The internal secretions : for the use of students and physicians

Front matter

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Preface To The Third Edition

The scepticism with which many medical men formerly held off from the study of the internal secretions has been gradually replaced by the opposite tendency which, in many students of endocrinology, is exhibited as an endeavor to interpret every change in the living human organism as a disturbance of the endocrine balance. Such one-sidedness is a great danger to every new science; it gives its opponents an excuse for attacking the very foundation upon which the science rests. As a warning against such exaggeration, I pointed out in the concluding chapter of the first edition, that it is only by taking account of the other regulating systems of the human body, namely, the central and vegetative nervous systems, and by considering the manifold influences of the surrounding world on the organism, that the physiology of the internal secretions can be investigated, and the knowledge obtained which should furnish a valid explanation of the countless, ever-changing conditions of life. In this, the third edition, I have endeavored to emphasize these relationships. Certain additions in which new discoveries are considered have also been made to the text.

To Drs. G. Guijarra (Spain), N. Ischlonski (Russia), J. Gutman (United States) and Konishi (Japan), I wish x PREFACE TO THE THIRD EDITION to express my indebtedness for the interest they have shown in this book by translating it into their own languages.

ArtHuR WEIL.

New York, January, 1923.

Preface To The Second Edition

That my method of treating internal secretions from the physiologist’s standpoint has met with approval and success seems evident from the fact that scarcely a year had passed before it was necessary to begin revisions for a second edition of this work; and also from the fact that during this short period translations into Russian and Spanish have already appeared. I have, therefore, made no radical changes in the general structure of the book, but have limited myself to the sifting of evidence, and the insertion of new findings when these had been verified by several investigators. I have sought by additions, substitutions and new illustrations to elucidate the theoretical considerations.

I wish to thank the publishing house of Herr Julius Springer for the many courtesies extended to me and for the excellent manner in which the book was produced.

ARTHUR WEIL.

Berlin, February, 1922.

x

Preface To The First Edition

In the past the subject of internal secretion has generally been treated by considering the individual glands in the order of sequence in which progress was made in their study and investigation. Manifestations due to the removal of a gland and the phenomena of readjustment effected by its reimplantation, by feeding with the whole gland, or by injection of its extracts were carefully studied; disease syndromes attributed to assumed hyper-, hypo-, and dysfunctioning of glands were likewise described; also atypical constitutional manifestations resulting from congenital abnormalities of glandular development were scrupulously recorded. From the facts collected in this manner, as well as from the pharmacologic action of certain glandular preparations, information concerning the physiological functions of the endocrine glands was obtained, and hypotheses were advanced which would harmonize as far as possible with all these findings. In this way it was hoped to elucidate the relationship existing between separate living processes.

However, this mode of presentation makes it very difficult for the student of endocrinology to obtain a unified picture that will clearly show the meaning of the internal secretions in the life cycle. The information concerning these endocrine secretions is scattered, and xiii xiv PREFACE TO THE FIRST EIDTION to learn the réle played by the various glands with reference to a particular function, such as circulation, respiration, form-building, ete., necessitates the seeking, collecting and coordinating of data from many literary sources, comprising not only records of single investigations but of extended monographs.

This method puts the young student of endocrinology in danger of over-estimating the significance of the various glands in specific syndromes; he is likely, in making a clinical diagnosis, to be too much inclined to specialize, and to forget that the human organism must be considered as one unit, possessing an intimate connection between individual cell groups; and that a change in one species of cells produces changes in all others.

To avoid these objections, I have endeavored to present the subject of the endocrine glands from a different point of view. I have dealt with the incretions as agents concerned in the production and regulation of the separate bodily functions, and have described the part which the various incretions take in each particular life process. In this little volume, it was not possible to deal exhaustively with the entire subject of endocrinology; the book was designed only as a short survey of the physiology of the internal secretions; as an introduction to the subject for physicians and students who wish to familiarize themselves with facts that will help them to interpret for themselves the meaning of the changes in internal secretory glands which they see in particular diseases.

For a more exhaustive study of the subject I may refer to the voluminous text book of Biedl; to ‘‘The Diseases of the Endocrines,’’ by Falta; to the monographs

PREFACE TO THE FIRST EIDTION > a on the male and female glands by Tandler and Grosz, Aschner, Lipschiitz, Harms, and others; to the work of Oswald on the thyroid; and, finally, to the ‘‘Text Book of Organo-Therapy,’’ by Wagner von Jauregg and Bayer.

