A similar reciprocity exists in the case of the thyroid; it is stimulated to secretion by the sympathetic and the secretion lowers the threshold to sympathetic stimulation. The existence of sympathetic secretory nerves to the pituitary has been shown, but there is no definite evidence of a reciprocal action of its secretion on the sympathetic.
The endocrine group which cooperates with the parasympa- thetic must be looked for chiefly in the glands of the alimentary tract and its annexes, since the building up of energy must ultimately be derived from the food. Gastric secretion is started by the appetite and the taste of food reflexly stimulating the organs, but it is continued by a hormone in the pyloric glands of the stomach which spur the fundus glands on to renewed effort. In its turn the acid gastric juice entering the duodenum acts on its mucosa to form secretion, which stimulates secretion of pan- creatic juice. But the pancreas forms an internal secretion as well, which promotes the assimilation of sugar. Indeed, the metabolism of sugar gives a particularly good illustration of the general principle here laid down. Acting muscle requires three and a half times as much sugar as resting muscle, and the mobilization of sugar into the blood is a necessary preliminary to muscular effort. Accordingly sympathetic stimulation is found to produce this effect, through the adrenals, thyroid and pituitary, the secretion of each of which taken separately will lower carbohydrate tolerance and may excite glycosuria. On the other hand, the pancreas which is innervated by the parasympathetic has a precisely opposite effect, the antagonistic action of the glands being as definite as that of the associated nerves. Another example of this antagonism is seen in the continuous flow of pancreatic juice following removal of the adrenals, which can be temporarily inhibited by injection of suprarenal extract. Again, it is well known that adrenalin dilates the pupil of an excised eye but not of the intact eye of a normal individual. Therefore some- thing inhibits the adrenalin effect. In depancreatised dogs adrenalin does dilate the pupil, and it has been found to do the same in patients suffering from pancreatic disease, since the normal antagonism of the pancreas to the adrenals is then lost. This pupillary response may also be present in hyperthyroidism, suggesting that the thyroid excess inhibits pancreatic activity, allowing adrenalin to show its dilator action unchecked.
The sympathetic nervous system, the endocrine glands and the gonads form a basic tripod entrusted with the duty both of the preservation of the individual and the continuity of the species. Their relationship is shown in disease as well as in health, and is reflected in many neuroses and psychoses. Disease is the resultant of some external action and of the reaction of the organism against it. It therefore draws on the defensive mechanisms and connotes a position of less stable equilibrium in which the body works with more friction. It may demand an increased supply of hormones to com- pensate for this, which may ultimately lead to exhaustion of the gland that provides it. In this way the balance between the en- docrine glands is disturbed, either from overaction of a gland, or from its unopposed action through the loss of an antagonist.
The sympathetic-endocrine system is affected alike by toxic, nutritional or psychic factors, and is particularly jikely to be in- juriously influenced if more than one such factor is overtaxing it. As this system has to defend us against internal foes, such as bac- terial infections, as well as external enemies, we find that it plays an important part in the regulation of the body temperature. Since it has been shown that the cerebral vessels are remarkably impermeable to drugs and toxins as long as they maintain their integrity, it has become impossible to explain febrile reaction to infection by a , central mechanism. When the activity of the thyroid and anterior lobe of the pituitary is diminished, less heat is produced. When increased production is required, the thyroid and adrenals give histological evidence of increased secretion. Cramer has found this both in fevers and after exposure to cold. He has also experimentally produced such changes by the injection of a drug which causes fever. Infections such as gas gangrene which do not induce a febrile reaction do not produce these changes. He has traced the adrenalin into the blood vessels, whereby sympathetic nerve endings all over the body will be stimulated. At the same time more sugar is poured into the blood, largely through thyroid activity. The oxidation of this sugar increases heat production. It has long been known that the adrenals may show marked signs of exhaustion after a severe infection such as diphtheria, while the thyroid may suffer after typhoid fever. Such exhaustion appears to be an important factor in the psychoneuroses of convalescence.
