The internal secretions in practical medicine

Front matter

Class

Book

GqipglitW.

Table Of Contents

I Introduction : Broadening the Scope of the

Practice of Medicine 1

II The Internal Secretions with Special Reference

Preface

A NUMBER of phAT^sicians, especially those who have read or heard one or more of my papers on subjects related to the glands of internal secretion, have expressed a desire to have some of them available in more permanent form. Hence this collection of articles in book form.

Unlike my earlier book, "Practical Hormone Therapy : a Manual of Organotherapy for Practitioners" (which is referred to occasionally in the following pages), the units comprising this collection were not written originally with the inteniton of fitting them together as harmonious and consecutive whole. As a result of this there is a certain amount of redundancy which it has seemed best to leave unmodified. As these reiterations have been reread for publication in this present form, the fact has been emphasized that no harm can come from reading some essential more than once, especially when the repetition lends weight to some particular contention in one paper and to a different one in another.

Several additional paragraphs have been added to a number of the articles as originally published in the medical press, with the idea of making them more comprehensive and as up-to-date as possible. As a matter of fact quite a number of experiences have been reported in current literature which amplify my position in a previously published report.

X THE INTERNAL SECRETIONS

and their inclusion here adds emphasis to what may have been said.

No attempt has been made to cover the entire subject. It is far too vast. In fact it would take a small library to include all the information now at our disposal regarding the glands of internal secretion and their hormones. However some time has been spent in preparing a fairly complete index so as to facilitate the study of various phases of the subjects covered which may be of immediate interest to the reader and 3^et be discussed in more than one chapter in the book.

For a more complete consideration of the therapeutic side of this subject the reader is referred to my book mentioned above; and also to a quarterly journal entitled "ENDOCRINOLOGY" which is a periodical reviev/ of the current literature on all phases of this subject. This journal is published by the Association for the Study of the Internal Secretions, which I assisted in starting in 1916. Further information regarding the activities of this Association will be sent to any interested physician on request.

My thanks are due to a number of colleagues for the encouragement given me to have these papers collected in this form, as well as to the publishers of various medical journals in the United States and Great Britain in which some of the chapters already have appeared, for the privilege of reprinting them in this form.

IN PRACTICAL MEDICINE ix

I realize that some of my statements are open to criticism, and I will welcome any constructive critical remarks or queries. I do not profess to be more than an ardent student of what is to me a very fascinating subject.

I need not apologize for my interest in this subject, nor for the enthusiasm it has engendered. I only hope that some hint in this book may serve to make a real difference to some reader's consideration of a difficult case; and that as a result of reading it some tangible advantage may accrue to both patient and physician.

HENRY R. HARROWER.

Glendale, California.

July, 1917.

THE INTERNAL SECRETIONS IN PRACTICAL MEDICINE

INTRODUCTION:

BROADENINCx THE SCOPE OF THE PRACTICE OF MEDICINE

AS our knowledge of physiology becomes more intimxate and our application of some of the ideas set forth by the experimentalists are put into practice, we find the scope of medical practice broadening in a remarkable manner. Revolution follows revolution until the standardized procedures of to-day differ as radically from those of, say, 25 years ago as do the present conceptions of the physiologic relations of the various parts of the body compared with those held at that time.

Undoubtedly the most radical as well as important advance in medicine is our better knowledge of the endocrine system — that interlocking, though widely separated, collection of glands of internal secretion wdiich we now know is in supreme control of growth, both physical and mental; metabolism; the sympathetic nervous system, with its regulation of vascular tone and blood pressure; as well as the indefinite and complex factors gathered together into the one well-known term "constitution." The hormones produced by these wonderful glands are secreted into the blood and serve to correlate function and harmonize many of the widely differing functions of the body. Their chemical messages are of such a nature that to ignore them and their subtle influence is to miss a very large and important part of the information which may be at the disposal of any observant physician.

