Resorption, Transport und Bioverfügbarkeit von Schilddrüsenhormonen

Abstract

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.

Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming

“…Dopamine, glucocorticoids, and somatostatin analogs suppress TSH release (371). Thyroxine absorption is altered by multiple substances including caffeine, bile acid sequestrants, sucralfate, ferrous sulfate, and aluminum hydroxide (372). This results in disruption of the enterohepatic circulation of thyroid hormones, thus contributing to reduced half-life.…”

Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research

“…Additionally, this platform paved the way for the development of an improved protocol for bioequivalence studies. Thyroid hormones are critical dosage drugs, i.e., small changes in concentration may exert major metabolic effects, and the absorption rate is highly sensitive to multiple influencing factors including meals, coffee, concomitant medication, and gastrointestinal disease ( 38 ). Moreover, l -T4 preparations of different brands cannot be considered bioequivalent ( 39 , 40 ).…”

TSH and Thyrotropic Agonists: Key Actors in Thyroid Homeostasis

“…Additional mechanisms of homeostasis include autoregulation, where clearance of iodothyronines increases with their plasma levels [64–66], increased degradation of TSH in hyperthyroidism [67], possible ultrashort feedback control of TRH secretion, [68] and numerous mechanisms involving control of thyroid hormone transporters and receptor density [15, 17, 69–73]. Moreover, iodothyronines are subject to enterohepatic circulation that is a target of additional control signals [16, 74] and due to the prokinetic effects of iodothyronines possibly including thyroid hormones themselves [75, 76]. …”

“…In NTIS, however, disruption of thyroid hormone signalling by cytokines, metabolites, toxins or drugs may contribute substantially to the clinical phenotype of affected patients [242]. Possible mechanisms of acquired thyroid hormone resistance include impairments of transmembrane transport [15, 16, 243], deiodination [19, 227, 228, 244], entry into nucleus [245, 246], receptor binding [243, 247–253], and nongenomic effects of iodothyronines [28, 254–264]. Similar effects may ensue from exposure to endocrine disruptors [265] like phthalates [266–268], brominated flame retardants [266, 267, 269], perfluorinated compound [266, 267, 270], polychlorinated biphenyls [271–276], bisphenol A [254, 266–269, 274], or bisphenol F [277].…”