304 CLINICAL CONSIDERATIONS 



of an otherwise normal skin. The pigment is intracellular 

 and forms a cap above the nucleus of the basal cells. 458 



Pigmentation is not confined to Addison's disease but may 

 occur in abdominal growths, pregnancy, uterine disease, hemo- 

 chromatosis, vagabonds, chronic arsenic poisoning, pernicious 

 anemia, ochronosis, von Recklinghausen's disease, et cetera as 

 well as in apparently normal individuals. 



The usual explanation of the pigmentation is that it results 

 from disease of the medulla rather than of the cortex. The 

 diseased medulla being unable to retain its normal store of 

 epinephrine is supposed to release this substance into the cir- 

 culation which deposits it (or possibly its oxidation product or 

 a precursor) in the epidermal layers where it is retained as 

 melanin. This hypothesis would account for the cases of 

 Addison's disease which are unaccompanied by pigmentation 

 by assuming little involvement of the medulla. It would ac- 

 count also for the clinical fact that the more chronic form of 

 the disease is more apt to be accompanied by deeper pigmen- 

 tation than the acute, rapidly fatal form. In the former, it 

 is the medulla which is most extensively involved, while in the 

 latter, the cortex is chiefly affected. 260 



There have been several reports of pigmentation in lower 

 animals following adrenalectomy (Nothnagel, 474 Tizzoni, 628 and 

 Marino-Zucco 437 ). Boinet went so far as to see the pigmenta- 

 tion not only in the skin of rats but as hematoidin granules in 

 the blood. The careful observations of recent years on thou- 

 sands of rats, cats, and dogs have not confirmed the appearance 

 of any pigmentation. This is not unexpected if one assumes 

 that disease of the medulla is responsible for the appearance 

 of pigmentation in man, since in animal experiments not only 

 the cortex but the medulla as well is removed. Only in ani- 

 mals in which the medulla is injured would one expect the pig- 

 mentation to appear on shaved portions of the skin subjected 

 to the sunlight. Indeed Kellaway and Cowell 348 observed pig- 

 mentation under these conditions in two animals in which the 



