Some Points on THE ETIOLOGY, PROGNOSIS, AND TREATMENT OF GRAVES'S DISEASE
BMJ (Clinical Research Edition)
IT is irot my intention to attempt to deal fully w-ith the several aspects of Graves's disease, but ather to touch orr certain points in etiology, pronglosis, and treatment hich in my opinion are worthy of some consideration. The subject is one of wlhich our kniowledge is steadily growing, and about which there is much variation in opinion anid practice. This is as it should be, for there is plenlty of scope for trial and observatioin in many directions in this disorder at the present time, but
... little excuse for dogmatic assertions or rule-of-thumb proceduires. ETIOLOGY. A tenet which has materially delayed advanice in our ulnderstaniding of Graves's disease is that hiyperthyroidisrn is a sufficient explanation. The conception is a simple one, and suggests a sim)le remedy. If tire symptoms arid effects are due to hyperthyroidism, let us cripple the thvroid in some *w-ay or otlher, and n-ecessalrily the symptomlis must abate. Such a simllple conception, enitrenciihed as it is in the textbooks by the use of Graves's disease -anid hylperthyroidisnm as synonymous terms, we know now is untenable, an1d must be modified in various ways. Tire discovery and pr-eparation of a product of thyroi.d activity thyro-iodia .or thyroxin-led to its beinig regarded as the peccanit substanice to excess of which tire symptoms are due, hut 'A1illiaminson and Pearsel have, shown1i t1hat distural)alice of the iodo-colloid ftunietioni ilas onlly ani iil(lire-ct relation to the thyro-toxicosis. These workers have denonstrated that the thyroid gland has two distiniet fulnctionial activities-one the production of tlryro-iodin, the other of a secretionand tirat it is this latter which is directly elated to the tliyro-toxicosis of Graves's disease. Eveni so, the question we muist answer beforie we cail approach tire lpreveltive niedicinie of Graves's disease or remnain satisfied with its present treatmeent is: " Why is the secretory activity enhariced? " When the correct ainswer to that question is prov-ided the present methods of tr eatment, directed tow ards destroying the activity of the glanid by local means, will be a subject chiefly of historical interest. I do ilot wish to attempt to belittle the present-day value of suclh metlrods, but I feel that it slrould be oUraimii to minimize the need for their employmeirt, which will assuredly be attained when we cain explain tire overproduction of thyroid secretion. This pai-t of tlhe field of etiology is, then, well worthy of exploration, aiid onie likely to yield results of the greatest practical value. Stimulation -of Thyroid Actit ity. It is generally agreed now that the thyroid -reacts to toxic factors, as well as to sympathetic sti'mulation, by inereasinig its functional activity.' Another stimulus arises from the sex glands in the female, probably from the uterus, for there is slight but noticeable enlargement of the gland at puberty, during pregnancy, and even durinig menstruation in many subj-ects; whilst with the termiinationi-of the climacteric the opposite is prone to occur, the gland shriniking andI per-hapsbecoming -so insufficient as to permit of the development of myxoedema. Perliaps this extra duity of the thyroid in the femiale may explain the greater incidlence of Graves's disease in women, especially during tire childbearing-period. Despite th-e careful wor-k of -McCarrison anid others, the colnception of the thyroid as an antitoxic gland was lo'ng it gaoining criedence, tlhongh it seelus now to be acknowledged. I believe this activity to be of great importance in tIre etiology of Graves's disease. Like otlhers, I have been esp)ecially impressed with the frequenicy of tonsillai sepsis ill mly expe-ienwce. This lhas led me to make particular inlquir'-y aiid investigation inito thel point in my last 50 cases of Graves's disease. In 22, or 44 per cent., I obtained a definite spontaneous history of severe recur-rent sore tlhroats or' quiiisies. In 8 of these (16 per' cenit.) ani attack occurred while the patients were in the war-ds. It mulst be emplsasized that simiple sor e thlroats w-ere disegarded in these figuires, anid onily sever e and recurr ent toirsillitis or' quiinsies were considered. Stimulation of the thvroid gland by toxins, either actinig alonie or in combination with othier: exciting influenees, seems to miie to be amIionlg the mnost imnportant causes of thyro-toxicosis or Giaves's disease. It is temptinig to suppose that tIre effect of local sepsis, such as that of the tonsils, is to create a (leruand for the iodo-colloid secretion, but that by this demand the whole gland is stimulated, the true secretion being also iniereased. It is this excess of tirue secretio n which lprovides the symptoms of Graves's disease. Bearing upon these points it 'must not, however, be forgotteni that hyper-plasia of the secretory tissue of the thyroid seems to hold in cheek tire development of iodocolloid, for removal of some of the hyperplastic tissue is folloued by a re-accumulation of iodo-colloid in the alveolar spaces ('Williamson and Pear se). The Ad,reials in, Graves's Disease. The part played by tIre adrenal glands in Graves's disease cannot be igniored, but is not easy to assess. Psychical causes, suchi as worry, excitemnent, miental stress, and fright, have long beeri recognized as precursors. Mor1eover, tile cliniical pictuire of tIre disease is the very piesentmenit of fear-the startinig eyes, the flushing, the tachyeardia, the trenior, eveni the diarrhoea and the hyperglveaemia, together delinieate the features of fear. But fear and the pieparationi for fighlt or flight we believe to be intimately conlnected wA-ith activity of the -adienal gland, the hormone of the meduilla of whicl huiirr ies up) the heart, br aces up the bloo(d vessels, and mobilizes sugar for imiiiediate effort (Cannion). Glieii Graves's disease begi us abruptly, followinig a period of excitem-leint and alarim sIIchi as a motor accident, it is difficult to excluide the adrlenials ill its piroductioni, for the increase of adrenaline whiclh arises, by stimulating tile sympathetic system, miust plrovoke also increased thyroid secretion. DUIing the war' onle saw mnany examiples of imieni who, after exposure to danger, piresenited a picture w lich (luring tiln-e of peace one hI4d been acculstomed to recocmnize as mild Graves's disease, for they showed tremiior, tachycardia, flutshing, sliglht starinig of tle eyes, with retractioni of tire upper lids anid visible sclerotics beloN them. In most inistanices these symptoms subsided q1ite quickly, being gone in a few hliours or days, hnut occasionaliy tr ue Graves's disease folloNwed and persiste(l. There was, I believe, a nlotable increase in Graves's disease in London during the war period, wvhich has been ascribed to the air iaids (Lanigdon-Brown). If we accept the modern phyrsiological explanation of the reaction to fear, the prominent part plaved by the suprarenals in the iniception of Graves's disease in these cases can hardly be dnnied. A more difficult question is as to how .long this adrenal activity pelrsists, and how far it contributes to the picture of the. developed disease, for it must not be forgotten that admrinistration of thiyroid alone in excessive doses is capable of producing nearlyall the symptoms. Yet it is reasoniable to infer that with overaction of the thyroid there is accomiapanying overaction of the adrenals, for thyr-oid secretion stimulates the. synmpathetic, which in turn stimutlates the adrenals. Assuming that my contention is right that suprarenal activity precedes 'that of tle thyroid in responise to psychical disturbances in certain cases of Graves's disease1 it is easy to see how a vicious circle may be set up. The -outpouring of ads enaline stimiulatese'the sympathetic, which in turn stimulates the thyroid and the suprarenal itself, wlhilst the increased thyroid secretion for its part stimulates the adrenals still more.