476 PATHOLOGICAL PIGMENTATION 



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 

 described a melanotic adrenal tumor which produced pigment by 

 oxidizing epinephrine. On this basis the pigmentation of Addison's 

 disease would seem to be the result of an abnormal accumulation or 

 distribution of aromatic compounds, because of their failure to be 

 converted into epinephrine. In support of this hypothesis is the 

 observation of Meirowsky that the human skin contains an enzyme 

 capable of oxidizing epinephrine to a pigment, and that pieces of 

 skin kept warm will develop a postmortem pigmentation, and this is 

 supported by Konigstein-^ who found that the pigmentation was 

 greater in animals deprived of their adrenals or given injections of 

 epinephrine. Bloch^^ believes that the pigmentation results from the 

 precursor of epinephrine, 3.4-dioxyphenylalanine, which is oxidized 

 in the epidermal cells to melanin. 



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 mel- 

 anin, 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 pigment that contains much sulphur, 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 hematoidin in the pigmented tissues. 



Ochronosis'^ is a condition characterized bj^ a black pigmentation 

 of the cartilages, first described by Virchow in 1866. In 1904 Osler'^ 

 reported two cases, and found but seven others in the literature to that 

 time. Virchow suspected that the condition was due to a permeation 

 of cartilage by hematin derivatives, but Hansemann, finding a case 

 associated with melanuria, considered that the pigment is probably of 

 metabohc origin. Hecker and Wolf studied the urine of a similar 

 case, and concluded that the pigment must be melanin. Albrecht,^* 



" See r6s\im6 by Schmidt, Ergeh. der Pathol., 1896 (Bd. 3, Abt. 1), 551. 



" Wien. klin. Woch., 1910 (23), 616. 



29 Giorno R. Acad. med. di Torino, 1896. 



'" Zeit. klin. Med., 1910 (69), 393; full discussion on the pigment of Addison's 



dlSGA-SG 



»iVirchow's Arch., 1888 (114), 65. 



32 See Adler, Zeit. f. Krebsforsch., 1911 (11), 1; Poulsen, Ziegler's Beitr., 1910 

 (48), 346. 



"Lancet, 1904 (i), 10 (literature). 



»< Zeit. f. Heilk., Path. Abt., 1902 (23), 366. 



I 



