Proceedings Eighth Annual Meeting of the American Academy of Pediatrics

American Academy of Pediatrics Proceedings EIGHTH

ANNUAL

MEETING OF

OF

THE

AI~[ERICAN

ACADEMY

PEDIATRICS

DEL, MONTE, CALIF., J U N E 9, 1938

Panel Discussion on the Thymus Gland Chairman: Assistants:

Dr. Dr. Dr. Dr. Dr. Dr.

A. Graeme Mitchell, Cincinnati, Ohio E d i t h B o y d , M i n n e a p o l i s , Minn. W. Edward Chamberlain, Philadelphia, Pa. Nathan H. Einhorn, Philadelphia, Pa. Henry F. Helmholz, Rochester, Minn. A l f r e d H o w a r d S p o h n , V a n c o u v e r , B . C., C a n .

C H A I R M A N M I T C H E L L . - - I n this panel we want to arrive at some conclusions among ourselves which we can present finally and which we hope will be of some assistance to the clinician. Some questions we wish to ask pertain to the possible functions and the physiology of the thymus gland and Dr. E'inhorn will certainly take part in t h a t part of the discussion. Dr. Boyd will discuss the roentgenographie diagnosis and treatment. I n my opinion, Dr. Helmholz belongs in the group of thymus skeptics, and I hear that Dr. Helmholz thinks t h a t Dr. Spohn is a thynms enthusiast. There are several questions,

and I am

going

to ask some

of those questions.

As

a beginning, ~CHas this particular bi't of tissue called the thymus any function and if so what is the proof? ~' Dr. Einhorn, will you open the discussion? Dt~. N A T H A N H. E I N t I O R N . - - I have taken from the literature a nmnber of the more important evidences indicating t h a t the thymus may have an endocrine function. Briefly, the following contributions may be mentioned: 1. Experimentally its behavior resembles that of other endocrine glands. Thymus excess produced by injection o~ thymus extract has resulted in an acceleration in the growth and development of the offspring" in successive generations of trea~ed parent r a t s . . This increased rate of growth is most pronounced prepubertally when the thymus is at its largest and in its most succulent state. Thymus deficiency produced by removal of the thymus causes the opposite effect; namely a retardation in tho rate of growth and development of the offspring. Thymus deficiency in %he pullet has been shown to lead to the production of shell-less eggs. The effects of thymus deficiency can be readily overcome by administration of thymus extract or by thymus implants. The iodine-reducing substances, glutathione, asearlie acid, and apteine found by Dr. N. K. Shaffer to be present in thymus extract, accelerate growth and development in the offspring of normal rats but are ineffective in thymeetomized rats, indicating that these substances have trophie actions. As with the admittedly well-known endocrine glands, there seems to be an interrelationship between the thymus and other glands, as is indicated b y the following evidence: A t puberty the gonads undergo marked c~evelopment, while the thymus undergoes marked recession. 534

A3{ER,ICAN ACADEMY OF PEI)IATR-1CS

535

2. C a s t r a t i o n causes p e r s i s t e n c e a n d h y p e r p l a s i a of the t h y m u s . 3. A d r c n a l e e t o m y causes a p e r s i s t e n t e n l a r g e m e n t o f the t h y m u s . Conversety, it h a s been observed tttat a n i m a l s with l a r g e t h y m u s g l a n d s have s m a l l adrenal glands. 4. T h y r o i d e e t o m y r e s u l t s in a n increase in 'the size of the t h y m u s , while t h e a d m i n i s t r a t i o n o f p i t u i t a r y t h y r o t r o p i c h o r m o n e r e s u l t s in a r e d u c t i o n in the size of the t h y m u s . H y p o p h y s e e t o m y done p r e p u b e r t a l l y delays involution of tile t h y m u s . I r r a d i a t i o n of t h e t h y m u s in one- to two-day-old r a t s r e s u l t s in r e t a r d a t i o n in growth a n d virility in t h e male, a n d finally t h e a d m i n i s t r a t i o n of t h y m u s e x t r a c t to n o r m a l r a t s produces e a r l y m a t u r a t i o n of the ovaries a n d testes as well as increase in t h e n m n b e r of eosinophilie a n d basophilic ceils in ~he pitui'tary gland. DR. M I T C H E L L . Dr. E i n h o r n will show a m o v i n g picture later to bear out some of t h e s t a t e m e n t s he h a s m a d e here. Dr. E i n h o r n , this work of which you speak h a s been done entirely on rats, h a s it not? DR. E I N H O R N . - - Y e s , a n d m u c h of the work t h a t I have quoted h a s been t h e work of other i n v e s t i g a t o r s . My own work has, of eours% been with Drs. L e o n a r d Rowntree, A r t h u r S t e i n b e r g , a n d W. g . Shaffer. DR. l~IITCIdEI~L. I s t h e r e a n y a p p l i c a t i o n of these e x p e r i m e n t a l s t u d i e s which c a n be tra~tslated to t h e clinician~. DR. E I N H O R N . - - T h e r e are no clinical results f r o m out' work as yet. N a y I note t h a t t h e absenee of the thyroid g l a n d produces an increase in the size of the thymus. DR, I-IENRY F. H E L M H O L Z . - - I would like to ask 1)r. E i n h o r n w h e t h e r be h a s f o u n d in cases where death h a s occurred f r o m toxic goiter t h a t there is not an enlarged 'thymus. 9I{. E I N t { O R N . - - - I c a n n o t answer this question f r o m personal experience. observation has, however, b e e n recorded in t h e l i t e r a t u r e by H a m m a r . Dtl. M I T C H E L L . t h y m u s gland.

t

a m g o i n g to a s k Dr. Boyd

This

what eonstitu'tes a normal

I)R. E D I T H BOYD. W h e n we come to consider the question of n o r m a l t h j m u s ~ we are f a c e d with the f a c t t h a t t h e t h y m u s is one of the m o s t sensitive o r g a n s in tile body. I n a n i t i o n f r o m a n y cause whatsoever, ina,tition front lack of w a t e r alone, i n a n i t i o n f r o m lack of water and food, i n a n i t i o n f r o m infeetioi b reduces the size of tile t h y m u s w i t h i n three d a y s to a b o u t one-third of its size in a wellnourished animal, including the human. i will show s o m e l a n t e r n slides which set u p a reasonable s t a n d a r d of n o r m a l size of the t h y m u s gland based u p o n atrtopsies of t h y m u s e s f r o m i n d i v i d u a l s d y i n g of accident w i t h i n 24 h o u r s of their i n j u r y . All other eases h a v e been excluded. W e consider t h e cause of .death as a d e q u a t e w h e n t h e child fell f r o m a t h i r d story window or was knocked down by a n anlomobile a n d picked up dead with a f r a c t u r e d skull; or when we recovered 25 rag. of s t r y c h n i n e f r o m his stomach, a n d t h e like. I n Fig. ] I w a n t to p o i n t out what we consider a n o r m a l t h y m u s g l a n d w h e n we pick i n d i v i d u a l s who were in a good s t a t e of n u t r i t i o n at t h e t b n e of their death. H e r e I h a v e n o r m a l s t a n d a r d set on tile basis t h a t tile middle 50 percentile line r e p r e s e n t s the average, so t h a t it is expected t h a t h a l f of the w e i g h t s of n o r m a l t h y m u s e s will f a l l above t h i s middle ]in% a n d t h a t 50 per cent will fall between t h e 25 a n d 75 percentile lines. I t is expected t h a t 80 per cent of n o r m a l i n d i v i d u a l s will fall between the 10 a n d 90 percentile lines, a n d t h a t 20 of ~the n o r n m l s u b j e c t s will fall entirely outside t h e shaded zorie. N o w I have i n d i c a t e d the u p p e r l i m i t of n o r m a l w e i g h t of t h e t h y m u s as ordinarily given in t h e literatux% n a m e l y , 20 g,m. Y o u will notice t h a t i't a l m o s t h i t s t h e lower 10 percentile on the line in children f r o m 5 to 15 y e a r s of age, a g d t h a t a f t e r a b o u t six m o n t h s it is below the a v e r a g e w e i g h t of t h e t h y m u s .

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I t is very hard f o r me to consider as abnormal any organ t h a t is below the average size of tha't o f well-nourished individuals; it is certainly not an enlarged gland, since it is in the lower h a l f of tile normal range. The next slide (]Pig. 2) b r i n g s up another question. The thymus is made up of three distinct tissues: a medulla which contains H a s s M l ' s corpuscles, the cortex

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m a d e up of f r a m e w o r k t h a t c o n t a i n s chiefly lymphoeytes~ a n d the s u p p o r t i n g connective tissue. Tile slide d e m o n s t r a t e s t h a t t h e cortex c o n s t i t u t e s the l a r g e s t p o r t i o n of the weight of t h e t h y m u s in t h e early y e a r s of life. A f t e r puberty~ however~ t h e connective tissue and f a t m a k e up the g r e a t e r p a r t of the w e i g h t of t h e t h y m u s , So t h a t p a r e n e h y m a l t i s s u e is decreasing. W h a t a b o u t this p a r e n e h y m a l t i s s u e ? I n Fig. 3 in the middle p a n e l I show t h e whole p a r e n e h y m a . Tile m~ddle~ dark shaded zone includes t h e middle 50 per cent, a n d tlte outer zones include t h e middle 80 per cent of n o r m a l p a r e n c h y m a l weights. }:[ere I am entirely w o r k i n g f r o m I-Iammar's material. T h e s e g r a p h s of c o m p o n e n t p a r t s are based entirely on his extensive data. I t h i n k his m o n m n e n t a l work is not recognized p r i m a r i l y because his G e r m a n is difficult to read. The I r i s h . w o m a n who t r a n s l a t e d the m o r e difficult sections f o r ate wrote: " W h e n an I r i s h m a n t r a n s l a t e s into E n g l i s h t h e G e r m a n w r i t t e n by a 'Swed% w h a t you are a b o u t to receive is t h e best t h a t can" be e x p e c t e d . '

538

TIIE JOURNAL OF PE,OfATRICS

H.ere you see the demonstration that purenchyma increases with age in the ear]y ~eriod of four or five years and then sometime aroun4 puberty, or a little before puberty, it begins to decrees% while at the same time the connective tissue and fat eonti~me to increase in a rather uniform manner. Now~ ~his parenchyma is made up ef two quite different tissues, the cortex and medulla. Fig. 4 strews you these separately. 36 ~r~'------r

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Age m years Fig. 4. And here you see the certex which is made up ehietty of leucocytes which migrate from ttle thymus during all types of inanition. You see that the growth in the e o z t e x takes ]place in the firs~ six years, then -i"Lis about stationary in weigh% and then b e a n s decreasing slightly before puberty. The medulla i~self increases rapidly in the firs~ few years~ then increases slowly to sometime aromld the age of 12 to

13 years, and then ,decreases in size.

