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As a general rule infants of both sexes look very much alike, so much so, indeed, that sometimes it is only possible, upon close inspection, to determine the difference in sex. This, however, can only be so for a certain period until certain changes take place in the ductless glands, especially in the sexual glands and the thyroid.

The latter contains but very little, if any, colloid substance in infancy, and the colloid increases only gradually until it is present in abundance at the time of puberty, when also the changes in the sexual glands reach a climax coincident with the ripening of the follicles in the ovaries and their rupture at a menstrual period. This latter process is, as we have mentioned before, under the influence of the thyroid. Puberty and menstruation do not take place, as a rule, in persons with a degenerated thyroid gland.

With the onset of puberty there is seen, also, a change in the external appearance of the individual and the attributes of virility—e.g., moustache, hair in the pubic region, alteration of the voice, etc., appear. In the female the development of the breast, hair on the pubis, etc., occurs. At the same time the features attain the peculiar characteristic which distinguishes the male face from the female, even without the aid of a moustache.

In those persons in whom puberty has not occurred at the usual age (fourteen to sixteen years in our climate) the attributes of sex are absent. In these cases the male looks very much like the female. A similar phenomenon may be seen in women after castration and the climacteric, when they may even show a tendency to develop a moustache and hair on their face in places, corresponding to the male beard.

This we can also observe in women whose ovaries have been altered by disease or by sexual excesses.

These attributes of sex are also called external sexual characteristics, and they are the direct result of the internal secretion of the sexual glands. They only develop through the presence of such a secretion, and this is easily demonstrated by the fact that after castration of the infant, they do not appear at all. Hence, if we see grown-up men with no trace of a moustache it may indicate an undeveloped condition of the testicles. Again, we castrate a young cock, he will not grow a comb and spurs, and other cocks will pass by, too proud to fight with a degenerate deprived of its male attributes. If we now take the extirpated testicle of such cock and graft it under his skin, the other cocks will commence to fight with him, for his comb and spurs will develop as in other normal cocks.

That the whole external appearance of a castrated animal or man is changed, is also demonstrated by important changes in the skeleton and size of such animals or persons.

As Poncet^[30] has shown, the extremities of a castrated rabbit become abnormally long, and it is a well-known fact that eunuchs have abnormally long arms and legs. This also occurs in cases of infantilism, which, as we know, is due to a non-development of the sexual glands. Moreover, the thyroid of such individuals is also found to be in a pathological condition, as was shown by Hertoghe.

Men who have been castrated before puberty or whose testicles are undeveloped, present such an external appearance. They have no moustache, as above mentioned; their hair is dry and brittle and remains short; their faces are pale, and of a yellowish hue; their hands are cold and reddish blue. Often the skin of the face is like parchment and has many wrinkles. Their intelligence is often diminished, as we will show later on, and they are usually anæmic.

Women with undeveloped ovaries have flat breasts and hips; their faces are often irregular in structure, and their jaws are often prominent; their gums are shrunken and their teeth are long and soon fall out. Some cases may show a colossal obesity, but in the partial forms of ovarian insufficiency they may be remarkably thin. They also are, as a rule, anæmic or chlorotic.

In some parts of the Orient, as in India, there are female eunuchs, such as Roberts has seen on the way from Delhi to Bombay. Such eunuchs had no bosom; the pubic hair was absent, and their buttocks were like those of men; but the rest of the body was stouter. Of course these women had been castrated during their childhood.

If we make a Roentgen-ray examination of the skeleton of a person castrated in childhood, we shall find that the epiphysial cartilages remain unossified for a long time after puberty.

It is a very interesting fact that, both after castration and in myxœdema, the same persistence of the epiphysial cartilages and retardation of ossification have been observed by means of the Roentgen-rays: by Hertoghe in 1896; Springer and Serbanesco in 1897; Gasne and Laude in 1898; Legry and Renault in 1902; Jeandelize in 1903. The same thing has also been observed by Hertoghe in “Infantilism of the Type of Lorraine.”

The influence of the thyroid upon the skeleton and size of the body is easily shown by simple observations.

Children of parents with cachectic diseases like chronic tuberculosis, syphilis, alcoholism, etc., in which the thyroid gland is, as a rule, found degenerated (Gamier,^[31] Hertoghe^[32]), are (as shown by Prof. Perrando^[33] and Garnier) born with a congenital atrophy of the thyroid. Just as young animals with an extirpated thyroid, so these children will not grow, and we know that cretins (degeneration of the thyroid) remain as a rule dwarfs all their life long. We can now produce in such persons certain and very curious changes by feeding them with thyroid extract, and we can see them, as Hertoghe has shown, grow inch by inch in a short period; their mental faculties improving at the same time in an incredible manner.

The influence of the thyroid upon the skeleton is also shown by the fact, established by Gauthier,^[34] that in a fracture with but little tendency to the formation of a callus, union takes place much more quickly after administration of thyroid extract.