I have refrained from giving references to literature. It would be practically impossible to enumerate without omission all the publications on the subject, continually increasing in number as they are. In his third edition, published in 1916, Biedl quotes about 11,000 references; hence, even an approximately complete bibliography would more than treble the size of the present volume.

ARTHUR WEIL.

Halle, November, 1920.

Table Of Contents

TRANSLATOR’S PREFACE .

Preface To The Third Edition

PREFACE TO THE SECOND EDITION PREFACE TO THE First EpItTIon

CHAPTER THE ORIGIN OF THE IDEA oF INTERNAL SECRETION x;

II. AND Its DEFINITION

THe EmsBryYoLoGy AND HISTOLOGY OF THE ENDo-

CRINE GLANDS

THE PHYSIOLOGY OF THE BLOOD .

THE CIRCULATION OF THE BLOOD

RESPIRATION AND VOICE PRODUCTION

METABOLISM Ee TOTS Stee Sa ve ES 1. Metabolism of Gases and Heat Regulation 2. Metabolism of Proteins, Fats and Carbohyd-

3. Metabolism of Inorganic Compounds . 4. Water Control and Kidney Function 5. Activities of the Stomach and Intestines. 6. The Vitamines and the Endocrine Glands 7. Metabolism and Museular Activity

VII. GrowrH anv Bopity Form 1. Growth of the Skeleton 2. Rapidity of Growth . 3. Shoulder and Pelvie Girth : 4. Structural Proportions of the Body . 5. Secondary Sex Differences . 6. Transformation of Sex 7. Hermaphroditism

VIII. Repropuction xvii

XVlil

TABLE OF CONTENTS

CHAPTER

TX.

THe SexuaAL IMPULSE : 1. The Germ Glands and Wagan induame, 2. Inversion of the Sexual Impulse

THE MIND AND THE INTERNAL SECRETIONS THE CHEMISTRY OF THE INCRETIONS MeEtTHOps oF TESTING FOR INTERNAL SECRETIONS

THe INTERRELATIONSHIP OF THE ENDOCRINE GLANDS

INTERNAL SECRETIONS AND THE NERVOUS Seine

222 222 236

243 252 266

271 277 283

Chapter I

THE ORIGIN OF THE IDEA OF ‘‘INTERNAL SECRETION’? AND ITS DEFINITION

The great progress of knowledge relating to the subject of internal secretion that has taken place during the last few decades was possible only because modern medicine had achieved a scientific status, and because the fact was recognized that the same natural laws which physics, chemistry and the other exact sciences have demonstrated operating in the non-living world as likewise control all the processes of the living world.

The science of endocrinology has developed from two sources which are in their very nature diametrically opposed to each other. One source, which is analytical, comprises the highly advanced subject of biological chemistry—with its task of discovering the building stones of living substances, and of tracing the course and fate of food stuffs from their ingestion through their passage into the body cells and their conversion into the final products of excretion; and the subject of histology which is engaged in penetrating farther and farther into the minute structure of living tissues. The second source which is synthetical has a goal which is the opposite of the aims of histology and biological chemistry; its purpose is to conceive the human body as a unified organism, to exhibit the close relationship between the cells and the organs, to explain the connection which exists between form and function—endeavors which find expression to-day in our modern conceptions of ‘‘constitution,’’ comprising the subject of ‘‘syzygiology’’ (science of relation).

In 1842, in the introduction to his ‘‘Organic Chemistry in its Application to Physiology and Pathology,’’ Liebig pointed out the fact that until the beginning of the nineteenth century the prevailing tendency in modern physiology was the analytical one, saying that, ‘‘ Investigation of the purposes and functions of separate organs, and their mutual relationships in the animal body, a subject which had once constituted the principal object of physiological research, was thereby placed in the background.’’ But these early theories of the mutual relationship of organs mentioned by Liebig had only a superficial likeness to our modern views, which strive for a unified conception of life processes. These newer views were ushered in when the cell, hitherto treated as a completely isolated object, became reinstated in its place as a component pert of the whole organism.