As age increases there is also a deerease in

539

AME~R,ICAN ACADEMY O,F PEDIATRICS

va~'iability. T h i s slide also shows t h a t the corpuscles which are part of the m e d u l l a t e n d to parMlel in t h e i r ~ u m b e r s t h e g e n e r a l p a t t e r n of t h e medulla. N o w t h i s gives a g e n e r a l p i c t u r e of w h a t h a p p e n s to t h e t h y m u s when we limit our d a t a to those persons who have died of accident w i t h i n t w e n t y - f o u r h o u r s of their i n j u r y a n d in which t h e r e h a s been no question w h a t s o e v e r in t h e m i n d of p a t h o l o g i s t s t h a t d e a t h w a s due either to t r a u m a or to some such cause as p o i s o n i n g by strychnine or carbon monoxide. t60

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Fig. 5. I t h i n k t h a t gives t h e n o r m a l picture, lXTow t h e question h a s a l r e a d y been b r o u g h t up concerning e n l a r g e m e n t of the t h y m u s in e x o p h t h a l m i c goiter, a n d Fig. 5 will give the evidence on this. Here y o u see t h a t in e x o p h t h a l m i c goiter we u n q u e s t i o n a b l y have e n l a r g e m e n t of t h e t h y m u s . I have rarely seen a n y t h y m u s above 60 g r a m s ~n w e i g h t in tile ease of a n i n d i v i d u a l killed in an accident, a n d y e t here you see w e i g h t s r a n g i n g u p well above 65 grn. So here is evidence in the h u m a n b e i n g o f a n e n l a r g e m e n t of t h e t h y m u s in e x o p h t h a l m i c goiter, a n d also, as Fig. 6 shows, t h i s e n l a r g e m e n t is due to increase in f u n c t i o n a l tissue, t h e p a r e n e h y m a , a n d not due to increase in the connective tissue. DR. M I T C H E L L - - W h a t significance do yon t h i n k all t h i s h a s in relation to such a m a t t e r as s u d d e n d e a t h as r e l a t e d to t h e size of t h e t h y m u s ? DR. B O Y D . - - W h a t h a s been called t h e enlarged t h y m u s is the n o r m a l t h y m u s of t h e well-nourished individual. DR. 1WITCtIELL. s t a t e m e n t ~-

Does a n y o n e on this panel take exception to t h a t p a r t i c u l a r

540

THE

JOUI~NAL

0]0"

PEI)IATR,ICS

DR. ALF~RED H O W A R D S P O H N . - - S o m e t i m e s we g e t eo-called t h y m i e s y n d r o m e s y m p t o m s w h e n r o e n t g e n o g r a p h i c shallow of t h e t h y m u s is n o t p a r t i c u l a r l y l a r g e or is wlthil~ n o r m a l limits. DR. M I T C H E L L . - - I t is a good t i m e to a s k Dr. C h a m b e r l a i n , our radiologist in the panel, w h a t he c a n tell u s of t h e t h y m u s ~ l d its e n l a r g e m e n t . I n other words, w h a t is this b u s i n e s s of e n l a r g e m e n t of the t h y m u s on the r o e n t g e n o g r a m a n d w h a t does it m e a n ? gxophrhalmic Goitre

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DE. W. E D W A R D C H A M B E R L A I N . - - R a d i o l o g i s t s have m a d e the d i a g n o s i s ~ ' e n l a r g e d t h y m u s " a g r e a t m a n y t i m e s when no such e ~ l a r g e m e n t w a s present. Some yea~s ago this mis• was very prevalent, l'qeither we n o r our clinical coll e a g u e s were a w a r e of the actual limits of n o r m a l variation. N o w Dr. :Boyd's m a t e r i a l shows very p l a i n l y t h a t w i t h i n the limits of n o r m a l v a r i a t i o n t h e t h y m u s g l a n d m a y v a r y f o u r f o l d in Mze; in other words, the r o e n t g e n o g r a m m a y reveal t h y m u s s h a d o w o f g r e a t e r t h a n c~verage size w i l h o u t j u s t i f y i n g a d i a g n o s i s of ' ' ~hymic e n l a r g e m e n t . ' ' W e do hold to t h i s - - t h a t r o e n t g e n o g r a m s m a d e before am] a f t e r i r r a d i a t i o n of a d e m o n s t r a b l e t h y m u s will show a decrease in t h e size o f the o r g a n as a result

AMERICAN ACADEMY OF PEDIATRICS

541

of the t r e a t m e n t . Such d e m o n s t r a t i o n s prove t h a t t h e size of the t h y m u s c a n be successfully visualized b y r o e n t g e n e x a m i n a t i m b b u t t h e y do n o t j u s t i f y the conclusion t h a t t h e t h y m u s was a b n o r m a l l y l a r g e b e f o r e the a d m i n i s t r a t i o n of t h e x - r a y treatmen% A g r e a t m a n y r a d i o l o g i s t s are b e g i n n i n g to d o u b t t h e significance of the t h y m i e B u t some of u s continue to shadows which were f o r m e r l y labeled "enlarged." a d m i n i s t e r x - r a y t r e a t m e n t to t h e s e children. W e are u n d e r a considerable p r e s s u r e to do so. Sometimes *he p e d i a t r i c i a n i n s i s t s npon it. W e know t h a t x-ray t r e a t merit o f t h y m i e e n l a r g e m e n t , w h e t h e r fanciful or real, is h a r m l e s s w h e n p r o p e r l y given. W e know t h a t cases of s u d d e n d e a t h in children are likely to be ascribed to t h y m i e e n l a r g e m e n t a n d t h a t even t h o u g h the shadow we are c o n s i d e r i n g m a y be w i t h i n t h e n o r m a l limits, i't will recede as a result of x - r a y t r e a t m e n t . And, finally, we know t h a t while we ourselves m a y be skeptical, m a n y "otherwise c o m p e t e n t " observers, b o t h r a d i o l o g i s t s a n d p e d i a t r i c i a n s , will a g r e e with us i f we s a y t h a t the t h y m u s is enlarged. So we are: b u t following t h e line of leas* resistance when we decide t h a t one of these children n e e d s i r r a d i a t i o m

Fig'. 7. I a m b e g i n n i n g to wonder how m u c h of the shadow we so glibly call " t h y m u s " is actually due to t h a t organ. We have all of the superior m e d i a s t i n a l s t r u c t u r e s to cope with in this region. T h i s m o r n i n g , at tile " b r e a k f a s t t a b l e p a n e l , " I received a severe lesson in this m a t t e r of the a n a t o m y of t h e superior m e d i a s t l n u m . Dr. B o y d ' s d e m o n s t r a t i o n h a s shot some o f m y f o r m e r ideas full of holes. F o r example, m a n e u v e r s like t h e V a l s a l v a e x p e r i m e n t ( i u s p i r a t o r y effort a g a i n s t a closed glottis while i n an e x p i r a t o r y p h a s e of r e s p i r a t i o n ; e x p i r a t o r y effort aga~ns't a d o s e d gqottis while in a n i n s p i r a t o r y pimse of r e s p i r a t i o n ) always produee c h a n g e s in t h e w i d t h of the superior m e d i a s t i n a l shadow. I h a v e been in t h e h a b i t of e o n s i d e r l n g t h e s e c h a n g e s as p a r t l y due to c h a n g e s in t h e blood c o n t e n t of t h e t h y m u s . B u t Dr. ]~oyd h a s convinced me t h a t t h e t h y m u s is no* a v e r y vascular o r g a n a~d I realize t h a t the g r e a t vessels m u s t have been t h e chief f a c t o r s in t h e c h a n g i n g shadow.

542

TI~E

JOURNAL OF

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N o w I think I ought to say something about the connection between thymie enlargement and respiratory embarrassment, even though I think~ or at ]east I hope, t h a t clinicians r a t h e r t h a n radiolegists were the ones who raised t h a t ques'tion. I have never b e e n able to see how t h e s t r i d e r t h a t children have could possibly have a n y t h i n g to do with t h e t h y m u s . I t jus't is n o t in t h e cards t h a t a l a r g e o r g a n in t h a t region would produce the k i n d of s t r i d e r t h a t h a s been h e a r d i n these eases. Fig. 7 is a r o e n t g e n o g r a m of a p a t i e n t who did have a real e n l a r g e m e n t o f t h e t h y m u s due to a t h y m o m a . These s y m p t o m s a r e s o m e w h a t rare~ b u t this (me was a proved ease. Y o u will notice a very l a r g e t h y m u s shadow, a n d I w a n t to tell ;you w h a t t h e b r e a t h i n g of this child was like. I n s p i r a t o r y as well as e x p i r a t o r y p a s s a g e of t h e air w a s impeded. This little p a t i e n t was given i r r a d i a t i o n ; b e f o r e the r o e n ~ g e n o g r a m showed a n y decrease in the size of t h a t t h y m u s , r e s p i r a t o r y e m b a r r a s s m e n t was a b o u t 50 per cent i m p r o v e d ; a n d b y t h e t i m e t h e s l i g h t e s t decrease in the, size of t h a t t h y m u s could be m e a s u r e d on t h e r o e n t g e n o g r a m , t h e r e was complete relief f r o m the r e s p i r a t o r y embarrassmen't. I n o t h e r words, in this ease t h e t r a c h e a was compressed, and i n s t e a d of h e a r i n g the l a r y n g e a l s t r i d e r which we have so o f t e n ascribed to the t h y m u s we h a d t h e i n s p i r a t o r y a n d e x p i r a t o r y stri.dor t h a t I have j u s t illustrated. D1%. M I T C H E L L .

