The Significance of Albumosuria in 
Medical Practice; 
Suggested by a Fatal Case of Albumosuric Myxoedema 
Treated with Thyroid Extract. 
BY 
REGINALD H. FITZ, M.D., 
OF BOSTON. _ 
FROM 
THE AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 
July, 1898. Extracted from The American Journal of the Medical Sciences, July, 1898. 
THE SIGNIFICANCE OF ALBUMOSURIA IN MEDICAL PRACTICE ; 
SUGGESTED BY A FATAL CASE OF ALBUMOSURIC MYXCE- 
DEMA TREATED WITH THYROID EXTRACT.1 
By Reginald H. Fitz, M.I)., 
OF BOSTON. 
The following case of myxoedema is reported more particularly for 
the purpose of calling especial attention to the presence of a symptom 
which, with but a single exception, so far as I am aware, has hitherto 
been unrecorded in this disease except as a mere statement of fact in 
the Practice of Medicine, by Wood and Fitz. The patient therein re- 
ferred to was seen by me in consultation with Dr. M. L. Chamberlain, 
of Boston, to whom I am indebted for permission to give the following 
account and for information concerning the progress of the malady. 
The case is of further interest, if not importance, in showing that the 
prognosis of myxoedema still may be grave despite the immediate and 
repeated benefit so generally resulting from the use of thyroid prepara- 
tions. 
I first saw Mrs. — November 17, 1895. She was fifty-three years 
of age, and had lived the greater part of her life in Vermont. The 
last two years had been spent in California. She never had been 
pregnant. 
As a girl she suffered considerably from discomfort referred to the 
stomach, in the region of which there would be a sense of distention for 
a day or two at a time. Cramps would occur suddenly, and tender- 
ness along the spine was complained of. With these exceptions she en- 
joyed good health throughout the greater part of her life, recalling to 
mind solely an operation for anal fistula when she was about forty-seven 
years old. 
At the age of forty-nine, while in Vermont, she observed a gradual 
loss of flesh, strength, and color. A year later, when tired, would feel 
a griping sensation in the back of the neck and a pain between the 
shoulders. These discomforts were noticeable especially on going down 
hill. There was also a temporary stiffness of the joints in the morning. 
At this time the eyelids were slightly swollen and an increased flow of 
saliva began, a symptom which has continued since, and persists at 
present. 
In the following year, 1893, while in California, the joints again be- 
came appreciably stiff, and she felt a senseof n undmessAnthe righrbeel. 
1 Read at the annual meeting of the Association of9mm<;an Physicians, WashingtCfh,Df. C., 
May 3, 1898. 2 
FITZ: ALBUMOSURIA IN MEDICAL PRACTICE. 
iii the knees immediately above and below the joint, and in the fingers of 
the right hand. In 1894 the stiffness diminished somewhat, but the 
numbness persisted. In the fall of this year the teeth were troublesome 
and, despite the care of a dentist, became painful, and since have re- 
mained in this state. An upper canine tooth is said to have extended 
into the bone one-fourth of an inch. There was a metallic taste in the 
mouth, and she became unable to masticate resistant food, being obliged 
to live upon soft articles of diet. Walking now caused so much fatigue 
that she was obliged to give up active exercise. The griping at the back 
of the neck and the pain between the shoulders continued to be annoy- 
ing at times, and she suffered also from wakefulness. 
In January, 1895, superficial swellings first were noticed. They ap- 
peared as an enlargement of the back of the neck, a lump beneath the 
jaw, hypertrophy of the tongue, and, later, indurations in the legs and 
arms. At first the swellings would vary temporarily in size, and that 
in the neck would lessen somewhat under the influence of fomenta- 
tions ; but later the enlargement remained constant. The voice was 
now changed, and the increased flow of saliva became a more or less 
constant drooling. In the course of a few months, in consequence of 
a loose molar tooth, the jaws were prevented from closing. The tooth 
was extracted, but the jaw and the neighboring portion of the tongue 
became sore and, finally, a fragment of dead bone was removed. 
At the time of my first visit Mrs. — was unable to walk, on account 
of muscular stiffness. There was no evidence of mental impairment, 
nor had such been observed by her friends. Her face was pale, moder- 
ately swollen, and expressionless from partial effacement of wrinkles 
and furrows. In sharp contrast was the elevation of the eyebrows and 
wrinkling of the forehead from apparent tension of the occipito-frontalis 
muscle. The upper eyelids were relatively normal, but the lower lids 
were somewhat puffy. The lips were slightly thickened and everted, the 
surface roughened. Especially conspicuous was the greatly enlarged and 
resistant tongue, filling the partially opened mouth. The dorsum of the 
tongue was dry, although the flow of saliva was constant. The submax- 
illary region was prominent, presenting the appearance of a double chin, 
and both submaxillary salivary glands were greatly swollen and dense. 
