been reported in early childhood and in old age. Heredity has some influence
as a predisposing factor and the condition seems more likely to affect those
of neurotic tendency. It has been known to follow such acute infections as
enteric fever and rheumatism. The theory that exophthalmic goitre is the
result of intestinal auto-intoxication has been advocated in the past, but the
hypothesis that the disease is a specific toxaemia due to hyperthyroidism or
excessive production of the secretion of the thyroid gland or of certain elements
contained in this secretion, is the most recent and the results of experimenta-
tion seem to prove that this is the true cause of the affection, and that it is the
antithesis of myxoedema which is due to lack of proper function of the thyroid.
Pathology. The changes which occur in the thyroid gland in exophthal-
mic goitre are indefinite, various chronic lesions, however, have been found.
524 DISEASES OF THE DUCTLESS GLANDS.
all of which are of such character as to render the hypersecretion theory tenable.
Persistence of the thymus gland is not unusual and changes in the muscles,
probably occurring as a result of the toxemia, may account for the extreme
muscular weakness which is characteristic of the disease.
Symptoms. Both acute and chronic forms of exophthalmic goitre are
described; in the former the onset of the disease is very rapid with pronounced
exophthalmos, greatly increased heart action, thyroid enlargement and per-
sistent vomiting and diarrhoea. Cerebral symptoms are not usual but delirium
appears in some instances. This type of the affection may prove fatal within
a few days.
The chronic type of the affection is usually of slow development. The
characteristic symptoms are four in number.
1. Rapid heart action is constant and, as a rule, extreme, the pulse rate
often reaching, in the more advanced stages of the disease, 100 beats per
minute or even more. Emotion augments the pulse rate to a marked degree.
Irregularity is not infrequent, there may be pulsation in the vessels of the
neck and visible p\ilsation of the superficial arteries and of the capillaries
is often present. Physical examination reveals a forcible apical impulse
which is in marked contrast to the weakness of the pulse. The apex beat is
not displaced but late in the disease may be diffuse. Percussion may show
cardiac enlargement due to a secondary hypertrophy and dilatation. The
heart sounds may be audible at a distance from the patient; apical ventriculo-
systolic murmurs are common and are due to a relative mitral insufficiency;
basic murmurs of soft blowing character, usually occurring with the first
sound, are common. There is frequently an accentuation of the sounds
due to valvular closure. Acute dilatation may supervene, accompanied by
dyspnoea, cough and the expectoration of blood-stained froth.
2. Exophthalmos is common; it may not develop until some time after
the incidence of the cardiac symptoms and it varies in degree in different
patients and even from time to time in the same subject. It may be slight,
even hardly discernable, or very extreme, instances of entire dislocation of
the eyeball having been observed. The patient winks more seldom than in
health; the pupil and the vision are unaffected. Optic nerve changes are not
common but retinal pulsation is often observed. Distiirbances of conver-
gence may occur. In marked instances of exophthalmos the eyelid does not
follow the movement of the eyeball when the latter is moved downward (von
Graefe's sign). This is a characteristic but not constant manifestation.
Retraction of the upper lid resulting in widening of the palpebral fissure is
common (Stell wag's sign).
3. Thyroid enlargement usually appears with the exophthalmos; the increase
in size is usually not extreme. The enlargement may be uniform or localized
and may vary with changes in the circulatory function. The gland may be
EXOPHTHALMIC GOITRE. ' 525
felt to pulsate and a thrill may be palpable, auscultation often reveals a loud
ventriculo-systolic bruit; a double murmur may be detected and is said to
be pathognomonic.
4. Tremor is the final symptom of the tetrad; it may appear early or not
until late in the disease. It is observed when the patient holds out his hand
in the prone position. The entire hand moves, the muscles of the wrist being
the ones affected; the fingers do not vibrate independently. The tremor is
fine and of small extent; its rate is about eight or nine times per second.
Rarely the foot or even the entire body may be involved.
