ENDOCRINE, GLANDS. — In contrast to exocrine glands, which produce enzymes with biochemical activity (secreted) or eliminate unusable or harmful materials from the organism (secreted), there exist endocrine glands (e. g.) that release their processed products directly into the bloodstream or lymphatic vessels that pass through them; these products are called "hormones" (βαρυάσα) due to their stimulating action on various organs and the autonomic system of vegetative life.
Through these regulators of vital processes, whose action complements that of enzymes (q.v.), vitamins (q.v.), and certain metals and metalloids present in the organism—capable, even in minimal quantities, of exerting significant biological actions (oligodynamic activity)—this remarkable and perfect unity of action is achieved. Despite the myriad cellular elements and the vast number of organs and functions, the human organism maintains functional balance. This unity rests, on one hand, on the coordinating function of the nervous system, particularly the vegetative life, and on the other, on the humoral balance of the circulating fluids in the body (blood, lymph, cerebrospinal fluid, and the fluid of the cerebral ventricles), whose delicate physical, chemical, and biological composition is influenced by the aforementioned elements.
Within this framework of actions, endocrine glands, rather than being organs of labor, should be conceived as highly delicate apparatuses for regulating and coordinating vital functions. Their activity manifests through morphoregulatory functions—stimulating, inhibiting, orienting, or coordinating the construction of the bodily mass or the morphological differentiation of the individual organism, directing it toward a particular constitutional type (q.v.)—or through chemoregulatory functions, activating or moderating the complex chemical processes underlying vital phenomena. They also exert neuro-psychoregulatory activity on major neurovegetative systems (sympathetic-parasympathetic) or even on the nervous functions that underlie the highest processes of psychic life and the balance of cortical and subcortical nervous centers of intelligence and emotion.
At present, the endocrine system and the various glands that constitute it are not yet fully understood. While some aspects are well known, others are only beginning to emerge in the realm of knowledge. Among the better understood are: the pituitary gland, the thyroid, the parathyroids, the adrenal glands, the endocrine portion of the pancreas (islets of Langerhans), and the endocrine portion of the sexual glands (testicles, ovaries). The thymus and the pineal gland, organs definitively endocrine in nature, are also well understood. To these hormone producers, many others will undoubtedly be added in the future; some authors already include certain functional aspects of the liver (the liver's anti-anemic hormone or Asher's hepatic hormone), the spleen, the tonsils, the intestinal mucosa, the kidneys, etc.
A comprehensive study of endocrine glands and their hormones would exceed the scope of this article; therefore, only a brief functional profile of the most important ones will be provided, with particular emphasis on their potential interactions with higher psychic functions (emotional and intellectual).
I. THE PITUITARY GLAND OR HYPOPHYSIS
The size of a pea or small bean, weighing about half a gram, the pituitary gland is located (in a small depression [sella turcica] formed at the expense of the underlying sphenoid bone) at the base of the brain, with which it maintains special connections through a stalk (infundibulum) that unites it to the diencephalic region of the brain. This region houses higher nervous centers of vegetative life and is indirectly connected to the centers of emotional life. Its close relationship with nervous centers and its ability to control almost all other endocrine glands through its complex hormonal system places the pituitary gland in a privileged functional position, earning it the names "endocrine brain" or "master gland of the endocrine orchestra." It consists of three parts: an anterior portion distinctly glandular, a posterior portion of nervous tissue in developmental and synergistic relationship with the brain, and an intermediate portion of epithelial nature, poorly developed in humans. The anterior lobe (adenohypophysis), rich in hormones to the extent that few bodily functions escape its influence, produces: a growth hormone that stimulates the development of bodily mass, particularly in height, hence its excess during growth leads to gigantism and, after development is complete, to acromegaly; hormones that stimulate the thyroid and the adrenal cortex; regulators of the endocrine function of the pancreas; stimulants for the liver to release its glycogen reserves (diabetogenic hormone); hormones that stimulate the mammary glands to secrete milk during the puerperium (prolactin); and gonadotropic hormones (gonadotropin A and B) that promote or inhibit the specific activity of germinal tissues and the endocrine tissues of the sexual glands.The posterior portion of the pituitary gland produces a hormone that inhibits urinary secretion (its deficiency causes "diabetes insipidus," a polyuria without glycosuria); a hormone (vasopressin) capable of raising blood pressure by constricting small capillary arteries; and oxytocin, which, upon reaching a particular concentration in the blood toward the end of pregnancy, induces expulsive contractions of the uterus. The intermediate lobe, of lesser importance in humans, produces intermedin, which, particularly in some animals, acts by altering the size of pigment cells in the skin, thus producing varied patterns and colors (e.g., the nuptial livery of the male stickleback during mating season). Even in humans, this hormone appears to be related to reproductive function, producing increased pigmentation in specific skin areas during pregnancy. This suffices to illustrate the pituitary gland's role in the economy of the entire organism and the necessity of a perfect balance and mixture of its multiple hormones. This balance ensures the organism avoids the opposing anomalies of gigantism and dwarfism; maintains equilibrium in the complex interplay of germinal and endocrine activity of the sexual glands, during pregnancy, childbirth, and lactation; ensures normal deposition of adipose tissue in appropriate topographical distribution; regulates water retention in the body, a condition for the regular intake and output of saline substances, particularly sodium chloride; governs sugar metabolism; maintains the balance between wakefulness and sleep, preventing persistent insomnia or lethargic hypersomnia; and ensures optimal blood pressure, among other functions.