The back of the neck was smooth and much swollen, like that of a very 
obese person, but was dense and resistant to the touch. It measured from 
sixteen and one-half to seventeen and one-half inches in circumference. 
The hands and feet were cold. The skin covering the back of the hands 
was thickened, coarsely wrinkled, the surface being rough and of a dirty- 
yellowish tint, the whole appearance suggesting that of a fowl’s claw. 
The skin covering the front of the chest and abdomen was normal, but 
that of the forearms, legs, feet, back, and buttocks was pale, dry, 
smooth, tightly drawn, not displaceable from the subjacent structure in 
consequence of the resistance of the subcutaneous tissue. The anterior 
wall of the vagina was smooth, thickened, and dense like the abnormal 
portion of the skin. There were no supraclavicular swellings. The 
hair was coarse and dry, but the nails were normal in appearance. 
The thyroid gland was not palpable. Nothing abnormal was found 
on auscultation and percussion of the chest and on palpation of the 
abdomen. The temperature was 98.4° F. The examination of the 
blood by Dr. R. C. Cabot showed 5,030,000 red corpuscles, 11,600 
leucocytes, and 35 per cent, of haemoglobin. The differential count FITZ: ALBUMOSURIA IN MEDICAL PRACTICE. 
3 
gave 74 per cent, of polynuclear leucocytes and 23 per cent, of lympho- 
cytes. 
On the addition of nitric acid to the urine a dense, white precipitate 
was formed, occupying nearly one-half the volume of urine. The pre- 
cipitate was dissolved when the specimen was boiled, but reappeared on 
cooling. When the urine in a test-tube was boiled it became opaque 
until the boiling-point was reached. It then became clear, and thus 
remained until the liquid was cool, when a white precipitate formed. 
Under the microscope a few red blood-corpuscles and an occasional 
hyaline and granular cast were seen. 
The dissolving of the nitric acid precipitate by heat and the forma- 
tion of a white precipitate when the boiled urine was cooled led me to 
suspect the presence of albumose, and Prof. E. S. Wood was asked to 
test further for this substance. He informed me that after boiling and 
filtering the urine to free it from albumin the clear filtrate, when acid- 
ulated with acetic acid and heated gently, became opaque, but the 
opacity disappeared on boiling, and a white precipitate formed when 
the fluid was cooled. Acetic acid and ferrocyanide of potassium gave 
a precipitate which dissolved when the mixture was boiled, and reap- 
peared as the temperature fell. The biuret reaction was positive. 
Professor Wood analyzed the urine from this patient repeatedly 
during a period of six weeks. A trace of albumin was present usually, 
but albumose was found constantly, by estimate varying from i per 
cent, to I per cent. December 10, 1895, a quantitative determination 
was made and showed 0.93 per cent, of albumose. The per cent, of 
urea on this day was 3.63, and the total quantity 18.66 grammes. 
The diagnosis of myxcedema was made, and the treatment with 
thyroid extract begun, the five-grain tabloids of Burroughs, Wellcome 
& Co. being used. The dose of five grains on the first day was increased 
by one tabloid daily, but on the third day there was a sense of prsecor- 
dial oppression, and the pulse became quickened. The dose then was 
diminished to one or two tabloids daily for a week, when it again was 
raised to three five-grain tabloids in each twenty-four hours. 
I saw Mrs. — a second time December 10, 1895, a little more than 
three weeks after my first visit. The change in her appearance had 
greatly improved, although previous to the use of the thyroid extract 
her condition was steadily deteriorating. At the end of the first week 
of thyroid treatment the oedema suddenly left the eyelids, but a watery 
oedema, pitting on pressure, appeared and persisted in the feet. The 
flow of saliva diminished, the swollen tongue became smaller, and the 
pain in the shoulders was less disturbing. In the third week of treat- 
ment the swelling of the neck and of the submaxillary glands was 
noticeably lessened, and the expression of the face became more mobile. 
The weight at the beginning of the thyroid treatment was one hundred 
and twenty-five and one-half pounds, and there had been a loss of about 
three pounds each week. The quantity of urea eliminated increased 
from eleven to sixteen grammes. The appetite was unaffected, but the 
pallor and debility were greater than when first seen. The pulse varied 
between 83 and 107 beats per minute, and the temperature remained in 
the vicinity of 99.7° F. 
It was considered desirable to continue the use of the thyroid extract 
under careful supervision, that cardiac weakness might not prove a 
source of danger. The especial discomforts produced by it were fleeting 4 
FITZ: ALBUMOSURIA IN MEDICAL PRACTICE. 
pains in the muscles or in one joint or another, pnecordial constriction, 
and a choking sensation, all more likely to occur at night when the 
greatest quantity of the thyroid preparation had been taken within a 
limited number of hours. 
