620 CHEMICAL PATHOLOGY OF THE DUCTLESS GLANDS 



and later may lead to an interstitial myocarditis (Pearce). These experiments 

 suggest the possibility that oversecretion of epinephrine may be a cause of arterio- 

 sclerosis, but there is no evidence that this actually occurs in man. 



ADDISON'S Disease" 



As pointed out before, the profound deficiency in the pressor prin- 

 ciples evident in the manifestations of Addison's disease imphes loss 

 of function, not only of the adrenal medulla, but also of the rest of 

 the chromaffin tissues which produce this same sort of material. 

 Therefore it is possible to have any amount of destruction of the ad- 

 renals without Addison's disease, if there is sufficient compensation 

 by the other chromaffin structures, or, conversely, Addison's disease 

 may occur when the adrenals seem morphologically little altered, which 

 occurs in about 10 per cent, of all cases. In typical cases, however 

 the adrenals have been found entirely devoid of epinephrine,"^ and 

 usually the. structural alterations are conspicuous. While some have 

 held that the destruction of the adrenal cortex is of importance in 

 Addison's disease, this does not seem to have been conclusively 

 demonstrated. 



The pigmentation of the skin'^^ has not yet been explained, but in 

 view of the fact that oxidizing enzymes readily convert epinephrine, 

 tyrosine, and related aromatic substances into pigments, and that in 

 Addison's disease we have a deficiency in a tissue which is known to be 

 concerned in the metabolism of aromatic compounds, it seems probable 

 that the pigmentation is the result of this defective metabolism of the 

 chromogenic aromatic compounds. In support of this view is the ob- 

 servation of Bittorf^" that the skin of persons with Addison's disease 

 has an augmented power of oxidizing epinephrine and tyrosine to pig- 

 mented substances. Bloch^^ believes the pigmentation to result from 

 the presence of excessive quantities of 3.4-dioxyphenylalanine, which 

 may be a precursor of epinephrine, and which is oxidized to a melanin 



H 

 O 



ho/ NcHs.CHNHj— COOH 



by special oxidizing enzymes ("dopaoxidase") present in the skin. 

 Until the pigment of Addison's disease has been isolated and analj^zed, 

 however, these hypotheses will probably remain unproved. (See 

 pigmentation. Chap, xviii.) Addison's disease can occur without 

 pigmentation. 



That there is a deficiency in the formation of epinephrine is at- 



" Literature on Chemistry, by EiseU, Zeit. klin. Med., 1910 (69), 393. 

 " Ingier and Schmorl, Dent. Arch. klin. Mod., 1911 (101), 125. 

 " According to Straub (Deut. Arch. klin. Mod., 1909 (97), 07) pigmentation 

 may occur within 17 days after throndiosis of the adrenal vein. 

 «» Arch. exp. Path., 1914 (75), 143. 

 8' Zeit. exp. Mod., 1917 (5), 179; Arch. f. Dermatol., 1917 (124), h. 2. 