Teachings treating of the inter-relationship of organs, described as the ‘‘concensus partium,’’ were based upon the older view of Aristotle, as expressed in his “*Correlationes,’’ and upon the writings of Hippocrates, which Galen afterwards (130-201 A. D.) made the basis of his humoral theory. Galen believed that the blood, the splenic fluid, the bile and the mucus (phlegma) were the four juices or ‘‘humors’’ produced by the various organs, and that an abnormal mixture of these humors resulted in a variety of dyscrasias and diseases. Venesection was the practical outcome of such theories, since by blood letting abnormal humors could be removed from the body. Through Bordeau (1775) the conceptions of humors were particularized even further. He ascribed to every organ the generation of a specific substance to be conveyed into the blood stream. Thus even at this early period there was already a slight resemblanee to our modern endocrinology, which teaches that certain products of definite glands are conveyed into the blood and lymph streams, and that under- or overfunctioning of these glands causes an abnormal mixture of their secretions which results in disease.

The theory of nervous correlation originated with the progress made in histological technic and with the intensive study of the nervous system. The assumption was, that the brain was the ruler of the body; that stimuli carried by the peripheral nerves to the central nervous system kept the brain informed as to the state of the particular organs, and that this communication served to mediate the connection of the organism with the outer world. In this way the brain was thought to be able at all times to coordinate the separate activities of the distant organs into a single harmonious manifestation constituting life. This the brain was assumed to accomplish by means of stimulating and inhibiting impulses transmitted over centrifugal paths to the body organs.

With the concepts stimulus and reflex substituted for the concrete notion of humors ideas were introduced into medicine which involved the danger that they would lead into philosophical speculation rather than to the firm ground of scientific knowledge. Efforts were made to avert this. danger by advancing the hypothesis that the constant chemical changes of metabolic origin occurring in the cells acted as stimuli to the nerve endings, and that the transmission of these stimuli was an electro-physical phenomenon. These stimuli were supposed to influence the metabolism of certain ganglion-cell centers in the brain, and the resulting changes in these ganglion cells would act again as stimuli to be transmitted to the peripheral cells. Furthermore, it was soon learned that the masses of ganglion-cells in the intestines, heart and other organs are independent nerve centers which control the automatic activity of the respective organs, and which, like the glands of the body, are connected with the brain and spinal cord through the autonomic nervous system.

These views concerning the nervous regulation of all the life cycles dominated physiology until very recently. To the blood was assigned only an auxiliary task, that of a carrier whose function it was to deliver nutritious material to the individual cells, to relieve them of their waste products of metabolism and to transport these to glands and other structures concerned with the elimination of useless, excretory substances. Although, in general, the main function of the blood was thus correctly assumed, one fact was nevertheless overlooked, namely, that the blood was a genuine connecting link between the numerous organs, and that these organs might influence each other through the excretions they poured into the blood stream.

Other pictures also fitted very badly into this frame; for example, certain glands, like the thyroid, have no excretory ducts; hence, these organs were thought to be simply useless survivals from an earlier developmental period. Little attention was also paid to the manifold observations made in the clinic, and to the many illuminating physiological experiments which indicated beyond a question of doubt that the conception of all-powerful nerve centers was not justified; that many metabolic processes were carried out automatically and without any participation of the nervous system; and that the brain can be directly stimulated by products of cell metabolism circulating in the blood and lymph currents without the intervention of peripheral nerves.

In 1849 Berthold showed for the first time that after the severance of all nerve connections between the brain and the testicles the sexual impulse remained normal. Through removal of the testicles from young cocks and transplantation of these organs under the skin of some other part of the body, this investigator succeeded in retaining in the cock its masculine characteristics, whereas in those birds in which the transplantation was not made, or was unsuccessful, features were obtained that were characteristic of the castrated type, the capon. These facts caused the theory of nervous correlation to be discredited.

