PATHOLOGY 385 plastic activity in its ceils and fibres. Of eighteen cases of com plete removal of the enlarged thyroid at the hospital of Bern this condition followed in sixteen, and in the two which escaped it an "accessory" thyroid had arisen. The condition is that which had been described by Ord as myxoedema (from the mucous dropsy of the skin), a progressive disease, with hebetude and other symptoms of impaired higher functions, and tending to a fatal result in a few years. The interesting fact is that in such cases of idiopathic myxoedema the thyroid has very generally been observed to be small or wanting ; where the diminished organ has been examined after death it has been found practically re duced to a mass of connective tissue infiltrated with mucus, like the connective tissue elsewhere. The relation then between the cases of myxcadema following operative removal of a goitre and the idiopathic cases would seem to be that, in the one, a mucous condition of the whole connective tissue of the body follows when the thyroid, enlarged to meet the metabolic needs of the body, has been removed by the surgeon, while, in the other, the same condi tion has followed where the thyroid lias either proved too small for the ordinary metabolic ends that it is adapted to serve, or has degenerated under an unusual call upon its metabolism. Of the nature of this metabolism we are ignorant ; we know only that a material fluid is elaborated, and that the fluid is of the mucous kind. Cretinism. If reference be made to fig. 40, showing the more spongy tissue of the placenta, it will be seen that there also a fluid is elaborated and added to the blood from the richly protoplasmic walls of the vessels ; and that fluid is also of the mucous kind. It is the "uterine milk" of earlier authors, and it would appear to exude through the densely nucleated marginal tracts of the placenta where the fcetal vessels and their plasmatic supporting tissue touch it. It is this great metabolic function, so essential to the vigorous development of the child, that is probably at fault in the poor and over- worked or otherwise over-taxed mothers whose offspring become rickety ; and the fault may be said more particularly to be deficient quantity or quality of the placental mucous secretion. The simi larity of the thyroid and placental metabolisms cannot but come into account in considering the very peculiar condition of cretinism, proper to the offspring of goitrous mothers, or of mothers who had resided during their pregnancy in a goitrous district. Under the same endemic circumstances which cause the com pensatory enlargement of the thyroid in the parents we meet with cretinism in the offspring. Although the defects of develop ment and growth in cretinism are on the whole different from and much more universal than those of rickets, yet there is a certain parallelism between the two conditions. The cretin, like the child who becomes rickety, must have been born with the disposition. The condition is not inherited, but it is congenital, that is to say, it is derived from the mother in respect of her pregnancy only, and that means that it is derived most of all from the placenta. Cretinism is to goitrous districts what rickets is to other localities. And, although there is no positive evidence as to the placental function either in the one case or in the other, yet the placenta is clearly pointed to in both cases; and we may conjecture that cretins are the offspring of those mothers whose maternal nutriment is impaired, not by the general hardships of those who bear rickety children, but by the special endemic conditions which serve also to tax that other mucus-producing organ, the thyroid gland. The endemic conditions may not have caused goitre in the mother, although, as a matter of fact, they generally do ; but, under a special concurrence of circumstances, as common in goitrous districts as are the determining causes of rickets elsewhere, they have caused a cretinous habit of body in the child, and to do so they must have affected the placental efficiency in some manner as yet unknown. This mode of associating goitre and cretinism assumes an error in the placental function which has not been shown by direct observation of the placenta to have existed. It has probably not been looked for ; and, even if it had been, there would have been some difficulty in making out its morphological characters. Under the circumstances of the case the evidence can hardly be other than deductive. Graves s Disease, or Exophthalmic Goitre. In certain cases of anaemia in women there is enlargement of the thyroid, fluctuating in amount or permanent, but not liable to the common develop ments or degenerations of endemic goitre. Associated with the ansemia and the enlarged thyroid there are disturbance of the func tions of the sympathetic nervous system and a remarkable promi nence of the eyeballs. It is probable that another aspect of the thyroid function than the mucus-making is involved here. It is an old contention of Kohlrausch that the droplets of hyaline substance, often with a yellowish or pale reddish tint, that are found in the thy roid mixed with the ordinary mucus of its alveoli were an embryonic form of blood-globules. In the thyroid of the dog these droplets may be often seen of a more uniform size, and so like blood-corpuscles (allowing