No less significant is the importance of pituitary hormones regarding the neuro-psychic and intellectual manifestations of the individual. The equilibrium of affective life, normal intellectual development—especially in its particular characteristics—are linked to the functioning of the pituitary gland. The neuro-psychic temperament and individual disposition, which vary according to individual type, may be influenced by an excess or deficiency in pituitary function. This must be considered in education and in forming a moral judgment of the individual.
II. The Thyroid
The thyroid is situated in front of and to the side of the larynx and the first rings of the trachea, and immediately follows the hypophysis in importance; it is the first among all the other endocrine glands to have earned the name of “queen of the endocrine glands.” The functions of its hormone are numerous, with points of attack on both vegetative and relational life. Through its neuro-glandular activity, the thyroid hormone influences the development of many tissues: connective, cutaneous and its appendages (hair and nails), skeletal, blood elements, and the nervous system, as well as other endocrine glands. Among other things, the thyroid is responsible for regulating biochemical activities, the substrate of relational vegetative phenomena; it directly stimulates oxidative processes and, indirectly through the sympathetic nervous system, the exchange of materials and energy that occur between the organism and its surrounding environment (metabolism), particularly with regard to fats, nitrogenous substances, water, salts, carbohydrates (glycogen), as well as influencing the production and regulation of body heat. Of particular importance is the stimulating action that, also through the sympathetic nervous system, is exerted on the nervous activities of the organism, both neurovegetative and those of relational life, whence the special importance of the thyroid on the development and characteristics of the psychic functions of the individual (hyperemotivity, readiness and rapidity of action and ideation).
The thyroid maintains collaborative relationships (synergy) with the germinative portion of the genital glands, the adrenal medulla, and the anterior hypophysis; opposition (antagonism) with the thymus, the pancreatic islets, the parathyroids, the adrenal cortex, and the posterior hypophysis. The aforementioned bioregulatory elements (vitamins, oligophanic minerals) establish links with it: vitamins A and B hinder its function; an increased iodine content in the blood, of which the principal thyroid hormone (thyroxine) is very rich (65.3%), strongly stimulates its action; violent emotional states, capable even of doubling the iodine content of the blood, frustrate the action of the gland, producing in the individual an accentuation of the catabolic phase of metabolism, leanness, and nervousness; a particular stimulating action is exerted by the substance (leanness and nervousness of smokers).