- D r . Boyd, do you have a n y t h i n g to say here?

DR. B O Y D . - - I will b r i n g up w h a t w a s discussed at the b r e a k f a s t table. Dr. C h a m b e r l a i n asked m e w h a t was the l a r g e s t vein g o i n g into t h e th.~mus gland, a n d I said t h a t it was t h e one %hat goes directly into t h e i n n o m i n a t e vein a n d m e a s u r e d a b o u t 2 ram. in diameter. I t h i n k t h e t h i n g t h a t is overlooked is t h a t t h e t h y m u s vein fits closely a r o u n d the i n n o m i n a t e vein. I f t h e r e is congestion in t h e mediast i n u m , it is p r o b a b l y clue to d i l a t a t i o n of the i n n o m i n a t e vein, a n d t h a t is p r o b a b l y what :is seen on the r o e n t g e n o g r a m . A t least Dr. C h a m b e r l a i n w a s e n o u g h of a g e n t l e m a n 'to g r a ~ t t h a t t h a t m i g h t be :it. T h e t h y m u s itself is n o t p a r t i c u l a r l y vascular. T h e r e is a n o t h e r p o i n t whicl~ m a y he applicable in some cases of relief of s y m p t o m s following i r r a d i a t i o n . I n children d y i n g of a c u t e r e s p i r a t o r y i n f e c t i o n s ( p n e u m o n i a ) w i t h i n t h e first few days of illness, the m u c o u s m e m b r a n e s of t h e t r a c h e a a n d bronchi a r e f r e q u e n t l y engorged. U n q u e s t i o n a b l y in i n f e c t i o n s there ~s e n l a r g e m e n t of l y m p h nodes d r a i n i n g %hat i n f e c t e d area, a n d r e d u c t i o n of these by i r r a d i a t i o n would c a u s e improvement. I r a i s e the q u e s t i o n t h a t , i f relief is obtained f r o m i r r a d i a t i o n in such eases, w h y n o t s a y it m i g h t be due to a r e d u c t i o n of h y p e r t r o p h y of t h e lymphoi~d tissue? I n children d y i n g of i n f e c t i o n s u n d e r ~ h o u r s of t h e onse't o.f their illness, in very r a p i d f u l m i n a t i n g infections, t h e w e i g h t of t h e t h y m u s is still w i t h i n the n o r m a l zone of variation. I n d e a t h f r o m one d a y to one week a f t e r o n s e t of illness we gel obvious r e d u c t i o n in t h e size o f t h e t h y m u s . I can show this on a slide. DR. M I T C t t E L L . - - P a r d o ~ me a m o m e n t , Dr. Boyd. I f I u n d e r s t a n d you e e l reetly, Dr. C h a m b e r l a i n , you demons'trated r o e n t g e n o g r a m s here in w h i c h t h e p a t i e n t did ha~e s y m p t o m s w i t h an e n l a r g e d m e d i a s t i n a l r e g i o n a n d t h e s e s y m p t o m s disappeared a f t e r x - r a y t r e a t m e n t s , b u t b e f o r e t h e r e h a d been a r e d u c t i o n i n size. DR. C H A M B E I ~ L A I N . - - B e f o r e t h e r e d u c t i o n w a s visible on t h e r o e n t g e n o g r a m b u t t h e r e d u c t i o n in size m u s t have t a k e n place. DR. ~ I I T C I - I E L L . - - I j u s t w a n t Dr. ~ e l m h o l z to be t h i n k i n g a b o u t the n e x t question I a m g o i n g to ask him, which is w h e t h e r he t h i n k s t h a t t h e t h y m u s g l a n d b y e n l a r g e m e n t c a n c a u s e s y m p t o m s o f d y s p n e a a n d cyanosis. DR. B O Y D . - - N o w on this p a r t i c u l a r slide ( P i g . 8) I h a v e the middle zone and t h a t is t h e 75, 50 a n d 25 percentile f r o m b i r t h to 90 y e a r s t h e cases of i n f e c t i o n a c c o r d i n g to t h e l e n g t h o f t i m e t h e i ~ d i v i d u a l onset o f s y m p t o m s . T h e d a t a p r e s e n t e d show t h a t w i t h i n f r o m one to

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of illness there is significant reduction in thymus weight and that in infections which have lasted over one week, 94 per cent of the thymus weights fall below in the ]o~er 25 per cent group of weights. Now these are the thymus weights froin which the standards wm'e set up when it was stated that any organ above 20 gin. in weight was hypertrophied, and yon see actually that the patholog[c reduc%ion was considered normal. DR. M I T C t I E L L . - - I think we ought to stick for the moment to what we really started discussing, namely, whetker enlargement of the ~hymus can cause symptoms. What Dr. Boyd has told us, I think we accept. There is no argument from the anatomical viewpoint thas what in the past was considered enlargement of the tllymus was the normal thynms, and I think Dr. I~oyd has demonstratad that to the satisfaction of all of ns. A question does arise at times because this is necropsy

544

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m a t e r i a l , a n d it is queried w h e t h e r p e r h a p s s o m e t h i n g h a p p e n s a f t e r d e a t h which c h a n g e s the picture. Therefore, we come back to t h e m a t t e r of r o e n t g e n o g r a m s . So f a r we have discussed 'the m a t t e r of r o e n t g e n o g r a m s r a t h e r briefly. T h e p l a t e which you h a v e showed us, Dr. C h a m b e r l a i n , was a n a n t e r o p o s t e r i o r view. W h a t does such a p i c t u r e m e a n in relation to p r e s s u r e s y m p t o m s ? DR. C H A M B E R L A I N . - - W e m u s t , of course, s t a r t out with r e c o g n i t i o n of t h e f a c t t h a t the l a t e r a l lobes o f %he t h y m u s c a n be v e r y l a r g e w i t h o u t p r o d u c i n g a n y difficulty, for t h e r e a s o n t h a t t h e r e is p l e n t y of space for t h e l a t e r a l lobes to occupy alongside t h e p e r i c a r d i u m on both sides. DR. H E L M H O L Z . - - O n w h a t basis, Dr. Chaalberlain, do you u s u a l l y give x-ray t r e a t m e n t in c a s e s of t h y m i c e n l a r g e m e n t ? DR. CHAMBERLA-IiNT. I: have u s u a l l y been p e r m i t t e d to decide w h e t h e r t h e e n l a r g e m e n t w a s significant. Now when I s a y ~ ' s i g n i f i c a u t enlarge~nent '~ I ~mlst go on t h e ~defensive i m m e d i a t e l y because y o u m a y s a y t h a t it is n o t of significance, b u t I 'think I should tell you a story because I a g r e e t h a t we m a y h a v e a very l a r g e thymus shadow without symptoms. L a n g l e y P o r t e r w a s w r i t i n g a book in 1919 a n d he asked m e to g e t for h i m a n o r m a l r o e n t g e ~ o g r a m of t h e chest of a 1-year-old child. I said t h a t w e a l d be e a s y because m y sister h a d a little girl who was born j u s t a y e a r ago, a n d at t h e a g e of 1 year she h a d never h a d a~ i n f e c t i o n or a n y t r o u b l e of a n y sort. ~ So I got t h e niece to come over a n d be x-rayed on her b i r t h d a y . To m y a m a z e m e n t she h a d a h u g e t h y m u s , b i g g e r t h a n h e r h e a r t ; she h a d a b s o l u t e l y no signs of s y m p t o m s , a n d never h a d had. I ,did n o t h i n g about it, I did n o t t r e a t t h e child b e c a u s e I t h o u g h t t h a t would be meddlesome. I h a d discovered t h i s 'thing a c c i d e n t a l l y , and for all I k n e w it was w i t h i n t h e l i m i t s of n o r m a l variation. T h r e e y e a r s later, however, w h e n she was 4 y e a r s e old, a nose a n d t h r o a t specialist decided to give t h e child a n a n e s t h e t i c f o r t h e p u r p o s e o f seeing w h e t h e r she h a d adenoids i n her n a s o p h a r y n x . W h e n t h a t short a n e s t h e s i a (it @as g i v e n for t h e p u r p o s e of g i v i n g h e r j u s t a b r i e f m o m e n t of u n c o n s c i o u s n e s s ) was adnlinistered, she i m m e d i a t e l y went into a deep eyanosls a n d was absolntely choked up. DR. t t E L M H O L Z . - - D o e s shadows?

