INTERNAL SECRETIONS
=Thyroid Gland.=—On either side of the windpipe, rather below the
thyroid cartilage (Adam’s apple), lies a somewhat conical mass of
tissue. The two masses are connected by an isthmus; lobes and isthmus
make up the thyroid gland. The whole weighs about an ounce. In health
it is so soft that only the finger of an anatomist could detect it
through the skin and the thin flat muscles which connect the hyoid
bone and the thyroid cartilage with the breast-bone. It makes no
visible prominence on the front of the neck. The thyroid gland is,
however, liable to enlargement, especially amongst the people who live
in certain districts. In the Valais, “goitre,” as it is termed, is
so frequent that anyone walking up the Rhone Valley is sure to meet
a number of persons—for the most part women—whose swollen necks
overhang their collar-bones, like half-filled sacks. Goitre is even
more common in the Valle d’Aosta, on the Italian side of the Alps. In
England this condition, comparatively rare, is known as “Derbyshire” or
“Huntingdonshire” neck.
In the majority of cases the tumour in the neck develops slowly, and
does not reach its full dimensions until after middle life. Goitre in
this form, although inconvenient, causes no serious discomfort. But
when it appears in early life, it is associated with an extraordinary
complex of malformations and ill-performed functions. The condition
into which a goitrous child sinks is known as cretinism. With the
exception of the skull-case, its skeleton does not attain to its proper
proportions; and, since the soft parts do not equally submit to arrest
of growth, the dwarf is heavy and ungainly, with large jowl and
protuberant abdomen. The appearance of distortion is extraordinarily
heightened by hypertrophy of the skin and the subcutaneous connective
tissue. Ears, eyelids, nose, lips, fingers, are thick and heavy. The
hair and nails are coarse. The skin is folded, wrinkled, rough.
The bodily ungainliness of a cretin has its counterpart in the
deformity of his mind. He is an idiot whose deficiency is chiefly
marked by apathy.
Cretinism exhibits itself in varying degrees. The description that we
have just given would not be accurate for all. For the sake of brevity,
we have chosen a case which might be that of a goitrous cretin of a
certain type, or that of a cretin whose thyroid gland, in lieu of
showing what looks like overgrowth, has failed to properly develop.
Nothing is more remarkable with regard to this organ than the fact
that the condition associated with its overgrowth and the effects of
its atrophy, or inadequate growth, are the same. A consideration of
the function of the gland will suggest an explanation of this seeming
paradox.
The inconvenience caused by goitre induced surgeons, about twenty-five
years ago, to remove the tumour in simple uncomplicated cases. Owing
to the accessibility of the gland, the operation is both safe and
easy; but its removal was found to be followed by symptoms of a very
serious nature, especially overgrowth and œdema of subcutaneous
tissue, muscular twitchings and convulsions, mental dulness. About
the same date, physicians recognized that the disease myxœdema—so
called because the œdema is not watery, as in dropsy, but firm and
jelly-like—is due to deficiency of the thyroid gland.
No other organ of the body has so weird an influence upon the
well-being of the whole. No other organ has an equally mysterious
ancestral history. Assuredly the thyroid gland was not always such
as we see it now. In prevertebrate animals it must have been quite
different, both in structure and in function. From fishes upwards,
however, its structure is always the same. It is composed of spherical
vesicles or globes. Every globe is lined by a single layer of cubical
epithelial cells. Its cavity is filled with a homogeneous semi-solid
substance known as “colloid.” The globes are associated into groups
or lobules. They are in contact with large wide lymphatic vessels.
The organ has a lavish supply of blood. It is also well supplied with
nerves. Colloid is the secretion of the epithelial cells which line
the globes. As these globes have no openings, the secretion must be
passed by osmosis into the lymphatic vessels. There is abundant reason
for believing that by this route the products of the gland reach the
blood, and are distributed by the blood to all the tissues of the body.
And here it is important to notice that associated with the thyroid
gland are certain very small masses of tissue termed “parathyroids.”
There may be four of these—two on the course of the large arteries
which supply the thyroid gland from above, two related with the almost
equally large arteries which supply it from below; but the number
varies. The parathyroids do not contain vesicles. They are solid
masses of epithelial cells, traversed by bloodvessels and lymphatics.
Yet, like the epithelial cells of the vesicles, they secrete colloid.
Granules of this substance are to be seen within their cells. We cannot
pass over the parathyroids without this reference, since, small though
they are, they seem to be quite as important as the thyroid gland
itself, judging from the effects which follow their removal.
