Paper - Some observations on the thymus in early infancy (1930)

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Shannon EH. Some observations on the thymus in early infancy. (1930) Can. Med. Assoc. J : 775-785.

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This historic 1930 paper by Shannon describes the postnatal thymus development.



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Some Observations on the Thymus in Early Infancy

By E. H. SHannon, M.B., D.Rap.,

Radiologist, St. Michael’s Hospital, Toronto


In the year 1928 we examined radiographically the chests of 100 infants, born in the Maternity Department of St. Michael’s Hospital, with reference to the thymus gland. Our object was to determine the limits of variation in the thymus-chest. ratio of the normal infant, so that we might, if possible, be able to infer with greater accuracy the presence or absence of symptoms from the appearance of the thymus shadow on an x-ray plate. This study of the normal was amplified in 1929 by a second series of 119 cases, 33 of which were rayed on two or mere occasions, to determine any variation in the size of the thymus occurring in the first few days of post- natal life.


The voluminous literature was reviewed and despite the acknowledged confusion on the subject, certain items appeared to be held in more or less common agreement. It is for the purpose of erystallizing the available information and of adding to it the small amount of data we have gathered that this article is written.


Gross Anatomy

The thymus is situated in the anterior mediastinum in contact with the sternum in front, while posteriorly it lies on the right auricle and may touch the esophagus and the trachea at its bifureation. It is in elose relationship to the vagus, recurrent laryngeal and phrenic nerves, and is adherent to the left innominate vein. Its capsule is usually attached to the pericardium posteriorly. It derives its arterial supply chiefly from the internal mammaries, with branches from the pericardial vessels, and has a free lymphatic drainage to the retro-sternal lymph nodes. Its average weight at. birth, according to Hammar, is 15 grm. The -figures given by various authors however, vary considerably.


Grossly, the organ is more or less bilaterally symmetrical, presenting usually two equal lobes, subdivided into lobules. It is encased ina capsule which dips in between the lobules and is composed of cortex and medulla. Not infrequently —in about 20 per cent. of cases — the gland is either unilobed or trilobed. In about 10 per cent of cases it is conglomerate. (Noback). These varieties, according to Piersol, merely indicate variations of the fibrous septa.

Histology

The cortex is rich in lymphocytes, while in » the medulla, in a rather loose cell network, a lymphoid type of cell is found, forming the characteristic Hassall’s corpuscles. In the opinion of Hammar, these corpuscles are derived from the reticular cells of the medulla and are consequently of epithelial origin. Crotti observes that mitotic figures are seen in the cells of the cortical substance in old age, which would indicate a continuance of function even at that: stage of life. The vascular supply is rich, and engorgement of the vessels may at times contribute to the enlargement of the gland. The capillary network has little supporting tissue in and about the individual lobules so that. hemorrhages readily occur.

Involution. — Hoskins notes that, relative to the general body weight, the thymus is seven times larger at birth than at. puberty, an observation which would point to a definite and important function of the gland in the infant. It increases in weight, according to Cretti, during the period of growth, attaining a maximum size at puberty. It then undergoes involution but never entirely disappears. Some observers have reported an increase in weight occurring after puberty, probably due to an increase of connective tissue and fat deposition.


The weight of the gland at birth, according to Hammar, averages 15 grm., increasing to 35 grm. at puberty, and returning again to 15 grm. by the age of fifty. More recent-work done by Scammon has served to corroborate Hammar’s results, Seammon’s figures being 14 grm. at birth, 32 grm. at puberty, decreasing with age.


He has also shown a parallelism of growth of the thymus and mesenteric lymph nodes, coneluding that, as indicated by weight, the thymus acts as a lymphoid organ.


It has long been accepted that the thymus undergoes a post-puberty involution, but, as Hammar and Hoskins both point out, the relative weights in the child and adult have been based on estimates made from autopsy specimens taken from patients who have died of. wasting diseases which of themselves produce atrophic changes in the gland.


