or be much larger than normal. In Ross's case it weighed six ounces.
The heart and blood-vessels do not present any constant changes: the
heart has been found small in some cases. Venous engorgement of the
abdominal viscera has been noted in a few cases, but it is not a common
feature. It was not present in two typical cases which I have examined.
{944} In the nervous system the condition of the abdominal sympathetic
has received special attention, and in a number of cases definite
changes have been met with, chiefly of a sclerotic or chronic nature
and intimately associated with the fibroid induration about the
capsules. The nerve-cells of the semilunar ganglia are described as
degenerated, deeply pigmented, and often present a new growth of
connective tissue about and between the cells. There are at least
thirty or more cases in which such alterations have been found. In some
instances the medulla of the nerves passing from the ganglia has been
found wasted and the fibres in a state of fatty degeneration. In some
cases these parts have been found normal (Foa,[205] Huber,[206]
Hebb,[207] and Hadden[208]). In a most typical case under Ross at the
Montreal General Hospital, I could find no differences in the cells and
nerves, comparing them with those of a woman dead on the same day of
heart disease. More recently, I have examined a case for Pepper in
which the right semilunar ganglion was imbedded in the sclerotic tissue
of the right adrenal; the nerve-cells were undergoing atrophy from
compression; and there were fatty changes and degenerations in the
nerves connected with this ganglion. The left was uninvolved, and the
cells and fibres appeared normal.
[Footnote 205: _Virchow-Hirsch_, 1879.]
[Footnote 206: _Virchow's Archiv_, 86.]
[Footnote 207: _Lancet_, 1883, i.]
[Footnote 208: _Loc. cit._]
Jacquet has described pigmentary changes in the ganglia of the cord as
well as in those of the abdomen, and Guermonprez[209] alterations in
the brain similar to those of senile dementia. At the Congress in 1881
at London, Semmola of Naples showed a figure illustrative of
degeneration of the ganglia of the abdomen, and also an infiltration of
leucocytes in the neighborhood of the central canal of the cord, from a
case of Addison's disease without affection of the adrenals.
[Footnote 209: Quoted by Burger, _loc. cit._]
PATHOLOGY.--The suprarenal organs are usually grouped with the
blood-vascular organs. From the number of nerve-fibres--sympathetic,
pneumogastric, and even phrenic--passing to the medullary part, and
from the presence of cells resembling nerve-corpuscles, Leydig and
others have thought that this portion belonged to the nervous system.
We know absolutely nothing of their functions. They do not appear to be
essential to life, but may be removed, crushed, or destroyed with
impunity, though the operation is not without danger from their close
proximity to important structures. They are sometimes congenitally
absent. They are proportionately larger during foetal life, but they do
not appear to atrophy as age advances; indeed, it would appear from the
observation of Mattei (Jaccoud) that they augment in volume with
increasing years. Their chemistry has attracted much attention. Vulpian
has described a material which gives a green, blue, or black color with
perchloride of iron, and with oxidizing substances a rose-red; and the
same observer found also hippuric and taurocholic acids. Leucin,
margarin, myeline (Segilsohn), and a special coloring matter (Arnold),
have been described. Henle has pointed out that the central part in the
horse became of a rich brown with bichromate of potash from the
reduction of the brown oxide of chromium. MacMunn's[210] observations
on the spectroscopic appearance of the pigment of the suprarenals point
to these glands as in some way concerned with the transformation of the
effete coloring matters of the body.
[Footnote 210: Paper read before the Physiological Society of London,
_Journal of Am. Med. Assoc._, 1885, March 21.]
An immense number of experiments have been made with a view of
ascertaining the function of these bodies, and extirpations, crushings,
etc. have been made--among others by Brown-Séquard,[211]
Gratiolet,[212] Phillipeaux,[213] Harley,[214] Nothnagel,[215] the
general result of which appears to be that they are not {945} important
organs and that they have no influence in the production of pigment.
Recently, Tizzoni[216] has stated--as Brown-Séquard had done--that
pigmentation followed extirpation in the rabbit; but there is a large
amount of negative evidence by most careful observers; as, for example,
Nothnagel, who found no changes in 153 animals in which he had
destroyed the suprarenals.
[Footnote 211: _Archives générale_, 1858.]
