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were tongue tremors, licking movements, anemia, con-
junctivitis, general tonic and clonic spasms, inflammation
of gums, with occasionally a falling out of the hair, accom-
panied with an itching of the skin, producing an edema-
tous appearance not unlike myxedema. This latter symp-
tom only occurred when the wound did not heal by first
intention. He next experimented with piecemeal removal
of the gland and observed that the same symptoms were
produced, the amount of gland removed in order to pro-
duce them varying in different dogs, probably on account
of the size and number of the accessory glands and to
individual peculiarities, one dog doing well and remaining
in good health with only one-eighteenth of the gland re-
maining. During the experiment a female who had had
the left and the lower third of the right lobe removed was
impregnated by a healthy unoperated dog. She gave
birth to eight puppies, whose thyroid glands were at least
twelve times larger than normal. It is remarkable that
in this case and also in a similar one that a few hours
before whelping the symptoms of complete thyroid de-
privation manifested themselves although each animal
possessed much more thyroid than was actually required
for her wants. It had previously been observed that
tetany had appeared previous to labor in cases with con-
genital thyroid insufficiency. These experiments have
been repeated recently with the same result by Edmunds
and are suggestive. It would be interesting to observe if
an excessive secretion or administration of thyroid during
pregnancy would not produce a reduced thyroid in the
produce, which, if it took place, might account for some
cases of sporadic cretinism.


Horsley divides the symptoms of thyroidectomy into
those of over action and of want of action. The first
symptom of over action is fibrillar muscular tremor, re-
sembling tetany. The individual contractions of the
mnscles follow one another in monkeys at the customary
rate of clonus, viz : eight to ten per second. Summation
next occurs, tetanoid spasms follow and finally rigidity
and contraction. Symptoms of want of action are motor
paralysis and anesthesia, the toxemic condition producing
functional neurosis, epilepsy, hemiplegia, etc. Tissue
changes are also marked, emaciation of an acute form,
with mucin in the connective tissue. If, however, the
cretinoid condition supervenes there is no increase of
mucin, but fibroid changes occur, coupled with emaciation.
Virchow suggests that the edema characteristic of myxe-
dema is a metaplasia of the subcutaneous fat into mucus,
with an increase of volume ; the skin becomes coarse and
dry from the absence of secretion ; the subcutaneous tissue
thickened and inelastic; the hair falls out, becoming thin
and gray. Disorders of temperature also occur. The
intrinsic changes, viz : the modifications which are intro-
duced into the normal heat balance ofT the subject after
elimination of the traumatic factor, consist of a rise of
from 4 degrees to 5 degrees during the acme of the mus-
cular twitching. The coincidence of this rise in tempera-
ture with the nerve disturbances suggests that it may be
dependent on a derangement of the heat controlling cen-
ters. Before death the temperature is subnormal. Ex-
ternal heat has a great effect on the operated animal, ex-
ternal cold precipitating the symptoms. Animals which
were apparently in good health while kept in a high tem-
perature developed the characteristic symptoms at once
on being exposed to cold.

The blood changes show a connection between the gland
and the blood metabolism. Normal! v the leucocvtes are


present in a greater proportion in the veins than in the
arteries of the gland, and this proportion is greater than
that fonnd in the veins of the limbs. After thyroid-
ectomy there is an increased venosity of the blood, with a
great diminntion of the amonnt of oxygen. This decrease
of oxygen in the arterial blood may be so great as to be
less than the oxygen in normal venous blood, a condition
which wonld account for many of the symptoms.

If a portion of the thyroid gland be removed there is
a compensating hypertrophy of the remaining part which
undergoes histological changes, the cubical cells become
columnar, the vesicles become oblong or branched and the
colloid substance becomes more watery, changes which
are almost identical with those found in the gland in Base-
dow's disease. These changes are not affected by division
of the sympathetic. SchifT found, after destroying the
sympathetic nerve fibres acconrpanying the blood vessels
to one lobe, that the lobe remained identical in minute
structure. Horsley tried similar experiments with re-
spect to the recurrent laryngeal nerve with the same re-
sult. Katzenstein could find no difference in the two
lobes after stimulating one and not the other. Edmunds
excised the superior laryngeal nerve and a considerable
length of the vasosympathetic lower down on the same
side, thus any secreting fibres passing by the recurrent
laryngeal nerve would be cut off. On this side the thyroid
lobe was not touched or even seen. On the other side the
lobe, together with the parathyroids, was excised. Of the
ten dogs experimented upon three died in one, two and
three days. No symptoms occurred, but death appeared
to be due to the operation, as the thyroid lobe was found
to be almost free from colloid and the secreting cells mul-
tiplying into the vesicles. Seven of the dogs lived longer,
six showing symptoms ; one, howerer, was operated on
again after twenty-eight days without having shown any