Function

Passing from theory to theory the last analysis yields only a filtrate of uncertainty as to the function of the thymus gland. The well-known experiments of Park and McClure on the effect of extirpation of the thymus in young dogs re “sulted in a doubt as to whether there was any definite effect that was due directly to removal of the gland. No indication of abnormality in the skeletal structures was: noted, no ten dency to developmental changes in musculature, strength, activity or intelligence, no change in hair or teeth; nor were they of the opinion that any effect was produced on the glands of internal secretion. The authors conclude that the thymus in the dog is not necessary to life. The slight changes reported, such as the retardation or diminished growth of the skeleton, slight hyperplasia of thyroid, hypertrophy of supra . renals and retarded development of testes, they believe to be due to various factors coincident. with the severity of the operation performed on the animals and their subsequent confinement. Hammar’s experiments on extirpation of the thymus in frogs and Pappenheimer’s on young rats produced no constantly demonstrable physiological or pathological changes. Soli’s isolated observation on thymus extirpation in pullets is of interest in view of the possible réle played by the thymus in calcium metabolism. It happened at. intervals that the birds would lay eggs without shells or with very thin shells, indicating a relationship in birds between the thymus and ova.


Extracts of thymus were reported by Swale Vincent to result in no specific action. A depressor effect noted by him and other workers is thought to be similar to that following injection of many organ extracts. Injection of thymus extract has been found to cause convulsions.


Feeding experiments conducted by Gudersnatch on tadpoles were thought to produce an increase in their rate of growth and to have delayed their metamorphosis. Uhlenhuth points — out that the effect is not obtained if normal food is added to the diet, and attributes the result to improper feeding.


Henderson believes that castration in cattle causes a persistent growth and a retarded atrophy of the thymus, and thinks there is a similar effect in guinea pigs and rabbits. Crotti, in summing up experimental evidence, says: ‘All these observations and experiments seem to convey the conclusion that an antagonism exists between the genital system and the thymus.’’ It has frequently been noted that in children with incompletely developed genitalia, involution of the thymus occurs at an earlier date. Hoskins on the other hand concludes that the literature affords little or no reliable evidence of any true endocrine function of the thymus. He believes that it takes part in the physiological and pathological processes of the body only by virtue of its lymphoid character, which, is concerned with the bodily defense against infection. It appears that the production of leucocytes is undoubtedly a function, possibly the chief function, of the thymus gland.


Various workers are at, present investigating the possibility of a relationship between the varying number of Hassall’s corpuscles noted in the thymus and pathological processes apparently associated with the gland.

Pathology

As mentioned previously, the thymus is rich in vascular supply with a loose supporting connective tissue network. As a consequence, hemorrhages are prone to occur, usually small and petechial in character, occasionally as large effusions, either circumscribed or diffused throughout the gland. Pathological studies show that petechial hemorrhages occur very frequently in still-born children as a result of asphyxia. The hemorrhages in these cases are usually subcapsular. A similar finding is noted frequently after difficult labours and after autoinfections. To these gross hemorrhages Friedelben has applied the term ‘‘thymus apoplexy.”’ It seems possible for rapid enlargement of the gland from hemorrhage to cause sudden death from pressure, and in a series of 13 cases collected from ‘the literature by Wahl and Walthall sudden death occurred in seven. Such a cause must certainly be an inconspicuous factor in the production of thymic death. It should also be noted that, of the 13 cases mentioned, hereditary syphilis was definitely diagnosed, in seven.


The effect of acute infections and wasting diseases is to produce a definite diminution in size. Arguing the converse, it has been stated, probably somewhat illogically, that. the largest thymi are found in the healthiest children. (Morse) .


Anatomical studies, such as those conducted by Noback, demonstrate that the thymus is forced back into the mediastinum by the expanding lungs, laterally and inferiorly around the heart, so that projections from the gland often extend backward to the trachea and vertebral column and in exceptional cases, downward to the diaphragm. It, is evident from the material collected by Noback that when displaced sufficiently far posteriorly, the gland may cause symptoms from pressure on the recurrent laryngeal nerve or other mediastinal structures. He found definite post-mortem evidence of tracheal and even of esophageal compression, and evidently associates compression in these cases with the result of moulding by respiration.

