Document Detail


A novel thyroid stimulating immunoglobulin bioassay is a functional indicator of activity and severity of Graves' orbitopathy.
MedLine Citation:
PMID:  20237164     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: Immunoglobulins stimulating the TSH receptor (TSI) influence thyroid function and likely mediate extrathyroidal manifestations of Graves' disease (GD). OBJECTIVES: The aim of this study was to assess the clinical relevance of TSI in GD patients with or without Graves' orbitopathy (GO), to correlate the TSI levels with activity/severity of GO, and to compare the sensitivity/specificity of a novel TSI bioassay with TSH receptor (TSH-R) binding methods (TRAb). DESIGN: TSI were tested in two reporter cell lines designed to measure Igs binding the TSH-R and transmitting signals for cAMP/CREB/cAMP regulatory element complex-dependent activation of luciferase gene expression. Responsiveness to TSI of the novel chimeric (Mc4) TSH-R (amino acid residues 262-335 of human TSH-R replaced by rat LH-R) was compared with the wild-type (wt) TSH-R. RESULTS: All hyperthyroid GD/GO patients were TSI-positive. TSI were detected in 150 of 155 (97%, Mc4) and 148 of 155 (95%, wt) GO patients, in six of 45 (13%, Mc4) and 20 of 45 (44%, wt) mostly treated GD subjects, and in 0 of 40 (Mc4) and one of 40 (wt) controls. Serum TSI titers were 3- and 8-fold higher in GO vs. GD and control, respectively. All patients with diplopia and optic neuropathy and smokers were TSI-positive. TSI strongly correlated with GO activity (r = 0.87 and r = 0.7; both P < 0.001) and severity (r = 0.87 and r = 0.72; both P < 0.001) in the Mc4 and wt bioassays, respectively. Clinical sensitivity (97 vs. 77%; P < 0.001) and specificity (89 vs. 43%; P < 0.001) of the Mc4/TSI were greater than TRAb in GO. All 11 of 200 (5.5%) TSI-positive/TRAb-negative patients had GO, whereas all seven of 200 (3.5%) TSI-negative/TRAb-positive subjects had GD only. CONCLUSION: The novel Mc4/TSI is a functional indicator of GO activity and severity.
Authors:
S D Lytton; K A Ponto; M Kanitz; N Matheis; L D Kohn; G J Kahaly
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-17
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-06     Completed Date:  2010-05-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2123-31     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine I, Gutenberg University Medical Center, Mainz 55101, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Aged, 80 and over
Animals
Antithyroid Agents / therapeutic use
Female
Graves Disease / blood,  drug therapy,  radiotherapy,  surgery
Graves Ophthalmopathy / blood*,  drug therapy,  genetics,  radiotherapy,  surgery
Humans
Hyperthyroidism / blood,  drug therapy
Immunoglobulins, Thyroid-Stimulating / blood*
Iodine Radioisotopes / therapeutic use
Male
Methimazole / therapeutic use
Middle Aged
Rats
Receptors, Thyrotropin / metabolism
Reference Values
Severity of Illness Index
Thyroidectomy
Young Adult
Chemical
Reg. No./Substance:
0/Antithyroid Agents; 0/Immunoglobulins, Thyroid-Stimulating; 0/Iodine Radioisotopes; 0/Receptors, Thyrotropin; 60-56-0/Methimazole

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