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GLAND 
k^OF DOGS, ilTB ESPECIAL CONSIDERATION OF 
HYPERTROPHY OF THIS GLAND 



WILLIAM S. HALSTED, M, D. 

Pmrt-TB/Sonun '" '*' ■'■'*"■ ff'T*'"* (-'••ir'rmtii ami 8»fiimihin-CM'f 
la Ih4 JtKiti Hopkins ll^pH^'f 



tasPJUMTW) FIIOM JOIIWa eOPKIKa UiWPlTAL imi-Uli. 



BAl.T IMulll-; 



L-',yf- "?■■• 



AN EIFERIHEMTAL STUDHF THE THYROID GLAND 

OF DOGS, WITH ESPECIAL CONSIDERATION OF 

HYPERTROPHY OF THIS GLAND. 



WILLIAM 3. HALSTED, M. D. 

[*ytmi Ui« FaiHuloatial LalioTMi>ru of th< Jithni iiiiphliw VntuentUu and HiMpltol.] 



(KBPUINTBD FROM JOHNt) HOl'KINd HOSPITAL UKPUKTS, VOL, I.) 






BALTIMOR^: 
The Johss II..i-itiss Pn 



• • ••• 

• • - • 


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• • • 


1 • • 


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• • 



• • 



I* 4 



•• • 

• • • • 



-TX^ — 

Hl'd 




AN EXPERIMENTAL STUDY OF THE THYROID 
GLAND OF DOGS, WITH ESPECIAL CON- 
SIDERATION OF HYPERTROPHY 
OF THIS GLAND. 



[Fiom the PathologicaL Laboratory of the Johns Hopkins UniTeFsity and 

Hospital.] 

In 1887 Munk*" made the remarkable statement that dogH survived 
experiments which deprived them of the function of the thyroid gland 
(Ausschalteversuche), provided that the wounds healed "well" by 
first intention ; but if swelling of the wound supervened, swelling of an 
inflammatory or cedematous nature, swelling dependent upon hemof- 
rhiige or upon an accumulation of the secretions of the wound, then 
very soon appeared the symptoms characteristic of extirpation of the 
thyroid gland. These symptoms, developing possibly somewhat 
slower than after extirpation of the gland, became gradually more 
and more pronounced and finally the animal succumbed. In some 
cases, those in which the swelling subsided in a short time, the 
symptoms disappeared and the dog made a perfect recovery. If there 
was an accumulation of pus in the depths of the wound, or if there 
was suppuration enough to be perceptible, the dogs, 
tion, died as promptly as if compieleextirpation had been performed. 

Munk performed his operation for complete isolation of the 
thyroid gland as follows: after doubly ligating and dividing the 
veins which leave the lower ends of the thyroid lobes and, when 
necessary, doubly ligating and dividing the vessels which go to and 
from the sides of the glands, he lifted them out of their so-called 
capsules and completely severed their active connection with the 
body of the animal by ligation of the vessels and nerves of the 
hiluB. He then returned the lobes to their original position, and in 

'HermanD Munk: nntersachungen dber die Rchilddruse. Bitiungebe- 
ricbte der kuniglich-preuseiscbeD Academie der WisaenBchaften ed Berlin, 

1887. 



order to keep them the more i>erfectly io place he tied together the 
ligatures which had been applied to their lower veins. 

Nine dogs survived Munk's isolation experiments. He does not 
give the number of his experiments. At Munk's instigation, Bogin- 
sky repeated these experiments and reported identical results. 

Particularly surprising was the statement that " whenever a con- 
siderable portion of the lobes became attached the symptoms of 
thyroid extirpation manifested themselves, and the dogs with few 
exceptions died; whereas the other dogs whose lobes had either 
entirely disappeared or had in exceedingly small parts become 
attached, remained free from all symptoms and continued to live in 
the enjoyment of good health." 

Whenever the wounds healed well by first intention the thyroid 
gland had in eight or ten days entirely or almost entirely disappeared. 
When there was a transitory swelling of the wound and when, never- 
theless, the dogs recovered from the experiment, he found even after 
from two to five months that the thyroid lobes had become attached 
and were of considerable size. Munk reserved for a subsequent com- 
munication* his explanation of these resnlts. He compelled one, 
nevertheless, to anticipate that he proposed to regard the thyroid 
glandasaeuperlluous organ and to attribute the fatal results which 
attend extirpation of the thyroid gland to injuries done to nerves. 
That the injury to the nerves should necessarily be less from the 
operation for isolation than from the operation for extirpation of 
the thyroid glands 1 could not conceive. 

Of the several unsatisfactory interpretations of the results of 
Munk's experiments which suggested themselves to me was one 
which promised for these experiments an important practical bear- 
ing upon surgery, and induced me soon after the appearance of 
Munk's paper to repeat them. Although Munk believed his experi- 
ments to be a refutation of SchiS''s transplantation experiments I 
thought that I saw in them a possible confirmation ofSchitTs work. 

Munk could not find in dogs the accessory thyroid glands which 
are probably invariably and certainly almost invariably present, and 
might, I thought, have failed to see the attached remains of an 

■ SitzungBberichte der kOuiglich-preuiMiachen Academie der Wiseen- 
Bcbaftea zu Berlin, 18S8. Munk speaks here o( lesions of the laryngeal 
and V ago-sympathetic nerves. 



I 



Sxperimfnial Study of Ou Thyroid Gland of Dogs, 375 

iBokted thyroid lobe, or to observe that a little active thyroid tissue 
remained in the otherwise necrotic gland. His isolation experi- 
ments were practically transplantation experiments; and I was 
encouraged from my interpretation of his results to believe that 
it might be possible to transplant a thyroid lobe from one dog to 
another, and a part of the thyroid gland from man to man. 

To repeat Munk's work was to make three experiments in one. 
For whatever might be the effects produced by isolation of the 
thyroid lobes the experiments would at least be equivalent to trans- 
plantation experiments under most favorable conditions, and should 
the glands become necrotio and fail to be reinstated as glandular 
organs the isolation experiments would be equivalent also to extir- 
pation experiments. 

Examples op Complete Isolation of both Thyroid Lobes. 

Example 1. Isolation of both Thyroid Lobes by Liffaiion. Munk's 
Operation. Dog 23. February 28, 1888. 

The wound was closed with buried skin sutures of silk and 
dressed with horse-hair. The dressing was held in place by a plaster 
of Paris bandage. 

March 2. The dog has trismus. Tonic spasms of his legs 
developed while his temperature was being taken. These spasms 
subsided completely before the thermometer was removed. T*m. 
39°. Resp. 33. 

March 3. The dog has conjunctivitis of both eyes. It is more 
pronounced in the left than in the right eye. 

March 4, The right eye is clear. The conjunctivitis in the 
left eye is worse. Temp. 39°. Resp. 1 9. There is a persistent erec- 
tion of the penis. There are fibrillary tremors of the tongue and of 
the muscles in general. Temp. 38.5°. Resp. 18 and labored. 

March 9. The dog drinks milk freely, but is very weak. His 
tremors are less marked. 

March 12. The dog is found dead. 

Avtopsy. The wound is beautifully healed, the cicatrix scarcely 
visible. The thyroid lobes are firmly adherent to the surrounding 
tissues. There is a greyish yellow semi-fiuid zone beneath the cap- 
sules of the thyroid lobes. The left lobe is completely surrounded 
by this zone, which is about 2 mm. thick. The right lobe is aur- 




376 



miMam B. Halsted. 



rounded only at its lower end by this zone. The upper two-thirds 
of the right lobe is of a mottled color. All the organs appear to be 
healthy. 

Microscopical Exaviinalion of the Fluid 'Subscapular Zone. The 
fluid contains no pus, but is rich in large cells which ore filled 
with fat molecules. These cells have about the size of large leuco- 
cytes. 

Microscopical Examinotioii of the Upper Port oj the Might Thyroid 
Lobe. There is an exquisite fatty degeneration of the periphery of 
the lobe. This zone of degeneration is about 3 mm. deep. In the 
central portion of the lobe the f^land structure can be made out. The 
follicles seem to be lined and sometimes partly filled with epithe- 
lium. The epithelial cells contain no fat, and the nuclei either do 
not stain at all or stain very feebly with Bismark brown. The 
cells have a homogeneous, glistening appearance. There are many 
colorless ucicular crystals (fat crystals) among the epithelial cells. 
Yellow amorphous and crystalline hamatodin is scattered through the 
central portion of the lobe and also in the peripheral fatty zone. In the 
peripheral zone the outlines of the follicles are almost lost. I^euco- 
cytes have wandered in from the capsule of the lobe along the con- 
nective tissue septa between the follicles. 

Example 2. Isolation of both Thyroid Lobes by Ligation. Dog 
24. . February 28, 1888. 

The wound was closed with buried sutures and dressed with 



I 



horse-hair. 
bandage. 

March I. 
bad effects. 

March 4. 

March 5. 

March 8. 

March 9. 

March 13. 



The dressing was held in place by a plaster of Paris 
The dog takes milk eagerly and without immediate 



Soft yellow stools. Temperature 39°. 
The dog has fibrillary tongue spasms. 
The fibrillary spasms continue. 
The dog has no tongue spasms. 
There are fibrillary contractions at the tip of the 
dog's tongue, but no other spasms. The dog drinks milk freely. 
March 1-1, The dog is found dead. 

Autopsy. The wound is beautifully healed. The tip and edges 
of the tongue have sloughed away. Both thyroid lobes are firm and 
very large and adherent to the surrounding tissues. 



Experimental Study of the Thyroid Oland of Dogs. 



877 



MicroBcopical ExaminuUon of Frozen Sections. Organization of 
the glands is going on from the periphery towards the ceutre. The 
leucocytes liave wandered in along the eepla of the glands, and new 
tissue is forming in place of tlie old which is necrotic. 

