Endocrinology

ENDOCRINOLOGY. This science deals with the structure and function of the organs of internal secretion (endocrine or in cretory organs), in health and disease, and has been vigorously developed since 191o. Through observations upon man in private clinics and in university hospitals, and through experimentation upon animals in laboratories, many important new facts have been accumulated concerning these organs, their products (increta) and their functions during different periods of the life-cycle of in dividual organisms. Attempts are being made to co-ordinate these recent discoveries with what was known before, in order that knowledge in this domain may be better systematised and formulated and that the diagnosis and treatment of endocrine disturbances in man may find securer foundations than the specu lative suppositions, often groundless, that have been advanced in a period of expanding research to eke out a store of facts that was felt to be lamentably meagre.

Limitation of the Field.

There is, as yet, no general agree ment as to the limits to be set to the field of endocrinology'. (The figures throughout the text refer to the bibliography at the end of the article.) Some would include all parts of the body in the cate gory of organs of internal secretion, on the ground that all organs give off chemical substances to the blood and lymph; others would limit membership in the class to a few organs—(a) the ductless glands and (b) certain glands that, despite the possession of ducts and the production of an external secretion, yield to the blood di rectly (or through the lymph) materials that are of profound sig nificance either for the growth and differentiation of distant parts or for the automatic regulation of the physiological functions of those parts. In this latter and more restricted sense, the endocrine organs include the thyroid gland, the parathyroid glands, the hypophysis cerebri (or pituitary gland), the suprarenal glands, the islands of Langerhans of the pancreas, and, perhaps, the endocrine portions of the sex glands or gonads. Organs, the products of which serve merely the nutrition of the body or are mere waste substances to be excreted from the body by other organs, would not be so included.

Even with this restriction there is doubt as to just how many organs should be classed as "incretory" and, particularly, as to whether the pineal gland, the posterior lobe of the hypophysis cerebri, the thymus, the liver and the chromaffin tissues should, or should not, be so classed. For practical reasons it would seem better to regard endocrinology, for the present at least, as limited in its field to the structure and functions of the organs of internal secretion in the narrower sense mentioned above rather than to extend its scope so as to include all the organs of the body whose products on entering the blood play any part in chemical regula tion. The science which deals with the "hormones" or "chemi cal messengers" (cf. E. H. Starling) in general within the body has been called "hormonology" ; endocrinology in the narrower sense would appear to represent an important part or domain of that more comprehensive subject.

Histology and Embryology of the Endocrine Organs.- The gross and microscopic appearances of the principal duct less glands are described elsewhere (see DUCTLESS GLANDS). Re cent advances in the morphology of these glands have consisted (a) of intensive studies of their finer structure by means of more delicate histological technique and (b) of more accurate deter minations of the mode of origin and the chronological development of these structures in the embryos. Systematic (and quantita tive) statistical studies of the normal variations of these organs and their relations to the body as a whole have been undertaken for certain animal species (e.g., the rat). An attempt is also be ing made to determine precisely the evolutionary processes re sponsible for the organogenesis and histogenesis of the structures that manufacture the internal secretions, a phase of research re garded as important by biologists and especially by embryolo gists'.

Physiology of the Endocrine Organs.

The increta pro duced by the endocrine organs and delivered to the blood, either directly, or by way of the lymph, appear to be of great impor tance for the organism as a whole in all phases of the life-cycle (evolution, maturity and involution) . During the period of evolution, the progressive phases of the life-cycle (that is, during the development of the individual), these increta play a role in the processes of growth, of organ formation and of tissue dif ferentiation'. The endocrine substances that participate in the building of the bodily organs and are of significance in the initia tion and the continuance of the metamorphoses that occur dur ing growth have been called "harmozones." It is believed that they react with the autochthonous chromosomal substances of the cells of different regions of the body, perhaps in an enzyme like way, and so form a part of the stimulative and assimilative processes concerned in normal growth and differentiation.

