Therapeutic activity of desiccated thyroid substance, sodium L-thyroxine and D,L-triiodothyronine: A comparative study

Abstract

T HE development of a commercially practical method for synthesizing thyroxine,’ the identification of 3,5,3’-L-triiodothyronine in human plasma2 and the recognition of its physiologic importance 3,4 have stimulated considerable interest in the re-evaluation of thyroid hormone therapy. Several reports have already appeared describing the oral or intravenous use of sodium L-thyroxine,617 L-triiodothyroninell1a,16--20 and D,L-triiodothyronine16*17 in patients with myxedema. That desiccated thyroid substance, thyroxine and triiodothyronine are all hormonally active in such trials is universally agreed. However, reported investigations with the best human test subject, the myxedematous patient, are not yet of sufficient number to settle completely the relative intensity, speed and duration of action, as well as the variations in responsiveness. The present report deals with experiences with twelve patients suffering from adult myxedema. The manner of approach differs in one respect from most if not all of the other studies of human subjects. In the present work, following attainment of a euthyroid state under therapy, the patient has been allowed to lapse into a measurable degree of hypothyroidism prior to the beginning of therapy with the same or a second thyroid preparation. This has afforded us repeated comparisons under conditions as nearly identical as possible for us to achieve. average age of fifty-three and a half years, were the subjects of this study. Each had the classical symptoms and signs of myxedema. The diagnosis was further confirmed by determination of the basal metabolic rate, serum cholesterol and, in some instances, the serum protein-bound iodine, thyroidal uptake of radioactive iodine and the twenty-four hour excretion of creatine of a person on a meat-free diet. Manifestations of myxedema had been present for periods varying from six months to twelve years prior to recognition, with an average duration of 3.7 years. In seven subjects the development of myxedema was spontaneous; in three it followed thyroidectomy; in one radiation therapy, and in the remaining one the prolonged use of an antithyroid compound. The initial basal metabolic rates of the group ranged from minus 16 to minus 47 per cent, with an average of minus 34.9 per cent. Serum cholesterol values, performed by the method of Pearson, Stern and McGavack,23 varied from 291 to 443 mg. per 100 cc. with an average of 358.4 mg. per 100 cc. The serum protein-bound iodine, carried out by the method of O’Neal and Simmsz4 was initially 3.9 pg. per 100 cc. or less. Because of the changes initially present, serial determinations were made throughout the study, as well as repeated estimations of the urinary 17-ketosteroids, blood counts, electrocardiograms and cardiac roentgenograms.