| A novel thyroid stimulating immunoglobulin bioassay is a functional indicator of activity and severity of Graves' orbitopathy. | |
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MedLine Citation:
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PMID: 20237164 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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S D Lytton; K A Ponto; M Kanitz; N Matheis; L D Kohn; G J Kahaly |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-17 |
Journal Detail:
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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:
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Created Date: 2010-05-06 Completed Date: 2010-05-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: 2123-31 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine I, Gutenberg University Medical Center, Mainz 55101, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/Antithyroid Agents; 0/Immunoglobulins, Thyroid-Stimulating; 0/Iodine Radioisotopes; 0/Receptors, Thyrotropin; 60-56-0/Methimazole |
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