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DR. C H A M B E I % L A I N . - - ( I f you will do your h e c k l i n g when I finish m y story) I think, Dr. Hehnholz, t h a t you are t r y i n g to t a k e a w a y f r o m me m y m o s t precious theories r e g a r d i n g m y mos~ r e m a r k a b l e cases. A t a n y r a t e t h e p o i n t t h a t I t h o u g h t was significant was that, w h e n t h e child h a d become absolutely limp a n d relaxed, she b e g a n to b r e a t h e again, a n d I b e g a n to q u e s t i o n w h e t h e r t h e s e so-called ~hymic deaths a r e really due to t h e t h y m u s . I said to m y s e l f : " W h y should room for a i r w a y be re-established w h e n the s t r u g g l e s stop a n d the child is r e l a x e d ? " 1V[y niece is now a girl of 19 or 20 years, a n d we have n e v e r i r r a d i a t e d h e r t h y m u s , not even a f t e r t h a t episode, b u t we did t a k e fihns once in a while. The n e x t film was t a k e n w h e n she w a s abou~ 12 y e a r s old, a n d she h a d a p e r f e c t l y n o r m a l m e d i a s t l n a l shadow. DR. H E L M I : [ O L Z . - - I t h i n k you know, Dr. C h a m b e r l a i n , t h a t I j u s t w a n t to e m p h a s i z e stone of t h e points, t h a t y o u a r e m a k i n g , b e c a u s e I could n o t have a b e t t e r case to b a c k up m y s t o r y t h a n ~he one you h a v e told. U n f o r t u n a t e l y I h a v e h a d similar cases where t h e child at t h e o~set of a n e s t h e s i a stopped b r e a t h i n g a n d only b y artificial r e s p i r a t i o n were we able to revive him. I do n o t believe t h a t such a n i n c i d e n t proves at a]] ~that t h e t h y m u s is in a n y w a y responsible. DR. B O Y D . - - W h a t is the b a s i s for s t a n d a r d s of t h e u o r m a l t h y m u s limits on t h e r o e n t g e n o g r a p h i c plate ? DR. CI:[A~CfBERLAIN.--I have no organized data. I carry in my head sonle data which allow me to form

I can only say that I believe opinions. I believe also that

A3KEt~ICAN ACADEMY OF PEDIATRICS

545

I can recognize the v a r i a t i o n s of "the n o r m a l a n d t h a t i know when a thymh', shadow is b i g g e r t h a n t h e a v e r a g e or b i g g e r t h a n 80 per cent of the cases t h a t I consider normal. DR. B O Y D . - - W h a t do you consider the significance of s o m e t h i n g t h a t is b i g g e r t h a n a v e r a g e .~ Dt~. C J c l A M B E R L A I N . - - I keep a biological d i s t r ; b a t i o n c h a r t c u r r e n t l y in :front of m e - - f o r hear'c size, f o r position of t h e viscera, an,] for the size of the t h y m u s . However, I do n o t become hysterical w h e n I see v a r i a t i o n s f r o m tile average, a n d I give as evidence of t h a t the ease a l r e a d y cited i~ which w h e n t h e t h y m u s w a s b i g g e r t b a ~ t h e c h i l d ' s h e a r t I did n o t even a d m i n i s t e r irradiation. DR. M I T C H E L L . - - D o you t h i n k a n increased size of the shadow in the media s t i n a l r e g i o n o n ' t h e r o e n t g e n o g r a m c a n be associated with such s y m p t o m s as d y s p n e a or eyanosis? Do you t h i n k t h a t a l a r g e t h y m u s does cause s y m p t o m s of o b s t r u c t i o n ? DR.. S P O I - I N . - - I t m a y or it m a y not cause s y m p t o m s of obstruction, b u t s y m p t o m s d u e to o b s t r u c t i o n arc in m y opinion v e r y rare. Our c h a i r m a n h a s s u g g e s t e d t h a t b e f o r e this d e m o n s t r a t i o n was t h r o u g h we m i g h t be able to t h r o w out t h e t e r m " s t a t u s t h y m i c o l y m p h a t i e u s . " I quite agree with him, b u t I would s a y t h a t i f we do it we m u s t s u b s t i t u t e s o m e t h i n g else for it such as ' ~ t h y r o - t h y m i c o l y m p h a t i c u s . ~' Y e s t e r d a y I a t t e n d e d a der~onstration on fluid a d m i n i s t r a t i o n at a rourLd t a b l e conference, a n d I was a m a z e d to find t h a t t h e y have in tile E a s t c e r t a i n p r o b l e m s t h a t some o f us h a d a h n o s t f o r g o t t e n a b o u t in Vancouver. I m e n t i o n t h i s to e m p h a s i z e t h a t there is a c e r t a i n g e o g r a p h y of disease a n d because, i f c e r t a i n c o m p e t e n t observers in one p a r t of A m e r i c a do n o t observe c e r t a i n clinical conditions, this does n o t n e c e s s a r i l y m e a n t h a t such conditions do not exiss in other p a r t s of the continent. I would like to limit m o s t o~ m y r e m a r k s to tile relationship ana'tomieally, physiologically, a n d p a t h o l o g i c a l l y between t h e t h y r o i d a n d t h e t h y m u s glands. Also I would s u g g e s t t h a t t h e r e is some significance in the decrease in incidence of occurrence o f t h i s s y n d r o m e in c e r t a i n goiter d i s t r i c t s following the g e n e r a l use of iodine t h e r a p y . Now I m i g h t s a y t h a t such m e n as Dr. Bilderback, Dr. D u r a n d , a n d Dr. B a r n e t t , a n d Dr. M e C o r m a c k , as well as m y s e l f , went on record twelve y e a r s ago a b o u t t h e g r e a t f r e q u e n c y of this s y n d r o m e , a n d I do n o t t h i n k we were seeing" t h i n g s . N o w we rarely see such s y m p t o m s , a n d I m a k e tile sngges'tion t h a t , when, for example, in B r i t i s h C o l u m b i a we can c h a n g e tile m a k e up of a n i m a l s aml plants, aml I t h i n k of h u m a n beings, b y t h e j u d i c i o u s a d m i n i s t r a t i o n of iodine, we should give m o r e c o n s i d e r a t i o n to t h i s t h y m u s - t h y r o i d relationship. I r e m e m b e r t h a t in 1929 P r o f . F e e r of Zurich told m e t h a t eases o f s~catus t h y m i e o l y m p h a t i c u s had decreased in Switzerland as io.dine t h e r a p y became more extensive. I e m p h a s i z e also t h e f a c t t h a t so-called s t a t u s t h y m i c o l y m p h a t i e u s s y m p t o m s m a y occur w h e n t h e r e is s l i g h t e n l a r g e m e n t or w h e n an enlarged s h a d o w i~t t h e ' t h y m u s r e g i o n c a n n o t be demonstrated. I n d i v i d u a l s e x h i b i t i n g this s y n d r o m e have c e r t a i n physical similarity. I t h i n k also t h a t x - r a y t r e a t m e n t over t h e region o f t h e t h y m u s produces a n alleviation of c e r t a i n s y m p t o m s wbleh are looked u p o n as b e i n g related to the s y n d r o m e u n d e r discussion. DR. 3 / [ I T C t I E L L . - - W o u l d you m i n d m e n t i o n i n g the s y m p t m n s of this s y n d r o m e at t h i s p o i n t ? DtK :HOWARD S P O H N . - - T h e y a r e d y s p n e a o f an ~ntermitten't t y p e not related to cardiac disease or a t e l e e t a s i s ; c y a n o t i c a t t a c k s n o t related to c a r d i a c p a t h o l o g y ; i n t e r m i t t e n t suffocative s p a s m s w i t h or w i t h o u t c r y i n g or t e m p e r a t t a c k s ; stridor, u s u a l l y e x p i r a t o r y and n o t connected w i t h a n u t r i t i o n a l s t a t e such as rickets or w i t h o b s t r u c t i o n of t h e l r a c h e a f r o m m e c h a n i c a l or other c a u s e s ; b r e a t h - h o ~ d N g s p a s m s accompanied b y c y a n o s i s a n d shock ; shock a n d collapse f r o m s e e m i n g l y insufficient causes such as o p e n i n g f u r u n e l e s , a d m i n i s t e r i n g anesthetles, etc. Dt~. t t E L N H O L Z . - - D r . Spohn, do I u n d e r s t a n d y o u to m e a n t h a t all these symptoms a r e due to an. insultieieney of iodine?

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you state that since tile introduction

of iodine

these cases have practically disappeared in your goiter belt.~ DR. SPOItN.--No, I do not think that is the right conclusion. I think that just because iodine relieves or changes certain conditions in tile 'thyroid~ it is quite unscientific to say that these things are produced by lack of iodine. For example, in malaria quinine is a curative agent in the treatment of this ,disease, and yet malaria is not caused by lack of quinine. Another point: x-ray treatment over the thymus region produces alleviation of these symptoms, and there appears to be no scientific proof whatever that irradiation in competent hands and in recognized dosage has produced any physical oi' mental deterioration. Other physiologic observations also~ such as those made by Dr. Einhorn, with which I am perfer in accord, indicate that the thymus is a gland of internal secretion. May I say this: according to Warthin, Williamson, Barry and Pierson, l~IeCarrison and others~ especially Warthin, who is familiar to you, practically every adult dying of certain types of toxic goiter showed pathologic changes in the thymus gland and an enlargement which in normal adult life is unusual. Only las't week in Vancouver we saw a girl of 24 years of age with a toxic goiter who succumbed unexpectedly. She had a small hypersecretory thyroid and a large thymus. On the train I met a pathologist from Portland who had witnessed a similar occurrence. In regard to anatomical connection: Williamson states that quite eomnmnly a series of cysts can be followed ahnost in sequence from the hilum of the thyroid into the upper pole of the thymus along the so-eMled stalk or ligament of the thymie lobe. These varicosities often ex%end into the substance of the thymus in the mediastinum. The region of distribution of the lymph cysts coincides with tile region of distribution of flaymie tissue from the hilum .downward into the mediastinum. ']2hat isolated, as well as compact, masses of lymph tissues in this region are thymic tissue, is demonstrated by the finding, even in the hilum of the thyroid lobe, of the characteristic Hassall corpuscles. Careful dissection of the stalk of the thymus reveals the fact that it takes origin in the hilum of the thyroid lobe. This stalk, when it is well defined, is seen to be composed of vessels which have all tile characteristics of lymphatic vessels. Lymph is encountered in the channels. F~equently the component lymphatics, with care, can be dissected from the lateral surface of 'the trachea, on which they lie, and traced to their origin in the hilton of the thyroid lobe. On the other hand, these vessels may not be collected together into a cord or leash, but may spread over the tracheal surface of the thyroid lobe and run down almost independently into the thymus. Thus i~ seems clear that there is a very definite lymph system which emerges at the hilum of the thyroid a~ld passes directly into the lymph spaces of the thymic nodes. There are two processes that occur in the normal thyroid gland: one is passive accumulation of colloid, or colloid storage; the other is the active process of secretion. Colloid is not secretion but is possibly of the nature of a carrier or vehicle which, like the taurocholates and glyeolates of the bile, is continually in circulation in the body. Only the excess or reserve of the bile is stored in tile gall bladder, and Williamson suggests that only the reserve of the colloi,d is stored in the thyroid gland by the process of colloid storage. There are three physiological phases in the thymus gland: (1) a lymphocytic stage, (2) a granular lipoid stage, and (3) a vesieulated f a t stage, These phases of physiologic change are similar to changes described by Gulland and Job in the so-called secondary lymphatic glands. The thymle gland~ like other secondary Iymphatle glands, exhibits great difference in appearance during the course of its activity. During the normal active secretory phase of tile thyroid, a lymphocytic secretory phase can be demonstrated in the thymus by sections made at such times.

