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Article: Characterization of thyroid-stimulating blocking antibodies that appeared during transient hypothyroidism after radioactive iodine therapy

TitleCharacterization of thyroid-stimulating blocking antibodies that appeared during transient hypothyroidism after radioactive iodine therapy
Authors
Issue Date2000
PublisherMary Ann Liebert, Inc Publishers. The Journal's web site is located at http://www.liebertpub.com/thy
Citation
Thyroid, 2000, v. 10 n. 10, p. 909-917 How to Cite?
AbstractHypothyroidism after radioactive iodine (RAI) therapy for Graves' disease can be transient or permanent. The cause for early transient hypothyroidism is unknown. We evaluated 11 patients who developed transient hypothyroidism within 6 months of RAI and 12 who remained euthyroid after RAI. Approximately equal numbers of patients in each group had thyroid-stimulating antibody (TSAb) that increased cyclic adenosine monophosphate (cAMP) levels in Chinese hamster ovary (CHO) cells transfected with the recombinant human thyrotropin receptor (TSHR) (WT cells). Approximately equal numbers of patients from both groups had an increase in TSAb activity post-RAI. All TSAbs had their dominant functional epitope on the N-terminus of the TSHR extracellular domain, requiring residues 90-165 for activity because they, but not TSH, completely lost stimulating activity in a receptor chimera, wherein TSHR residues 90-165 were substituted by equivalent residues of the lutropin/choriogonadotropin receptor (LH/CGR). Although equal numbers of patients in both groups had thyrotropin-binding inhibiting immunoglobulin activity (TBII), as measured by radioreceptor assay before RAI, patients with transient hypothyroidism had a surge in TBII activity and all except one became positive for thyroid-stimulating blocking antibodies (TSBAb), as measured by inhibition of TSH-stimulated cAMP from WT cells. When immunoglobulin G (IgGs) were epitope-mapped using TSHR/LH-CGR chimeras with different substitutions, 8 hypothyroid subjects had TSBAbs directed against residues 90-165 of the TSHR, as well as TSHR residues 261-370. Two had functional epitopes directed at residues 9-89 as well as TSHR residues 261-370. None of the euthyroid control patients developed TSBAbs and their TBII activity decreased post-RAI. When patients with transient hypothyroidism reverted to a euthyroid state, TSAb was still detectable in 5; however, TBII was present in all and TSBAb, although decreased, was still positive in 9. In summary, RAI therapy was associated with a change in thyroid antibody characteristics in most patients. Additionally, patients with a surge in TBII and the appearance of TSBAb developed transient hypothyroidism after RAI.
Persistent Identifierhttp://hdl.handle.net/10722/162378
ISSN
2015 Impact Factor: 3.784
2015 SCImago Journal Rankings: 1.458
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorKung, AWCen_US
dc.contributor.authorLau, KSen_US
dc.contributor.authorKohn, LDen_US
dc.date.accessioned2012-09-05T05:19:24Z-
dc.date.available2012-09-05T05:19:24Z-
dc.date.issued2000en_US
dc.identifier.citationThyroid, 2000, v. 10 n. 10, p. 909-917en_US
dc.identifier.issn1050-7256en_US
dc.identifier.urihttp://hdl.handle.net/10722/162378-
dc.description.abstractHypothyroidism after radioactive iodine (RAI) therapy for Graves' disease can be transient or permanent. The cause for early transient hypothyroidism is unknown. We evaluated 11 patients who developed transient hypothyroidism within 6 months of RAI and 12 who remained euthyroid after RAI. Approximately equal numbers of patients in each group had thyroid-stimulating antibody (TSAb) that increased cyclic adenosine monophosphate (cAMP) levels in Chinese hamster ovary (CHO) cells transfected with the recombinant human thyrotropin receptor (TSHR) (WT cells). Approximately equal numbers of patients from both groups had an increase in TSAb activity post-RAI. All TSAbs had their dominant functional epitope on the N-terminus of the TSHR extracellular domain, requiring residues 90-165 for activity because they, but not TSH, completely lost stimulating activity in a receptor chimera, wherein TSHR residues 90-165 were substituted by equivalent residues of the lutropin/choriogonadotropin receptor (LH/CGR). Although equal numbers of patients in both groups had thyrotropin-binding inhibiting immunoglobulin activity (TBII), as measured by radioreceptor assay before RAI, patients with transient hypothyroidism had a surge in TBII activity and all except one became positive for thyroid-stimulating blocking antibodies (TSBAb), as measured by inhibition of TSH-stimulated cAMP from WT cells. When immunoglobulin G (IgGs) were epitope-mapped using TSHR/LH-CGR chimeras with different substitutions, 8 hypothyroid subjects had TSBAbs directed against residues 90-165 of the TSHR, as well as TSHR residues 261-370. Two had functional epitopes directed at residues 9-89 as well as TSHR residues 261-370. None of the euthyroid control patients developed TSBAbs and their TBII activity decreased post-RAI. When patients with transient hypothyroidism reverted to a euthyroid state, TSAb was still detectable in 5; however, TBII was present in all and TSBAb, although decreased, was still positive in 9. In summary, RAI therapy was associated with a change in thyroid antibody characteristics in most patients. Additionally, patients with a surge in TBII and the appearance of TSBAb developed transient hypothyroidism after RAI.en_US
dc.languageengen_US
dc.publisherMary Ann Liebert, Inc Publishers. The Journal's web site is located at http://www.liebertpub.com/thyen_US
dc.relation.ispartofThyroiden_US
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThis is a copy of an article published in the [Thyroid] © [2000] [copyright Mary Ann Liebert, Inc.]; [Thyroid] is available online at: http://www.liebertonline.com.-
dc.subject.meshAdulten_US
dc.subject.meshAgeden_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntibodies, Blocking - Immunology - Metabolismen_US
dc.subject.meshAutoantibodies - Immunology - Metabolismen_US
dc.subject.meshCho Cellsen_US
dc.subject.meshCricetinaeen_US
dc.subject.meshEpitopes - Immunologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshHumansen_US
dc.subject.meshHypothyroidism - Immunologyen_US
dc.subject.meshImmunoglobulin G - Immunologyen_US
dc.subject.meshImmunoglobulins, Thyroid-Stimulating - Immunology - Metabolismen_US
dc.subject.meshIodine Radioisotopes - Therapeutic Useen_US
dc.subject.meshMaleen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshReceptors, Thyrotropin - Genetics - Immunology - Metabolismen_US
dc.subject.meshThyroid Gland - Immunologyen_US
dc.subject.meshThyrotoxicosis - Immunology - Radiotherapyen_US
dc.subject.meshTransfectionen_US
dc.titleCharacterization of thyroid-stimulating blocking antibodies that appeared during transient hypothyroidism after radioactive iodine therapyen_US
dc.typeArticleen_US
dc.identifier.emailKung, AWC:awckung@hku.hken_US
dc.identifier.authorityKung, AWC=rp00368en_US
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.1089/thy.2000.10.909-
dc.identifier.pmid11081257-
dc.identifier.scopuseid_2-s2.0-0033769016en_US
dc.identifier.hkuros57615-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0033769016&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume10en_US
dc.identifier.issue10en_US
dc.identifier.spage909en_US
dc.identifier.epage917en_US
dc.identifier.isiWOS:000165124300010-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridKung, AWC=7102322339en_US
dc.identifier.scopusauthoridLau, KS=35205833900en_US
dc.identifier.scopusauthoridKohn, LD=8887452100en_US

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