Hyperfunction of the thyroid, exceeding the limits of normal individual variability, gives rise to the clinical picture of “Basedow’s disease” or “exophthalmic goiter,” more frequent in females (6:1) and in early adulthood (20-40 years). In this disease, an hyperfunctioning enlargement of the thyroid is accompanied by an exaggerated increase in pulse rate, exceeding 100 (tachycardia), the protrusion of the eyeballs, excessively prominent between the widened palpebral fissure (exophthalmos), a “worsening of internal oxidation processes with a greater consumption of oxygen, the predominance of the catabolic phase of metabolism, sometimes accentuated to an extreme degree. Other ocular symptoms, trembling of the outstretched hands, excessive sweating, skin and skin appendage alterations, disturbances of intestinal function (diarrhea, etc.) complete the picture of pathological hyperfunction of the thyroid. A decrease in thyroid activity, falling below normal individual variability, conversely gives rise to the clinical picture of so-called myxedema, a particular form of elastic swelling of the skin, associated with a slowing and more or less severe decline of all the functions of vegetative and relational life with defective bodily development, so that if the defect was present from birth, the individual remains a cretin. In particular, the nervous system and the psychic activity of the subject suffer, with torpor of action, mental apathy, up to the most absolute lack of intelligence (cretinism). Often the picture is completed by an enlargement of the thyroid in its connective supporting part, which, with its exaggerated development, suffocates the secretory portion of the gland; it gives the characteristic prominence in front of the neck, i.e., goiter. This, together with thyroid hypofunction and a more or less severe degree of cretinism, constitutes a disease of endemic character in some mountainous regions of Switzerland, the Pyrenees, Germany, Venezuela, and in Italy in Piedmont (Aosta Valley), Lombardy (Valtellina), in some areas of Liguria, Sicily, and Sardinia. The cause of endemic goiter is still under discussion; according to some authors, the phenomenon would be due to the presence of particular goitrogenic substances, in a colloidal state, contained in the water drunk in those places (gypsum, fluorine); N. Pende speaks of “endemic mountain disease” and admits multiple causes (scarcity of iodine, solar radiation, certain foods, hygiene, consanguinity in marriages, etc.). Because of the aforementioned relationships between the thyroid and the sexual glands, in thyroid hypofunction there is a lack or delay in pubertal development with more or less marked deficiency of primary and secondary sexual characteristics. In hyperthyroidism, on the contrary, precocious sexual transformation. The functional balance of the thyroid or its shift toward excess or defect, within the limits of normal individual variability, imprints particular constitutional characteristics on the organism, deviating it toward the longilinear (v.) or brevilinear (v.) type, as well as differently influencing the temperament and disposition.
III. The Parathyroids
The parathyroids are located posteriorly, resting against the thyroid, normally in the number of four, about the size of a rice grain, and, despite their smallness, are so important in the endocrine balance of the individual that their removal leads to the most serious consequences. Their function is sufficiently clear to reveal their great importance as regulators of the mineral metabolism of calcium and phosphorus, basic elements for the mechanical equilibrium of bone tissue and the biochemical equilibrium of the nervous system. Bones owe their rigidity, capable of giving the organism the necessary firmness and resistance in its form, to calcium carbonate (10%) and tricalcium phosphate (90%). The nervous system undergoes variations in its excitability in relation to the changing molecular equilibrium of mineral salts dissolved in the blood plasma; calcium, in combination with magnesium, exerts a sedative action on neuromuscular and psychic excitability, while sodium and potassium, on the contrary, increase its irritability. Thus, all life seems to revolve around these two “chemical poles” (Rondoni): on the one hand, asthenia, i.e., decreased neuromuscular excitability, due to the predominance in the osmotic equilibrium of the circulating fluids of the calcium-magnesium pair, and on the other, the predominance of sthenia, increased neuromuscular excitability, due to the predominance of the sodium-potassium pair. In all this, the delicate regulation of the exchanges and equilibrium of calcium marks the wonderful importance of the parathyroids in the economy of the organism.
In parathyroid deficiency, due to the decreased amount of circulating calcium in the blood (hypocalcemia) compensated by an increase in phosphorus (hyperphosphatemia), the bones do not acquire the proper amount of calcium while neuromuscular irritability increases, up to the spastic contraction and convulsive forms of tetany, eclampsia, and spasmodic conditions. Revealing signs of deficient parathyroid function may be: brittle and grooved nails, defects in the enamel of the incisor teeth, dark circles under the eyes, a tendency to grimaces, facial “tics,” staring eyes, certain forms of migraine, asthma, neuralgia, and a tendency to swellings. Particular morbid forms are produced by a state of hyperfunction of the parathyroids (osteitis fibrosa or Recklinghausen’s disease).
The parathyroid hormone is linked by relationships of collaboration with vitamin D3 (vitamin D3, the calcium-fixing vitamin) and with other hormones, such as those of the thyroid and thymus.
