212 ADDISON'S DISEASE 



general nutritive disturbance nor to a simple chronic intoxication; on the 

 contrary, in many particulars it points to a direct implication of various areas 

 of the nervous system. 



Most difficult of all to understand is the principal clinical symptom, the 

 Ironzing of the skin. It must first be pointed out that in many investigations 

 of extirpation of the adrenals in animals, even in those animals which were 

 kept alive a long time, this symptom could never be produced. But too much 

 stress is not to be laid upon this point, for there is justiiication for the view, 

 shared by many observers, that the comparatively early death of the animals 

 experimented upon may have checked the deposition of pigment. Further, 

 we do not know whether abnormal pigmentation of the skin occurs in animals 

 as readily as in man. 



But neither do our investigations furnish anything which can be looked 

 upon as proof that by destruction of the adrenals pigmentation of the skin 

 is directly caused or even favored. We may concede most readily the possible 

 truth of the theory (which is frequently expressed) that under normal condi- 

 tions there is a substance circulating in the body which furnishes material 

 favoring pigmentation, but which is rendered inoperative by the internal 

 secretion of the adrenals. That the chemical investigation of the parenchyma 

 of the adrenals has furnished no positive points of support for this has already 

 been mentioned. Such a connection, too, is untenable without a demonstrable 

 pathologic change in certain fluids of the tissues and in the blood; for such 

 demonstration, however, there is no further experimental evidence, for exam- 

 ple, in the blood and in the urine. 



Of the blood it has already been stated that an estimation of the blood- 

 corpuscles and the amount of hemoglobin shows for the most part but slight 

 change, and upon exact counting of the leukocyte varieties no important 

 deviation from the normal has been found. In these investigations signs of 

 abnormal amount of pigment of the white blood-corpuscles or of the serum, 

 analogous to melanemia, have never been observed, nor does the finding of 

 cells containing blood-corpuscles and pigment granules in the marrow of the 

 tubular bones, mentioned in one case, permit positive conclusions. ISTor is 

 much added to our knowledge by certain reports, according to which there is 

 a qualitative change in the blood with increase of reduced hemoglobin and 

 appearance of methemoglobin (Tschirkoff). 



Even slighter deviations from the normal were shown by the tirine in 

 most cases. Apart from polyuria, which is not infrequently noted, in some 

 patients an increase in indican, and in one a decided increase of urobilin, has 

 been found. In one case an abnormal coloring material (urohematoporphy- 

 rin) was determined spectroscopieally (McMunn). Furthermore, there are 

 reports regarding decrease of urea and creatinin. Opposed to this, however, 

 are a large number of reports of cases in which a normal condition of the 

 principal urinary constituents, particularly of indican, of urea or nitrogen, 

 has been determined. A new amin base (Ewald) obtained from the urine 

 in a single instance has not been satisfactorily explained. 



Nevertheless while there is no evidence which points with certainty to a 

 direct importation of the pigment from the adrenals to the skin, the possibility 



