Chapter LXV: Part 65

The pulse is frequent and small, the heart's action weak--sounds clear; a venous murmur may sometimes be heard. In some cases there appears to be a special enfeeblement of the heart and a liability to fainting attacks, and without any warning a fatal syncope may occur. Cold feet and hands result from the weak circulation, and may be a most annoying symptom.

Symptoms in connection with the respiratory system are not common. There may be dyspnoea, and the complication of phthisis may give rise to all the features of that disease. There may, however, be extensive lung trouble with but few symptoms. The temperature is rarely elevated, more often it is subnormal.

Gastric disturbances are very common--anorexia, nausea, vomiting--particularly toward the close, but they may be early and prominent features, persisting in spite of all remedies and proving the most formidable symptoms of the malady. They appear to be of nervous origin, and not referable to changes in the organ itself. It is doubtful if the case reported by Gilliam,[189] in which there was degeneration of the gastric mucosa, was Addison's disease. The state of the bowels is variable; constipation is more frequent than the normal condition. Diarrhoea is common, and may come on suddenly without obvious cause, and is a not infrequent cause of death.

[Footnote 189: _Phil. Med. and Surg. Reporter_, xxiv.]

The urine is usually pale, free from albumen, not often increased in amount. It is interesting to note, in connection with the involvement of the abdominal sympathetic, that in a few cases there has been polyuria. The nitrogenous elements may be greatly reduced, the urea to 13-20 grammes daily, and the amount of indican may be increased as much as 64-75 milligrammes in 1000 c.c. (Samuel). In one case Thudichum found the urinary pigments greatly reduced in amount, the uromelanin not amounting to more than one-twelfth the normal quantity. A recent observation of Nothnagel is of interest.[190] In a patient aged twenty, who had the typical symptoms of the disease for two years, death took place by coma and the condition of acetonuria was determined.

[Footnote 190: _Zeitschrift für klin. Med._, Bd. ix.]

The symptoms connected with the nervous system are the most prominent in the disease, and are more constant than the anæmia or the bronzing. The most marked is a depression and enfeeblement of the nervous forces, a profound asthenia out of all proportion to the general condition. The patients complain of a lack of energy, mental and bodily; the least exertion is an effort, and there is a feeling of tire and weariness with which the facial expression is quite in keeping. The fainting fits, giddiness, noises in the ears, may also be due to faulty innervation, as they occur in cases in which the anæmia is by no means advanced. Headache, lumbar and abdominal pains are frequent, and in a considerable proportion of cases there is tenderness on pressure in the lumbar region. With the advance of the disease the prostration becomes more marked, the patient remains in the recumbent posture, the voice gets weak and small, the intelligence dulled, and occasionally there is delirium. Head symptoms may suddenly supervene, and death by coma or convulsions cut short the progress even early in the disease (Pye-Smith). In Jaccoud's series convulsions were noted in 19 cases.

The disease may be said to be invariably fatal, but the course presents many variations. The majority of cases die within eighteen months of the first onset of the symptoms. B. Fenwick, in an analysis of 30 recent cases,[191] calls attention to the fact that when bronzing does not occur the course is more rapid. Thus the average duration of the non-bronzed cases was only 4.8 months, while for bronzed ones it was 23.6 months. There are acute cases {942} in which, with great weakness, vomiting, and diarrhoea, the fatal end may occur in a few weeks. Some of these rapid cases resemble typhus. Syncopal attacks, coma, or convulsions cut short not a few cases. In a few instances it is much prolonged--six years (Niemeyer) or even ten years (Greenhow). Whether recovery ever takes place is doubtful. Finney[192] has reported an apparently genuine case which got well. Some French observers (Potain) think that recovery takes place more often than is supposed. Sir Wm. Gull mentioned a case of recovery.[193] Periods of improvement lasting many months may occur.

[Footnote 191: _Path. Soc. Trans._, vol. xxxiii., London.]

[Footnote 192: _Dublin Med. Journ._, April, 1882.]

[Footnote 193: _Int. Med. Congress_ (London) _Transactions_, vol. ii.]