The endocrine organs themselves undergo changes during growth and development ; the several organs appear at some what different times in the embryo, and vary somewhat in size, in structure, and doubtless, too, in function, at different stages of an organism's unfolding. That the functions of these organs are correlatively connected is certain; and that there are indi vidual, racial and generic variations in these correlations seems very probable. The different varieties of habitus (pyknic, as thenic, athletic) met with inside the limits of normal variation in a single human race, and the skeletal and other somatic peculiar ities that characterise the different races of man (e.g., Nordic, Mediterranean, negro, etc.) or of any other animal, say the dog (e.g., bulldog, dachshund, greyhound), though dependent in part on regional chromosomal specificities, are believed to be also in part determined by the differing endocrine "formulae" or "con stellations" of their bearers, the hypophysis being dominant, per haps in one, the thyroid in another, the gonads in a third and so forth. The different combinations and permutations of the in cretory influences that are possible are interesting and at the same time appalling to the student of human and animal consti tutions'.

Function of Hormones.

During the period of maturity the hormones from the incretory organs are believed to subserve many important functions, particularly those concerned with automatic adjustments within the organism when disturbances endanger equilibriums. Thus a hormone from the thyroid gland participates in the control of the basal metabolic rate, one from the parathy roid in the control of calcium metabolism, and one from the islands of the pancreas in the control of sugar metabolism. These hormones may act, as is gradually being found out, through the utilisation of various mechanisms; sometimes they exert their in fluence through affecting other endocrine organs than those by which they are produced, sometimes through the vegetative nerv ous system and sometimes through direct attack upon the body cells in general. Ignorance here is as yet profound. Slowly, how ever, facts are emerging, as a result of clinical-pathological studies, of experimental removal of an endocrine organ and observing what follows, of transplantation experiments and of experiments in which substances derived from endocrine organs are fed to, or injected into, healthy or diseased organisms.

Senescence and Rejuvenation.

During the period of in volution of an organism, the incretory organs change as do all the other parts of the body. In the ageing process of normal involu tion, there may be steady general decline through a long series of regressive phases to physiological death. But premature sene scence, partial or general, may appear as a result of abnormalities of one or more endocrine organs (gonads, thyroid, etc.), for such abnormalities lead to disturbances of equilibrium of the correlat ing systems of the body. To a certain extent, "rejuvenescence" can be experimentally achieved by injection or transplantation of certain endocrine tissues (see REJUVENATION) . It is possible that the appearance of certain malignant growths may come to be correlated with changes in the incretory glands, for in man, altera tions in the thymus, thyroid, hypophysis and suprarenals have been found in association with neoplastic growths and, in experimental animals, definite influences of incretory conditions upon the "tak ing" and growth of neoplastic grafts, have been Adenocarcinomata, for example, are transplantable to certain nor mal mice but not to castrates of the same species, though if a young testis be also grafted into the castrate, the neoplastic graft can then be made to grow.

Isolation of Chemical Substances.

Physiological chemists have made progress in isolating various potent chemical substances from the organs of internal secretion. Among the more important of these may be mentioned epinephrin (or adrenalin) from chro maffin tissues, thyroxin from the thyroid gland, pituitrin and antuitrin from the hypophysis cerebri, lutein from corpora lutea of the ovary and insulin (q.v.) from the islets of the pancreas. Recently, from the parathyroid glands has been extracted a para thyroid hormone that will prevent or control tetany due to para thyroid insufficiency and will regulate the level of the calcium content of the blood; from pituitrin has been isolated an active principle of great potency that will in extremely dilute solutions cause contraction of uterine muscle ; and from ovarian follicular fluid has been separated a hormone that will, on injection, induce a sexually mature condition in immature females'.