In support of this observation Boyd notes that most children do not develop thymic symptoms till from one month to six weeks of age, and further that these children often exhibit, together with expiratory stridor, a sort of crowing cry comparable with the brassy cough of aortic aneurysm, and probably due to pressure on the recurrent laryngeal nerve. Keeping in mind the fact that our observations in a general hospital have been practically confined to the newborn, the former statement is not in accordance with our experience, though we have no means of estimating the relative frequency of symptoms accompanying thymic enlargement in the newborn as compared with later infancy. As will be mentioned later, we have shown that moulding is usually almost completed in the first few days of post-natal life.

Symptomatology

Breath-holding spasms are of frequent occurrence, and have been found by many to occupy the most conspicuous réle in the symptomatology. These attacks are usually occasioned by erying, the child suddenly holding its breath with development of cyanosis. The infant may then become perfectly limp and may show a transient loss of consciousness.


‘been termed ‘‘thymic stridor.’’


Dyspnea, constant or intermittent, may occur in varying severity, with or without cyanosis, and may result in violent choking spells. Associated with these symptoms there is sometimes a crowing type of respiratory sound which has There is also at times the peculiar cry mentioned above, which has been compared with the brassy cough of aortic aneurysm. Between attacks respiration may be normal or stridor may persist. Hyperextension of the head or a position of dorsal decubitus aggravates the dyspnea. This is probably due to the combined action of the thyrothymic ligament in elevating the thymus and to the narrowing of the upper thoracic inlet which also occurs on hyperextending the head, causing pressure by the thymus on the incompletely developed and therefore easily compressible tracheal rings of the infant. or young child. The choking’ spells usually last but a few minutes but may endure for a considerably longer period. In rare instances the child has been known to die, but as a rule the spell subsides, respiration becomes normal, dyspncea becomes less and an interval occurs before the next seizure.

Morgan, Rolph, and Brown have called attention to certain symptoms, which they have found associated with large thymuses, viz., noisy nasal breathing, hoarse cough, attacks of syncope, restlessness and sleeplessness. They consider the method of production of these symptoms to be vagal stimulation due to pressure.

Convulsions occur at times, though this cannot In our experience be considered a characteristic or constant feature of the disease. A short preliminary tonic spasm of the muscles of the body may more often precede the attacks of pallor and relaxation previously mentioned.

It seems highly probable that certain instances of asphyxia of the newborn are directly due to large thymuses. Respiration in these cases is usually difficult to initiate and continues irregular. Cyanosis is marked and persistent. In many instances death ensues from respiratory failure. within the first day. Such a case was on one occasion kept alive for over an hour in the x-ray laboratory by artificial respiration. Breathing would be resumed after an interval of manipulation, with marked effort, calling into play the accessory muscles of respiration. Death oceurred about four hours after birth. Radiographic examination revealed a markedly large thymus gland. An autopsy was not obtained.


When one recalls that the superior thoracic inlet in infants measures only from two to three centimetres it will probably be admitted that sufficient pressure might be exerted on the trachea to produce compression and death in this-way. It is to the upper inlet, the ‘‘critical space of Grawitz,’’ to which the thymus is pulled on hyperextension of the head, with resulting aggravation of dyspnea, in cases exhibiting symptoms caused by a large thymus.

A diverse type, with which this paper does not deal, is seen in the older apparently healthy infant who suddenly becomes cyanotic, with well marked dyspnea and stridor. After a few minutes the muscles relax, the face becomes pallid, lips livid, pupils enlarge and the child presents a picture of profound shock which may go on to death. - Probably one of the most convincing statements, yet issued in favour of the mechanical theory of the cause of death is that of Chevalier Jackson whose observation, being on the living child, is doubly valuable: ‘‘On passing one of my bronchoscopes I discovered a scabbard trachea with a chink not over 2 mm. on inspiration and 1 mm. on expiration, the obstruction extending from the second to the fourth rib. The tracheal muscle was collapsed from before backward almost into contact.’’ Permanent relief in this case followed thymectomy.