The thyroid lobes of twenty-four dt^s were isolated in the way which 
Munk describes. The wounds of twelve of these healed absolutely 
per primara.* All of the doga died in from two to nineteen days, 
and with the symptoms which are characteristic of extirpation of 
both lobes. The isolated lobes of the dogs whose wounds healed per 
primam were without exception necrosed. Absorption of the lobes 
began almost im mediately, and in some instances bad progressed so 
far that no trace of them remained except a yellowish stain of the 
tissue iu which they had been imbedded (vid. Table II). One 
dog {No. 59) remained perfectly well for sixty days after the isola- 
tion of both lobes and until killed by other dogs. His neck was so 
mangled by the teeth of the dogs that it was impossible to find the 
accessory thyroid glands or any trace of the isolated lobes. I regard 
this as one of the "very few but undoubted instances of survival 
of dogs after extirpation of both thyroid lobes. We consider it a 
very great misfortune that this dog, which interested us perhaps more 
than all of the others, should have been killed, and furthermore, so 
mangled that we could learn nothing from the autopsy. The con- 
stant or almost constant presence of accessory thyroids explains the 
fact that dogs occasionally survive the extirpation of both lobes'. 
Our piecemeal extirpation experiments have proved that some dogs 
may live with the one-eighteenih part or less of both lobes. But 
we have occasionally found the sum of the accessory thyroids to be 
apparently greater than this and still insufficient for the life of the 
dog. 

The quality of the gland and the individual requirements of the 
animal are factors about which we know little, and which may be 
more important than the actual quantity of thyroid tissue. 

* The wounde of eight doga euppumted. Two dogs die<) on the Becood day 
or too early to permit one to say positively that the wounds had healed per 
primam ; and in two InetauceB the wounds were fouod ilistended with 
blood at the autopsy. If it had occurred to me at the outset to use the buried 
skin sutures I believe that fewer cases would have suppurated ; tor of the 
five caBBB which antedated the use of buried akin sutures, four suppurated, 
and of the nineteen cases in which these BUtares were used only four suppu- 



378 



miHam 8. Hoisted. 



We have made sixty-three total extirpations of the thyroid lobee.* 
All of the doga escejit the one referred to (No. 59) died in from two 
days to three weeks, and almost invariably with the typical symptomB 
(vid. Table III). Of eighty-eight traneplantationat of the thyroid 
lobe into the neck not one was successful. In fifty-three of these the 
wound healed per primam. In two or three instances small vessels 
had invaded the periphery of the necrotic gliind and had converted a 
thin zone of the cort«x into connective tissue. In the genuine trans- 
plantation experiments the transplanted lobes were absorbed just as 
promptly as the isolated lobes in Munk's experiments {vid. Tables 
U and IV). 

Partial Isolation of both Thtboid Lobes. The Larrb 
Branch of the Thyroid Artery which goes to the 
Upper Pole and the Vein from the Lower Pole abb 
sot Ligated; otherwise both Thyroid Lobes are com- 
pletely ISOLATED. 

Example 1. Dog 104. April 19, 1889. Open wound. 

April 28, The dog seems perfectly well. The wound is healed. 

April 30. The dog has tongue tremors and makes the licking 
movemeDts with the tongue which we have frequently observed in 
dogs whose thyroids have been extirpated. 

May 1. The tongue tremors are leas pronounced. The licking 
movements are still vigorous. 

May 7. The tongue tremors are pronounced. The dog has no 
general spasms. 

May 14. The tongue tremors are very faint. 

May 28. Dog seems perfectly well. 

June 24. Hair is falling out, particularly over the eyes. 

June 25. The dog has escaped. 

June 27. Returned of his own accord. The hair is very thin 
all over his body. He scratches himself constantly. The oedema 

■Thirty-seven of these are recorded as such. Twentj-sii piecemeal 
experimentaare not eo recorded, for they are at interest chiefly in tliis, tliat 
they were made to determine approximately the time of the Gret indications 
of hypertrophy in one lobe after excision of the other. 

IMuDk's isolation experiments, as already explained, are equivalent to 
trans plantations, and have been counted as such. 



1 



Experimmtal Study of the Thyroid Gland of Dogs. 379 

caused by the scratching gives to the akin about the face and head 
somewhat the appearance of myxoedema. 

July 10. Has lost most of his hair. He is very ansemic. His 
blood is used for direct transfusion into dog 109. 

Autopsy. Both thyroid lobes are large and hard and very firmly 
bound down to the surrounding tissues by adhesions. With the 
microscope they were found to be hypertrophied. I believe, judging 
from the next example (dog 103), that this dog would have died ulti- 
mately with the symptoms of thyroid extirpation. 

Example 2. Dog 103. April 19, 1889. The wound is left 
open. The dog was profoundly depressed after the operation. 

April 27. There is conjunctivitis of both eyes. The wound Is 
doing well. 

April 28. The dog has symptoms which are characteristic of 
extirpation of both thyroid lobes. He shivers, has tongue tremors 
and general tonico-clonic spasms. His gums are inflamed. The mem- 
branie nictitantes are conspicuous. He groans with each expiration. 

April 30. The tongue tremors persist. The general spusma have 
ceased. The conjunctivitis is more pronounced. There is a very 
offensive gingivitis. Dog makes peculiar, almost incessant licking 
movements with his tongue. These peculiar licking movements 
have been frequently observed by me in dogs whose thyroid glands 
have been extirpated. 

May 1. Seems better. He still has tongue tremors, 

May 3. His hind legs are slightly stiff. The tongue tremors are 
scarcely perceptible. 

May 7. The tongue tremors are a little more distinct. The oon- 
juDCtivitifi has almost subsided. 

May 14. The tongue tremors are very faint. There is no con- 
junctivitis. 

May 19. All the symptoms of extirpation of both thyroid lobes 
have reappeared. 

May 21. The dog seems much better. The tongue tremors are 
very faint. There are no other symptoms. There is a slight sub- 
conjunctival injection. 

May 23. Except forthe taint tongue tremors the dog seems fairly 
well. He eats well, but is very thin. 

May 24, Has no tongue tremors, but strong clonio spasms of the 



WiUiam 8. . 

flexor muBcles of all of his legs. The spaEiuB of the temporal and 
ear muscleB are especially pronoimced. 

May 26. Dog has no spasms and is much better. 

June 14. All the symptoms of double extirpation have re-ap- 
peared. 

June 15, A. M. Is found dead. 

A'utopsy. The left thyroid weighs 3 grms. and is very hard. 
The right thyroid weighs 1 grm. For the microscopic appearance 
of both lobes see Plate X, Fig. 7. The fatal result in this and the 
preceding case (104) is to be attributed probably to extensive 
destruction of the glands by blood extravasation. Otherwise we could 
not regard the changes which we designate as hypertrophy as very 
highly compensatory ; for, notwithstanding the fact that the glands 
weighed two or three times as much as normal and.showed the most 
advanced stage of hypertrophy, one dog died with symptoms of total 
extirpation and the other had the symptoms which I have described 
(dog 104], and would probably have died of thyroid privation. 



Piecemeal Extirpation of the Thyroid Gland. 

Example 1. Dog 81. OperaUon 1. Oct. 4, 1888. Removed 
the lowir half of the lejt thyroid lobe. The piece removed weighs 
0.45 grm. and is normal. The wound was leA open and without a 
dressing. 

Oct. 13. The dog seems quite well. His gums are abnormally 
pale. There are no symptoms of thyroid extirpation. 

Nov. 22. Has been quite well since the operation. 

Operation 2. Nov. 23. Fifty days after the first operation. 
Removed the upper, the reiaaiiiing half of the left thyroid and the 
lower third of the right thyroid lobe. The wound was left open and 
without a dressing. The upper half of the left thyroid weighs 0.70 
grm. The right gland is large and would weigh about 2 grms. 

Nov. 24. Seems perfectly well. 

Deo. 5. The dog has apparently been well ever since the last 
operation. The membransa nictitantes seem to be abnormally con- 
spicuous. 

Jan. 10, 1889. Three or four days ago began to cough. He ia 
less lively than heretofore, and has a slight conjuuctivitis. He eats 



ExperimerUal Study of Vie Thyroid Gland of Dogs. 381 

Feb. 1. Acts as if he were partially blind and abnormally 
stupid. He doea not see meat which is thrown to him; he finds 
it by the sense of smell. Dr. Randolph has to-day examined the 
dog's eyes ophthalmoscopically and pronounces them normal. 

April 30. Is stupid and partially blind ; otherwise apparently 
well. 

Operaiion 3. April 30. Removed the lower half of what remained 
of tfie right thyroid — its middle third. The piece removed weighs 
1 grm. 

August 9. The dog is well', but is slow to see and catch his 
food. 

Operation 4, August 9. Retiioved the second sixth of tlie right 
thyroid gland — the hirer half of the remaining third. There remains 
to the dog one-sixth of one thyroid lobe. 

August 24. Has been well since the last operation. This A.M. 
he was strangled to death by the impaction of a large piece of meat 
in his cesophflgus. 

Aiitopay, The dog is very well nourished. The wound ia healed. 
There are two accessory thyroids under the arch of the aorta, and 
one at the lower border of the liyoid bone on the thyro-hyoid mem- 
brane. All the organ.i are apparently healthy. The aortic thyroids 
show a more advanced stage of hypertrophy than does the gland 
which was found on the thyro-hyoid membrane. Usually the accee- 
HOry thyroids and the remainder of the thyroid lobes are hyjiertro- 
phied to a like degree. 



Piecemeal Extirpation of the Thyboid Glasd. 

Example 2. Dog 86. Operation 1. Oct. 23, 1888. Excised 
tiie lower half of the left thyroid lobe. The wound is left open 
and without a dressing. The piece weighs 0.6 grm. Its structure 
is normal. 

Dee. 12. Dog has beeu perfectly well since the first operation. 

Operation 2. Deo. 12. KvciM-d tlie upper half of the hft and the 
lower half of the right thyroid lobe. The wound was left open and 
without a dres^^ing. The upper half of the left thyroid lobe weighs 2 
grms., and the lower half of the right 1 grm. The left lobe was 
slightly adherent to the surrounding parts. For the structure of 



382 



thi 



William S. Halsled. 



I see Plate X, Figa. 5 and 8, and Plate IX, 
Dog has been perfectly well since the last opera- 



pieces removei 
Fig. 8. 

Feb. 12, 181 
tion. 

Operation 3. Feb. 12, Excised one-half of the rt-mainhiff upper 
half of the right lobe (ita second fourth). The wound is left open. 
The excised piece is typically hypertrophied {vid. Plate X, Fig. 8). 

April 27. Dog has been perfectly well since the last operation. 

Operation 4. April 28. Excised the lower half of the remaining 
upper fouHk of the right lobe — the second eighth of the right thyroid 
(vid. Plate X, Figs. 6 and 7). 