symptoms. One was allowed to live 242 days, dying with
a thyroidal symptoms. Another was killed at the end of
271 days suffering from severe symptoms. The other
four were operated on a second time. The pathological
findings in these cases varied somewhat. In one, in which
the lobe was removed by a second operation, the gland was
devoid of colloid, the cells multiplying into the cavities of
the vesicles. In another, which had well marked tremors
but recovered, the gland was found to be much enlarged,
weighing 3.5 grins., or about three or four times larger
than normal. The colloid had disappeared, the increase
in size being due to growth of young tissue between the
vesicles, the secreting cells were not multiplying into the
vesicles. The animal which lived 242 days, dying with
severe symptoms, had a normal gland and a normal para-
thyroid. In the animal killed after 272 days there were
some normal vesicles, but there were also vesicles filled
with multiplying cells from which the colloid had wholly

Hiirthle has experimented on the effect of the stimula-
tion of various nerves by the f aradic current on the secre-
tion of the gland, and has had negative results from both
the laryngeal nerves and the vasosympathetic. On the
contrary, Gr. A. Schaefer found that the cells of the thy-
roid show the same changes as those of other glands after
the injection of pilocarpine. As pilocarpine only pro-
duces its effects by nerve stimulation it follows that the
secretion of the thyroid must be influenced by the stimula-
tion of some nerve or nerves. Hiirthle suggests that the
stimulation of the gland is due to the presence of certain
unknown substances in the blood, and states that tying
the gall duct in dogs produced homogeneous globules in
the epithelial cells and lymph spaces of the gland, which
showed the same inclination to solidify and gave the same
staining reactions as the follicular colloid substance, prov-


ing that the passing of certain constituents of the bile
into the blood produced increased secretion of the gland,
and that any nervous influence that may exist is not cen-
tral, but is due to the ganglia either in or in the imme-
diate neighborhood of the gland, and further, that the
enlarged gland of Basedow's disease is not primarily of
central origin.

Sandstrom discovered the parathyroids in 1880, and in
1881 Cresswell Baker independently also observed the
glands but did not recognize them in animals, describing
them as undeveloped portions of the thyroid gland. In
1884 Horsley identified and described the parathyroids,
but they were not thoroughly studied till 1892, when Gley
published a set of papers recording his experiments.
Under the name of "glandules thyroidiennes " he de-
scribed in the rabbit two glands, one on each side of the
trachea, situated at some distance below the thyroid, so
that in previous operations for thyroidectomy in that ani-
mal these glands had probably not been removed. In the
dog, on the contrary, the corresponding structures were
so closely incorporated with the outer surface of the lat-
eral thyroid lobes that they must have been almost, in-
variably removed with the thyroid. On account of these
different anatomical arrangements he suggested the causes
for the relative insusceptibility of the rabbit to thyroid-
ectomy; he removed both the thyroids and the parathy-
roids from a series of rabbits with the result that in the
majority of cases acute symptoms and speedy death en-
sued. Further, he found that the removal of the thyroid
alone, leaving the parathyroids in situ, produced in the
dog and the rabbit little or no result. At the time of these
experiments (1892) the existence of the internal para-
thyroids was not known, and Gley's work only applies to
the external parathyroids. No really accurate knowl-
edge of the position of these glands was published till


1895, when Kohn's elaborate monograph on the thyroid
gland of the cat demonstrated the fallacies underlying all
previous operations. He found that in the cat, dog, rab-
bit, and probably in other mammalia, there were four
parathyroids, and he further showed conclusively that
these bodies were not thyroids but were independent spe-
cific structures, naming them "the external and internal
epithelial corpuscles of the thyroid."

