Popular Science Monthly/Volume 85/December 1914/Ductless Glands, Internal Secretions and Hormonic Equilibrium I

by Fielding Hudson Garrison

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DUCTLESS GLANDS, INTERNAL SECRETIONS AND HORMONIC EQUILIBRIUM

By FIELDING H. GARRISON, M.D.

WASHINGTON, D. C.

IN the year 1749 there came up to Paris from the Pyrenees a young medical graduate of Montpellier who was destined to become, by reputation, at least, the most distinguished French practitioner of his time. At the age of twenty-three Théophile de Bordeu (1722-76) was already professor of anatomy at Montpellier and inspector of mineral waters at Auch and Pau; at twenty-five he had been elected a corresponding member of the Royal Academy of Sciences, and, except for an empty purse, his Parisian success was assured, not only through his handsome presence, his attractive meridional disposition and his newly acquired fashionable connections, but in part through the influence and reputation of his father, who was one of the best known Montpellier physicians of his time. In order to launch himself it was necessary for young Bordeu to pass the examinations of the Paris Faculty (his Montpellier degree counting for nothing here) and to gain the good will of its members; yet, in spite of these handicaps, he began to loom large in public consideration, when his fortunes took an unexpected turn. Bouvart, a rich and powerful practitioner of the day, became so envious that he pursued Bordeu with venomous hatred, and accused him of stealing jewels from the body of a dead patient.^[1] On this charge he actually succeeded in having his name stricken from the list of Parisian physicians, and it was reinstated, after long dispute, and only through powerful influence and by two acts of Parliament. The reason for this savage manifestation of professional jealousy (the charge of theft is said to have been false) was not because the young Béarnais physician possessed any very formidable, overtopping ability, but on account of the ease with which he glided into a fashionable practice and aristocratic consideration. In an age in which the byword was "Le ridicule tue," his morals and his moral life were those of the courtiers of the period, and he seems to have succeeded largely through the good graces of women, one of whom, in fact, raised the money start him in practice. In his early days he had not found the rustic patients of the provinces to his liking and he aimed at a court clientèle with such success that shortly before his death he was called to the bedside of the moribund Louis XV. He himself was found dead in bed on the morning of the day before Christmas, 1776, and his old enemy, Bouvart, who seems to have always kept him in mind for judicial hanging, vented his glee in an epigram which, for venom, matches up with what Louis XIV said as the cortège of la Montespan passed by in the driving sleet: Je n'aurais pas cru quil fût mort horizontalement!"