There now remains to the dog one-eighth of one thyroid lobe, or 
one-sixteenth of the gland. 

May 19, A. M. Is found dead. Has had all the symptoms of 
double thyroid extirpation for about two weeks, and has refused 
food since May 2. 

Aviopsy. The wound is healthy and nearly healed. Over the 
thyro-hyoid ligament in the median line, and partially concealed 
behind the hyoid bone, is an accessory thyroid about the size of a 
very small bean. The remaining eighth of the right lobe weighs 
about 0.8 grm. 

There is a small bean-like accessory thyroid gland under the 
skin about one inch above the sternum; also a chain of four en- 
larged aortic thyroids. The accessory thyroids have the structure 
which we call hypertrophy. The hypophysis cerebri has the size of 
a large French pea. All the organs appear to be healthy. 



PiBCEUBAL ExTIltPATION OF THE TlIYKOID GlAND. 

Example 3. Dog 90. Operation 1. Oct. 1888. Etcised the 
loKCf half of the left thyroid lobe. The wound is left open and 
without a dressing. The piece removed weighs 0.3 grm. Its 
structure is normal. 

Nov. 20. The dog has been fairly well since the operation, but 
his hair is falling out. He is entirely bald about the right eye. 

Dec, 30. Has a cough and been quite sick for three or four 
weeks. Has probably had pneumonia and is now convalescing. 

Jan. 29, 1889. The dog has been well since Jan. 1. 



i. 



Ei^pmmenial Sltidy of the Thyroid Glaiul of Dogs. 383 

Operation 2. Removed the uppei' half of the kft and tlie lower tieo- 
fifthti of the right thyroid lobe. i 

Both lobes seem to be hjpertrophied, and both are adherent to 
the surrounding tissues. The left one is very firmly bound down 
by adhesions. For the stage of hypertrophy of the pieces removed 
see Plate X, Fig. 8, and Photo. V. 

April 30. The dog has been perfectly well since the last opera- 
tion. He is sire to the pups with the enormously hypertrophied 
thyroids thrown by bitch 97 on the 13th of April. 

Operation 3, April 30. Bemovid the lower half of the remainivg 
thret-fiftha of tJie right thyroid lobe. The piece removed weighs 
1.5 grm. For the minute structure see Plate X, Fig. 8, and Photo. 
V. 

June 20. Since the last operation the dog has been growing 
sluggish and stupid. When released from his cage he takes a few 
steps and then lies down. He has hiid no convulsions nor tremors. 

June 21. Died this morning. 

Autopsy. The remaining portion, the upper three-tenths of the 
right thyroid lobe, weighs 2 grma. For the'structure see Plate X, 
Figs. 6 and 8, and Photo. V. It is very firm and has a nearly 
globular shape. Accessory thyroid glands were not found at the_ 
autopsy which, however, was made in my absence. There is general 
pulmonary (edema. The other organs appear to be healthy. Th6 
dog was not emaciated. There is no apparent cederaa of the subcu- 
taneous tissues. 



Piecemeal Extirpation op both THYitoiD Glands. 

Example 4. Dog 97. Operation 1. Nov. 14, 1888. Removed 
the upper t/iird of the left lobe. 

The piece removed has u normal structure. The wound was left 
open. 

Dec. 12. The dog (bitch) has been perfectly well since the 
operation. 

Operation 2. The neck w>as opened ihrov^h the cicatrix for the 
purpoxe of remoring what remained of the left thyroid. 

The ligature which had been applied at the first operation was 
found imbedded in a little new tissue. iNot a trace remained of the 
left thyroid. 



384 



miliam 8. HaUfrl. 



April 11, 1889. The bitcli is at full term. Has coiivulaioiiB and 
behaves precisely as do the dogs whose thyroids have been com- 
pletely extirpated. 

April 12. Had to-day three or four convulsive seizures. Each 
attack IaHt«d about one hour. Otherwise the bitch seems well and 
in good spirits. 

April 13. Bitch has whelped five pups. Two alive and three 
dead. Dog 90 is aire of the pups. He impregnated this bitch when 
he had been deprived of all of one lobe and two-fifths of the other, 
and when she possessed only one lobe. The pups which were born 
alive died this evening. The thyroid glands of these pups are many 
times (at least 20 times) larger than normal. See Plate X, Fig. 9, c 
Compare with normal thyroid of new-born pup, Fig. 9, a, and 
photographs. 

Operation 3. April 30. Rivioved tht lower half of the right iltyroid 
ghind. The gland is very large and decidedly spindle-shaped. It 
is hypertrophied. See Plate X, Fig. 7. 

Nov. 11. Has been well since the last operation. 

Opfration 4. Nov. 11. Rniiorcd what I liellevcd to bi' thv second 
Jourik—Uif lower half of tbf rrmainhig half —of the right thyroid lobe. 
, Jan. 1, 1890. Tlie piece removed Nov. 11th was to-duy exam- 
ined and supposed to be lymphatic gtand tissue. Unlbrtunately 
the specimen of this piece has been lost. 

I now suspect that it was thyroid gland and not lymphatic* tissue. 

Operation 5. Jan. 6. Explored the right side of the dog's neck 
very carefvlly. Could find vofhing Irtit a manll nodule, at the lower 
end of which was whut seeined to be a ligature of tlie previous operation. 
Removed fhii nodule. It proved to be hypertrophied thyroid tisene. 
Vid. Plate X, Fig. 7. 

Jan. 13. The dc^ has tongue tremors and general spasms and 
behaves as do the dogs whose thyroids have been extirpated. 

Jan. 14. Is dead. 

Autopsy. Nothing remains of either thyroid lobe. An unusual 
number of hypertrophied accessory thyroids are found ; viz., one in 
front of the arch of the aorta ; three behind the arch near the origin 
of theductuB Botali ; one largegland, 3nim. X4mm.,behind the ster- 



* We have twice labeled a 
qiiently (ound to be tbyroid ti 



lymphatic t 



ich we subBe- 
itreme stage of hjipertrophy. 



Experimental StuSy of (ke Thyroid Gland of Bogs. 385 

num. For the minute stnicture of these hypertrophied glands vid, 
Plate X, Fig. 7. This figure is intended to represent the moet 
advanced stage of hypertrophy ; but it is very badly executed. 



Piecemeal Extirpation op the Thyr 



I Glan 



Example 5. Dog 126. Operation 1. Dec. 1888. The lowrr 
end of the hfl thyrokl gloml wan ligaied at about 2 mm. above itji tip. 
The wound is lefl open. 

April 22, 1889. The dog has been perfectly well since the operation. 

Operation 2, One hundred and thirty-two days after the first 
operation. Remored the remainder of the left mid the lower two-ffth'i 
of tjie right thyroid gland. Both glands were hypertropliied, Vid. 
Plate X, Figs. 6 and 7, and photograph. There were no adhe- 
sions binding the thyroids to the surrounding tissues. The tied-off 
tip of the left lobe is converted into connective tissue. Here and 
there traces of follicles remain in this tip.* 

Aug. 9. Dog huB been perfectly well since tlie last operation. 

Operation 3. Reutoced the loirei- half of the remaining three-fifths 
of the. right Uiyroid gland. 

For the minute structure vid. Plate X, Figa. 6 and 7. 

JTov. 11. Dog has been very weak since the third operation and 
was scarcely able to walk when he was put on the table to be 
aneesthetized. 

AiUopHy. What remains of the right thyroid gland weighs 0.76 
grm. and is hypertrophied. Four accessory thyroids were found, 
two below and one behind the arch of the aorta, and one behind the 
hyoid bone at the upper end of the thyro-hyoid membrane. The 
accessory thyroids were all hyjwrlrophied, although verysmail. Not 
one of them was larger than a grape-seed. The dog has no 
myxocdema. For the minute structure of the hypertrophied acces- 
sory thyroids vid. Plate X, Figs. 5 and 8, and Photo. V. 



Piecemeal E.xtirpation of the Thyroid Gland. 
Example 6. Dog 127. Opmtdon 1. Dec. 11, 1888. Ligated 

Vie lower end of the left thyroid gland at about 3 mm. from its tip. 
The piece ligated was not cut off. The wound is left open. 

•In dog 127 the tied-off lip retained its original structnre, and llie opera- 
tion (ligation of tip) was not followed by hypertropliy. See Example 6. 



386 



mlHtm S. Halttti. 



^ 



April 22, 1889. The dog has been perfectly well since the opera- 
tion. 

Operation 2. Removed the remainder of ike left thyroid and fhe 
lower third of the right thyroid gland. The wound was left open. 
The pieces removed were, much to my surprise,* normal 132 days 
after ligation of the inferior tip of the left lobe. 

August 30, About nine weeks ago the bitch was impregnated by 
ft good-sized, healthy, unoperated dog. 

She is about at full term and has to-day developed the symptoms 
characteristicof extirpation of both thyroid glands. She has tongue 
tremors and general clonico-tonic spasms. 

Sept. 1. Last night she gave birth to eight dead pups and seems 
perfectly well this morning. The thyroids of these pups are at least 
twelve times as large as normal. 

Nov. 11. The dog has been well since the last note. 

This is the second opportunity that we have had to observe the 
effect of pregnancy upon a bitch deprived in part of the thyroid 
gland. In both cases for a few hours, less than twenty-four, just 
prior to whelping the symptoms of complete thyroid privation mani- 
fested themselves although each animal still possessed much more 
than enough thyroid gland for her ordinary wants. 

It is interesting to note tliat pregnancy has already been supposed 
to have an influence in producing tetany, and that in at least two or 
three instancest it has been suspected that the tetany was caused by 
the complete or partial absence of the thyroid gland. 

Operation 3. Remortd tlic lower half of the remaining two-thirds 
of the right thyroid gland. The gland is large, hard and very vas- 
cular, and shows, microscopically, an early stage of hypertrophy. 



*lBa7 much to i»r turprtH, because in the preceding case (dog 126) the 
BRiue operation was followeti by bvperlropb; in the eame number (132) of 
days. But longitudinal eectione of tbe entire lobes revealed the cauae of tbe 
hypertrophy in the one case and the reason for its absence in the other. In 
botti caaea fragments of the ligature were found imbedded in a narrow con- 
nective tiBHue zone two or three millimeters above the inferior pole ; but in 
127 tbe gland tissue below the ligature was intact or very Blightly modified 
by a little increase In connective tissue, wbereas In 126 only an occasional 
trace of the gland remained. 

f Thomas, H. M. Tetany in Pregnancy, Johns Hopkiaa Hospital Bulletin, 
May 20, 1895. 