In all vertebrate animals the thyroid gland has the characters which
we have described. What was it like in the ancestors of the vertebrate
races? Its microscopic appearance in vertebrates, the only animals in
which we know it, is so anomalous as to convince an histologist that
it is a makeshift; it looks like an organ which, at a period no longer
visible through the mists of time, had a quite different function to
perform. This function it has lost—some other organ has taken it
on—yet it must do something which is useful to the organism. Otherwise
it would not have been preserved. It has been retained for the sake
of its by-function, for the sake of the internal secretion which it
produces. This is now the only work it has to do.
What was its prime function? It is an axiom of biology that an
animal in its individual development recapitulates, albeit with many
omissions and abbreviations, the ancestral history of its race. The
thyroid gland appears in the embryo as a diverticulum of the anterior
wall of the pharynx. It is remarkable in being a single, median,
unpaired diverticulum, whereas almost all other organs are bilaterally
symmetrical. The parathyroids are formed on the two sides in connection
with certain of the branchial pouches. In its earliest development the
thyroid gland resembles any other gland—a salivary gland, for example.
Until a late stage it retains its connection with the back of the
mouth. Occasionally indications of this primitive connection persist
throughout life. In most cases the place where the duct of the thyroid
gland used to open is clearly marked. At the back of the tongue—too
far back to be seen without the aid of a dentist’s mirror—there
is a =V=-shaped row of large papillæ (papillæ circumvallatæ). Just
behind the meeting-point of the two limbs of the =V= a pit is to be
seen—foramen cæcum. This pit is the vestige of the mouth of the duct
of the thyroid gland which opened into the pharynx in the ancestors of
fishes. It is an inconceivably long time since fishes diverged from
other races of animals. We do not know which of the various orders of
invertebrate animals now existent most nearly resembles our prepiscine
ancestor. The organ which has developed into the thyroid body of
mammals may possibly have disappeared from all the other descendants of
the common stock from which vertebrates and their nearest relatives in
the invertebrate sub-kingdom were evolved; but it is much more likely
that it has been preserved, and is still performing its prime function
in the higher invertebrate animals. Probably it is a functional organ
in a cuttle-fish or a scorpion or a worm, but so unlike the thyroid
gland of vertebrates that we fail to recognize its homology. There are
other instances in the body of the persistence of an organ long after
it has fallen into such ruin that not even archæologically-disposed
biologists can guess what it was like, or what purpose it served in
the days when it was at the height of its efficiency; but perhaps
there is none other which so pregnantly illustrates the physiological
doctrine of functional interdependence. Nature shows herself amazingly
conservative in retaining primal organs—the pituitary body, the
thymus gland, the thyroid gland, the suprarenal capsules—organs which
millions of years ago forgot the very rudiments of their craft; but
her conservatism is not mere force of habit. Although she no longer
has any use for the wares which she created these pieces of apparatus
to make, she cannot do without their refuse. Even the vermiform
appendix may have its use. Dr. Gaskell’s theory of the thyroid gland
involves a transformation so fantastic that it would provoke a smile
of incredulity were we to set it forth without a prologue far more
lengthy than our space permits. Yet Dr. Gaskell may be right. We can
but guess as to the nature of the prime functions of the thyroid and
parathyroids. For many geological epochs they have not been exercised.
But whatever else they did when they were indispensable constituents
of the organism, their activity was accompanied by the secretion of
colloid. Colloid is not made by other organs; therefore the otherwise
obsolete thyroids are retained. It is of course not impossible that, in
a certain degree, Nature, like a thrifty housewife, finds a new use for
superseded apparatus; but we are probably justified in believing that
the use is never really new. Not wanting the organ for its original
specific purpose, Nature relegates to it alone work which hitherto it
had shared with other of her tools.
A comparatively short while ago the attention of physiologists was
wholly concentrated upon the obvious or prime functions of organs.
Muscles contracted. The stomach digested. The pancreas secreted
pancreatic juice. The brain made thought. Now they understand, to put
it somewhat metaphorically, that gastric juice is made in the calves
of the legs; the ferment of pancreatic juice in the small intestine;
thought of a certain emotional quality in the large intestine. The
chemistry of the laboratory is far behind the body’s chemistry.