IV. The adrenal glands
There are two of them, situated like caps, one on each side at the upper pole of the kidneys, measuring a few centimeters (maximum: 6 x 3 x 1 cm); due to their specific activity they have earned the name of “glands of energy.” Each adrenal is not a single organ, but combines within itself a cortical portion (cortex) and a medullary portion (medulla), each elaborating different hormones.The cortex, once thought to be anatomically and functionally unitary, modern studies have revealed it to be composed of three distinct zones: the “glomerulosa,” whose hormones (the most important being desoxycorticosterone, the only one currently obtained synthetically) regulate water and salt metabolism, causing retention of sodium (sodium chloride) and quinine salts (and water in the tissues) and elimination of potassium in the urine; they also increase arterial pressure. The “fasciculata” zone produces another group of hormones, among which corticosterone is notable; it regulates carbohydrate metabolism and their formation at the expense of proteins, and if in excess, manifests a diabetogenic action with an increase in blood sugar and elimination in the urine. The “reticularis” zone also elaborates a certain number of substances not yet well defined, such as adrenosterone, which has an action similar to that of sex hormones, predominantly male, though much less potent; their effects appear in cases of hyperfunction of the adrenal cortex. The first two groups of adrenocortical hormones are truly indispensable for life: their complete deficiency produces “Addison’s disease” or “bronze disease,” which, within a few years, leads the individual to cachexia and death. It is extremely rare in childhood; in a high percentage of cases it is due to tuberculosis of the adrenals; clinically it manifests as progressive intense weight loss, neuromuscular weakness, lowered blood pressure, decreased sodium chloride and blood sugar, inconstant disturbances of the sexual sphere (impotence, anemia), decreased resistance of the organism to toxic and infectious causes, particularly painful involvement of the skin and mucous membranes (whence the name), and loss of hair, especially in the axillary and pubic regions. Hypercorticism, ranging from total cases (Cushing’s syndrome) to partial hyperfunction, presents the greatest variety of symptomatic intensity and combinations, reflecting the described activities of the glomerulosa, fasciculata, and reticularis zones. In it, the symptom “hypertrichosis” (excessive hair growth) is always characteristic, not only on the trunk and limbs but also, in women, on the face. In relation to the perfection of the reticularis zone and the exaggerated quantity of sex hormones (particularly the androgenic fraction) with masculinizing effects (more rarely feminizing and estrogenic), in similar partial hypercorticism one may observe various pictures of alterations in the sexual habitus of the individual, both in primary and secondary sexual characteristics, in the form of “adrenal virilism” and “adrenal feminilism,” and of “precocious puberty” associated with Addison’s disease. In the first case, if hyperfunction of the reticularis occurs in an individual of the female sex during fetal life, a picture of “pseudo-hermaphroditism” is seen, in which the individual (at birth) is both a carrier of female sex glands (ovaries) and of external sexual organs of the opposite sex (v. ERMAFRO-DITISMO); if it occurs before puberty, the picture of “heterosexual precocious puberty” or “prepubertal virilism” appears; in adult women it causes the addition of masculine characteristics to previous feminine ones; in the male, androgenic hypercorticism beginning before puberty manifests as an early appearance of puberty. In some cases, in adult males, due to a particular excess of estrogenic hormones, “adrenal feminilism” may occur with loss of masculine characteristics and deviation toward the feminine type. On the other hand, cases are known in which atrophy of the fasciculata and glomerulosa zones, combined with hyperfunction of the reticularis zone, leads to the form of pseudo-hermaphroditism or precocious puberty that unfolds within the framework of Addison’s disease.
If these are the nodal aspects of pathological hypo- and hypercorticism, one may admit, in the physiological functional equilibrium of the adrenal cortex, an entire series of subtle gradations spanning the boundaries of individual variability, which, while explaining many constitutional, functional, and neuropsychic anomalies, show the immense importance of these studies with regard to the educational and moral orientation of the individual and the moral judgment of his actions. The adrenal cortex has close synergistic relationships with vitamins C, A, and B6; its hormones, with regard to the regulatory apparatus of vegetative life, have vegetative functions (v. NEUROVEGETATIVE SYSTEM).
The medullary substance of the adrenals carries out its hormonal function in the production of *adrenaline* or “proseminine,” which has a hypertensive action and selectively stimulates the sympathetic proteins of the autonomic apparatus of vegetative life; it is extremely active, capable of exerting its specific action on the sympathetic even when diluted in the blood to the ratio of one to a billion; on the isolated heart it remains active even when diluted in the ratio of 1:1,000,000,000,000,000,000,000,000,000,000,000,000,000.
