The pancreas-The pancreas shows more interlobular fat tissue than is common. In addition there is some increase in the connective tissue of the organ, much pigmentation and certain changes in the Islands of Langerhans. The increase in connective tissue is only moderate in amount, partly cellular, partly fibrous. The Islands of Langerhans are in general made out with some difficulty; at times they are so changed that they cannot be definitely recognized. In the relatively small number that are best preserved the chief change from normal is a swelling of the capillary wall underneath the endothelium. Other islands show a more marked increase in connective tissue. In still other islands there is a change in a part of the cells. Instead of the small immature cell characteristic of these islands the cells are larger with considerable cytoplasm which takes but little stain. These cells show more or less alveolar arrangement, and here and there in the alveolar spaces are hyaline casts which stain red with eosin. There are also found small collections of cells which from the size of the group of cells and from their arrangement and staining properties appear to be Islands of Langerhans which have been entirely changed to the condition just described. The pigment is present both in the cells and the connective tissue in abundance. It is found in the Islands of Langerhans as well as in the other parts of the pancreas. The granules of pigment in the connective tissue are in general coarser than those within the cells. The pigment has the same color as in the liver.

The lymph nodes which lay anterior to the head of the pancreas also show an abundance of brownish yellow pigment, mostly in the sinuses. The stomach shows chronic gastritis with pigmentation. The mucous membrane is uneven due to thinning in numerous small areas. Here the glands are more or less completely replaced by cellular interglandular tissue. Aside from these areas the mucosa in general is fully as thick as normal and shows considerable increase in cells, chiefly lymphoid in shape and size. In many of the cells lining the glands of the mucous membrane there are brownish-yellow granules, particularly in the deeper part of the glands. A few of these granules are also seen in the intertubular cells. The small intestine shows nothing of note.

The kidney shows a slight increase in connective tissue in the cortex with a little arteriosclerosis; also some parenchymatous deger.eration in the tubular epithelium

The suprarenal glands-A few of the cells in the outer part of the cortex show fine pigment granules similar in color to those in the liver and pancreas.

The skin of the forearm-This shows slight brownish pigmentation of the basal cells of the epidermis. It appears as a diffuse slight pigmentation of the cytoplasm caused by a collection of minute granules of pigment in this.

Sections from several of the different organs were stained by the potassium ferrocyanide method for hemosiderin. In the pancreas nearly all the granules gave the reaction for this. In the liver, many of the coarser granules failed to give the reaction, remaining brownish-yellow in color. The same was true in the lymph nodes. The intracellular granules in the spleen and suprarenal glands also gave the reaction for hemosiderin. In the skin the pigment was mostly iron free and looked like the ordinary pigment of the rete malpighii. In the sweat glands a few granules of iron containing pigment were apparent. The fact that some of the pigment granules, particularly in the liver, retained their yellowish color indicated these as containing hemofuscin instead of hemosiderin.

The case here reported presented the triad of symptoms and signs which characterize typical examples of bronzed diabetes. The clinical features of the disease vary somewhat in different cases according to the time of appearance of the manifestations in the skin, liver, and pancreas. Most frequently these patients consult a physician for the symptoms of diabetes, but occasionally gastro-intestinal symptoms present themselves first, indicating disease of the liver, and in still other cases the pigmentation of the skin is the earliest manifestation.

The form of diabetes which is usually associated with this condition is, as a rule, an acute one. In thirty cases in which the history of the diabetes is clear the duration of life from the onset of symptoms to the death of the patient was less than a year in twenty-three. In only one did the patient live more than two years after the onset of the diabetes. So that in a great majority of cases the clinical picture is that of the severer form of diabetes. The symptoms are marked, the emaciation is great, the percentage of sugar is large and but little influenced by diet, and the fatal ending usually results from acid intoxication. In some of the patients, however, the sugar disappears completely from the urine in the last stages of the disease and this disappearance undoubtedly accounts for at least some of the reported cases of hæmochromatosis with marked pancreatic lesion without glycosuria.

The skin pigmentation, which according to Roessle is entirely lacking in about one-sixth of the cases, varies greatly in intensity in different cases. The descriptions of the color vary very

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largely. It is described as blue-black, gray-black, brownish-gray, grayish-brown, dirty gray and yellowish. In some cases it has been compared to the color of Addison's disease. In others the patient has been described as looking like an Arab or a mulatto. Almost all observers state that the pigmentation is most marked in the exposed portions of the body, the backs of the hands, the face, the forearms, and also the legs. In some instances the pigmentation has been especially well-marked in the portions of the body which are normally pigmented. It is usually stated, very emphatically so by some observers, that the pigmentation is always uniform. In the case just reported the pigmentation of the forehead was not uniform, and patchy pigmentation has been described in one or two other recent cases. The mucous membranes nearly always escape pigmentation, though in a few of the reported cases there has been a grayish discoloration of the gums. The relation of the onset of pigmentation to other symptoms, especially to the diabetes, is not stated in the majority of reports. In some cases, as in our own, it is obvious that the onset of pigmentation could not be determined, as neither the patient nor his family had noted it. In the few instances where definite information is obtainable it would seem that pigmentation may be present for years before the diabetes appears, that it often begins about the same time as the diabetes, and that it may not appear until after the diabetes.

