329 
Art. II.-Addison's Disease, and its, Delations with Anaematosis 
{Essential Anaemia). By William Pepper, A.M., M.D., Professor 
of Clinical Medicine in the University of Pennsylvania. 
In the number of this Journal for October, 1875, I gave some account of 
a rare form of disease, under the name of " progressive pernicious anaemia." 
I endeavoured to show that this affection, which has lately been made the 
subject of numerous interesting memoirs, is identical with the "idiopathic," 
or " essential" anaemia of .Addison. Attention was also drawn to the 330 
Pepper, Addison's Disease. 
[April 
remarkable resemblance between the chief symptoms of progressive per- 
nicious anaemia, and of some forms of leukaemia and pseudo-leukaemia ; 
and also to the fact, as appeared from one of the cases reported at 
length (Case No. III. p. 325), that there is a lesion of the marrow of the 
bones in the former disease similar to that which has now been repeatedly 
found in the latter affections. I ventured, therefore, to suggest the view 
that the progressive pernicious anaemia of recent writers may be, in some 
instances, at least, the medullary form of pseudo-leukaemia; although 
of course it is necessary that a careful examination of the marrow in a 
number of such cases should confirm or refute this opinion before it can 
be disposed of definitely. Finally, I called attention to the fact that 
the various accepted forms of leukaemia and pseudo-leukaemia (including 
progressive pernicious anaemia) are so much alike that they can only be 
distinguished by the varying degrees of increase of the white corpuscles 
of the blood, and the preponderance of the lesions of the spleen, the 
lymphatic glands, or the marrow; and that they are all associated with 
lesions of the blood-making tissues, and are especially characterized by 
a profound alteration of the blood-making function (htematosis). Con- 
sequently I suggested the name of anaematosis (a privative; ai/xa-roots, 
elaboration of blood), signifying impairment, defect, or disease of the 
blood-making function, for this entire class of affections, specifying their 
various forms by the terms lymphatic, and medullary. 
I have recapitulated these points, in order to bring the consideration of 
another interesting affection, Addison's disease, more directly into connec- 
tion with the study of these cachexise. The affection known as Addison's 
disease is one about whose nature and pathology many different views 
have been, and still are held. Besides the above name, given to it in 
honour of the first describer it has been called the bronze disease, supra- 
renal cachexia, melanopathia, asthenie sur-renale, and melanodermie 
asthenique. These and other names, of themselves indicate our ignorance 
of the true nature of this disease, and the attempt to designate it merely 
by naming some of its chief symptoms. 
It is undoubtedly a rare disease in America, and but few complete cases 
have been placed on record in our journals. In the number of this Jour- 
nal for January of the present year (p. 75), I have published a detailed 
account of a typical case of Addison's disease, to which reference will occa- 
sionally be made in this article. I shall refer to it as the case of Mr. C. L. 
So soon as I met with cases of so-called progressive pernicious anaemia, or 
anaematosis, I was struck by the numerous analogies presented by their 
symptoms and course with those of Addison's disease ; and in consequence, 
I awaited anxiously the publication of reports of eases vf the latter affection, 
in which microscopical examination of the marrow of the bones should 
have been made. But as no such examinations have yet, to my knowl- 
edge, been made, the following cases and remarks, in connection with the 18H.J 
Pepper, Addison's Disease. 
331 
case above referred to, are offered as a contribution to the clinical study 
of this interesting question. No attempt will be made to present a com- 
plete historical sketch of Addison's disease, and it will be necessary to 
avoid even a passing allusion to most of the interesting memoirs lately 
published on this subject. Nor will it be possible in the limits assigned 
to this article to present all the arguments for and against the various 
theories which have been advanced, as to the nature and pathology of 
Addison's disease. The object is rather to present a broad sketch of 
the leading characteristics of the affection, and then to bring them into 
comparison with the symptoms of certain other conditions. In dis- 
cussing questions of so much difficulty as that upon which we are now 
writing, it is peculiarly important to avoid preconceived opinions, or 
hasty conclusions; and, in offering some considerations which appear to 
favour a view of Addison's disease different from that which is generally 
adopted, the hope is merely entertained that they will seem of sufficient 
value to receive attention from future investigators of these important 
subjects. 
It would occupy too much space to quote in full the classical descrip- 
tion which Addison first gave in 1855, and to which scarce anything has 
been added by subsequent writers ; but the following brief summary, which 
he gives, of the leading and characteristic features1-"anaemia, general 
langour and debility, remarkable feebleness of the heart's action, irrita- 
bility of the stomach, and a peculiar change of colour in the skin," will 
show the identity of the case of Mr. C. L. with the morbid state which 
Addison was the first to connect with diseases of the supra-renal capsules. 
As, however, a certain degree of irregularity is frequently to be ob- 
served in the development of the symptoms or in the course of the affec- 
tion, it is necessary to discuss its principal features more in detail. 
Mode of Origin. Early Symptoms.-As a general rule in this, as in 
other cachectic conditions, the appearance of the symptoms is so insidious 
that the patient can rarely refer to any particular date or occurrence as 
marking the beginning of the disease. Occasionally, however, it seems to 
be more abrupt in its development, and to run a more acute course. In 
these cases, which occur especially in young persons, the lesions generally 
show that latent disease of the supra-renal capsules has been progressing 
for an uncertain length of time, and that the constitutional symptoms have 
been quite suddenly developed in their full form. In most cases, the earliest 
symptoms complained of by the patient are slowly-increasing debility and 
loss of energy. It may be that dull, deep-seated pain in the loins has been 
noticed for some time previously ; thus Mr. C. L. had observed, for a con- 
siderable time before the development of the characteristic symptoms, that 
1 On the Constitutional and Local Effects of Disease of the Supra-renal Capsules; 
Syd. Soc. Ed. of his works, p. 211. 332 
Pepper, Addison's Disease. 
[April 
certain exertions, such as bending or lifting, caused dull pain in the loins. 
Disturbances of digestion, capricious appetite, nausea, occasional vomiting, 
may also appear early. The discoloration of the skin, which justly 
attracts so much attention, very rarely appears as the initial symptom. 
Among the more rare symptoms, which have been occasionally noted as 
preceding or accompanying the development of the disease, are transient 
attacks of jaundice, rheumatoid pains, excessive urination (polyuria), 
diarrhoea with colourless stools, and marked pulsation of the abdominal 
aorta, simulating aneurism. After the symptoms are well established, we 
may note with care the differences which exist in individual cases in re- 
gard to the following features :- 
Nervous Symptoms.-The muscular debility, to which reference has been 
already made, ranks first among these, and merits careful study. Fre- 
quently the very earliest symptom noticed, it continues throughout the 
case to be the most remarkable. At first, the patient merely observes that 
he tires in the performance of his day's work more readily than usual. 
The debility increases with greater or less rapidity until the patient is 
barely able to leave his bed, or even to sit up without urgent symptoms 
of exhaustion. In some cases the disease lasts between two and seven 
years before it reaches this extreme degree ; in others, it is attained 
in the course of as many months. In some instances, so rapid and 
sudden is the loss of strength that the disease may be mistaken for an 
attack of typhoid fever; and it will be observed that in the case of Mr. 
C. L. this mistake was made by the family of the patient. Scarcely ever 
does it progress continuously ; but, as will be observed in a very marked 
manner in the case which furnishes the basis of this article, from time to 
time there is a rapid and marked return of strength, so that, for example, 
a patient who has been barely able to sit up in bed, will soon be strong 
enough to walk about or even to do light work. This improvement is 
very deceptive, and as in some cases it lasts a considerable time, it has 
led to some confusion with regard to the beneficial effects of certain modes 
of treatment. In almost, if not actually in every case, however, this 
improvement is but delusive; and, after lasting an uncertain period, is 
rudely interrupted by some apparently causeless attack which rapidly re- 
duces the patient's strength to a point even lower than at any previous 
time. When this symptom has become well developed, there may be, even 
during entire quiet, a profound sense of exhaustion ; or, as was noted in 
Mr. L.'s case (p. 78), there may be an utter loss of desire for exertion or 
even for movement, a profound lassitude which leads the patient to repose 
contentedly in perfect quiet day after day. The power of clasping with the 
hand may seem to be fair, and while the patient is lying down, he may 
appear to still have considerable strength, but the act of rising to the feet, 
or even of sitting up, induces rapid and extreme exhaustion. In the case 
here referred to, the patient, after his debility became advanced, preferred 1877.J 
Pepper, Addison's Disease. 
333 
making no effort to sit up, and when obliged to leave bed in order that the 
clothes might be changed, would slip down in a minute from the chair 
where he was placed on to the floor, where he would lie at full length. 
It appears to me that the characters of this excessive debility are best 
explained by the view that it is dependent upon an anaemic state of the 
nerve centres, associated with great enfeeblement of the heart's action. 
Months before the fatal result of the case, and when perhaps the patient 
will still rally several times and become able to make considerable exer- 
tion, we meet with a degree of muscular weakness scarcely equalled even in 
the last stages of any chronic disease. It is more closely approached by 
the debility described in the cases of " progressive pernicious anaemia" 
reported in the number of this Journal for October, 1875, than by other 
condition I know of. In Addison's disease, moreover, as will be here- 
after seen, it is probable that (in many cases at least) there is a state of 
irritation of the abdominal ganglia of the sympathetic or of other nerves 
which aids, by inhibitory action on the spinal cord, in the production of 
such intense asthenia. 
In addition, it will be noted that Mr. L. complained of a peculiar 
sense of straining in the joints or muscles when he made any sudden 
movement. 
Other nervous symptoms are occasionally met with, but cannot be 
ranked among the characteristic features of the disease. Among these 
may be mentioned convulsions, which sometimes occur shortly before death, 
or more rarely precede the development of the disease. In the few 
instances where the latter has occurred, it is difficult to determine what, if 
any, is the connection. 
