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From the moment of our birth we are constantly exposed to the incessant attacks of innumerable bacteria and to the effects of a large amount of poisonous material formed within our body or introduced from without, and if we survive this ceaseless battle it is due to the powerful weapon we possess in the internal secretion of the ductless glands, especially of the thyroid gland. That this gland possesses very energetic antitoxic properties can be shown by the fact that when it is extirpated animals or persons very readily acquire infectious diseases of all sorts. Thus, the late Professor Charrin,^[44] of Paris, showed several years ago how readily dogs that have lost their thyroid succumb to all possible infections. Professor W. S. Greenfield,^[45] of Edinburgh, has found that persons suffering from myxœdema (athyroidia) very often die from tuberculosis, and Professor Pel,^[46] of Amsterdam, found a great frequency of tuberculosis in the families of myxœdematous persons. This coincides with the conclusions of Prof. G. R. Murray,^[47] Professor Lanz, and ourself, that the properties of the thyroid can be inherited. Sajous has shown, moreover, that the pituitary, the adrenals and the thyroid constituted the autoprotective mechanism of the body against disease, a fact not only sustained by the above evidence, but also by a vast number of additional facts.

As we showed at the last Congress of Tuberculosis in Paris, 1905, tuberculosis is especially frequent as a sequel to any process deleterious to the thyroid gland, as after the puerperium, especially with prolongated lactation; after sexual excesses, as there is a relation between the sexual glands and the thyroid; after various infectious diseases; after rapid growth in puberty, due to hyperactivity of the thyroid which influences the growth of the body; after severe diabetes due to exhaustion of the thyroid; and after previous hyperactivity in chronic alcoholism due to the action of alcohol upon the thyroid. On the other hand, all those agencies which excite thyroid activity may be a preventive against tuberculosis, such as raw meat and milk. It has been shown that milk contains the internal secretion of the thyroid.

The thyroid protects us against poisons of different origin, such as the products of decomposition of protein food. This fact is shown by the experiments of Dr. Leo Breisacher, of Detroit,^[48] formerly assistant of the late Professor Munk, of Berlin, and from those of Dr. Blum,^[49] of Frankfort. The experimental results of Dr. Chalmers Watson,^[50] showing alteration of the thyroid in certain animals after an exclusive diet of raw meat, and those of Dr. D. Forsyth^[51] concerning the pituitary body in some animals, may be correlated with this fact. As is well known, the thyroid and pituitary body stand in very close relationship. Galeotti and Lindemann,^[52] in 1897, have also shown that the products of decomposition of meat produce an increase of the colloid substance of the thyroid.

The antitoxic properties of the thyroid against different products is also shown by the observations of Lanz^[53] and Walter Edmunds,^[54] who have found that animals without thyroid resist narcosis badly; and, as we have shown in a communication to the Paris Biological Society,^[55] chloroform, like alcohol, produces a condition of hyperactivity in the thyroid gland, which results also in an excited mental condition. The observation that cases of Graves’s disease and of severe diabetes cannot stand narcosis may be related to this fact.

It has been shown recently by Hunt^[56] that the thyroid protects us against poisons like acetonitril, and that iodine acts through the thyroid. Garnier,^[57] of Paris, has found that certain chemical products, such as iodine, produce great alterations in the thyroid. As is well known, cases of Graves’s disease (hyperthyroidia) have been observed after iodine treatment. That the thyroid fulfils a protective rôle against infectious diseases may already be considered proved by the fact that, as Roger and Garnier,^[58] Crispin,^[59] Torre,^[60] Bayon,^[61] of Würzburg; de Quervain, and others have found, the thyroid is, as a rule, altered in infectious diseases. As Roger and Garnier have shown by a series of investigations confirmed by the above-named authors, the thyroid shows in acute infectious diseases with fever an increased activity with enlargement of the follicles, which are filled with a large quantity of colloid substance which may even enter into the adjacent lymphatic spaces. However, this hyperactivity of the thyroid gland may be followed by its exhaustion, and thus after a certain duration of high fever there may be no colloid substance at all in the folliculi.