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AS w i l l be m e n t i o n e d l a t e r , a d i f f e r e n t p h a s e is s h o w n i n t h e t h y m u s i n s a d l a~l abn o r m a l s t a l e as t o x i c g o i t e r . I n a p u b l i c a t i o n W i l l i a m s o n d e m o n s t r a t e s t h a t the t h y m u s a n d t h y r o i d m a y i n m a n y w a y s be r e g a r d e d as one o r g a n a n d t h a t t h e t h y m u s n p t o p u b e r t y is e n g a g e d Jn d e t o x i e a t i n g one of t h e t h y r o i d seeretions~ n a m e l y , t h e s e c r e t i o n of h y p e r p l a s i a . A l s o , one o t h e r p o i n t : one h e a r s of m a n y d e d u c t i o n s in r e g a r d to s t a t u s t h y m i e o l y m p h a t i e u s t h a t a r e m a d e on o b s e r v a t i o n s of c h i l d r e n l]roln "~ to 10 y e a r s o f age. S t a t i s t i c s h a v e b e e n e o l l e e t e d o f t h o u s a n d s of e a s e s t a k e n a r o u n d ~che t o n s i l age. I n m y e x p e r i e n c e , 98 p e r c e n t o f all s o - c a l l e d t h y m i c syndrome deaths occur within the first eighteen months of life.

Fig. 9.

~'ig. 10.

s 9 . - - S q u a m c u s t y p e of e n l a r g e d t h y m u s in a f e m a l e i n f a n t a t the a g e of 9 m o n t h s . T h i s s h a d o w could h a r d l y be m i s t a k e n for the s h a d o w of o t h e r s t r u e t u r e s . Fig. 1 0 . - - C a s e of G. T.. a g e d 19 m o n t h s . T h i s c h i l d s h o w e d v e r y a I a r m i n g clinical s y m p t o m s a s d e s c r i b e d in t e x t . The s h a d o w w a s i n t e r p r e t e d a s b e i n g due to a n enl a r g e m e n t of the t h y m u s . T h i s p i c t u r e w a s t a k e n b e f o r e x - r a y t r e a t m e n t . No o t h e r t h e r a p y w a s employed.

1Pig. l l . - - C a s e of G. T. ~rery m a r k e d t h y m i c s h a d o w . P a t i e n t s h o w e d a l a r m i n g c l i n i c a l syl]:l.ptorrls. T h i s p i c t u r e w a s t a k e n a f t e r t h e s e c o n d x - r a y t r e a t m e n t . G r e a t c l i n i e a I i m p r o v e m e n t w a s a p p a r e n t a t t h i s t i m e a l t h o u g h the s h a d o w is s t i l l l a r g e . I j u s t w a n t to show one or t w o s l i d e s i l l u s t r a t i n g t h e t y p e a t l e a s t t h e Wes't C o a s t pediastrieians believe exhibit symptoms to which they must pay attention (Fig. 9). I k n o w o f no o~her t h e r a p y b u t x - r a y f o r s u c h eases.

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This (Fig. 10) slide demonstrates tile t h y m u s x-ray in a child who was brought to me dying on a pillow. I am not particularly concerned about what influenced his thymus or what tissues were affected by the irradiation, but I want to emphasize tile resul't, which was quite as spectacular as any operation in brain surgery. This second slide (l~ig. 11) is a f t e r tile second treatment. DR. M I T C H E L L - - W h a t

syinptoms did this child have, Dr. Spohn?

DR. S P O t I N . - - H i s father called me and said: " D o c t o r , I have a child 19 months of age who h a s been seen by a great number of p h y s i c h ~ s . I am losing my business through s t a y i n g at home watching the child; my wife is in a highly nervous s t a t e ; and i f we canno't get relief, we think it would be almost better for the child to die. Tile child has repeated attacks, during which he becomes limp and slightly blue~ and appears to be d y i n g . ' The child was brought in. for examination and found to have a very nmrked secondary anemia. There was a history of sudden attacks in which he wou~d become flaccid and cyanotic and yet with a peculiar characteristic pallor. He appeared to be dying. A f t e r a thorough examination he was found to have an enormous thymus. He was irradiated and had two of these attacks the following week, one attack the next week~ a n d no further attacks. His anemia improved with dietetic measures and in two weeks he was in perfec't health. Now he is a wMl-known football player on one of our high school teams. I do not care what you t e r m it, whether you call it status thymieolymphaticus or something entirely different, lVfy opinion is t h a t I saved the child frmn de~th wi'th x ray therapy, and the p~rents were very grateful. Now m a y I show some anatomical sections to illustrate some previous statements? These disseeti0ns from the Royal College of Surgeons in London have met with the approval of Sir Arthur X e i t h i they are from reprints of Williamson of London. I t is very difficult to inject the lymphatics in these c a s e s - - v e r y difficult i n d e e d - - a n d yet it is interesting to know t h a t in 1882 Sir Ashley Cooper was able to inject the lymphatics of a calf and demonstrate the connection of the lymphatics of the t h y n m s and the thyroid. ~{is secqcions are still on view at the Royal College of Surgeons in London. The slides demonstrated the connections of the lymphatics. DR. BOYD.

How old a person is t h a t section from~

DR. SPO:[{N.--~Pi~ese are nearly all taken f r o m young adults. May I point this out: Willimnson has shown that, when a patient has died of 'toxic goite% with symptoms which in my opinion resemble very closely the s y m p t o m s of death in the thymie shmdrome seen in childhood~ there is ~ hyperseeretory stage and an absence of colloid in the thyroid. Therefore, we examine the t h y m u s of t h a t individual expecting it to show t h a t it is in the lymphocytic secretory stage. But this is not the ease. W h a t we find is a peculiar g,.uo~lar s'tage in the thymus. One could deduce f r o m this t h a t during t h a t peculiar toxic condition the secretion, which we know is present, m u s t find its way into the blood stream and m u s t produce toxic symptoms. Some continental workers suggest tha't Graves' disease should be called toxic status thymieolymphadcus. There are in the Royal College Museum in London thirteen Gases of carcinoma of the thyroid gland. N i n e of them show secondary changes only in the thymus, not in the lymphatics of the neck. Therefore~ I think there is here some pathologic evidence of a connection b6tween the thymus and the thyroi d. Dl%. H E L M H O L Z . - - W i t h regard to the findings of the carcinoma of the thyroid, we, ha.re observed seven patients now with t h a t disease, and they have all metastases in the gla~ds of the neck. DR. S P O } I N . - - T h a t does not alter the fact t h a t in other cases metastases occurred in the thymus. DR. N I I T C H E L L . - - I f I understand your belief, Dr. Spohn, it. is t h a t there is a, relation between the thyroid and the thymus, b u t I did not quite unders'tand what t h a t relationship has to do with the symptoms of obstruction, dyspnea, and eyanosis.

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I mean, do you believe that the thymus causes these symptoms by its enlargementS. Or do you think that some of these symptoms come about because of alteration of its internal secretion? DR. S P O H N . - - I think it is a matter of internal secretion. A t the beginning of this discussion your chairman described me as a thymus enthusiagt. I am not quite sure just what that implies, but in order to clarify my views, might I state my present beliefs? 1. Status thymicolymphaticus is more prevalemt in goiter districts, i t is, however, less frequent in such .districts since the more general use of iodine for endemic goiter. 2. Status thymieolymphaticus is a real clinical entity which is much more frequently observed in children under 18 months of age; and statistics concerning tonsillectomy and other operations at the ages of 3 to 10 years include an age period during which so-called thymic symptoms have always been rare. 3. This condition implies a lowered threshold of resistance against physical shock~ infections, foreign protein ingestion, etc. Deaths due to so-called status thymicolymphaticus are due in the large majority of cases to an apparent toxic metabolic disturbance which resembles the deaths occurring in exophthalmie goiter of adults. 4. There are anatomical~ physiologic relationships between the thyroid and the thymus glamd. 5. Death from pressure of an enlarged thymus or of other vital structures is an extremely rare occurrence. 6. Prophylactic nmternal ingestion of thyroid and iodine is necessary i1~ all goi trous regions. 7. X-ray diagnosis of an enlarged thymus is only an indication of the 9ossibility of the exlstenee of status thymicolyr~q~haticus. 8. An enlarged ~hymus is often a normal physiologic oecurrc'nce and may there fore give no clinical symptoms. 9. X-ray or radium treatment usually relieves the clinical symptoms of so-called status thymieolymphaticus and should be used conservatively until a better therapeutic measure is available. 10. There appears to be practically no scientific evidence that the use of x~rays by a competent radiologist, and with the doses ordinarily employed, has ever produced elther physical or mental deterioration. 11. The status thymicolymphaticus syndrome is not a dead issue and requires further study to enable the profession to explain satisfactorily these peculiar sudden deaths to the public and themselves. DR. ]~OYD.--What is the evidence for internal secretion from the thymus? DR. E I N K O R N . - - T h e r e is no experimental evidence available that wouhl prove that the thymus has an endocrine secretion. This can only be inferred from some of ~he evidence available to,day. I have already presented material which makes one strongly suspect that the thymus may possibly have an endocrine secretion. This is suggested by its relationship to other glands as well as by its biologic activity f o r ]owing injection or implantation. DR. 1V[ITC}IELL.--However, Dr. Einhorn, the nmterial which you presented and which you and Dr. Rowntree have published, while suggesting an internal secretion, has nothing to do with the matter of dyspnea, cyanosis, or sudden death. In other words these animals do not die, they do quite the opposite; they want to live apparently because they develop early both somatically and sexually. DR. S P O H N . - - I th~nk these individuals die with a derangement in internal secretion as in toxic goiter. DR. B OYD.--Have you any evidencG ])l~ Einhorn, that t]~e ~ame thing e'~nnot happen from extracts of lymphoid tissues or tissues other than the thymus~ DR. E I N I [ O R N . - - E x t r a c t s of various glands and tissues, s~ch as liver, spleen, lymph gland, and tonsil, have been prepared in a manner identical to theft used in the