Exip&imetUal Study nf the Thynttd Qland of Bogs. 



387 



Jan. 14,1890. The dog baa been perfectly well since the last 
operation and has grown very iat. 

Opernflon 4. Jteinoi-ed tkf- lower Iwo-thirdu of ihe remainiiig upper 
third — the second and tiiird ninths — of tJie right thyroid gland. 

The piece removed weighs 1.5 grms. It shows, microscopically, 
an advanced stage of hypertrophy. The gland was very adherent to 
the tissues surrounding it. 

The dog is now reduced to one-eighteenth of both thyroids. The 
pieue remaining — the upper ninth of the right thyroid — would prob- 
ably weigh as much as the entire right thyroid originally weighed. 
The dog has been getting steadily fatter since the first operation, and 
now ia enormoualy fat and well. There are no e\-idence8 of myxce- 
dema. The dog seems mentally as active as ever. 

Operation 5. Jan. 1891. Removed the superior ninth, the 
remainder of the right thyroid gland. 

The dog died within three days of the last operation. 

Autopsy. A chain of accessory thyroids was found behind the 
arch of the aorta, and one accessory thyroid on the thyro-hyoid mem- 
brane, behind the hyoid bone. 

These glands were not as large aa I have several times found 
them. They were preserved, but cannot be found. What I have 
eaid about them is from memory. 

The piecemeal resection experiments demonstrated conclusively 
that the symptoms which manifest themselves atler extirpation of 
both thyroid lobes are due to the loss of thyroid tissue, and not to 
the injury to the nervee of the neck, as Munk and others have 
supposed. 

What part of both lobes a dog requires we have not tried to deter- 
mine. It is probably never precisely the same for two dogs, and 
may depend somewhat upon the time allowed to intervene between 
the operations. Very few dogs can live with the accessory thyroids 
alone. 

Dog 81 survived the excision in four operations of eleven-twelfths 
of the two thyroid lobea. He was in good condition when he died 
of strangulation from swallowing too large a piece of meat. Three 
small accessory thyroids were found at the autopsy. 

Dog 86 enjoyed good health with one-eighth of the two lobes ; but 
he died twenty-one days after the fourth operation, at which he was 



WiUiam 8. Raided. 



reduced to one-sixteenth of the two lobes. The fourth operation was 
performed six monthB after the first operation. For two weeks 
before his death he had the symptoms character! s tit; of total exci- 
sion. At the autopsy five accessory glands were found, and the 
remaining piece of the hypertrophied right lobe weighed nearly one 
grm. 

Dog 90 was reduced to about one-tenth of both lobes in six 
months by three operations. He died three weeks after the third 
operation, without active symptoms. The superior fifth or perhaps 
three-tenths of the right thyroid which was excised at the autopsy 
weighed one and one-fifth grammes. 

Dog 97 when deprived of only one lobe developed the typical total 
extirpation symptoms a few hours before her pups were bom. 
Nevertheless she recovered completely from the two subsequent 
operations and did not die until the final fragment of the right lobe 
was removed at the fifth operation. She died oneweek after the last 
operation — fourteen months after the first operation, and when noth- 
ing remained to her of the two thyroid lobes. An unusual number 
of accessory thyroids were found at the autopsy. What proportional 
part of both lobes the final piece represented I cannot say. 

Dog 126 lived only three months with about one-tenth of the two 
lobes and with at least four accessory thyroid glands. The four 
operations were performed in eleven months. 

Dog 127 enjoyed good health with one-eighteenth of the two lobes. 
This eighteenth weighed almost as much as the two lobes normally 
weigh. He died after the fifth operation, two years after the first 
operation, and not until the final piece had been excised. The 
accessory thyroids were not as large as we had expected them to be, 
nor as large as we have several times found them. 

One of the most interesting discoveries to which our ex|ieriments 
led was the hypertrophy of the thyroid glands of the new-born pups 
of dogs whose thyroid lobes had been in part excised. The glands 
of all five of the pups of bitch 97 were about twenty times as large 
as normal. See Plate X, Fig. 9, a and c, and Photograph 10. In 
all of the pups the two lobes seemed to be connected by a deep 
isthmus. Vid. Plate X, Fig. 9, u, and Photograph 10. The 
lobes and isthmus together made a horse-shoe -shaped gland which 
embraced and almost surrounded the trachea. Our efforts to con- 



t of tha Thyroid Oland of Doge. 

firm this tliacovery were rewarded in less than a year by a litter of 
eight dead-born pups from bitch 127. (See full history.) The thy- 
roid lobes of these pups were connected by a very short, thin 
isthmus, and were at least twelve times as large as normal. 

Later a third litter of five pups, presumably at first from unoper- 
ated parents, was discovered in the kennels of the laboratory by the 
janitor, John Schutz, to whom I am greatly indebted for most intelli- 
gent asaistauce in ray experimental work. The thyroid lobes of 
these pupa were, much to my surprise, almost as large as the thyroid 
lobes of the pups of bitch 127, and for a short time our theory 
seemed to be insecure. Upon investigation, however, we found 
that the mother of the pups had been twice operated upon. The 
first operation was a laparotomy for the introductioD of a syringe- 
ful of a bouillon culture of staph, aureus into the abdominal 
cavity. A few months later the left thyroid lobe of this bitch had 
been excised, and found on microscopical examination to be hyper- 
trophied. Impregnation occurred after the excision of the left 
lobe of the thyroid gland. The bitch was killed soon after the pups 
were whelped, and the above facts verified by the autopsy. The 
right lobe showed an advanced stage of hypertrophy. 

We were, accordingly, so fortunate as to have three Htters of 
puppies from bitches deprived in part of the thyroid gland. Bitch 97 
was impregnated by dog 90, after his left and two-fifths of his right 
lobe had been excised. The other two bitches were impregnated 
- by normal dogs. The thyroid glands of the puppies of bitch 97 
were much larger than the glands of the puppies of the other litters. 
The former were, as I have said, about twenty times as larg^ as our 
largest normal gland of a puppy at birth, whereas the latter were 
only twelve and ten times as large as they normally should be. In 
the minute slructure, too, the former differed somewhat from the 
latter ; for there was absolutely no colloid, and rarejy a trace of a 
vesicle in the very large glands of the former, \vhite in the latt«r 
there were still a very few vesicles and still occasionally a trace of 
colloid. The normal gland of a puppy at birth has many acini 
filled with colloid, but they are much smaller and much less pre- 
ponderant than in the adult gland. The epithelium is much higher 
and the colloid much thinner in the puppy's than in the adult gland. 
The structure of these greatly hypertrophied glands of puppies 
resembles closely that of the glanduta parathyroidea. 



William S. HaUtetl. 



It occurred to us, naturally, to inquire whether hypertrophy of the 
thyroid lobes might not occaeionally exist in dogs whose neck had 
not been molested. I excised, accordingly, the left lobes of five dogs 
into whose abdominal cavities some months previously syringefuls 
of a bouillon culture of staph, aureus had been introduced. The 
thyroid lobes of fonr of these dogs were hypertrophied. 

The lobes of a dog which had fallen from the third-story window 
of the laboratory were hypertrophied. 

Those of a dog which had just recovered from pneumonia were 
hypertrophied and most of the follicles were tilled with cells, 
whereas those of a dog which had died of pneumonia were normal. 

The thyroid glands of two dogs which had been confined for a long 
time in the laboratory were not hypertrophied. 

Dog 136 was inoculated, February 4, 1890, with diplococous 
pneumoniiG. Fourteen days later the left thyroid lobe was normal. 

Dog 1-51, March 3, 1890. Excised the greater part of the left 
humerus for blood elot experiment. Dead space allowed to fill with 
blood. March 24, three weeks later, ana-sthetized to death. Ad- 
vanced hypertrophy of thyroid gland. 

The janitor, John Schutz, who, as I have said, took a most intel- 
ligent interest in these experiments, examined for us the thyroid 
lobes of one hundred dogs in the city pound. Certainly one and 
probably two of these dogs had hypertrophied glands. 

The left Ipbes of the dogs used for complete or piecemeal extir- 
jiation experiments were without exception, on microscopical exam- 
ination, found to be normal. 

The value of the closed wound experiments may well be ques- 
tioned, for it will be observed that most of the dogs with closed 
wounds and plaster of Paris dressing died sooner or later, irrespec- 
tive of the experiment. The one-sided transplantations and isola- 
tions, for example, resulted eventually in the death of the animal. 
These experiments should not ordinarily have been fatal. In some 
instances pneumonia, perhaps due to distemper, was the immediate 
cause of death. But in most cases the dogs died with a peculiar 
scurvy-like cachexia, ia which most of the dogs with closed wounds 
and plaster of Paris dressing during the year 1888 succumbed. 

Hence we cannot consider the question as to the possibility of 
transplanting the thyroid lobe into the neck of another dog as posi- 



Doffs. 

tivelv settled. We cannot account satisfactorily for the peculiar 
Bcurvy-like cachexia which bo many of the dogs with closed wounds 
developed. 1 am inclined to suspect that it may have heen due in 
some way to the confinement caused by the dressing. The wounds 
were covered with a large pad of horse-hair, and this was held in 
place by a plaster of Paris bandage which immobilized to a certain 
extent tlie neck and the forelegs of the dogs. 

Not one of the many dogs with oi>en wounda developed this pecu- 
liar condition, nor did one of them die until enough, and usually 
more than enough, of his thyroid lobes had been excised to account 
satisfactorily for his death. 

On September 20, 1888, Dr. Welch kindly presented at the meet- 
ing of the Association of American Physicians in Washington, an 
abstract of my experimental work on the thyroid glands of dogs and 
described the hypertrophy of these glands, upon which especial 
emphasis was laid. He demonstrated microscopical sections of tJie 
glands, and reported regarding the histological changes character- 
izing the hypertrophy and the conditions under which hyjwrtrophy 
was observed. Dr. Welch's remarks on this subject were published 
at the time,* but they have escaped the notice of subsequent writers. 
Our published obBervations concerning hypertrophy of the thyroid 
gland, which will now be described in detail, date from the year 1888. 

Before the first publication of my results in 1888 there was little 
evidence that after extirpation of a part of the thyroid gland the 
remainder hypertrophied. 