The. older conception that sexual instinct and secondary sexual characteristics are dependent upon steady ‘stimuli sent to the central nervous system from the cells . of the reproductive glands and transmitted over the peripheral nerves, and that, by a reverse process, the masculine or feminine organization of the brain determines a growth of body cells into certain specific sexual forms, was contradicted by these experiments. In spite of their importance. Berthold’s observations were searcely noticed, and they were soon completely forgotten. Forty years later, however, Brown-Sequard, who was then seventy-two years old, reported to the French Academy of Sciences his personal. experiences with testicular extract. This announcement created a great uproar and aroused the interest of the whole world. He reported his remarkable rejuvenation through the use of testicular extract: increased muscular power; a subjective feeling of greater pleasure in work; improved functioning of the gastro-intestinal tract, and other regenerative symptoms similar to those that have lately been produced by Steinach in senile rats and in old men in whom the vasa deferentia were ligated. Brown-Sequard’s experiments, which have since been repeated and substantiated many times, constituted a new argument against the overwhelming influences that had been ascribed to the central nervous system in the regulation of life phenomena. His experiments showed for the first time that there were in the body chemical combinations of still unknown composition which directly affected either the body cells themselves or definite nerve centers, and that the effect could be produced through the circulating blood, and did not necessarily arise as a stimulus travelling over centripetal paths to the brain. These experiments also constituted a practical confirmation of the older views of

THE ORIGIN OF INTERNAL SECRETION .

Claude Bernard who had taught many years before that besides the secretions which the glands of the body poured out through their ducts they also made specific compounds which found their way into the circulation, and that by means of these substances transmitted into the blood stream other glands and distant organs could be influenced. He spoke of a sécrétion interne, and a ““sécrétion externe,’’ and thus he is, indeed, the originator of our modern expression internal secretion.

As to the nature of these specific gland products, or as to the exact place where they were produced, there were at first only hazy conceptions; workers were satisfied to accept the interna secretions as given entities and to study their functions through observations derived from an abundant clinical material; through the manifestations produced by removal or transplantation of the glands; through gland feeding, and through injection of glandular extracts. These studies brought an _ everstronger conviction that besides the nervous correlation of organs there must exist other means by which these organs act upon one another—means independent of the nervous system and competent to stimulate or inhibit the activity of separate organs through the action of specific substances carried to them in blood or lymph. These substances were looked upon as messengers from cell to cell and, in accordance with the proposals of Bayliss and Starling, were named hormones. Later, Abderhalden, following a suggestion of Roux, introduced for them the term incretion, in contradistinction to the term excretion. Other names, such as autocoids, for stimulating hormones, ‘and: chalons, for depressing hormones, proposed by Schafer, have not been adopted, because, as we shall see later, the same hormone may have, in accordance with its point of attack, either a stimulating or an inhibitory action upon a particular function.

The development through which this subject of research has passed may be best understood tf the first definition of Brown-Sequard is taken as a starting point. He states: ‘‘We assume that every single tissue and, in general, every separate cell of the organism secretes certain products or ferments which are poured into the blood current, and which through the medium of the blood may influence every other cell. In this way a solidarity is established between all the cells of the organism by means of a mechanism other than the nervous system.’’ In this definition the idea of an incretion is still quite general; every product of cell metabolism which enters the blood, even an end product which is later destined to leave the organism as waste, is here included in the category of the internal secretions. Urea and carbon dioxide, for instance, while on their way to the kidneys and the lungs, and still able to influence other organs, would thus come under the definition of hormones. Indeed, animal experimentation has shown that urea injected subcutaneously causes an increase in the decomposition of protein substances, and that carbon dioxide in the blood excites the activity of the respiratory center—facts which according to this definition would make them hormones.

Should we go into the study of internal secretions from this standpoint there would be no solid ground upon which we could work; for.the extreme multiplicity of intermediate and end-products of metabolism, and the countless different relationships between the numerous cell groups, would make any general apprehension of the subject impossible. Moreover, Brown-Sequard’s definition assigns to each cell a twofold function, one of doing its own specific work, the other of forming a special ferment to serve for humoral correlation. It was recognized, by degrees, that the latter task is not allotted to every cell of the organism, but only to groups of cells arranged in a certain manner and forming a peculiar type of glands. In these glands the histological structure, consisting essentially of groups of secretory epithehal cells surrounding abundant blood vessels, and with no outlet in the shape of ducts, clearly indicates the direction which their output must take, 7.e., their secretions must pass into the blood current. These structures were, accordingly, named endocrine or blood glands, the purest type being represented by the parathyroids, the thyroid, the pineal gland, and the anterior and middle lobes of the pituitary.