We cannot detect in the blood coming from contracting muscles the
stimulant—possibly a precursor of pepsin—to which the stomach reacts,
although the magical benefit of exercise seems to prove that there
is a chemical connection between the activity of the muscles and the
activity of the glands of the alimentary canal. It has been proved by
experiment that a substance produced in the epithelium of the small
intestine is the messenger upon whose call depends the potency of
pancreatic juice. The clearing of the brain effected by a judicious
pill shows that poisons of some kind are absorbed into the blood from
an overloaded large intestine. None of the organs lives altogether for
itself. The chemical products which it throws off, absorbed by the
blood, regulate the activity of other organs. Formerly the several
parts of the body were looked upon as independent. Their activity was
regarded as a direct response to the commands of the nervous system.
If it varied in kind, the variations were supposed to depend upon the
quality of the nervous impulses which reached the organ. Evidence is
rapidly accumulating that many exhibitions of function are evoked by
the calls of “hormones,” or chemical messengers, not by command of the
nerves.
Internal secretions, using the expression in its general sense, are
necessary for the co-ordination of the work of the various parts of
the animal mechanism. Colloid is the internal secretion of the thyroid
gland and of the parathyroids. Unlike most other internal secretions,
it is a substance easily analysed, and startlingly definite in its
chemical characteristics. It is composed mainly of a protein which
contains iodine. From this protein a substance termed “iodothyrin”
may be obtained, of which no less than 10 per cent. is iodine; but
it is uncertain whether iodothyrin is preformed in the gland. The
exact nature of the active substance of the internal secretion of the
thyroid gland matters little. Whether it be iodothyrin or a protein,
its activity depends upon the fact that it contains iodine in large
quantity. Iodine amounts to from 0·3 per cent. to 0·9 per cent. of the
weight of the whole thyroid gland in Man.
Iodine is very widely distributed in Nature. It is present in the air,
in rain-water, in herbage. It is also present in all parts of the
body, although in quantities which are infinitely minute. It is found
in sea-water, and is relatively abundant in marine plants. There is
no reason for supposing that it is deficient in districts in which
_goitre_ is common. It would appear more likely that the soil has
properties which result in the fixing of iodine in a form in which it
is not available for plant-food, and that in consequence animals are
unable to obtain a sufficient supply. Careful analyses have shown that
the thyroid glands of sheep bred in mountainous districts where goitre
is common contain but one-thirtieth part as much iodine as the thyroid
glands of sheep bred in places where goitre is rare. In ancient times
burnt sponge and seaweed were esteemed useful in the treatment of
goitre. Later, iodide of potassium given internally, and tincture of
iodine as an outward application, were the approved remedies. It is
now known that myxœdema and certain forms of goitre may be checked,
and even cured, by administering uncooked thyroid gland or even
tabloids of dried extract. Fortunately, it is not necessary to inject
it subcutaneously; the iodine-containing compound is so stable as to
resist the action of gastric juice.
Iodine stored in the thyroid and parathyroid glands is distributed
to all the tissues. The remarkable symptoms which indicate that the
tissues are not receiving an adequate supply may occur under either of
two conditions. Iodine may be deficient in the food, or the thyroid
gland may be incompetent; the former is the commoner cause. And here
we see the explanation of the formation of a goitre. By increasing the
size of the organ which selects iodine, Nature attempts to obtain and
store an adequate supply for distribution to the tissues.
Cretinism has been observed in animals. If attention were directed to
this inquiry, it might be found that it is not so exceedingly rare as
would be judged from the few observations that have been recorded. A
cretin, if a wild animal, falls an easy prey. If a domesticated animal,
little trouble is taken to insure its survival. A myxœdematous pig
is a dwarf with coarse, sparse hair, thick, warty hoofs, large jowl,
heavy ears. It is apathetic. A piglet presenting these characteristics
is not altogether uncommon in a litter. Among chickens and pigeons,
also, individuals appear which might, judging from their uncouth
appearance and mental dulness, be suffering from cretinism. The only
way of proving that this is the case is to feed them on thyroid glands;
it does not matter from what animal the gland is obtained. Operative
cretins, produced by removing the thyroid gland soon after birth,
recover their natural characters on a diet containing a daily allowance
of thyroid gland. The coarse hairs, or wiry towsled feathers, fall off,
and are replaced by a smooth, supple growth. The thickened skin becomes
soft and pliant. Mental apathy gives place to alertness. They make up
for lost time by growing more rapidly than other animals of the same
age, which have not been operated upon, although they never surpass the
normal stature.