The influence of nutritional factors on the apparatus is seen in the way in which ( i) pregnancy enlarges the thyroid and pituitary ;
(2) vitamine defects cause enlargement of the adrenals and pituitary while causing some atrophy of other endocrine glands; (3) deficiency of assimilable protein in the food causes pellagra in which the adrenals suffer, while the sympathetic nervous system shows actual structural degeneration. While toxic and nutritional influences play chiefly on the glandular part of the apparatus, psychic factors naturally act primarily on the nervous part, though ultimately both parts will become affected, whichever is involved first. The sym- pathetic is the lowest level of the nervous system and retains several characteristically primitive features, such as peripheral ganglion cells, myenteric nerve nets, connector fibres lying outside the central nervous system, and urgent widespread responses, rather than accurately localized and discriminative ones. This is in accordance with the evolution of the nervous system for defense, and with the maintenance of this primitive function by the sympathetic. Pain has been shown by Trotter to be the specialization of the primitive sensation of lower animals, and fear might similarly be regarded as a specialization of a primitive emotion. It is to such sensation and emotion that the sympathetic nervous system preeminently responds. Both pain and fear are apt to become intense when the appropriate motor response is prevented, though they may not be appreciated when vigorous response is possible. Thus during the excitement of a fight neither fear nor pain may be experienced under conditions which would ordinarily induce them. In the civilized state the response appropriate to primitive man has often to be repressed. The effect of this repression may show itself either as an anxiety neurosis, at the psychic level, or at the sympathetic-endo- crine level in certain affections of the associated glands, and in cardiac or digestive neuroses. Such repressions are particularly likely to be necessitated when the great instincts of self-preservation, repro- duction and gregariousness, which relate respectively to the life of the individual, of the species and of the community, come into conflict with one another. The constant demand for adrenalin when sympathetic action is increased in fear and anxiety may lead to exhaustion of the gland. Addison's disease presents a clear- cut picture of adrenal deficiency in its symptoms of muscular weak- ness, low blood pressure, pigmentation and vomiting. Although this is due to organic changes, slighter degrees of a similar condition are now recognized and it has been suggested that this enters into many war neuroses and other functional states characterized by vasomotor instability, low blood pressure and myasthenia. Conversely, pro- longed oversecretion by the adrenals must tend to raise blood pres- sure through the sympathetic, tending in turn to arteriosclerosis, with all its widespread effects. The well-known influence of anxiety in producing this condition can thus be explained.
There is a close association between the thyroid, the reproductive organs and the sympathetic. The thyroid tends to enlarge at pu- berty, marriage and in pregnancy, while myxoedema is most apt to occur after the climacteric. Amenorrhoea is common even in the minor degrees of hyperthyroidism. The effect of sympathetic irri- tation in producing thyroid enlargement and Graves' disease is now recognized. Gushing showed that if in cats he sutured the phrenic nerve to the cervical sympathetic so that every respiration stimulated the latter, he could produce the symptoms of Graves' disease. The influence of distressing emotions in producing hyperthyroidism was well shown during the air-raids on London during the World War. Epidemics of Graves' disease also followed the Kishinev massacres and the San Francisco earthquake. Again, if a distressing emotion has a matrimonial origin, it is particularly likely to induce Graves' disease, for here each limb of the basic tripod is involved. The disease has been compared with a state of continuous fear, a descrip- tion which tallies with its general appearance.
The pituitary body also shows the two-fold association with the reproductive organs and the sympathetic nervous system. The anterior glandular part has an effect on temperature, the growth of bone and skeletal tissues and the reproductive organs. The inter- mediate lobe influences carbohydrate metabolism, while the secre- tion of the posterior lobe is mainly a stimulant to plain muscle and to the secretion of milk. The effect of the secretion of the posterior lobe on diuresis is still a matter of controversy, but it is clear that disease of the posterior lobe is often found in diabetes insipidus and that stimulation of the sympathetic nerves to the gland will cause polyuria. Probably hysterical polyuria is thus produced.
It is also clear that some cases of glycosuria are of sympathetic nervous origin; the physiological mechanism by which this can be brought about has already been explained. Diabetes is character- ized, like sympathetic stimulation, by an exaggerated katabolism. This shows its effect first on the most abundant and most easily metabolised of the food-stuffs, the carbohydrates, which are also essential for muscular action, to which sympathetic stimulation should normally be a preliminary. Sympathetic stimulation induced by various disagreeable emotions will increase metabolism generally and specially lower carbohydrate tolerance. The influence of ex- citement and emotion in causing glycosuria is well recognized. It is commonest in Jews, a notoriously emotional race. When stocks go down in New York, says Crile, diabetes goes up. Temporary zlycosuria occurred in a number of men who merely watched a foot- ball cup-tie without participating in it. Glycosuria has been, un- fortunately, comparatively common in young officers entrusted with heavy responsibilities during the war. Singer and Clark have