Clinical Endocrinology.-Knowledge

of clinical syndromes due to disorders of the endocrine organs has also made rapid strides since 191o, and the symptomatology of the endocrine dis orders has been extended and made more precise. Thus the prin cipal endocrine disturbances manifested as Graves' disease, myxoe dema, tetany, acromegaly, adiposogenital dystrophy, eunuchism and eunuchoidism, Addison's disease, suprarenal virilism and hirsutism and diabetes mellitus are now far better understood than ever before. There has been a tendency, however, to at tempt to push the clinical applications of the scientific advances in endocrinology further than is warranted, and much confusion has arisen both in the profession and among laymen because of failure to distinguish between mere speculations and well-estab lished facts'. Fortunately, warnings have been sounded, and more careful workers emphasise the necessity of a more rigidly critical approach to the solution of clinical endocrine problems. This is particularly true of endocrine therapy, which has recently almost run riot. The wishful thinking of unskilled practitioners and their uncontrolled impulses therapeutically to act by ad ministering endocrine products singly and in the form of di vers "polyglandular formulae" bade fair, for a time, to become scandalous, aided and abetted as such ill-founded therapy was by ignorant or unscrupulous vendors of endocrine products. Organotherapy and hormonotherapy have scored genuine tri umphs; it is unfortunate that their reputation should be sullied by uncritical The effects of thyroid extract or thyroxin in myxoedema, of iodine in the prevention of colloid goitre (q.v.), of surgical removal of part of the thyroid gland in exophthalmic goitre and of insulin (q.v.) in diabetes (q.v.) are brilliant examples of therapeutic successes in endocrine domains. The utilisation of certain hormones for their pharmacodynamic effects in disorders not primarily of endocrine origin is proving profitable; the control of paroxysms of bronchial asthma by in jections of epinephrin and the restriction of water-excretion through the kidneys in diabetes insipidus by injections of pitu itrin, and the use of pituitrin in obstetrics and surgery, of adrenalin in local anaesthesia and of lutein in ovarian dysfunc tion are notable examples. Organotherapy and hormonotherapy undoubtedly have an important future, but genuine success in these fields can be achieved only by thoughtful, painstaking, rigidly controlled work; progress is only too likely to be retarded and science to be discredited by the rash enthusiast and the credulous ignoramus.

In the United States the Association for the study of Internal Secretions and its journal, Endocrinology, are doing much to foster development of endocrine research. See also HORMONES. BIBLIOGRAPHY.-For summaries of the present status of clinical endocrinology, the reader may consult: Endocrinology and Metabolism, 5 vol. (1922), ed. by L. F. Barker; A. Biedl, Innere Sekretion (Berlin, 1922) ; W. Falta, The Endocrine Diseases (York, Pa., 1923) ; M. E. Gley, Les Secretions Internes (1914) ; R. Porak, Les Syndromes Endo criniens (1924) ; W. Timme, Lectures on Endocrinology (1924) ; A. Weil, The Internal Secretions (3rd ed., 1924) ; and H. Zondek, Die Krankheiten der endocrinen Driisen (1923) .

References in text: (I) cf. A. Kohn Ueber den Begriff der inneren Sekretion, Med. Klinik, Berl., 1924, 20, 1272-74.

(2) For summaries of the morphological and developmental discov eries of recent years, the reader may consult E. A. Schafer's Endocrine Organs; an Introduction to the Study of Internal Secretion (1916). Swale Vincent's Internal Secretion and the Ductless Glands (2nd ed., 1922), and the series of articles in the first two vol. of Endocrinology and Metabolism (1922).

(3) cf. Harms, "Das Wesen der Inkretion and ihre Bedeutung fur das normale and experimentell beeinflusste Geschehen innerhalb der Lebensphasen der Tiere," Deutsche Med. Wchnrchr., 1925, 51, 631-633.

(4) cf. G. Draper, Human Constitution: a Consideration of Its Relation to Disease (1924) ; also, J. Bauer, Die konstitutionelle Disposi tion Zn inneren Krankheiten (3. Aufl. 1924) .