MORBID ANATOMY.--The panniculus adiposus and subperitoneal fat may be in normal quantity. There is rarely great emaciation, nor are the organs blanched and bloodless. The most constant lesion is in the suprarenal organs, which present a caseo-fibrous change, more rarely simple atrophy or other alterations. So frequent is the caseo-fibrous condition that some writers (Wilks) hold that it is the specific lesion of the disease. The organs are enlarged--may weigh several ounces each. The capsules are thickened, and may present caseous or even calcareous masses. The normal shape of the gland is lost, and it forms an irregular nodular mass closely adherent to contiguous parts--liver, kidney, and cava on the right side, kidney, spleen, and often pancreas, on the left. There is usually a good deal of fibrous thickening and matting in the vicinity, and the adhesions to adjacent structures may be very strong. The peritoneum often shows patches of fibroid induration. On section the diseased organ cuts with great resistance, and to the touch has an almost cartilaginous hardness. The exposed surface shows caseous masses of a yellow or grayish-white color, varying in size from a pea to a walnut, imbedded in a grayish semi-translucent fibrous tissue, pale when first cut, becoming reddish on exposure. These caseous masses may undergo softening or calcification, and pockets of pus are not uncommon. Definite small miliary granulations are not often seen, though nodular grayish-yellow bodies the size of small peas may occur. The strands of fibrous tissue which separate and enclose the caseous masses have often a very peculiar translucent, infiltrated appearance. When the cheesy lumps are small, the amount of this tissue is considerable and gives a remarkable character to the section. Wilks has described a case in which this tissue made up the entire mass. The substance of the gland is usually destroyed. The vessels and nerves can be traced to the organs where they become imbedded in the fibrous tissue.

Histologically, the soft translucent tissue consists chiefly of spindle-shaped fibre-cells, and in firmer older parts of ordinary fibrous stroma. In the immediate neighborhood of the cheesy masses there are round corpuscles--about the size of or a little larger than white blood-cells--imbedded in a fine reticulum of fibres. Giant-cells are sometimes found, but they have not been common elements in the specimens which I have examined. The caseous substance consists of granular débris in which the remains of cells and fibres can be seen. In coarse and microscopical features the lesion resembles closely local tubercular affections. The extension is by a small-celled growth, which gradually invades the adjacent parts, extending peripherally as the central portions caseate. Distinct miliary granulations are not often met with. The relation of this local growth to tuberculosis is a very interesting question. It is usually regarded as a scrofulous or tuberculous process, to which in its general features it quite conforms. I have been interested in ascertaining whether the bacillus tuberculosis existed or not in the local lesion. In Cohnheim's laboratory Karl Hüber kindly gave me an opportunity of examining the adrenals in two cases, in only one of which were the {943} bacilli evident. Since then I have re-examined the fibro-caseous tissue in Ross's case,[194] which was a most typical one, the suprarenals alone involved, and in the recent case reported by Pepper,[195] and in neither have I been able to demonstrate bacilli. Future examinations must decide whether the local affection is inflammatory or whether it belongs to the infective granulomata.

[Footnote 194: _Can. Med. Assoc. Trans._, vol. i., 1877.]

[Footnote 195: _Phila. Med. Times_, 1885.]

That other alterations may occur in cases of Addison's disease appears well established, though some still regard the caseo-fibrous change essential and specific. Atrophy of one or both glands has been frequently seen. Jaccoud gives 7 cases in his tables. Good recent cases have been described by W. B. Hadden,[196] Hebb,[197] and Goodhart.[198] The atrophy is due to a chronic interstitial process similar to cirrhosis of the liver. Hadden[199] states that the lesion is identical with that in the thyroid gland in myxoedema.

[Footnote 196: _British Medical Journal_, 1885.]

[Footnote 197: _Lancet_, 1883, i.]

[Footnote 198: _Path. Soc. Trans._, 1882.]

[Footnote 199: _Loc. cit._]

Absence of one or both the capsules has been noted by Legg, Spender, Borland[200] and Hubbard.[201]

[Footnote 200: _Boston Med. and Surg. Journal_, 1867.]

[Footnote 201: _Proceedings of Conn. Med. Society_, 1868-71.]

Cancer of the adrenals, by no means uncommon as a secondary process, rarely produces any special symptoms; but there are cases which are difficult to exclude from the category of Addison's disease. Jaccoud gives several, and in the case of Edes, often quoted,[202] the asthenia and discoloration may have been due to the capsular affection, but there was also extensive peritoneal cancer.

[Footnote 202: _Boston Med. and Surg. Journal_, 1878.]