In other cases numbness or partial anaesthesia, tremors or muscular 
twitchings have been noticed, but none of these occur with sufficient fre- 
quency to make them rank among the symptoms of the disease. They 
probably depend upon some special minute lesion of the nervous system. 
The giddiness which is occasionally noticed, is probably dependent upon 
the anaemia and the feeble condition of the systemic circulation. 
Digestive Symptoms.-In nearly all cases there are marked disturbances 
of digestion present. The appetite remains fair for a time, but then grows 
capricious and irregular or fails in a marked degree. On page 80 (report 
of Mr. C. L.'s case) will be found a detailed account of some of its peculiari- 
ties. Nausea is often present, and in some cases the presence of food in 
the stomach causes marked distress. Vomiting is scarcely ever absent 
throughout the course of the disease, but, like the other symptoms, is sub- 
ject to marked alternations. At times, during the temporary spells of 
improvement already described, the appetite may become quite good and 
neither nausea nor vomiting occur. But in a variable time, often without 
any assignable cause or from some trifling over-exertion or indiscretion in 334 
Pepper, Addison's Disease. 
[April 
diet, a severe attack will occur attended with anorexia, nausea and fre- 
quent vomiting. 
The peculiar irritability of the pharynx and oesophagus described on p. 
80 is an unusual symptom. 
The condition of the bowels is equally variable. In some cases, diar- 
rhoea, due to follicular enteritis, appears among the earliest symptoms ; 
and has even been ascribed as an occasional cause for the subsequent 
development of Addison's disease. It is true that, in many instances, 
enlargement of the solitary follicles of the intestine is found, but as a rule 
the condition of the bowels is one of moderate constipation, with occa- 
sional alternations of diarrhoea with thin, serous stools. In Mr. L.'scase 
these spells of diarrhoea were attended with cutting abdominal pain and 
great nervous restlessness, agitation, and prostration. 
The abdomen is usually rather retracted ; and may be indolent through- 
out the case, while, on the other hand, tenderness of quite marked charac- 
ter may be present. In Mr. L.'s case this was found at the epigastrium, 
and was associated with unusually great reflex irritability of the abdomi- 
nal muscles. There is no alteration in the size of the liver, but a slight 
degree of enlargement of the spleen is generally present. 
The urine presents no characteristic changes. It has been found to be 
excessive in some cases, but usually it continues normal or even reduced 
in quantity. It is reported to be frequently of low specific gravity and 
deficient in solid ingredients. It never contains albumen unless there be 
coincident organic disease of the kidneys. 
Respiratory Symptoms.-In uncomplicated cases of Addison's disease 
the only symptom connected with the lungs is dyspnoea on exertion, 
resulting from the conjoined effect of anaemia and debility. This is at least 
true of the early period of the disease, though later it is quite common to 
note the appearance of cough with slight muco-purulent sputa, and the 
physical signs at the apex of one or both lungs of tuberculous(?) disease, 
of limited extent. In the case here reported, no dyspnoea was noticed 
until towards the close, when debility was extreme and a small degree of 
pulmonary disease had occurred. 
The circulatory system furnishes much more important symptoms. The 
heart's action is feeble, and the pulse is very small and weak. During 
quiet it may rise but very little above the usual rate ; but even slight 
exertion accelerates it and is apt to bring on palpitation. During the 
paroxysmal exacerbations of the disease, the pulse is usually much dis- 
turbed, becoming more rapid, 100 to 120, and at the same time extremely 
small, thread-like, and feeble. In the last stages of the disease the pulse 
is apt to be accelerated, but in some cases it is unusually slow, as in one 
reported by Dr. H. Thompson, where it varied from 52 to 60 within a fort- 
night of the death of the patient. 
Cardiac or vascular murmurs of haemic origin, connected with the 1877.] 
Pepper, Addison's Disease. 
335 
altered condition of the blood, are occasionally detected, but by no means 
so frequently as might be expected. In neither of the cases I have had 
the opportunity of carefully studying, were such murmurs present. 
Abnormal pulsation of the aorta is present in a large proportion of 
cases; and its detection is rendered more easy by the retraction of the 
abdominal walls which often exists. In some cases there has been an 
apparent dilatation of the vessel (Gerhardt), but, as is well known, this is 
not an unusual sensation in connection with excessive local pulsation of 
large arteries. 
The state of the blood is one of the most important conditions in this 
disease, and bears directly upon some of the most interesting questions as 
to its pathology and the nature of the symptoms. Unfortunately, however, 
the number of careful examinations which have been made is so small, and 
the results are so indefinite and even contradictory, as to render it very 
difficult to form a correct opinion as to the condition of this fluid. 
Partly in consequence of this we find one of the most able and zealous 
investigators of the nature and symptoms of Addison's disease, Dr. 
Greenhow,1 in his latest publication on the subject, expressing his opinion 
that the composition of the blood does not undergo any important altera- 
tion in uncomplicated cases of this affection. On the other hand, the exist- 
ence and extreme degree of the anaemia occupied a prominent place in the 
group of symptoms which Dr. Addison established as characteristic of the 
disease he first described. It is true that accounts of the condition of the 
blood very rarely describe it as presenting the thin, watery consistence 
and light colour so characteristic of anaemia. On the contrary, in a fair 
proportion of the cases where its condition is referred to at all, the colour 
and consistency are spoken of as normal, and in one case reported by Green- 
how the blood is even described as thicker than natural, with an excess of 
red globules. Still it must be remembered that these are but superficial 
means of judging of the blood. I have, in a former article already 
referred to (in the number of this Journal for October, 1875), spoken 
of the vague meaning of the term anaemia, and of its utter insufficiency to 
express all of the important forms of defective constitution of the blood. 
It seems to me evident that, though the blood may not present the 
characters of ordinary anaemia, there must be grave interference with the 
healthy state of this fluid. In the first place, it appears undoubted that a 
great reduction in the mass of the blood usually takes place. This is sug- 
gested by the appearance of those parts of the surface which are free from 
the peculiar discoloration whioh is so characteristic of the disease. Thus 
the conjunctivae are pearly white, and the matrix of the nails appears 
peculiarly white, far more so than could be explained merely by contrast 
with the surrounding discoloured skin. The marked degree in which this 
1 Med. Times and Gaz., June 12, 1875, p. 630. 336 
Pepper, Addison's Disease. 
[April 
appearance exists is shown by the frequency with which such terms as 
anaemic or chlorotic are used to describe the condition of the patient. 
Many of the symptoms, as will be further pointed out, seem to indicate and 
depend upon a deficiency of blood in the vessels. Finally, at the post- 
mortem examination, there is extremely little blood in the vessels or in the 
viscera with the exception of the lower part of the lungs and the right cavi- 
ties of the heart. In the case of Mr. C. L. this decrease in the amount of 
blood in the vessels and tissues was very marked. 
Again, in a great majority of those cases in which microscopic exami- 
nation of the blood has been made, an excess of white corpuscles has been 
noted ; according to Hayden, it has been detected in every instance where 
careful examination has been made. In some instances this excess is 
slight, in others marked ; in a case reported by Severini (Schmidt's Jahrb. 
cxlii. p. Ill), the white and red corpuscles seemed about equal in number. 
It has not been determined in what proportion of cases this increase takes 
place, nor whether it depends upon an actual increase in the number of 
white corpuscles, or is merely relative and dependent upon a great reduc- 
tion in the number of the red globules. Possibly here, as is the case in 
other forms of disease of the blood-making function, both of these condi- 
tions may be present; in one set of cases, the element of increased formation 
of white corpuscles being present, while in another set there is only an 
apparent increase, due to the deficiency of red globules, which would seem 
to be more constant. It must not be forgotten that the dark colour of the 
blood may in part be due to some alteration in character or increase in 
quantity of its colouring matter. 
The fibrin of the blood is apparently not greatly decreased, since it is 
usual to find small clots in the cavities of the heart. In Mr. L.'s case 
there were such clots, and on expressing the serum which they contained, 
they presented a peculiar and unusual whiteness. 
I know of no instance where a careful analysis of the blood in Addison's 
disease has been made, but, on the whole, it seems clear to me that there 
is in this affection a profound interference with the elaboration of the 
blood, marked by decrease in the amount of blood and of the red globules, 
with or without actual increase in the proportion of the white corpuscles. 
If this be so, it would justify the use of the term " aneematosis," which I 
have suggested for the condition present in the group of diseases compris- 
ing leukaemia, pseudo-leukaemia and progressive pernicious anaemia, and 
would indicate the possibility of further analogies between them and 
Addison's disease. I shall have occasion to return later to this interesting 
question. 
Hemorrhages.-Closely connected with the question of the condition of 
the blood is that of the liability to hemorrhages which, in Addison's dis- 
ease, are far from being common. It will be seen, hereafter, that minute 
extravasations of blood may be found after death in various parts, but 1877.] 
Pepper, Addison's Disease. 
337 
daring life the liability to hemorrhages is much less than in some appa- 
rently allied diseases, such as progressive pernicious anaemia. 
Emaciation usually exists to a slight or moderate degree ; but, unless 
there is some complication of a serious character, there is no such wasting 
present as is seen in many chronic diseases. 
Temperature.-Among the symptoms recorded in some cases, especially 
in the early stages of those which run a comparatively rapid course (as in 
a case by Heckford, Lancet, March, 1867), are slight rigors with very 
moderate febrile reaction (100° to 100.5° F.); and occasionally there is 
slight, irregular fever at intervals during the course of the case. But 
such cases are, perhaps, the exceptions, and it would seem to be the rule 
for the temperature to remain normal, or even to show a tendency to fall 
below the natural standard. In Mr. L.'s case it was never observed above 
100° F.; more frequently it varied from 98.5° in the morning to 99.5° 
in the evening. But at times, when the exacerbations occurred, which we 
have already described, although the temperature of the trunk did not vary 
much, the extremities grew very cool, even so far up as the thighs and 
elbows. The difficulty in maintaining the bodily warmth is shown by this 
tendency to coolness of the extremities, and, in a very marked manner, by 
the severe effects of exposure to even moderate cold. 