Horeleyl" and WagnerJ were the only ones who thought that they 
had observed hypertrophy of one lobe after excision of the other. 
Wagner's testimony was supported merely by his belief that in two 
instances the remaining lobe was larger than the one first extirpated; 
but Horsley had with the microscope observed changes which were 
described as follows : "The acini were found to undergo very remark- 
able changes. The epithelial cells lining them multiplied in num- 
ber and increased in size, so that there was a plication of the acinal 



• The Kew York MeJiual Record, 188S. The Medical News (Pliilailelpliia). 
1888. 

t Horsley : The Pathology of the Thyroid Gland, Luncet, Dec. 18. 1886. 

t Waiiner : Ueber die Folgen der Exatirpation dcr Schilddrilse nach Ver- 
siicbeD an Thieren. Wien. Med. Blntter, 1884, Nob. 26 an<I 30. 



392 



mmnm 3. Halsted. 



wall. The full reason for tliis folding was not clear. There was 
no increase in the number of the parenchymatous cells of Weber, and 
no metamorphosis of the embryonic tissue into acini. The colloid 
material did not increase in amount, but chanj^ed in consistence, 
became softer, more viscous and less solid, so that at one time it 
appeared like a network of viscosity, and later on had a watery 
aspect. Increased activity of the organ appeared therefore to caiite 
a diminution in the consistence, and this was contrasted with the 
greater soliditication of the acinal contents that occurred when the 
function was less active." " If the animal wasted after the removal 
of the lobe of the thyroid gland, then there need be, and probably 
would be, no hypertrophy of the remaining lobe." Horsley gives 
Lorenz credit for Insisting on the importance of this mutter of 
weight in determining hypertrophy, and has himself observed that 
if one kidney is e.xcised and the animal loses in weight, the other 
kidney does not hypertrophy. I am not sure that this statement 
should not be reversed. I believe rather that the loss of weight 
was due to the fact that the remainder of the gland did not become 
hypertrophied, than that the abseuee of hy|iertrophy was caused by 
the loss of weight. 

Fuhr* afiirmed unreservedly that the observation of Wagner as to' 
the hypertrophy of the remaining portion of the gland was disproved 
by his experiments and by those of Sanguirico and Canalis.t 

To determine this point, Fuhr made six experiments. 8, 25, 27^ 
28, 33, aud 41 days intervened between the first operation when oue 
lobe or parts of both lobes were removed, aud the second operation 
when the remainder of the gland was excised. A glance at my table 
of hypertrophies (Table IV) will perhaps explain bow it could 
happen that Fuhr did not in these esperiments obtain hypertrophy 
of the thyroid gland. 



p. 449. 

iXtirpated 



*Fahr: Archiv fiir espenmentelle Patliologie, No- 31 
t Sanguirico and CanaltB: PrcmiC-re communication preli 
ives Italiennes .le Biologie, T. V. 1884, p. 3110. These investigati 
one entire lobe and the superior two-thirdsof the other lobeof two animals. 
Both animalH died, one on the third day, the other on the g^xth day. The 
remainiag pieces, as we should expect, showed no change ; the time waa 
too short for the development of hypertrophy. In two instances they extir- 
pated one lobe and the interior two-thirds of the other lobe. Both animals 
lived. The remaining piece was not examined in either case. 



ExperiTMmtal Study a/ the Thyroid Gland of Dogs. 393 

With two exceptione I did not encounter advanced hypertrophy 
until after the 43rd day. Fuhr might nevertheless have had hyper- 
trophy in every case except the one in which only eight days inter- 
vened between the two operations, and we might have expected it in 
the 41-day case. The fact that hypertrophy did not occur in this 
last case was probahly due to the natureof the experiment; for all of 
the arteries and veins at the hilus of both lobes were ligated and the 
upper poles of both lobes exsected. 

Mr. Horsley was in America in 1889 and it gave me pleasure to 
show him my Bpecimens. In 1891, in his famous article on the 
function of the thyroid gland,* he very courteoualy declines to say 
anything about the microscopic changes in the hypertrophied thyroid 
gland, and refers for this to my workf which was to have been pub- 
lished four or five years ago. 

Notwithstanding the fact that Dr. Welch, in his abstract of my 
work on hypertrophy, described more than seven years ago the prin- 
cipal changes in the structure of the gland, subsequent writers and 
investigators do not seem to suspect that a structural change is to be 
looked for in hypertrophy of the thyroid gland. Nor has any one 
observed the hypertrophy which almost invariably takes place in the 
remaining thyroid lobe within perhaps 40 days of the time of the 
removal of the other lobe. The isolated observations of Wagner 
and Horsley are referred to with scepticism or are discredited, and 
my work seems to have escaped observation, von EiselsbergJ per- 
formed on two oats extirpation of both lobes in two acts. Seven 
and fourteen days intervened between the acta in these cases. That 
hypertrophy of the remaining lobe might not take place we can 
readily understand; the time was almost too short. He believes, 
however, that there was " uvideute hypertrophic " in four of fourteen 
transplantation experiments, I am inclined in this instance to 
doubt the observations of this excellent investigator, because (1) he 
trusted to naked eye appearances, and (2) the time which elapsed from 



• Horsley: Die Fiinctiou derSchilddriiee ; Bine higtorisch-kritiBcbe Studie. 
Internationale Beitriige zur wiasenHChaFtlichen Medicio (Festschrift, Bu- 
dolpb Vircliow, gewidmet), Bd. I, p. .169. 

IHoreley : he. «(,, p. 387. 

{Anton Biselaberg: Ueber Tetaate in Aasscblusse an Kropfoperationen. 
Wien, I8i)0, Alfred Tlalden. 



394 



mniam S. HalaU<i. 



the removal of the first lobe for transplantation to the removal of 
the Becond was too short (3, 4, 4, 11, 11, 14, 15, and 15 days) for 
the development of this hypertrophy. The diagnosis of hyperlrophy 
cannot be made with the naked eye. There are eertain structural 
changes which are uniform and constant in hypertH'phy and without 
which we cannot venture to assert that it is present. Even if there 
were no changes in Btructure, the naked eye, handicapped by memory, 
might easily make a wrong eetimate as to size. Furthermore, an 
absolute increase in volume and weight might be due alone to tissue 
iniiltratioii. Hypertrophy of the thyroid without change of struc- 
ture at some period of its evolution is, as I have said elsewhere, 
inconceivable. Apparently the only observations of von Eieeleherg 
in this series which were controlled by the microscope were the only 
ones in which he would have been at all likely to encounter hyper- 
trophy, and in these he says it was not present. I refer to two cases 
in which the intervals between the operations were 21 and 115 days, 
von Eiselsberg's description of the microscopic appearances in 
the latter case interests me very much. He describes conditions 
which in the dogwould indicate hypertrophy — at least an ear)y stage 
of it. 

He says, "The injected material (artificial injection of the blood- 
veasels) penetrated everywhere even into the transplanted (between 
peritoneum and fascia) gland in which, as in normal animals, the den- 
dritic branching of the vpssels could be observed." "In some 
places the colloid degeneration which often occurs normally was to 
be found in the interior of the vesicles." This dendritic branching 
of the blood-vessels is one of the characteristic structural changes 
in the hypertrophied gland of the dog, and produces or keeps pace 
with the production of the involutions into the follicles. What von 
Eiselsberg designates as colloid degeneration is possibly the change 
in the colloid which we always observe in hypertrophy. It becomes 
thin and vacuolated, and after a time disappears entirely. 

Wagner* is regarded as the aulhority for the generally accepted 
notion that the thyroid gland hypertrophies aftera part of it has been 
removed. In support of his views he has only two observations to 
offer, one upon a dog and one upon a cat. In the case of the dog, 35 
days intervened between the first and second operations. The lobe 

* Wien. Med, Biiitler, So. 30, p. 1132. 



Experimenio! Study of the Thyroid Qtand of Dogs, 395 

which waB supposed to be hypertrophied had 35 days for the devel- . 
opment of thehypertrophy.-'Wagiierdoesnot givetbe dateof the sec- 
ond operation upou the cat, lience we do not know how long a time 
the cat's thyroid had in which to become hypertrophied. We know 
(see Table No. rV') that hypertrophy is poesible in 15 days, but we 
consider such early hypertrophies as exceptional. It Sb more than 
probable that Wagner observed hypertrophy in the case of the dog, 
although a microscopic examiuatiou of the gland was not made. 
His description of the enlarged thyroid arteries is quite convincing. 
I have repeatedly made the same observation, viz. that the thyroid 
biood -vessels, arteries and veins, of the hypertrophied lobe seem to 
be dilated or enlarged. But cue cannot make a positive diagnosis 
of hypertrophy from the naked eye appearances. At one time, after 
considerable practice, I thought that I could, without the microscope, 
diagnosticate the existence of hypertrophy, but I discovered subse- 
quently that my diagnosis was fallible. I believed that a certain 
succulence, due, so I thought, in part to the high epithelium and 
perhaps principally to an increase in vascularity, was characteristic 
of hypertrophy, particularly when at the same time the color of the 
gland indicated an uniiaually great blood supply. But I have found 
microscopic evidence of advanced hypertrophic changes in glands 
that seemed to be unusually hard and that looked more aneemicthau 
the normal gland. Hence the microscope must, as I have said else- 
where, be our criterion of hypertrophy. 




The Struotcre op the Hypertrophied Thyroid Glands. 

In the normal gland of the dog the follicles as they appear in sec- 
tion vary in size more than in shape. They incline to roundness in 
shape, are lined by a single layer of cubical, sometimes almost flat 
epithelium, and are filled with an apparently homogeneous substance 
called colloid. This colloid material is semi-solid in the normal gland 
and seems to distend the follicles. Even in the hardened specimen a 
cleft between the colloid and the cells which line the follicle is 
exceptional. 

The thyroid gland is richly supplied with blood-vessels. Each 
follicle is embraced by a vascular network. The distribution of the 
small vessels and capillaries assists one greatly in the interpretation 



»96 



WilHam 8. HaMM. 



of the minute anatomy of the bypertrophiad gland. Even in the 
normal gland the blood-vessels sometim^H unravel an interfollicular 
puzzle. They indicnte, for example, the primitive follicles where 
they surround a few epithetial cells, and Pometimes in this way they 
differentiate for us epithelial cells in what might otherwise seem a 
jumble of interfollicular cells without arrangement (see Fig. 6, 
Plate X). 