There are various other manifestations associated with the four cardinal
symptoms. Muscular weakness and painful cramps are not uncommon;
even muscular atrophy has been observed. Flushing of the skin with inter-
mittent sweating is frequent and pruritus and pigmentation may occur. A
brawny oedema of various parts is often noted and excessive micturition may
take place; glycosuria and albuminuria may complicate the disease. Rapid
breathing with dyspnoea, sometimes accompanied by cyanosis, is not rare,
and marked diminution in the cutaneous resistance to electricity has been
described by Charcot. Mental symptoms, such as excitability, depression,
melancholia and mania are not unusual and such complications as epilepsy,
hysteria and chorea have been noted. Symptoms referable to the digestive
tract such as those which usually usher in the acute type of the disease may
occur from time to time in the chronic form.
Attacks, which strongly indicate the probability of the toxic origin of the
affection, take place in most serious instances of the disease and in fatal cases
they are a very constant manifestation; they are frequently induced by the
incidence of some mild affection such as tonsillitis, bronchitis or influenza,
and consist of definite febrile exacerbations, associated with acute cardiac
dilatation, increased intensity of the existing murmurs or the appearance of
new ones, extreme trachycardia and cardiac distress, digestive disturbances,
such as abdominal pain, vomiting or diarrhoea, sweating, dyspnoea, rest-
lessness and sleeplessness, erythema of the skin and oedema of the extremities.
The theory is that such exacerbations of symptoms are the result of a specific
toxaemia due to h}'perthyroidism.
The diagnosis in well-marked instances is extremely simple. In the
masked form of the disease difficulty may be experienced, for at times the rapid
heart action and tremor may be present without thyroid enlargement; later,
however, the goitre may appear and remove the doubt.
The prognosis is usually good as to life but recovery is rare in patients in
whom the disease is well marked and has persisted for a considerable period.
Spontaneous cure sometimes takes place in the mild forms. Acute instances
of the disease and acute exacerbations of the chronic type of the affection
may result fatally within a short time; yet patients in whom the attack appeared
526 DISEASES OF THE DUCTLESS GLANDS.
suddenly and gave evidence of great severity have gone on to recovery within
a few days.
Treatment. The importance of absolute rest cannot be too strongly
emphasized; the patient should be put to bed and strict quiet enjoined,
the application of an ice coil to the chest and the administration of cardiac
sedatives, veratrum viride or aconite, will lessen the cardiac irritability, while
the nervous excitability should be controlled by means of the bromides. Digi-
talis and strophanthus have been advised upon account of their action in
slowing the pulse rate but these drugs, and aconite and veratrum viride as
well, should be given with great care. The use of ergot has been advised
and good results have followed its use in combination with strychnine and
digitalis; the same is true of belladonna and sodium phosphate. Relief is
said to have followed the administration of sodium salicylate in doses of 10
to 15 grains (0.66 to i.o) 3 or 4 times daily and 20 grain (1.33) doses of sodium
glycerophosphate given at similar intervals, are also highly recommended.
Treatment by means of th}Toid extract or by ingestion of the gland itself
has been tried but has proved unsuccessful save in instances where there
have been myxoedematous manifestations. Suprarenal extract has been
employed and has proved sometimes beneficial, and the same may be said of
th)T3ius extract.
Electricity has given good results in some instances and the use of both
the faradic and galvanic currents as well as of the sinusoidal current, has been
advocated. Faradic electricity has been employed as follows: the positive
pole is placed in the nuchal region while the negative pole is applied to the
sterno-mastoid muscle at the angle of the jaw, thence it is moved to the middle
of the muscle, the application being continued for about a minute on each
side of the neck; the negative electrode is then applied to the eyelids and
around the margin of the orbits for about two minutes for each eye, the infra-
and supra-orbital nerves being avoided. A plate electrode is then substituted
for the olive shaped one previously employed and is placed over the thyroid
tumor and allowed to remain for about five minutes. This form of treatment
should be continued for from six months to a year.
The galvanic current is believed to exert a more active effect upon the
glandular secretion and has given good results in the hands of some ob-
servers. The technique is variable but as a rule the negative electrode is
applied to the region of the thyroid and the positive to the back of the neck.
The strength of the current may vary from 25 to 60 miUiamperes. Guilloz
moistens the negative electrode with a solution of potassium iodide.