Besides this pure type, another, an atypical group of glands, soon became recognized as belonging to the endoerine system. This group is represented by the pancreas and the gonads. These organs were first regarded as functioning only by means of products poured out from their ducts, but it is now known that within their parenchyma reside special types of cells that add to the blood a specific hormone. In the pancreas these cells comprise the islands of Langerhans; in the germ glands it is the interstitial cells lying between the germinal portions which produce the internal secretion. In a third type of endocrine glands, incretion is associated with the production of morphologic elements which find their way into the blood stream. To this group belongs the thymus; the latest investigators also add the spleen to this class.

The posterior lobe of the hypophysis and the medulla of the suprarenal gland deviate from the epithelial structure characteristic of all other endocrine glands. These glands are, nevertheless, counted as members of the endocrine chain because they possess the specific chemical attributes of an endocrine gland; they produce a specific substance (pituitrin and adrenalin) which no other organ produces. All these types of endocrine glands have one common property which they owe to the peculiar characteristic of hormones, i.e., they can stimulate organs far removed from themselves.

Among the endocrine glands, Gley includes the liver. This would be justifiable if the classification were made on the basis of its histological structure (epithelial cells, glandular arrangement, adjacency to blooa vessels), but if the nature of the substance it contributes to the blood is taken as the basis of classification, then its inclusion among the endocrine glands is not justified, for glycogen is neither a product specific of the liver alone, nor does it possess the characteristics of other incretions; that is, it has no appreciable action if used in very minute quantities, but, on the contrary, the action of glycogen is in direct proportion to the amount of energy it contains, and, hence, does not resemble the action of a catalytic—a property which characterizes all genuine hormones. Glycogen serves purely as nutritive material like fat.

The panniculus adiposus, a ‘‘non-glandular organ which plays, nevertheless, the role of an endocrine gland,’’ is according to our conception also no internal secretory organ. The same is also true of the plexus choroideus and its secretory product the liquor cerebrospinalis, a secretion to which not only the ependyma of the ventricles contributes, but most probably also the pia; this fluid, originating from two different sources, is evidently not a true incretion.

Gley, in accordance with his more generalized conception, classifies the internal secretions as follows:

(1) Internal secretions which serve as nutritive material; (2) morphogenetic substances, hormozones, which play their important réle through the control of tissuebuilding during the ontogenetic period; (3) hormones which stimulate the functional activity of organs; and (4) parhormones which produce detoxication through bringing about the conjugation of injurious metabolic products. This classification cannot well be followed, since the difference between hormozone and hormone cannot be strictly upheld. We shall see later, for instance, that the morphogenetic effect produced by the interstitial cell secretion of the germ glands depends precisely upon whether the secretion stimulates or inhibits organic functions thus bringing about alterations of metabolism that accelerate or retard cell division. The mucous glands of the duodenum and jejunum, though they do not fit into our classification, must nevertheless be added to the endocrine system, since these glands produce a specific substance, a hormone, secretin, which stimulates the secretion of pancreatic juice.

The definition of ‘‘internal secretory gland,’’ which we shall adhere to in our subsequent treatment of an internal secretion, is the following: Glands conforming to a definite histologic type, with a structure peculiar to each gland; manufacturing specific chemical combinations and delivering these to the organism through the blood and lymph channels, producing by means of infinitisimal quantities of these specific substances certain definite effects upon the functions of other body cells, without furnishing material for cell building.