(follicle of Graaf) and the corpus luteum. The former, by virtue of their internal secretion (folliculin), promote the perfection of the primary sexual characteristics already formed at birth; the appearance and development of secondary sexual characteristics during puberty, in women between the ages of 13 and 15; and they nourish libido, albeit in the more moderate form usually observed in women. The onset of folliculin action at the beginning of puberty is marked by the appearance of the first menstruation, which then repeats periodically with each ovum maturation (on average every 28 days in 70% of cases), throughout the duration of female sexual life, until the time of menopause (CLIMATERIC, AGE) around 45–50 years, sometimes 55–60, with the extreme limit of 65 being highly doubtful.
Menopause marks the cessation of the folliculin function of the ovum; once this has occurred, the characteristics of femininity regress no less: the matured external forms, the development of facial hair, the coarsening and lowering of the voice, and changes in temperament impress upon women increasing signs of masculinization, which tend to narrow the gap between the two sexes.
Alongside the action of folliculin, that of the corpus luteum must also be recalled, an endocrine formation that periodically revives, with each rupture of a Graafian follicle, in the empty follicular cavity. The hormone it secretes (progestin or progestanone or luteosterone), chemically akin to testosterone, is the guardian of pregnancy (v.), since, during the approximately 12–16 days between the rupture of the follicle and the possible next menstruation (if the ovum was not fertilized), progestin promotes changes in the uterine mucosa that render it suitable for the implantation and development of the ovum. These favorable changes are maintained by the corpus luteum for the first four months of pregnancy, if the ovum was fertilized; thereafter, the protective activity of the corpus luteum is assumed by the endocrine function of the placenta. Until the fourth month, the action of the corpus luteum is enhanced by that of "vitamin E" or "antisterility vitamin." It should be noted that the endocrine activity of the follicle and the corpus luteum is under the control and stimulation of the A and B gonadotropic hormones of the anterior pituitary and of a sexual nervous center.
VI. THE PANCREAS
Located in the abdomen in the loop formed by the first portion of the intestine (duodenum), besides being a gland secreting digestive juices, through the islets of Langerhans it is an endocrine organ that produces insulin, a hormone regulating carbohydrate metabolism (sugar, starches) in glycogenesis, i.e., the transformation and storage of these substances in the form of "glycogen" in liver cells and muscles, and in making cells more fully utilize the portion of sugar dissolved in the blood. Antagonistic to insulin is the aforementioned adrenaline, the hormone of the adrenal medulla, which stimulates the mobilization and breakdown of hepatic glycogen (glycolytic function), thereby leading to an increase in the percentage of glucose (in a normal individual about 1 per thousand) present in the circulating blood.If one considers that carbohydrates are par excellence our dynamic foods, fuel that, through its oxidation within muscular tissues in particular, is the source of the energy we expend, one can appreciate the importance of the endocrine balance between insulin and adrenaline as regulators of the metabolism of accumulation and utilization of carbohydrate substances. Vitamins B1, B2, C, and zinc in an oligodynamic function collaborate with insulin.
VII. THE PINEAL GLAND OR EPIPHYSIS
It is about the size of a large pea, weighing barely a quarter of a gram, situated above the isthmus of the brain, between the corpus callosum and the cerebellum, symmetrically below the pituitary gland. It also plays a particularly important role with the third ventricle, the seat, as has already been mentioned, of important nervous centers regulating vegetative life. Its hormone may still be considered unknown in its constitution, but not in its action, which is particularly important in the early period of an individual’s life. The pineal gland acts upon the sexual glands with an action opposite to that of the pituitary; while the latter, as is well known, through gonadotropins, promotes the activity of the gonads, the pineal gland, which deserves the name of "guardian of childhood," through an anti-gonadotropic hormone, prevents pubertal development and sexual differentiation. From about the tenth year of age, in relation to the preparation and subsequent unfolding of the individual’s sexual development, the gland undergoes a natural process of atrophy and functional regression. Confirmation of this is found in the fact that experimental removal of the pineal gland in animals, or its destruction before the tenth year of life in humans, through morbid lesions that affect it—particularly pinealomas—leads to excessive bodily development and precocious puberty (pineal macrogenitosomia, hypergenitalism), with a gradual and full appearance of primary and secondary sexual characteristics, and the onset of menstruation in girls even in the earliest years of life. It appears that pineal preparations are useful in schizophrenia and can enhance hair growth.The pineal gland protects the existence of the thymus, which is also condemned to gradual atrophy with the awakening of the activity of the sexual glands; it is in functional opposition to the anterior portion of the pituitary, the sexual glands, the thyroid, and the adrenal cortex.
