INTKODUCTION 39 



optimum of circulating hormones is maintained. The chief apparent de- 

 fect of the method is the difficulty of interpreting any results secured. 

 There are present all the possibilities of interaction among the endocrin 

 organs of both mother and fetus. The actual practical utility of the 

 method has not been adequately determined. 



Clinical Studies of Excessive Hormone Secretion. Some of the most 

 significant data in regard to the internal secretions have been obtained 

 by the study of patients suffering from "spontaneous" overactivity of 

 endocrin structures. The functions of the pituitary gland, for instance, 

 were completely unknown up to the time Marie noted a relation between 

 changes in that organ and the development of the symptomatology of 

 acromegaly. The most striking information which we have, pointing 

 toward the function of the suprarenal cortex, is that subjects having neo- 

 plastic hyperplasia of that tissue are likely to show anomalies of the sex 

 functions. These are, in the female, "masculinization" and in the male 

 exaggerated development of the secondary sex characteristics. The per- 

 tinent data are discussed in a subsequent chapter. Many of our ideas as 

 to thyroid physiology have been derived from a study of the symptoma- 

 tology of the thyrotoxicoses, particularly those due to toxic adenomata. 

 Similarly, clinical studies have added largely to our knowledge of the 

 physiology of the ovaries and of the internal secretion of the pancreas. 



This type of investigation, however, is beset with many difficulties. 

 The chief of these, perhaps, is to determine what is the primary and what 

 are secondary factors in the pathogeny of any given clinical syndromy. 

 That the various endocrin organs are intimately interrelated and materi- 

 ally influence the functions of each other is generally believed. When 

 associated with a given syndromy some endocrin gland is found to show 

 hyperplasia the most obvious conclusion would be that this is a sign of 

 overactivity in the gland and that the overactivity is the essential etiologic 

 factor. Such an assumption is, in fact, usually made. In most cases, 

 however, the organ hyperplasia may as well be regarded as a secondary 

 effect of the same noxa as that which produced the syndromy. In other 

 words, the hyperplasia may play a concomitant rather than a causal role. 

 This point is illustrated by the unfinished debate now going back for years 

 as to whether the thyroid hyperplasia in Graves' disease is a primary or a 

 secondary manifestation of the disorder. The obviously necessary check 

 on this type of study is to produce the symptoms of the patient by aug- 

 menting in a normal subject his supply of the hormone in question. As 

 regards the thyroid this experiment has been made both in human and 

 in animal subjects. In no case has the symptomatology of Graves' disease 

 been thus reproduced in a manner entirely satisfactory, despite frequent 

 claims to the contrary. In Carlson's laboratory desiccated thyroid was 

 administered in large amounts but without the production of anything 

 at all closely similar to the clinical picture of exophthalmic goiter in 