At the present time, the scientific reputation of Bordeu is of the slenderest kind. He is one of the gods of the old Montpellier faculty. In his relation to the fashionable mineral springs of the Pyrenees—Pau, Barèges, Bagnères—he seems the original, indeed, the archetypal Badearzt. He was a good anatomist, a piquant writer on medical history, a promoter of variolation. His view of the brain, the heart and the stomach as "the tripod of life" made its fortune in its day, and he achieved a great reputation by his revival of the complex pulse-lore or ars sphygmica of Galen and the Chinese physicians, a phase of eighteenth century medicine which Dr. Weir Mitchell pithily described as "observation gone minutely mad." In the history of medicine these distinctions count for very little. Bordeu, who died on the eve of the Revolution, was doubtless one of the giants before the flood, but, as compared with the great names of those who came aprés le deluge—Bichat, Louis, Laënnec, Bretonneau, Andral, Pinel, such clinical "genius" as he had acquires the ghostly implication conveyed in the original meaning of the term. It has been said that every physician of florid or fashionable reputation has in him something of the charlatan, and there are anecdotes about Bordeu which show that he was no exception to the rule. But there are one or two things which make him an important connecting link between the outmoded, pompous, pedantic French medicine of the old régime and the brilliant and truly scientific output of the Napoleonic period and after. Bordeu appears to have been the first anatomist to employ the term "tissue," and his "Recherches sur le tissu muqueux ou l'organe cellulaire" (1767) immediately suggest the great Bichat, whom he influenced, it is true, but in a most untoward way. By tissu muqueux, which he also calls l'organe cellulaire, Bordeu means neither cellular structures as Schleiden and Schwann saw them nor protoplasm as Purkinje and Schultze saw it, but simply such vague protoplasmic configurations as were visible through a lower-power microscope. It was his ambition to confirm and uphold the humoral pathology of Hippocrates, and he regarded the three Hippocratic stages of disease, irritation, coction and crisis, as dependent upon the glandular and other secretions. Corresponding with the different organs and secretions, he classified diseases, not according to their clinical or pathological manifestations, but arbitrarily as cachexias, of which he devised a prodigious list, e, g., bilious, mucous, albuminous, fatty, splenic, seminal, urinary, stercoral, perspiratory; with an equally complex classification of the pulse as critical, non-critical, nasal, tracheal, gastric, renal, uterine, seminal, etc. All this undoubtedly influenced Bichat in the fundamental error of his scientific work, viz., the ascription of specific vital property to each classifiable tissue. Bordeu's slender reputation to-day is concentered in a single idea—the doctrine that not only each gland, but each organ of the body, is the workshop of specific substance or secretion which passes into the blood, and that upon these secretions the physiological integration of the body, as a whole, depends. This doctrine is contained in his "Analyse medicinale du sang" (1776), the importance of which has been signalized by the eminent medical historian, Professor Max Neuburger, of Vienna.^[2] An examination of this work will hardly realize the expectations which are raised by Professor Neuburger's panegyric. It is a typical example of the purely theoretical reasoning so common in the medical literature of the eighteenth century, in which an intolerable deal of verbiage is spread over the smallest substructure of fact. Cases are frequently cited but they are not true clinical delineations, only gossipy personal anecdotes, not unlike those of Brantôme. A great deal is said about the sexual side of man, and indeed the most interesting part of Bordeu's theory is his observation of the effects of the testicular and ovarian secretions upon the organism. He regarded the sexual secretions as giving "a male (or female) tonality" to the organism, "setting the seal upon the animalism of the individual," and as a special stimulus to the human machine (novum quoddam impetum faciens). He described in detail, the secondary sexual changes, not only in eunuchs and capons, but also in spayed animals of the female sex. In connecting all this with specific secretions, discharged, not externally, but into the blood, Bordeu was, as Neuburger rightly contends, very close upon the modern theory of the internal secretions, but, as he made no experiments, his ideas can only be regarded as an interesting phase of eighteenth-century theorizing. Aside from Bordeu's deduction from what he saw, almost any stock-raiser or poultry-fancier might have noted the same facts, and facts of equal moment had been noticed long before his time.

To begin with, one of the oldest therapeutic notions is the idea that such unsavory materials as the viscera or excreta of animals, administered either singly or as a maximum compositum might avail in the treatment of disease. This mode of therapy was a common feature of the Egyptian medical papyri, was known to the Greeks and Romans, made great headway during the dark ages, and reached its height in the seventeenth century. The four London Pharmacopœias of 1618, 1650, 1677 and 1721 abound with such remedies as the bile, blood, bones, brains, claws, eggs, excrement, eyes, fat, feathers, hearts, horns, intestines, marrow, milk, omentum, placenta, rennet, sexual organs, skin, teeth and urine of all manner of animals; also bee-glue, civet, cock's comb, coral, crayfish, earthworms, pearls, perspiration, saliva of a fasting man, scorpions, raw silk, silkworm's cocoons, moss from the skull of a man who has met a violent death, spermaceti, sponge, spider webs, cast off snake's skin, sea shells, swallows' nests, suet, viper's flesh, wax and woodlice; and along with these went those relics of the old Arabian polypharmacy, the theriacs and mithridates, which consisted of grand mixtures of anything and everything in the way of vegetable simples. In the seventeenth century there were actually "filth-pharmacopœias" (DreckApotheken). The only physician of the time who did not attach much importance to these remedies was the one who had the greatest fund of practical sense, Thomas Sydenham. In the pharmacopœias of 1721 and 1746, these nauseating remedies begin to disappear. One year before the latter date, William Heberden, who was probably the greatest English clinician between Sydenham and Bright, published his satirical pamphlet "Antitheriaka" (1745), which was, in effect, a critical onslaught on polypharmacy. Charles Lever tells of a certain individual who was "laughed out of Ireland." Heberden banished the theriacs and mithridates from medicine with the scholar's ironical smile, and with them went the filthier features of the materia medica. As a result of this cool douche of common sense, the Pharmacopœia of 1788 retains but a single animal remedy—woodlice. Yet these things were the crude elements of the present theory of treating certain diseases by means of animal extracts. Before the time of Brown-Séquard, the only animal extracts in our present pharmacopoeia were the antispasmodics, musk and castoreum, which used to be described to gaping students, receiving their first instruction in the action of drugs upon the human frame, as derivatives of the preputial gland and follicles of the Tibetan musk deer and the beaver, respectively.

