322 INTERNAL SECRETION 



exhibition of this substance have formed the subject of manifold 

 investigation ; further evidence, moreover,, has been furnished of 

 the internal secretory activity of the organ. 



The chemistry of the hypophysis has, up to now, been hardly 

 sufficiently investigated. We know that it contains a relatively 

 large proportion of phosphorus and calcium ; iodine (Ewald and 

 Schwitzler), bromine (Paderi), and traces of arsenic (Gautier) have 

 all been discovered. According to Gautrelet, the hypophysis, 

 like many other organs, contains cholin. 



Of the active pharmacodynamic substance of the hypophysis 

 we know only that it is dialyzable ; that it is not destroyed by 

 reducing agents, such as boiling; and that it is insoluble in 

 alcohol and ether. For experimental purposes, as well as in 

 clinical medicine, the dried organ obtained from cattle, sheep, 

 horses, cats, and dogs is employed, or extracts prepared from 

 the dried or fresh organ in normal saline solution are used. As 

 may be imagined, the dosage of such pituitary preparations is 

 not very exact. An extract obtained with chloretone from the 

 posterior lobe of the hypophysis has recently been put upon the 

 market by Messrs. Parke, Davis and Co., under the name of 

 hypophysin or pituitrin ; the manufacturers state that i c.cm. of 

 this extract is equal to o.i grm. of the fresh, and .01 grm. of the 

 dried, substance. 



Pituitrin does not react either to ferric chloride or to the 

 sublimate test given by Comessatti for adrenalin, or to the 

 Frankel-Allers test. It does, however, produce mydriasis of 

 frogs' eyes. According to Allers, when boiled with caustic soda 

 solution it gives off a distinct odour of alkylamin, while the liquid 

 becomes brown ; this author considers it probable that the hypo- 

 physis contains a substance which, similarly to adrenalin, 

 possesses an alkaline amino-nitrogen constituent. 



The general toxicity of pituitary extract is inconsiderable and 

 not to be compared with that of adrenalin or suprarenal extract. 

 Numerous accounts are given of extracts equal to ij to 3 fresh 

 hypophyses (Mairet and Bosc, Conti and Curti, Gamier and 

 Thaon, Salvioli and Carraro, Etienne and Parisot, Renon and 

 Delille, Hallion and Carrion) being exhibited as a single dose, 

 while Urechia reports a case in which the extract of ten ox-hypo- 

 physes was tolerated in a single dose. The direct effects of 

 intravenous or subcutaneous injection of pituitary extract are 

 transient apathy, somnolence, occasionally accelerated respiration 

 and increased secretion of urine. After the intraperitoneal injec- 

 tion of large quantities of pituitrin (10 to 15 c.cm.), I observed 

 transient excitement, followed by marked depression and muscular 

 weakness, which afterwards developed into complete paralysis of 

 the hinder extremities and terminated, at the end of twenty-four 

 hours, in death. The intravenous injection of large quantities of 

 pituitrin is sometimes followed by a sudden arrest of cardiac 