Just as the discovery of the hormones and the unravelling of the intricate skein of their relationships has revolutionized physiology, so the knowledge we have been able to deduce from these facts is revolutionizing therapeutics, for it is now generally recognized that organotherapy is making possible the successful treatment of many chronic and complicated disorders.

The study of these endocrine glands will well repay the interested reader of the hundred and one articles and abstracts now appearing in current medical literature; and as he applies the obvious treatment in a given case, he will be both surprised and pleased at the results which so often follow the application of this altogether scientific and reasonable branch of therapy.

It is not necessary within the limits of this brief introduction to do more than direct attention to the great possibilities of this phase of medicine; and to outline the essential facts upon which the science of practical hormone therapy has been built.

By far the greatest principle is that of "homostimulation," which is included in what has come to be known as Hallion's law, which is as follows: "Extracts of an organ exert on the same organ an exciting influence which lasts for a longer or shorter time. When the organ is insufficient it is conceivable that this influence augments its action and, when it is injured, that it favors its restoration." This has been demonstrated experimentally and clinically so many times, that it is almost axiomatic, though it is not infallible, and may still be criticized occasionally by some. Granting what Hallion has said, functional insufficiencies of many of these organs may be expected to be favorably influenced by giving suitable doses of the corresponding gland secured from animals.

Closely allied to this is another slightly different phase of organotherapy. Frequently it is not sufficient to attempt to stimulate a lagging gland. One must replace, in part at least, the missing substance that it should have been furnishing to the body. This is what is known as "substitutive organotherapy." In conditions like cretinism or infantilism where the thyroid or gonads are absent, one can measurably restore the activity that is reduced or absent because of the lack of the hormone stimuli from the glands in question. In severe functional conditions we expect to benefit from organotherapy in at least two ways — by substituting for the missing hormones and, also, by causing what is known as homostimulation, the principle so well described in Hallion's law just quoted.

Again the chemical substances produced in the normal physiologic action of certain of the ductless glands have a definite pharmacological action and its application in medicine is the so-called "specific organotherapy," for the influence of the drug — these extracts must be considered purely as drugs — favors some desirable action as, for instance, the stimulation of the uterus with the posterior pituitary principle during a delayed labor. In such a case there is no evidence whatever to prove that this hormone principle is absent or even that the pituitary is not working normally. We simply make use of the specific action of this substance.

Finally in our clinical and laboratory experimenal work we have found that the administration of certain "extracts" (as they are usually but, in some instances, erroneously, called) cause certain physiologic reactions and we make use of these facts by applying what is, strictly speaking, "empirical organotherapy."

No matter in what conditions organotherapy may be used, irrespective of its "scientific" or its "empirical" basis, it is a valuable addition to our medical armamentarium, for where its application is physiologically proper one may expect it to give results and therefore be rational, while in the not infrequent cases where there may be a question about the the exact raison d'etre of a certain organotherapeutic remedy, it is rational because it is resultful. "We care not how the results come, provided they come, and come quickly."

Organotherapy, however, is only a small part of endocrinology; a part of it which has not yet recovered from the rank empiricism and quackery of a few decades ago. The study of the relations of the glands of internal secretion whether followed by the application of organotherapeutic procedures or not, is of great importance; and as various phases are considered from certain practical points of view, it will be clear that the remark of one writer — ''in these days the internal secretions are beingstudied as never before, and most assuredly are coming into their own" — is perfectly true; and that there is plenty of excuse for the widespread interest now being accorded to this growing branch of medicine.

The more time and attention that is given to the practical study of endocrinology, the broader will be the scope of the practice of medicine and the greater the professional prestige and profit of the aggressive physician who measures and applies the advances in medicine by the only reasonable standard — the standard of ''tests-and-results."

II

THE INTERNAL SECRETIONS WITH SPE- CIAL REFERENCE TO THE TREAT- MENT OF CHRONIC DISEASE

THE rapidly increasing fund of information which students of endocrinology are making available for interested members of the profession, is modifying many of our conceptions of internal medicine as well as changing some of our ideas regarding treatment.

