472 PATHOLOGICAL PIGMEXTATION 



Priinavera '^ found the iiriiie in a case of melanosarcoma contain- 

 ing free tyrosine, fluctuating in amount with the pigment. 



Addison's disease is associated with the deposition of a pigment 

 in the skin that is generally considered to be a melanin, differing 

 from that produced normally in the skin only in quantity' and not in 

 origin or composition.^'' No satisfactory explanation of the relation 

 of the adrenal to this pigmentation seems yet to have been made, al- 

 though it is natural to assume that when the function of the adrenal 

 is destroyed, substances accumulate in the blood that have a stimu- 

 lating effect on the pigment-forming cells. Abnormal protein catab- 

 olism, with excessive accumulation of the chromogenic constituents of 

 the protein molecule, has been suggested, as also have alterations in 

 the influence of the sympathetic nervous system upon the chromo- 

 phore cells, for nerve lesions (e. g., neurofibroma) often are accom- 

 panied by pathological pigmentation of the skin.-" 



It is significant that the active constituent of the adrenal medulla, 

 the epinephrin, is an aromatic derivative closely related to tyrosine, 

 since the production of pigment by the action of oxidizing enzymes 

 upon such substances is well known. Furthermore, Neuberg has de- 

 scribed a melanotic adrenal tumor which produced pigment by oxi- 

 dizing epinephrin. On this basis the pigmentation of Addison's dis- 

 ease would seem to be the result of an abnormal accumulation or dis- 

 tribution of aromatic compounds, because of their failure to be con- 

 verted into epinephrin. In support of this hypothesis is the obser- 

 vation of ^leirowsky that the human skin contains an enzyme capable 

 of oxidizing e])inephrin to a pigment, and that pieces of skin kept 

 warm will develop a postmortem pigmentation, and this is supported 

 by Konegstein -^ who found that the pigmentation was greater in 

 animals deprived of their adrenals or given injections of epineph- 

 rin. 



As exact chemical studies of the pigment in Addison's disease have 

 not been made, however, we have no positive proof that it is a mela- 

 nin, hence any speculation as to the cause of its formation is prema- 

 ture. Carbone -- claims to have isolated from the urine in Addison's 

 disease a pi^iment that contains much suljiliur, and which he considers 

 similar to or identical with the melanogen of melanuria. A similar 

 observation is reported by Eiselt.--' v. Kahlden,-^ however, has ob- 

 served crystals resembling hematoidiii in the pigmented tissues. 



isfiiorn. Int. Scicnze Med., 1908 (29), 978. 



19 Concerning histogenesis of the pigment see Pfuiringcr, Cent. f. Path., 1900 

 (11), 1. 



20 See r68iim^ hv Schmidt, Ergeb. der Pathol., 1896 (Bd. ,3. Abt. 1), 551. 

 -■1 Wicn. l<lin. Woch., 1910 (2.3), GIG. 



22 (Jioino H. Acad. nied. di Torino, 1S9G. 



2't Zeit. kiln. Med.. 1910 ( G9 ) . 393 ; full discussion on the pigment of Addison's 

 disease. 



24 Virchow's Arcli., 1SS8 (114), Go. 