Preparations of iron, arsenic, manganese, strychnine, digitalis, and 
nitroglycerin were given from time to time as the indications for their 
use were apparent. On account of the progressive weakness of the 
patient, despite the early improvement in the surface manifestations, 
the thyroid preparations were discontinued from time to time. 
At a third visit, February 25, 1896, Dr. C. F. Folsom also saw the 
patient. At this time, although the expression was brighter, she was 
pale, weak, and emaciated. The especial improvement was in the con- 
dition of the skin, which was smooth, moist, and free from the yellow 
discoloration so marked at the outset. The hands were warm, the hair 
was moist and less bristling, but the brawny induration of the back of 
the neck and the swelling of the tongue and submaxillary glands had 
not materially diminished in the previous two months. It was decided 
to continue the use of the thyroid, and from seven to nine grains were 
daily given for a week, during which time the pulse was about 100 and 
the temperature varied from 99.33 to 100.4J F. A sudden severe 
attack of pnecordial pain then occurred, and the use of the thyroid was 
discontinued for four weeks. During this time the pulse fell to the 
normal and became stronger, the salivation lessened, the weight in- 
creased somewhat, but the tongue felt as if it was somewhat enlarged. 
The thyroid extract was then given in one-grain doses, and, for greater 
convenience in supervision and care, Mrs. — entered the Boston City 
Hospital, where she came under the charge of Dr. Folsom, to w hom I 
am indebted for the report of her further progress. 
She was admitted to the hospital April 18, 1896. The circumference 
of the neck then was fifteen inches, the tongue was about four inches 
wide and one inch thick. The head could not be bent backward, nor 
could the chest be touched with the chin. The hands and feet were 
cold, the skin was smooth, and the hair moist. The blood examination 
showed 84 per cent, haemoglobin, 4,532,000 red corpuscles, and 10,500 
leucocytes. The patient received one grain of thyroid extract daily, but 
she gradually became wreaker, took little nourishment, decidedly failed 
on April 26, and died early on the following day. There was no autopsy. 
There having been some difference of opinion among the physicians 
who saw this patient as to the exact nature of the disease, the reasons 
for the diagnosis of myxoedema may be summarized. There were present 
“ the firm swelling of the skin, not pitting on pressure, inelastic, ad- 
herent to the parts beneath, and not affected by gravitation ; the dry- 
ness and roughness of the skin, tending, with the swelling, to obliterate 
all lines of expression ; the imperfect nutrition of the hairs . . the 
local tumefaction of the skin and subcutaneous tissue noticed in various 
parts of the body . . an affection of the teeth homologous with that 
of the hairs just mentioned; the remarkable physiognomy; the slow 
. . monotonous voice . . and elimination or apparent absence of 
the thyroid gland.” These are among the characteristics of myxoedema 
described in the Report of the Committee of the Clinical Society of London, FITZ: ALBUMOSURIA IN MEDICAL PRACTICE. 
5 
1888 vol. xxi., Supplement, p. 178. The mental impairment and sub- 
normal temperature alone are lacking to complete the picture. But 
mental disturbances were absent in twenty-seven out of forty-six cases 
tabulated by the committee.1 The temperature was normal in eight 
cases, and in a few was 99.6 F., or even higher, though never above 
100° F. The swelling in the back of the neck was duplicated in Dr. 
Ord’s case, No. 87, in which there was a “ swelling at the back of the 
neck over trapezius, so that he cannot bear to wear a collar.” Salivation 
was present in three of the committee’s cases, and the submaxillary 
gland of Hale White’s cases2 showed marked changes. A large, swollen 
tongue was noted in fifty-two cases. 
If the correspondence in clinical characteristics is not considered as 
sufficient for the confirmation of the diagnosis, additional evidence is 
furnished by the effects of the treatment with the thyroid extract. 
According to Murray3 there are rise in temperature, disappearance of 
swelling, loss of weight, a soft, smooth, most condition of the skin, 
growth of the hair, improvement in the mental condition, and increase 
in the elimination of urea. Her temperature became somewhat higher, 
and the previously cold hands were warm. The swelling diminished, 
there was a loss of weight, the skin became soft, smooth, and moist, and 
the elimination of the urea increased. A growth of hair was not con- 
spicuous, since there was no tendency to alopecia, but a considerable 
improvement in its nutrition was apparent from the return of its normal 
characteristics. 
The failure of the thyroid treatment to accomplish more marked 
relief is in striking contrast to the almost constant benefit derived from 
its use in the treatment of myxoedema. Mitchell Clarke,4 however, 
reports two cases in which thyroid treatment proved unsuccessful, and 
Macphersou,5 although causing improvement by thyroid grafting, did 
not remove the myxoedematous condition. Byron Bramwell6 gives an 
account of two fatal cases of myxoedema during or shortly after thyroid 
treatment. In each instance the death was sudden. 
I am indebted to my colleague, Dr. E. G. Cutler, for the following 
summary of a fatal case under his charge. 