As we bring these facts to bear upon numerous and widely differing phases of medical practice, it soon becomes clear that a great fundamental principle is involved, which neither the skepticism of the ignorant nor the passage of time can change. The hormones, or active principles elaborated by the glands of internal secretion, exert a decided influence upon those factors concerned in the causation as well as the cure of the majority of chronic diseases. Hence, hormone therapy, or the use of animal extracts in therapeutics, contains potentialities worthy of practical consideration by those who treat the numerous persistent and intractable ills which the flesh seems to be inheriting in increasingdegree.

An address read before the Southern California Medical Society at Los Angeles, California, December 2nd, 1915.

The subject is still in its formative stage, and occasionally one finds those who look at it askance, despite the innumerable encouragements which we are constantly meeting from day to day. I just happened to pick up the current issue of the American Journal of Obstetrics (Nov., 1915, p. 885), and read an interesting discussion on the value of corpus luteum therapy. One of the participants, Dr. A. T. Jones, of Providence, made a statement which I would like to repeat : 'With reference to organotherapy, I think the profession is divided into two classes. As a rule one class loses its head over organotherapy and believes everything can be cured by organic extracts" — and, by the way, I have been put into this class because my recent book, "Practical Hormone Therapy," merely for the sake of comprehensiveness, takes up some forms of organotherapy with which I have no experience, because I have little faith in them — "while the other class is that group who would not give organic extracts even if they knew they were going to get a good result. They will not take it up; they never have tried it. I believe these extracts are of value, and particularly the corpus luteum extract."

The writer fully agrees with Dr. Jones, and while one meets more men who should be in the second as compared with the first class, I am finding an increasing number of progressive physicians who are open to conviction and who, realizing the vast possibiHties of this study, are exploring its depths and finding many most pleasing experiences there. In the same discussion just referred to, Leighton, in concluding, said: ''This therapy has its limitations. It is not a cure-all. There is one trouble, and that is we do not use it enough!" And this applies in other equally practical phases of the subject to which brief allusion shortly will be made.

With very few exceptions, all chronic diseases have associated with them, and are aggravated by, a disturbance in one or more of the internal secretory organs. If this position is correct, we have another angle from which to consider those of our patients who are chronic sufferers. Many articles and editorials in our own and foreign medical literature (and, parenthetically, it must be admitted that abroad the}^ do more work in this line, hence more information is to be found in the French, Italian and English literature) direct attention to the new avenues of therapeutic endeavor that are being opened up. And they are being well traveled. Organotherapy is being studied as never before, and those who are attracted by its fascinations, are learning that the results sometimes attained are not simply good, but wonderful.

You all have personal knowledge of the diverse therapeutic possibilities of the principle from the 'infundibulum of the pituitary body first suggested as a remedy by Blair Bell, of Liverpool, as late as 1909. You know of its startling effects upon the uterus in labor and of its value as a postpartum remedy, its influence in such remote conditions as intestinal paresis, anuria and agalactia; and finally of its definite value as a heart tonic. In fact in a personal letter from the late Sir Lauder Brunton, he remarked that pituitrin was a more efficient heart stimulant than either digitalis or strychnia, and it is none too often used for this purpose either. Now I haAX not enumerated all the advantages of this single remedy and there are other organotherapeutic preparations almost as wonderful.

None the less to some ''it is still too early to pass judgment," and as another put it, ''we are still groping in the very dimly lighted recesses of this new study." However, it is encouraging to recall that a single experience is worth ten times as much as an argument; and the tests-and-results method is the only way to convince one's self that what may be said here to-night is not just the dream of a visionary crank.

Obviously we cannot more than refer to the mere fundamentals involved in the relation of the internal secretions to the incidence and control of chronic disease. We can, however, refresh our minds on a few of the better known matters and, perhaps, hint briefly of some of the other possibilities of this rapidly advancing and increasingly interesting siibject.