Another set of observations which bears upon our subject is that connected with the universal interest in giants and dwarfs, the acromegalics and achondroplasics of modern pathology. The acromegalic giants go back to the legendary lore of the Nephelim in Genesis (VI. 4), of Og, king of Bashan, the Anakim, Goliath of Gath, the Titans, Antæus, Polyphemus, Fafner and Pasolt, Gog and Magog, down to the huge images of Manchuria, the innumerable reports of excavations of giant skeletal remains and the Irish, Chinese and Russian giants of more recent date. The achondroplasic dwarfs suggest the short-limbed satyrs, the dwarf gods of Egypt (Bes, Phtah and others),^[3] the black pygmy races,^[4] the court dwarfs and buffoons figured by Velasquez and other great painters, and the athletic, acrobatic and humoristic dwarfs of our vaudeville shows.

Among the ancient Romans, it was customary to test the increase in the girth of a young woman's neck, in connection with defloration or pregnancy, by measurement with a thread, as indicated in the lines of Catullus:

Non illam nutrix oriente luce revisens
Hesterno collum poterit circumdare filo,

but there is no evidence that they associated this cervical enlargement with the thyroid gland. Endemic goiter, however, was so well known in antiquity that Juvenal (XIII, 162) has preserved its commonplace aspects in a single line: "Qais tumidum guttur miratus in Alpibus" ("Who wonders at goiter in the Alps?"); and Pliny, in his Natural History (XL 68), hinted at one theory of its causation when he said that "only men and swine are subject to swellings in the throat, which are mostly caused by the noxious quality of the water they drink." In the sixteenth century Paracelsus found goiter to be endemic in the Salzburg region, again attributed it to metallic and mineral constituents in the water, and noticed that it coexisted with another disease of the same locality, cretinism or myxœdema. While goiter is not a necessary characteristic of idiots (proprium stultorum), says Paracelsus, yet it is most commonly found among them (so trifft es die am meisten)^[5] after which, he wanders off into his usual astrological theories, in which few can follow him. The important point is that in goitrous regions, as Dock says, cretins may have goitrous mothers while the marriage of two cretins is usually sterile,^[6] which makes the observation of Paracelsus fit in very well with his main theory of the provenance of idiots (generatio stultorum).

In 1614 Felix Plater, another Swiss physician, published an observation which seems truly modern, an autopsy of an infant who had died from enlargement of the thymus gland ("thymus-death").^[7]

As we begin to perceive the relation of these varied phenomena to the glands of internal secretion, it will not seem strange that Bordeu, who-first stated the modern theory, should have hit upon the sexual gonads as the most obvious illustration, for nearly all these glands are in some way connected with the sexual characteristics of the individual. We may now pass from the stage of hap-hazard observations to that in which certain diseases were closely and accurately described, like objects in natural history, and it is worthwhile to range these in chronological order, as illustrating the slow growth of a certain phase of inductive science.

 

II

On the continent of Europe, the disease "exophthalmic goiter" is variously known as "Basedow's disease," or morbo di Flajani, after the two observers who in Germany and Italy are thought to have originally described it. Basedow, a physician of Merseburg, published, in 1840, a description so complete that the Germans regard it as the classical one. The three symptoms which he signalized—swelling of the thyroid gland, protrusion of the eyeball and palpitation of the heart—the Germans sometimes call the "Merseburg triad,"^[8] which they also designate by the simple telegraphic epithet "Basedow." Among English-speaking people, exophthalmic goiter is usually known as Graves's disease, after the well-known Irish clinician who printed an accurate account of it in 1835. But more than fifty years before Basedow, Caleb Hillier Parry, an eminent physician of Bath, England, made a notation of all phases of the Merseburg triad, part of which deserves citation, if only on account of its historic interest.