for irregularities of form and size) that they have been actually regarded as such, and put down, when in considerable quan tities, to " Haemorrhage " from the vessels that run on the other side of the epithelial wall of cells. There is not the slightest reason to sup pose that these droplets have escaped from the blood-vessels ; they are produced from the epithelium of the organ along with the otheV mucus-like fluid. They point, indeed, to a hsematoblastic function of the cells, somehow correlated to their ordinary mucus-yielding function. There are analogies among the connective tissues, at least, for this correlation between mucous and hamatoblastic pro duction, in new growths, and there is an analogy in the early stage of embryonic fat -formation, in the production of red blood -disks from the same mesoblastie cells at one stage of their existence and of mucus-like fluid within them at the next. Now, although there is no evidence that the enlargement and increased functional activity of the thyroid in these peculiar cases of antemia has a more special relation to the hsematoblastic side of the function than to the mucous, yet the coexistence of an enlarged thyroid with certain cases of amemia becomes intelligible in the light of these indications of hrematoblastic function. The enlargement of the thyroid may be considered a special effort, comparable to the effort of the bone -marrow in pernicious anaemia. The profound dis turbance of the vascular system which goes with this condition must stand as an empirical fact, but it may be classed with the analogous sympathetic disturbances in Addison s disease ; both the suprarenal and the thyroid are to be considered as organs in which disorder of function has a special relation to the sympathetic, the abdominal sympathetic in the one case and the cei vical in the other. It is to be observed that in common goitre, where there is not so much an alteration, diversion, or disorder of function as a com pensating increase of the ordinary function, there are no symptoms referable to the sympathetic ; so that the relation in the enlarged thyroid of ana inia cannot be a mere mechanical one. Secondary Tumours of the Thyroid. The last special liability of the thyroid to be mentioned is a very peculiar one ; there is a number of well-authenticated cases in which a simple enlargement or hyperplasia of the organ has been associated with the new forma tion of masses of the proper thyroid -texture, with the proper mucous secretion, in the lungs and at various points of the sub cutaneous tissue. In these cases the hyperplastic thyroid exhibits the property of an infective tumour, the new growth of thyroid- tissue at remote points being the secondary products of infection. Is there anything in the normal overgrowth of the thyroid to account for its infectiveness as manifested on rare occasions ? One of the unsettled questions of thyroid physiology is the mode of development of the new alveoli when the organ enlarges. It is apt to be too readily assumed that the new structure is formed by continuous extension from the pre-existing, by expansion or germi nation ; but the point has been raised by observers whether the new alveoli are not formed interstitially at numerous independent centres throughout the stroma or supporting tissue of the organ, at first as small groups of cells which come to develop a space in their midst, and to group themselves as epithelium round the periphery. This is the ordinary mode of interstitial development in cancerous infection ; and, if that mode be substantiated for the physiological increase of the thyroid (and the facts in the dog s thyroid point that way), it would enable us to understand how 7 it is that some times, as if in a freak, the simple hyperplastic thyroid plays the part of an infective tumour, reproducing its own likeness at dis continuous and even distant centres. 1 11. ERRORS OF METABOLISM. In the foregoing sections metabolic functions have been claimed for the placenta, for the suprarenal, and for the thyroid. Connected with these obscure and hitherto al most unregarded metabolic functions are several important morbid conditions, which are mostly of the so-called con stitutional sort ; with errors of the placental metabolism we connect such defective intra-uterine endowments of the foetus as gave rise to rickets and cretinism in the child (and, it may be added, to some of the manifestations of congenital syphilis) ; with loss of the suprarenal meta bolism we connect Addison s disease ; and with a compen sating or conservative increase of the thyroid metabolism we connect goitre, a condition which is harmless but for its mechanical effects. It will now be convenient to pass to those greater but hardly better understood metabolic 1 See Thomas Addison, On the Constitutional and Local Effects of Disease of the Suprarenal Capsules, Lond. , 1855 ; Greenhow, On Addison s Disease, Lond., 1875 ; Id., in Trans. Internal. Med. Con gress, Lond., 1881, vol. ii. ; Wilks, "Addison s Disease," in Reynolds s Si/ stem of Med., vol. v., Lond., 1879. Goitre, Cretinism, &c. Hirsch, Historisch-gcographisclie PatJiologie, 2d ed., vol. ii., Stuttgart, 1883 (Engl. trans.) ; Virehow, Ges. Abhandl. zur u-iss. Med., Frankfort, 1856, p. 891; Old, "On Myxoedema," in Med. Chir. Trans., 1878; and various authors in Clin. Trans., 1882-84. XYIIT. 49