“A patient in whom I made the clinical diagnosis of myxoedema had 
gradually over a period of a year and a half come into the following 
condition : The skin of the face, neck, shoulders, hands, arms, legs, and 
feet was pale and a little glossy, rather dry, much distended by a sub- 
cutaneous growth which did not pit and apparently was not fat. The 
wrinkles in the face were obliterated, the hair on the head had become 
1 Report of the Committee of the Clinical Society of London, 1888, vol. xxi., Supplement, 
p. 14. 
2 Op. cit., p. 41. * Twentieth Century Practice, 1895, vol. iv. p. 712. 
4 British Medical Journal, 1892, vol. ii. p. 451. 
5 Edinburgh Medical Journal, 1892, vol. xxxvii. p. 1021. 
8 Edinburgh Hosp. Rep., 1895, vol. iii. p. 116. 6 
FITZ: ALBUMOSURIA IN MEDICAL PRACTICE. 
sparse and dry, the hands and feet were much wrinkled, and the skin 
and nails coarse and rough. Speech was slow and peculiar. The 
mental condition was variable: at times the patient was rather inclined 
to be talkative, but the range of subjects was limited; at other times 
the patient would be quiet for hours and rather somnolent. Frequently 
there was mild delirium at night, with occasional hallucinations of 
sight. The patellar reflex was absent. The pulse was slow, the surface 
cool, and the temperature in the mouth 98° F., though no complaint 
of cold was made. The urine was free from albumin. The thyroid 
could not be made out. Toward the end there was marked tendency 
to somnolence. Thyroid tablets, five grains each, were given up to nine 
a day for two months, beginning with small dose, but with little effect. 
Death was sudden and apparently due to syncope.” 
The novel feature of my case was the albumosuria, which continued 
throughout the progress of the disease from the time it first was ob- 
served. Occasional or slight traces of albumin were noticed in twenty 
out of ninety cases, and in one a large quantity, in the series tabulated 
by the London Clinical Society’s Committee,1 in which mention was 
made of this condition, and in twenty-one out of one hundred and 
twelve cases collected by Hun and Pruddeu.2 Murray3 states that 
“ mucin ” has not been found in the urine of human myxoederaa, but 
refers4 to Halliburton’s discovery of an abundance of “ mucin ” in the 
urine of a sheep that developed myxcedema two years after the thyroid 
Avas removed by Horsley. Buzdyan,5 however, found traces of mucin, 
but no albumin, in the urine of a patient examined by him. The only 
instance of myxcedema in which I have found mention of the occur- 
rence of albumosuria is the patient of von Jaksch.6 The case was one 
of typical Basedow’s disease in which there were present a swelling of 
the legs, regarded as myxoedematous, and an albumosuria observed 
during a period of six months. 
As is well known, this term is applied to the presence in the urine 
of a peculiar substance first observed by Bence Jones7 in 1845. As 
described by him, “ It gave no precipitate with an excess of nitric 
acid unless left to stand, or unless heated and left to cool, Avhen it became 
solid. This solid redissolved by heat and again formed on cooling. 
Continued boiling with strong nitric acid evolved but little gas, and did 
not quickly hinder this reaction. Hydrochloric acid gave the same 
solid precipitate, soluble by heat. Strong acetic acid gave only a 
slight precipitate, which redissolved by heat. Caustic potash and sul- 
phate of copper gave a splendid bright-blue, clear liquid, passing over, 
1 Op. cit., p. 21. 
2 The American Journal of the Medical Sciences, 1888, vol. xcvii. p. 1. 
« Loc. cit., p. 722. * Loc. cit., p. 726. 
6 Wien, klin, Wochenschr., 1891, Band iv. p. 510. 
6 Prag. med. Wochenschr., 1892, Band xvii. p. 602. 
7 Philosoph. Trans. Royal Soc. London, 1848, Pt. i. p. 55. FITZ: ALBUMOSURIA IN MEDICAL PRACTICE. 
7 
when heated, to a claret color, . . coagulated firmly with heat, 
very perfectly with a drop or two of acetic acid.” 
