View larger version (26K):
[in this window]
[in a new window]
|
Figure 1 Diagram depicting pathogenetic mechanisms of the rapid responder Graves' disease. (a) In a typical Graves' disease patient, increased concentrations of TSI increases thyroglobulin synthesis and increases iodine turnover with increased substrates for iodination and thyroid hormone formation. (b) In a typical Graves' disease patient treated with antithyroid drugs (ATDs), where the iodide to ATD ratio is high, there is a reversible inhibition of thyroid peroxidase (TPO) enzyme with a decrease in thyroid hormone formation with periods of escape, wherein the concentrations of thionamides drop. (c) In Graves' disease with high iodine turnover, wherein the iodide:ATD ratio is low, ATD irreversibly inhibits the TPO enzyme. This coupled with possibly a lesser degree of thyroid hyperplasia and relatively lower thyroglobulin synthesis may rapidly deplete the substrates available for thyroid hormone formation. On withdrawal of the drug, rapid iodination resumes when new TPO enzyme formation occurs. Size of the boxes indicates size of pool with smaller pools indicated by smaller boxes. ATD, antithyroid drug; c-AMP, cyclic adenosine monophosphate; DIT, di-iodotyrosine; H2O2, hydrogen peroxide; I–, iodide; I+, oxidized iodide; MIT, mono-iodotyrosine; mRNA, messenger ribonucleic acid; PDS, pendrin; T3, triiodothyronine; T4, thyroxine; TPO, thyroid peroxidase; TPO–, inhibited TPO after combination with ATD; TRAb, thyroid receptor anitbody
|
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