(5) cf. W . B. Cannon and Associates, "Studies on Conditions of Activity in Endocrine Glands," Am. Jour. Physiol., 46; 153 ; 1925, 72, 283 ; 295 ; also G. N. Stewart, Physiol. Rev., 4, 163--19o.

(6) cf. Brown and Pearce, "Malignant tumor of rabbit: results of miscellaneous methods of transplantation, with discussion of factors influencing transplantation in general." J. Exper. Med., 37, 385, 40, 603.

(7) For references to some of these newer studies, the reader may consult A. C. Crawford's "Chemistry of the Suprarenal Glands," Endo crinology and Metabolism (1916), 2, 77-98; E. C. Kendall's "Isolation of Thyroxin," J. Am. M. Assn., 1915, 64, 2042-2043 ; J. J. Abel's "Physiological, Chemical and Clinical Studies on Pituitary Principles," Bull., Johns Hopkins Hosp., 35, ; F. G. Banting and C. H. Best's "Internal Secretion of the Pancreas (insulin) " J. Lab. & Clin. Med., 1922, 7, 251-464; J. J. R. McLeod and F. G. Banting's "Antidiabetic Functions of the Pancreas and the Successful Isolation of the Antidiabetic Hormone-Insulin" (1924) ; E. Allen and E. A. Doisy's "Ovarian Follicular Hormone," Am. J. Physiol., ; J. Biol. Chem., 1924, 61, ; and J. B. Collip's "Parathyroid Hormone," J. Biol. Chem., 1925, 63, (8) cf. H. A. Christian, "The Use and Abuse of Endocrinology," Canada M. Assn. J., 1924, 14, 102-106.

(9) cf. H. Lisser, "Organotherapy ; Present Achievements and Future Prospects," Endocrinology, 1925, 9, 1-20. (L. F. B.) ENDOCRINOLOGY IN ANIMALS Since the term "internal secretion" has been used by some authors so indefinitely as to cover the whole realm of chemical exchange in the animal body, it is necessary for the purpose of this definition to restrict it to the production of substances which are liberated into the body fluids by the specific activity of par ticular structures, and may thus evoke responses in more remote parts. In practically all familiar animals, visible manifestations of activity involve a receptive surface on which the stimulus operates, e.g., retina a structure specialized for the performance of the appropriate response (e.g., muscle or gland), and intervening be tween these two a mechanism of co-ordination. Co-ordination in animals is of two kinds. Cellular animals in general possess tissues endowed with special powers for the conduction of disturbances from the receptive surface to the seat of response. Such tissues constitute the nervous system. But in animals possessing a cir culatory system, the latter also provides an avenue through which, not only the chemical equilibrium of the body, but the active responses of the organism, too, can be regulated. Thus, in addi tion to nervous, there is chemical or endocrine co-ordination. Knowledge of endocrine co-ordination at present is wholly con fined to vertebrate species. This is partly because the study of endocrinology has centred round the attempt to define the role of certain organs of an apparently secretory structure, though lacking any connection by duct with the exterior, with the ali mentary tract, or with the cavities of the reproductive and ex cretory organs. The chief of these so-called ductless glands is the pituitary, which lies attached to the floor of the brain; the adrenals, which lie in close propinquity to the kidneys; the thyroid in the ventral aspect of the pharyngeal region ; and finally certain masses of cells amid the enzyme-secreting tubules of the pancreas. named islets of Langerhans after their discoverer. The islets of Langerhans in certain bony fishes are separate glandular structures unconnected with the pancreas.

