title: Elevated Serum Tetrac in Graves Disease: Potential Pathogenic Role in Thyroid-Associated Ophthalmopathy.
abstract: The sources and biological impact of 3,3',5,5' tetraiodothyroacetic acid (TA4) are uncertain. CD34+ fibrocytes express several proteins involved in the production of thyroid hormones. They infiltrate the orbit in Graves disease (GD), an autoimmune process known as thyroid-associated ophthalmopathy. It appears that the thyrotropin receptor plays an important role in the pathogenesis of thyroid-associated ophthalmopathy.
  
  
  
  To quantify levels of TA4 in healthy participants and those with GD, determine whether fibrocytes generate this thyroid hormone analogue, and determine whether TA4 influences the actions of thyroid-stimulating hormone and thyroid-stimulating immunoglobulins in orbital fibroblasts.
  
  
  
  Patients with GD and healthy donors in an academic medical center clinical practice were recruited.
  
  
  
  Liquid chromatography-tandem mass spectrometry, autoradiography, real-time polymerase chain reaction, hyaluronan immunoassay.
  
  
  
  Serum levels of TA4 are elevated in GD. TA4 levels are positively correlated with those of thyroxine and negatively correlated with serum levels of triiodothyronine. Several cell types in culture generate TA4 from ambient thyroxine, including fibrocytes, HELA cells, human Müller stem cells, and retinal pigmented epithelial cells. Propylthiouracil inhibits TA4 generation. TA4 enhances the induction by thyrotropin and thyroid-stimulating immunoglobulins of several participants in the pathogenesis of thyroid-associated ophthalmopathy, including interleukin 6, hyaluronan synthase 1, prostaglandin endoperoxide H synthase 2, and haluronan production.
  
  
  
  TA4 may be ubiquitously generated in many tissues and enhances the biological impact of thyrotropin and thyroid-stimulating immunoglobulins in orbital connective tissue. These findings may identify a physiologically important determinant of extrathyroidal thyroid-stimulating hormone action.
authors: Department of Ophthalmology and Visual Sciences and.
authors: Roshini
authors: R
authors: Fernando
authors: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon 97239.
authors: Ekaterina
authors: E
authors: Placzek
authors: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon 97239.
authors: Edmund A
authors: EA
authors: Reese
authors: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon 97239.
authors: Andrew T
authors: AT
authors: Placzek
authors: Department of Ophthalmology and Visual Sciences and.
authors: Samantha
authors: S
authors: Schwartz
authors: Department of Ophthalmology and Visual Sciences and.
authors: Aaron
authors: A
authors: Trierweiler
authors: Department of Ophthalmology and Visual Sciences and.
authors: Leslie M
authors: LM
authors: Niziol
authors: Department of Ophthalmology and Visual Sciences and.
authors: Nupur
authors: N
authors: Raychaudhuri
authors: Department of Ophthalmology and Visual Sciences and.
authors: Stephen
authors: S
authors: Atkins
authors: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, Oregon 97239.
authors: Thomas S
authors: TS
authors: Scanlan
authors: Department of Ophthalmology and Visual Sciences and.|Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48105; and.
authors: Terry J
authors: TJ
authors: Smith
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001345:Autoradiography; D016022:Case-Control Studies; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D063928:Ependymoglial Cells / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005434:Flow Cytometry; D014453:Glucuronosyltransferase / Q000378:metabolism; D006111:Graves Disease / Q000097:blood* / Q000150:complications; D049970:Graves Ophthalmopathy / Q000097:blood* / Q000209:etiology; D006367:HeLa Cells; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism; D007118:Immunoassay; D018828:Immunoglobulins, Thyroid-Stimulating / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009915:Orbit; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D011989:Receptors, Thyrotropin / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism; D012737:Sex Factors; D053719:Tandem Mass Spectrometry; D013972:Thyrotropin / Q000378:metabolism; D013974:Thyroxine / Q000031:analogs & derivatives* / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D055815:Young Adult
chemical_list: C508600:IL6 protein, human; D018828:Immunoglobulins, Thyroid-Stimulating; D015850:Interleukin-6; D011989:Receptors, Thyrotropin; D014284:Triiodothyronine; D013972:Thyrotropin; D006820:Hyaluronic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D014453:Glucuronosyltransferase; C523794:HAS1 protein, human; D000076002:Hyaluronan Synthases; C011126:tetraiodothyroacetic acid; D013974:Thyroxine