Discoloration of the Skin.-I have postponed until the last the dis- 
cussion of this symptom, which has erroneously been regarded as the most 
important and characteristic feature of the disease. It is to this error 
that very much of the confusion which still surrounds the subject of Addi- 
son's disease is due. It is essential, then, that we should endeavour to 
obtain clear and definite ideas of the character and value of this symptom. 
In the first place, it is evident from a study of the recorded cases, that the 
discoloration of the skin is not among the earliest symptoms of the dis- 
ease, but that the disease of the supra-renal capsules, with the consequent 
debility and changes in the blood, has often been progressing for an inde- 
finite time-months, or even a year or two-before discoloration of the 
skin makes its appearance. 
Again, it appears that it cannot be regarded as an essential symptom, 
and that there is no definite relation between the degree of discoloration 
and the development of the general symptoms and the extent of the lesion 
of the capsules. As a general rule, it is most intense in cases which run 
a very slow and chronic course. On the other hand, in some cases where 
the characteristic symptoms were very marked and severe, and the charac- 
teristic lesion of the capsules present, it is stated that there was no dis- 
coloration at all; and although it is possible that in some of these a 
slight shade of discoloration may have existed and been overlooked, it 
appears certain that in others (cases by J. B. S. Jackson, Gull, Niemeyer) 
it was entirely wanting. 
It is probable that the explanation of these instances is that death has 
No. CXLVI.-April 1877. 22 338 
Pepper, Addison's Disease. 
[April 
been induced by exceptional individual weakness or unusually severe func- 
tional disturbances before time was given for any marked accumulation of 
pigment. 
It is further to be remembered that discoloration of the skin (not 
always to be distinguished, even by the most careful study, from that 
which attends Addison's disease of the supra-renal capsules) may be pro- 
duced by various causes, such as uterine disease, malarial fever, hepatic 
disease, or cancerous or tuberculous peritonitis. (See Case I.) 
Finally, it has been clearly shown that various diseases of the supra- 
renal capsules, such as cancer, tubercle, or hemorrhage, may occur without 
the production either of discoloration of the skin or of the characteristic 
general symptoms ; and that it is only one form of disease, viz., chronic 
inflammation with cheesy degeneration and sclerosis of the capsules, that 
induces the symptoms recognized by Dr. Addison. (See Case II.) 
It is evident, therefore, that it is only by studying the discoloration of 
the skin in connection with the general symptoms that we can, in any 
case, assign to it its proper significance. 
The discoloration itself is also deserving of close study, both in regard 
to its character, its distribution, and its progress and mode of develop- 
ment. 
In typical cases the skin assumes a peculiar yellowish-brown colour, 
which can be best described by saying that the patient comes to look 
closely like a mulatto. Sometimes the brown colour predominates and 
the surface assumes a light mahogany tint, or as though the skin had been 
washed with walnut-juice. The term bronzing of the skin, which has been 
very frequently used, serves to describe the general character of the disco- 
loration very well. Niemeyer speaks of the skin sometimes presenting a 
pure gray colour, inclining to black, like plumbago ; but this certainly 
cannot be regarded as usual or in any way characteristic. 
The discoloration does not extend uniformly over the surface. It 
seems that there is a general tendency to excessive formation and deposit 
of pigment, and it is probable that in many cases there is discoloration 
all over the body, though very faint excepting in those places which are 
most exposed, or where there is a natural tendency to the deposit of 
pigment. 
Thus the face and hands are most frequently discoloured, and dark 
patches are also found about the genitals, in the axillae and the popliteal 
spaces, and along the spine and the linea alba. These darker portions of 
skin gradually shade off into the surrounding lighter surface ; very rarely do 
they pass abruptly into skin of normal colour. In Mr. L.'s case, the dark 
areas shaded gradually off into surrounding lighter skin, excepting on the 
hands, where the discoloration was abruptly limited on the sides. It is 
not rare to observe small spots of much darker colour upon the deeply 
discoloured areas. In addition, it has been frequently noticed that intense 1877.] 
Pepper, Addison's Disease. 
339 
discoloration is developed wherever an abrasion has occurred, or a blister 
has been applied, or wherever pressure has been exerted, as in the line of 
a strap worn over the shoulder, or of a dress-string around the waist. 
The discoloration does not extend to the palms of the hands or the 
soles of the feet, though these have in some cases been observed to present 
dark spots. The roots of the nails remain free, and, indeed, owing to the 
coexisting anaemia, they are unusually white and present a very marked 
contrast with the dark colour of the back of the hand. 
The discoloration often affects the mucous membrane of the mouth, and 
irregular bluish-black streaks or spots are frequently found on the lips and 
inside of the mouth, and more rarely on the tongue Greenhow states 
that similar streaks exist in Lascars, thus supplying a further illustration 
of the resemblance between the pigmentation in Addison's disease and 
that which exists in the darker races of mankind. Niemeyer is inclined 
to regard these patches on the mucous membrane as pathognomonic of 
Addison's disease, since he finds no mention made of them in any of the 
recorded cases of bronzed skin without disease of the supra-renal capsules. 
On the other hand, the conjunctivae remain normal, and in only two 
cases have I found it recorded that they presented a peculiar dirty-brown 
colour. Small dark spots of pigment have also been noticed in the iris. 
Another singular illustration of the general tendency to excessive pigmen- 
tation, is the fact that the hair has been noticed to grow darker. Dr. 
Addison stated (Zoe. cit., p. 215) that the irregular and excessive distri- 
bution of pigment was also occasionally manifest in the internal organs. 
The mode of appearance of the discoloration is peculiar. It has been 
observed in cases where the symptoms have lasted only four months ; but 
it does not usually appear among the early symptoms, and it certainly 
becomes most intense in slow chronic cases. It has frequently been 
noticed, and this was very well marked in Mr. C. L.'s case, that the colour 
varies considerably from time to time during the course of the disease. 
Allusion has already been made to the,remarkable paroxysmal progress of 
this affection-periods of comparative ease and apparent improvement 
following the most alarming conditions. It is found that during or soon 
after (Bristowe) the exacerbation of the general symptoms, there is a 
marked deepening of the colour, while during the following period of remis- 
sion the discoloration grows decidedly lighter. Not only so, but after the 
bronzing has become very marked in a certain place, it may fade away 
there, while some other area is growing much darker. The microscopic 
appearances of the discoloured skin will be alluded to under the head of 
morbid anatomy. 
The skin is usually dry and harsh, and in some cases a peculiar disagree- 
able odour of the perspiration has been observed. 
Having thus spoken of the peculiar symptoms of Addison's disease, it 
remains to allude briefly to its course and termination. Occasionally the 340 
Pepper, Addison's Disease. 
[April 
development of the early symptoms is more rapid and abrupt than usual, 
and the disease runs a rapid course, terminating fatally in a few months. 
It is probable, however, that in such cases, latent disease has been pro- 
gressing in the supra-renal capsules for an uncertain length of time, and 
that finally an abrupt outbreak of the general symptoms has occurred. 
But in the more typical and ordinary cases, the course of the affection is 
a very chronic one, extending over from two to five or seven years, or 
even longer. Allusion has also been made to the remarkable alternations 
of apparent improvement and of rapid progress of the symptoms which are 
presented during this course, so that a patient whose condition appears 
almost hopeless may slowly rally, regain strength, and even be able to 
resume light occupation ; in most instances, unfortunately, only to be 
abruptly reduced in the course of a few days to a condition of even greater 
prostration than at first by some apparently causeless attack of vomiting, 
diarrhoea, or some such disturbance. Several of these alternate paroxysms 
and remissions may be presented in the course of the disease. Finally, 
however, the patient sinks into a state of excessive prostration, the appe- 
tite fails, the pulse becomes extremely feeble and small, the temperature 
falls, there may be slight delirium, with a tendency to coma, or, on the other 
hand, convulsions may occur, and death follows from exhaustion. In some 
cases, death is preceded by a quite sudden and extreme collapse, not a 
little resembling that of cholera, excepting that there are no discharges, 
or at most only occasional vomiting. I would also call particular atten- 
tion to the great liability to sudden death in Addison's disease. It is not 
uncommon in cases where the prostration is extreme for death finally to 
occur, as it did in Mr. L.'s case, very suddenly with or without some 
muscular effort to cause it. But it also occasionally happens that, in 
cases where the debility has not yet become so alarming, some rather 
excessive exertion may be followed by sudden and fatal syncope. Thus in 
an unpublished case, the details of which were communicated to me, the 
patient was removed from Philadelphia to Chicago, but died almost 
instantly on making some slight muscular effort after this fatiguing 
journey. So great is the danger of this fatal accident in cases of Addi- 
son's disease, that the relatives should be warned of the possibility of its 
occurrence, aud positive injunctions be laid upon any unnecessary or 
unusual exertion. 
The prognosis is almost invariably unfavourable as regards the final 
termination of the case; though life may be very greatly prolonged. In 
a few cases on record, very great improvement occurred, and, at the time 
of the report, had lasted so long as to give rise to strong hopes that it 
might prove permanent. Nor, so far as is known, is there any insuper- 
able reason why recovery may not occur in Addison's disease. But as a 
matter of fact in nearly every case, if not in every one where the disease 
had been observed to the close, it has resulted in death. 1877.] 
Pepper, Addison's Disease. 