In Graves’s disease, with exaggeration of the thyroid activity, there is, on the other hand, an increased elimination of the most important constituent of the skeletal tissues: calcium carbonate, and this occurs also in acromegaly and diabetes, in which conditions the thyroid is very frequently altered (Lorand^[35]).

Osteomalacia, which is associated with an enormous elimination of calcium carbonate is, as we at present consider, due to an exaggerated ovarian activity (Fehling), and can be favorably influenced by castration or, by what would be more reasonable, thyroid treatment.

No less powerful than that of the thyroid is the influence of the pituitary body upon the skeleton, especially upon the hands, feet, and skull. And if we wish to demonstrate how much the ductless glands influence the looks of a person, it is sufficient to point out the great changes that take place in the face of a patient with acromegaly. This disease makes such persons look very much as “Punch” is depicted.

The skin and complexion of persons suffering from changes in the ductless glands are also very different from normal. Thus Addison’s disease, due, as well known, to a degeneration of the adrenals, makes a white man look more or less like an Indian, and there is a pigmented skin also in persons affected by the

partial form of that rare disease. We can also easily show that changes in the thyroid are followed by changes in the condition of the skin. Thus, with thyroid degenerations, as in myxœdema, the skin is pale with a yellowish tinge. In Graves’s disease pigmentation of the skin can often be observed, and not rarely cutaneous eruptions.

In affections of the sexual organs in woman similar conditions of the skin can occur. Such persons often present wrinkles at a very early age, and certainly look older than their years. Infants suffering from congenital degeneration of the thyroid gland often look withered and present a face as wrinkled as a sexagenarian. We see this also in congenital syphilis (atrophy of the thyroid).

The hair also very often shows alterations in diseases of the thyroid, or ovaries. Thus, in myxœdema there is an atrophy of the follicles of the hair, which falls out, even in the case of the eye-brows.

It is particularly interesting that, by thyroid medication, a new growth of hair has been observed in places where it had fallen out years previously, as we have observed, with other authors, in several cases after thyroid medication. And, very strange to say, this newly-grown hair was quite dark while the hair that had previously been in its place was gray in color. It has been authentically stated by several authorities that old persons of sixty or seventy have acquired black hair under thyroid treatment.

On the other hand, in much younger persons, perhaps under thirty, who are suffering from complete or partial degeneration of the thyroid gland, the hair very often turns gray; so much so that Hertoghe considers this to be one of the typical symptoms of such a condition.

The falling out of hair, or its turning gray, after acute infectious diseases or after grief and sorrow, may have some connection with the well-known changes in the ductless glands, especially in the thyroid, in these conditions. This is made quite clear by Sajous’s demonstration that these glands collectively govern the activity of general oxidation, that is to say the vital process itself.

As we have previously mentioned, a moustache or whiskers may grow in women suffering from disease of the ovaries, just as after castration or the climacteric. It is also very interesting that a premature grayness often occurs in cases of insanity, and can be attributed to the frequent changes in the thyroid and sexual glands in these conditions.

The nutrition of the skin is entirely under the influence of the thyroid. After extirpation or degeneration of the thyroid, there occurs atrophy of the sebaceous and sudorific glands.

In myxœdema the skin is dry and never perspires. On the contrary, in Graves’s disease, or after thyroid medication in large doses, there is abundant perspiration.

Deposits of tartar are common symptoms in all forms of thyroid degeneration. Retraction of the gum follows and the teeth loosen and fall out. This is also a common symptom in diabetes, but here only in advanced cases. In such cases there is, as we^[36] have shown, an exhaustion of the thyroid gland, which develops as a consequence of the previous hyperactivity of the thyroid gland in the early stages of the disease. As a rule the teeth of a diabetic only fall out in the severer form of the disease, generally after acetone has begun to show itself in the urine.

Important changes take place in the subcutaneous tissue after extirpation of the thyroid gland. In such cases there is either augmentation of connective tissue or of fat. Thus, in the case of a young bull, whose history we followed, there has been an increase of thirty pounds of fat within a few months after extirpation of the thyroid. The same thing happened in the case of a young horse, whose thyroid was also extirpated.

There are, however, still more facts which show the great influence of the thyroid upon the metabolism of fat. Thus we know very well that by thyroid medication we are able to reduce fat considerably. This is due to the action of the thyroid which, as shown by many authors, increases the process of oxidation. In Graves’s disease these processes are augmented. In the opposite condition (myxœdema) they are diminished. By giving thyroid extract we are able to augment, positively, the processes of oxidation in the tissues, as shown by Professor Magnus-Levy,^[37] of Berlin, and many others.

