title: Comparison of practical methods for urinary glycosaminoglycans and serum hyaluronan with clinical activity scores in patients with Graves' ophthalmopathy.
abstract: OBJECTIVE
  Immunosuppressive treatment of Graves' opthalmopathy (GO) should be restricted to patients with active eye disease, but assessing disease activity is difficult. Several methods to evaluate GO activity have been introduced, but none of them is satisfactory. Glycosaminoglycans (GAGs) are complex polysaccharides that participate on the pathogenesis of GO and attempts to correlate its local increase to urinary GAGs (uGAGs) or serum hyaluronan (sHA) have been made, but the available techniques are labourious, time-consuming and difficult for routine use. The aim of the present study is to develop practical and simple methods for uGAGs and sHA and compare them to the activity and severity of thyroid-associated ophthalmopathy.
  
  
  METHODS
  We developed a microelectrophoresis technique for uGAGs and a fluoroassay for sHA and assessed each in 152 patients with Graves' disease, 25 without GO and 127 with GO, classified according to the Clinical Activity Score (CAS). All patients had been euthyroid for > 2 months.
  
  
  RESULTS
  Patients with inactive disease (CAS = 2, n = 100) had uGAGs (4.2 +/- 1.3 micro g/mg/creatinine) and sHA (11.1 +/- 7.2 micro g/l) that did not differ from normal subjects (3.1 +/- 1.1 micro g/mg/creatinine, n = 138 and 13.9 +/- 9.6 micro g/l, n = 395). In contrast, patients with active eye disease (CAS = 3, n = 27) had uGAGs (8.4 +/- 2.7 micro g/mg/creatinine) and sHA (32.3 +/- 17.8 micro g/l) 2-3 times higher than those patients with inactive eye disease. Using a cut-off of 6.1 micro g/mg creatinine for uGAGs and 20.7 micro g/l for sHA we found, respectively, 85% and 81% sensitivity and 93% and 91% specificity for each test. The positive and negative predictive values were 77% and 96% for uGAGs and 71% and 95% for sHA.
  
  
  CONCLUSIONS
  Employing these two new methods we have established a significant relationship between the levels of uGAGs and/or sHA and the clinical activity of GO. Therefore, together with CAS, uGAGs determination, and, to a lesser degree, sHA, would be very useful in the discrimination from active and inactive ocular disease and aid in deciding on the best therapy for GO patients.
authors.affiliation: Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.
authors.forename: João R M
authors.initials: JR
authors.lastname: Martins
authors.forename: Reinaldo P
authors.initials: RP
authors.lastname: Furlanetto
authors.forename: Lhoyane M
authors.initials: LM
authors.lastname: Oliveira
authors.forename: Aline
authors.initials: A
authors.lastname: Mendes
authors.forename: Carlo C
authors.initials: CC
authors.lastname: Passerotti
authors.forename: Maria Izabel
authors.initials: MI
authors.lastname: Chiamolera
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Rocha
authors.forename: Paulo G
authors.initials: PG
authors.lastname: Manso
authors.forename: Helena B
authors.initials: HB
authors.lastname: Nader
authors.forename: Carl P
authors.initials: CP
authors.lastname: Dietrich
authors.forename: Rui M B
authors.initials: RM
authors.lastname: Maciel
mesh_terms: D000208:Acute Disease; D000328:Adult; D016022:Case-Control Studies; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005260:Female; D005470:Fluorometry / Q000379:methods; D006025:Glycosaminoglycans / Q000652:urine*; D006111:Graves Disease / Q000097:blood* / Q000652:urine*; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D012907:Smoking
chemical_list: D006025:Glycosaminoglycans; D006820:Hyaluronic Acid