[Footnote 212: _Ibid._, 1856, ii.]
[Footnote 213: _Ibid._, 1858.]
[Footnote 214: _Med.-Chir. Review_, vol. xxi.]
[Footnote 215: _Zeitsch. f. klin. Med._, Bd. i., 1879.]
[Footnote 216: _Lancet_, 1884, ii.]
Various attempts have been made to explain the phenomena of the
disease, to two or three of which we shall refer:
1st. That the disease is directly dependent upon destruction of the
capsules and consequent abnegation of their functions. This was the
view of Addison, and it appeared to be supported by the experiments of
Brown-Séquard (performed shortly after the publication of Addison's
memoir), who held that after extirpation of the glands pigment
accumulated in the blood; which he explained on the supposition that
their function was the disposal of a material in the blood readily
converted into pigment. Subsequent experiments appear to have
demonstrated conclusively that, like the spleen, the adrenals are not
necessary to life, and that no important changes occur after their
removal, or even after the induction of caseous and fibroid induration
(Nothnagel). A much stronger argument against this view is found in the
fact that cases have been reported in which the capsules presented
little or no change.[217] Taylor[218] held that the pigmentation was
induced by destruction of the cortical part of the organs, and the
general nervous phenomena by involvement of the central part, which has
such close relation with the nerve-structures. This view has again been
advanced by B. Fenwick.[219]
[Footnote 217: Care must be exercised in the examination of apparently
normal capsules. There may be extensive small-celled infiltration and
destruction of the gland-elements without either reduction or increase
in size.]
[Footnote 218: _Loc. cit._]
[Footnote 219: _Path. Soc. Trans._, xxxiii., 1882.]
2d. That it is an affection of the abdominal sympathetic system,
induced, most commonly, by capsular disease, but also by other chronic
affections which implicate the solar plexus and its ganglia. Addison
hinted at this explanation, and had the ganglia examined in one of his
cases, but Schmidt of Amsterdam (1859) was the first to point out the
possible connection and to record a case. Many corroborative
observations have since been made, and this view has the support of the
leading authorities. The changes which have been met with are very
varied--fibroid thickening of the sheaths with atrophy of the
nerve-tubes, fatty degeneration and wasting, excessive pigmentation of
the cells, myxomatous degeneration of the stroma of the semilunar
ganglia, and in a few instances there have been changes in the spinal
cord. The chronic caseo-fibrous process in the capsules seems specially
prone to involve contiguous tissues, and the close proximity of the
semilunar ganglia renders them more liable to be attacked by the
sclerotic process than in other affections in the vicinity, such as
aneurism or tumors. According to this view, the symptoms of Addison's
disease are to be regarded as the expression of a severe nutrition
disturbance caused by a morbid state of the sympathetic ganglia, or, as
Semmola puts it, the entire affection, beginning with disturbance of
digestion and running its course with asthenia, low temperature, and
marked debility in the oxidation and nutritive processes, is a
pathological demonstration of the physiological functions of the
sympathetic ganglia. The pigmentation may have its origin in changes in
the trophic nerves, and the pronounced debility is the outcome of the
disturbed chemical activity in the tissue-elements. It is, in short, a
disease of the nervous system of organic life. Greenhow, who is a
strong advocate for this view, also thinks that the circulatory,
respiratory, and digestive symptoms may in part be due to implication
of the pneumogastrics, the peripheral branches of which are frequently
{946} involved in the thickened tissues about the capsules. The feeble
action of the heart, small pulse, the nausea, vomiting, and the gasping
respiration, may arise reflexly from irritation of these branches.
There are about thirty cases on record in which changes have been found
in the sympathetic system. Riesel[220] compares the symptoms of
Addison's disease with those which follow extirpation of the semilunar
ganglia in animals. There is a paralysis of the vaso-motor nerves of
the abdominal viscera, induced either by degeneration of the ganglia or
reflexly by irritation, and consequently the blood accumulates in these
parts, and there is a corresponding spanæmia of other organs, which
explains the weak circulation, anæmia and the heart symptoms, fainting,
and loss of energy. Recently this theory has been advocated by F. P.
Henry.[221]
[Footnote 220: _Deutsches Archiv f. klin. Med._, Bd. vii.]