Cause Of Symptoms, Etc.

Despite the foregoing it is nevertheless undoubtedly true that all cases of sudden death in infancy are not due to the thymus, and it is highly probable that a fairly large percentage of deaths in which the gland is thought to be implicated do not at least result from tracheostenosis. The opinion is gaining ground that the so-called ‘‘thymic death”’ or even the term ‘‘thymie syndrome,’’ is undoubtedly translated too loosely to cover a number of varied conditions. It has however been the experience of every radiologist to note after radiation therapy such a consistent and marked improvement in children exhibiting the symptoms outlined above, with or without radiographic evidence of large thymus, that one is impelled to the conclusion that, since radiation of the gland relieves these symptoms, a disarrangement of its function or an enlargement of its size must be responsible for their production. It seems also possible that, as frequently suggested, a toxic substance of thymus manufacture may, when associated with some type of trauma due possibly to infection or anesthesia, result in collapse and death. Pappenheimer’s reference to the marked disintegration of nuclear material as evidenced by the thymus probably pointed the way to Symmers’ theory of anaphylaxis which, however, more recent experiments in sensitization have failed to confirm. Symmers holds that necrosis occurring in large numbers of germinal follicles in the lymph nodes results in the sensitization of the body by a specific nucleoprotein, and when, at a suitable period, the tissues are again ‘subjected to the action of the same type of protein derived from nuclear breakdown in the same sort of tissue the anaphylactic reaction is completed.


In addition to the mechanical, endocrine and anaphylactic theories, the production of symptoms is by some attributed to other factors, such as sudden swelling of the gland due to engorgement with blood; laryngo-tracheal reflex; vessel rupture in the substance of the thymus. With the exception of the mechanical and endocrine theories, all have been practically discarded. Wahl and Walthall, while admitting the possibility, of large hemorrhages of diffuse or localized type due to the small amount of connective tissue supporting the capillary network in and about the lobules, consider it questionable whether death results from rapid enlargement of the thymus from that cause. A few. such cases have been reported, mostly in syphilitic infants, following on the hyperemia associated. with simple hyperplasia, the pathological specimen presenting the appearance of a hemorrhagic infarct. Cases of this nature are undoubtedly rare.

It is of course understood that thymic enlargement may exist as an entity, without associated changes of the general lymphatic structures of the body and arterial hypoplasia, commonly referred to as status lymphaticus, with which this paper is not meant to deal in detail. In this connection the recent observation (Boyd) that the condition described by Paltauf as status lymphaticus represents the normal thymic and Iymphoid tissue of the well nourished child, affords at least a fair example of the present state of flux of medical opinion on this matter. Symmers, describing a series of 118 cases of status lymphaticus, states that the thymus was hyperplastic in every instance, which would argue that the finding of a large thymus shadow radiographically should suggest the presence of status lymphaticus and contraindicate surgical procedures though other features of the disease were absent.

It may be stated here that it is our experience that, associated with thymic enlargement, certain pulmonary complications may occur, namely, pneumonia and atelectasis. The former is frequently an accidental occurrence and may result from long second stage labours with premature rupture of the membranes. Its typical clinical and roentgenographic appearance is not often subject to misinterpretation. Atelectasis, on the other hand, is more difficult. of detection both clinically and radiographically, and is not infrequently associated with, and is presumably a direct result of large thymus, the presence of which is sufficient to prevent expansion of large or small areas in the parenchyma of the lung. It seems beside the question whether death in these cases results, as has been reported (Cortelle), from atelectasis or from some other mechanism of thymic origin.