Probably more has been written about the thyroid than about any of the other glands of internal secretion. It has been most carefully studied for many years and its pathology and physiology are only just beginning to be fairly well understood; in fact, though this is probably the best known of the endocrine glands, we are not yet able to isolate its active principles,* and we have still much to learn of the intricacies of its physiologic relations. The epoch-making work of George Murray, now of Manchester, in the original application of thyroid therapy in the major thyroid disorders myxedema and cretinism, seems to have directed attention far beyond the much more common minor thyroid insufficiencies, and evidence of this is found in the last U. S. P., for in it the dosage of desiccated thyroids is given as 5 grains, an altogether preposterous dose in the majority of the conditions in which thyroid is now used. Instead of this pharmacopoeial dose, which, by the way, may be quite reasonable in certain cases of athyroidia and severe thyroid disorders, we now rarely use more than one grain and frequently a quarter or half a grain three times a day is quite sufficient to bring about very satisfactory results.

The thyroid gland is functionally disturbed, slightly in some cases, more in others, in many every-day conditions, many of which are chronic in their manifestations. Those disorders which are dependent upon perversions of the metabolism —

♦Since this was written a communication from the Mayo Clinic by E. C. Kendall announces the discovery there of what appears to be the active principle of the thyroid gland.

IN PRACTICAL MEDICINE II

rheumatism, gout and perhaps, in some degree, diabetes — usually have a thyroid element of greater or less importance. Following the original work of my very good friend. Dr. Eugene Hertoghe, of Antwerp, Leopold Levi and his associate. Baron Henri de Rothschild, of Paris, have made a most minute study of the part that the thyroid plays in almost every disorder. Every patient who comes to their hospital virtually is studied as a thyroid case, and in their recent book, "La Petite Insufifisance Thyroidienne et son Traitement," it is remarkable to note how large a variety of conditions have a distinct thyroid aspect and, more practical yet, are either directly benefited by the administration of thyroid or the regular treatment is made more effective by the addition of one or two centigrammes of thyroid per day. More than forty disorders are in this category from neurasthenia to psoriasis. Yet, like most enthusiasts, they have been laughed at, and sneered at, too, for fifteen years or more. Still Levi and de Rothschild have mastered the technique of thyroid medication and use it with much advantage in many conditions, both distinctly thyroid in origin and in which no obvious thyroid disturbance can be found. In this country we have still a few things to learn in this particular corner of this field.

Closely related to thyroid hypofunction is the condition known as pluriglandular insufficiency, an extremely common symptom complex which is more than occasionally overlooked. The statement recently has been made that disorders of the hormone-bearing organs always affect more than one gland, since the intimacy of these organs renders it impossible for one gland to be disturbed without an associated disturbance in one or more of the others related to it. There are two principal forms of pluriglandular insufficiency, the organic and the functional. The former commonly asserts itself in certain developmental disorders and in syphilis. Right here is a phase of syphilology which deserves cloesr attention. In a paper which I prepared for a special issue of The Practitioner (London), on Pluriglandular Insufficiency,* a number of reports were collated showing the relation of syphilis to ductless glandular syndromes. In such cases the information has usually been elicited at the autopsy table, though several cases of obvious endocrine disorder were traced to syphilis and treated with comparative satisfaction. The chief deduction that may be made from this is that syphilis as a generalized disease, may and does affect the hormone producing system and its treatment may be extended by adding to the usual arsenic or mercury treatment, suitable organotherapeutic extracts to stimulate the various semi-active ductless glands and thus cause a general betterment not otherwise attained.