[Footnote 221: _Philada. Med. Times_, 1885, No. 452.]
The occasional occurrence of pigmentation of the skin in abdominal
tuberculosis, retro-peritoneal tumors, cancer of pancreas, and in
uterine irritation lends support to this view.
The weak points of this view are--the doubtful nature of the changes in
the ganglia and the nerves in many cases. Mere increase of the normal
pigment, slight fatty degeneration or swelling, so often recorded,
should not be regarded as important, for they occur under a variety of
conditions. Of positive swelling and redness of the ganglia, fibroid
atrophy with destruction of nerve-cells and degeneration of the
nerve-fibres, there can be no doubt, but about less marked alterations
opinions will differ whether they are truly morbid or not. The fact
that in certain well-observed cases the ganglia and nerves were found
normal is hard to reconcile with a theory that the disease is an
affection of the abdominal sympathetic. Burger states[222] that there
are nine cases in which changes could not be found, and there are the
recent cases of Huber,[223] Hebb,[224] Foa,[225] and Hadden.[226]
[Footnote 222: _Loc. cit._]
[Footnote 223: _Virchow's Archiv_, Bd. lxxxviii.]
[Footnote 224: _Lancet_, 1883.]
[Footnote 225: _Virchow-Hirsch_, 1879.]
[Footnote 226: _Brit. Med. Journ._, 1885, i.]
Hale White's recent observations,[227] as well as those of
Saundby,[228] on the histological changes in the sympathetic clearly
show that many of the changes which have been described in cases of
Addison's disease are common in other affections, and have probably no
direct association with the characteristic symptoms of the malady.
[Footnote 227: _Ibid._]
[Footnote 228: _Ibid._, 1883, i.]
Then, again, the absence of the characteristic symptoms of Addison's
disease in so many cases in which the matting and implication of the
nerves seems quite as great as in capsular disease. In aneurism of the
abdominal aorta in the neighborhood of the coeliac axis the tissues in
the vicinity may be indurated and cicatricial, the semilunar ganglia
compressed, and the nerve-fibres atrophied, without bronzing and
without the constitutional symptoms. Cases, too, of retro-peritoneal
cancer rarely induce pigmentation, though in some instances--as in a
case of Paget's (Geo.),[229] in which there was extensive lymphadenosis
with involvement of the abdominal sympathetic--the bronzing may be
intense. Induration about the pancreas and stomach in cancer has
induced the same change, and recently Jürgens has recorded a case of
aneurism[230] of the abdominal aorta with symptoms of Addison's disease
and degeneration of the sympathetic nerves.
[Footnote 229: _Lancet_, 1879, i.]
[Footnote 230: _Berliner klin. Woch._, March, 1885.]
3d. That the essence of the disease is to be sought in some injurious
agent--a poison introduced from without or possibly arising within the
body as a result of faulty metabolism. There is not the slightest
evidence for the existence of any such specific poison, which Averbeck,
in his monograph, brings forward to account for the anæmia and the
local disease in the capsules.
A more plausible theory, one closely related to the first one
mentioned, is {947} that the blood is gradually poisoned by the
retention of some material the destruction or alteration of which it is
the function of the adrenals to effect. The disease is in this view
analogous to chronic uræmia.
The relation of affections of the thyroid gland to myxoedema and
cretinism, and the experimental production of these conditions by the
removal of the thyroid, have widened our view of the importance of the
ductless glands. It is interesting to note the analogy between
myxoedema and Addison's disease. In both there are distinct
histological changes in the tissues--in one an increase in the mucin,
in the other an increase in the pigment--and in both marked nervous
phenomena: mental dulness, a progressive dementia in myxoedema, a
profound asthenia in Addison's disease. We regarded the thyroid as
unimportant to life until the experience of surgeons and extirpation in
monkeys by Horsley demonstrated that abolition of its function was
followed by a serious train of symptoms; and perhaps the experimental
removal of the suprarenals in monkeys--so much more closely allied to
man than the animals hitherto experimented upon--may demonstrate that
these little bodies are also not without their influence upon health.
