602 CHEMICAL PATHOLOGY OF THE DUCTLESS GLANDS 



(thyro-oxy-indole) with the following structural formula which has 

 been confirmed by its synthetic production: 



HI 



HI 1^ C— CH2— CH2— COOH 



HI 



\^-g-co 



The activity of this substance is referable to the CO-NH groups, 

 since acetylating the imino group removes the physiological effect. 

 In the body the indole ring seems to exist in the open form shown 

 below, corresponding to the open and closed structure of creatine and 

 creatinine. 



HI 

 HI /\ C— CH2CH2COOH 



HI I I COOH 



\^\NH2 



This substance is highly active, causing rapid pulse, nervous 

 irritability, and increased metabolism. 



Through its action on the metabolism of all the cells of the body 

 thyroxin relieves all the manifestations of myxedema and cretinism. 

 It is estimated that one-third milligram increases the basal metabolism 

 of an adult by 1 per cent., on which basis it may be calculated that 

 from 23 to 50 mg. are functioning in the entire body. It acts like a 

 true catalyst in carrying on action for two or three weeks after being 

 administered. It contains only one-fourth of the iodin of the thyroid 

 but the nature of the other iodin compounds is unknown, bej^ond 

 the observation that they have no appreciable effects on normal 

 persons but greatly improve the condition of cretins, presumably they 

 represent intermediate stages in the formation of thyroxin. AVhen 

 fed to tadpoles, Kendall's active principle produces the characteristic 

 thyroid effect. ^^ 



Persons with complete atrophy of the thyroid have a basal meta- 

 bolism 60 per cent, of normal, which can be brought to normal by thy- 

 roxin, but what carries the 60 per cent, metabolism when the thyroid 

 is functionless is unknown. Presumably thyroxin merely increases 

 the rate of metabolism that goes on at a lower level without it, in 

 which case the function of the thyroid seems to be merely to permit a 

 greater range of flexibihty in energy output. A single large injection 

 has little effect while repeated small doses cause death, indicating that 

 thyroxin of itself is not toxic, but only through its effect on metabolism. 

 The limit of tolerance is 2 mg. daily. 



Iodin Content of Thyroid. — The physiological activity of thyroid 

 preparations, according to nearly all investigators, is in direct propor- 



" Rogoff andMarine, Jour. Pharmacol., 1916 (9), 57. 



