Studies on the Changes with Time in the Concentrations of Serum Triiodothyronine, Thyroxine and Thyrotropin after the Oral Administration of Various Thyroid Hormones

Abstract

The changes with time in the concentrations of serum triiodothyronine (T3), thyroxine (T4) and thyrotropin (TSH) levels after the oral administration of various thyroid hormones were investigated in order to find an adequate way for the administration of these hormones in hypothyroid patients.The subjects employed were 3 cases of untreated hypothyroidism, 138 cases of treated hypothyroidism, 72 cases of postoperative adenomatous goiter and 56 cases of postoperative thyroid cancer.The blood was drawn at 0, 1, 3, 8 and 24 hours in untreated hypothyroid patients and at three to five or 18 to 24 hours in the long-term treated patients after the administration of various thyroid hormones. Then serum T3, T4 and TSH levels were determined.The peak levels of serum T3 were observed at one and three hours after the administration of a single dose of 10-20μg and 30-40μg of synthetic T3, respectively, and then the levels of serum T3 decreased gradually and returned to pretreatment levels by 24 hours. The mean peak levels of serum T3 were 120,217,352 and 472ng per 100ml after the administration of a single oral dose of 10, 20, 30 and 40pg of synthetic T3, respectively. In the patients given a long-term treatment with synthetic T3, the levels of serum T3 were observed to be 180-480ng per 100ml at three to five hours after the administration of the last doses of 30-70μg and to become within normal values at 18 to 24 hours.After the administration of synthetic T4 in untreated hypothyroid patients, the levels of serum T3 and T4 were found to show a nonspecific diurnal variation, the basal T3 and T4 levels increased slowly, and the levels of serum TSH decreased very slowly day by day. After three weeks of treatment with 100μg per day of T4, serum T3 and T4 levels reached normal values of 5.4μg and 100ng per 100ml, respectively, while the serum TSH level decreased to 20μU per ml. And then, after another three weeks of treatment with 150/μg per day of T4, serum T4 and T3 levels increased to 10.0μg and 140ng per 100ml, respectively, and the serum TSH level decreased to the normal range.In the patients given a long-term treatment of from 50 to 250μg daily of synthetic T4, the levels of serum T3 and T4 remained within normal ranges at any time observed.After the single daily doses of 50 and 100mg of desiccated thyroid in untreated hypothyroidism, the levels of serum T3 were observed to increase to peak values of 320 and 460ng per 100ml at the end of three hours, respectively, and then, the levels of serum T3 decreased gradually and returned to basal values by 24 hours, whereas the levels of serum T4 were found to increase gradually.In the patients given a long-term treatment with 50mg (o.m.), 75mg (t.i.d.) and 100mg (b.i.d.) per day of desiccated thyroid, the serum T3 levels were observed to be 320,292 and 326ng per 100ml, respectively, at three to five hours and within the normal range at 18 to 24 hours after the last dose, whereas the levels of serum T4 were within the normal range at either point observed. A significant correlation was observed between the dose of desiccated thyroid per kilogram of body weight and serum T3 levels at three to five hours after the administration of the drug.From these data, it was thought that the reason why the severe side effect was observed after T3 but not after T4 administration was that serum T3 reached an unphysiological high level 1-3 hours after the administration of certain amounts of T3,