Resorption, Transport und Bioverfügbarkeit von Schilddrüsenhormonen

 

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Zusammenfassung

Klassische Schilddrüsenhormone (Jodothyronine), die zu den häufigst verordneten Präparaten zählen, weisen als Pharmaka kritischer Dosierung eine geringe therapeutische Breite auf. Mittlerweile konnten die Mechanismen ihrer Resorption teilweise aufgeklärt werden – sie findet insbesondere distal des Duodenums statt. Die Bioverfügbarkeit der Jodothyronine, die an einem enterohepatischen Kreislauf teilnehmen, liegt bei ca. 70 %. Multiple Einflussfaktoren wie gleichzeitig eingenommene Medikamente, Nahrungsmittel und bestimmte Krankheitsbilder wirken sich auf ihre Resorption aus. Im Plasma zirkulieren Schilddrüsenhormone nur zu einem Bruchteil frei, der größte Anteil ist an Plasmaproteine gebunden, wobei die Bindung wiederum vielfältigen Einflüssen unterliegt. Verantwortlich für ihre intrazelluläre Akkumulation sind mindestens zehn unterschiedliche aktive und energieabhängige Transportmechanismen, die unterschiedlich im Gewebe verteilt sind. Bei bestimmten Krankheitsbildern und physiologischen Situationen ändert sich die Plasmaproteinbindung, Bei Betrachtung der Gesamthormone kann dies zu differentialdiagnostischen Schwierigkeiten führen. Veränderungen der Proteinbindung und ebenso des Membrantransports von Jodothyroninen sind insbesondere bei kritisch Kranken (NTIS) häufig. Bei der Substitutionstherapie hypothyreoter Patienten erwiesen sich unterschiedliche Handelspräparate als nicht bioäquivalent, so dass nach Umstellung der Therapie eine Kontrolle der Stoffwechsellage notwendig ist.

Summary

The frequently prescribed classical thyroid hormones (iodothyronines) are critical dose drugs with a narrow therapeutic index. Nowadays the mechanisms of their absorption, which takes place predominantly in the jejunum and ileum, have only partly been elucidated. Bioavailability of iodothyronines whose kinetics is subject to enterohepatic circulation, is about 70 %. Several factors influence their absorption including nutrients, drugs and concomitant diseases. After being absorbed only a small fraction of thyroid hormones circulates freely in plasma, whereas the greater portion is bound to plasma proteins. This binding, too, may be influenced by numerous factors; alterations by certain diseases and physiological conditions may lead to ambiguities in differential diagnosis. Intracellular accumulation of iodothyronines is accomplished by at least ten different active and energy-dependent transporters with variable tissue distribution. Particularly in critical illness (non-thyroidal illness syndrome) alterations of protein binding and membrane transport are common. In therapy of hypothyroid patients different brand-name products lack bioequivalence and thus requiring subsequent monitoring of thyroid status after treatment has been changed among different brand-name versions.

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Dr. med. Johannes W. Dietrich

Medizinische Klinik I, Allgemeine Innere Medizin, Endokrinologie und Diabetologie, BG Universitätsklinikum Bergmannsheil GmbH, Ruhr-Universität Bochum

Bürkle-de-la-Camp-Platz 1

44789 Bochum

Phone: 0234/302-6400

Fax: 0234/302-6403

Email: johannes.w.dietrich@bergmannsheil.de