A combination of faradization and galvanization may be employed, a large
plate electrode being applied to the th}Toid region and the positive electrode
is placed at the back of the neck. A galvanic current of 15 to 30 miUiam-
peres is used and the faradic ciirrent is given to the limit of the patient's toler-
I
EXOPHTHALMIC GOITRE. 527
ance. In some subjects this treatment brings about a marked amelioration
within two or three months, the general irritability being lessened, together
with the sense of oppression and the diarrhoea, and the goitre diminishing in size.
The tachycardia and the tremors react more slowly.
Quick and permanent results are said to follow the use of the sinusoidal
current, the patient being placed in a bath of water, the whole body surface
thus receiving the benefit of the treatment.
The electricity is supposed to be favorable in that it excites the rapid elimi-
nation of the thyroid toxins and that the treatment also has a certain mental
effect upon the patient through suggestion.
The Rontgen rays have been used in the treatment of exophthalmic goitre
in various ways. In the milder types of the affection they may be employed
energetically in connection with regulation of the patient's general hygiene;
in the severer instances of the disease, after the extirpation of a portion of the
gland, the exposures are begun as soon as the wound has well united. The
exposure of the gland to the influence of the rays for twelve minutes every
four to seven days has caused a complete disappearance of the thyroid
tumor in at least one instance.
Tubes containing radium have been inserted into the incised gland for a
period of fifteen minutes and after several weeks' of the treatment a diminution
of the tumor has been observed but the tachycardia has persisted.
Upon the toxsemic theory as a basis numerous experiments along the line
of treatment by means of the blood or serum from thyroidectomized animals
have been undertaken and some of these have produced rather remarkable
results. The serum appears to be preferable to the blood since it is more
active and less repugnant to the patient. The serum may be either that of
the goat or the sheep; the best results are said to be obtained, however, from
that of the latter. The animals operated upon should be between the ages
of two and five years. The thyroid is wholly excised but the parathyroids are
left in place. The blood is first drawn by means of jugular puncture about
three or four weeks after operation; the serum is filtered and rendered absolutely
sterile; the addition to it of antiseptics such as phenol does not seem to impair
its efl&ciency. The dosage varies from 35 to 45 minims (2.33 to 3.0) every
two days depending upon the patient's condition, and the serum is taken in water
or wine. The serum is continued in this dosage for from three to four weeks; it
may then be discontinued for a week and later resumed for two weeks in each
succeeding month. The entire duration of the treatment is variable but
usually is from six months to a year, the periods of intermission being length-
ened as the patient improves. Under the influence of the serum the size
of the thyroid, the exophthalmos, the tachycardia and the tremors diminish
progressively. After the establishment of cure it is best to advise the patient
to take the serum for about fifteen days during each following year.
528 DISEASES OF THE DUCTLESS GLANDS.
The milk of thyroidectomized animals has also been employed as a means
of treatment, but, while to a certain extent effective, is inferior to the serum.
Very recently most remarkable results have been reported from the admin-
istration of a cytotoxic serum produced by passing an extract of the thyroid
gland of human beings who have died while afflicted with exophthalmic goitre
through the blood of living rabbits; from these a serum is derived containing
both a cytotoxin and an antitoxin. This serum when injected in doses
of 7^ to 30 minims (0.5 to 2.0) into patients suffering from exophthalmic
goito"e, especially those who exhibit the symptoms of febrile exacerbations,
produces a most extraordinary reaction. Although for the first few days
after administration the serum may seem to accentuate the symptoms, a general
improvement, even recovery, takes place, in most instances, oftentimes only
two or three doses being necessary to cause this effect. The only untoward
effect of this treatment seems to be an erythema, not only at the site of the
injection, but upon remote parts of the body. The work done by Rogers and
Beebe upon this serum bids fair to revolutionize our theories concerning the
origin and management of exophthalmic goitre. The only drawback to
this method of treatment would seem to be the manifest difficulty of obtaining
diseased human thyroid glands, for experiments of analogous character have
been undertaken with extracts of the healthy human gland, and, while not
wholly negative, have been by no means so remarkable in their results as
those with the extract of the thyroid gland of exophthalmic goitre.