We look to the epithelium (perhaps also to the colloid) for the 
first indication of hypertrophy, and sometimes find in one gland all 
of the stages of transition from low cubical to high cylindrical epithe- 
lium. How rapidly these changes may take place we cannot as yet 
Bay. Coincident with the increase in the height and breadth of the 
epithelium are changes in the colloid material and in the shape of 
the follicles. The follicles lose their roundish form and acquire 
increasingly irregular contours. Little bud-like processes sprout 
from the walls of the follicle. These sprouts seem to be a folding 
in (involution or plication) of the wail. The circumference of the 
follicle necessarily increases to accommodate the epithelium as it 
becomes broader. If the formation of normal colloid kept pace with 
the changes in the epithelium we might expect to have tremendous 
follicles still distended with colloid and retaining their more or less 
oiroular shape. But the colloid substance vanishes as the hyper- 
trophy advances. It becomes vacuolated and apparently very thin, 
and eventually disappears or is represented by a delicate reticulum 
(see Fig. 2, Plate IX, Fig. 8, Plate X and Photo. V}. 

There seems to be no intrafoUicular resistance. The wall of the 
follicle, very much longer than it was when lined with low epithelium, 
accordingly becomes folded upon itself. Little undulations and buds 
and digitatione, short and long, appear. These involutions or digi- 
tations are oftener simple than compound. Sometimes they have 
several processes or branches. The shape of the central cavity of a 
follicle is the reverse cast, wemayaay, of its involutions. It is often 
roughly star-shaped. Sometimes it is like a bay with many abort 
branching estuaries. In the very advanced hypertrophy the central 
cavity and its ramifications are pressed, so it seems, into elongated 
channels. These channels are often reduced to scarcely recognizable 
slits. It is then sometimes easier to differentiate the original fol- 
licle by the interfollicular blood-vessels than by the intrafoUicular 



Experimental Study of the Thyroid Gland of Dogs. 397 

canals. The central axU of each involution is occupied by blood- 
vBHsels. The change backwards from hypertxophy to normal would 
be a simple matter. The shrinkage of the epithelium, the atrophy of 
the new — if indeed they are new — blood-vessels, and the formation 
of normal colloid, would accomplish the transition. 

Hypertrophy. The Time required fOr its Development. 

In my second dog, and 71 days after excision of the hft lobe, 
hypertrophy was discovered. One could not have faiiwi to be sur- 
prised at the -great size of the right lobe, which weighed 2.5 grm., 
or more than four times as much as the leii, the weight of which was 
0.6 grm. The right lobe showed the histological and morphological 
changes which we soon learned to recognize as an advanced stage of 
hypertrophy. Not a vestige of normal thyroid structure remained. 

Only a few of my experiments were made solely to determine the 
time required for the production of hypertrophyafter excision of one 
lobe. Nevertheless we have a sufficient number of observations to 
justify the statement that if one thyroid lobe be excised in whole or 
in part, or mutilated, however slightly, hypertrophy of the other lobe 
will, to a greater or less degree, almost surely supervene within 40 
days, and sometimes much earlier than this. 

To estimate the time required for the development of the hyper- 
trophy we must exclude, I am convinced, most of the dogs whose 
wounds were closed and then dressed with a plaster of Paris bandage — 
a bandage which, as I have explained, encircled the neck and confined 
the shoulders and upper part of the forelegs. The operations upon 
the dogs so treated were as follows : thirteen isolations of the left lobe, 
or one-sided Mnnk's operations; four extirpations of the left lobe 
followed immediately by substitution transplantations;* one manip- 
ulation enucleationf of the left lobe, and one extirpation of the 
left lobe. 

The wounds healed absolutely per primamt in all of the cases except 

*The lol>es of two dogs are exebanged and transpUnted accurately in Htu. 

T The f!land is raised ont of ite heA eomewhat roughly, its loose counective 
tisane attscbmente are torn through, and it is then dropped back into place. 
Ita principal blood-vessels are not injured. 

X I attribute the excellent results in wound-heating to the buried skin 
suture, ''subcuticular auture." Only a amall proportion of my wounda in 



3Se WtKam & UatibxL 

two (dogn 48 sod 69). In one of tb«se cases (dog 69) the sappa- 
ntion wu entirelv SBiierGcisI sod vcn' slight. XevertbelcSG most 
or the nioetecti dogx to treated (closed wonods ai>d plastcT of 
Paris drcaeings) develo|)ed »oon after operatioD peculiar STmptoms 
and di«d, whereas the dogs with open wounds wer« perfectly well 
even when reduced to une-fourih and leee of the thyroid gland 
(vid. TabiM III and TV). The most etrikin^ g^mptoms which 
the dogM with pl«t>l(^r of Paris drefisings developed were a pro- 
found auffimia, a |>ec-Hliar'»CDrvy-like condition of the gums and 
a falling out of the bair. The doge would become exceedingly 
anaemic a few dayn after the operation, and within- a week or ten 
dayti of the operation the afiection of the gums would manifept itE«)f. 
Thi« acurvy-like condition of the gums was so severe in several 
iDBtancm thai the body of the lower jaw was entirely denuded except 
at its lower border. An excessively foul-smelling breath accom- 
panied this condition of the gums. Nine of these dogs died within 
twenty-five days (vid. Tabic IV): on the laih day 1, on the 17th 
day 1, on the IHth day 2, on the 20th day 3, on the 24th day 
1, on the 25th day 1, The rigln lobes of the nine dogs obtaineil 
post mortem showed, with two exceptions (dogs 58 and 68|,* no 
jierceplible change in t»trueture, but the follicles of these glands were 
in greater part filled with cells — cells which clearly had their origin 
in the epithelium which lined them. Another dog of this group 
(No. 72) which died on the 3Uth clay with the same symptoms had a 
thyroid gland (right lobe) which showed the described change— fol- 
licles filled with cells. 



doKB healed before I devised this sature. To take Ihe etitfhes, the 
needle is flrat pasted into llie under surface of tbe skin as near to the 
deeper angle of its cut edge as possible, and iacludint! only the deeper lasers 
of the skin, ie made to emerge' in the same plane. Sebaceous follicles and 
t follicles should not be perforated by the stitches. We now use the 



, buried skin 
Knots are unnecessary, becaui 
closely thai Blipping does not 
or nilver eulure emerge at the 
drawal at the end of ten duyg i 
not, of course, withdrawn, and may be tied. Th; 
in the .lohns Hopkins Hoajiital Bulletin. Vol. 1. p. 13. 

■ Dog BS, early stage of hypertrophy on 15th day. Dog 
of hypertrophy on 26th day. 



preference to the interrupted suture. 

the tisaues hug the uniuterrupted eulure so 

:cur. Long enda of the uninterrupted ailk 

ngleaofthe wound, to make eaay its with- 

ks. If calgut IB uaed the auture is 

t deacrihed 



i, early stage 



E-rprrimmtal mtidy of the Thyroid Ohnd of Doffs. 399 

These ten cases died from the isolation or extirpation of one thy- 
roid glund, which under ordinary conditions are harmlesa prooedures. 
The profound antemia, the scurvy of the gums and the sndden and 
very rapid falling out of the liair must be ascribed, I believe, as well 
as the fatu! results, to dimiuished functional activity of the remaining 
lobe of the gland. A iicrverted functional activity is indicated per- 
haps by the proliferation of the cells of the follicles. 

Of the nine remaining cases of this plaster of Paris group, one 
(dog 56) died on the 65th day, Fourdaysliftertheremovaloftheleft 
lobe he developed the tongue tremor, which is always seen when both 
lobes have been extirpated. This tremor subsided in txv-o or three 
days. But already a conjunctivitis and central cornea! ulcer of the 
left eye had developed. Within a month the dog became exceed- 
ingly aneemic; his gums were discolored at the edges, separated 
from the jaws, anil beginning to slough. Before his death there was 
complete loss of hair. It is to be observed that this dog soon after 
the first operation had symptoms of extirpation of both thyroid 
lobes, that he recovered from these and lived altogether 65 days after 
the operation. The right lobe, obtained post mortem, was unmis- 
takably hypertrophied to a certain extent (see Table IV) ; the epi- 
thelium was cuboidal or cylindrical, and the follicles were some- 
what angular and contained the thin reticulated colloid material. 

Seven dogs of the plaster of Paris group recovered perfectly from 
the operation : four (77, 43, 65, 2) without, at any period, a symptom ; 
three (69, 70, 45) with temporary symptoms of thyroid privation. 
The remaining lobes of all of these seven dogs were hypertrophied 
to an advanced degree. One dog (67) of this group remaina to be 
considered. He had not been well at any time since the first opera- 
tion, and was very much emaciated when, on the 61st day after the 
first operation, the right (remaining) lobe was removed. The right 
lobe was perfectly normal. It was not hypertrophied, as we should 
have expected it to be had the dog made a good recovery from the 
first operation, nor were its follicles filled with cells, as we might, 
possibly, have expected them to be if the dog had died from the first 
operation. It is evident, therefore, that to estimate the time required 
for the development of the hypertrophy, we must exclude most of the 
dogs whose wounds were closed and dressed with a plaster of Paris 
bandage. Four of these dogs, however, as we have seen, made a 



perfect recovery from the first operatioii and without a symptom of 
thyroid privation. 

[Deluding these four we have thirty-six unquestionable observa- 
tions on whith to base our conclusions: dogs 116, 110, 118,120, 121, 
108, 119, 124, 88, 125,122, 123, 112,93,92,109,87,81,86, 106,83, 
77, 103, 96, 43, 55, 2, 91, 104, 84, 82, 90, 94, 86, 126, and 127 
(see Table IV). 