In 1896 Vassali and Generali published the result of
their experiments. They removed all the four parathy-
roids, leaving the thyroid in situ in ten cats and in nine
dogs. Of the cats nine died by the tenth day, while one
was living at the end of a month. All the dogs died
within eight days, the symptoms in both cats and dogs
being the same as those previously recorded as the result
of thyroidectomy. As a rule, however, conclusive attacks
were absent or only very slight, but on the other hand,
the phenomena of diminished nervous excitability pre-
dominated in the form of paralysis, which rapidly killed
the animal. Rouxeau performed on the rabbit what Vas-
sali and Generali had done on the dog and cat, viz: he
removed the four parathyroids, leaving the thyroid intact.
The results were not uniform, but he concludes that re-
moval of the parathyroids is much more serious than re-
moval of the thyroid alone in the rabbit. Moussu comes
to the conclusion that the functions of the thyroid and
parathyroids are different ; that suppression of the thyroid
produces only chronic symptoms, while the suppression
of the parathyroids induces acute symptoms. He also in-
duced experimental cretinism in the dog, cat, and birds
by the removal of the thyroid, the parathyroids being left
intact. Welsh, after a number of very careful experi-
ments, comes to the following conclusions: (1) Removal
of all four parathyroids in the cat leads to acute and severe
symptoms, with a rapidly fatal issue, even though the thy-


roid be retained practically uninjured. (2) Eemoval of
three parathyroids does not lead to death, but may cause
transient symptoms similar to those which result from
removal of all the glandules; loss of two parathyroids
does not produce any appreciable result. (3) Eemoval
of the thyroid and some of the parathyroids may lead to
death with acute symptoms, if only one parathyroid is
left, but may not induce any obvious derangement if two
parathyroids are retained, at least not for several months.
(4) Administration of fresh parathyroid by the mouth has
no effect, either in mitigating the symptoms or in averting
death after removal of the thyroid and parathyroids in
the cat, even though relatively enormous doses are given.
In 1898 Edmunds published the results of his very elab-
orate experiments as to the functions of the parathyroids,
of which the following are the most important. In two
dogs about one quarter of one lobe and the external para-
thyroids were left, the rest being removed. Neither of
these dogs showed any symptoms during the nine and
twenty-six days they were allowed to live. In two other
dogs the upper part of the thyroid was left on each side,
with the addition that in each a length of the vasosym-
pathetic was removed on one side. One of the dogs suf-
fered from tetany, rigidity of the limbs, tremors, emacia-
tion, and a trophic lesion of the skin, in the second dog
the only symptom was emaciation ; twenty-nine days later
the remaining portion of the gland was removed, the dog
dying with the usual symptoms. In eight dogs one ex-
ternal parathyroid was left and only just sufficient thyroid
to avoid interference with the blood supply. The dogs
had no symptoms, except that one of them became thin.
Three of these dogs were subsequently killed and the
parathyroids identified by microscopical examination. In
the other five it was attempted to remove the parathyroids
during life. In two this was successfully accomplished,


with the result that the animals had the usual symptoms.
In the other three dogs the part removed proved not to be
parathyroids and no symptoms resulted, the parathyroids
being found on postmortem examination. In seven other
dogs it was intended to leave the external parathyroids,
but microscopical examination proved that the tissue left
was not parathyroid, all three dogs dying with the usual
symptoms. As dogs live when the parathyroids are left
and die when it is subsequently removed, or when only a
small piece of thyroid proper is left instead, it seems evi-
dent that the excision of the parathyroids is the cause of
the acute symptoms, tremors, rigidity, convulsions, dysp-
nea and death, which follow the total excision of the
thyroid and parathyroids, and further it suggests that
the excision of the thyroid proper only causes the symp-
toms of myxedema. In four rabbits, from which the
thyroid was removed, leaving the parathyroids, the health
failed, the hair fell out, edema occurred in the lower part
of the face, followed by death. Vassali and General!
have found that if all the four parathyroids in the dog are
excised and the whole of the thyroid left the dog will die
with the usual symptoms in a few days, while if one of
the parathyroids is left and the whole of the thyroid re-
moved the animal will live. Grley found that if the whole
of the thyroid proper and one parathyroid were removed
in rabbits the animal would live, but if the remaining
parathyroids were excised the rabbit would die with the
usual symptoms. In dogs in which a single parathyroid
was left and a minute piece of the thyroid no symptoms
of any kind appeared, even after five months. The ani-
mals were kept so long in order to see if the parathyroids
developed into thyroid tissue. They did not, but the cells
became more definitely arranged in rows, small collections
of secretion were seen and the trabecule of connective
tissue were much thickened.