The surgical treatment of the disease must be considered in the event of
the failure of treatment by other means. Ligation of the th)T-oid arteries is
productive of benefit in some instances and bilateral sympathectomy may
produce good results in that the consequent ptosis will diminish the exoph-
thalmos; entire recoveries have been reported as due to this operation. It
appears, however, that the most effective surgical measure is partial thyroi-
dectomy. While death takes place following the operation in a small propor-
tion of the cases so treated, a large number of complete cures has been observed
and improvement follows the procedure almost without exception. Sup-
plementary operation becomes necessary in some instances. Complete
thyroidectomy would seem inadvisable because of the possibility of producing
myxoedema.
MYXCEDEMA.
Synonyms. Athyrea; Cachexia Thyroidea vel Strumipriva vel Thyreapriva.
Definition. A constitutional disease characterized by dryness of the skin,
myxoedematous infiltration of the subcutaneous tissues and atrophy of the
thyroid gland.
iEtiology. The specific cause of this affection is disease or removal of the
MYXCEDEMA. 529
thyroid gland resulting in the deprivation of the body of the normal secretion
of this organ.
Pathology. Autopsy discloses the presence of a mucous oedema of the
subcutaneous connective tissues and absence or atrophy of the thyroid body.
In cretins the pituitary body has been found enlarged and the cerebral con-
volutions may be indistinct. The lack of development of the nervous system
may be associated with a similar condition of the blood-vessels of the brain.
Sjrmptoms. Three types of the condition may be described.
1. The Myxcedema of Adults (Gull's Disease). This form of the affection
is much more common in women than in men and is observed chiefly during
young adult life and middle age. Several instances may occur in one family
and heredity through the female line is sometimes a factor in its incidence.
It seems to bear no relation to the genital system.
The onset may be characterized by the symptoms of exophthalmic goitre
but with the appearance of the myxoedema, which involves the face especially,
although the other parts of the body, including the tongue and at times the
viscera may be affected, the countenance becomes swollen. This is the result
of a firm infiltration of the subcutaneous tissues with a mucoid substance
which causes a broadening and flattening of the face, together with a loss
of expression. The lips and nose become thickened and the myxoedema
of the skin of the neck produces folds which may even extend below the clavicle.
The skin itself becomes dry and scaly and may assume a yellowish color and
a waxy appearance; a reddish flush is sometimes present upon the cheeks
and nose and the nutrition of the hair is imperfect. The hands and feet
become misshapen, movement is slow and the mentality becomes sluggish.
The memory is impaired and the disposition irritable and suspicious; hallu-
cinations and even dementia may ultimately appear. There is no febrile
movement, indeed the temperature is often subnormal and the patient is
very susceptible to the influence of cold. There is no interference with the
functions of the various organs although albuminuria and glycosiuria may
be observed. The thyroid gland is atrophied and may become converted
into fibrous tissue.
The course of the affection is slow and is usually prolonged over a period
of a number of years, death taking place, as a rule, from intercurrent
disease.
2. Cretinism. The cretinoid condition is a result of absence or a loss of func-
tion of the thyroid gland and may evidence itself at birth or make its appear-
ance during childhood. It is a type of idiocy characterized by an impairment
of both physical and mental development. At birth cretinism may fail of
recognition but by the time the child has reached the age of a few months
it becomes evident that the growth, mental as well as bodily, is not normal;
the face is large and of unintelligent expression, the size of the tongue is
34
530 DISEASES OF THE DUCTLESS GLANDS.
increased and the organ protrudes, the skin is dry and the hair scanty;
gradually these manifestations become more and more apparent and by the
time the patient has become two or three years old the condition is quite unmis-
takable. In addition to the characteristics mentioned above, the lips become
thickened, the eyelids puffy, the nose fiat and the neck thick. The child's
limbs are short and the abdomen is protuberant; the extremities are poorly
developed, dentition and the closure of the fontanelles are delayed. The
muscles are weak and as a consequence the child does not walk until late.
Fatty pads are present above the clavicles and the arrest of mental develop-
ment results in various t^'pes of idiocy. The cretin may live to adult life but
remains dwarfed in body and mind.