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preparation of thymus extract; no crltiea] evidence of any effect on either growth or development has been noted from the injection of any of these extracts. DR. BOYD.--I think that is a very significant and critical experiment. If it can be demonstrated that the extracts of lymphoid tissue have no effect and extracts of thymus d% there is offered critical evi,denee that tlle thymus does have some secretion other than lymphoid tissue itself.

I)11. MITCIIELL.--I want to know the opinion of each member of this panel on the matter of enlargement of the thymus gland as a cause of symptoms of obstruetion~ dyspnea~ and eyanosis. I am going to ask~ beginning with Dr. Chamber]ain~ whether each one believes thas enlargement of the ~hymns can cause an obstruction which will lead to dyspnea. Answer that one, Dr. Chamberlain. Is it true er false? DR. C t I A M B E I ~ L A 1 N . Wellj p e r h a p s it is significant t h a t I have~ r i g h t here in this room~ Mr. C h a i r m a n , f r i e n d s who have r e f e r r e d p a t i e n t s to m e a n d h a v e either insisted u p o n or p e r m i t t e d x-ray t h e r a p y to be a d m i n i s t e r e d to t h e p a t i e n t a f t e r the d i a g n o s i s of e n l a r g e m e n t of t h e t h y m u s was made, a n d I am v e r y m u c h on 'the spot. Ilowever, I s h a l l certainly be t r u t h f u l , but I mu n o t g o i n g to be v e r y dogmatic. I c a n say this. I have s h o w n yon an i n s t a n c e in which t h e r e w a s a very l a r g e t h y m u s ( F i g . 7). I t was a t h y m o m % it is true, and n o t e n l a r g e m e n t of t h e t h y m u s in ~he or.dinary b e n i g n sense. I n this case, as il said, we f o u n d s y m p t o m s such as s h o r t n e s s of breath, b o t h i n g r e s s a n d egress of the air b e i n g i n t e r f e r e d with. Now, I c a n n o t go a g a i n s t eertMn f r i e n d s of mine, clinicians, who insis't t h a t the s t r i d o r t h a t they n o t e d was improved a f t e r i r r a d i a t i o n . I t certainly should be significant t h a t when I h a d showli t h a t t h e r e was a n e n l a r g e d t h y m u s shadow ( a n d I h a d employed a special technique in the l a t e r a l p r o j e c t i o n to show c o m p r e s s i o n ) , irradia~cion of t h e t h y m u s n o t only caused t h e shadow to d i s a p p e a r or become smaller, b u t t h a t t h e clinician s t a t e d t h a t t h e child was t a k i n g :food belier, b r e a t h i n g better, and t h a t t h e stridor h a d disappeared. On t h e other h a n d , there are some very i n t e r e s t i n g a n a t o m i c a l p o i n t s t h a t have not been e m p h a s i z e d as yet. I t is f o u n d ~that in some eases certain p a r t s of the t h y m u s are up i n t h e apices of t h e t h o r a x , where t h e j u g u l a r veins a n d t h e g r e a t vessels are s i t u a t e d . A t a c e r t a i n p h a s e of respiration, p a r t i c u l a r l y w i t h t h e inspirat o r y effor~ a g a i n s t a closed glottis such as t h e b a b y exhibits at t h e end of a cry, there is no q u e s t i o n t h a t t h e s e s t r u c t u r e s cau become well j a m m e d up. T h i s m a y be of some significance. I t h i n k c e r t a i n l y tttat e v e r y t h i n g I h a v e j u s t m e n t i o n e d could h a p p e n in a p a t i e n t whose t h y m u s was w i t h i n the limi'ts of n o r m a l size. I)1{. M I T C I I E L L . - - I n other words y o u do t h i n k t h a t causes t h e s e o b s t r u c t i v e s y m p t o m s . DR. C I I A I M B E R L A I N . - - I

occasionally the t h y m u s

do.

DI{. l V H T C H E L L . - - Y o u do n o t think t h a t h a p p e n s very o f t e n ? I)t{. C t I A M B E R L A I N .

No.

DR. M I T C I - I E L L . - - I 3 u t it does happenS. DR. C t I A M B E 1 { L A I N . - - I I)R. M I T C H E L L . - - I ) r .

t h i n k so.

tIelmholz~ will you answer t h a t question~

DR. t I E L M H O L Z . - - I n view of t h e f a c t t h a t Chevalier J a c k s o n h a s demons'trated by e x a m i n a t i o n of t h e l a r y n x a n d t r a c h e a t h a t n a r r o w i n g of t h e t r a c h e a c a n occur f r o m p r e s s u r e exerted b y a tlnymus, we m u s t a s s u m e t h a t t h i s can h a p p e n . The only q u e s t i o n is how o f t e n does it occur9 I h a v e been in practice for florae %hirty years, a n d I have y e t to a d m i n i s t e r i r r a d i a t i o n to a p a t i e n t t h e r a p e u t i c a l l y or preoperatively for so-called t h y m i e e n l a r g e m e n t for a n y r e a s o n other titan a n e w g r o w t h of t h e t h y m u s . I do u o t m e a n t h a t t h y m i c e n l a r g e m e n t , as we arc c o n s i d e r i n g it today~ does n o t occur, b u t f r o m m y experience both in Chicago a n d ~n M i n n e s o t a

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(both of these places are in the goiter belt) I feel t h a t obstruction caused by thymie enlargement other t h a n t h a t owing to ~. new growth is extremely rare. t have net seen a single case in which the inspiratory and expiratory striders, as pointed out by Dr. Chamberlain, were owing to an enlarged thymus. I h a w seen eight eases in which sudden death was caused by, or was associated with~ the production of anesthesia. W i t h regard to obstructive symptoms: in m a n y instances patients who have received irradiation because of a so-called enlarged t h y m u s are being treated by irradiation um~eeessarily and without any beneficial results. The great problem, 1 think, is the relationship of the t h y m u s to the adn~nistration of anesthetics. F r o m 1991 to 1938 at the Mayo Clinic, 4~214 tonsillectomies were performed. During and immediately after operation there was exactly one death, and t h a t occurred in a severe case of aerodynia. The p a t i e n t ' s condition was becoming worse very rapidly and in view of tile excellent results of tonsillectomy in cases of acro.dyni~ reported by Rodda, it was considered advisable to attempt tonsillectomy. The patient died within a few minutes a f t e r administration of the anesthetic was started. I n none of these cases I have mentioned was the t h y m u s subjected, to irradiation therapeutically, although there were m a n y eases in which the roentgenographic shadow of the t h y m u s appeared to be larger t h a n the usual so-called normal shadow. I might say, however, t h a t every one of these patients was carefully examined the day before operation. Roentgenologie examination of the thorax was performed, and, examinations of the blood and urine were made. Operation was not performed on any patient who had an elevated temperature. There were m a n y patients who had a severe reaction following operation, b u t not a single death occurred with the exception of the one mentioned. I might say t h a t from 1921 to 1928 there were 525 patients less t h a n five years old whose tonsils were removed. Se-ealled thymic death is supposed to be most frequent during the first eighteen months of tlfe. I have the records of 1,110 patients who were operate(] on for harelip and cleft palate d u r i n g t h a t period, and, of these, ]1 died. Two died of congenital heart disease, and in these two instances the operation was done at the request of the parents b u t against our advice. Three died of infection one to fernteen days after operation; two died during operation; and four died three and a half to ten hours after operation. Six of these were in a sense instances of m~dden death~ but, as f a r as we could determine, uone of these patients had evidence of thymic enlargement which could cause death. DR. N[ITCJ:IELL.--Dr. ]3oyd, would you answer this question? Do you think that enlargement of the thymus gland can cause symptoms of obstruction? [DR. B O Y D . - - I think t h a t an enlarged thymus itself, when i t ' s 'truly enlarged, ea~ tmquestionably cause obstructive symptoms, such as in the ease of t h y m o m a which Dr. Chamberlain ilustrated, t[owever, the occurrence of the truly enlarged t h y m u s is so rare t h a t ft is not something to be looked for in the ordinary healthy child. DR. MITCI-IELL.--])r. Spohn~ ])R. S P O t I N . - - I think t h a t tile so-called obstruction from enlargemeut of the thymus is rare b u t m a y happen, i f I n m y answer Dr. IIelmholz, who interjected the remark concerning goiter belts: there are goiter belts and goi'ter belts. I t has been pointe,d out t h a t there are large areas in India in which there is no iodine or salt in the water b u t in which the water is boiled and in these districts there is no endemic goiter. W h e n I am speaking of a goiter belt I am speaking of a belt witll marked clinical m a n i f e s t a t i o n s such as we have in British Columbia, Washington, and Orcgom DR.. MITCI-II~L[L--May I ask again what is the relationshil~ of this ~o the symptoms t h a t m a y be produced by the t h y m u s ?

