Thyroid-stimulating immunoglobulins and thyroid function tests in two siblings with neonatal thyrotoxicosis

Wit, Jan M.; Rees-Smith, Bernard; Creagh, F. M.; Bruinse, Hein W.; Heide, D. van der; Docter, R.; Gerards, L. J.

doi:10.1007/bf00441879

Cited by 9 publications

(4 citation statements)

References 24 publications

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“…In occasional reports appearing over 20 yr and using different assay methods, the half-life (tVfe) of the antibodies has been reported to vary from a few days (42,43) to a few weeks (1,2). Recently, however, Tamaki et al (44) have reported detailed studies of TSH receptor antibody halflives in seven neonates using a receptor assay.…”

Section: Trab In the Neonatementioning

confidence: 99%

Autoantibodies to the Thyrotropin Receptor

1988

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This review considers recent developments in our understanding of the properties of TRAb, particularly measurement of the antibodies and their sites of action and synthesis. Two new assay methods have allowed considerable improvements in the sensitivity, specificity, precision, and ease of measuring TRAb. In particular: 1) receptor assays based on inhibition of receptor-purified labeled TSH binding to detergent-solubilized TSH receptors and 2) bioassays based on stimulation of cAMP release from monolayer cultures of isolated thyroid cells. Detailed studies with the two assays indicate that TSH receptor antibodies nearly always act as TSH agonists in patients with a history of Graves' hyperthyroidism. Studies in areas of dietary iodine sufficiency suggest that measurement of the antibodies at various stages in the course of treating Graves' disease can be of value in predicting the outcome of therapy. However, in areas of iodine deficiency, difficulties in the ability of patients' thyroid tissue to recover from the effects of antithyroid drugs may prevent the receptor antibodies from causing a relapse of thyrotoxicosis. Consequently, the predictive value of receptor antibody measurements would be expected to be lower in these geographical areas. Although patients with a history of Graves' hyperthyroidism nearly always have TRAb which act as TSH agonists, about 20% of patients with frank hypothyroidism due to autoimmune destruction of the thyroid have TRAb which act as TSH antagonists (blocking antibodies). There is some evidence that these blocking antibodies can cause hypothyroidism particularly in the neonate. With regard to the site of synthesis of TRAb, there is now direct evidence that they are synthesized by thyroid lymphocytes, particularly the lymphocytes in close proximity to thyroid follicular cells. This is consistent with the well established effects of antithyroid treatment (drugs, radioiodine, or surgery) on TRAb levels in addition to their effects on thyroid hormone synthesis. Recent studies using affinity labeling with 125I-labeled TSH have enabled elucidation of the structure of the TSH receptor. TSH receptors in human, porcine, and guinea pig thyroid tissue have a two-chain structure in which the TSH binding site is formed on the outside surface of the cell membrane by a water-soluble A subunit (Mr approximately 50 K). The A subunit is linked by a disulfide bridge and weak noncovalent bonds to the amphiphilic B subunit (Mr approximately 30 K). This subunit, which penetrates the lipid bilayer, probably forms the site for interaction of the receptor with the regulatory subunits of adenylate cyclase.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Trab In the Neonatementioning

confidence: 99%

Autoantibodies to the Thyrotropin Receptor

1988

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“…In one case TSIs were suspected to be present in the breast milk, although with other assays this observation could not be confirmed [ 17]. So there are insufficient data on TSIs in breast milk to dissuade breast feeding.…”

Section: Practical Guidelines For Diagnosis and Treatmentmentioning

confidence: 89%

Fetal Treatment for Thyrotoxicosis in Non-Thyrotoxic Pregnant Women

Bruinse¹,

Vermeulen-Meiners

Wit³

1988

Fetal Diagn Ther

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Euthyroid or even hypothyroid pregnant women without antithyroid medication but with a history of treatment for thyrotoxicosis, almost always a subtotal strumectomy, may still produce thyroid-stimulating immunoglobulins. This can induce fetal and neonatal thyrotoxicosis. Without treatment this results in a high fetal and neonatal mortality and morbidity. Fetal treatment by administering antithyroid drugs during pregnancy improves this prognosis remarkably. A case is described, the literature is reviewed and guidelines for diagnosis and treatment are presented.

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“…Hohe TRAK-Titer können eine thyreostatische Therapie erforderlich machen (5,7,9). Die Wirkungsdauer diaplazentar übertragener T R A K wird in der Literatur sehr unterschiedlich beurteilt, wobei die Angaben zwischen wenigen Tagen und mehreren Monaten schwanken (2)(3)(4)10). Dies erklärt sich unter anderem durch die starke Variabilität der biologischen Halbwertszeit von IgG-Antikörpern.…”

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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Thyroid-stimulating immunoglobulins and thyroid function tests in two siblings with neonatal thyrotoxicosis

Cited by 9 publications

References 24 publications

Autoantibodies to the Thyrotropin Receptor

Autoantibodies to the Thyrotropin Receptor

Fetal Treatment for Thyrotoxicosis in Non-Thyrotoxic Pregnant Women

Frühgeborenenhyperthyreose durch diaplazentar übertragene TSH-Rezeptor-Antikörper der Mutter

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