It is only logical to suppose that with anatomo-pathological alterations of the thyroid, indicating a condition of hyperactivity, there must be corresponding clinical symptoms and that these must necessarily be similar to those found in another condition of hyperactivity of the thyroid gland—i.e., in Graves’s disease, the condition of hyperthyroidia. And, indeed, such must be the case, for, as we shall try to show, fever and Graves’s disease have similar clinical symptoms. Thus their most typical symptom is the same: tachycardia or increased frequency of the pulse, without which no case of Graves’s disease should be diagnosed. There is a sensation of heat in most of the cases of Graves’s disease, and the temperature sometimes reaches a dangerous degree in fully developed cases of this disorder. Thirst, frequent in fever, is also a frequent symptom in Graves’s disease (polydipsia in 14 out of 59 cases recorded by Albert Kocher^[62]), and can also be produced by thyroid feeding (Lanz,^[63] Georgiewski,^[64] and others). After a certain duration of fever further symptoms of an increased activity of the thyroid appear, such as abundant perspiration—a typical feature of Graves’s disease. Vaso-dilatation and excessive perspiration can also be produced by thyroid feeding. The latter symptom of fever is a device by which nature tries to eliminate toxic products, and accordingly there generally follows upon it a fall in the temperature and an amelioration of the symptoms of fever. The diarrhœa which we find in some infectious diseases, like that of typhoid fever, trypanosomiasis, etc., is also a typical symptom in Graves’s disease. When the fever subsides there appears another typical symptom of this condition: polyuria. To complete this analogy we may mention toxic decomposition of proteins, diminution in the body weight, great muscular weakness, and increased elimination of urea and uric acid as typical symptoms of both conditions. As in Graves’s disease, there is also in fever an augmentation of the processes of oxidation. Glycosuria is frequent in both conditions, and acetonuria may occur in fever and also in Graves’s disease. Glycosuria and diabetes in consequence of infectious diseases are, as we have shown in a paper read before the London Pathological Society,^[65] probably due to the increased activity of the thyroid, and their disappearance, occasionally after a high fever, may be ascribed to the exhaustion of the thyroid after a previous hyperactivity. We know that a condition of Graves’s disease may be followed by a myxœdematous condition in which, as we have shown previously, glycosuria is very rare. In the few hitherto published cases there was no complete myxœdema.

Both in Graves’s disease and fever there is an augmentation of the processes of oxidation. After convalescence, however, oxidation may be diminished, and this explains, as we have shown at the French Congress of Medicine in 1904,^[66] why obesity so frequently occurs after infectious diseases on the basis of degenerative changes of the thyroid, which governs oxidation; during the course of infectious disease with fever increased activity of the thyroid and loss of weight occur, and these are followed by exhaustion of thyroid activity and obesity.

The conditions of delirium and maniacal exaltation in cases of high fever are analogous to the condition of mental exaltation that may occur in Graves’s disease. According to the late Moebius,^[67] in cases of Graves’s disease there are sometimes symptoms like those of alcoholic intoxication due to the toxins of the thyroid. We believe that the mental exaltation in chloroform narcosis and alcoholic intoxication stands in relation with the action of these drugs upon the thyroid. That alcohol acts upon the thyroid has been shown by de Quervain, Hertoghe,^[68] and others. Sajous in his work on the “Internal Secretions,” urges that the thyroid is not directly excited by toxins and other poisons which produce fever, but that these toxics excite primarily the thyroid center (or better the adreno-thyroid center, for he holds that the adrenals are also governed by this center) thus increasing the secretory activity of the gland. The correctness of this view is proved by the fact that, as shown by Sawandowski,^[69] section of the basal tissues, and, therefore, between the pituitary and the bulb, prevented the production of fever, due to putrid materials, and also the influence of antipyretics, antipyrin, for instance.

Cutaneous eruptions may occur in fever or in Graves’s disease. In the same way as in many skin diseases they may be considered as the expression of an elimination of toxic products through the skin.

All the above symptoms of fever may be considered as expression of the efforts of nature to defend herself by eliminating toxic products. All toxic products which are the causes of infection act upon the thyroid gland, this organ, through increased activity, produces symptoms such as we see in Graves’s disease. That these symptoms, especially abundant perspiration, polyuria, and diarrhœa, typical in some infectious diseases, may be considered as the direct consequence of thyroid activity, can best be shown by the fact that the thyroid gland governs the functions of the skin, intestines, and kidneys.

That the symptoms of fever may be considered as due to increased thyroid activity is also shown by the fact that nearly all such symptoms may be produced by thyroid preparations. We have personally taken for experimental purposes, during ten months, thyroid tablets and experienced the sensation of heat, flushings, and abundant perspiration. It is interesting to note that all kinds of wounds and contusions we got during the time we took these tablets, healed with surprising rapidity with fine granulations far better than previously; on the other hand, we very frequently suffered from tonsillitis and acne eruptions.