The pituitary and adrenal glands are microscopically complex structures. The former consists of three distinct glandular por tions with different histological characteristics, the anterior lobe, the pars tuberalis, and the pars intermedia-the last two, together with a mass of nervous tissue developed from the floor of the embryonic brain, constituting the posterior lobe. The adrenals of land vertebrates consist of two kinds of cells. One type, which forms the core of the gland in mammals, is distinguished by its very specific reaction to chromium compounds, hence called the chromaphil or chromaffine tissue. The chromaphil tissue of fishes is diffuse. The tissue corresponding to the cortical portion of the mammalian adrenal is an entirely separate entity (interrenal body) in the cartilaginous fishes. The thyroid in all vertebrates, including the lampreys and hagfishes, has a very definite and characteristic microscopic structure, consisting of vesicles of epithelial cells surrounding a jellyish mass (colloid).

In the closing years of the 19th century Oliver and Schafer showed that watery extracts of the adrenal (chromaphil portion) and pituitary (posterior lobe) glands have highly specific and potent effects on the circulatory system of the mammal. Murray demonstrated the efficacy of administration of sheep's thyroids in connection with clinical manifestations (myxoedema and cretin ism) associated with atrophy or under-development of the thyroid gland. But it was not till 1902 that the conception of chemical co-ordination became clarified through the work of Bayliss and Starling, who first clearly demonstrated the reality of internal secretion as a means of regulating active responses in the normal animal. it had been known, previous to their researches, that by the introduction of acid alone into the intestine, intermittent activity of the pancreas, which normally occurs in response to the passage of acid food into the former, could be brought into play, even after all the nervous connections of the gut had been sev ered. Bayliss and Starling showed that an acid concoction of the mucous membrane of the intestine will, if injected into the blood stream, evoke an immediate flow of pancreatic juice. These and other experiments showed that liberation, by the acid food, of a soluble product, whose precursor is present in the enteric mucosa, provides the signal for pancreatic secretion. Diffusing into the blood stream, this product, called by its discoverers, secretin, pos sesses the specific property of stimulating the pancreatic cells to secrete: thus the production and translocation of secretin is a mechanism by which the outpouring of one of the most important of the digestive juices is co-ordinated with the entry of food into the portion of the gut into which it is discharged. To substances of such a kind Bayliss and Starling applied the term hormone. Schafer has also used the word autacoid for specific physiologically active, i.e., drug-like substances which can be extracted from dif ferent organs of the body ; as there are several autacoids whose role in the intact animal has not as yet been ascertained, the dis tinction is a valuable one.

Properties of Autacoids.

Of the specific physiologically active constituents of extracts in the ductless glands, adrenaline claims prior attention, since it was isolated in chemically pure form as early as 1902. Adrenaline is the active constituent of the chromaphil tissues of vertebrates ; it also appears to be present in certain invertebrates, such as the mollusc Purpura and in the nerve ganglia of leeches. It is the only autacoid known with cer tainty to be present in the body of animals outside the vertebrate series. Injection into the circulation in all land vertebrates pro duces a marked rise of blood pressure due to arterial constriction. In the pupillary muscles it produces dilation. It produces con traction of the melanophores or black pigment cells in the skin of reptiles, amphibia and fishes. It causes stoppage of movement and loss of tone in intestinal muscle, generally inhibition of the blad der, acceleration of the heart in land vertebrates, and either in hibition or excitation of uterus muscle in mammals, depending on the species. The intestinal response is especially diagnostic and sensitive, being obtainable in dilutions from 1:20,000,000 to I In general there is a noteworthy parallelism be tween the effect of adrenaline and of sympathetic stimulation on the same structure; drugs which block the sympathetic impulse at the nerve-muscle junction antagonize the action of adrenaline. The pharmacological properties of the extracts of the pituitary body of vertebrates are manifold. The three most specific are: (a) Pressor activity, i.e., prolonged rise of blood pressure followed by tolerance to successive injections in the mammal, as described by Oliver and Schafer; (b) Oxytocic activity, i.e., powerful con strictor activity on the mammalian uterus discovered by Dale ; (c) Pigmentary effector activity, i.e., power to evoke expansion of amphibian melanophores studied by Hogben and Winton. The first of these is common to the pituitaries of all land vertebrates and bony fishes; the last two to extracts of the posterior lobe of all vertebrates. The activity of other organ extracts may be de ferred to a consideration of the role of chemical co-ordination (vide infra) .

