0000000000310105
AUTHOR
Christian Wüster
A Novel Long-Term Graves’ Disease Animal Model Confirmed by Functional Thyrotropin Receptor Antibodies
<b><i>Introduction:</i></b> A novel long-term murine model for Graves’ disease (GD) using repeated, long-term immunizations with recombinant adenovirus expressing the extracellular A-subunit of the human thyrotropin receptor (Ad-TSHR) was applied to evaluate the functional anti-TSHR-antibody (TSHR-Ab) profile. <b><i>Methods:</i></b> BALB/c mice received 7 immunizations with either 10<sup>10</sup> plaque-forming units of Ad-TSHR or control Ad-GFP. Naïve (nonimmuized native) mice were also studied. Three 3-weekly immunizations were followed by 4-weekly boosts until the 7th immunization. Blocking (TBAb) and stimulating (TSAb) TSHR-Ab …
Comparison of a Novel Homogeneous Cyclic Amp Assay and a Luciferase Assay for Measuring Stimulating Thyrotropin-Receptor Autoantibodies.
Objective: Stimulating thyrotropin-receptor antibodies (TSAb) cause Graves’ disease (GD). We tested a novel homogeneous fluorescent 3′,5′ cyclic adenine monophosphate (cAMP) assay for the detection of TSAb in a bioassay. Methods: Chinese hamster ovary (CHO) cell lines expressing either a chimeric (MC4) or wild-type (WT) TSH-R were incubated with the adenyl cyclase activator forskolin, a human TSAb monoclonal antibody (M22), and with sera from GD patients. Intracellular cAMP levels were measured using a Bridge-It® cAMP assay, and the results were compared with a luciferase-based bioassay. Results: Both cell lines were stimulated with forskolin concentrations (0.006–200 µM) in a dose-dependen…
A cyclic peptide significantly improves thyroid function, thyrotropin-receptor antibodies and orbital mucine /collagen content in a long-term Graves’ disease mouse model
BALB/c mice which received long-term immunizations of adenovirus (Ad) expressing thyrotropin receptor A-subunits (TSHR) developed stable Graves' disease (GD). TSHR-derived cyclic peptide 19 (P19) was identified as effective therapy in this model.In Ad-TSHR mice, we investigated shorter disease intervals up to 4 months for histological alterations of the orbits, fine tuning of anti-TSHR antibodies (Ab) and free thyroxine (fT4) hormone levels by using novel detection methods in an independent laboratory. Therapy (0.3 mg/kg P19 or vehicle) was given intravenously after the fourth Ad-TSHR immunization (week 11) and continued until week 19.Thyrotropin binding inhibitory immunoglobulins (TBII, br…
Consensus Statement on the Use of Bone Turnover Markers for Short-Term Monitoring of Osteoporosis Treatment in the Asia-Pacific Region
Osteoporosis is a major health issue. By 2050, a greater than 2-fold increase in patients number with hip fractures will occur in Asia representing 50% of all hip fractures worldwide. For the Asia-Pacific (AP) region, more efforts on controlling osteoporosis and the subsequent fractures are crucial. Bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) is commonly used to diagnose osteoporosis and monitor osteoporosis treatment. However, the inconvenience, cost, limited availability of DXA and the delay in detection of BMD changes after treatment initiation support an important role for bone turnover markers (BTMs), as short-term tools to monitor therapy. With regards to low …
Performance and Specificity of 6 Immunoassays for TSH Receptor Antibodies: A Multicenter Study
Background: The measurement of TSH receptor (TSHR) antibodies is warranted for diagnosis of Graves’ disease (GD). Objective: The performance, detection sensitivity, and specificity of 6 TSHR immunoassays were compared. Methods: Two bioassays and 4 binding assays (Kronus, Immulite, Kryptor, Dynex) were compared in a dilution study performed in patients with autoimmune thyroid disease. Both bioassays were compared to 2 binding assays using stimulatory (M22) and blocking (K1–70) monoclonal antibody (MAb) mixtures. Results: Thirty samples from stimulatory (TSAb)-positive/blocking (TBAb)-negative patients with GD were diluted serially and measured in all assays. Samples were positive until dilut…
High Titers of Thyrotropin Receptor Antibodies Are Associated With Orbitopathy in Patients With Graves Disease.
AbstractContextSerum TSH receptor autoantibody (TSH-R-Ab) is a biomarker of Graves disease (GD). Studies have shown that the levels of this TSH-R-Ab have clinical significance.ObjectiveTo differentiate between thyroidal GD only and Graves orbitopathy (GD + GO).DesignControlled, follow-up study.SettingAcademic tertiary referral center for GD + GO.SubjectsSixty patients with GD, GD + GO, and controls.InterventionSerial serum dilution analyses with six automated, ELISA, and cell-based assays for TSH-R-Ab.Main Outcome MeasureDifferentiation among GD phenotypes.ResultsAll undiluted samples of hyperthyroid-untreated GD patients were positive with the six assays but became negative at dilution 1:9…
Binostril versus mononostril approaches in endoscopic transsphenoidal pituitary surgery: clinical evaluation and cadaver study.
OBJECTIVE Over the past 2 decades, endoscopy has become an integral part of the surgical repertoire for skull base procedures. The present clinical evaluation and cadaver study compare binostril and mononostril endoscopic transnasal approaches and the surgical techniques involved. METHODS Forty patients with pituitary adenomas were treated with either binostril or mononostril endoscopic surgery. Neurosurgical, endocrinological, ophthalmological, and neuroradiological examinations were performed. Ten cadaver specimens were prepared, and surgical aspects of the preparation and neuroradiological examination were documented. RESULTS In the clinical evaluation, 0° optics were optimal in the nas…
Endoscopic endonasal pituitary surgery: Surgical and outcome analysis of 50 cases
Abstract Objective Microsurgical transsphenoidal surgery for pituitary tumors has been standard therapy for decades and was established by Harvey Cushing in the early twentieth century. Today, endoscopy is increasingly accepted in the therapy of pituitary lesions. In this retrospective study, we analysed the surgical technique and outcome of 50 patients with pituitary lesions treated with an endoscopic endonasal trans-sphenoidal approach. Methods Between January 2004 and July 2005, 50 patients (30 female and 20 male) with pituitary tumors were operated upon using an endoscopic endonasal trans-sphenoidal procedure without nasal speculum or postoperative nasal packing. The follow-up period ra…