=Suprarenal Capsules.=—Each of the kidneys is capped by a pyramidal
body weighing about ⅛ ounce. Small though it be, this organ is
essential to life. As Dr. Addison was the first to discover, in 1855,
its disease results in a cycle of symptoms which invariably has a fatal
termination. A college friend of the writer suffered from “slackness.”
Before he had finished a set of tennis, he abandoned the game, and
spent the rest of the afternoon lying on the grass, wrapped in a rug.
After hall, although he earnestly desired to conquer the subtleties of
the Greek grammar, he fell asleep over his books. As his countenance
was not ruddy merely, but bronzed like that of a man who has just
returned from a yachting cruise, he was the butt of many a joke.
Although already a qualified medical man, who had been in practice—he
had come to the University with a view to adding the degree of M.D. to
his M.R.C.S.—he had no suspicion that he was ill. Thought he wanted
“freshening up.” Took a trip across the Atlantic. Stumbled over a rope
on landing; broke his thigh. Spent two months in a New York Hospital,
but the bone did not mend. At last, the surgeons, growing anxious, sent
him back to London. He was seen by a leading physician, who told him
that he was suffering from Addison’s disease. Two months later he died
of failure of the heart. Disease of the suprarenal capsules is usually
of tuberculous origin. Its symptoms: muscular weakness and excessive
liability to fatigue; abnormal pigmentation of the skin; lowered
blood-pressure, and consequent sensitiveness to cold; cardiac weakness.
As the pigmentation of the skin and mucous membrane is not invariable,
and since it may occur without disease of the capsules, it is not
improbable that it is due to disease of the abdominal sympathetic
ganglia, which are usually affected at the same time as the capsules.
The suprarenal capsules are composed of columns of epithelial cells,
which radiate from a large vein in their centre. They are abundantly
supplied with blood and with nerves. The cells near the vein are much
larger than those in the peripheral portions of the columns. Amongst
them are nerve-cells resembling those of the sympathetic system.
The history of the suprarenal capsules is almost as obscure as that of
the thyroid gland. In the embryo they are relatively very large—larger
at one period than the kidney. At this period bloodvessels are formed
in them with great rapidity by a curious process of boring through and
channelling out of their cells. There are other facts connected with
their development in the individual and their varying form in different
classes of vertebrate animals which point to a “previous existence,”
but there is nothing to indicate that they were ever open glands. In
all vertebrates they are closed masses of cells, the only function of
which, so far as we know, is to produce an internal secretion; but the
importance of this chemical messenger in bringing about the proper
working of other organs is almost startlingly evidenced by the collapse
which follows disease, or removal of the organ which produces it.
The suprarenal capsules yield a substance which has been termed
“adrenalin.” It contains nitrogen, is crystallizable and dialysable;
but its chemical relationships have not been made out as yet. It is not
destroyed by boiling, nor by digestion with gastric juice. Injected
into a vein, it causes, amongst other effects, an immense rise in
blood-pressure, even though the amount injected be extraordinarily
small. Applied locally as a wash or spray, a solution of 1 part in
10,000 produces marked blanching of the surface; and it is useful,
in consequence, as a means of checking bleeding in small operations,
especially those on the eye or the nose. It is a most energetic poison.
Even ¼ milligramme is sufficient to kill a rabbit. In short, adrenalin
acts like the most powerful drugs known to physicians; and this drug,
manufactured by the suprarenal capsules, is constantly added to the
blood. Disastrous consequences follow a failure in the regular supply.
The tone of the vascular system is maintained by adrenalin. The nature
of its influence upon muscles is not known, but probably the complete
loss of muscular strength, which is one of the most noticeable symptoms
of disease of the suprarenal capsules, is an indirect result of the
lowering of blood-pressure. The muscles, it must be remembered, make up
about one-third of the weight of the body of a muscular man. For the
exchange of their waste products for food, they are dependent upon an
efficient circulation. They are unable to display their normal vigour
when the vascular system is not up to its work.
=The Pituitary Body= is another ductless gland of dubious history. It
is a round body, the size of a small marble, which occupies a deep
recess in the floor of the skull, beneath the centre of the brain.
It is composed of epithelial cells collected into irregular groups.
No homologue of the pituitary body can be found in the invertebrate
sub-kingdom. Its strange mode of development in vertebrate animals—it
is present in them all, from fishes to mammals—and the mystery in
which its prevertebral existence is hidden, provoke to speculation.