341 
Morbid Anatomy.-The lesions which are found after death from this 
affection are deserving of careful study. I have already spoken of the con- 
dition of the blood (p. 335), and will now call attention first to those 
appearances which are most constant and characteristic, and then to those 
which are less frequently met with. 
The skin, where it is the seat of discoloration, presents the same condi- 
tions as are found in the darker races of men. The pigment, in the form 
of fine granular particles, is deposited in the rete mucosum, while the 
more superficial layers of the epidermis and of the true skin usually remain 
free from any coloration. 
The lesions of the supra-renal capsules which are to be regarded as 
characteristic may be traced exclusively to a process of chronic sclerotic 
inflammation with caseous degeneration of parts of the newly formed 
exudation. It occasionally happens that true tuberculous granulations 
will be also found developed in the stroma of the gland surrounding the 
areas of cheesy degeneration. A minute description of these lesions will 
be found at page 83 (Mr. L.'s case), and I shall, therefore, in this place, 
merely sketch in general terms the different stages which the morbid process 
passes through, and the general and microscopical characters of each. 
In the early stage, which is scarcely ever seen excepting in the cases 
which run a comparatively acute course, the capsules are enlarged and 
heavy ; their envelope is usually inflamed and thickened. On section, the 
pigment layer, which is so marked in the healthy capsules, is absent, and 
there is no line of demarcation between the cortex and the medulla. If 
the process has involved the whole gland uniformly, the section may pre- 
sent a uniform grayish, semi-translucent structure. This is due to inflam- 
matory hypertrophy of the interstitial fibro-cellular tissue, the gland 
elements having undergone atrophy. On microscopic examination, a 
finely fibriHated stroma is observed, with numerous lymphoid cells and 
nuclei. This corresponds to the first stage of sclerosis. A little later, 
the capsule is still enlarged as before, but a section presents a marbled 
appearance, the grayish, semi-translucent surfaces being dotted with 
irregularly-rounded, opaque, yellowish or cream-coloured patches, where 
fatty degeneration of the new-formed tissues has begun. The subsequent 
changes which the capsules undergo are familiar in other forms of scle- 
rosis. The grayish, fibriHated stroma develops into a more and more 
dense fibroid tissue, contracting and causing puckering and shrivelling of 
the capsule. The patches of fatty degeneration undergo the various 
stages of retrograde metamorphosis. The fibrils disintegrate, the cells 
become shrivelled and filled with oily and granular matter. In some in- 
stances a process of fatty liquefactive change occurs which reduces the 
degenerating spot to a pseudo-cyst, filled with a diffluent, creamy matter, 
which is really of oily nature, though often erroneously described as puru- 
lent. Occasionally such cysts persist for a long time, and remain with 342 
Pepper, Addison's Disease. 
[April 
their peculiar fluid contents after other parts of the organ have passed 
into further stages of degeneration ; but usually the fluid parts are slowly 
absorbed, leaving a dryish, friable, and cheesy residue. In other instances, 
this stage of cheesy degeneration is gradually induced without passing 
through the intermediate stage of liquefactive softening. Subsequently 
the organic portions of these cheesy collections are slowly removed by ab- 
sorption, and more or less complete calcification results. It will be seen, 
therefore, that the affected capsules present different conditions, according 
to the duration and stage of the morbid process, although this is in all 
cases one and the same. It has already been mentioned that occasionally 
true tuberculous granulations are found in the stroma surrounding the 
areas of cheesy degeneration. This does not, however, justify the view 
that the morbid process is essentially a tuberculous one, since a similar 
development of tuberculous granulations, due to the infectious influence 
of areas of cheesy degeneration, is familiar as a secondary phenomenon 
in mauy localities. In the last stages of the change, as seen in typical 
chronic cases, the capsules are very irregular in shape, puckered and 
nodulated. They may be smaller than normal, owing to contraction 
and absorption. Their envelope is dense, thickened, and often closely 
adherent to adjoining parts. On section they present the various stages 
of degenerative change above described. In nearly every case (all but 4 
out of 128 - Greenhow) both capsules are affected, but far more fre- 
quently it has not advanced equally in the two. 
It will be seen that many of the symptoms of Addison's disease appear 
to indicate some implication of the sympathetic nervous system, or of 
the pneumogastric nerves, and accordingly, in a small number of cases, a 
careful examination has been made of the condition of the supra-renal 
and solar plexuses. 
Considering the close proximity of the supra-renal capsules to the 
large abdominal nervous ganglia, and the fact that there is marked thick- 
ening of the envelopes of the capsules, as well as of the surrounding cel- 
lular tissue, it is but what might have been expected that the ganglia 
and plexuses should be invested with indurated and condensed tissue. In 
a few instances the fibrous tissue in the ganglia is stated to have been 
increased, with or without alteration of the nerve-cells. Examination- of 
the nerve-trunks connected with these plexuses has also shown that the 
morbid process had extended to their sheaths, causing fibroid thickening with 
or without atrophy of the nerve-fibrils from pressure. It cannot yet be said, 
however, that such lesions are constant or even frequent, since careful ex- 
amination of the parts has been made in but few instances ; and, in some of 
these, with negative results. Thus, in the case of Mr. C. L., minute exami- 
nation of the abdominal sympathetic nerves and ganglia revealed an entire 
absence of any lesion. It is much to be regretted that this point has not 
more frequently been examined with such care as to establish positively 1877.] 
Pepper, Addison's Disease. 
343 
the existence or non-existence of any definite changes in these nervous 
tissues, since, as will be seen later, one of the most popular theories for 
explaining the peculiar symptoms of Addison's disease rests entirely upon 
the serious complication of the sympathetic nerve. Apart from this, no 
lesions are known to occur in the nervous system, although careful exami- 
nations of the brain and spinal cord are still much needed. 
Thorax.-The lungs very frequently present caseous nodules, sur- 
rounded by fibroid induration. Frequently, also, softening of the cheesy 
matter has occurred with the production of small cavities, such as I have 
described in Mr. C. L.'s case. The amount of lung-tissue involved may 
be limited to a patch one inch in diameter, or a considerable part of the 
upper lobes may be consolidated. The cavities are, as a rule, old, and 
there may or may not be a development of miliary tubercles in the surround- 
ing tissues. In other cases, on the contrary, the lungs present the lesions 
of diffused miliary tuberculosis, resulting, I believe, from constitutional 
infection from the caseous nodules in the supra-renal capsules. In many 
cases, the existence of long-continued irritative action in the lungs is 
shown by the existence of old pleural adhesions and fibroid thickening of 
the pleurae. It is unusual to find any pleural effusions. The heart has, 
unfortunately, not been often subjected to careful microscopical examina- 
tion in this affection. In cases where it has, fatty degeneration of the 
muscular substance has generally been detected, as might be anticipated 
from the extreme anaemia and the evidences of failure of heart-power. 
There is no tendency to valvular disease. In a few cases, recent peri- 
carditis has been found. 
Abdomen.-Occasionally spots of excessive deposit of pigment have been 
observed on the peritoneum or in some of the viscera. Cellular adhesions 
may exist between different organs or between folds of intestine, and in 
cases where general tuberculosis has been developed, miliary granulations 
are apt to exist upon the peritoneum also. 
The liver and kidneys are, as a rule, found healthy. 
The spleen, though sometimes mentioned as healthy, is usually de- 
cidedly enlarged, swollen, and soft. Its colour is most frequently dark, 
so that it has been compared to the spleen in typhus fever; but in Mr. 
L.'s case I have noted it as rather pale. 
The mucous membrane of the stomach is rarely healthy. In some 
cases enlargement of the gastric follicles is found, as described at page 84 ; 
in others a mammillated condition is observed, which is due, according to 
Coupland and Schafer, to local outgrowths of lymphoid tissue. Small 
ecchymoses are occasionally found on the mucous membrane, and, more 
rarely, small abrasions or ulcers. 
The intestine usually presents the evidences of chronic intestinal catarrh ; 
and, although in the present case there was no enlargement of the soli- 
tary glands or of Peyer's patches, these lesions are present in very many 344 
Pepper, Addison's Disease. 
[April 
instances. I would call special attention to the numerous subperitoneal 
and submucous ecchymoses which existed in Mr. L.'s case (see page 84). 
Ulcerations are but very rarely found. The mesenteric glands are enlarged 
and occasionally caseous ; in the present case they contained abnormal 
deposits of pigment, possibly the result of the ecchymoses above described. 
The retro-peritoneal glands in the neighbourhood of the supra-renal cap- 
sules may also be found enlarged, and in a state of cheesy degeneration. 
Bones.-In a typical case of. seven years' duration, reported by Gnll 
{Medical Times and Gazette, October 21, 1865, p. 441), the patient had 
complained of pain in the left foot. At the autopsy, characteristic lesions 
of the supra-renal capsules in the last stage were observed. The bones 
forming the left ankle joint (tibia and astragalus), as well as others of 
the tarsal bones, were soft, and easily cut by the knife. On section they 
presented either a yellow (fatty) or a red appearance. None of the 
joints, including ankle joints, were at all diseased. No mention is made 
of the other bones. I trust that in future examinations the state of the 
marrow may be carefully determined. 
Causes and Nature. Explanation of Symptoms.-It has been seen 
that the lesion of the supra-renal capsules, which is characteristic of Ad- 
dison's disease, is a chronic inflammation of low grade, with sclerosis and 
cheesy degeneration. It is interesting to inquire what causes induce such 
a condition of disease in these organs, about whose functions our knowl- 
edge is so imperfect. It is evident that the affection is not primarily 
tuberculous in character ; and, indeed, from an examination of the antece- 
dents of patients, and from the age at which it chiefly occurs, it can scarcely 
be classed as scrofulous. It is true that Greenhow and others speak of it 
as frequently occurring in persons of a tuberculous diathesis; but this 
appears doubtful to me, since I should be inclined to regard the Lung 
trouble as secondary, the result of infection from the cheesy, degenerating 
capsules. Indeed, it would seem that the number of cases in which general 
miliary tuberculosis has followed from such constitutional infection is very 
small relatively, so that it would not indicate that the subjects in whom 
Addison's disease has been observed were at all strongly predisposed to 
tuberculosis. 