Technique of Radiography

The child is placed prone on the cassette at. a focal skin distance of 30 inches, using 30 M.A., 80 K.V., and 14 second exposure. In each case care must be taken to accurately centre the target over the thymus, as it has been found that even small variations of the angle of the incident rays produce distortion of sufficient magnitude to destroy the value of comparative measurements. Even a slight lateral deviation of the tube has the effect of shifting the central shadow toward the opposite side, producing an effect simulating enlargement of one or other lobe. A shift in the sagittal plane is of lesser importance but tends to produce an obliquity of the costal shadows point on the lateral chest wall sufficient to render accurate measurements more difficult, and comparative estimations at times impossible, more particularly where a series of plates is made of a given case and a variation of even a few millimeters is of importance. A point one inch below the sternal notch was chosen as a routine in our series, and films were excluded in which the technique was not beyond question. A three-inch cone, ten inches long, was employed. As an impulse timer was not used, slight variation in film density resulted but this was not sufficient to be a factor of importance in measurement.

THE AVERAGE THYMUS SHADOW

In 1928 a consecutive series of 100 children born in our maternity department was studied, and from the series were excluded prematures and all cases presenting symptoms referable to the thymus. Of the remainder, 74 cases, accurate measurements were made.

On account of slight variations in the obliquity of the ribs, even in normal cases, measurements were made at the level of the third thoracic vertebra rather than at any fixed Measurements were made of the total transverse diameter of the gland and of the external diameter of the chest at the same level and a ratio established between the two. Unilateral enlargement of a lobe provides a weak point in the clinical application of measurements taken in this way, as we have at times seen a large lobe on-one or other side, while the total transverse diameter of the thymus was within normal limits. Oceasionally, also, the gland may be widest above or below the third dorsal vertebra. Antero-posterior films have not in our experience been found of practical value, on account of technical difficulties, though claims of merit have been attached to them by others.

The smallest thymus found in the series of a full term infant measured 2.2 cm., the largest 5.4 em., the average of all cases being 3.2 em. Prematures, as mentioned above, were excluded from the series, comprising a separate group of twenty-two cases. The smallest of this group was 2.2 em., the largest, 4.7 em., the average, 3.4 cm. The average period of prematurity was 2.25 weeks.

The ratio of thymus to chest in the full time child was as 1:2.2, (1:2.18) in the premature group as 1:2.1.

In 1929 a second series was studied, comprising 119 cases. Measurements were made in the same manner as in the first series. Of this group 76 cases were under one day old, the remainder, 43 cases, over two days, and averaging less than four days old.

The average transverse diameter of the thymus for the entire group of 119 cases was 3.44 em., the thymus chest ratio being 1:2.1 (1:2.08). These figures check fairly well with the results from the previous series, but are probably somewhat more accurate on account of improved technique.


Further estimations were carried out in a similar way on a group of 50 consecutive cases referred to us for radiographic examination or treatment with more or less definite symptoms pointing to thymic enlargement. The age average was about the same as in our series of normals. It is of interest to note that the largest gland in the full time child in this group measured only 4.6 cem., as compared with 5.4 em in the normals, the smallest 2.4 em., as compared with 2.2 em., the average being 3.4 em., as in our series for the normal. The thymus chest ratio in this group was only slightly greater than in the normal, being 1:2.07. It would, therefore, seem that the presence of a large thymus shadow on the x-ray plate has no direct or definite interpretation in terms of pathology or clinical symptoms, and that therefore clinical manifestations should be the sole index as to the advisability of treatment. While the discrepancy between the size of the gland and production of symptoms favours the endocrine theory of thymic disease, those who uphold the mechanical theory offer the obvious and irrefutable argument that where an apparently small gland appears to produce symptoms, there actually exists antero-posterior enlargement not demonstrable in the roentgenogram.


From a study of the cases in these two series we are of the opinion that the word ‘‘enlarged’’ as applied to the thymus in early infancy should not be employed as a radiographic diagnosis, as it carries with it. what we believe is often an erroneous impression of disease, due to its significance as applied to the heart and other organs. The presence of disease of the thymus can be determined with aceuracy only by the clinician.


