Organotherapy (a2076)

ORGANOTHERAPY (syn. opotherapy), in the literal and primitive sense of this word as a method of treating humans with animal organs, was known in antiquity, but it becomes scientific only with the development of the doctrine of the glands of internal secretion, and acquires an increasingly restrictive meaning, up to the point of identifying it with hormonotherapy. The use of organopreparations in antiquity was associated with mythical concepts, with primitive animism, which endowed organs with mysterious physical and psychological properties. Thus, it was assumed that bravery was hidden in teeth; in case of infertility, the patient was given hare meat, because the hare was considered very prolific; the meat of a rooster, considered passionate, was supposed to increase potency. According to the principle similia similibus, in liver disease, the patient was prescribed liver, etc. In the first century of the Christian era, Pliny prescribed the testicles of an ass and a deer to increase potency. In the middle ages, the preparation cranium humanum praeparatum, which was prepared from the brains of executed criminals, was used as a remedy against nervous diseases. The beginning of the scientific development of organotherapy must be considered 1889, when Brown-Séquard made an attempt at self-rejuvenation by injecting himself with an extract from testicles. But still, until the very last time, crude empiricism dominated organotherapy, and practice significantly outpaced theory, which often led to negative consequences. Methods of administering organotherapeutic preparations are diverse. The most convenient method of administration is orally, but it is, unfortunately, not suitable for all organopreparations. Thus, preparations of the adrenal gland, pituitary gland, and pancreas easily lose their activity under conditions of acidity or alkalinity of the contents of the gastrointestinal tract. The best therapeutic results upon oral administration are given by thyroid gland preparations, and less definite ones by sex gland preparations. Another method of administration is parenteral—in the form of subcutaneous, intramuscular, or intravenous injections, wherein aqueous extracts should be preferred to oil ones. Sometimes, due to an admixture of proteins in the preparation, on the 8th to 10th day after the injection, anaphylactic phenomena are observed at the injection site—swelling, redness, which are sometimes mistaken for abscesses. True anaphylactic shock is possible only with intravenous administration. For repeated injections, desensitization according to Bezredka is necessary, i.e., the preliminary administration of small doses. The different effect depending on the method of administration of the preparation must be especially taken into account when using pluriglandular preparations, when for one component a given method may be appropriate, and for another—not. The question of dosage is of very great importance, because depending on the amount of hormone, a different qualitative effect can be obtained, for example, instead of excitation—inhibition. It should be borne in mind that the action of many hormones is biphasic, sometimes polar-opposite depending on the dose. Thus, adrenaline at a too small dose may cause dilation of blood vessels instead of constriction. Meanwhile, determining the necessary dose presents significant difficulties. The attempt to crudely transfer a dose from an animal to a human, let alone a patient, by recalculation per unit of weight has not justified itself. When administered orally, it is not always possible to take into account absorption conditions, enzymatic influences of the gastrointestinal tract, and so on. That is why one often has to establish the dose empirically, dose cautiously, by trial and error, starting with lower doses. But at the same time, one should not use doses that, even if they do not harm, will a priori not exert a therapeutic effect; such a fear of large doses exists in particular with regard to adrenaline. Only in rare cases is there an opportunity for objective control of the preparation; thus, in studying the effect of thyroid gland preparations, the indicator of the therapeutic effect is the determination of gas exchange. Since in most cases preparations are given for a long time, it is necessary to take breaks during treatment, otherwise there is a risk of causing phenomena of thyrotoxicosis, insulin poisoning, and so on. In organotherapy, habituation phenomena, similar to those with narcotic drugs, are almost not observed; such phenomena were noted only for thyroidin (Sereisky). The mechanism of action of organopreparations is diverse. Basically, we can speak of three types of organotherapy: substitution, stimulation, and inhibition. Substitution therapy has the purpose of making up for the insufficiency of hormonal activity either by direct replacement of function or by sparing one or another endocrine organ, which, thanks to a smaller load, begins to function properly over time even without the help of organopreparations; this is especially clearly seen in the action of insulin in cases of pancreatic insufficiency. Substitution therapy is very successful in underdevelopment of the endocrine apparatus and less effective in its pathological lesion. Transplantation of endocrine glands can also be attributed to substitution therapy (see Transplantation). Stimulating therapy is possible only where there is still functioning tissue; it finds its greatest application in disorders of the sex glands and pituitary gland. It is completely obvious that elements of stimulation are also present in substitution therapy, however, for stimulating therapy, first of all, the action of X-rays is used. Inhibitory therapy is carried out mainly by the surgical method, for example, operative removal of the thyroid gland in Graves' disease, or by irradiating it with X-rays; in the latter case, one should act very cautiously, not giving too small