In this connection an abstract in the Journal of

*Chapter V of this book.

the American Medical Association (October 2, 1915, p. 1223), is instructive. ''A striking case is reported by Korczynski in which inherited syphiHs seems to have impaired the functioning of the thyroid, hypophysis, ovaries and blood-producing organs. The child was mentally backward. Thyroid treatment and treatment for syphilis were given together, and a pronounced change for the better was soon apparent and has continued to progress. . . ." The functional forms of pluriglandular insufficiency are not associated with the obvious manifestations that the more marked organic conditions usually show. The reduced production of the ''chemical messengers" is none the less present, for when an individual is run-down, for instance, when the elimination is not as it should be, when the muscles are easily fatigued, the nerves easily excited and there are present the other usual manifestations of neurasthenia and debility, one can hardly believe that 4:he glands of internal secretion alone are working normally. In such cases pluriglandular therapy is an exceptionally useful treatment, alone or combined with other treatment which the exigencies of the case may indicate. It may be w^ell, incidentally, to remark that in ovarian disorders where luteal therapy is indicated and likely to be effective, the addition of some of the extracts of glands known to be intimately related to the gonads, the thyroid and the pituitary, will more than likely make the response to treatment more decided and resultful.

The control of the sympathetic nervous system by the chromaffin hormone produced in the medullary portion of the adrenal glands, makes these organs of supreme importance in numerous conditions. Take that most common of all clinical manifestations, pain, and recall that it has been shown by competent investigators to be a decided stimulant to the adrenals and thus 'Vears them out." This is a partial explanation, at least, of the clinical value of preparations of this character in many disorders including cholera (with its extreme pain and collapse), shock (with its associated acute adrenal insufficiency first intelligently discussed by Sajous, of Philadelphia about 13 years ago), postfebrile collapse or asthenia (conditions definitely traced to hypoadrenia and just as definitely benefited by the obvious therapeutic procedure — the administration of adrenaHn or similar products), and other important disorders.

Crile's valuable studies which have given us anoci-association and the power to reduce or entirely eliminate post-anesthetic shock by removing the stimuH which unduly overwork the kinetic system, are based in a large measure upon the physiological chemistry of the adrenal medulla, and while his most profitable work has been of a prophylactic nature — to prevent the unpleasant results at one time not infrequently following operations, the same principle applies in therapeutics, for when the adrenals have been depleted and the body is suffering from the lack of the normal amount of adrenin, with low blood pressure, asthenia and collapse, the natural thing to do is to secure the missing substance from animals and give it as quickly and directly as possible, just as we have learned to do the same thing with thyroids from sheep or corpora lutea from sows.

Now you realize, of course, that this subject which was chosen on the spur of the moment as the result of a telegraphic request by your Secretary to my friend. Col. McCullough, of the Surgeon-General's Library in Washington, has been considered only in its broadest general aspects. It is as broad as the influence of the hormones upon physiology, and the limits of its practical usefulness have not yet been reached, although we have already learned many, many things.

There is much more, and the more we study and apply these principles in our work, and especially that part of it which concerns the treatment of chronic disorders, the more we appreciate the enthusiasm of many who are daily delving into these secrets and are finding in them so much that is available in the every-day routine of medicine.

Ill

THE RELATION OF THE ENDOCRINE GLANDS TO FUNCTIONAL DISORDERS

WHILE the study of the glands of internal secretion has received a great impetus in the past few years, and the science underlying the diagnosis and treatment of endocrine disorders certainly has advanced greatly in this period, there is still a v^elldefined tendency to consider ductless glandular disease per se rather than the functional pathology resulting from modifications in the chemical activities of these glands.

Disorders of function obviously are of far greater clinical importance than organic disease not merely because of their much greater frequency, but because the former are merely more or less slight aberrations from the average, whereas the latter involve structural changes which in many cases are only partially amenable to the very best of treatment.

The discovery of cretinism, myxedema, the Addison, Froehlich or Graves syndromes is comparatively easy, for each of these conditions is a disease with a more or less definite pathology and symptomatology. But the insidiousness of func-

Read in a Symposium on Functional Pathology before the Sections on Medicine and Neurology, California State Medical Society at Coronado, April, 1917.

tional pathology of the glands of internal secretion and the frequency with which disturbances of their functions play a part in many acute as well as chronic conditions of every day occurrence, makes their study of greater clinical importance than the more definite and easier demonstrated ductless glandular diseases of which a few have just been enumerated.