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DR. S P O H N . - - I shall answer it this way. Formerly we had a large number of eases presenting symptoms apparently due to thymie disturbance and now we rarely see them. I am just suggesting that there may be a relationship between iodine therapy in goiter regions anti a decreased incidence in status thymicolymphaticus. In certain districts where we have had somewhat similar deaths and other manifestations oecurring in calves, coltsj and other animals, these peculiar occurrences have practically ceased since iodine administration. DR. MITCI-IELL.--Th~t is, it is your belief that the administration1 of iodine had something to do with the goiter in these animals and in the hmnan. But we a~'e trying to get t h e relationshtp between goiter and the thymus. Do you mean, ])r. 8pohn, tha~, as iodine was given, the goiter disappeared anti the symptoms which eould be attributed to the thymus disappeared also. Is that right? DR. 8POHN.--Yes, entirely. Routine iodine therapy in goiter regions appears to have grea*ly diminished the incidence of dangerous so-called thymie symptoms. DI{. MITCHt0LL.--Dr. ]~inhorn, what have you to say? DR. EINI-IORN.--I can only repeat what some of the others who have preceded me have said. Although true enlargement of the thymus is possible, I have not seen serious obstructive symptoms produced by such a condition. The symptoms, dyspnea, eyanosis, and strider, are not specific of thymus enlargement, they are nacre often found in ~ large group of well-recognized clinical conditions. To illustrate my point, I have seen a 0-month-old infant who received six therapeutic irradiations for an enlarged shadow in tlle upper mediastinum associated with dyspnea, cyanosis, and strider. This child did not improve after the sixth treatment even though a follow-up roentgenogram showed complete disappearanee of the superior mediastinal shadow. A elosor examination of that child by means of a bronehoseope showed that it had congenital defects in the laryngeal cartilages. I t is my feeling that these obstructive symptoms too often are attributed erroneously to enlargement of the thymus. DR. MITCHIELL.--A very important point that we all must stress has just been mentioned. The symptoms we are discussing, such as dyspnea and cyanosis, and even sudden death, are eertainly nonspecific symptoms. They can be caused by a number of conditions, and we all realize that one has to be very careful before he attributes these symptoms to "thymus. There is a question which we lind on our original list. Can any harm come about from the usual dosage of radiologie treatment %o 'the thymus gland? I have heard it stated that idiocy fellows such treatment. Do you believe that, Dr. Chamberlain~a Answer yes or no. DR. C H A M B E R L A I N . - - N o . I t is worth a trip across the continent to get a ehanee to help lay that ghost. When my very good friend Leonard Rowntree sugges*ed that idiocy could result from such irradiation, he was jumped on very severely by me and others. That is one thing that does not happen. I am sure that we can say that no matter hew unnecessary and superfluous irradiation of the thymus may be, and certainly we have to admit that ~t may be such, we have not harmed the individual with the type of :irradiation that is administered by a modern radiologist for this condition. I have ease histories of three b~bies in which actual damage was dane by irradiation for presumed enlargement of %he thymus~ but in every case the treatment was improperly gi~een~ and even the original diagnosis was wrong, t n one ease slight kinking of the trachea and a mediastinal shadow which was entirely within normal limits were mistaken for an enlarged thymus, perhaps because the flint was taken in an expiratory phase of respiration when tile bizarre appearance produced is hard to iaterpree. Irradiation therapy was administered, and then, because the x-ray appearance did not change (and it did not el~ange because there was no enlargement of the

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t h y m u s there to b e g i n witll)~ t l m r a p y was c o n t i n u e d u n t i l the child received t w e n t y six t r e a * m e n t s . I n a n o t h e r case s e v e n t e e n t r e a t m e n t s were a d m i n i s t e r e d , a n d in still another~ t w e n t y - t h r e e t r e a t m e n t s . Two of t h e s e p a t i e n t s died of aplastic, anemia, a n d t h e other h a d aplastic a n e m i a b u t is still alive. These children were all grievously overtreated. l wang to a s k this question. W h a t h a p p e n s when t h e s t r i d e r is i m p r o v e d a f t e r i r r a d i a t i o n of t h e t h y m u s ? l will a s k y o u that~ Mr. C h a i r m a n . DI~. B O Y D . - - I t h i n k the question arises w h e t h e r tim benefit f r o m i r r a d i a t i o n is n o t d u e to its effects on s t r u c t u r e s in t h e m e d i a s t i n u m ~ther t h a n the tllymus. DR. M I T C H E L L . - - N o w we m u s t t r y to get some answer to this i m p o r t a n t question of s u d d e n d e a t h as r e l a t e d to "cite t h y m u s . F r o m t i m e to time one h e a r s a story like t h i s - - i t w a s p e r h a p s the s t i m u l a t i o n f o r this p a n e l discussion: I n a certain c o m m u n i t y a child h a d died suddenly. One p h y s i c i a n had n o t ordered a n x - r a y of t h e c h i l d ' s t h y m u s arLd s u g g e s t e d i r r a d i a t i o n t r e a t m e n t of it. I t was s t a t e d t h a t , if this h a d been done, t h e child would n o t h a v e died. T h a t became a m a t t e r of legal tes"cimony a n d record. I t would be h e l p f u l if we were able to t h r o w some l i g h t on this question. Is it true, or is it n o t t r u e - or do we n o t know? Of course, t h a t b r i n g s up the mat"cer of. t h e t e r m which Dr. Boyd s a y s we c a n n o t use~ " s t a t u s t h y m i c o l y m p h a t i c u s . " She will teli y o u w h y we cannot u s e such a term w h e n she a t t e m p t s to answer t h i s question. N o w I should like to ask Dr. C h a m b e r l a i n a question. W o u l d t h e mere f a c t t h a t tim "thymus was i r r a d i a t e d Itave a n y t h i n g to ,do witit p r e v e n t i n g s u d d e n d e a t h even i f it could be a s s u m e d t h a t s u d d e n d e a t h h a s a n y t h i n g to do w i t h t h e t h y m u s ? DR. C H A M ] 3 E R L A I N . - - I hope~ Dr. iMitehell~ t h a t m y slight a n d w a v e r i n g d e f e n s e of "the practice of occasionally i r r a d i a t i n g the t h y m u s does n o t i n d i c a t e t h a t I am a believer in t h e t h e o r y t h a t s u d d e n d e a t h can be due to e n l a r g e m e n t of the t h y m u s . P e r s o n a l l y I t h i n k t h e t h y m u s h a s n o t h i n g to do w i t h s u d d e n death. DR. M I T C H E L L . - - I t h i n k we all a g r e e t h a t , simply because the cause of s u d d e n dea"ch c a n n o t be fourLd~ t h e r e is no p a r t i c u l a r r e a s o n for believing t h a t it m a y be due to t h e t h y m u s . DR. I ~ E L M H O L Z . - - W i t h r e g a r d to t h i s m a t t e r : it seems to me t h a t we m u s t rule out all of t h e possible c a u s e s t h a t m i g h t , d u r i n g an operative procedure or d u r i n g t h e course of a n illness, give rise %o s u d d e n den"cir. I a m a n y of t h e s e eases we a r e not able to p u t our finger on t h e a c t u a l cause of death. W e are doing actual h a r m in h i d i n g behind t h e d i a g n o s i s of s t a t u s t h y m i e o l y m p h a t i e u s as the cause of s u d d e n death. DR. M I T C H E L L . - - D r . Boyd~ do y o u t h i n k t h a t t h e t h y m u s , either by enlargem e a t or by a n y a l t e r a t i o n of its i n t e r n a l secretion could ever cause s m h l e n death~ DR. B O Y ] ) . - - I h a v e no record which indicates it does. W e have p e r f o r m e d a good m a n y a u t o p s i e s in cases of s u d d e n d e a t h at t h e request of physicians. I n a good m a n y of t h e m we tlnd defini"ce evidence of infection, i\iy i m p r e s s i o n is t h a t these d e a t h s i n children occur more f r e q u e n t l y d u r i n g grippe epidemics. The situation varies. Some of t h e citildren h a d ha,d a slight cold and seemed to be recovering b u t were s u d d e n l y f o u n d d e a d ; some h a d h a d slight s y m p t o m s of ehest i n f e c t i o n b u t n o t e n o u g h to a p p e a r serieusj b u t t h e n died u n e x p e c t e d l y ; some had been obviously seversly ill a n d died w i t h i n t w e n t y - f o u r h o u r s of t h e o n s e t of s y m p t o m s . T h e t h y m u s g l a n d s of those children who died quickly were w i t h i n t h e l i m i t s of n o r m a l variation. T h e o r g a n i s m t h a t we f o u n d o f t e n e s t in c a r e f u l l y selected a r e a s f r o m the l u n g s was t h e streptococcus. I n some eases m e n i n g i t i s was discovered, occasionally only w h e n we used G r a m s t a i n s of sections of t h e m e n i n g e s and located streptococci there.

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THE JOURNAL 01o PEDIATRICS

~Iy own impression, which only is a n impression~ is tlmt p r o b a b l y m a n y of these deatl,s were really due to t h e filtrable viruses a n d t h a t the s e c o n d a r y invaders, t h e streptococci, were j u s t b e g i n n i n g to appear. DR. M [ T C H E L L . - - D r . death?