doses, which can lead not to inhibition, but to irritation. In some cases, for the purpose of inhibition, one can use the antagonistic action of glands, for example, large doses of sex glands can inhibit the action of the thyroid gland, adrenaline—the influence of insulin, and the like. To this same kind of therapy belong concomitant therapeutic effects by drugs, psychotherapy, physiotherapy, also leading to inhibition. Indications for the use of one or another type of therapy are rather complex, since phenomena of hyper- and hypofunction are often observed simultaneously. In addition, besides the activity of endocrine glands, it is necessary to take into account the influence of those effector organs upon which organopreparations must exert their action and which give a different reaction depending on one or another physical and chemical conditions of the environment at the periphery, on the state of the autonomic nervous system, and so on (thus, for example, calcium inhibits, and potassium stimulates the action of thyroxine). Finally, it must be emphasized that organotherapy not only does not exclude, but, on the contrary, requires additional measures, such as diet therapy, climatotherapy, and physiotherapy, and above all psychotherapy, which exerts a tremendous influence on the endocrine-autonomic system. From what has been said, it is clear how complex the interrelationships are in organotherapy. Therapeutic failures may depend on the quality of preparations, incorrect dosage, incorrect routes of administration, incorrect diagnosis, and so on. Interrelationships are especially complex during the action of pluriglandular preparations. Their relative harmlessness is explained by the fact that—in this case fortunately—these are mostly very weak preparations and only for that reason do no harm. However, if organotherapeutic failure, thanks to all the indicated complex relationships, does not indicate an incorrect indication, then, on the other hand, therapeutic success does not necessarily speak in favor of the recognized pathogenetic connections of a given case. Endocrinologists make this mistake very frequently, sinning against elementary logic. For example, if in toothache, adrenaline applied locally relieves pain, it does not follow from this that toothache is associated with a disturbance of adrenal functions. Particular organotherapy. Thyroid therapy finds its application primarily in diseases associated with thyroid gland insufficiency (see). This therapy is used either in the form of transplantation (see Transplantation) or in the form of preparations. As for preparations, they can be reduced to 4 groups. The first group is fresh thyroid gland. It is best to use a sheep's gland; one lobe weighs 1.5 g. Dosage: for a child ¹/₂ lobe, for an adult 1–2 lobes, in warm broth. This method has a number of drawbacks. Thus, at the slaughterhouse, instead of the thyroid gland, the thymus gland and the like are often given; besides, this preparation easily decomposes, and is subject to rapid putrefaction. The second group is glycerin extracts of the thyroid gland, obtained by macerating the fresh gland in glycerin water for two days. They are used in the form of injections, but since they have no advantages over the dry powdered preparation, at the present time they have almost completely gone out of use. The third group is dry preparations of the thyroid gland, obtained by drying this gland. After drying, a powdered preparation is obtained by grinding. This type of preparation is the most commonly used, applied orally. On average, such a preparation is 5 times more effective than the fresh gland. Dose 0.1–0.3–0.5. The fourth group is active substances of the thyroid gland: iodothyrin, thyroglobulin (see Thyroidin, Iodine), and so on.

These preparations do not possess such a therapeutic effect as the aforementioned ones, because they apparently contain only a part of the active substances of the thyroid gland. Mention should be made separately of thyroxine (see), the genuine hormone of the thyroid gland, obtained in 1919 by Kendall. Parathyrotherapy. In contrast to the brilliant successes of thyrotherapy, parathyrotherapy has achieved only very insignificant successes. Parathyrotherapy finds application in diseases associated with hypofunction of the parathyroid glands (tetany, spasmophilia), and then in a number of other diseases whose connection with the parathyroid glands is more or less hypothetical, such as shaking palsy, chorea, epilepsy, myoclonus, congenital myotonia. In cases of idiopathic and postoperative tetany, transplantation of the parathyroid glands often yields good results. The preparations of the parathyroid glands used until recently led to the goal only in rare cases. There is an assumption (Sainton) that this depends on insufficient doses, and that doses corresponding to 25 g of fresh gland extract should be given. But most likely the therapeutic success depends mainly on the quality of the preparations. In 1925, Collip managed to isolate a hormone, at least one of the hormones of the parathyroid glands, which was named parathyroid hormone-Collip (see Parathyreoidin). Adrenal therapy. The first preparations from the adrenal glands were extracts in physiological saline or glycerin, but already a very short time later, Stolz and Dakin in 1905 prepared the adrenal hormone adrenaline synthetically (see). Indications for treatment with adrenal preparations are Addison's disease, as well as cases of adrenal insufficiency, both acute and chronic, in connection with various kinds of infections and intoxications. In acute adrenal insufficiency, the use of preparations per os enhances the tendency to vomiting and therefore has now been abandoned. Adrenal preparations can cause a number of side effects, such as gastrointestinal disorders, tinnitus, headaches, dizziness, and in rare cases even shock. These symptoms quickly disappear with a decrease in the dose or cessation of treatment. In