Three hours was the shortest interval between the first and second 
operations, and 162 da™ the longest. The intermediate intervals 
were 24 hours, 4 days, 7 d., 7 d., 10 d., 10 d., 13 d., 15 d., 17 d., 19 
d., 19 d., 22 d., 26 d,, 42 d., 43 d., 49 d., 50 d., 50 d., 51 d., 53 d., 
56 d., 57 d., 63 d., 67 d., 69 d., 70 d., 71 d., 71 d., 82d.,82d., 85d., 
95 d., 104 d., 132 d., 132 d. No change was observed until the seventh 
day, and this was a barely perceptible change (vid. dog 120, Table 
IV). It was observable in one only of the two seven-day observa- 
tions. In one of the two ten-day observations an undoubted but very 
slight increase in the height of the epithelium was noted. On the 
15th day quite advanced hyjiertrophy followed the extirpation of the 
inferior half of the left lobe.* An early stage of hypertrophy of 
both lobes on the 17th day followed ligation of everything at 
the upper poles except the arteries. We have two right lobes 
removed 19 days after the extirpation of the left lobe. One is normal, 
the other is very slightly hypertrophied (vid. Table IV). On the 
22nd day after extirpation of the left lobe we find a normal right lobe. 
A perfectly normal remaining lobe later than 22 days after extir- 
pation or isolation of the first we have not seen.f 

The specimens of the 26th, 42nd, and 43rd days show early hyper- 
trophy. Dog 92, from which the 42-day specimen was taken, fur- 
nished a most interesting piece of thyroid tissue at the unexpected 
autopsy. The first operation on this dog was the extirpation of the 
inferior half of the lefl lobe. Forty-two days later, the dog being 
apparently perfectly well, the remainder of the left lobe and the 
inferior half of the right were removed. These pieces we must 
remember were very slightly hypertrophied, although not apparently 

'One of the dogs dresaed with plaster of Farie also showed an unmis- 
takable hypertrophy on the 15th dty, 

tDag 67 is the only exception, and this we have excluded for 
already given. 



L. ^ 



Experimental Study of Vu'Thyroitl Gland of Dogs. 401 

increased in size. The epithelium was higher than that of the piece 
exciseil at the first operation (the inferior half of the left lobe), but 
the colloid was still present in its usual form ; there were no involu- 
tions, and the shape of the follicles was not much chimged — on the 
whole, then, only a (ecblc or unsncoessful attempt at hypertrophy. 
Ab a rule, a dog not only survives this second operation, but has no 
symptoms of thyroid privation from it. Dog 92, however, died 
within four days of the second operation. The remainder of the 
thjToid gland, the superior half of the right lobe, obtained at the 
autopsy, presented the picture with which we have become so familiar 
in the dogs with closed wounds and plaster of Paris bandages, whioh 
died after extirpation or isolation of one lobe. The follicles were 
everywhere completely filled with disarranged cells, cells which had 
evidently i)een rapidly proliferated. The original follicles could be 
traced with difficulty and, as a rule, only by the blood-vessels. There 
was no evidence of an advance towards a true hypertrophy. 

Dog 96 furnishes another specimen of this peculiar change, which 
for the present we designate merely as follicles filled with cells. In 
this instance the superior half of the left lobe was removed. The 
wound was left open. The dog was apparently perfectly well for 
about 40 days, then became sick and died on the 63rd day after 
the operation. The right lobe was tremendously hypertrophied, 
weighing 3.6 grms. With the microscope, the changes which indi- 
cate advanced hypertrophy were present, and in addition the fol- 
licles and the follicular channels" were filled with cells. 

We are convinced that this apparently rapid proliferation of cells 
within the follicles cannot be a post-mortem change. It is incon- 
ceivable that such striking morphological changes should be accom- 
plished by post-mortem cell exfoliation. There seems to be a great 
increase in the number of the cells in the cases under consideration. 
Furthermore, these experiments were, for the most part, conducted in 
winter and many of the autopsies were made soon after deulh. All 
specimens obtained later than 43 days after the extirpation of the 
whole or one-half of one lobe sliowed without exception the changes 
which we designate us advanced hypertrophy. In two instances (dogs 

•In the very advanced stage of hypertrophy the folHoleB.aBi have eaid, 
have lost their circular outline on section, and are drawn out into fantastic 
shapes and channels. 



402 



WiUinm S. HttlaUd. 



103* and 104) mnnipulatioQ enucleation, accompliBlied willioiit in- 
jury to the principal arteries and veins of the gland, was followed by 
hypertrophy of both lobea in 57 aud 82 days after the experiment. 

A ligation of everything at the upper poles of both lobes except 
the principal arteries (dog 105), produced no structural changes in 
the gland in 51 days. 

Ligation of the left lobe 2 or 3 mm. above the inferior tip was 
practiced twice {dogs 126 and 127). t One hundred and thirty-two 
days after this experiment the left lobe and a portion of the right 
(inf. J) were removed from each of the dogs, and found in one (126) 
to be fully hypertrophied and in the other (127) to be perfectly 
normal. 

In March, 1895, GleyJ described certain cellular changes which 
take place in the " glandules tliyroidiennes " after thyroidectomy in 
the rabbit, and wonders if the observed changes are to be considered 
as transitional and as the first phases of an evolution which will 
ultimately give to the entire glandule the structure of the thyroid 
gland. He and Nicolas have been more fortunate than others, if 
they have observed in two cases (6 and 7 days after thyroidectomy) 
karyokinetic figuresg in the glandules thyroidiennes. It had, they 
say, for some time been considered that the glandules became hyper- 
trophied after thyroidectomy, but no one hitiierto hud succeeded in 
discovering any histological changes or positive multiplitstion of cells 
to explain an increase in the size of the glandules. Our observations 
on hypertrophy would lead us to believe that whalever the final 
change in the glandules thyroidiennes (parathyroid glandules) after 
thyroidectomy might be, the transformation to follicles filled with 
colloid would certainly not be an early manifestation. The colloid 

* KotTCttlietanding the aiipareotly tremendonB hypertrophy, dog 103 died 
with typical symptoms of thyroid privation. The iucrease in the eixe of tho ' 
thyroid lobea io dogs lO'S and 104 was due in part to parenchymatous bemor-; 
rhaje. See full histories in text. 

tThe history of both of these dogs ia given in full in the text. See aisc 
foot-note, page 38S. 

}PrJmi^res ri^siiltatB de rechevches sur les modifiuntions histologiques 
dea glandnles thyroidiennes aprOs la thyroidectomie. E. Gley and Nicolss, 
Comptea Hundu Hcbdom. 

gl have observed very few karyokinetic figures, even in tile thyroid 
gland, although most of my glands were hardened in Flemming's eol. 
stained with eafranin, and carefully studied for mitosis. 



Experimmtal Study of the Thyroid G!and of Dogs. 



403 



material is possibly a reserve secretion which is called upon to supply 
the requirements of the organism so soon as it is deprived of a part 
of the gland. If this is so, the balance is not under all circumstances 
nicely adjusted, for cutting oS' the tip of one lobe stimulales to trt- 
mendouB hypertrophy of both the lobes and the accessory glands and 
exhausts the reserve supply of colloid. It is accordingly conceivable 
that a transient auto-intoxication* might be caused by resectiun of a 
small portion of one lobe or by any manipulation which would induce 
hypertrophy. It is doubtful, however, if we should be able ordi- 
narily to detect this intoxication, inasmuch as tlie hypertrophy and 
the coincident resorption of colloid take place ag a rule so very slowly. 
In some dogs, however, hypertrophy develops quite rapidly, and in 
all the disappearance of the colloid is perhaps the earliest change. 

I have said that the greatly hypertrophied glands of the puppius 
of parents deprived in part of the tliyroid glands bear a striking 
resemblance in structure to the ])arathyrnid glandule of dogs. In 
some instances it seems to be impossible to distinguish the one 
from the other. | The enormously hypertrophied thyroids of the 
puppies of bitch 97, for example, liave neither colloid nor acini nor 
solid follicles, and preseul a structure which is, so far as one can 
judge from the specimens which I have preaerved, identical with 
that of the parathyroid glandule.J Both parents of these puppies had 
been deprived in ]»art of their thyroid gland. In the two instances 
in which only the female parent was subjected to a partial thyroid- 
ectomy, the hypertrophied glands of the puppies had still in some 
places small follicles filled with colloid, but for the most part there was 
little left to remind one of the original structure. It happens, fortu- 
nately, that the parathyroid glandule appears in several of my sections 
of normal and hypertrophied thyroid glands of adult dogs. I can 
therefore assert quite positively that no structural change took place 
in this glandule after partial extirpations of the thyroid lobes. 

Furthermore I cannot believe it to be a fact that dogs regularly 
survive the removal of the entire thyroid gland priivitied that the 

■Couli) reeorptioD of this material during the operation explain eonie or 
tlie many deatlis which occur during or soon after operations for exophthal- 
mic goitre? 

fl attach little, if aay, importaRce to this res em hi an ce of the greatly 
hypertrophied glands of the new-born puppiee lo the parathyroid glandules. 

t Photo. I shows parathyroid glaadule mugnified 40 diameters. 



404 maiam 8. Haltted: 

"glandules thyroidienneB" (parathyroid glands) are enucleated and 
left in place — to say nothing of the difficulty of such an experi- 
mental I'eat. 



Description of the Photographs. THVRon) Glands op Dogs. 

Photo. I. 40 diameters. Normal gland. Shows a parathy- 
roid glandule near the hilus of the lobe. Just at this pointonesees 
the projection inwards of the delicate capsule of the lobes, embracing 
first the parathyroid lobule and then supporting tlie large blood- 
vessels. The follicles are filled with the colloid material and are 
lined with a single layer of low cuboidal epithelium. In a few of 
the follicles, particularly the larger ones, the colloid material has 
apparently contracted and drawn away from the epilhelium. As a 
rule thp follicles are not merely tilled, but seem to be distended with 
colloid. 

Photo. II. 275 diameters. Normal thyroid gland. Shows 
in the centre one of the more solid and so-called interfoUicular 
portions of the gland. The cells of the interfoUicular portion 
are for the most part epithelial and are grouped like young or 
very small follicles with little or no colloid. The long nuclei of 
the minute blood-vessels assist one to differentiate the immature or 
interfoUicular follicles. 

Photo. III. 275 diameters. Early stage of hypertrophy. High 
epithelium, rarefied (vacuolated) colloid. Angular foiliclefr. In 
centre solid area of gland. 

Photo. IV. 275 diameters. Right thyroid only 17 days after 
excision of left. Hypertrophy more advanced than in Photo. III. 
^Epithelium already cuboidal in must follicles. The vesicles are 
irregular in shape. The irregularity is due to a tendency to wave 
involutions. The colloid substance is abnormal. The nuclei of the 
blood-vessels well shown iu this photograph. 

