Comparison of practical methods for urinary glycosaminoglycans and serum hyaluronan with clinical activity scores in patients with Graves' ophthalmopathy.
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.
Martins
João R M
JR
Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Sao Paulo, Brazil.
Furlanetto
Reinaldo P
RP
Oliveira
Lhoyane M
LM
Mendes
Aline
A
Passerotti
Carlo C
CC
Chiamolera
Maria Izabel
MI
Rocha
Antonio J
AJ
Manso
Paulo G
PG
Nader
Helena B
HB
Dietrich
Carl P
CP
Maciel
Rui M B
RM
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
D006025:Glycosaminoglycans; D006820:Hyaluronic Acid