Symptoms similar to fever have also been produced in animals by thyroid feeding; thus, very often elevation of the frequency of the pulse from 100 to 140-160 beats (Lanz), and from 150 to 200 beats (Georgiewski), while Ballet and Enriquez^[70] produced regular fever in their animals; Easterbrook^[71] also produced “some pyrexia” in his animals and an increase of pulse-rate of about 40 a minute. As Dr. Tanberg, former assistant of the Physiological Institute in Christiania, told us, he has produced an increase of the temperature of two and a half degrees in animals, whose thyroid he had extirpated, after giving very large quantities of thyroid gland.

It is of great interest to the question at issue that the remedies which we employ to fight fever should also produce symptoms like the thyroid does when it is in increased activity. Thus salicylates produce a vaso-dilatation and abundant perspiration, and afterward diminution of the temperature. We have, ourself, taken salicylates or acetonitril preparation and felt the sensation of heat and afterward perspiration. When we take a hot air or steam bath for cold or gouty pains we produce first, great heat, tachycardia, and then abundant perspiration, and the typical symptoms of fever or increased thyroid activity.

We know that certain drugs, as found by Garnier, have an exciting action upon the thyroid, such as iodine, and what is especially important, pilocarpine. The great sudorific action of this drug may stand in some relation to its effect upon the thyroid. It is permissible to suppose that the different drugs which antagonize fever do so by acting first upon the thyroid gland and exciting its increased activity to fight infection. But if we gave too much of these we might exhaust the activity of the gland in the same way as Garnier found an exhaustion of the colloid of the thyroid after too much iodine. This shows that we should not give antipyretics in too large doses. We should excite thyroid activity but not overdo it.

That the thyroid is able to protect us against infectious diseases can be best shown by the fact that it exercises a great influence upon phagocytosis. According to the findings of Fassin, the alexins disappear from the blood after the extirpation of the thyroid gland; and, according to Sir Almroth Wright, the production of opsonins is dependent upon internal secretions. Hence, it is of the greatest value to us that Stepanoff^[72], and Marbé have proved by experiments conducted in the Pasteur Institute of Paris that the opsonins disappear after the extirpation of the thyroid gland but increase after thyroid treatment, these experiments thus proving the correctness of our clinical observations on the rôle of the thyroid gland as an organ for protection against infections, as published in The Lancet two and one-half years ago. Sajous, who was first (1907) to point out that the thyroid secretion was the agent which Wright termed “opsonin,” is also shown to have been right by the investigations of Fassin, Stepanoff and Marbé, thus proving further the intimate relationship between the thyroid and our immunizing functions.

Fever can be produced with similar symptoms by toxic products of different origin, as from small elements of the vegetable kingdom like bacteria, certain plants, and even fruits, as is shown by the urticaria which follows in some persons after eating strawberries. Certain minute elements of the animal kingdom have a similar power, such as protozoa like trypanosomes, and we may also instance certain kinds of animal food like oysters in certain persons, the poison of snakes, and certain insects like tarantulas and scorpions; also certain minerals like arsenic and phosphorus can produce fever. Besides these poisons coming from without, fever with similar symptoms can also be produced by poisons formed within our body by the hyperactivity of a gland—the thyroid. When so many different poisons produce the same result it lies near to suppose that they do this by means of the same agency, which, according to the aforesaid observations, is very probably a thyroid hyperactivity. The modus operandi of all these agents is well studied in Sajous’s work, to which the reader is referred.

As is well known, a condition of hyperactivity of the thyroid may be followed by its exhaustion, and thus Graves’s disease may often be followed by myxœdema, i.e., athyroidia. In the same way the hyperactivity of the thyroid gland in infectious diseases may also be followed by its exhaustion and a myxœdematous condition. Even complete myxœdema most frequently appears after a previous infectious disease—a fact recognized by the earliest English authors on this disease. Accordingly, it is not surprising if an infectious disease like trypanosomiasis is followed by a condition like sleeping sickness, which, as we have shown at the German Congress for Internal Medicine in 1905, presents all the clinical symptoms of, and identical anatomico-pathological alterations of the central nervous system noted in, myxœdema. On the other hand, trypanosomiasis presents all the typical symptoms of Graves’s disease. In syphilis also, after the fever with eruptions in the secondary stage, in which we not infrequently see, especially in women, a swelling of the thyroid, we find in the tertiary stage many symptoms of a condition of myxœdema or hypothyroidia, and with the iodine treatment we add to the blood the main element of the thyroid gland. Iodine is also especially active, if not given in too large doses, in exciting thyroid activity, and sometimes it even provokes Graves’s disease.