By far the most constant morbid change after that in the adrenals is a more or less widely distributed tuberculosis, particularly of the lungs. A very considerable proportion of the cases are complicated with chronic phthisis. Regarding the disease of the suprarenals as primary, the general tuberculous affection may be secondary; and it is just in these organs, as Weigert has shown, that the veins are apt to be perforated by tubercles and systemic infection induced. The retro-peritoneal and mesenteric lymph-glands may also be tuberculous. Ulcers of the ileum may occur, and swelling of Peyer's glands and the solitary elements in the bowels is very common. In Ross's case there were numerous lymphoid infiltrations of the mucosa of the stomach, chiefly about the pylorus and cardia. The changes in the skin are confined to an increase of the pigment in the cells of the rete mucosum, most pronounced in the deeper layers and in the deeper parts in the connective-tissue cells of the papillæ and subcutaneous tissues. The condition is not to be distinguished from a deeply-pigmented scrotum or from the dark skin of the negro. The pigment resembles the ordinary coloring matter of the skin, but is possibly different from it in containing no iron.[203] Nothnagel has made[204] an exceedingly interesting study of the pigmentation in Addison's disease, and concludes that it is identical in distribution with that in the skin of the dark races; that it does not originate in the cells of the rete mucosum, but is elaborated in deeper cells, about the vessels of the cornium, and transported by them to the more superficial layers--a mode which recent observations seem to show is the normal one; and, lastly, that it is a process induced through the nervous system in some way as yet unknown.

[Footnote 203: Arnold, _Virchow's Archiv_, xxxv.]

[Footnote 204: _Loc. cit._, Bd. ix.]

The spleen has been found enlarged. The thymus gland may also persist 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.

Morbid processes affecting the spleen have been and remain involved in great obscurity. Older writers, who were accustomed to reach their conclusions in great measure through the observation of symptoms alone, were obliged in the absence of anything like correct knowledge of anatomy, physiology, and pathology to supply from the imagination most of their theories of disease. Untrammelled by the bonds of accurate investigation and ignorant of pathological anatomy, they found no difficulty in ascribing to various parts and organs peculiar groups of symptoms, both physical and moral; and for a number of these the spleen was held responsible. We now know that many of the symptoms thus supposed to indicate splenic disease depend upon alterations in other parts of the body, and may be observed in persons possessing perfectly healthy spleens. But while we have learned that symptoms formerly supposed to depend upon splenic disorder may, in reality, have nothing to do with this organ, we still remain ignorant of many of the real symptoms of splenic disease, as well as of many of the morbid conditions that induce them. Such knowledge as we have, however, is based upon comparisons of symptomatology with dead-house revelations and the experience of the laboratory, and, while as yet imperfect, cannot fail to increase under modern methods of research.

In order to begin the study of diseases of the spleen in an intelligent manner it is manifestly necessary to have some settled ideas regarding its anatomy and physiology. No apology is needed, therefore, for the brief anatomical and physiological descriptions that follow.

The spleen is the largest of the ductless glands, and is situated in the left hypochondriac region. It is of a dark slate or bluish-gray color, and often of wrinkled appearance. It is of soft, friable structure. It rests between the stomach, diaphragm, and left kidney, and in form resembles a flattened oval. It extends from the level of the eleventh rib, beginning one or two centimeters distant from the vertebral column, downward and forward to a position about four centimeters from the point of the eleventh rib (Lushka). It is separated from the ninth, tenth, and eleventh ribs by the diaphragm. It presents two surfaces--one external and convex, facing the diaphragm; the other internal and concave, applied to the cardiac end of the stomach. The hilum divides the internal portion into two parts by a deep fissure, which marks the line of attachment of the gastro-splenic omentum. The larger and anterior part is bound to the fundus of the stomach by delicate areolar tissue, and the posterior and smaller portion to the left pillar of the diaphragm and the left suprarenal capsule. The upper portion is connected with the diaphragm by peritoneum forming a suspensory ligament. The bottom of the hilum is perforated by a number of openings for the transmission of blood-vessels, nerves, and lymphatics. The anterior border of the organ is notched and thinner than the posterior border. The pointed lower end touches the splenic flexure of the transverse colon and rests upon the costo-colic ligament. {952} The spleen varies in size and weight within wide limits. Its average weight in adults is 250 grams, its length from 11 to 13 centimeters, and its thickness from 4 to 6 centimeters (Orth). Its volume is from 150 to 180 cubic centimeters. According to Gray, the proportionate weight of this organ to that of the whole body varies from 1:320 to 1:400, gradually diminishing until old age, when the proportion becomes as 1:700.