Enlargement of the thyroid gland in connection with enlargement or palpitation of the heart.—The first case of this coincidence which I witnessed was that of Grace B., a married woman, aged thirty-seven, in the month of August, 1786. Six years before this period she caught cold in lying-in, and for a month suffered under a very acute rheumatic fever; subsequently to which she became subject to more or less of palpitation of the heart, very much augmented by bodily exercise, and gradually increasing in force and frequence till my attendance, when it was so vehement, that each systole of the heart shook the whole thorax. Her pulse was 156 in a minute, very full and hard, alike in both wrists, irregular as to strength, and intermitting at least once in six beats. She had no cough, tendency to fainting or blueness of the skin, but had twice or thrice been seized in the night with a sense of constriction and difficulty of breathing, which was attended with a spitting of blood. She described herself also as having frequent and violent stitches of pain about the lower part of the sternum.

About three months after lying-in, while she was suckling her child, a lump of about the size of a walnut was perceived on the right side of her neck. This continued to enlarge till the period of my attendance, when it occupied both sides of her neck, so as to have reached an enormous size, projecting forwards before the margin of the lower jaw. The part swelled was the thyroid gland. The carotid arteries on each side were greatly distended; the eyes were protruded from their sockets, and the countenance exhibited an appearance of agitation and distress, especially on any muscular exertion which I have rarely seen equalled. She suffered no pain in her head, but was frequently affected with giddiness. [After outlining his scheme of treatment, Parry concludes:] From this time no further application was made to me respecting this patient, who probably soon paid her debt to nature.

Between 1786 and 1815, Parry collected eight cases of this malady, which were published after his death, in 1825.^[9] He undoubtedly is entitled to the credit of the original and classical account of the disease, although he did not, as the French say, afficher, that is advertise, his discovery by attempting to label it.

In 1833, Flajani published his account of the disease, in which he recognized two of the cardinal symptoms, the goiter and the cardiac palpitation. In discussing palpitation of the heart at the Meath Hospital in 1835, Eobert Graves, the Dublin clinician, published his classical description of exophthalmic goiter, in which the exophthalmic feature was noted. He records that, in one patient, the beating of the heart could be heard at least four feet from her chest. After the time of Graves and Basedow, many similar observations were collected by clinicians, but it was not until the year 1886 that the condition was attributed to an excessive outpouring of the thyroidal secretion by the German neurologist. Möbius,^[10] who at the same time, described a number of related symptom-groups which he regarded as due to qualitative or quantitative changes in the secretion itself ("dysthyroidism"). In connection with the cretins observed by Paracelsus around Salzburg, it is of record that Curling, an English pathologist, first observed that absence of the thyroid body is accompanied by "symmetrical swellings of fat tissue at the sides of the neck, connected with defective cerebral development" (1850). The classical account of this condition is due to Sir William Gull (1873) and it was called myxœdema by William M. Ord, of London, in 1877.

It is a curious fact that the same volume of the journal in which Basedow published his account of exophthalmic goiter contains an observation by Benhard Mohr,^[11] a privat docent at Würtzburg, of a remarkable and fatal obesity in an elderly gardener's wife, attended by incipient imbecility (läppisches und kindisches Benehmen), loss of memory, general somnolence and scotoma, which, coming to autopsy, revealed a tumor-like degeneration of the pituitary body produced by inmixture and copious effusion of a serous fluid, the discharge of which had induced pressure phenomena in reference to the adjacent parts of the brain. This was the first recorded case of what is now known as pituitary obesity (1840), the "dystrophia adiposo-genitalis" of Fröhlich and Bartels.

In spite of the amount of original clinical delineation already on record in the first half of the nineteenth century, these lesions of the ductless glands attracted little attention. More interest was excited by the appearance, in 1855, of what we must now regard as the principal milestone in the history of the subject, the monograph "On the Constitutional and Local Effects of Disease of the Supra-renal Capsules," a quarto of 43 pages by Thomas Addison, senior physicion to Guy's Hospital, London. In the history of medicine, this work was destined to have an immortality of its own. In the very opening lines of his preface, Addison clearly states, for the first time, the true paths by which, as subsequent experience has proved, the problems of these mysterious glandular structures have been best approached and attacked:

If Pathology be to disease what Physiology is to health, it appears reasonable to conclude, that in any given structure or organ, the laws of the former will be as fixed and significant as those of the latter; and that the peculiar characters of any structure or organ may be as certainly recognized in the phenomena of disease as in the phenomena of health. When investigating the pathology of the lungs I was led, by the results of inflammation affecting the lung-tissue, to infer, contrary to general belief, that the lining of the air-cells was not identical and continuous with that of the bronchi; and microscopic investigation has since demonstrated in a very striking manner the correctness of that inference—an inference, be it observed, drawn entirely from the indications furnished by pathology. Although pathology, therefore, as a branch of medical science, is necessarily founded on physiology, questions may nevertheless arise regarding the true character of a structure or organ, to which occasionally the pathologist may be able to return a more satisfactory and decisive reply than the physiologist—these two branches of medical knowledge being thus found mutually to advance and illustrate each other. Indeed, as regards the functions of individual organs, the mutual aids of these two branches of knowledge are probably much more nearly balanced than many may be disposed to admit; for in estimating them, we are very apt to forget how large an amount of our present physiological knowledge, respecting the functions of these organs, has been the immediate result of casual observations made on the effects of disease. Most of the important organs of the body, however, are so amenable to direct observation and experiment, that in respect to them the modern physiologist may fairly lay claim to a large preponderance of importance, not only in establishing the solid foundation, but in raising and greatly strengthening the superstructure of a rational pathology.

Tbus did Addison set forth the fact that Nature herself is sometimes the physiologist's best vivisector, even as Billroth and the followers of Marion Sims elucidated the pathology of the abdominal and pelvic viscera by making "autopsies in vivo."

On March 15, 1849, Addison read a paper before the South London Medical Society^[12] in which he described the symptoms of what is now styled pernicious anasmia, cases in which the whole surface of the body "bear some resemblance to a bad wax figure." Only three of the cases came to autopsy, but "in all of them was found a diseased condition' of the supra-renal capsules." Was this a mere coincidence? Addison inquires.

Making every allowance for the bias and prejudice inseparable from the hope or vanity of an original discovery, he confessed he felt it very difficult to be persuaded that it was so. On the contrary, he could not help entertaining a very strong impression that these hitherto mysterious bodies—the supra-renal capsules—may be either directly or indirectly concerned in sanguification; and that a diseased condition of them, functional or structural, may interfere with the proper elaboration of the body generally, or of the red particles more especially. . . . Indeed, not only had he found the anæmia in question occasionally occurring in connection with purpura, but had observed in cases of the latter disorder certain local symptoms which pointed somewhat significantly to the supra-renal capsules; whilst the bloodless and waxy appearance of certain chlorotic females bore so close a resemblance to the anaemia described, that it was difficult not to suspect the existence of something common to both.

In his monograph of 1855, after referring to "an ill-defined impression" that the suprarenals, in common with the spleen, thymus and thyroid body, "in some way or other minister to the elaboration of the blood," and after a modest reference to the "curious facts" upon which he had "stumbled," Addison proceeds to develop the symptoms of what is now called Addison's disease—anæmia, general langor and debility, feeble heart action, irritable stomach, with a dingy or smoky discoloration of the whole surface of the body, sometimes reaching a deep amber or chestnut brown—and elucidates its pathology in eleven cases, accompanied by striking and life-like colored plates. From these records, it appears that the earliest known case of Addison's disease was reported by his great colleague at Guy's, Richard Bright (of Bright's disease) in 1829. In another, reported by Addison himself, the post-mortem section was furnished "by my distinguished friend Dr. Hodgkin" (of Hodgkin's disease). While developing his subject with the firm hand of the master in descriptive pathology, Addison draws no such striking conclusions in this memoir as we find in his paper of 1849 or as are indicated in the preface to the memoir itself. He does, however, draw attention to the important fact that even malignant disease may exist in both capsules without giving rise to the Addisonian discoloration of the skin. It was this memoir which led Brown-Séquard to reproduce the fatal disease experimentally by excising the suprarenal capsules in animals. The pouring out of the thyroidal and adrenal secretions during surgical shock or under the passion of fear (psychic shock) was emphasized long after by Crile and W. B. Cannon.