As we have shown in our previous researches, there is an abundant formation of fat in the early cases of degeneration of the thyroid gland, which sometimes progresses to a colossal obesity, which obesity has nothing to do with overfeeding. Such individuals have, as a rule, but poor appetites, and eat very little. Therefore, in a communication to the French Congress of Internal Medicine in Paris, 1904, we differentiated two kinds of obesity: 1. Exogenous obesity—i.e., arising by agencies coming from without by the food we introduce into our body. 2. Endogenous obesity, having its origin within our economy, and depending on changes in certain glands which govern the processes of oxidation—e.g., thyroid sexual glands, pituitary body. This second form is independent of our feeding. As we have shown, this latter can be produced by any of those agencies which are harmful to the ductless glands, especially the thyroid and sexual glands, as, for example, infectious diseases, frequent pregnancies, certain toxic products (alcohol), sexual excesses, climateric. All these conditions may have the effect of producing obesity, which can be explained by an exhaustion of the thyroid and ovaries following a pre-existing hyperactivity.

The influence of the ovaries upon the production of obesity can be demonstrated by the sequels of castration, and also by the fact that women, after one or more, especially several pregnancies, or after sexual excesses, may become very fat. In such women this obesity may be only partial and limited (as we have shown in a recent communication to the International Congress of Medicine in Lisbon, 1906) to certain parts—e.g., the mammary glands or hips.

There can be no doubt that the sexual glands influence the nutrition of the tissues in a powerful manner, and this has also been shown, experimentally, by the researches of two Berlin experimenters, Professors Loewy and P. I. Richter,^[38] performed in the physiological institution of Professor Zunz. These savants have shown that after castration there is a diminution of oxidation. By giving extracts of dogs’ testicles to castrated male dogs, they were able to augment the processes of oxidation. These processes, however, were still more increased after the administration of female extracts to these castrated male dogs. The administration of ovarian extracts to the spayed bitch has, of course, given still better results. Thus there was here an increase of 67.7 per cent. after castration, and 37.6 per cent. of the original value. The increase of the oxidation in male dogs was 44.5 per cent. after castration, by the treatment with ovarian extracts, and 24.8 per cent. above the normal value. If the results after feeding with male extracts were not so successful, it must be attributed to the circumstance that we are at present unable to produce testicular extracts of the same efficacy as ovarian extracts.

The action of the pituitary body upon metabolism has been shown by Narbuth, who found a diminution of oxidation after degeneration of the pituitary body, and an increase after medication with extracts of the same organ. This fact is also shown clinically by cases of obesity after degeneration of the pituitary body in acromegaly, and by the interesting fact (shown by a great number of authorities and recently by Fröhlich,^[39] Berger,^[40] and Erdheim^[41]) that cases of pituitary tumor may be met with, associated with obesity, and without any of the symptoms of acromegaly. Especially interesting is the case of Madelung^[42] showing a colossal obesity in a girl aged 9 years, after a gunshot injury of the pituitary body. This observation sustains, and is clearly explained by, Sajous^[43] who showed that the posterior or neural lobe of the pituitary body contained a nerve center which governed the functional activity of the thyroid, and that the secretion of the latter insured the catabolism of fats by increasing their vulnerability to oxidation.

The external appearance of such cases of obesity, which we have described before the French Congress of Medicine in 1904, and the London Pathological Society, February 21, 1905, as endogenous obesity, is also clinically different from the appearance of those caused by overfeeding. As we have shown, persons addicted to rich food, with little exercise, are often red in the face, and are plethoric; they easily become overheated and perspire freely. They seldom complain of constipation. On the other hand persons suffering from endogenous obesity generally look pale, always complain of cold and dry skin, and perspire very seldom, if at all. As a rule they are also very constipated.

There is still another ductless gland which influences metabolism in a powerful way. This is the pancreas which, by its three enzymes, brings about the assimilation of the proteid carbohydrate and fatty materials. To these may also be added its production of labferment. By its internal secretion, which is probably produced by the islands of Langerhans, it aids in the oxidation of the sugar, introduced into our alimentary canal in the shape of starchy food, or contained in the carbohydrated radicle of the albuminous molecules, as demonstrated by Pavy. The entire degeneration of the pancreas, especially of the part containing the islands of Langerhans, produces a disease that is, as a rule, characterized by loss of weight and the production of emaciation often to an astonishing degree—i.e., diabetes.

Persons suffering from the milder form of this disease often present a rosy and healthy appearance, and as we have pointed out previously, often look younger than their age. We believe that, as we shall show further on, this fact is not without relation to the condition of the thyroid in this disease. We have shown by researches made in the laboratory of Professor Minkowski, then of the Augusta Hospital in Cologne, that in diabetes the thyroid contains large, sometimes enormous, quantities of colloid substance, thus indicating a condition of thyroid hyperactivity.

As we have mentioned in the first chapter, corpulence is often one of the first symptoms of old age, and we have also insisted upon the fact that this can be brought about by infectious diseases (e.g., typhoid, pneumonia, scarlet fever, etc.). As we have also mentioned the fact, in the first chapter, that old age can be brought about by an infectious disease which acts upon the ductless glands, especially the thyroid, we believe it will be necessary to enter a little more in detail into this subject, to which we will devote the next chapter. We will enlarge upon the fact that our immunity against infectious diseases is entirely dependent on the proper working order of certain ductless glands.