It appears from the analysis which Greenhow has published of nearly 
all cases on record that Addison's disease is far more frequent in the male 
sex, and occurs almost exclusively in those who are engaged in active 
manual labour, the cases being pretty equally distributed over the laborious 
period of life, and being almost entirely confined to that period. In a few 
instances the beginning of the disease has been referred to the occurrence 
of some strain or injury to the back ; and, from the character of occupa- 
tion of the vast majority of the patients, it is highly probable that such a 
cause may have very frequently existed without attracting especial atten- 
tion. I would refer here to the marked pain which was experienced by 1877.] 
Pepper, Addison's Disease. 
345 
Mr. L., for years before the development of definite symptoms, whenever 
he engaged in such work as digging, which requires straining efforts with 
the back. Further, in a considerable number of cases, there has been 
chronic inflammatory disease of parts adjacent to the supra-renal capsules, 
such as caries of the vertebrae; and it is altogether probable that the lat- 
ter disease was the primary one, and that the capsules became affected by 
extension of inflammation. It is, of course, impossible to decide in how 
large a proportion of all cases of Addison's disease the above direct causes 
are operative, and in how many instances, if at all, the disease arises from 
general constitutional causes alone. It is quite possible that there may 
exist in certain persons a peculiar tendency to this low grade of inflamma- 
tory action in the supra-renal capsules, which is readily excited by slight 
mechanical causes. 
According to various writers climate would seem to play a marked part 
in the causation of Addison's disease. Thus it appears to be far most 
frequent in England, and then, according to Jaccoud, Italy, the Low 
Countries, Germany, and finally France follow. It is certainly a rare 
affection in America. Still I doubt if much value can be attached to any 
of these statements, since they are based merely on the proportion of all 
the recorded cases (but little over 300 in number) which has occurred in 
each of the respective countries. Before the true influence of climate can 
be determined, it will require a far larger range of observation, directed 
with equal attention, in the various localities. Hitherto the attention of 
the profession in England has naturally been closely directed to this sub- 
ject, and, it is probable that, in consequence, cases have there been de- 
tected which elsewhere might have been overlooked. It must also be re- 
membered that the real frequency of any affection must be calculated in 
relation with the number of inhabitants of each country ; and especially 
with the extent of population in the large cities, from which the great 
proportion of records of such cases is drawn. It will be readily under- 
stood why a disease, plausibly thought to be due, in many cases, to 
strain or injury, should occur with comparative frequency in such a city 
as London, with its vast numbers of male inhabitants engaged in every 
species of hard work. It seems to me probable that climate will be found 
to have no special influence whatsoever. 
If the causes of Addison's disease be not definitely ascertained, the rela- 
tion between the lesion of the capsules and the characteristic symptoms of 
the affection are equally the subject of discussion. 
In the first place it must, I think, be admitted that these symptoms are 
not directly dependent upon the disturbance or abolition of any function 
the supra-renal capsules may be supposed to possess. It has been shown 
by Harley and others (see Brit, and For. Med.-Chir. Review, 1856), 
despite the experiments of Brown-Sequard, that the supra-renal capsules 346 
Pepper, Addison's Disease. 
[April 
are not in any way essential to life, and that their removal leads to no 
definite disturbance. 
The capsules may be the seat of other forms of disease, as hemorrhage, 
cancer, cysts, fatty degeneration, to such an extent as to lead to entire loss 
of the healthy structure, and yet without the development of the peculiar 
discoloration of the skin or the characteristic general symptoms. There 
are quite a number of cases which demonstrate this position ; And I will 
merely give the following brief summary of a case in which cancerous 
nodules were found in the left supra-renal capsule, without the presence 
of discoloration or any characteristic symptom. 
Case I.-Sarah S. aat. 29 years, married but sterile, was in ill health during 
1866, with symptoms of severe irritation of rectum and bladder, followed by the 
appearance of a hard tumour in left iliac region. In fall of 1867, symptoms of 
acute cerebral softening (attributed to presence of a cancerous tumour in 
brain) made their appearance, and death followed within a fortnight. There 
was marked emaciation, but no discoloration of the skin in any part. 
At the post-mortem examination, a small tumour was found in the brain 
with red softening surrounding it. There was scirrhous cancer of left ovary. 
The right supra-renal capsule was healthy, the left was enlarged and hardened, 
and on section presented several nodules of scirrhous cancer. There were 
some old and quite firm local peritoneal adhesions. 
It is evident from the stage which has been reached by the morbid 
lesion in some cases where the symptoms have existed for but a compara- 
tively short time, that even extensive degeneration of the supra-renal 
capsules may occur before the development of any recognizable symptoms. 
And further, it appears from the record of a small number of cases, that 
when the disease has been limited to one capsule, the general symptoms 
and course of the case have not been different from those of the more common 
form where both capsules are affected, even if not to exactly the same 
degree. 
As it seems indisputable, therefore, that the peculiar features of Addi- 
son's disease cannot be dependent upon the mere impairment or abolition 
of any function which the supra-renal capsules may possess ; and yet as it is 
established beyond question, that the occurrence of the peculiar form of 
inflammatory degeneration of these organs which we have described, is the 
characteristic and primary lesion in Addison's disease ; it becomes evident 
that the symptoms must depend upon some influence exerted by the dis- 
eased capsules upon the rest of the economy. 
This brings us directly to consider the two principal ways in which 
such an influence may be supposed to be exerted. 
The first of these, which has attracted a great deal of attention and 
favourable comment from some of the most distinguished investigators of 
this subject, is through the medium of the nervous connections of the 
supra-renal capsules. The second is by the slow induction of cachexia, 
with grave disturbance of the elaboration of the blood, and interference 
with general nutrition. 1877.] 
Pepper, Addison's Disease. 
347 
The first supposition is based upon the following data :- 
1. The unusually rich nervous supply of the capsules. 
2. The proximity of the solar plexus and the semilunar ganglia. 
3. The connection of the nerves of the capsules with the phrenic and 
pneumogastric nerves? 
4. The character of many of the principal symptoms which follow 
degeneration of these organs. 
There has been a good deal of doubt about the exact anatomical 
structure of the supra-renal capsules, though all authorities agree as to 
the large number of nervous branches which are connected with them, 
and as to the existence of a certain number (probably quite small) of 
nerve-cells, in the central medullary substance. Some writers have been 
led, in consideration of this, to rank the capsules among the nervous 
structures; but the most elaborate and apparently reliable investigations, 
those of Grandry,1 appear to finally decide their place to be among the duct- 
less glands. It is not possible at present to assign any function to them, 
though it would seem from analogy, that they are in some way connected 
with the elaboration of the blood. It has been already seen that they are 
not essential to life. 
It is evident, however, that if a chronic inflammatory process should 
extend from the capsules to the connective tissue surrounding them, and 
at the same time along the sheath of the nerve-branches connected with 
them, such a degree of hyperplasia and thickening might result, followed by 
such contraction and condensation of the affected tissues, as would seriously 
irritate and involve, and ultimately cause atrophy and degeneration of 
the nerve-branches and even of the solar plexus and the semilunar ganglia. 
It may even be conceived that, before any gross lesions of the sheaths of 
the nerves connected with the capsules, or of the cellular tissue investing 
the ganglia, should be developed, so much irritation Of the terminal fila- 
ments in the capsules might exist as to give rise, by reflex action, to very 
marked results. 
Granting that such irritation and such morbid changes should be 
present, it is not difficult to trace an explanation of some of the most 
characteristic symptoms of Addison's disease. 
Thus the extreme muscular debility may be attributed to the prolonged 
reflex irritation of the nerve centres; the frequent action of the heart with 
small feeble pulse, and the disposition to breathlessness or even syncope on 
exertion may be referred to implication of the pneumogastrics and phrenics, 
or to irritation of the thoracic ganglia of the sympathetic; the irritability 
of the stomach with nausea and vomiting, and the occasional abdominal 
pain and diarrhoea would point to interference with the solar plexus and 
semilunar ganglia; and it is further possible, if certain experiments of 
1 Journ. de 1'Anat. et de la Phys., 1867, pp. 225 and 389. 348 
Pepper, Addison's Disease. 
[April 
Pincus (quoted by Greenhow from Funke's Physiology) are reliable, that 
the evidences of catarrhal irritation of the mucous membrane of the 
stomach and intestine may depend upon the disturbance of these same 
great nervous ganglia. It has been shown by careful experiments (Jasch- 
kowitz), that section of the abdominal sympathetic is followed by a mode- 
rate degree of swelling and enlargement of the spleen, such as is observed 
in a great number of cases of Addison's disease. 
Finally, there is good reason to attribute the unusual tendency to pig- 
mentary deposition in the skin, and elsewhere, to a morbid irritation of 
the nerves of the abdominal plexus. It has been already seen (see page 
331) that there is no definite relation between the extent of the lesion of 
the supra-renal capsules and the degree of the discoloration ; that discol- 
oration of the skin is known to occur only in. connection with chronic 
sclerotic and caseous inflammation of the capsules, while various other 
organic lesions of these organs occur without any such result; and that 
consequently it cannot be held that the bronzing of the skin depends 
upon the disturbance of the function of these organs. 
