Effects of the Administration of Thiouracil to Dogs

Abstract

It has been previously shown [Glock, 1944] that rats fed thiourea or thiouracil develop adrenal cortical deficiency in the terminal stages. Gross histological changes were observed in the adrenal cortex and growth of the animals could be restored by injecting adrenal cortex extract. To obtain confirmatory evidence and to determine whether this effect was the result of functional thyroidectomy or of a direct action of the goitrogenic drug on the adrenal cortex, it was decided to use dogs as experimental animals. The degree of hypothyroidism could also be followed more easily than in rats. METHODS General dietThe dogs were fed on a diet consisting of dog biscuits 53 %, meat 38 %, whole milk powder 5 %, dried yeast 2 % and cod-liver oil 2 %, moistened with sufficient water to bind the ingredients. They were fed once daily in the morning. Water was allowed ad lib. The dogs receiving thiouracil had 0\m=.\1 % of the drug mixed in the diet. They were weighed twice weekly.Exper. 1. A fitter of five 8-week-old puppies (nos. 7-11) was used. Two (one female and one male) were given the control diet and three (two female and one male) the diet containing thiouracil. Total serum cholesterol estimations were carried out at intervals and the animals killed after 8 months on the diet. At autopsy, the pituitary, adrenals, kidneys, liver, spleen, pancreas, thymus, lung, and ovary or testis were removed and examined histologically. Of the two thyroid lobes, one was used for histological examination and for estimation of the total iodine content and the other for the determination of the respiration rate of tissue slices.Exper. 2. Six adult male dogs (nos. 1-6), two on the control diet and four on the diet containing thiouracil, were used. Blood analyses were carried out at intervals, namely Hb, urea N, serum Na and K, and blood volume, to detect any adrenal cortex deficiency, and total serum cholesterol as an indication of the degree of hypothy¬ roidism.' A few weeks before the animals were killed, metabolic rate determinations were carried out and an extra dog (no. 13) put on the control diet to use for this purpose. The dogs were killed after 14 months on the diet and various organs examined histologically as in Exp. 1. Total and thyroxine iodine were determined in the thyroid and total iodine in the liver.Methods of estimation Blood urea nitrogen.