Radioimmunological Studies on the Long-Acting Thyroid Stimulator

Pinchera, Aldo; Rovis, L; Grasso, Lucia; Liberti, Paul A.; Martino, Enio; Fenzi, Gianfranco; Baschieri, L

doi:10.1210/endo-87-2-217

Cited by 16 publications

(4 citation statements)

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“…Seit langem ist bekannt, daß schilddrüsenspezifische Antikörper plazentagängig sind (3,6). Die ungehinderte Passage der Plazentaschranke wird in unserem Fall durch quasi identische TRAK-Titer im mütterlichen und kindlichen Kreislauf zum Zeitpunkt der Geburt belegt.…”

Section: Diskussionunclassified

Frühgeborenenhyperthyreose durch diaplazentar übertragene TSH-Rezeptor-Antikörper der Mutter

Rink¹,

Wieg²,

Schroth³

et al. 1999

Nuklearmedizin

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ZusammenfassungDie Wirkungsdauer diaplazentar übertragener TSH-Rezeptor-Antikörper (TRAK) wird am Beispiel einer 23jährigen Patientin mit M. Basedow und manifester Hyperthyreose diskutiert, die sechs Wochen nach Diagnosestellung schwanger wurde und die thyreostatische Medikation eigenverantwortlich absetzte. Bei einer Kontrolluntersuchung in der 20. Gestationswoche fand sich dementsprechend erneut eine hyperthyreote Stoffwechsellage, die zur Einleitung einer Thyreostase mit Propylthiouracil führte. Auch diese Medikation wurde von der Patientin jedoch bereits kurze Zeit später wieder abgebrochen. In der 32. Woche endete die Schwangerschaft mit einer Frühgeburt. Das männliche Neugeborene zeigte bereits deutliche Zeichen einer thyreotoxischen Krise und entwickelte im weiteren Verlauf einen zunehmend reduzierten Allgemeinzustand mit einer Sinustachykardie bis 190/min, Fieber, Tremor und respiratorischer Störung. Erwartungsgemäß fand sich eine ausgeprägte Hyperthyreose. Der TRAK-Titer lag bei 180 U/l (normal <15). Eine Therapie mit Propranolol und Prednisolon führte bereits zu einer deutlichen Besserung der Symptome. Als sich nach zwölf Tagen noch kein klarer Rückgang der Schilddrüsenhormonspiegel zeigte, wurde zusätzlich eine thyreostatische Medikation eingeleitet. Hierunter konnte nach neun Tagen eine periphere Euthyreose erreicht werden. Nach Absetzen des Thyreostatikums entwickelte sich jedoch innerhalb von einer Woche erneut eine manifeste Hyperthyreose, die nochmals eine thyreostatische Therapie in niedrigerer Dosierung für 26 Tage erforderlich machte. Danach war der TRAK-Titer auf 25 U/l abgefallen, und es kam zu keinem weiteren Hyperthyreoserezidiv. Die biologische Halbwertszeit der TRAK betrug in unserem Fall 20 Tage.

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Section: Diskussionunclassified

Frühgeborenenhyperthyreose durch diaplazentar übertragene TSH-Rezeptor-Antikörper der Mutter

Rink¹,

Wieg²,

Schroth³

et al. 1999

Nuklearmedizin

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“…Thionamide therapy is, however, also associated with a reduction in thyroid autoantibodies, including thyroid stimulating autoantibodies (TSAbs) [l, 2, 80, 81, 961. One hypothesis to explain this was that thionamides had an immunosuppressive action on lymphocytes or antigen presenting cells, particularly those in the thyroid [I, 2,[96][97][98]. The immunosuppressive action of thionamides on lymphocytes was, however, questioned [80, 99, 1001 and a direct thyroid action, possibly reduced antigen signalling was postulated [80, 99, 1001. Treatment of rat thyroid FRTL-5 cells with the antithyroid drug, MMI, results in decreased class I RNA levels (Fig.…”

Section: Regulation Of Mhc Class I Gene Expression In the Thyroid Andmentioning

confidence: 99%

Molecular Basis for the Autoreactivity Against Thyroid Stimulating Hormone Receptor