According to Maly1 the product of the gastric digestion of albuminous 
substances was designated albuminose by Mialhe in 1846, but subse- 
quently Lehmann named it peptone. Meissner and his pupils, in a series 
of articles published between 1847 and 1853, assumed the existence of a 
number of products of digestion intermediate between albumin and 
peptone, to which the terms parapeptone, metapeptone, dyspeptone, 
a, /3, and y peptone were applied. In 1869 Kiihne received from 
Stokvis a specimen of urine which presented reactions similar to those 
observed by Bence Jones, and Kiihne regarded the substances as iden- 
tical. In the same year Gerhardt3 sought in the urine for other albu- 
minous substances than serum albumin, and discovered a variety, called 
by him “ latent,” which resembled in its characteristics one of the pep- 
tones described by Meissner. He found it in a number of diseases, and 
observed that it was to be met with in persons whose temperature, 
frequently or constantly, was in the vicinity of 104° F. Senator3 later 
observed in the urine easily distinguishable quantities of what he re- 
garded as peptone. He recognized that this substance might have 
been produced in albuminous urine by the process of boiling used in 
its isolation, but suggested that it may have been present in the freshly 
voided urine. In support of this view he referred to Gerhardt’s dis- 
covery of a substance resembling peptone in urine in which no evidence 
of ordinary albumin was to be obtained. Leick,4 however, states that, 
although boiling may produce albumose from albumin, such a result 
does not necessarily follow, since numerous specimens of albuminous 
urine were so treated without the formation of albumose. Even in 
experiments on isolated albumin the quantity so transformed was too 
small to be significant. It was recognized also by Senator as possible 
for the albumin or albuminous urine, on its passage from the kidneys 
to the bladder and during its retention in this viscus, in part to be con- 
verted into peptone, in accordance with the statement of Eichwald, that 
fluid albumin in contact with animal tissues at the temperature of the 
body is readily transformed into peptone. Eichwald found this sub- 
stance in the urine of nephritis, and Obermiiller, in 1873, in that of 
scarlet fever and Asiatic cholera. Gowers5 a few years later noticed 
its presence in a patient who previously had suffered from glycosuria. 
About this time Kiihne gave the term heinialbumose to this substance, 
which was considered to correspond with the a-peptone of Meissner, and 
Schmidt-Mtilheim6 designated it propeptone. Its properties were studied 
1 Herman’s Handb. d. Physiol., 1881, Band v. S. 94. 
2 Deutsches Arch. f. klin. Med., 1889, Band v. 8. 212. 
3 Arch. f. path. Anat., etc., 1874, Band lx. S. 476. 
4 Deutsche med. Wochenschr., 1896, Band xxii. S. 22. 
3 Lancet, 1878, vol. ii. p. 3. « Arch. f. Physiol., 1880, S. 33. 8 
FITZ: ALBUMOSURIA IN MEDICAL PRACTICE. 
also by Salkowski.1 All these observers recognized the resemblance 
between this so-called peptone, hemialbumose, or propeptone, and the 
substance discovered by Bence Jones. The methods employed for the 
recognition of the “ peptone” were faulty, especially from the difficulty 
of wholly removing the albumin often associated, and from the frequent, 
if not constant, presence of “ mucin,” which also was precipitated by 
the alcohol used in isolating the substance, and which gave rise to 
reactions similar to those attributed to the peptone. Hofmeister2 con- 
sequently devised a method for the isolation of the so-called peptone 
which should free it from these sources of error. This method and the 
improvement subsequently made by Salkowski served as the basis of 
numerous contributions to the study of what has been designated 
“ peptonuria.” 
The researches of Kiihne and of Iviihne and Chittenden3 led to the 
use of the term albumosuria as a substitute for propeptonuria. Ac- 
cording to these investigators albumose, hemialbumose, or propeptone 
was a mixture of four albumoses which were designated protalbumose, 
deuteroalbumose, heteroalbumose, and dysalbumose. Each varied 
slightly from the others, especially with reference to the degree of solu- 
bility in water and in behavior toward solutions of sodium chloride, 
being either soluble or insoluble in dilute solutions and precipitated by 
concentrated solutions alone or in the presence of an acid according 
to the variety of albumose concerned. When in solution they were 
not precipitated by heat alone, but if precipitated by acids or salts were 
redissolved at a boiling temperature and were precipitated when the 
solution was cooled. According to Huppert, Mathes, and Rosin they 
become opaque at temperatures of 150°-152° F., and clot at 166°- 
178° F. They were precipitated by nitric acid and by acetic acid, by 
magnesium sulphate, concentrated solutions of sodium chloride, and of 
ammonium sulphate in an acid, alkaline, or neutral solution, and gave 
the biuret reaction. 
Like albumin, they were precipitated by nitric acid, ferrocyanide 
of potassium and acetic acid, sodium chloride and acetic acid, and 
ammonium sulphate, but they were not coagulated on boiling. They 
resembled peptones in being soluble at a boiling temperature, pre- 
cipitating as the fluid became cool, and in giving the biuret reaction. 
They differed from peptone, according to Kiihne/ in being precipitated 
by ammonium sulphate. 
The search for albumose then became instituted, and the term albu- 
mosuria soon replaced that of propeptonuria, although for a long time 
it was considered to be a different condition from peptonuria. 
