ADDISON'S DISEASE. .347 



As an introduction to this, a brief sketch of the development of the 

 adrenals is given. 



The cortex of the adrenal is developed from the mesodermic epithelium which 

 covers the mesial aspect of the forepart of the Wolffian body, in front of the 

 germinal epithelium. Masses of sympathetic formative cells exist between this 

 primitive adrenal and the aorta, groups of which grow into the adrenal and 

 eventually form the cells of the medulla. These cells increase in size, their nuclei 

 become enlarged and vesiculated, and they acquire the property of staining brown 

 with chromium salts. However, not all of these formative cells enter the adrenal; 

 many remain along the course of the sympathetic nerves in the abdomen and there 

 undergo the same change into chromophil cells. These cells were termed "chro- 

 mophil cells" by Stilling,(2l) "chromaffin cells" by Kohn,(22) and "phaochrome 

 cells" by Poll. (23) Granules or globules of a substance yielding this reaction have 

 been described in the blood within the medullary sinuses and in that of the 

 suprarenal vein. This forms strong histological evidence that the medullary 

 cells pass a secreted substance into the blood. 



PATHOGENESIS OF ADDISON'S DISEASE. 



A year after his original communication, Addison himself found changes in the 

 abdominal sympathetic in certain cases, and from that time until the present 

 there has been constant discussion as to whether the lesions of the sympathetic 

 system or adrenals are responsible for the symptons. Experiments directed toward 

 the production of Addison's disease by adrenal enucleation succeeded in reproduc- 

 ing all the clinical symptoms except pigmentation, which was not evident during 

 the brief period that the experimental animals lived. 



Neusser(24), from a consideration of the cases previously reported and from 

 what was then known of the physiology of the adrenals and sympathetic system, 

 promulgated the following theory: "The suprarenal gland is a gland with an 

 internal secretion. It possesses a double function: first, the neutralization of 

 the toxiq products of the metabolic activity of other organs ; second, the synthetic 

 production of a substance which is essential to the sympathetic system, maintain- 

 ing its nutrition and a normal tone. In every case the symptoms of Addison's 

 disease result from impairment, or eventually complete suppression, of these func- 

 tions of the suprarenal capsules, brought about by disease of the capsules them- 

 selves, or of the nerve tracts controlling their functions. These nerve tracts extend 

 from the spinal cord through the splanchnic nerve and the eoeliac ganglion. Tliis 

 impairment and eventual suppression of the function of the suprarenal capsules 

 account for the nutritive and functional disturbance of the sympathetic system, 

 on the one hand, and for the general autointoxication, on the other. In addition 

 to these two principal factors, extension of the pathologic process in many 

 \ cases to the abdominal sympathetic is responsible for the occurrence of some 

 of the symptoms of Addison's disease. Pigmentation of the skin and mucous 

 membranes is not an integral part of Addison's disease, and, though of decided 

 diagnostic significance, is not an essential feature. It is rather an indirect than 

 a direct suprarenal symptom, arising only through the agency of local or general 

 disease of the sympathetic system." The antitoxic property of. the adrenal cortex 

 lacks definite proof. 



Previous to this time numerous observers had reported the presence of changes 

 in the spinal cord, spinal ganglia, and splanchnic nerves. 



It has been known since the time of Henle(25) (186.5) that the cells of the 

 adrenal medulla possess a peculiar staining reaction after fixation with chromium 