Atrophy of the thyroid gland may occur in previously healthy children as a
result of one of the acute infections and subsequent critinism has been ob-
served.
The cretinoid state occurs in two forms, the sporadic, which is the t^^pe de-
scribed above, and the endemic. The latter form is met in regions where goitre
is also endemic, particularly certain parts of Switzerland, France and Italy.
Its cause is unknown, the condition developing in previously normal subjects
coincident with change in the thwoid gland.
Cretinism is easily recognized on account of its distinctive characteristics;
the condition which most closely resembles it is chondrodystrophia fcetalis
or achondroplasia. Here the limbs are short and ciirved and the articiilations
are enlarged as a result of hj^ertrophy of the cartilages of the extremities
of the bones. The affected individual is dwarfed but there is no such lack
of mental development as occurs in cretinism.
3. Cachexia Slnimipriva or operative myxoedema is the term applied to
myxoedema resulting from removal of the th}Toid gland. It is more common
after total th}Toidectomy than when only a part of the gland has been excised,
but does not result in every instance of entire removal of the organ, possibly
because portions of the gland have been inadvertently allowed to remain or an
accessory thyroid may have been present.
The diagnosis of myxoedema, on account of the very characteristic appear-
ance of the patient, is simple. The oedema of nephritis and of endocarditis
pits on pressure and is associated with the presence of albumin and casts in
the urine (which may, however, be observed in myxoedema), cardiac symp-
toms and physical signs; there is no lack of mental and bodily development
in these latter affections.
The prognosis under proper treatment is good, the results obtainable being
little less than marvelous.
Treatment. It is in the treatment of myxoedematous conditions that
organotherapy is most successfully exemplified. The thyroid gland of the
sheep is chiefly used either in its raw form, as the glycerin extract, or in tablets
MYXCEDEMA. 53 1
made from the cleaned, dried and powdered gland; the gland itself is inferior
to either of the other preparations, particularly on account of its inconven-
ience. The usual dose of the glycerin extract is from 15 to 30 minims
(i.o to 2.0) daily; that of the dried and powdered gland about 4 grains (0.25)
three times a day; iodothyrin in dose of 3 grains (0.20) may be employed.
Unless improvement is noted within a short time the dosage should be increased
until there is distinct amelioration of the symptoms. In instances which
react well the body weight diminishes,the skin becomes moist, the pulse becomes
more rapid and there is distinct improvement in the mental state. At the
beginning of treatment the patient should be carefully observed lest heart
failure, of which a few instances, following excessive dosage, have been reported.
As a rule no ill effects are observed but sometimes over-doses produce symp-
toms analogous to those of exophthalmic goitre, cutaneous irritation, rest-
lessness, rapid heart action and mental excitation. These disappear upon
the diminution of the quantity of the gland administered. Arsenic when
given in connection with the preparations of the thyroid gland is said to
lessen the possibility of toxic effects.
As the symptoms disappear the dosage should be diminished and when
cure becomes evident our object should be merely to prevent a recurrence.
Since the thyroid gland of the patient is absent or functionless, it follows
that when the treatment is stopped we are practically certain to be confronted
with a reappearance of the symptoms of the disease. Such a circumstance
may be prevented by the administration of a daily small dose of the thyroid
extract or powdered substance. The amount necessary must be determined
independently for each patient but in general it may be said that it should
be sufficiently large to prevent the occurrence of such symptoms as an abnor-
mal temperattire and subcutaneous infiltration. It is usually necessary to
continue this second stage of the treatment indefinitely.
Myxoedematous patients suffer more in cold weather than in warm, conse-
quently when practicable, they should seek the warmer climates and when
this is not possible all means should be employed to prevent chilling of the
body. Warm baths and frequent massage of the scalp will to some extent
relieve the tendency to dryness of the skin and improve the nutrition of the
hair.
Cretinism should be treated in the same way as myxoedema and with the
same precautions; cretinoid children, however, may take relatively larger
doses of the thyroid preparations than myxoedematous adults. The results
of treatment are often astounding and comprise a diminution of the deformity,
an increased growth and a disappearance of the idiotism. The treatment