Although the view of disturbed innervation consequent upon involvement
of the abdominal sympathetic meets the case, theoretically, better than
any other, and is at present widely held, yet there are signs of a
return to the old view of Addison, which has been so consistently
advocated by Wilks.[231] The data are not yet forthcoming for a final
decision of the question, but it is possible that future investigations
may establish the truth of Addison's view, that suspension of the
function of the glands is the essential factor in the causation of the
disease. That the sympathetic may be normal in genuine cases, and again
that all the symptoms of the disease may occur without affection of the
adrenals, are, however, facts difficult to harmonize with either
theory.
[Footnote 231: Discussions at Pathological Society of London, session
1884-85.]
DIAGNOSIS.--It is of the first importance to remember that an increase
in the pigment of the skin is by no means confined to Addison's
disease, and, on the other hand, that the constitutional symptoms may
be present without a trace of bronzing; and in their absence a positive
diagnosis cannot be made. The conditions which give rise to a deepening
of the color of the skin are--(1) Abdominal growths, tubercle, cancer,
lymphoma. The patches of pigmentation in such cases are usually
scattered, most often about the face and forehead. Occasionally the
pigmentation may be deep and extensive, as in one case I saw of
abdominal tuberculosis believed to be Addison's disease. Guéneau de
Mussey[232] has called special attention to the frequency of this
complication in chronic tuberculous peritonitis. Pigmentation may also
be on the mucous surfaces in these cases. (2) Pregnancy, in which the
discoloration is usually limited to the face, the so-called masque des
femmes enceinte, and which, it is to be remembered, does not always
disappear with the pregnancy. Chronic uterine disease, especially
fibro-myoma, is a very common cause of patchy melasma. (3) Hepatic
disease, which may induce definite pigmentation as well as the
yellow-brown color of jaundice. Overworked persons of constipated habit
and sluggish livers may present a patchy staining about the face and
forehead. (4) The vagabond's discoloration, caused by the irritation of
lice and dirt, may reach a high grade, and has been mistaken in several
instances for the pigmentation of Addison's disease. (5) In rare
instances there may be deep discoloration of the skin in connection
with melanotic cancer--so deep and general that it has been confounded
with melasma suprarenale. Wagner,[233] Wickham Legg,[234] and
Falls[235] have {948} described remarkable cases of the kind. The
occurrence of melano-sarcoma of the choroid or skin should render the
diagnosis in these cases easy enough, but if deep seated a difficulty
might readily occur.
[Footnote 232: _Étude sur la Pigmentation de la Face dans la
Tuberculose abdominaire_, Paris, 1879.]
[Footnote 233: _Archiv der Heilkunde_, Bd. v.]
[Footnote 234: _Path. Soc. Trans._, London, vol. xxxv., 1884.]
[Footnote 235: _Philada. Med. Times_, 1883.]
It must be borne in mind that there are cases without bronzing, in
which the profound asthenia and gastric symptoms are the prominent
features, and, as mentioned above, these cases seem to run a very acute
course. Indeed, they have been mistaken for typhus.
TREATMENT.--As cure is out of the question, the treatment is
symptomatic and directed to the avoidance of certain perils associated
with the disease. We have no means of checking the progress of the
capsular affection. Pepper advises counter-irritation, and in the early
stages the cautery may be used. Rest of mind and body must be enjoined,
and the dangers of exertion and exhaustion set before the patient. Even
in the early stage fatal syncope may occur.[236] The sense of weakness
and tire at times becomes greatly aggravated, and may deepen into
attacks of the most profound asthenia, during which the patient should
be strictly confined to bed. It is in these paroxysms that special
dangers occur. General tonic measures must be employed for the support
of the strength. When there is anæmia, iron may be given, and Greenhow
speaks of the good effects of the citrate or perchloride given with
glycerin. Arsenic, strychnia, phosphorus, have been found useful in
individual cases. Galvanism has been used, but without much benefit.
The paroxysms of profound asthenia call for stimulants--wine, brandy,
and ammonia. The gastro-intestinal symptoms require the most careful
treatment. Bismuth, hydrocyanic acid, creasote, soda-water, ice, and
champagne will be found useful in allaying the vomiting and
irritability of stomach, but in some cases these symptoms prove most
intractable. Purgative medicines must be given with very great caution
on account of the liability to profuse diarrhoea and serious collapse.
