We have previously shown that some oral cholecystographic agents induce marked increase in basal and TRH-stimulated TSH concentrations in normal subjects. To define the relationship between circulating iodothyronines and pituitary secretion after oral cholecystography, temporal changes in the responses of serum TSH and PRL to a fixed dose of TRH (500 micrograms iv) and in serum T4, T3, and rT3 concentrations were assessed before, immediately after, and then at weekly intervals after the three daily doses of iopanoic acid (Ip). Both basal and TRH-stimulated TSH concentrations were significantly increased at the end of the period of Ip administration when the serum T3 concentration was decreased, were still above the pretreatment level 1 week after the course of Ip when the serum T3 had returned to pre-Ip levels, and returned toward normal 2 weeks after the course of Ip. The changes in serum T3 concentration were accompanied by reciprocal changes in rT3 concentration. PRL secretion was not significantly changed. To evaluate further the relationship between the enhanced TSH secretion and the changes in serum iodothyronine concentrations, subjects were given oral doses of T3 (5 micrograms every 4 h) or T4 (50 micrograms every 8 h) during the administration of Ip. In the subjects given Ip plus T3, serum T3 concentrations were maintained at pre-Ip levels, and both basal and TRH-stimulated TSH concentrations were not different from the control. Administration of T4 did not completely prevent the Ip-induced increment of TSH secretion. It is suggested that in subjects given Ip, 1) the serum T3 level is, at least partly, a determining factor for TSH secretion; and 2) the set-point of TSH secretion is appropriately tuned to either reduction or elevation of serum T3 concentration by a mechanism that is different from that in fasting subjects.
To re-evaluate the clinical utility of the prolonged management of hyperthyroidism with sodium tyropanoate (TP), an oral cholecystographic agent, we studied the changes in the scoring of thyrotoxic signs and symptoms (thyrotoxic index; TI), serum concentrations and binding of thyroid hormone, and circulating TSH receptor antibodies (TRAb) in two groups of patients with Graves' disease; seven patients (TP group) received TP (1.5 g daily) alone for 14 weeks, and six patients (TP + MMI group) received methimazole (MMI; 30 mg daily) in addition to TP for 8 weeks and MMI alone thereafter. In the TP group, the TI reduced significantly, but it failed to reach a euthyroid level in all except one. Serum total T4 (TT4), free T4 (FT4), and T3 uptake (T3U) values declined by the third week of treatment, but an 'escape' occurred thereafter. Serum rT3 and T4 binding globulin (TBG) levels were increased. The TRAb titres were increased slightly but significantly. Serum T3 levels fell within a week but remained higher than normal during the treatment. In the TP + MMI group, all patients achieved a normal TI by the end of the treatment. Serum TT4, FT4 and T3U fell more significantly than those in the TP group, indicating no escape from the effect of TP. The serum TRAb decreased significantly. Serum T3 levels showed a greater reduction than those in the TP group, and remained decreased even after withdrawal of TP. In a further 9 patients receiving TP alone for 4-14 weeks (7.3 +/- 5.0 weeks on the average), TP was withdrawn and replaced by MMI.(ABSTRACT TRUNCATED AT 250 WORDS)
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