In order to obtain an obvious case of myxedema, the
whole of the thyroid gland was removed from four mon-
keys. In the first there was muscular weakness, the hair
fell out extensively from the front of the chest and there
was some swelling about the face, but only temporarily.
Four and a half months after the operation a well-marked
edema occurred in the face but quickly passed away, and
in six and a half months the monkey was well. The other
three monkeys died with the usual symptoms. The fail-
ure to obtain true myxedema in these cases was appa-
rently caused by the animals dying from the nerve symp-
toms before the myxedema had time to develop. Four
other monkeys were operated upon as before and treated
with thyrocolloid, prepared according to Hutchinson's
method. The first monkey died in six days in spite of
treatment, and the second had slight symptoms on the
first day which passed off. On the twenty-seventh day
the treatment was stopped, three days later symptoms ap-
peared but passed off, when treatment was renewed, the
animal, however, dying on the forty-first day. The third
monkey had no symptoms from the first; the treatment
was stopped on the sixteenth day ; on the twenty-first day
symptoms appeared, treatment was resumed, the symp-
toms disappeared, and five months after the operation the
monkey was well. In the fourth monkey symptoms ap-
peared on the third day and the monkey died on the
seventh day in spite of treatment. Though three out of
four of the monkeys died yet treatment had some effect.
Edmunds summarizes the results of his experiments, com-
ing to the following conclusions : ( 1 ) the parathyroids of
dogs have as much or more to do with saving them from
acute myxedema as the thyroid proper; (2) although the
extract from the thyroids of sheep may keep off and re-
lieve the symptoms in thyroidless monkeys it will not, as
a rule, save their lives; (3) a parathyroid will not by


process of compensatory hypertrophy develop into thyroid
tissue; (4) the mortality was 44 per cent after total ex-
cision of the parathyroids, and after excision of both thy-
roid and parathyroids the mortality was 80 per cent, even
with thyroid feeding; (5) the symptoms produced by the
excision of the parathyroids are the same as by the com-
plete operation (thyroid and parathyroids), viz: tremors,
a slow and unstable gait, passing into paralysis of the
hind limbs, emaciation and muscular weakness.

The microscopic changes found in the thyroid lobes in
cases of excision of the parathyroids are marked in these
cases which survive the operation a few days. There is
a diminution in the amount of colloid in the vesicles, the
vesicles themselves becoming oblong and branched, the
secreting cells columnar or multiply so as to fill the cavity
of the vesicle and there is an excessive amount of young
thyroid tissue between the vesicle. Edmunds considers
these changes to be identical with those described as com-
pensating hypertrophy of the thyroid and with the
changes found in Basedow's disease; there is, however,
an apparent decrease in the size of the gland.

In two of the dogs, after partial parathyroidectomy,
there were marked eye symptoms. Auld and others have
noted eye symptoms after thyroid feeding, Beclere re-
porting a case where a patient, partly by mistake, took 60
grins, of sheep's thyroid in a week, which was followed
by thyroidismus and a certain amount of exophthalmos.
Edmunds performed a number of experiments to investi-
gate the point, the subject being of great importance from
the possibility of its offering an explanation of the pathol-
ogy of Basedow's disease.