1 Arch. f. path. Anat., 1880, Band lxxxi. S. 552. 
2 Ztschr. f. Physiol. Chem., 1880, Band iv. S. 253. 
a Ztschr. f. Biol., 1883, Band xix. S. 159, 219; 1884, Band xx. S. 11 
4 See article by Wenz: Ztschr. f. Biol., 1886, Band xxii. S. 1. FITZ: ALBUMOSURIA IN MEDICAL PRACTICE. 
9 
The distinction made between albumoses and peptones, based upon 
the insolubility of the former in ammonium sulphate, was opposed by 
the observation of Neumeister1 that this agent does not precipitate 
entirely all the albumoses, especially deuteroalbumose. Stadelmann 
in 1894 concluded that peptone as distinguished from alburaose never 
occurred in fresh urine, although it might be found in stale albuminous 
urine from the action of bacteria upon the albumin. Yon Noorden 
and Senator2 accepted this view, and maintained that both peptonuria 
and propeptonuria were albumosuria. According to Senator, if a part 
of the urine which gives a positive reaction to Salkowski’s test, and, 
therefore, is considered to contain peptone, is slightly acidified and 
treated with ammonium sulphate in excess and filtered, there will be 
no biuret reaction in the filtrate, indicating the absence of Kiihne’s 
peptone, which should be soluble in the ammonium sulphate. 
Albumose was found not only in the gastric contents during the 
digestion of albumin, but also in artificial peptone preparations and by 
Fleischer1 in normal bone-marrow. The discovery of its presence in 
semen is generally attributed to Posner,4 but this observer and others 
who have written upon the subject, with the exception of Kahler,5 have 
overlooked the fact that Bence Jones,6 the discoverer of albumose, 
found it not only in the urine and in pus, but also “ in the secretion 
from the vesiculse seminales.” Virchow7 recognized in the bone-marrow 
of osteomalacia a substance which he considered to resemble that de- 
scribed by Bence Jones. Salkowski8 sought successfully for it in the 
liver and spleen of leukaemia and in the liver of acute yellow atrophy. 
Miura9 observed it in the liver, heart, and kidneys of phosphorus poi- 
soning produced experimentally, and in the organs of a case of puerperal 
fever. Schiiltzen and Riess10 previously had found albumose in the 
urine of phosphorus poisoning. Fischel11 stated that albumosuria was 
present almost constantly during the involution of the puerperal uterus, 
and Kottnitz12 when there was a macerated foetus. 
Albumosuria has been produced experimentally by Lassar13 by rub- 
bing petroleum into the skin of animals. Plosz and Gyergai14 and Hof- 
1 Ztsotar f. Biol., 1888, Band xxiv. S. 267. 
2 Deutsche med. Wochenschrift. 1895, Band xxi. S. 217. 
8 Arch. f. path. An at., etc., 1880, Band Ixxx. S. 482. 
4 Berlin, klin. Wochenschrift, Band xxv. S. 417. 
6 Prag. med. Wochenschrift, 1889, Band xiv. S. 33. 
6 Arch. f. path. Anat., etc., 1852, Band iv. S. 309. 
7 Loc. cit. 
8 Loc. cit., 1880, Band lxxxi. S. 166; 1882, Band lxxxviii. S. 394. 
9 Loc. cit., 1885, Band ci. S. 316. 
10 ADn. d. Char-krankenh. zu Berlin, 1869, Band xv. S. 1. 
11 Arch. f. Gyniikol., 1884, Band xxiv. S. 400. 
12 Deutsche med. Wochenschrift, 1888, Band xiv. S. 613. 
13 Arch. f. path. Anat., etc., 1889, Band lxxvii. S. 157. 
14 Arch. f. d. ges. Physiol., 1875, Band x. S. 53. 10 
FITZ: ALBUMOSURIA IN MEDICAL PRACTICE. 
meister1 caused it by the injection of peptone into the veins, and Jitta 
by the subcutaneous injection of glycerin. Rosenheim3 states that he 
has seen albumosuria follow the ingestion of large quantities of albu- 
mose in a case of severe intestinal disturbance. 
The clinical importance of albumosuria has been made a matter of 
study by many observers whose results in the main agree. Although 
published under the titles of peptonuria, propeptonuria, or albumosuria, 
the method used for the purpose of determining the presence of the albu- 
mose was that of Hofmeister, or, in more recent years, by this method 
as modified by Salkowski.4 The chief advantages of the modification 
are gain in time and the use of a much smaller quantity of urine. 
The urine to be tested must first be freed from any albumin present 
by acidifying from 30 to 50 c.c. with acetic acid, adding an equal quan- 
tity of saturated solution of common salt, boiling, and filtering. The 
albumins and albumoses are precipitated, but the latter are redissolved 
at the boiling temperature. The filtered fluid containing the albumose 
in solution is to be placed with a few drops of hydrochloric acid in a 
beaker, and then a solution of phosphotungstic acid is to be added 
while precipitation continues. The precipitate is to be consolidated by 
gentle heat into a coherent or powdery substance. The supernatant 
fluid is to be poured off, and the precipitate, washed with water, 
is to be dissolved in a solution of soda (specific gravity 1.16), which 
is to be added drop by drop until a blue or a colorless solution results. 