The evidences of disease of the liver were present in a number of reported cases years before the appearance of the other manifestations. Some of the patients entered hospitals with gastrointestinal disturbances, the resultant examination showing liver enlargement, a considerable time before they returned with the classical picture of bronzed diabetes. When the signs of diabetes have appeared evidence of the liver involvement is nearly always marked. Of twenty-eight cases in which there is information on this point the liver was enlarged and palpable in twenty-four, and in some of the remaining ones it would have been palpable but for marked ascites. In about one-half of the fully developed cases the spleen is palpable, and in somewhat less than one-third of them ascites is present. It is to be

noted that while the liver is considerably enlarged, jaundice, which is so essential a part of the clinical picture of the true hypertrophic cirrhosis of Hanot, is lacking in this disease, so that so far as the liver picture is concerned it is essentially that of ordinary Laennec's cirrhosis, but with an enlarged liver as the rule rather than the exception.

The occasional occurrence of clinical evidences of blood destruction must be noted. In a few cases, as in the one here reported, purpuric eruptions have been present. In two cases, one reported by Hess and Zurhelle, and one reported by Elmer, hæmoglobinuria was present. The occurrence of purpura and hæmoglobinuria has been cited as evidence in favor of the view that hæmochromatosis is associated with blood destruction. It is necessary to point out that these hæmorrhagic complications have practically all of them occurred in the terminal stages of the disease long after the pigment formation had taken place.

Regarding the etiology of the disease, it is to be noted first of all that it is confined almost exclusively to males. The cases of Berg and Murri, which occurred in women, are both of them doubtful, as Berg's case was the subject of another disease occasionally associated with pigmentation, and Murri's patient recovered. The only undoubted case of hæmochromatosis in a woman is that reported by Maude Abbott, and in this case the patient did not have diabetes.

In 33 patients of whom the age was given 29 occurred between 30 and 60; only two occurred between 20 and 30, and the same number between 60 and 70.

There seems little question that alcohol plays an important part in the etiology of many, but by no means all of the reported A history of a preceding syphilis was obtainable in some In many of the patients, however, no adequate cause for the disease is found, and the exciting etiological factor is still wrapped in mystery.

cases. cases.

The picture presented by the gross and histological lesions in this disease is a very characteristic one. Pigmentation, with or without cirrhosis of various internal organs, is its chief characteristic. The color of the different organs is variously described

by different writers; it varies in intensity just as does the color of the skin. In well marked cases it may perhaps be best described as a reddish-brown or ochre brown. The pigmentation involves mostly the abdominal organs, especially the liver, the pancreas and the lymph nodes. Pigmentation of the intestines may be marked. The spleen, kidneys and adrenals are usually comparatively free from pigmentation. The thoracic organs may also show pigmentation and there may be marked pigmentation of the thyroid and salivary glands. The choroid plexus of the lateral ventricles and other portions of the brain may show pigmentation.

The cirrhosis of the liver is not invariably present, but the exceptions are very few. It is in type a portal cirrhosis and is associated with the deposition of pigment both in the liver cells and in the new formed connective tissue. Even in the cases with well-marked diabetes the cirrhosis of the pancreas may be comparatively slight. In recent cases it has been demonstrated, however, that even where the cirrhosis is slight there are definite changes in the Islands of Langerhans, usually in the form of pigmentation and degeneration of their constituent cells. In organs other than in the liver and pancreas a fibrosis may occur. In the abdominal lymph nodes, in which the pigmentation is usually intense, there is little fibrosis as a rule. The comparative absence of pigmentation in the spleen is to be noted in view of the theory of a hæmolytic origin of the disease. There is often considerable fibrosis of the spleen.

The character of the pigment which is present in different organs has been carefully studied with relation to its iron content, especially since the publication of von Recklinghausen's important monograph on hæmochromatosis. The amount of iron which is present in some organs is very considerable. In the case of the liver iron may constitute as much as 7.6 per cent. of the dried organ, the normal being a very small fraction of 1 per cent. All observers agree in describing two forms of pigment in the lesions, hæmosiderin, an iron containing pigment, and hæmofuscin, an iron free pigment. Letulle considers that the pigmentation of the skin is due to an increase in the normal skin