Chemical Constitution of

Autacoids.—Adrenaline was iso lated in pure form independently by Takamine and Aldrich in 1902. It has since been synthesized, and an iodine compound first isolated in pure form by Kendall (1917) and later by Harrington (1927). Highly concentrated extracts of the pituitary (posterior lobe) have been prepared by Dudley and by Abel and his col leagues. The latter has obtained a preparation which constricts the mammalian uterus in a dilution of I:1,250,000,000. Like insulin, the active constituents of the islets of Langerhans, and like secretin they are crystalloidal substances destroyed by tryp sin ; they are, therefore, possibly polypeptidee.

Methods of Investigation.

Suggestive indications that an organ is one of internal secretion, in the sense defined above, is provided by a study of the biological action of these drug-like substances or autacoids extracted from certain tissues. Charac teristic clinical or post operative consequences of disease, atrophy and removal also suggest lines of investigation. But either of these alone is inadequate as a criterion of endocrine activity. Fresh extracts of the pituitary gland of vertebrates have the property of raising the blood pressure. This is an important fact in phar macology, since extracts of the pituitary have been used to ameliorate the condition of surgical shock, and the existence of this property of pituitary extracts naturally prompts investigation into the possible relation of the pituitary gland to the regulation of blood pressure in the mammal; but there is no justification for assuming without further evidence that such a relation exists. It is contrary to the principles of scientific method to assume that every chemical entity found in the body must necessarily be pro pitious to its efficient working. Again the fact that removal of the testis in the mammal prevents the assumption of the male sec ondary sexual characters does not of itself justify the common references in medical literature to an internal secretion of the testis. On this evidence alone, no economy of hypothesis is ef fected by assuming that the testis discharges specific exciting sub stances into the circulation in preference to the equally plausible alternative that it removes or neutralizes something.

The question of the regulation of active responses by chemical co-ordination is more accessible to experimental study. If it is known that an organ contains a substance which evokes a specific local reaction in some organ or response (muscle, gland, pigment cell, etc.) its endocrine function is sufficiently established by applying one of two methods. In some cases it is possible to show that reactions which follow administration of the organ extract are associated in the intact animal with the appearance of some substance in the blood, having similar chemical and biological properties to the active constituent of the extract. This line was pursued with the study of the adrenals, and it was formerly thought that the dilation of the pupil, quickening of the pulse, etc., characteristic of fright in the mammal, were not wholly of nervous origin but in part reinforced by liberation of adrenaline into the circulation. This view has been quoted widely and accepted by many psychologists. It appears, however, from later more quan titative observations of Stewart and his colleagues that the evi dence of previous investigators was founded on inadequate tech nique. Stewart's work shows that small quantities of adrenaline do make their way into the circulation more or less continuously. Whether such small quantities are really significant to the efficient neuromuscular activity of the animal, and whether special condi tions exist in which a large outpouring of adrenaline into the blood stream occurs is still uncertain. The method which has been applied in the study of adrenaline secretion is essentially similar to that which has been adopted in the study of pancreatic regulation by secretin formation, as mentioned above. An alterna tive method of investigation consists in compensating for the effects of removal of a supposedly endocrine organ by introducing its extract into the circulation. In the case of amphibia (frogs and salamanders), the black pigment cells responsible for the colour responses can be induced to expand after the injection of exceedingly minute traces of extract of the pituitary gland. Re moval of the gland (posterior lobe) on the other hand results in a state of permanent pallor due to complete contraction of the pig ment cells. Here the immediate agency involved in co-ordinating the synchronous response of the pigmentary effector organs of the skin with the external conditions that evoke colour response is evidently the secretion of the pituitary gland. In frogs removal of the gland results in the dilatation of the minute vessels (capil laries) of the skin, and Krogh has shown that perfusion of these vessels with a fluid containing a trace of pituitary extract results in their constriction. It is possible that the rise of blood pressure following injection in the mammal arises from the same reaction, and Krogh has obtained some evidence that pituitary secretion regulates capillary tone in mammals as well as amphibia.

