ADDISON'S DISEASE 307 



by the use of a strongly concentrated aqueous solution. Alezais and Ar- 

 naud, however, as a result of their experiments believed that the fresh 

 gland substance contained no toxic principle. Vincent (/) observed, fol- 

 lowing the subcutaneous injection of sufficiently large doses of suprarenal 

 extract, slowed muscular movements., paresis, and finally paralysis of the 

 limbs, bleeding from the mouth and nostrils, hematuria, respiratory dis- 

 turbance, and occasionally convulsions preceding death, before which the 

 temperature often fell very low. This author regarded the paralysis as 

 central, and the effects as due to the medulla of the gland, the cortex 

 containing no toxic substance. He further noted that the oral administra- 

 tion of the glands in animals gave rise to no noticeable physiological 

 effects. Blum(6) first made the important observation that glycosuria can 

 be produced by the subcutaneous or intravenous injection of suprarenal 

 extracts into animals. 



Several important observations concerning the physiological action of 

 epinephrin have a bearing upon the therapeautic indication for the use 

 of this drug in the treatment of Addison's disease. Here it may be stated 

 that there is good evidence to believe that the chromaphil tissue, outside 

 of the suprarenal medulla, contains an active principle identical in its 

 physiological action with the epinephrin of the medulla (MacLeod). 

 The first and most important observation was that of Oliver and Schafer 

 of a rise in the blood pressure, which they regarded as due to a constriction 

 of the arterioles, as well as to an increase in the rate and energy of the 

 heart beat, i. e., the maintenance of vascular tone. But Moore and Purin- 

 ton first noted that very small doses of suprarenal extract cause a fall in 

 blood pressure, an observation that has been confirmed by several ob- 

 servers. Ho>skins has demonstrated by animal experimentation, that the 

 quantity of epinephrin required to produce a minimal hypertension is 

 several times (10-20) the amount normally secreted by the suprarenal 

 glands. Another important observation is that of Elliott (a) who found 

 that the injection of epinephrin caused identically the same effects as the 

 stimulation of the sympathetic (thoracico-lumbar autonomic) nervous sys- 

 tem, the injection affecting all structures innervated by sympathetic fibers. 

 Following epinephrin injection either stimulation or depression may be 

 produced in a structure, according to the role of the sympathetic fibers. 

 Among other physiological actions described, of interest in this connection, 

 are : a redistribution of blood in the body, vasoconstriction in the skin and 

 splanchnic areas, and vasodilatation in the skeletal and heart muscles, 

 lungs, and central nervous system (Cannon) ; the production of hyper- 

 glycemia, and of glycosuria; increase in body temperature, increase in 

 the lymphocytes and polynuclear leucocytes, and in the erythrocytes in 

 the blood. In general, as Hbskins has pointed out, epinephrin is neither 

 a vasoconstricting nor a vasodilating agent in any broad sense, but is 

 either one or the other depending on the vessels involved. Furthermore, 