In the vicinity of the spleen are often found a number of small bodies similar to it in structure. These are known as accessory spleens, and are usually situated in the gastro-splenic or in the greater omentum. The attachments of the viscus are not very close, and much variation in size and position is possible.

Except at the hilum the peritoneum forms everywhere one of the coverings of the spleen. Its peculiar sheath or capsule is composed of fibro-elastic tissue of a whitish color, prolongations of which extend into the substance of the organ and form the trabeculæ that constitute its supporting framework and sheaths for blood-vessels and nerves. A close meshwork is thus created in which are contained the splenic vessels and pulp. This fibrous coat and these trabeculæ contain involuntary muscular fibres. These, with the elastic fibres, provide for the changes in size that the organ undergoes. When incised, the normal spleen presents a reddish-brown color, and its substance may be readily broken down with the finger into a pulp. This pulp consists of a mass of branched intercommunicating connective-tissue corpuscles of different sizes, within the substance of which remains of red blood-corpuscles may often be detected. The interstices of these cells are filled with blood. The very large splenic artery enters the spleen by numerous branches, ramifying within the trabecular sheaths and terminating in pencils of minute size.

The external coats of the smaller arteries are converted into lymphoid tissue, which, suddenly expanding here and there, forms the bodies known as the Malpighian follicles, which are supplied with capillary vessels, and which may often be distinguished by the naked eye as points of whitish color, sometimes attaining the size of pinheads. These small arteries end in capillaries, which, according to Müller, gradually lose their cylindrical character and emerge into a system of connective-tissue corpuscles, inosculating with the corpuscles of the splenic pulp in such a manner that the blood passes into the pulp-tissue freely, and is gradually brought to the veins by the transition of this tissue into that of the blood-vascular system. The splenic lymphatics originate in the arterial sheaths and in the trabeculæ. In the former case they accompany the blood-vessels; in the latter, they communicate with a superficial network in the corpuscle. All join at the hilum and enter the neighboring lymphatic glands. The splenic nerves are from the right and left semi-lunar ganglions and right pneumogastric nerve. They accompany the branches of the splenic artery, and have been traced deeply into the tissue of the organ.

It is perfectly established that under normal conditions the volume of the spleen may vary considerably, and especially during the act of digestion, and that this does not occur through simple engorgement of the vessels. The very important experiments of Roy show that, in cats and dogs at least, the splenic circulation does not depend upon the ordinary blood-pressure, but is carried on "chiefly, if not exclusively, by a rhythmic contraction of the muscles contained in the capsule and trabeculæ of the organ."[1] This rhythmic contraction and expansion Roy observed to occur with great regularity at the rate of about sixty contractions an hour, with extremes of rapidity of rhythm of forty-six seconds for the most rapid and two minutes three seconds for the slowest. He also observed that stimulation of the central end {953} of a cut sensory nerve, or of the medulla oblongata, or of the peripheral ends of both splanchnics and both vagi, causes a rapid contraction of the spleen. Unsatisfactory as is our knowledge of splenic physiology and of its exact relations to the maintenance of life (for that the spleen is not the seat of a peculiar and exclusive function has been demonstrated by the survival of individuals after extirpation of the organ), at present certain theories of its nature find pretty general acceptance. Thus, it is considered that in the lymphoid tissue of the blood-vessels and Malpighian corpuscles leucocytes are produced--that the cells of the splenic pulp appear to take red blood-corpuscles into their interior, where their disintegration takes place. There are not sufficient grounds for believing that in the spleen red blood-corpuscles are formed. Recent observations of Tizzoni, Crédé, and Zesas have led them to the conclusion that they are made in the spleen; but Bizzozero and others deny that this occurs except after serious hemorrhage.

[Footnote 1: _Journal of Physiology_, vol. iii., 3 and 4, p. 203.]

It is impossible to detect by palpation any part of a healthy spleen. Its area may be approximately defined by percussion alone, though even by this method it is not always easy to determine its position and size. Loomis advises that the patient be placed upon his right side in order to facilitate the examination. The anterior border of the spleen is then "readily determined by the tympanitic resonance of the stomach and intestines. Inferiorly, where the organ comes into contact with the kidney, it is difficult, and often impossible, to determine its boundary. Its superior border corresponds to the line which marks the change from flatness to pulmonary resonance." The vagueness of these directions is necessitated by the difficulties of the subject, the splenic outlines being liable to frequent variations. Schuster and Mosler give excellent reasons for prosecuting the investigation with the patient in the right semi-supine position.