We must be content to state that it is undoubtedly masquerading under
an assumed name. “Pituitary body” is reminiscent of a long-abandoned
theory that it secretes fluid into the upper chamber of the nose.
Disease of the pituitary body is associated with a perversion of
growth even stranger than that due to disease of the thyroid gland.
The condition has been termed “acromegaly,” to indicate that all
extremities—toes, fingers, nose, lips, tongue—undergo enlargement.
With these three organs—the thyroid gland, the suprarenal capsules,
and the pituitary body—we must leave the subject of internal
secretions. Each of these organs is a ductless gland. Each has a
history which the zoologist is unable to transcribe. The document is
a palimpsest, the earlier script so faint as to be illegible beneath
the dark letters which a new era has written over it. Even the modern
script is smudged and blotted. The laws which it sets forth seem, as
a rule, to be destitute of sense, but a sinister meaning is evident
at times. We are tempted to regard these codes as obsolete, until the
mischief which follows their suppression calls our startled attention
to the fact that they are, in the most lively sense, extant. Myxœdema,
Addison’s disease, acromegaly, are ominous warnings that the three
ductless glands are no mere monuments of a past epoch, which owe
their survival to Nature’s indolence. They teach us that we must not
attribute the persistence of such organs to a conservatism which
resists innovation, or suppose that they would long ago have been
wiped off the statute-book if her inertia could have been overcome.
Undoubtedly Nature gives us many excuses for adopting this attitude of
mind. The “chestnuts” on a horse’s legs, the “dew-claws” of a dog’s
foot, are vestiges which would have disappeared if every part of the
body had to establish its claim to be regarded as useful before it
became entitled to share in the common supply of food; so, at least, we
are disposed to think. But, tempting though it be to attribute to sheer
conservatism the retention of an organ which has been superseded in its
original functions, and for which we cannot recognize any new use, it
is a temptation which must be severely checked. It is safer to suppose
that the fact that it has been retained is _prima-facie_ evidence that
the body has need of it.
There can be no doubt as to the importance of the internal secretions
of the three chief ductless glands. What about other organs—the glands
which make external secretions, for example? Does each of them make
also an internal secretion which influences the activity of other
organs? It is very difficult to prove the production of internal
secretions by such organs as the salivary glands, the pancreas, the
kidneys, because all the effects which result from their removal may
be due to the suppression of their external secretions. It is almost
impossible to distinguish the consequences which might be due to
the abolition of an internal secretion from those which ought to be
attributed to the loss to the body of the chief functions of the organ.
Certain physiologists are inclined to think that all organs—not only
the glands, but the liver, spleen, muscles, etc.—produce chemical
messengers which are discharged into the blood; and recent discoveries
tend to justify this view. As the time approaches when milk will be
wanted for the nourishment of offspring, it begins to appear in the
breast. Hitherto this has been attributed to nervous control. It is now
known that the secretion is provoked by a chemical messenger. If this
messenger, extracted from the organ in which it is formed, be injected
into the veins of an animal which has no call to secrete milk, it sets
up a condition of activity in its mammary glands. Such an illustration
of the possibilities of chemical, as distinguished from nervous,
control inclines us to attribute the harmonious working of the body in
large measure to the mutual influence of its several parts, instead of
invoking in every case, as used to be the custom, the directing power
of a somewhat bureaucratic nervous system.
It is curious to note that an internal secretion is essentially a drug.
Faith in drugs has suffered eclipse in latter days, and with good
reason. The medicines of fifty years ago so little resembled Nature’s
pharmacy that there is cause enough for astonishment at the credulity
of a generation that believed them to be charms by the exhibition of
which they could direct the working of the body. To be quite just,
our forebears did not exactly adopt this view. They still believed in
remedies. Docks grew in the same hedgerow as nettles. Therefore the
juice of the dock was an antidote to nettle-stings. Washerwomen found
wasps vexatious, but, fortunately, “blue-ball” cured the pain of their
stings, and prevented the swelling which otherwise would have occurred.
A new pharmacology is rapidly developing. The physiological action of
every substance likely to be of service as a drug is put to the proof.
Having ascertained what is wrong, and knowing exactly what effects his
drugs are capable of producing, the physician devises the adjustment
which he may attempt without risk of making matters worse. He then
seeks, if possible, a chemical messenger near akin to the messenger
whom Nature herself would send; at least, this is the ambition of the
modern pharmacologist.