With our added knowledge of the physiology of the endocrine glands and its importance, we are enabled to study many a functional condition from a viewpoint which is considerably different from that of past years, and this may enable us so to modify our treatment that many of the hitherto intractable disorders may now respond to our efforts.

In an editorial in the New York Medical Journal (1) published a few months ago, the importance of functional medicine was emphasized and it was remarked that in order that the advances in the pathological sciences might be fully appreciated and be of the greatest usefulness ''there is need for a better understanding of fundamental physiological principles and a much wider appreciation of functional possibilities. To this must be added the ability to correlate new findings and to detect departures from the normal in their early stages. It is only from such studies as these that we may hope to acquire that breadth and keenness of vision so essential to-day to offset the narrowness and concentration of specialism/' As a result of this, in the words of the same editorial writer just referred to, "our diagnoses will become more fundamental and our therapeutics more vital."

I have seen many a case with the diagnosis of rheumatism or tuberculosis or neurasthenia or indigestion in which the ductless glandular element was not even thought of. Why should a physician study the thyroid activity of a patient with tuberculosis, or connect the adrenals with neurosis? As a matter of fact, it is impossible for a severe infection like rheumatism or a protracted disease like tuberculosis not to make a very decided mark upon one or more of the glands of internal secretion, and since these glands respond so easily to the influence of infections, toxemias or even psychological states, it takes but a short time to involve them.

It can be taken for granted that questions concerning therapeutics always must be matters of opinion in which unanimity is unlikely; but questions of pathologic physiology are now being ascertained with precision and the subject is being put upon such a basis that dissent is not so probable. At least the relations of certain functions of the body are now sufficiently understood so that we can refer to them with confidence and it is to some of these that I wish to direct your attention to-day.

Every function of the body is in some way directly or remotely connected with the work of the endocrine glands, hence disorder in them invariably, let me emphasize this word, spells disorder iti other functions. So really the functional pathology of the endocrine glands is reflected in almost every phase of the practice of medicine, for growth, metabolism, oxidation, resistance to infection and the more indefinable but none the less important fundamentals, constitution and temperament, are now considered to be dependent upon ductless glandular action.

Furthermore the clinical leading of information of this character prompts us to use measures in the place of or in conjunction with those to which we have become accustomed, and such modifications of the treatment are a decided advantage towards greater success. In other words, when we are considering a given disease we will find out more of value and be able to render a more satisfactory service if the functional pathology of the endocrine organs is also considered — if we consider the patient as a whole rather than his disease as a unit. As yet, however, this is not the rule, for there still seems to be a tendency to study diseases instead of patients, and to treat certain text-book symptoms with whatever measures may be uppermost in the physician's mind.

Our knowledge of clinical endocrinology might be considerably better, at least in so far as discerning the earliest beginnings of these subtle influences is concerned. It is not in the discovery of well-differentiated disorder, but in the appreciation of the ordinary chemical changes of the beginnings of disease — the early steps in functional pathological change — that one attains the best results and the greatest personal satisfaction.

In an editorial note on cancer, Clinical Medicine (2) remarks: "We still are in constant protest against the neglect of the study of physiology now prevalent in the entire profession. Over and over again v^e have urged upon the profession the importance of so studying the physiology of the human body that the very first departure from normal activity of any of the functions shall be detected and the cause of such departure removed. . . . To the chemistry of the blood, we must look for the essential cause of cancer."

Physiology is too complex for internal medicine, much less the other branches of medicine, to be reduced to one single phase of study. The broader our conceptions of the physiologic functions of the body, the more intimate is our knowledge of the cellular interrelationships of the various integral parts of the organism; and hence the greater is our appreciation of the importance of more or less insignificant modifications of these relationships — or ''functional pathology" as it is called.