Persons of healthy constitution with a good working thyroid may get the sensation of heat and perspiration spontaneously after a cold, or gouty pains, even without salicylates, and feel better afterward, whereas persons with a deficient thyroid have difficulty in producing the symptoms of fever. Recently we observed a young man, aged 22 years, with symptoms of hypothyroidia as described by Hertoghe, who had follicular tonsillitis. He presented none of the symptoms of fever, but it took him ten days to get over it and he felt very weak afterward. There was this summer an epidemic of typhoid fever in the lunatic asylum of Colorno, near Pavia. We have it from Dr. Gassenghi, of the University of Pavia, that half of the patients died; but it is very interesting to note that there was no fever. This may be explained by the fact that many cases of insanity and idiocy stand in etiological relation to alterations of the thyroid gland, and may get better after the hyperactivity of the thyroid through fever. Indeed, by some authors,—e.g. Wagner—an improvement has been observed to occur in insanity by producing fever through injections with tuberculin. We feel sorry not to be able to enter more fully into this interesting subject, but we may briefly mention that, as we have stated in the Neurological Society of New York (April 2, 1906), we have observed several cases of dementia præcox and melancholia with alterations of the thyroid and sexual glands in each case. Alcoholics suffering from pneumonia seldom get high fever, but often die in a short time. Alcohol in large quantities not only causes degenerative changes in the heart, but also in the thyroid. And we should not forget that there exist very close relations between the activity of these two organs.

It seems to follow from these observations that persons with a good sound thyroid have a better chance in fighting infections and intoxications than persons with a degenerated thyroid. In persons with an active thyroid, an increased activity of the gland, and thus a better functioning of the eliminative organs which are governed by it, can take place more easily than in persons with a degenerated thyroid, and, in consequence, with a dry skin, constipated bowels, and lazy kidneys. Some hints may be derived from these observations in the interest of prophylaxis and prognosis, and also for the purposes of life insurance.

It seems to us that the conclusion is not unjustified, that fever is a beneficial process of our organism which is produced by an increased activity of the thyroid gland as a reaction against toxic products and poisons in general. The symptoms of fever are the expression of this increased activity, and they are directed toward the elimination of noxious elements. It would be unreasonable to oppose this spontaneous healing tendency of nature by fighting these salutary symptoms, unless there be hyperpyrexia. Fever, as probably disease in general, serves the ends of nature in the interest of our conservation. In addition to the thyroid, the other ductless glands protect us from infections and intoxications. Thus, the pituitary body which Casselli,^[73] Guerrini,^[74] Torri, and many others found, as a rule, altered through infectious diseases. Torri noticed a hyperplasia of the chromophile cells of the pituitary body, and disappearance of the colloid from the follicles in the majority of cases of pneumonia, typhoid fever, tuberculosis, diphtheria, and other infectious diseases. Garnier also noted changes in this gland in chronic tuberculosis. Thaon,^[75] in his recent thesis, also found changes in the pituitary body in many cases of various sorts of infectious disease, and, what is most interesting, also in intoxications from intestinal origin. We must conclude with Sajous (1903) that the pituitary body reacts to the effects of infections and intoxications and that these anatomo-pathological alterations of the pituitary also provoke clinical symptoms. Renon^[76] and Delille have drawn attention to the fact that the decrease of the blood-pressure, and increase in the number of pulsations, in fever, as also the other symptoms of this condition, such as insomnia, heat, perspiration, etc., are due to the alteration of the pituitary body. When this is active and healthy it augments blood-pressure, according to Oliver and Schäfer,^[77] Cyon, Livon, Garnier, Thaon, Hallion, and Carrion, etc. At the same time the pulse is diminished, but when this gland is degenerated the pressure naturally falls and the pulsation goes up.

It is also very interesting that Renon, with his assistants, Delille and Azam,^[78] were able to increase blood-pressure in numerous cases of infectious diseases and diminish the pulse, and also produce a marked improvement in the feverish condition through the administration of extracts of the pituitary body.