The solution, if blue, is to be decolorized by heat, and a few drops of a 1 
per cent, solution of sulphate of copper are to be added to the soda 
solution, when a red or violet color, the biuret reaction, results if albu- 
mose is present. 
Recently Salkowski5 has called attention to a possible source of error. 
He has found that urobilin, which is precipitated by phosphotungstic 
acid, gives also the biuret reaction, and that consequently a specimen 
of urine tested by the Salkowski method may give a positive result, 
but due to urobilin and not to albumose. Urobilin in the urine does 
not necessarily produce this reaction, but is more likely to in case the 
spectroscopic examination of the urine gives a well-marked urobilin 
line. Leick6 already had suggested a modification of the Salkowski 
test, having found it necessary to use a stronger soda solution or a 
larger quantity of the weaker variety. After removing the albumin 
he added also the neutral lead acetate to the filtrate for the purpose of 
precipitating “ mucin,” coloring matter, and any remaining albumin. 
According to Salkowski, albumose also is precipitated by this reagent, 
1 Zeitschr. f. physiol. Chem., Band v. S. 127. 
2 Jahresb. u. d. Fortschr. d. Thier. Chem., 1885, Band xv. S. 474. 
3 Allg. med. Centr., 1897, Band lxvi. S. 1132. 
4 Centralblatt f. d. med Wissensch., 1894, Band xxii. S. 113. 
5 Berlin, kiln. Wochenschrift, 1897, Band xxxiv. S. 353. 6 Loc. cit FITZ: ALBUMOSURIA IN MEDICAL PRACTICE. 
11 
aud the negative results of the examination by this method could not 
exclude the possibility of albumosuria. Fortunately for practical pur- 
poses, the question relates to quantity and not to mere presence. Bang1 
also has devised a method for finding albumose in the urine, even in a 
dilution of 1 :4-5000, when urobilin is present in any considerable 
quantity. A test-tube containing 8 grammes of finely powdered am- 
monium sulphate in 10 c.c. of urine is to be heated till the former is 
dissolved. The contents are to be boiled for a minute, centrifuged 
for another minute, and the clear liquid poured off. The residue, con- 
taining albumose, albumin, urobilin, uric acid, and urates, is to be 
stirred in alcohol (97 per cent.), which dissolves the urobilin and is to 
be poured off. This residue is boiled with a little water and filtered ; the 
filtrate gives the biuret reaction if albumose is present. The centrifuge 
may be dispensed with, if the quantity of albumose is considerable, and 
the following method employed. After boiling some of the albumose 
adheres to the wall of the tube. The liquid is to be poured out and 
the adherent residue washed with alcohol to which a little chloroform 
is to be added if there is presumably much urobilin. The biuret test is 
to be applied to the filtrate from the residue dissolved in water. The 
presence of urobilin in the alcoholic extract is shown by a fluorescence 
when a few drops of a solution of zinc chloride are added. Hsemato- 
porphyrin may simulate albumose by causing a red color when the 
alkali of the biuret test is used. Its presence is to be suspected if the 
alcoholic extract is red and proven by the spectroscope. If, therefore, 
the alcoholic extract is red the urine should first be treated with barium 
chloride, which precipitates luematoporphyrin. 
Maixner,2 von Jaksch,3 and Pacanowski4 examined hundreds of 
cases of various diseases by Hofmeister’s method, and came practically 
to the same conclusion, that albumosuria was oftenest found in suppu- 
rative processes associated with the retention and disintegration of pus, 
in acute infectious diseases, and in affections with more or less exten- 
sive destruction of tissues. Koppen5 observed it in a number of insane 
persons, especially those who were maniacal or delirious. W. Rob- 
itschek,6 Senator,7 and Leick,8 using Salkowki’s method, arrived at 
a similar result. The albumosuria was relatively constant in deep- 
seated suppuration and in acute fibrinous pneumonia, especially during 
resolution. 
Gerhardt’s claim that ordinary or “latent” albuminuria occurred 
1 Deutsche med. Wochenschrift, 1898, Band xxiv. S. 17. 
2 Vrtljschr. f. d. prakt. Heilk. Prag., 1879, Band cxliv. S. 75; Ztschr. f. klin. Med., 1884, Band 
viii. S. 234. 
3 Zeitschr. f. klin. Med., 1883, Band vi. S. 413. 
* Ibid., 1885, Band ix. S. 429. 
5 Arch. f. Psychiat., 1888-1889, Band xx. S. 825. 
6 Zeitschr. f. klin. Med., 1884, Band xxiv. S. 556. 
7 Deutsche med. Wochenschrift, 1895, Band xxi. S. 217. 8 Loc. cit. 12 
FITZ: ALBUMOSURIA IN MEDICAL PRACTICE. 
in persistent or frequent elevations of temperature above 104° F., and 
the statement of Krehl and Matthes1 that albumosuria was almost con- 
stant in fever, are subject to a different interpretation in the light of 
Salkowski’s discovery concerning the reaction of urobilin. 
