprecision (CV) were determined at 3.78-7.02 IU/L and 13.5-21.2 IU/L respectively. A total of 124 samples which comprised of 46 GD, seven Hashimoto thyroiditis (HD), 11 non autoimmune nodular goitre (NAG), 2 thyroid cancers (Ca) and 58 normal controls were retrospectively analysed to determine the sensitivity, specificity and cut-off value. Inter-assay CV’s were 2.4% at a concentration of 3.90 IU/L (range: 3.78-7.02 IU/l) and 0.8% at 20.80 IU/L (range:13.5-21.2 IU/l). Total imprecision was 3.8% at a concentration of 3.80 IU/L (range:13.5-21.2 IU/l) and 1.0% at 20.8 IU/L (range:13.5-21.2 IU/l). The ROC analysis of patients with GD, other thyroid disorders and normal controls revealed that the highest sensitivity (94%) and specificity (98%) were seen at cut-off value of 1.69 IU/L. Positive predictive value (PPV) and negative predictive value (NPV) was 95% and 94% respectively. At this derived cut-off value of 1.69 IU/L, we found that the sensitivity of TRAb positivity within the group of 29 newly diagnosed GD patients was 94%. Our results demonstrate that this fully automated assay with testing time of 27 minutes has high sensitivity in detecting GD and high specificity for discriminating other thyroid disease and represent major improvement in the diagnosis and management of patients with thyroid diseases.

Matched MeSH terms: Receptors, Thyrotropin
Fulltext Gut Microbiome Associated With Graves Disease and Graves Orbitopathy: The INDIGO Multicenter European Study

Biscarini F, Masetti G, Muller I, Verhasselt HL, Covelli D, Colucci G, et al.

J Clin Endocrinol Metab, 2023 Jul 14;108(8):2065-2077.
PMID: 36683389 DOI: 10.1210/clinem/dgad030

CONTEXT: Gut bacteria can influence host immune responses but little is known about their role in tolerance-loss mechanisms in Graves disease (GD; hyperthyroidism caused by autoantibodies, TRAb, to the thyrotropin receptor, TSHR) and its progression to Graves orbitopathy (GO).
OBJECTIVE: This work aimed to compare the fecal microbiota in GD patients, with GO of varying severity, and healthy controls (HCs).
METHODS: Patients were recruited from 4 European countries (105 GD patients, 41 HCs) for an observational study with cross-sectional and longitudinal components.
RESULTS: At recruitment, when patients were hyperthyroid and TRAb positive, Actinobacteria were significantly increased and Bacteroidetes significantly decreased in GD/GO compared with HCs. The Firmicutes to Bacteroidetes (F:B) ratio was significantly higher in GD/GO than in HCs. Differential abundance of 15 genera was observed in patients, being most skewed in mild GO. Bacteroides displayed positive and negative correlations with TSH and free thyroxine, respectively, and was also significantly associated with smoking in GO; smoking is a risk factor for GO but not GD. Longitudinal analyses revealed that the presence of certain bacteria (Clostridiales) at diagnosis correlated with the persistence of TRAb more than 200 days after commencing antithyroid drug treatment.
CONCLUSION: The increased F:B ratio observed in GD/GO mirrors our finding in a murine model comparing TSHR-immunized with control mice. We defined a microbiome signature and identified changes associated with autoimmunity as distinct from those due to hyperthyroidism. Persistence of TRAb is predictive of relapse; identification of these patients at diagnosis, via their microbiome, could improve management with potential to eradicate Clostridiales.

Matched MeSH terms: Receptors, Thyrotropin
Expression of proteins related to thyroid hormone function in the uterus is down-regulated at the day of implantation in hypothyroid pregnant rats

Salleh N, Sayem ASM, Giribabu N, Khaing SL

Cell Biol Int, 2019 May;43(5):486-494.
PMID: 30761678 DOI: 10.1002/cbin.11114

Hypothyroidism has been linked to infertility, but the mechanisms underlying infertility-related hypothyroidism have yet to be fully elucidated. Therefore, in this study, effects of hypothyroidism on expression of the proteins related to thyroid hormone function in the uterus, which were thought to play a role implantation, including thyroid hormone receptor (TR), thyroid stimulating hormone receptor (TSHR), retinoic acid receptor (RAR) and extracellular kinase (ERK) were identified. Pregnant female rats were rendered hypothyroid by giving methimazole (MMI), orally. Following hypothyroid induction, rats were grouped into control (non-treated) and received subcutaneous thyroxine at 20, 40, and 80 μg/kg/day for five consecutive days. At Day 6, which is the day of implantation (GD 6), rats were sacrificed and the number of embryo implantation site in the uterus was calculated. Then, uterine horns were harvested and expression of the above proteins and their mRNAs were identified by Western blotting and real-time PCR, respectively. In non-treated hypothyroid pregnant rats, the number of embryo implantation sites decreased as compared to euthyroid and hypothyroid rats receiving thyroxine treatment. Similarly, expression of TRα-1, TRβ-1, TSHR, ERK1/2 and RAR proteins and mRNA in the uterus of non-treated hypothyroid rats also decreased (P

Matched MeSH terms: Receptors, Thyrotropin/analysis; Receptors, Thyrotropin/metabolism
Thyroid autoantibodies and associated complications during pregnancy

Nor Azlin MI, Bakin YD, Mustafa N, Wahab NA, Johari MJ, Kamarudin NA, et al.

J Obstet Gynaecol, 2010;30(7):675-8.
PMID: 20925608 DOI: 10.3109/01443615.2010.503908

This study was undertaken to determine the presence of thyroid autoantibodies and associated pregnancy complications from 49 pregnant women with thyroid disease. There were 31 (63%) women with Graves' disease (GD) and 18 (37%) with primary hypothyroidism (PHT). A total of 26 (53.1%) women, 19 (61%) with GD and seven (39%) with PHT, had positive antibodies. Six had thyroid peroxidase antibodies (TPO), one with thyroglobulin antibody (TG) and eight had TSH receptor antibodies (TR). Two had a mixture of antibodies involving TG/TPO (one GD vs one PHT), four with TG/TPO/TR (all had GD) and five with TPO/TR (four with GD vs one with PHT). There were associations in women with positive thyroid antibodies and pre-eclampsia (15.4%), abruptio placenta (4%), caesarean deliveries (31%), postpartum thyroiditis (19.2%) and abnormal neonatal thyroid function (15.4%). Women with positive thyroid antibodies in pregnancy need close care during and after pregnancy, as they can develop complications affecting both mother and fetus.

Matched MeSH terms: Receptors, Thyrotropin/immunology