THE METABOLIC EFFECTS OF THE ACETIC AND PROPIONIC ACID ANALOGS OF THYROXINE AND TRIIODOTHYRONINE*

Abstract

Thyroidectomized rats were used as sensitive test animals on which to determine the comparative metabolic effect of L-thyroxine triiodothyronine (Trit), and their respective acetic acid and propionic acid analogs. Four types of studies were made: (a) the in vitro response of kidney, liver and heart slices to the thyro-active materials; (b) the response of heart, diaphragm and skeletal muscle oxygen consumption to single large doses of the thyroactive materials injected into thyroidectomized rats; (c) the action of similar single large doses of these compounds on the basal metabolic rates of thyroidectomized rats; and (d) the effects of repeated subcutaneous injections of the thyroactive substances on the metabolic rate of 7 selected tissues of thyroidectomized rats. Clinical effects of these compounds were evaluated in 3 patients with primary hypothyroidism who were studied while being treated with 1 or more of the following compounds: Trit, triodothyroacetic acid, tetraiodothyroacetic acid, triio-dothyropropionic acid, tetroiodothyropropionic acid, thyroxine or desiccated thyroid substance. The acetic acid analogs produced an acceleration of oxygen consumption in animal tissue preparations only when they were preinjected in the animals. Both the acetic and propionic acid analogs were weakly thyroactive in man, with 5% or less, of the activity of thyroxine. All of the analogs had metabolic properties similar to the parent compounds. A dissociation of cholesterol and metabolic rate responses was obtained with all compounds, when small enough doses were used.