Serum reverse triiodothyronine

Meinhold H, Visser T. International survey of the radioimmunological measurement of serum reverse triiodothyronine. Clin Chim Acta 1980 105 343-50. 

Burger A, Dinichert D, Nicod P, Jenny M, Lemarchand-Beraud T, Vallotton MB. Effect of amiodarone on serum triiodothyronine, reverse triiodothyronine, thyroxin, and thyrotropin. A drug influencing peripheral metabolism of thyroid hormones. J Clin Invest 1976 58(2) 255-9. 

There was a modest rise in serum TSH concentration when rifampicin was given to a patient previously stabilized on thyroxine replacement (87). Rifampicin is believed to increase the metabolic clearance of both thyroxine and the inactive compound reverse triiodothyronine and in healthy volunteers it reduces circulating concentrations of total and free thyroxine, although in subjects without thyroid disease it has no effect on serum TSH (86). 

A wide range of serum thyroid hormones (T4, FT4, T3, reverse triiodothyronine (rT3), thyroxine sulfate (T4S)), TSH and thyroid binding globulin (TBG) were analyzed in our studies T4, but not FT4 levels were indicative of hypothyroxinemia (Williams et at, 2004 Simpson et at, 2005). In 23—27 week gestation infants, T4 serum levels decrease to a nadir at 7 postnatal days and fail to increase in 28—30 week infants. This is in marked contrast to 31—34 and 37—42 week term infants, who show an increase in serum T4 levels at day 7 (Williams et al., 2004 Simpson et at, 2005). 

Two hundred milligrams of amiodarone contains 75 mg of iodine. Patients treated with the common daily dose of 200 mg amiodarone, get a load of 7 mg free iodide/ day, which is 35-times the daily recommended iodine dose. Amiodarone is lipophilic and concentrates in adipose tissue, cardiac and skeletal muscle, and in the thyroid (Daniels, 2001). The amiodarone plasma half life is approximately 52 23 days (Hermann, 2004). Typical changes in thyroid function are an increase in serum T4 and reverse triiodothyronine (rT3), and a decrease in serum T3 concentrations related to the inhibition of 5 -deiodinase-activity, resulting in a decrease in the generation of T3 from T4 and a decrease in the clearance of rT3 (Martino et al, 2001) and an inhibition ofT3 receptor binding and action (Daniels, 2001). 

Amiodarone inhibits the peripheral and possibly in-trapituitary conversion of thyroxine (T4) to triiodothyronine (Tj) by inhibiting 5 -deiodination. The serum concentration of T4 is increased by a decrease in its clearance, and thyroid synthesis is increased by a reduced suppression of the pituitary thyrotropin T3. The concentration of T3 in the serum decreases, and reverse T3 appears in increased amounts. Despite these changes, most patients appear to be maintained in an euthyroid state. Manifestations of both hypothyroidism and hyperthyroidism have been reported. 

Abbreviations BAT, brown adipose tissue BrAc, /V-bromoacetyl- BSA, bovine serum albumin CNS, central nervous system DEP, diethylpyrocarbonatc DIT, diiodotyrosine DTT, dithiothreitol G, glu-curonide Grx, glutaredoxin GSH, reduced glutathione GSSG, oxidized glutathione IRD. inner ring deiodination MIT, monoiodotyrosine ORD, outer ring deiodination PTU, propylthiouracil S, sulfate rT3, 3,3, 5 -triiodothyronine (reverse T,) Trx, thioredoxin T2, diiodothyronine T3, 3,3, 5-triiodothyronine T4, 3,3, 5,5 -tetraiodothyronine (thyroxine). 

Selenium is a component of all three members of the deiodinase enzyme family, the enzymes responsible for deiodination of the thyroid hormones (Kohrle 1994 St. Germain and Galton 1997). The deiodinases contain a selenocysteine at the active site, which is required for catalytic activity. There are three types of deiodinases and they differ in terms of tissue distribution, reaction kinetics, efficiency of substrate utilization, and sensitivity to inhibitors. The first to be recognized as a selenoprotein was type I iodothyronine 5 -deiodinase which converts the prohormone thyroxine (T4) to the active form, triiodothyronine (T3) and to date, studies of the effects of excess selenium have focused on this protein. Under normal circumstances the human thyroid produces only 20-30% of its hormone as T3 the remainder is T4 (a minute amount of reverse T3 (rT3) is also produced), which is largely converted to active T3 by type I deiodinase located within the liver, euthyroid pituitary, kidney, thyroid, and brain. Type I deiodinase is a membrane bound protein and, thus, its activity has not been directly measured in studies of humans supplemented with selenium. Human studies have instead measured serum levels of T3, rT3, T4, and TSH. 

Addendum 1 (Section 2.3, p. Ill) Recently Chopra (C7a) demonstrated that 3,3, 5 -triiodothyronine or reverse Tj (rTa) is present in normal serum in a concentration of approximately 40 ng/100 ml and that there are large increases in rTa concentration in the serum of the newborn when serum Ta concentration is very low. As rTa has no physiological activity, he postulated that deiodination of T may switch from T, to rTa as regulatory mechanism controlling the biological action and metabolism of Ta. 

Addendum 2 (Section 3.7.2, p. 137, after 1st paragraph) The decreased concentration of serum Ta in tbe neonatal period is accompanied by a greatly increased concentration of 3,3, 5 -triiodothyronine or reverse Ta (C7a). 

Administration of "large doses" (dose not specified in English language abstract) of codonopsis in rats was reported to cause a reduction in weight gain and serum triiodothyronine (T3) levels, and an increase of reverse T3 and thyrotropin-releasing hormone (TRH) levels (Chen et al. 1989). 

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