With regard to the part played by internal secretions in relation to chemical equilibrium and development, the attempt to harmonize the effects of removal of organs and of injecting their autacoids into the circulation has yielded the only significant data. First and foremost comes the thyroid. In man, under-development of the gland is associated with the infantile condition known as cretinism, and in later life with the disease known as myxoedema. Both of these are characterized among other things with a lower respiratory activity of the tissues, which is remedied with the clinical manifestations by injection of thyroxine. In frogs and salamanders the larval or tadpole stage can be induced to develop into the adult with amazing precocity by thyroid feeding or injec tion, and the total elimination of iodine from the water or removal of the thyroid gland prevent the larval form from assuming the adult condition, so that it remains permanently in the aquatic form. A few larval forms in nature such as the axolotl larva of the Mexican salamander become sexually mature and never ordi narily assume the adult form if kept in aquaria. The axolotl will develop into a land salamander within ten days of thyroid feeding. Removal of the anterior lobe of the pituitary gland in frog tad poles has also been shown by P. E. Smith and Bennet Allen to prevent metamorphosis. In this case the thyroid remains under developed. Thyroid feeding causes the tadpoles to mature, as does also injection of pituitary anterior lobe extracts, which induce the thyroid to attain its normal development. Thus pituitary secre tion stimulates the development of the thyroid just as thyroid secretion promotes the assumption of the adult characters, and this interrelationship makes it easier to form a picture of the way in which the orderly chronological sequence in which new systems of organs make their appearance in the course of develop ment is brought about. In man, disorders of the anterior lobe are associated with clinical abnormalities of development (acromegaly, etc.), which at present remain obscure. In regard to sexual devel opment the main positive results have arisen in connection with ovarian extracts prepared first by Allen and his associates. Re moval of the ovaries brings about cessation of the oestrous phe nomena. Injection of ovarian extracts evokes oestrous activity, and Parkes has shown that menstruation in the human subject can be induced in this way. A great deal of interest has recently centred round the internal secretion of the pancreas. It has long been known that removal of the pancreas results in diabetes. In 1922 Banting and Best showed that the fatal results of removal of the pancreas can be prevented by specially prepared extracts of the gland, the active constituent of which has the power of lowering the sugar content of blood and urine. Collip has recently claimed that the lowered calcium content of the blood associated with clinical disorders of the parathyroid glands, or operative re moval of the same, can be compensated by the injection of an extract of the gland.

Practical

successful use of thyroid extracts for myxoedema and cretinism, the application of pituitary extracts to promote contraction of the womb in obstetrical practice, and to raise blood pressure in cases of surgical shock, the use of adren aline in superficial haemorrhage, and finally the importance of in sulin in relation to diabetes represent genuine positive achieve ments of no mean value in modern scientific medicine. The manu facture of glandular preparations, however, has been abused for commercial purposes, and a great deal of what is called glandular therapy or organotherapy is based on no proper information. So called polyglandular preparations are sold by a number of firms, and are extensively employed by medical men who have insuffi cient information at their disposal to sift the wheat from the chaff. Side by side with these abuses, descriptions of clinical manifestations, uncontrolled by critical experiment, has led to a large amount of speculation about the role of the ductless glands in determining differences of temperament. Much of this is pass ing into psychological and sociological works. It cannot be too strongly emphasized that, while such speculation may serve a useful purpose by stimulating further enquiry, it is for the most part entirely premature and often without any valid justification.

See L. T. Hogben, The Comparative Physiology of Internal Secre tion (1927) ; E. Schafer, The Endocrine Organs (1924-26) ; S. Vincent, Internal Secretion and the Ductless Glands (1924). (L. T. H.)