Total thyroidectomy was performed on ten monkeys,
five of whom had had thyroid feeding before the opera-
tion. Of the five which had no thyroid feeding two
showed narrowing of palpebral fissure, one at first widen-



ing, followed by narrowing, and in two no change. Of
the five which had thyroid feeding, in two there was
exophthalmos with widening of the fissures; in one nar-
rowing, and in two no change. In another monkey no
operation was performed, but it was fed with large doses
of an extract equal to about half a sheep's thyroid per
diem. A considerable widening of the palpebral fissures
resulted, with perhaps some protrusion of the eyeballs.
Edmunds, in further
experiments on six
monkeys fed with from
a half to three whole
sheeps ' thyroids per
day, produced prop-
tosis, dilatation of the
pupils, widening of the
palpebral fissure, erec-
tion of the hairs of the
head, falling out of the
hair in patches, paral-
ysis of one or more
limbs, emaciation and
muscular weakness,
followed by death from
asthma. The average
life of the monkeys
after the commence-

Fig. 10. вАФ Monkey in tetanic attack after
extirpation of thyroid, (v. Eiselsberg. )

ment of the treatment was seventy-six days. Microscopic
examination of the thyroids and of pituitary glands were
made, but no pathological condition could be detected.
Shortly before death the animal showed an objection to
light and to being looked at.

As the effect of thyroid feeding on the eye might be
produced by action on the central nervous system, com-
municating with the cervical sympathetic or by local action


on the ganglia in and about the eye, the cervical sympa-
thetic was divided on one side in two monkeys and the
animals fed in doses corresponding to about three sheeps'
thyroids per day. In twelve days the eyes on the unop-
erated side were seen to be more prominent and the palpe-
bral fissure wider than before treatment; the eyes on the
operated side also became very wide and prominent. A
considerable length of the nerve was removed to prevent
the probability of repair. This experiment is borne out
by a case reported by Boissou. The patient, a girl of
twenty years old, was submitted to resection of the cer-
vical sympathetics, first on one side and then on the other,
for Basedow's disease. Notwithstanding the operation
the exophthalmos continued and became so severe that the
eyes could not be closed, the cornea sloughed, sight was
lost, the patient dying in a short time.

This case and Edmunds' experiments show that the
cervical sympathetic is not the main factor in producing
the protrusion of the eyeballs, and it also seems probable
that thyroid extract acts partly through the cervical sym-
pathetic and partly locally. Experiments were also made
on rabbits, with the thyroid with the two smaller parathy-
roids removed. In one rabbit the eyes became more promi-
nent and remained so ; in one no change was observed for
nine months, when the eyes began to get narrow, becoming
very narrow before death. The cervical sympathetic was
excised on both sides to see if it produced further narrow-
ing; in two the eyes became very narrow before the ani-
mals died, which occurred in two or three days ; in three
the eyes narrowed and the animals lived, and in one there
was no change. The thyroids of the four surviving rab-
bits were excised, the two larger parathyroids being left
intact. In one there was a marked increase in the nar-
rowing, in the other two no immediate effect, but the ani-
mals died ten months later with very narrow eyes. In the


rabbit in which division of the sympathetic had produced
no symptom, the excision of the thyroid was followed by
death in three days with narrow eyes.

In further experiments to observe the effect of the ex-
cision of the parathyroid on the eye, Edmunds excised
both cervical sympathetica in a rabbit, which caused nar-
rowing of the palpebral fissures ; later he excised the thy-
roid together with the two smaller parathyroids, leaving
the two large parathyroids. This operation produced no
further narrowing. In five rabbits he excised the two
larger parathyroids, leaving the thyroid intact, together
with the two smaller parathyroids. In four animals the
eyes became somewhat wider for a time, reverting to nor-
mal : in one there was no change. In six rabbits the op-
posite operation was performed, namely, the two larger
parathyroids were left intact and the thyroid lobes with
the two smaller parathyroids were excised. The results
varied, in three of the rabbits it was noticed that the eyes
for a time were wider than normal, four of the rabbits died
and, at the time of death, their eyes were much narrowed ;
two were killed at a time when the eyes were normal.
Edmunds summarizes his results as follows :

(1) That after complete excision of the thyroid and
parathyroids the great majority of dogs die within a few
days and cannot be saved by thyroid feeding, but a small
minority survive even after the complete operation.

(2) In operations in which one or more parathyroids
are left the dogs as a rule survive.

(3) That when only the thyroid is left they die as a rule.

(4) That with respect to operations that paralyze the
secretory nerves of the thyroid the dogs often die, al-

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Online LibraryHubert RichardsonThe thyroid and parathyroid glands → online text (page 3 of 19)