Acute Congestion of the Spleen.

Except within the physiological limits already referred to, acute congestion of the spleen never occurs as a primary process. Under pathological conditions it is known to take place under a great variety of circumstances, principally, however, in connection with those states of the system in which disease is supposed to depend upon some specific principle or germ. To a minor extent it is probable that splenic congestion accompanies nearly all febrile conditions, and from the border-lands of health to that highest and most intense degree of hyperæmia by which the organ acquires a volume and prominence that have caused it to be designated as acute splenic tumor, all gradations may be observed, though in many instances these may be so slight as to be incapable of recognition clinically, and are only brought to our knowledge through necroscopic examination. The congestion becomes most marked in the course of the acute specific fevers. In typhus and typhoid fevers, in small-pox, scarlatina, diphtheria, in epidemic cerebro-spinal meningitis, in acute tuberculosis, in erysipelas, puerperal fever, in conditions of blood-poisoning and in malarial fevers, more especially those of more severe type, it reaches its highest development. According to Friedreich, a form of pneumonia (differing from ordinary croupous pneumonia in its serpiginous course), acute coryza, and acute pharyngitis and tonsillitis are accompanied by enlargement of the spleen in consequence of the septic nature of these disorders. During the fever of secondary syphilis a splenic enlargement purely hyperæmic in character may sometimes be detected. Similar conditions are occasionally observed in a number of other affections. This tendency of the spleen to active congestion is to be accounted for by its peculiar anatomical structure, whereby unusual facilities for hyperæmia are {954} afforded, more especially in the infective fevers, in the course of which the organic germs which are supposed to constitute their essential principles collect in the pulp, and by their accumulation and multiplication serve to excite a more or less intense determination of blood to the part, the organisms themselves being taken up by the leucocytes and connective-tissue corpuscles composing the pulp. We can thus account for the multitudes of these organisms to be found in the splenic pulp after various infective disorders, as in relapsing fever as observed by Ponfick, in pyæmia by Birch-Hirschfeld, and in splenic fever of animals by various observers. The less intense degrees of congestion occurring during the various specific fevers and in many simple febrile disturbances are usually so slight as not to attract attention. When the hyperæmia has been unduly prolonged, as more especially occurs as a result of chronic malarial poisoning, leucocythæmia, pseudo-leucocythæmia, or Hodgkin's disease, there is a well-pronounced tendency toward permanent structural changes and the development of hypertrophy.

SYMPTOMATOLOGY.--Milder degrees of congestion do not, generally, reveal their existence by symptoms, and those of more pronounced character give for the most part signs that are vague and nearly obscured by the more prominent features of the pathological processes that occasion or accompany the splenic changes. It may happen that acute splenic tumor of considerable size may be quite painless. It has been objected, indeed, that when pain accompanies splenic enlargements it is not attributable to any sensibility of the spleen itself, but to the participation of the investing peritoneum in the morbid action or to the dragging of the enlarged organ upon the parts with which it is connected (Mosler). Patients, however, will often complain of a dull, aching pain and a sensation of weight in the left hypochondrium. Occasionally, this pain may be severe and lancinating or may extend to the shoulder. Headache and various digestive disorders--anorexia, vomiting, flatulence, and diarrhoea--may prove distressing accompaniments. Other symptoms, such as melæna, voracious appetite, vertigo, extreme anæmia with its various concomitants, etc., belong rather to conditions of protracted congestion where new formation and true hypertrophy have been developed.

It is evident that it will often be extremely difficult, and sometimes even impossible, to determine the extent to which symptoms are occasioned by the splenic congestion or by the general affection to which it owes its origin. Mosler declares that he is nearly always able to detect during the cold stage of intermittent fever a peculiar murmur over the splenic region and upward and downward in the abdominal region, which he attributes to the contraction of the splenic artery. This murmur he has not been able to perceive in chronic splenic tumors.[2]

[Footnote 2: _Ziemssen's Cyclop._, vol. viii. p. 468.]