Albumosuria has been found in various chronic affections, as well as 
in those of an acute nature. Among these chief importance is to be 
attached to the albumosuria of osteomalacia or of affections regarded 
as of this nature. 
Such cases have been reported by Bence Jones,2 Kiihne,3 Kahler,4 
Stokvis and Ribbink, Matthes,5 Huppert,6 and Rosin.7 According to 
Kahler, these are not examples of true osteomalacia, but of myelogenous 
tumors, sarcoma, lymphoma, myeloma, especially of the bones of the 
thorax. Matthes,8 in four cases of osteomalacia which probably were 
of multiple myeloma, isolated from the urine a substance with the 
characteristics of albumose, but which, when digested for some time, 
gave rise to a ferrated nuclein. Hence the substance was regarded as 
a uucleo-albuminose arising from the ferrated nucleo-albumin of bone- 
marrow discovered by Nasse. It was not found in typical puerperal 
osteomalacia. 
Raschkes,9 on the contrary, states that albumosuria occurs in senile 
osteomalacia, and Hammer10 and Marckwald11 make no mention of the 
importance of albumosuria in their analyses of the reported cases of 
multiple sarcoma or of allied affections of the bones. 
In most of the diseases in which albumosuria has been found the 
albumose has been observed, as a rule, for a short time and in small 
quantity, although in rare instances for a long time and in large quan- 
tities. Pacanowski,12 indeed, subdivided the condition into acute and 
chronic albumosuria. But his distinction applied solely to the occur- 
rence of the symptoms in acute and in chronic affections. A more 
practical division is into transitory and persistent albumosuria. Tran- 
sitory albumosuria is to be found, despite the faulty methods and the 
opportunities of error, in such a variety of diseases as to have proven 
of but little practical value except in the diagnosis of acute pneumonia, 
deep-seated suppuration, including meningitis, and of macerated foetus. 
In all of these conditions the ordinary means of diagnosis are usually 
sufficient, and the leucocyte count affords a most satisfactory aid, and 
is an efficient substitute for the search for albumose. 
1 Deutsches Archiv f. klin. Med., 1895, Band liv. S. 501. 
2 Loc. cit. 3 Loc. cit. 
* Prag. med. Wochenschrift, 1889, Band xiv. 8. 85. 
6 Verhand. d. Cong. f. innere Med., 1896, Band xiv. 8. 476. 
6 Zeitschr. f. physiol. Chem., 1896-97, Band xxii. 8. 500. 
7 Berlin, klin. Wochenschrift, 1897, Band xxxiv. S. 48. 8 Loc. cit. 
9 Prag. med. Wochenschrift, 1894, Band xix. 8. 649. 
10 Archiv f. path. Anat., etc , 1894, Band cxxxvii. S. 280. 
11 Ibid., 1895, Band cxli. 8.128. i2 Loc. cit. FITZ: ALBUMOSURIA IN MEDICAL PRACTICE. 
13 
Greater value is to be attached to the recognition of persistent albu- 
mosuria, the importance of which in practice has become especially sug- 
gested of late years in connection with the diagnosis of multiple but 
latent tumors of the trunk. Such an albumosuria is sometimes nearly 
a pure form, and is spoken of as primary or typical, better, perhaps, as 
persistent or excessive. This variety thus far has been observed prin- 
cipally in multiple bone tumors and in myxoedema, and in but few cases 
of these affections. These observations, however, are so suggestive as 
to demand general attention. 
It has been my fortune in the past two years to have seen two cases 
of persistent and excessive albumosuria, so generally recognized as an 
exceedingly rare condition. The first case serves to introduce this com- 
munication ; the second, now in charge of my colleague, Dr. F. C. 
Shattuck, to illustrate it. In the latter the presence of albumosuria, 
and its extreme degree, led to the probable diagnosis of multiple tumors 
of the bones, and the use of the Rontgen rays showed such changes in 
the structure of the bones as confirmed this opinion. 
The source of the albumose in these cases may prove to be in the 
bone-marrow, as suspected by Virchow, but chemical analyses to deter- 
mine this point have yet to be made. It is important also that the 
subcutaneous tissues in myxoedema should be examined chemically for 
albumose, since the nature of the infiltrating substance in this disease 
is still a matter of conjecture, and the presence of albumose in the 
ui'ine of the two cases suggests a possibility requiring disproof, even if 
the search give no other information. 
Whatever the value of albumosuria may be in diagnosis, its per- 
sistent and excessive presence is apparently a sign of grave prognosis, 
since the cases in which this condition has been found have, almost 
without exception, proven fatal. The Medical News. 
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