The fact that Vulpian has found that the capsules and the blood pass- 
ing from them contain a substance which yields a peculiar deep-blue reac- 
tion with perchloride of iron does not appear to have any special con- 
nection with the peculiar bronzing of the skin in Addison's disease. 
Again, it is a perfectly familiar fact that very marked discoloration of 
the skin may be found in cases where the supra-renal capsules remain 
entirely healthy. In cases of hepatic or gastro-hepatic disease, or of 
chronic malarial fever, a discoloration of the skin may occur, which 
closely simulates that described in connection with Addison's disease. In 
cases of uterine disease I have known the bronzing of the skin to be so 
intense, and to occupy such positions as to give rise to serious doubts as 
to the nature of the case. So, too, where extensive disease of the abdomi- 
nal organs exists, as in the case of cancer of the peritoneum and ovary re- 
ported by Dr. S. Weir Mitchell (Amer. Journ. Med. Sciences, Oct. 1867, 
p. 413), or as in the case of tuberculous peritonitis reported below by us, 
very marked bronzing or discoloration of the skin may occur. It is true 
that in most of these cases the discoloration differs either in locality or in 
arrangement from the bronzing which is characteristic of Addison's dis- 
ease. It is also true that the peculiar stains on the inside of the lips, 
mouth, and tongue, are rarely, if ever, seen excepting in the latter affec- 
tion. But still, so great is the resemblance sometimes presented, that it is 
necessary to conclude that local discolorations, without the characteristic 
general symptoms, should not be regarded as diagnostic of Addison's dis- 
ease, and that even when the bronzing is marked and extended, we should 
hesitate about making a diagnosis of Addison's disease, unless no patho- 
logical condition of any organ (other than the supra-renal capsules) can be 
detected. 1877.] 
Pepper, Addison's Disease. 
349 
In considering the manner in which the discoloration of the skin is 
brought about in these various conditions, it appears that the only element 
they possess in common is irritation of the abdominal plexus of nerves. 
Accordingly, the explanation which is now generally accepted of the 
bronzing of skin in Addison's disease is that it is due to slow, progressive 
increase in formation of pigment under the influence of irritation of the 
vaso-motor nerves. One of the peculiarities of the discoloration-the fact, 
namely, that its intensity varies from time to time-would seem to be 
better explained upon this supposition than upon any other. 
When now we pass from this to the consideration of the various other 
symptoms of Addison's disease already mentioned, it must be conceded 
thatthe view so ably supported by Jaccoud,1 Greenhow,2 and others, which 
refers these symptoms also to morbid irritation, or entire loss of function of 
the nerves connected with the supra-renal capsules, is entitled to careful 
consideration. Attractive as it is, however, I cannot feel, even with a 
full appreciation of all that has been urged above, that this theory of 
the disease is entirely satisfactory and sufficient. I do not doubt that 
many of the symptoms are due to such interference with the nervous sys- 
tem ; but I incline to believe, also, that the element of constitutional in- 
fection from the foci of cheesy degeneration must also be taken into ac- 
count. 
It must be observed that the number of post-mortem examinations as 
yet recorded in which lesions of the abdominal sympathetic have been de- 
monstrated are but few in number. It is true, on the other hand, that we 
have comparatively few cases recorded where it is distinctly stated that 
careful examination of the solar plexus and semilunar ganglia revealed no 
lesions. In the case of Mr. C. L., however, it will be seen (p. 84) that 
careful study, both of the gross and microscopic structure of the abdominal 
sympathetic, gave purely negative results. It is difficult, therefore, to com- 
prehend how such a perfectly healthy condition could have been main- 
tained if the very marked and characteristic symptoms which existed for 
several years were dependent chiefly upon morbid irritation of these 
nerve-ganglia and branches. At the same time, it may very well be be- 
lieved that the thickening and induration of the envelope of the supra-renal 
capsules and of the surrounding cellular tissue which existed might pro- 
duce enough reflex irritation of the sympathetic ganglia to aid in the 
development of some of the more purely nervous symptoms of the case. 
It is to be observed, also, that in Mr. L.'s case certain phenomena which 
would seem to be most plausibly referred to mere nervous irritation, were 
not so marked as is usual in equally characteristic cases. 
1 Nouv. Diet, de Med. et Chir. pratiques, t. v., 1866. Article, Maladie 
Bronzee. 
2 On Addison's Disease, Croonian Lectures for 1875. 350 
Pepper, Addison's Disease. 
[April 
Further investigations are necessary before a positive opinion can be 
pronounced, but it would certainly appear to be established that in Addi- 
son's disease some of the symptoms are dependent upon interference with 
the ganglia of the abdominal sympathetic, and with other nerves con- 
nected with the supra-renal capsules ; and it seems probable, also, that the 
amount of this interference varies in different cases, and that, in conse- 
quence, the comparative prominence or slightness of certain symptoms will 
result. 
It is necessary now to consider the symptoms from the other stand- 
point, and to discuss how far they may bear explanation on the view that 
Addison's disease is a cachexia, attended with grave disturbance of the 
elaboration of the blood, and interference with general nutrition. 
In the first place it may be well to regard for a moment the. evident 
analogies between the symptoms of Addison's disease and those of other 
cachexiae, in which the existence of a special nervous element has not been 
suspected. In the article published in this Journal in October, 1875 
(p. 313), I expressed my belief in the essential identity of the vari- 
ous forms of leukaemia, with so-called progressive pernicious anaemia; 
and endeavoured to show that the differences between the symptoms of 
the several forms depend chiefly upon the special organs affected in each. 
If, now, we compare the symptoms of progressive pernicious anaemia, or 
anaematosis, as I have proposed to call it, with those of Addison's disease, 
a considerable degree of correspondence will be noticed. 
Progressive Pernicious Anoemia, or 
Medullary (?) Ancematosis. 
Insidious and apparently causeless 
development of languor, debility, and 
pallor of surface; weak, small pulse; 
tendency to palpitation of the heart, 
to attacks of dyspnoea, to giddiness 
and tinnitus, and later to dangerous 
and even fatal syncope. 
Failure of appetite ; sense' of pres- 
sure or discomfort at the epigastrium ; 
attacks of nausea and vomiting. 
In some cases slight, irregular, febrile 
action. Temperature sometimes normal 
throughout. 
Absence of emaciation in any marked 
degree. 
Occurrence of hemorrhage from nose, 
gums, etc., or of petechise under skin, 
or under serous membranes. 
Addison's Disease. 
Progressive, apparently causeless lan- 
guor and debility, with, in most cases, 
bronzing of the skin; weak, small 
pulse; palpitation of the heart and 
breathlessness on exertion ; faintness, 
and even tendency to dangerous or 
fatal syncope on exertion ; giddiness and 
tinnitus occasionally observed; so also 
tremors, partial anaesthesia or numb- 
ness, or even convulsions. 
Failure of appetite; epigastric'dis- 
tress; spells of nausea and vomiting. 
Febrile action very rare ; temperature 
normal, or even reduced. 
Absence of emaciation in any marked 
degree. 
Hemorrhages do not occur. Pete- 
chiae not rarely found after death. 1877.] 
Pepper, Addison's Disease. 
351 
Progressive Pernicious Ancemia, or 
Medullary (?) Ancematosis. 
Albumen not found in my own cases, 
but reported to be occasionally present. 
Strong anaemic murmurs over heart 
and great vessels very constant. 
Progressive reduction of the mass of 
the blood, and especially of the propor- 
tion of red globules. 
Steady progress of debility ; the oc- 
currence of wandering delirium, or in- 
creasing coma, and finally death. Oc- 
sionally, sudden fatal syncope. 
Enlargement of spleen, of solitary 
glands of intestines; ecchymoses ; fatty 
degeneration of heart, liver, and kid- 
neys. Passive serous effusions. 
Lesion of marrow of bones, in some 
cases at least. 
Occasionally a centre of chronic sup- 
puration. 
Addison s Disease. 
Albumen not present. 
Anaemic murmurs occasionally met 
with, but not frequent. 
Progressive reduction of the mass of 
the blood ; proportion of red globules 
not specially diminished ; increase in 
proportion of white corpuscles. 
Steady progress of debility ; wander- 
ing delirium ; increasing coma, or, in 
rare instances, convulsions, and finally 
death. Occasionally, sudden fatal syn- 
cope. 
Enlargement of spleen, of solitary 
glands of intestines, of gastric follicles. 
Ecchymoses occasionally. Fatty de- 
generation of heart frequent. Serous 
effusions rare. 
Marrow not yet examined. 
Chronic inflammation, with cheesy 
and sclerotic degeneration, and of supra- 
renal capsules constant. 
It appears to me impossible to consider carefully the resemblance thus 
sketched between the symptoms and course of these two affections, with- 
out being struck by its closeness, and being led to inquire whether it 
may not be possible that there is something in common between them. 
In speaking of progressive anaematosis, I have attempted to explain the 
symptoms there met with, by referring them to the diminution and deterio- 
ration of the blood, and the failure of cardiac power from fatty degenera- 
tion, and from impaired nervous force. And I think it will be noticed 
that very many of the symptoms of Addison's disease admit of a similar 
explanation. 
It is true that the bronzing of the skin prevents the development of the 
familiar anaemic appearance, but in some cases the disease is well advanced 
or death may even occur before bronzing of the skin appears, and in 
such cases the appearance of anaemia is very manifest; while in all cases 
the conjunctivae and the matrices of the nails are extremely pale and 
anaemic. The reduction in the amount of the blood and the increase 
of white corpuscles have been already referred to, and although the 
colour of the blood remains good and the red globules, while absolutely 
deficient, do not seem to undergo any great proportionate reduction, it 
seems altogether probable to me that some grave defect in the elaboration 
of blood exists. Some of the more usual nervous symptoms (tinnitus, 
vertigo, etc.) may be plausibly referred to the condition of the heart's 352 
Pepper, Addison's Disease. 