We must insist on the fact that the thyroid and the pituitary body are antagonistic; the thyroid diminishes, the pituitary augments, blood-pressure. The same antagonistic relations exist also between the thyroid and adrenals, as already mentioned.

The adrenals play an important rôle also in the defense of the organism against infections and intoxications, as we will point out in a separate chapter. We will only recall here that already (1903) Sajous^[79] has insisted upon the important rôle of the adrenals in the production of fever.

The co-operation of the sexual glands in protecting the body from infectious disease can be shown by the fact found by Professor Cornil,^[80] of Paris, that in infectious diseases, such, for instance, as typhoid fever, there is frequently sudden menstruation, with abundant metrorrhagia, the autopsy often showing hypertrophy of the corpus luteum.

Metschnikoff^[81] and Matschinski found, after injections of the bacilli of tetanus, or of diphtheria, the greatest number of them in the ovaries, or in the testicles, of the animals. It is also of great interest that Lingard^[82] found that the subcutaneous injection of testicular extracts into cattle induces a resistance to infection from bovine plague, against which other cattle can also be rendered immune through the serum of the treated animals—which seems very important to us. Brown-Sequard and d’Arsonval employed testicular extracts with good result in tuberculosis, and Uspenski in cases of Asiatic cholera.^[83]

In the chapter on the treatment of old age by organic extracts, we submit evidence showing that infectious diseases have been treated successfully by several authors by these extracts. Many others have also shown that spermin, prepared by Professor Poehl from the testicles of various animals, has also a marked effect against different infectious diseases, sometimes even in cases of desperate septicæmia. It has been shown by Professor Loewy and Dr. Richter, that after giving spermin there is at first a great diminution of the leucocytes in consequence of leucolysis, which is soon followed by hyperleucocytosis, and at the same time there was considerable increase of alkalinity in the blood.^[84]

Loewy and Richter were able to cure animals by injecting spermin even in cases of experimental pneumonia, where they had received three or four times the fatal dose of pneumococci. These observers also tried spermin in diphtheria, but here the results were less marked, although in some cases where the exact fatal dose was given, a cure was effected. According to Professor Poehl^[85] the increase of alkalinity of the blood through spermin, explains its action to increase immunity against infection. Sajous also urges that immunity is closely related with alkalinity.

It is interesting to observe that spermin has also given good results in intoxication through leucomaïnes, which play a great rôle in auto-intoxications in the body. This applies to neurin and cholin, as noted by Professor Prince Tarchanow, and Dr. Poehl.

We have already mentioned that the thyroid protects us against various poisons, such as chloroform, and it is of interest to note that the testicles may also have a similar action; for, as Tarchanow has shown in frogs, and also dogs, after injection of spermin, these animals were better able to resist chloroform narcosis, and could also withstand a greater dose of it. Weljaminoff found the same also in man. Krüger found that this applied also to ether narcosis.

The liver, as we shall show later in a separate chapter, also antagonizes intoxication. Another organ in close relation to the ductless glands—especially in infants—the thymus, must also be considered in the same way as the spleen as taking an important part in our protection against infections. As well known, the spleen is a foremost organ for the production of protective substances, the frequent swelling of the spleen in infectious diseases shows its co-operation in the defense of the body (see also Chapter X). Respecting the thymus, it has been shown by Brieger, Kitasato, and Wassermann, that cultures of cholera bacilli lose their toxic action in extracts of the thymus.

There can be no doubt whatever, from the foregoing, that our immunity against infections and intoxications depends on the intact condition of the ductless glands, the great importance of which, as defensive organs, has been demonstrated and explained by Professor Sajous in 1902.^[86] As he says: “The overactivity of the adrenal system is the inciting factor of leucocytosis, and, therefore, of phagocytosis;” and later in the second volume: “that the adrenal system, composed of the pituitary body, the adrenals, and the thyroid apparatus, constitutes the immunizing mechanism of the body.”

When the ductless glands are not in good working condition, there are three principal things which can occasion infection or intoxication. These are deficient nutrition, exposure to cold, and a depressed mental condition. By these the resistance of the cells against the energy of the invading microbes is lowered, and the greater the invasion the easier will be their victory.

We will often refer to this in the chapters on personal hygiene, and propose certain remedies for avoiding these predisposing sources of infection and intoxication.