As a basis for the assumption that the chemical structure of every glandular hormone is specific, we have the chemical composition of the incretory products so far isolated; adrenalin from the suprarenal gland; the erystaline hypophysin product from the pituitary; and the newly discovered thyroxin, which is evidently a hormone of the thyroid. The question whether every endocrine gland produces only one or a number of specific products remains unanswered for the present. We meet with further difficulty when we attempt to answer the question whether the incretions are products altogether newly manufactured from the nutritive materials and the intermediate substances of cell metabolism circulating in the blood current, or whether these hormones already exist in the food and blood, and are only appropriated and distributed by the glands. The great scepticism which prevailed in regard to the synthetic powers of the organism before Woehler accomplished the synthesis of hippuric acid from benzoic acid and glycocoll has lately been replaced by the opposite inclination, a tendency to credit the organism with immense synthetic powers, in spite of the fact that recent observations concerning protein building from aromatic amino-acids show specific bounds to the synthetic ability of the organism. In addition to this proof that there are limits to the capacity of the animal cell to manufacture its own materials, the knowledge which we possess concering the indispensable vitamines (nutramines), which cannot be manufactured by the animal organism and must be supplied by the food, should guard us against an overestimation of the synthetic powers of the body. The close resemblance existing between certain deficiency diseases (diseases due to lack of particular vitamines) and diseases of the endocrine glands —the resemblance of pellagra, for example, to Addis n’s disease—has recently led many investigators to question whether the vitamines may not be either precursors of particular hormones, or the hormones themselves, stored within the endocrine glands. We shall discuss this question more fully in a later chapter.

At the present moment the conception ef endocrine functions to which the greatest importance is attached is that these glands dominate the life cycle by the production of certain substances which act on other organs as stimulating agents. Another hypothesis supposes that it is the function of these glands to take poisonous products of metabolism and to render these poisons harmless by binding or reconstructing them. As a model for such hypothetical detoxication we have the known behayior of the liver, which renders the ammonia resulting from the desamidization of amino acids harmless by converting ammonia into urea; and which also transforms a great variety of other decomposition products into indifferent substances, storing them as glycocoll, urea, etc. Another such hypothetical detoxication function is attributed to the thyroid, which is thought to abstract iodine from the circulation and to combine it in the form of harmless proteo-iodine compounds—an hypothesis seemingly sustained by the presence of an iodine-containing protein discovered in the thyroid in 1895 by Baumann. But the detoxication hypothesis is not applicable to every ease; the experiments of Brown-Sequard indicate that the action of the testicular juices must have been of a stimulating character, for the small quantities he used excluded the likelihood of their possessing a detoxicating function. Besides, if the endocrine glands were detoxicating agents, poisonous symptoms of some sort would appear after their removal, since, in their absence, the toxic substances, being no longer bound, would not be restrained in their activities. But we know that though certain definite changes in metabolism may be produced by the loss of certain glands as, for example, in castration, there need, nevertheless, be no immediate serious toxie effects produced by their absence.

After the removal of the thyroid, toxic substances have never been found in the blood (Bachmann and Asher). Hence, it may safely be assumed, as a general truth, that the disturbances in the normal processes of life which appear after the removal of an endocrine gland are due to the lack of its secretion and not to a flooding of the organism with poisonous products of metabolism because of the absence of a detoxicating agent. This view has become the guiding principle in the application of endoerinological science to various disciplines of medicine; the diseases of the thyroid (Basedow’s disease, myxedema, cretinism, etc.), of the hypophysis (acromegaly, dystrophia - adiposo - genitalis), of the parathyroids (tetany), or of the gonads (eunuchoidism), are, in the light of our present knowledge, ascribed to an altered secretion of the respective glands as the result of their hyper- or hypo- or dysfunctioning, and not to a lack of detoxication. Upon this view also the therapy of endoerine gland disturbances is based; a deficiency in hormone secretion must be made up, however this may be accomplished; whether by implantation of a healthy gland; or by the administration of the whole gland or its extracts; or by the injection of appropriate gland preparations. In cases of abnormal secretion the remedy may be sought in the removal of the diseased portion of the secreting gland, as is not infrequently done in Basedow’s disease.

The theory of detoxication received its chief support from the rapid deterioration observed in animals after the removal of the parathyroids or the adrenals. Loewi and Gettwert found that the serum of adrenalectomized guinea pigs injected into frogs stops the heart in diastole. This action they could prevent by the use of atropine. They concluded from this that a poisonous substance, probably cholin, is present in the serum of an adrenalectomized animal. We shall learn in another chapter that the base cholin is found chiefly in the cortex of the adrenals, being combined there in the form of lecithins, while the adrenal medulla contains a blood-pressureraising substance, adrenalin, the absence of which is followed by a marked sinking of the arterial tension. Two entirely different functions seem to belong to this one endocrine gland, a detoxicating function associated with the storing up of cholin, which is capable of binding other metabolic poisonous products, and another, a genuine incretory function, which is dependent upon the action of adrenalin.