[April 
action, and to the cerebral anaemia due to the reduction of the mass of the 
blood; while others (such as tremors, partial numbness or anaesthesia) may, 
perhaps, be more properly referred to reflex nervous irritation ; though it is 
not impossible that these as well as the convulsions which are noticed in 
rare cases may be due to the state of the nervous centres. The weak, 
small pulse, readily accelerated by exertion; the feeble action of the heart; 
the breathlessness on exertion ; and the tendency to syncope, are certainly 
capable of plausible explanation by the frequent existence of fatty degene- 
ration of the heart and by the anaemia of the nervous centres. I would 
again refer to the remarkable resemblance between the progressive and 
extreme muscular debility which attends both pernicious anaemia and 
Addison's disease, and which would seem to be explicable by a similar 
condition of the brain and spinal cord. 
But it is not desirable, at the present time, to go more into detail in an 
attempt to show how plausibly many of the symptoms of Addison's dis 
ease might be explained without invoking the element of irritation of the 
abdominal sympathetic nerve. 
Important evidence in favour of the view that there is also in Addison's 
disease an element of constitutional infection with impairment of blood- 
elaboration is to be drawn from the anatomical changes. Much light has 
been thrown of late upon the gradual influence of foci of chronic suppura- 
tion or cheesy degeneration in producing infection of the constitution, with 
the development of secondary cheesy deposits, or even, in cases where the 
predisposition exists, of general tuberculosis. And in Addison's disease, 
in connection with the chronic inflammatory changes in the supra-renal 
capsules progressing slowly during years, we find, in the enlargement 
and occasional cheesy degeneration of the neighbouring lymphatic glands 
and of the mesenteric glands; in the swelling of the spleen ; in the 
enlargement of the gastric follicles and of the solitary glands of the in- 
testines ; in the increase of white corpuscles of the blood with reduction 
of its mass; in the very frequent occurrence of secondary cheesy deposits 
in the lungs, and occasionally of general tuberculosis, a train of patho- 
logical changes which is certainly suggestive. 
I do not desire to be understood as offering such an explanation of the 
pathology and symptoms of Addison's disease in place of the one now 
generally received in which the symptoms are so largely referred bo impli- 
cation of the abdominal nerves and ganglia. But I wish to call attention 
anew to the importance also of the blood-changes and the signs of con- 
stitutional infection in this disease ; and to the necessity for careful study 
of the splenic pulp, and especially of the marrow of the bones, in order 
to discover whether there is any such lesion there as has been found to 
exist in progressive pernicious amemia and medullary leukaemia. 
I do not think the microscopic examinations of the blood and tissues 
have yet been sufficiently numerous and accurate to enable a positive 1877.] 
Pepper, Addison's Disease. 
353 
opinion to be expressed ; but I incline to the belief that the essential 
pathology of Addison's disease may prove to embrace both elements, as 
follows: a primary chronic degenerative inflammation of the supra renal 
capsules; constitutional infection, with production of secondary caseous 
deposits (or, in some cases, of tuberculosis); impairment of the blood-elabo- 
ration (anaematosis), possibly with lesion of the marrow of the bones or of 
the splenic pulp; consequent fatty degeneration of the heart; extension 
of irritation from the capsules to the nerves connected with them, to the 
semilunar ganglia and to the solar plexus. These factors are not stated 
in what is supposed to be their order of occurrence, or of relative im- 
portance in regard to the production of the symptoms of the disease, and 
it is evident that upon the predominance of one or the other will depend 
certain peculiarities of individual cases. 
Diagnosis.-Many of the questions connected with the diagnosis of 
Addison's disease may be dismissed with a brief reference only. I have 
already called attention to the fact that in some cases the development of 
the muscular debility is so sudden and marked as to give rise to the suspi- 
cion that the patient is about to have an attack of typhoid fever. In Mr. 
L.'s case, his family, who were observant and experienced, were impressed 
with this belief. But although in a case seen for the first time in one of 
the sudden spells of prostration, or in a case where the constitutional 
symptoms make their appearance abruptly, such a doubt might exist for a 
day or two, a careful study of the peculiar symptoms, an examination of 
the history of the case, and the absence of the characteristic features of 
typhoid fever would soon enable a positive diagnosis to be established. 
In some cases of pityriasis versicolor or nigra, the patches of discolora- 
tion are of much the same shade as is observed in Addison's disease. But 
here, in addition to the absence of all the peculiar constitutional symptoms, 
the discoloration does not affect the same localities as in Addison's disease, 
there is a sharp line of demarcation between the healthy and the discol- 
oured skin, the surface is covered with a fine furfuraceous desquamation, 
and there are no pigmentary deposits in the mucous membrane. 
It is only necessary to mention the fact that the staining of the skin 
from the prolonged use of nitrate of silver has been mistaken for the 
bronzing of Addison's disease. In reality it would be difficult to make 
such a mistake, not only on account of the different colour and distribu- 
tion of the staining, but also on account of the absence of any of the 
characteristic general symptoms. 
We come now to the more difficult question of distinguishing between 
Addison's disease and other affections attended with bronzing of the skin. 
It is true that in these latter cases the discoloration rarely presents the 
same distribution as in Addison's disease, and also that there are no dark 
streaks on the mucous membrane of the mouth. But still, these latter 
are not constant in true Addison's disease, and, in some instances, it 
No. CXLVI.-April 1877. 23 354 
Pepper, Addison's Disease. 
[April 
would be impossible to make a differential diagnosis from the characters 
of the discoloration alone. In such cases we should turn to the consti- 
tutional symptoms, a careful study of which will generally enable a correct 
diagnosis to be made. Th<f following interesting case is reported, how- 
ever, to show how closely even these may be simulated by other condi- 
tions :- 
Case IT.-Lydia B., aet. 30 years, single, was admitted to the medical ward 
of the Philadelphia Hospital, April 4, 1870. She had been sickly from child- 
hood, having had smallpox, typhoid fever, and several pleuritic attacks. No 
history of syphilis. She had not menstruated regularly siuce March, 1869, and 
not at all for two or three months past. Three months before her admission 
she noticed a brownish discoloration of the skin just below the right breast. 
This extended so as to cover breast, abdomen, and back. At first it was of 
very light colour, and gradually grew darker. During this time she was not 
sick, though still delicate and weak. On April 2, 1870 (ten days before admis- 
sion), she was attacked with a chill, sharp pain in the side, fever, and loss of 
appetite. The symptoms soon subsided under appropriate treatment, but a 
second attack occurred in a fortnight, after which she continued very weak and 
almost entirely confined to bed. She had occasional severe attacks of digestive 
disturbance, failure of appetite, vomiting, and diarrhoea. There were also 
progressive emaciation, frequent complaints of pain in the lower part of the 
left side of the chest, and great weakness. On August 20th she was put on a 
diet of skimmed milk, beginning with fgiss q. t. h., and increasing gradually till 
she took Oj t. d. Her attacks of vomiting ceased, but she still had occasional 
diarrhoea, lasting for a few days. 
Oct. 10, 1870. A few weeks ago the discoloration of the skin had faded on 
the front of the trunk, in some partshaving almost disappeared, but it is again 
growing darker. The position of the darkest discoloration is below the um- 
bilicus and over the hypochondria, and from these points the tint gradually 
shades off, merging into the lighter intermediate portions. The linea alba 
is very dark. The dorsal surface of the trunk presents quite uniform dark- 
brown discoloration, beginning over sacrum and extending upwards to level 
of second lumbar vertebra, where it shades off very gradually to the colour 
of the remaining part of the back, which is decidedly darker than normal. 
There are numerous scattered spots of dead white skin (vitiligo) over the back. 
These vary in size from 1 to 4 lines in diameter, and are usually ovoid in shape. 
There is also a large discoloured patch, mottled with whitish spots, on the 
anterior part of each thigh, reaching nearly up to the groins, which are not 
discoloured. There are no spots of vitiligo on abdomen. 
The face is sallow and dingy, but the conjunctivae remain clear, and are pearly 
white. There is no discoloration of. the hands, the axillae, or of the popliteal 
spaces. There is, however, marked discoloration of the outer surface of arms 
from wrists up to shoulders. In several places where blisters have been applied 
there is very intense discoloration. 
The emaciation is not yet extreme, but there is very great loss of muscular 
power, so that she is scarcely able to walk, and even on attempting to get up 
she suffers from vertigo and faintness. A walk of even fifty yards causes great 
prostration, violent palpitation of the heart, and dyspnoea. She consequently 
scarcely ever leaves the bed. 
There are no marked nervous symptoms, except such as depend on the 
extreme anaemia and debility. The mind is clear, and she does not suffer from 
headache. She does not dream much, and usually sleeps fairly, though some 
nights she is very restless. 
The tongue is clean and moist, the bowels are now quiet. There is complete 
absence of appetite. 
For past two weeks there has been a painful swelling above the styloid pro- 
cess of the right radius, which is the seat of rheumatoid pain, worse at night. 
There is frequent, dry, hacking cough, without expectoration. There is 1877.] 
Pepper, Addison's Disease. 
355 
some tenderness, with sharp pain on coughing or deep breathing over lower 
part of left thorax. There is no dulness on percussion. There is blowing 
breathing with prolonged expiration at the right apex. At the left apex there 
are some crackling rales; and over left chest are friction sounds which vary in 
position and character. Respirations are not much accelerated except on 
exertion. 
The cardiac sounds are normal. The pulse varies from 85 to 115, is regular 
but small, quick, and feeble. No hectic fever. There is no complaint of pain 
in abdomen or in loins. The urine is passed freely and is normal. There is no 
oedema. 
