Nitrogen Retention, Creatinuria, and Other Effects of the Treatment of Simmonds' Disease with Methyl Testosterone.

One of the immediate effects of hypophysectomy is a loss of nitrogen (1) and a corresponding loss in weight (2). This change is reflected clinically by the so-called cachexia of Simmonds' disease (3). Nitrogen balance is then re-established at a lower level of body weight with lessened food intake. In the experimental animal, adequate replacement therapy is readily obtained with anterior hypophyseal substance or extracts (4, 5), including the production of nitrogen retention and gain in weight (1). Clinically, however, such attempts have been singularly unsuccessful (6, 35) except for one case treated with pregnant mare's serum (7), and another recent report by Williams (8), of treatment with a mixture of thyroid, desoxycorticosterone, and methyl testosterone. The recent reports of growth in cases of dwarfism treated by methyl testosterone (9) reveal that nitrogen retention and creatinuria are produced. The origin of some types of dwarfism has been attributed by many to a disturbance in the growth function of the anterior hypophysis.. This suggests that methyl testosterone may produce its effects on nitrogen metabolism in the absence of hypophyseal function, which is of great interest in view of the intimate role of the hypophysis in such metabolism (10). However, since the cause of the dwarfism cannot be definitely localized to the hypophysis (11), it would seem important to try methyl testosterone in cases of Simmonds' disease, in which hypophyseal function is known to be lacking and in which any effect on nitrogen metabolism is not complicated by concurrent growth. Positive results might well point to this hormone as a possible therapeutic agent in this disease. Accordingly, a study was conducted in the