The constipation, which may be obstinate, is best treated by mild
enemata. The greatest care should be exercised in the diet, which
should be plain and easily digested. Though the vomiting is not
directly dependent upon the state of the stomach, yet indigestible food
and irregularities in eating may induce the gastric attacks. When there
is much irritability of the stomach the patients seem to do best on a
strict milk diet.
[Footnote 236: Quite recently an active professional man consulted me
for bronzing of the face and hands, and he had had one fainting spell.
With the concurrence of Pepper he was advised to give up business for a
year and live quietly abroad. His general condition was so good and the
pigmentation so limited that there seemed just a possibility that it
was not Addison's disease. He went home and prepared to follow out our
advice, but a second sudden attack of syncope proved fatal.]
{949} OTHER DISEASES OF SUPRARENAL BODIES.
ANOMALIES.--There may be four glands, two on each side. More commonly,
there are small supplementary organs--glandulæ succenturiatæ--situated
in the neighborhood, seldom reaching the size of a pea. Grawitz has
recently shown that many of the small adenomas of the kidney are in
reality minute portions of suprarenal tissue which have become included
in the course of the development of these organs. Fusion of the two
glands has been observed (Klebs). They may be absent.[237]
[Footnote 237: Defect of adrenals is very rare. There are not a few
observations in which it is stated that the right gland was absent.
Now, if the examination is not made with care, and particularly if the
liver is removed first, the right gland may be taken away with it
closely lodged in the fossa suprarenalis, and so escape observation.
Time and again have I directed the attention of the student making the
autopsy to the right adrenal on the under surface of the liver.]
It is curious how liable the suprarenals are to anomalies in position
or form in connection with defective development of the brain and cord.
In anencephalous monsters the glands may be absent or very small.[238]
In one instance I found them normal in size, but they were below, not
above, the kidneys.
[Footnote 238: Lomer, _Virchow's Archiv_, Bd. xc.; Weigert, _ibid._,
Bd. c.]
ATROPHY.--Extreme wasting may be met with as an accidental
circumstance: there may be only a trace of gland-tissue left. Several
such specimens have been found in association with Addison's disease.
There may be an interstitial growth of fibrous tissue, cirrhosis, with
shrinking of the organ. More often the glands are larger and harder in
connection with the cyanotic induration of heart disease. It is stated
by some writers that the adrenals of the negro are larger than those of
the European races--a statement which I have not been able to confirm
in several observations.
APOPLEXY.--In the new-born and young children congestion is not
infrequent. Hemorrhage into the central medullary substance is by no
means uncommon, either on one side or bilateral. The amount may be
considerable, and the glands greatly distended, forming large tumors.
INFLAMMATION.--Suppuration is rare except in connection with the
caseo-fibrous change already described as specially associated with
Addison's disease. Abscesses in the vicinity, as from caries of the
spine, may involve one or both capsules.
DEGENERATIONS.--Fatty changes are very common, particularly in the
cortical layer, which then has a light-yellow color, instead of the
normal dark gray-red. Yellow oil-drops appear to be normal constituents
of the cells of the cortex.
Amyloid degeneration may occur, but only in connection with similar
changes in other organs. The glands are enlarged, very firm, and the
medullary part translucent. The iodine reaction shows it to be limited
to the fibrous septa and blood-vessels.
The brown pigment of the intermediate zone, zona reticularis, may be
greatly increased. Normally in man, the amount is very variable, and
the deeper color may be due to congestion of the blood-vessels.
CYSTS with serous or hemorrhagic contents are occasionally found,
chiefly in the cortical part. They may be multiple. Hydatid cysts have
been met with.
TUMORS are not very uncommon. Cancer may attack them primarily, but
more often they are involved in secondary growths after carcinoma of
stomach or other organs. They are not infrequently affected in cancer
of the kidneys {950} by direct extension of the growth. Sarcomas are
also not uncommon, and may form large masses the size of the foetal
head. They may be melanotic.
These varied pathological conditions are not usually associated with
any special or distinctive symptoms, and in the great majority of cases
have been unsuspected during life. The organs may be totally destroyed
without inducing any of the phenomena of Addison's disease. In a few
cases, however, bronzing of the skin has been met with.
{951}
DISEASES OF THE SPLEEN.
BY I. E. ATKINSON, M.D.