general, it must be said that treatment with the indicated preparations does not yield clear results: sometimes a general improvement is observed, more or less prolonged, and sometimes an improvement of only individual symptoms. In treatment, it is necessary to take into account the underlying cause that led to adrenal insufficiency, namely infections, especially diphtheria. It is appropriate to note that it is sometimes useful to simultaneously add cholesterol to organopreparations, since with adrenal insufficiency there is a sharp drop in the cholesterol content in the blood. Pancreatic therapy. Pancreatic preparations are prepared either from the whole gland or from the islet preparation of this gland. Before the discovery of the specific hormone of the pancreas (the so-called insulin), preparations from the whole gland were widely used both in diabetes and in other diseases, most successfully in diseases associated with insufficiency of the excretory function of the pancreas, namely in chronic pancreatitis and pancreatic stones. These preparations are successfully used in enterocolitis accompanied by diarrhea, as well as in diarrhea in patients with Basedow's disease (see Insulin). Pituitary therapy. The pituitary gland, as is known, consists of 3 lobes. The chemistry of the anterior lobe is in its infancy; more definite information is available regarding the posterior lobe, but nevertheless attempts to synthetically prepare the active substance have not yet been crowned with success (see also Pituitary gland, hormone chemistry). The most commonly used pituitary preparations are obtained from cattle, whose pituitary gland weighs on average 2.2 g. In preparing the pituitary preparation, autolysis is avoided, and the method of drying in a vacuum is used. After drying, about 0.5 g of powder remains for the entire gland. Of these, 0.4 g is accounted for by the anterior lobe and 0.1 g by the posterior. For therapeutic purposes, either powders or solutions are used; the latter preparations are obtained by purifying the powder from lipoids in the form of an alcoholic solution. Preparations are administered either internally, subcutaneously, intravenously, and recently also through the nose (in diabetes insipidus). Attempts to use fresh pituitary extracts have not yielded favorable results. Intravenous injections sometimes cause side effects and are therefore used less frequently. Powder and tablet preparations produce a weak effect. Thus, the most commonly used preparation is for subcutaneous injections, with the whole gland preparation being used most often, and preparations from the anterior lobe or the posterior lobe (along with the intermediate lobe) less frequently. Sex gland therapy. a) Female sex glands. Preparations of the female sex glands find application in diseases associated with the insufficiency of the functions of these glands. These preparations were formerly obtained predominantly from whole ovaries. At the present time, a differentiation has been made, and preparations are prepared separately from the follicular parts of the ovaries and separately from the corpora lutea (see Ovarin). b) Male sex glands. Attempts to isolate the hormone of the male sex glands have not yet been crowned with success. This failure will continue until a reliable test is found that makes it possible to measure the specific action in the hormones. First attempts in this direction, in particular in the USSR (Shkavera, Likhachev), are already being made; spermine, obtained in its time by Poehl, cannot be considered a specific hormone. It possesses a general tonic effect, especially on the nervous and muscular systems, and is capable of catalytically influencing the processes of oxidation and assimilation. Preparations of the male sex glands find application in hypogenitalism, eunuchoidism, infantilism, sexual neurasthenia, etc. It is important that the preparations be freshly prepared, since they lose their effect upon storage. In addition, it is necessary to give a large dose. Preparations are used internally, in the form of injections, and in the form of transplantations. Whether the prostate gland can be classified among endocrine organs is still unclear, but nevertheless an undoubted connection exists between this gland and the sex glands; thus, upon removal of the testicles, the prostate gland atrophies. Prostate preparations find application mainly in hypertrophy of this gland and in prostatitis. It would be irrational to dwell in detail on preparations of other glands, such as the thymus, spleen, etc., the hormonal nature of which is hypothetical; these preparations differ little from those that were prepared 25-30 years ago. Thymus preparations are used in Basedow's disease, in premature puberty, etc. Spleen preparations are used in various blood diseases (Rossiysky and others). In tuberculosis with irradiation of the spleen, it is possible to stop severe bleeding (menorrhagia, purpura fulminans, etc.). Liver preparations are now widely used in pernicious anemia. Patients are either given 200-300 g of fresh liver or a preparation representing a concentrated extract. - Among preparations of other organs, one can mention cerebrin from the Ukrainian Organotherapeutic Institute, a brain preparation used in diseases of the central nervous system, and a number of Poehl's preparations: pulmonin, enterin, kordin, etc., the effect of which is doubtful. Pluriglandular therapy. Pluriglandular preparations are appropriate where there is multiple gland lesion. (On the difficulties of this kind of therapy, see above.) The action of these preparations is usually based on the dominating influence of the preparation of one gland; thus, lipolysin, which is a combination of the thyroid gland, pituitary gland, pancreas, and sex glands and is used in obesity, acts predominantly as a thyroid preparation. Some of these preparations also contain pharmacodynamic substances (calcium, phosphorus, etc.) which enhance efficacy.

M. Y.