Photo. V. 275 diameters. The follicles, except the central one, are 
almost completely filled by the involutions of the high (cylindrical) 
epithelium. The epithelium may be traced uninterruptedly from in- 
volution to involution. In this section the vessels have, for the 
most part, been divided transversely. They are easily recognizable 
at the bases of the involutions of the central follicle by the long 



ExperlmeiUal Study of Iki: Thyroid Gland of Doga. 



405 



uticlei. Id aeveral of the vessels blood corpuscles are to be seen. 
The colloid material ie reduced to little more than vacuoles and a 
reticulum. The central cavities in this stage resemble very irregular 
bays with numerous estuaries, single, bifurcated, trifurcated, etc. 

Photo. VI. 275 diameters. Inferior half of right thyroid. 
Dog &2. Am almost normal gland ; but probably a very early stage 
of hypertrophy 42 days after resection of inferior one-half of left. 
The shape of the follicles and the higher epithelium indicate begin- 
ning hypertrophy. 

Photo. VII. 68 diameters. Superior half of the right lobe of 
dog 92. The inferior half of the very same lobe removed only 
four days previously is shown in Photo. 6. The dog died very unex- 
pectedly after the removal of the remainder of the left lobe and the 
inferior half of the right lobe. The wound, treated by the open 
method, was healthy. Aside from the inflammation the change in 
the gland is most striking. The follicles are completely filled with 
cells. These cells are evidently of epithelial origin and were pro- 
liferated or exfoliated in four days at most. 

Photo, VIII. 275 diameters. From one of the cases with closed 
wonnd and plaster of Paris dressing. Follicles filled with cells. 

Photo. IX. 12 diameters. Normal gland of new-born puppy, 
shows two accessory lobules. The one which projects so prominently 
from the surface is a so-called parathyroid glandule. The other, 
adjoining and to the left of the first, is thyroid tissue, but without 
colloid. 

Photo. X. 12 diameters. Hypertrophied gland of new-born 
puppy of dog 97. About twenty times as large (both lobes) as nor- 
mal gland. 



DEBCRlPriON OF THE FLATtS. TUYROID GlANDS OP DoGS, 

Plate IX, Fig. 1. 90 diameters. Normal gland. Gives the 
correct idea of the shape of normal follicles. Most of the follicles 
are filled with colloid. Some are empty. The epithelium is flat. 

Fig. 2. 530 diameters. Two follicles of a hypertrophieil gland. 
The epithelium is cylindrical and in places several rows deep. The 
colloid material is replaced by vacuoles and a reticulum. The follicles 
are distinctly defined by the long nuclei of the blood-vessels. 



406 



WiUiam S. Hahted. 



Fig. 3, 530 diameters. One follicle of normal thyroid gland of 
dog. The orange color indicates nlood. 

Fig. 4. 925 diameters. A portion of central canal of hyper trop hied 
follicle, with longitudinal or slightly oblique section of involution 
on the right hand, and transverse sections of involutions on the left. 
The blood discs in orange indicate the situation of the capillaries. 

Plate X, Fig. 6. 240 diameters. Injected specimen. Hypertrophy. 
The injection has reached the terminal rauiifications of the blood- 
veaaela in the involutions. In Beveral instances the follicles are 
seen to he almost completely Biirrounded by blood-vessels. The epi- 
thelium IB cuboidal. The colloid is replaced by the reticulum. 

Fig, 6. 240 diameters. Injected specimen. Hypertrophy. A 
more solid part of the gland whioh laight be called (erroneously) 
interfoUicular were it not for the injection. The injection defines 
follicles which have no central canal and which might be termed 
Bolid. It also diSerentiatee the intra- from the interfoUicular 
spaces. Compare with Fig. 7. 

Fig. 7. 240 diiimeters. Hypertrophy. Same stage as Fig. 6.' 
Designed to show the solid and very advanced stage of hypertrophy. 
The nuclei of the blood-veseela have unintentionally been omitted 
by the artist. It is interesting to note the confusion caused by the 
omission. Compare Fig. 6. 

Fig. 8. 240 diameters. Advanced hypertrophy. Natural injection 
indicated by daubs of orange. One large and ten or twelve small 
follicles. Colloid replaced by reticulum in all the follicles. 
. Fig. 9. a. Usual size of one lobe of dog's thyroid at birth as esti- 
mated from three litters of puppies (from 15 to 18 puppies). 

0. Actual size of thyroid gland of puppy whelped by bitch 
No. 97 when she had been deprived of her left lobe, and sired by 
d<^ No, 90, whose thyroid had been reduced to two-thirds of one 
lobe. See history of No. 97. 

6. Left lobe of dog No. 3. Actual size. 

d. Hypertrophied right lobe of same dog (No. 3). Actual size. 



After receiving the pt^e-proof of this article I had the good 
fortune, thanks to the courtesy of Di. Abel, bo make an autopsy 



Experiinental Stitdy of the Thyroid Gla7id of Dogs. 



407 




upon a dog whose thjToid lobes had been removed in loto by him 
just a year ago. The dog emaciated rapidly after the loss of 
the thyroid gland, became profoundly ansemic, loat most of hie hair,* 
seemed to suffer from a more or less constant itching, and developed 
by scratching a dermatitis which in aome places might have sug- 
gested myxcedema. He never developed convulsions or tetany or 
tremors or any of the more pronounced Bymptoms of complete extir- 
pation. Neither did he suffer from the ecorbiitic gingivitis which I 
have described as occurring in a special group of my cases. 

He was fed with thyroid glands or thyroid extracts for 2 months, 
but not with any very appreciable effect. The autopsy was uot 
performed until about 30 hours after the death of the animal. 

Avtopsy. Small dog seven years old, much emaciated and almost 
bairlesG. No lesions of the viscera macroscopically diRcoverable. 
The neck was dissected with great care. The thyroid lobes had 
undoubtedly been removed ; uot a trace of them remained. An 
accessory thyroid which is usually found behind the hyoid bone, 
on the thyro-hyoid membrane, was apparently wanting. This 
gland had been searched for by me during the life of the dog, but 
could not be found. 

In the neighborhood of the arch of the aorta three or four very 
minute reddish-brown bodies were discovered which proved to he 
epithelial bodies, almost if not precisely identical in structure with 
the so-called parathyroid glandules. These little bodies were 
certainly not ranch more than one-quarter the size of the head of 
an ordinary pin. Under the arch of the aorta and very near the 
ductus Botali were three very large accessory thyroids, two of them 
as large as a very small pea. The three accessory thyroids weighed 
together .08 gramme. After examining with Ihe micro8coi}e a 
number of sections of these accessory thyroids, I was impressed with 
the simplicity of their structure. Most striking was the fact that 
there were very few interfoUicular cells. Almost all the cells were 
engaged in the formation of follicles, and all of the follicles seemed 
distended to their utmost with apparently normal colloid. The 
celts lining the follicles (and there seemed, as I have said, to be 

•This lion was supposed to liave mange before he was operated upon. 
The loss of hair and the dermatitis were perhaps due to this skin ilieesse. 



r 



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408 



Tf^//tam iS. Halated. 



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very few other cells) were a little higher than normal. There were 
rather numerous little epithelial buddings into the follicles, and in 
some of the buds blood-vessels could be demonstrated. 

We may assume with considerable confidence that these aortic 
accessory thyroid glands have passed through the changes which we 
describe as hypertrophic. Hypertrophy of the thyroid as we have 
represented it is probably a transition stage — transitional ta the 
condition which makes possible the greatest fulfilment of functions 
in some (i. 6. Dr. Abel's dog) and a greater activity in all cases. 
How then shall we interpret what we see in these greatly enlarged 
aortic thyroids ? The enlargement, it would seem, must be due in 
this instance either to an increase in the size of the original follicles 
or to an increase in the number of follicles containing colloid, or to 
both. It cannot be due alone to the inconspicuous increase in the 
size of the cells. This increase in the size of the follicles and in the 
number of follicles containing and distended with colloid implies 
not only a greater amount of colloid, but also either a greater 
number of cells than the gland originally contained, or a rearrange- 
ment of the original cells. 






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Interesting caae because aymptoms ^^^^H 
of total extirpation appeared and ^^^^H 

died with symptoms of thyroid ^^^^H 
privation, notwithatanding the tre- j^^^H 
mendouB and bypertrophied lobes. ^^^^H 

Dog much emaciated when right ^^^^| 
lobe was removed. Has not been |^^^H 
well since tirat operation. I^^^H 


■ 


Scorbutic gums and loaa of hair |^^^H 
after first operation. Entire recov- ^^^^1 
ery before aecond operation. Two ^^^^H 
small gl. parathyroid, found oolside ^^^^H 
of cajwule'of right lobe. Precisely ^^^^H 
same structure as right lobe. ^^^H 


Scorliutict-uma. Central corneal ^^^^H 
ulcer of left eye. Extenaive loss of |^^^^| 
hair. Had tremora of tongue after ^^^^H 
first operation, which disappeared ^^^^H 
in a few days. j^^^H 


■ 

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lli 

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Dogwell ntsecond operation. There I^^H 
are four intracapsular glandular ^^^^H 
parathyroidete which have precisely ^^^^H 
the same structure as the hyper- ^^^^H 
tropbied right lobe. ^^H 






















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The Johns Hopkins Hospital Reports. 



Vol. I- Plate LXVII. 



J 




n.e Johns Hopkins Hospi 



'■Ml Reports. 



"«'■ I- Plate LXVUI. 




t^HOTOORAf-H It. 



4 




Photograph I|[. 




PHOTOGRAPH IV, 



J 



The Johns Hopkins Hospital Reports. 



Vol. I. Plate LXXI. 




Photograph V. 



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Vol. I- Pl»'= LXXII. 



The ].hnsH.ptos Hospital R.P»rt- 



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The Johns Hopkins Hospital Reports. 



Vol. I- Plate LXXni. 



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Photograph VII 



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The Johns Hopkins Hospital Reports. 



Vol. I. Plate LXXIV. 



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Photoobaph Vlll 




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Tbe Johns Hopkins Hospital Reports. 



Vol. I. Plate LXXII. H 



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The Johns Hopkins Hospital Reports. 



Vol. 1. Plate LXXIII 



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Photograph VII 



4 



The Johns Hopkins Hospital Reports. 



Vol. I. Plate LXXIV. 




PHOTCX-.RAPH VIU 



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PHOTOGRAPH IX. 



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The Johns Hopkins Hospital Reports. 



Vol. I. Plate LXXV, 



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To avoid fine, this hook should be returned on 
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