The normal splenic area can only be defined by percussion, and congestion to a not insignificant extent may occur without revealing itself by other symptoms than increase of the extent of percussion dulness. When the organ projects beyond the margin of the ribs and can be felt by the fingers of the examiner, it is enlarged, unless the patient is the subject of displaced or of wandering spleen. But whether the enlargement be due to hyperæmia simply or to hypertrophy can only be determined by a consideration of all the concomitant circumstances. Unless under the influence of chronic irritation or as a result of mechanical hyperæmia, congestions of the spleen are commonly of sudden development and of transitory duration. In ordinary inflammations, such as pleurisy, etc., the degree of congestion is so slight as to be unnoticeable; but as an epiphenomenon of the various specific fevers the enlargement occurs rapidly and acquires a prominent interest in many cases. Acute splenic tumor, for example, is almost of constant occurrence during the course of typhoid fever, and, according to Friedreich, its presence may {955} be ascertained some days before the specific symptoms of the disease have declared themselves. A similar early development has been claimed for it in diphtheria and other affections. The congested spleen of typhoid fever and of relapsing fever, however, differs from that of most other acute disorders in returning to its normal dimensions much more slowly; and it is important to remember that until the splenic tumor has disappeared there is reason to believe the danger of relapse still imminent. In most cases the enlargement disappears pari passu with the disorder that occasioned it. In malarial fevers and in septic diseases the splenic tumor may acquire excessive dimensions. Acute splenic tumor, however, never attains the dimensions often encountered in chronic congestion and hypertrophy.

PATHOLOGY AND PATHOLOGICAL ANATOMY.--Simple splenic congestion presents at first no anatomical features differing from purely physiological hyperæmia. There is simply more blood in the dilated vessels and vascular spaces, and consequently in the viscus, than is usual. Very soon, however, there is hyperplasia of the cells of the pulp. Enlargement, tension of the capsule, and diminished consistency of the spleen appear. The color will depend upon the condition of the capsule, being most dark and blue when this is thinnest. In high grades of congestion the parenchyma upon section will be found distended and semi-diffluent, and after acute malarial fever (pernicious remittent fever), the organ may resemble a bag of half-liquid pulp. Softening in varying degree may be found after acute congestion from whatever cause. In the congestions due to some infective processes at least additional factors are introduced, although as yet definite knowledge of their exact pathogenetic influence has not been attained. The observations connecting minute organisms with the origin of these affections have been so elaborate, so carefully and conscientiously reported, extend over such wide and varied fields, that it is difficult to refuse to place reliance in them. It seems that in a number of affections the presence of these microscopic organisms is constant and essential, and that the splenic congestion that accompanies them is a direct result of their presence in the spleen itself. The micro-organisms will be found infesting the cells of the pulp, and, so far as we have definite knowledge, they show peculiar characteristics according to the particular infectious disease to which the patient succumbed. While the conditions in acute splenic tumor are identical with those of inflammation, and in the affections properly designated as septic, should the life of the patient have been sufficiently prolonged, may be found to have led to the formation of embolic centres with hemorrhagic infarctions and abscess, in infectious diseases not septic they do not prove equal to the production of suppuration. Where the action is acute, resolution will speedily follow the subsidence of the febrile process. But in prolonged hyperæmia new formation will be developed, and the enormous collection of leucocytes will give a reddish-gray color to the organ. This change will also be sometimes observed in the spleens of those in whom the infectious diseases have run a more protracted course.

DIAGNOSIS.--Acute splenic tumor, if at all pronounced, may usually be diagnosticated without much difficulty. The development of an enlargement in the splenic region, with pain and tenderness to pressure, during the course of any acute febrile disease will nearly always indicate splenic hyperæmia. It may sometimes be difficult to determine whether the tumor may not have existed prior to the invasion of the present malady. In such cases one must have recourse to the previous history of the patient, or, failing in this, must observe the behavior of the tumor upon the subsidence of the general affection.

PROGNOSIS.--The prognosis of acute congestion and acute splenic tumor will depend rather upon the exciting cause. When of simple origin it is of but insignificant importance. Even in specific fevers the spleen will in most {956} instances return to its normal volume upon the establishment of convalescence. Rupture of the spleen has been known to occur in congestion from severe malarial fever, but this is a most rare accident in the absence of traumatic influences. The congestion may become chronic, and frequently does become so, in cases where the stimulus continues to exert an influence upon the spleen, as is done in chronic malarial poisoning.