VIII. THE THYMUS
This is also a gland characteristic of youth, as shown by the progressive decrease in its relative weight as one approaches puberty, after which it rapidly atrophies. It is located in the anterior mediastinum, enclosed in the chest between the sternum, the heart, and the two internal surfaces of the lungs; in common parlance it is called "sweetbread." Galen considered it the seat of courage and emotions.While the internal portion of the thymus is formed by lymphoid tissue, akin to lymph glands, the medullary portion (Hassal’s corpuscles) is the true endocrine producer of thymic hormone, which, although not yet certainly isolated or chemically identified, is empirically known in its actions: stimulation of the anabolic phase of metabolism, mainly with regard to glucose (collaboration with insulin), with an increase in body mass, particularly during periods of "turgor" in endocrine and prepubertal life (v. ETÀ DELLA VITA). In collaboration with vitamin D3, the thymic hormone facilitates the assimilation of calcium and phosphorus by the skeleton; by supporting and protecting the action of the pineal gland, it acts as a restraint on the pubertal development of the gonads, thus being in functional opposition to the anterior pituitary, the sexual glands, and the adrenal cortex. Excessive function of the thymus (Pende’s constitutional hypertimic syndrome) leads, in a large percentage (15%) of cases, to cryptorchidism (v.), provokes excessive bodily development (macrosomia) and of fat, with somatic, sexual, and psychic characteristics remaining childlike; exaggeration of the infantile lymphatic state (adenoid vegetations, hypertrophy of the tonsils and spleen, susceptibility to cutaneous exudative forms, etc.). On the other hand, removal of the gland in young animals or its deficient development in children produces a halt in bodily development, particularly in height, and a defect in bone calcification, leaving the bones soft and pliable.
The thymic hormone, with regard to the neurovegetative system, exerts an excitatory-vagal action, in contrast to the sympathicotropic action of adrenaline; in hyperthyroidism (Flajani-Baedow disease) there is marked hypertrophy and hyperfunction of the thymus, in an attempt to counterbalance the hypersympathicotonic state and the increased calcium base of metabolism. These are the most important and best-known endocrine glands; of others, only the existence or a presumed function can be glimpsed.
IX. CONCLUSION
Given what has been said, it is necessary to insist on the great importance of the function of the endocrine system for all phases of the development of the organism, from the earliest moments of endocrine life, when it is influenced by the action of maternal hormones, and subsequently, through the ascending path of childhood, adolescence, youth, the equilibrium of maturity, and the regression of old age; this applies both to the lower manifestations of vegetative life and to the higher ones of relational life, up to those that accompany and serve as instruments for the psychic functions of feeling, intelligence, and will.Because of the collaborative relationships that enzymes and elements from the plant (vitamins) and mineral (metallic ions, oligodynamic minerals) environment establish with hormones, the organism finds itself immersed, sustained, and to some extent determined by a complex atmosphere of physical and biological causes that interlink and subordinate the life of the macrocosm with that of the microscopic organism. Although some of these causes, particularly the vitaminic and mineral (and here meteorological factors must not be forgotten), to a certain extent act equally on groups of organisms living in a given environment, it is seen that, in fact, each responds differently, giving rise to that almost infinite variability of individual morphological-functional types characteristic of living beings. This is due to the action and mutual equilibrium of the endocrine glands, which, like a "constellation" (N. Pende), establish a specific equilibrium for each organism; it is due to the "credit ground" on which all this complex of causes acts, particularly on the tissue at the apex of the organic hierarchy, namely that of the encephalic nerve centers. If the organic terrain, if the various tissues on which the said macrochemical constellation regulating life must act present hereditary or acquired structural alterations, then hormonal actions, like vitaminic ones, will not be able to elicit a normal response from tissues already abnormally constituted. This is the fundamental principle to be kept in mind above all for understanding the relationships between neuropsychopathology and endocrinology or vitaminology, and for the application of hormonal and vitaminic therapies to diseases of development, metabolism, the nervous system, and the psychic sphere.