Spohn, w h a t is your a n s w e r to this question o~ s u d d e n

DR. S P O t I N . - - I ~hink that~ i f thyrotoxieosis can cause sad,den deathj so can peculiar d i s t u r b a n c e s of l y m p h a t i c a n d other secretory gland o r g a n s as the t h y m u s also lead to s u d d e n death. D R . M I T C t I E L L . - - D r . E i n h o r n , I t h i n k yon o u g h t n o t only a n s w e r this question~ if you wish to, b u t if you t h i n k t h a t s u d d e n d e a t h is related "to t h e t h y m u s you should s t a t e what y o u believe its relation is to a n i n t e r n a l secretion. D:R. E 1 N I I O R N . - - S e l y e , w o r k i n g in Collip's l a b o r a t o r y , has p o i n t e d ()at by m e a n s of a n i n t e r e s t i n g p h e n o m e m m which he d e s i g n a t e s the " a l a r m reaction, '~ a t h y m u s a d r e n a l relationship. I n adrenalectomized a n i m a l s , d e a t h follows surgical shock~ exposure to colJs or s u b c u t a n e o u s i n j e c t i o n of formaldehyde~ even t h o u g h the t h y m u s a t t e m p t s to c o m p e n s a t e by e n l a r g e m e n t . This is a n extrmncly i m p o r t a n t poin'c. :in a d r e n a l e e t o m i z e d animal% shock produces death. I n t h y m e e t o m i z e d a n i m a l s the same s t i m u l i a r e followed by a d r e n a l c o m p e n s a t i o n a n d survival of t h e animal. I n other words, where the t h y m u s g l a n d h a s been removed a n d 1,he a d r e n a l l e f t i n t a c t t h e a n i m a l s survive severe shock. Selye describes t h i s a l a r m reactiom s y m p t o m a t i c a l l y , and this description b e a r s a close r e s e m b l a n c e to t h e s y m p t o m s observed in so~ealled s t a t u s t h y m i e o ] y m p h a t i c u s . This work a t t e m p t s to explain t h i s comli'tion on t h e basis of a d r e n a l "insufficiency. In cases o f s u d d e n d e a t h wkere, af'ter a complete a n d t h o r o u g h search, the cause c a n n o t be found, it seems t h a t a d r e n s l insufficiency offers a b e t t e r explana'tion t h a n does s t a t u s t h y m i c o l y m p h a t i c u s . H e r e t o f o r e , t h i s t e r m has been used as u blind for a lack of know]cdge~ and it is time t h a t we drop it. DR. M I T C I I E L L . - - I f thm'e is such a relationship as h a s been described here, is 'there t r e a t m e n t of t h e t h y n m s t h a t would obviate tilts s u d d e n d e a t h ? DR. I E I N H O I I N . - - N o . l_)l~. M I T C H E L L . - - T h c r e is one question which I am going to ask Dr. B o y d to a n s w e r briefly. P l e a s e .define s t a t u s t h y m i c o l y m p h a t i c u s a c c o r d i n g to its original description. I n the m a i n the term h a s been v e r y badly m i s t r e a t e d , according to P a l t a u f ' s initial definition. DR. B O Y D . - - I am s o r r y I have not reread P a l t a u f ' s d e s c r i p t i o n recently. A s I remember, he described a pale, r u t h ] t i c i n f a n t with p r m n i n e n t l y m p h o i d tissue a n d a n a r r o w e d aorta. T h e n a r r o w e d a o r t a h a s more or less dropped out o f the picture. I have never f o u n d a narrowed aorta. T h e t h y m u s g l a n d s in this condition as described by P a l t a u f were w~thin tile o r d i n a r y r a n g e of those of well-nourished in rants. I)IR. M [ T C I [ E L b . - - T h m ' e is one more ques'tion which h a s been p a s s e d up f r o m the attdienee. P l e a s e explai n the condition in a child who h a s convulsive seizures, a l a r g e t h y m i e shadow a n d w]m, a f t e r x - r a y t r e a t m e n t , h a s no more convulsions. DR. C t I A M B E R L A I N . - - T h e r e is no question b u t t h a t occasionally convulsive seizm.es become less f r e q u e n t a f t e r a h n o s t a n y t h i n g y o u do. Sometimes, however, i m p r o v e m e n t m a y be due to release of back p r e s s u r e on the veins of %he neck. I t h i n k we h a v e seen e n g o r g e m e n t of these veins in conditions other t h a n an enlarged t h y m u s . I t is possible, als% t h a t occasionally t h e seizm'es of i d i o p a t h i c epilepsy are i n c r e a s e d in :frequency b y congestion of ~he v e i n s e f t h e hea.d a n d neck. Such congestion m i g h t possibly be caused by a~ enIarged t h y m u s a n d relieved b y i t s s h r i n k a g e . I t would be v e r y d a n g e r o u s to a t t e m p t a n y scientific explanation. I n some eases t h e r e is a r e d u c t i o n in tile n u m b e r of convulsive seizures a f t e r i r r a d i a t i o n

A~{ERICAN ACADEMY OF PEDIATRICS of the thymusj in others If we irradiate properly~ radiologist ean treat the think something is being

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frequency has been apparently increased after irradiation. we can say that we have not (lone any harm. The competent child and also by doing this treat the anxious parents, who (lone. The pediatrician is helpe.d~ too.

])R. MITCHELL--You take the pediatrician very seriously~ I think. r vulsions" is a symptom of so many things tha"c a combination of a questionably e n l a r g e d t h y m u s s h a d o w a n d convulsions is not a very significant one.

N o w I have no delusions t h a t [ can s u m m a r i z e t h i s discussion to your satisfaction. It is a very difficult situation we have attempted to solve, and 'there are many questions that we have not had time to dilate upon. It appears to be the opinion of this p a n e l t h a t it is proper to say ~chat the t h y m u s g l a n d occasionally causes s y m p t o m s of eompressien. Other causes f o r compression s y m p t o m s m u s t be searched for before the t h y m u s is i n c r i m i n a t e d . I t a p p e a r s also t h a t this p a n e l adm i t t e d t h a t it is possible t h a t certain e n l a r g e m e n t s of t h e m e d i a s t i n a l s t r u c t u r e s can cause s y m p t o m s of compression a~d t h a t radiologie t r e a t m e n t h a s some effect on those s y m p t o m s . This, however, is n o t merely u n c o m m o n b u t rare. Does a n y o n e d i s a g r e e with the f a c t tha% r e g a r d l e s s of t h e r o e n t g e n o g r a m s j t h e t h y m u s m a y oee~sionally cause s y m p t o m s of o b s t r u c t i o n ? I t seems to me t h a t t h a t is w h a t this panel admitted. DR. B O Y D . - - I

w a n t to s a y - - v e r y occasionally.

DR. M I T C H E L L . - - E x t r e m e l y occasionally, i have no r i g h t to a t t e m p t to smnmarize w h a t we said in this panel a b o u t c o n v u l s i o n s - - w e d i d n ' t discuss it suffieien%]y. I m a y s t a t e m y own belief t h a t t h e r e is no proved association of convulsions and thymus. Most of the m e m b e r s of this p a n e l feel t h a t p e r h a p s it m a y be j u s t as well to d i s c a r d t h e t e r m " s t a t u s t h y m i e o l y m p h a t i c u s . ~' W e are sure also tha% even i f the t h y m u s is in a n y w a y related to s u d d e n death, it could only be in a s e c o n d a r y eapacity~ there is no t r e a t m e n t of this o r g a n b y i n j e c t i o n of a n y e x t r a c t of it, b y radiologie t r e a t m e n t , or by e x t i r p a t i o n of it, which woul.d have a n y effect u p o n prev e n t i n g s u d d e n death. Is there a n y d i s a g r e e m e n t with t h a t ~ DR. S P O H N . - - [ do n o t agree entirely. There have been some clinical eases m e n t i o n e d this m o r n i n g where p a t i e n t s in e x t r e m e l y critical state~ a n d e x h i b i t i n g so-called t h y m i e o l y m p l m t i c s y m p t o m s , have appare~ttly b e e n restored by x - r a y t r e a t m e n t over t h e t h y m i c area. No other t r e a t m e n t was of a n y avail in t h e s e casts. P a r t of m y efforts t h i s m o r n i n g have b e e n to a d m o n i s h a g a i n s t ~ %oo unceremm~ious or p r e c i p i t o u s b u r i a l of the s t a t u s t h y l n i e o l y m p h a t i e u s s y n d r o m e . B u r i a l is n o t a sufficient answer to such a v e x i n g a n d u n s a t i s f a c t o r i l y explained condition. I f it is to be locked b e h i n d medical doors, it may, like t h e ghost in Hamlet~ a p p e a r on m o s t i n o p p o r t u n e occasions to t o r m e n t our medical consciences. DR. M I T C H E L L . - - T h e r e h a s b e e n a n opinion expressed "also b y Dr. Spolm t h a t there is some t y p e of relationship between the t h y r o i d gland a n d the t h y m u s . J u s t exaetly w h a t t h a t meatus to the clinician t o d a y is m)t p a r t i c u l a r l y clear, nor does it lead to a n y specific idea of trea'tment~ t h a t is, unless w h a t ])r. S p o h n h a s said sugg e s t s t h e a d m i n i s t r a t i o n of iodine~ which, a c t i n g on the thyroid, would have a secondary effect on t h e t h y m u s . I t h i n k it can be a s s m n e d t h a t whatever k n o w l e d g e we have g a i n e d e x p e r i m e n t a l l y concerning t h e f u n c t i o n s of 'the t h y m u s is n o t applicable in elinic, aI m e d i c i n e today. W e have agreed tidal g r e a t c a u t i o n is n e c e s s a r y before s t a t i n g t h a t t h e roentgenog r a m shows t h y m n s e n l a r g e m e n t . L a t e r a l p l a t e s are p e r h a p s b e t t e r t h a n anteropos%erler ones. T h e r e c e r t a i n l y is no r e l a t i o n b e t w e e n t h e size of t h e t h y m u s g l a n d a~d s u d d e n death. I do n o t believe t h a t I have a n y r i g h t to a t t e m p t a n y other t y p e of s u m m a r y of the opbLions of t h i s panel. A. Gt~AE~{E ~IITCHELL,M.D.