There remains one other affection which, on account of its present importance, may be briefly considered before passing to the experimental phases of the subject. The disease of acromegaly or gigantism was, as we have said, regarded as an abnormity from the days of Goliath of Gath up to the time of John Hunter's famous and expensive chase after the skeleton of the Irish giant (1783), but even before this definite cases had been reported, with good accounts of the deformities of the bones and the periodic coma, by Saucerotte (1772) and Noël (1779), and in the nineteenth century by Alibert (1822), Chalk (1857), by Friedreich in the case of the two Hagner brothers (1868), by Lombroso (1868), and by Sir Samuel Wilks, who in 1869 made a striking notation of the disease. The accepted classical account is that of Charcot's pupil, Pierre Marie, who differentiated the affection from myxcedema,osteitis deformans and leantiasis ossea, gave it its present name and, four years later, correlated it with disease of the pituitary body.^[13] Marie's claims to priority are somewhat vitiated by the fact that a lesion of the pituitary body in acromegaly had already been noted by Verga (1864), Brigidi (1877) and more particularly in the superb autopsy made by the late Edwin Klebs in 1884, which is the work of a veteran pathologist. This monograph,^[14] based upon a case furnished by Dr. Fritsche, of Glarus, Switzerland, contains two striking views of the patient and a remarkable diagram of the acromegalic skull; the hypertrophy of the pituitary body and the consequent widening of the sella turcica is strongly emphasized. But the opinion of the eminent pathologist is divided between this lesion and a proliferation of the thymus gland, which he found in the same autopsy, and after balancing the claims of the two lesions at length, he winds up by declaring that the cause of the disease must remain obscure. The view of Marie, which connects it directly with a lesion of the pituitary body,^[15] has been, with some reservations, the theory accepted up to the present hour. It is interesting to note that, from the time of Galen up to the seventeenth century, the pituitary body was held to be the source of the mucous discharges of the nose. Vesalius, for this reason, called it the "glans pituitam excipiens." This idea was overthrown in Conrad Victor Schneider's treatise on the membranes of the nose ("Decatarrhis," 1660) and by Richard Lower in 1672. Théophile de Bordeu, in his anatomical researches, states that the ancients thought the office of the pituitary ibody was to empty its humors through the nostrils, the moderns holding that it sent them to the sinuses of the sella turcica, and there the matter ends with him, although he indulges a few vague conjectures as to the possibility of the passage of the pituitary secretions into the circulation.

(To be continued)

1. Stealing from dead bodies was a favorite imputation against the eighteenth century doctor and is represented in an old water-color sketch of Rowlandson's.
2. Neuburger, Wien klin. Wochenschr., 1911, XXIV., 1367.
3. For a full account of these, with many illustrations, see the Munich dissertation of Franz Ballod: "Prolegomena zur Geschichte der zwerghaften Götter in Aegypten" (Moscow, 1913).
4. There are no white races of pygmies, and it is probable that most white dwarfs are myxœdematous or achondroplasic.
5. Paracelsus, "De generatione stultorum" (in his "Opera," Strassburg, 1603, pt. 2, p. 177.
6. George Dock on "Cretinism" in Osier's "Modern Medicine," Philadelphia, 1909, VI., 448.
7. Plater, "Observationum in hominibus affectibus. . .," libri III., Basel, 1614, 172. Cited by Friedleben.
8. Basedow, Wochenschr. f. d. ges. Heilk., Berlin, 1840, VI., 197: 220.
9. Parry, "Collective Writings," London, 1825, II., 111.
10. Möbius, Schmidt's Jahrb., Leipzig, 1886, CCX., 237.
11. Mohr, Wochenschr. f. d. ges. Heilk., Berlin, 1840, VI., 565-571.
12. Addison, London Med. Gaz., 1849, XLIII, 517.
13. Marie, Rev. de méd., Paris, 1886, VI., 297-333, and in the graduating dissertation of his pupil, Souza Leite (Paris, 1890).
14. Fritsche and Klebs, "Ein Beitrag zur Pathologie des Riesenwuchses," Leipzig, 1884.
15. For an interesting account of this disease, see "Acromegaly, A Personal Experience" (London, 1912), by Dr. Leonard Portal Mark, a practising physician who has given a graphic and pathetic description of the gradual onset of the distressing malady in his own body. Although his disease was privately diagnosed by most of his clinical associates and he was "spotted" as an acromegalic in a Parisian crowd by Marie himself, Dr. Mark did not begin to realize his condition until he was fifty.