21s£. Less pleuritic pain. Debility increasing, so that after walking a few 
steps she suffers from vertigo, dyspnoea, and palpitation. No syncope. Sleeps 
poorly, without apparent cause. There is utter anorexia, and occasional 
diarrhoea. 
Nov. 23. Physical signs much the same. No dulness ; rales near root of right 
lung. Emaciation and debility increasing. For past four days there has been 
frequent and causeless vomiting. There is now considerable tenderness over 
the stomach. The discoloration of the abdomen has grown much lighter; and 
so has that of the back, though to a less extent. 
Her treatment has consisted of quinia and cod-liver oil, which has been well 
borne by the stomach except during the attacks of vomiting. The vomiting 
has yielded most readily to small doses of morphia and chloroform, or of creasote. 
Her diet has consisted of milk, beef-tea, eggs beaten up with milk and whiskey ; 
but no solid food. 
Dec. 14. Has had another attack of vomiting lasting three days ; vomiting a 
clear, slightly acid fluid three times daily. Bowels regular. She has but little 
cough. Emaciation is advanced, and debility extreme, dyspnoea occurring on 
slightest exertion. She has not, however, a sense of profound feebleness. She 
sank steadily, and died December 21, 1870 ; oedema of the right leg having 
supervened. 
Post-mortem Examination.-Body extremely emaciated. Discoloration of 
abdomen very much diminished; that of back less so. Discoloration .of thighs 
persists. The oedema of the right leg and right labium is still present. .The 
brain and cord were not examined. 
Thorax.-Heart small, but healthy. The lungs showed patches of adhesions 
here and there. On cutting into them, numerous disseminated patches of cheesy 
consolidation were found. These patches were, for the most part, superficial, 
covered by a layer of healthy vesicular tissue, and showed no softening ; in a 
few places, however, central softening had occurred and led to small vomicae. 
Abdomen.-Liver fatty, pale yellowish in colour. Spleen somewhat enlarged; 
capsule much thickened and adherent to abdominal wall: pulp apparently 
healthy. The kidneys were healthy. The supra-renal capsules were also 
healthy. 
There was diffuse peritonitis with matting together of the folds of the intes- 
tines. The peritoneum was thickened, and was studded over with numerous 
small grayish-yellow granulations. 
The sympathetic ganglia of the abdomen were carefully examined, and pre- 
sented a healthy condition. The entire body was intensely anaemic. 
Unfortunately no microscopic examination was made of the blood or of the 
marrow of the bones. 
It will thus be seen that bronzing of the skin is of comparatively little 
value in the diagnosis of Addison's disease, without the presence of 
the characteristic general symptoms. It appears also that, since both 
the general symptoms and the bronzing of the skin may be produced by 
other serious abdominal lesions, it is necessary to determine that there 
is no such condition present (as tuberculous or cancerous peritonitis for 
instance) before deciding that the case is truly one of Addison's disease 
of the supra-renal capsules. If it be true, then, that both the bronzing 356 
Pepper, Addison's Disease. 
[A pril 
of the skin and the general symptoms may be closely simulated in cases of 
other serious abdominal diseases, it would follow that we have a certain 
very peculiar group of symptoms, often attended by bronzing of the skin, 
which are believed to be due to conjoined impairment of the elaboration 
of the blood (anaematosis) and irritation of the abdominal sympathetic 
and pneumogastric nerves ; and which may apparently be caused by various 
local lesions, but especially by chronic degenerative inflammation of the 
supra-renal capsules. It is only necessary to refer to the comparison of 
the symptoms of Addison's disease and of progressive pernicious anaemia 
(anaematosis) given at page 350, to appreciate the difficulty which would 
exist in distinguishing between the two, if it were not for the bronzing 
of the skin. Indeed I must confess that I see no means by which a posi- 
tive diagnosis could be established in the absence of that symptom. 
When we recall the fact that bronzing of the skin is not an essential 
symptom of Addison's disease of the supra-renal capsules, but gains its 
significance only in connection with the peculiar constitutional symptoms; 
it would seem desirable that so soon as the true nature of this peculiar 
group of phenomena (so closely analogous to those of progressive perni- 
cious anaemia, and which are closely simulated in some other forms of 
abdominal disease) is clearly understood, some new term which may seem 
appropriate-anaematosis with bronzing of the skin, or whatever else it 
maybe-should be chosen to designate it. Until then, it is more conve- 
nient to retain the term Addison's disease, although in reality this should 
be restricted to the peculiar anatomical lesion of the supra-renal capsules 
first connected with these symptoms by Dr. Addison. This view seems 
to me of very great importance, because it widens and enlarges our con- 
ception of the nature of these constitutional symptoms which form a 
well-marked group, and which may be developed by chronic degenerative 
changes in the supra-renal capsules or by other irritative morbid pro- 
cesses in the abdominal organs. 
Treatment.-Having already spoken of the prognosis, duration, and 
modes of termination, it remains only to speak of the treatment. Unfor- 
tunately there is but little of definite character or value to be stated. 
Many remedies have been recommended and tried, but in almost every case 
on record the case has progressed inevitably to a fatal issue. In some 
instances, temporary benefit has been thought to follow the use of some 
plan of treatment; but when we bear in mind the remarkable remissions 
which occur in the ordinary course of the disease, it is evident that great 
care must be used in forming any such conclusions. It cannot be doubted 
however, that it is possible to prolong life and relieve some of the symp- 
toms by appropriate treatment ; and in a very small number of cases it is 
possible that the progress of the disease has been checked, at least, for a 
considerable length of time, if not permanently. It will be remembered 
that at several periods in Mr. L.'s case, decided improvement occurred, 1877.] 
Pepper, Addison's Disease. 
357 
though only once did it last long enough to offer any encouragement as to 
the effect of his remedies, which were at that time nitrate of silver and 
iodide of iron, with faradization. 
One of the most important elements in the treatment is rest. So long 
as any threatening symptoms of debility are present, the patient should 
remain in bed, and during the periods of temporary improvement, he 
should indulge but very cautiously in any exertion This rule is not only 
important as tending to prevent excessive fatigue and relapses, but on 
account of the danger of sudden death from collapse, if any over-exertion 
is permitted. 
It is probable that prolonged counter-irritation over the region of the 
supra-renal capsules might be productive of some relief, but I do not know 
that it has been tried sufficiently to justify any expression of opinion. 
One of the most important indications is to avoid gastric disturbance, 
which is best effected by careful attention to diet. No general rule can 
be laid down upon this subject, owing to the capricious state of the ap- 
petite and taste which is often present. In most cases milk, with or 
without lime-water, may be freely given with advantage ; and at times 
an exclusive milk diet affords relief. More often it becomes necessary to 
vary the diet from time to time, choice being made especially of simple, 
nourishing and digestible articles of food. The condition of the bowels 
is usually one of moderate constipation ; but great care must be observed 
in the use of purgatives, owing to the dangerous prostration which is apt 
to follow their action. If it be impossible, therefore, to secure a suffi- 
ciently regular state of the bowels by laxative articles of diet, recourse 
should be had to simple enemas or to mild vegetable laxatives. During 
the attacks of gastric disturbance, attended with nausea and vomiting, 
which occur from time to time, the diet must be restricted to the adminis- 
tration at short intervals of small quantities of milk and lime-water or of 
beef-juice; associated with the use of iced seltzer water, iced dry champagne, 
powders of subnitrate of bismuth, etc. I obtained the most marked benefit, 
during these severe attacks in Mr. L.'s case from the use of chlorodyne in 
repeated doses. It may be necessary, owing to the obstinacy of the 
vomiting, to resort to the temporary use of nutritious enemas. 
Another important indication is to increase muscular strength. It is 
true that this is essentially connected with the disease, and probably de- 
pends upon the anaemia as well as upon the exhaustion of the nervous 
centres by reflex irritation, and consequently its rational treatment would 
resolve itself into the treatment of the primary disease itself. 
The use of strychnia appears indicated ; but I do not know that it has 
b«en found of service. I have employed it but for a short time with 
negative results. The remedy from which I found most advantage in 
this direction was undoubtedly faradization with mild currents. Bearing 
in mind the liability to fatty degeneration of the heart, I should recom- 358 
Brickell, Treatment of Pelvic Effusions. 
[ April 
mend the occasional use of digitalis, especially in those cases where a 
tendency to spells of palpitation and dyspnoea on exertion is marked. 
Alcohol should be administered in small quantities, and in whatever 
form is hest tolerated by the stomach. 
The great indication in the treatment, however, must certainly be to 
endeavour to modify the morbid process in the capsules and surrounding 
tissues, and to counteract, so far as possible, the interference with the 
elaboration of the blood. 
Among the remedies which prove most beneficial are, as might be ex- 
pected, cod-liver oil, iron, phosphorus, nitrate of silver. 
Iron especially should form an element of the treatment. T do not know 
that the form in which it is administered is of great consequence, provided 
that it be well borne by the stomach. Greenhow strongly recommends the 
tincture of the sesquichloride, to xx, with chloroform rrLXvto xxand 
glycerin 5'j- The iodide of iron would also seem likely to be of much value. 
Phosphorus, which was strongly recommended by Broadbent in the 
treatment of leukaemia and allied affections on account of its supposed 
power of influencing the elaboration of the blood, has not been approved 
by the results of more recent and extended experience. It may be said, 
however, that this drug is still deserving of a careful trial in Addison's 
disease. 
Nitrate of silver may be given with at least temporary advantage, espe- 
cially in cases where irritability of the stomach and bowels exists, probably 
associated with chronic follicular catarrh of the mucous membrane. It is 
not unreasonable to believe that it may also produce a favourable alterative 
effect upon the chronic inflammatory process going on in the capsules and 
the surrounding cellular tissue. I used it in Mr. L.'scase, simultaneously 
with the iodide of iron, and with apparent marked benefit.