We had an opportunity to examine young females who showed the clinical signs similar to those observed in patients with hyperthyroidism except a fall in the
131I uptake following a long term administration of Hydroflumethiazide (HFT) or chlorothiazide (CLT). This fact prompted us to investigate the effect of these drugs on the kinetic of thyroxine (T
4) in blood.
The addition of a certain amount of the drugs to serum (concentration HFT : 6 x 10
-7 -6×10
-6 mM, CLT : 1.4 x 10
-7 mM) was associated with a decrease in the distribution of T
4 to thyroxine binding prealbumin (TBPA) but no alteration in that of thyroxine binding inter α-globulin (TBG) as compared with those of untreated serum.
In in vivo, the similar findings such as a lowering of maximal TBPA capacity while no change in value of
131I-triiodothyronine resin sponge uptake after administration of HFT were noticed. To determine whether the drugs would have any effect on metabolism of circulating T
4, Space of Distribution (S.D.), Extrathyroidal Thyroxine Iodine (E.T. T.I.), Biological Half Life (B.H.L.), Fractional Rate of Turnover (K), Daily Volume Turnover (D.V.T. (I)), Thyroxine Degradation Rate (T.D.R) and the state of deiodination were studied in eleven healthy volunteers treated with 75 mg of HFT per day for seven days.
Administration of HFT caused a significant increase in S.D., E.T.T.I., and B.H.L. whereas a decrease in K, D.V.T. (I) and T.D.R. Furthermore, it was clarified that the recovery of
131I-diiodotyrosine (
131I DIT) in urines collected 1, 2, 4 and 8 hour after an intravenous load of
131I DIT was significantly higher in the HFT treated group than in the untreated control. The reduction of the activity of diiodotyrosine deiodinase in rat liver slice treated with HFT was also demonstrated. The fact that a new peak at 288 mμ on absorption spectra appeared after an incubation of T
4 with HFT, highly suggested the formation of a new molecular complex of both agents.
Because of formation of the complex, it was conceivable that T4 was protected from action of deiodinase, resulting in disturbance of deiodination and in T
4 remaining in the blood.
Consequently, the increase in E.T.T.I. and the decrease in K and T.D.R. resulted.
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