Kohn

Kosugi

Ban

et al. 1992

International Reviews of Immunology

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The present report identifies an important immunogenic region of the TSH receptor and determinants on the TSH receptor for the two types of autoantibodies seen in hyperthyroid Graves' disease and hypothyroid idiopathic myxedema, TSAbs and TSBAbs, respectively. The immunogenic domain with no important functional determinants, is contained within residues 303-382 and involves residues 352-366 in particular. There are determinants flanking the immunogenic domain on the C-terminal portion of the receptor which are the TSBAb and high affinity TSH binding sites: residues 295-306, 387-395, and tyrosine 385. Determinants on the N-terminal portion of the external domain, centered on residues 38-45, are TSAb interactions linked to low affinity TSH binding important for signal generation: threonine 40 and residues 30-33, 34-37, 42-45, 52-56, and 58-61. These determinants are conserved in human and rat receptors, are not present in gonadotropin receptors, and are each related to separate actions of TSH: binding vs. signal generation. They can, therefore, account for organ specific autoimmunity and the different disease expression effected by TSBAbs vs TSAbs, i.e. hypo- vs. hyperthyroidism, respectively. It is proposed that, in the thyroid, hormonal (TSH, insulin, hydrocortisone, IGF-I) suppression of class I genes might be one means of preserving self-tolerance in the face of the hormone action to increase the expression of tissue specific genes such as thyroglobulin and thyroid peroxidase. Inappropriately high class I expression in the thyroid, i.e. if induced by interferon, viruses, or some as yet unknown agent, would contribute to the generation of autoimmune disease. Thus, it would result in increased antigen presentation to the immune system, particularly those autoantigens increased by TSH and its cAMP signal such as thyroglobulin or thyroid peroxidase, or whose turnover is increased by TSH and its cAMP signal, such as the TSH receptor. In the case of the latter, peptide 352-366, known to be near a protease sensitive site on the receptor [41,49], would now act as a potent self-antigen and induce the formation of receptor autoantibodies. It is further proposed that methimazole and high doses of iodide are therapeutically effective agents in thyroid autoimmune disease because they, in part, decrease MHC class I gene expression. Speculation is presented which suggests that elimination of negative regulation of MHC class I and the TSH receptor is an important factor in the development of autoimmune thyroid disease.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…The observation that the biological activity of LATS [3] or TSAb [4] can be neu tralized by incubation with thyroid tissue is consistent with the view that the antigen responsible for the production of these anti bodies is a thyroid component. The concept that this neutralization reflects the interac tion with a thyroid antigen is supported by the finding that the neutralized biological ac tivity may be recovered by the use of agents such as 1.5 M thiocyanate [5], known to dis rupt antigen-antibody complexes. Fractiona tion of thyroid homogenate has shown that the most potent LATS-neutralizing compo nent is associated with plasma membranes, as assessed by electron microscopy and mea surement of appropriate enzymic markers.…”

Section: Nomenclature and Assaysmentioning

confidence: 99%

Thyroid-Stimulating Immunoglobulins

Pinchera¹,

Fenzi²,

Macchia³

et al. 1982

Horm Res

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The presence of thyroid-stimulating immunoglobulins in patients with Graves’ disease is well established. Considerable evidence has accumulated that these immunoglobulins are antibodies to a thyroid plasma membrane antigen whose precise nature remains to be identified. The question whether the antigen is related to the TSH receptor is still debated. The causative role of thyroid-stimulating immunoglobulins in the hyperthyroidism of Graves’ disease is widely recognized. The use of human specific stimulation assays has circumvented the objection of the relatively low frequency of long-acting-thyroid-stimulator-(LATS)-positive patients. Individual variations in the thyroid response may account for the lack of correlation between the levels of thyroid-stimulating immunoglobulins and most parameters of thyroid function. In this respect, the interference of nonstimulatory thyroid antibodies and of other autoimmune mechanisms may be of importance. An important clinical implication of thyroid-stimulating immunoglobulin determinations is their value in predicting the relapse of hyperthyroidism in treated patients. This clinical application has been so far limited by the technical difficulties of the assays. This emphasizes the need for a simple and reliable test, which can be used for routine measurements of thyroid-stimulating immunoglobulins.

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Radioimmunological Studies on the Long-Acting Thyroid Stimulator

Cited by 16 publications

References 0 publications

Frühgeborenenhyperthyreose durch diaplazentar übertragene TSH-Rezeptor-Antikörper der Mutter

Frühgeborenenhyperthyreose durch diaplazentar übertragene TSH-Rezeptor-Antikörper der Mutter

Molecular Basis for the Autoreactivity Against Thyroid Stimulating Hormone Receptor

Thyroid-Stimulating Immunoglobulins

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