It would appear preferable that the radiologist report whether the gland is large or small, with a statement as to whether it is or is not above the average as to its ratio with the external diameter of the chest at a given point. The point suggested is the level of the third dorsal vertebra. The external diameter of the chest is chosen as being more readily measured with accuracy than the internal. The slight error introduced by varying thicknesses of the chest wall is negligible.

It is our opinion that a roentgenogram of the thymus in early infancy has a very limited diagnostic value, unless we are to regard all large thymuses as pathological, and we believe that such is not the case. Roentgenograms are chiefly of service when they confirm an indefinite clinical diagnosis of large thymus or in checking the reduction of the gland in cases where symptoms of thymic origin are present, the disappearance of symptoms being usually found coincident with reduction of size. X-rays are also of value in such cases as show recurrence of symptoms after a varying interval, associated with re-enlargement of the thymus. In about 10 per cent of our treated cases this has occurred, and it is of interest to observe that, in this group, reduction of the size of the gland is repeatedly accompanied by disappearance of symptoms. We have seen several cases in which the thymus has twice enlarged after reduction had been effected by radiation.


The Effect of Respiration

To determine whether, as was indicated by the dissections of Noback, the thymus is moulded by the lungs in respiration, studies were carried out on a series of thirty-three newborns. These were not consecutive births, eases showing glands of 3.0 em. or more in diameter being chosen as most likely to undergo moulding. Films were at first made in the delivery room immediately after birth and again in from two to seven days. Later it was found that very little change occurred in the first few hours of post-natal life, and the radiograms were then routinely made in the x-ray department as soon after birth as convenient. In the majority of instances changes in the transverse diameter of the thymus were observed. The average size of the thymus in this group within five hours of birth, was 3.7 em., the average June 1930]

size measured three and a half days later was found to be 3.15 em., a diminution of 0.55 em. A few observations made at later periods would indicate that there is comparatively little further diminution in size after the third or fourth day. The greatest decrease in diameter noted was from 3.8 to 2.6 em., within three days. The size of the thymus at birth is no index as to its subsequent behaviour, although the change noted in small glands is less striking. A gland large at birth may remain so, or may recede to well within average limits. It is highly probable that in some cases this natural moulding or reduction in size of the thymus has been wrongly attributed to the effect of radiation. .

The practical conclusion to be drawn from this series of cases is that a diminution in the size of the thymus shadow may be anticipated within the first few days of post-natal life, and that, therefore, the radiographic examination of the thymus in the newborn should be delayed, unless urgently indicated until the third or fourth day after birth. |.

In view of this finding our two series of normal cases were re-examined and the thymuschest ratio calculated for 73 infants, of three to seven days of age. This ratio was found to he 1:2.5. This we have established as the average ratio of thymus to chest in the normal infant of three days or older, when measured at the level of the third dorsal vertebra.

One would expect that if this decrease in the lateral diameter of the thymus were due to simple moulding and were not accompanied by actual decrease in volume that, as the anteroposterior diameter would inevitably be increased, pressure symptoms would appear in certain cases, or undergo exaggeration if already present. So far as our limited observations can be relied upon, the reverse is true, and such symptoms as stridor, noisy respiration and cyanosis are more frequently relieved after the first few days following birth. This would argue against the theory of the origin of symptoms from pressure in these cases, or else would indicate an actual decrease in the total volume of the gland during the first few days of postnatal life.

The literature affords no reference to this subject from a radiographic standpoint. The dissections of the thymus in the fetus and newborn, performed by Noback, showed that an extension of the thymus in the posterior direction was present in 7 per cent of the individuals studied, surrounding in some cases the innominate and superior caval veins, at times causing pressure on the aortic arch and innominate artery. Noback believes that compression of the thymus by the lungs may occur in the first half hour of life- and continues for about two weeks. While it is probable that moulding actually does begin immediately on initiation of respiration, we have rarely been able to measure an appreciable degree of change in the transverse diameter in that time. After three or four days we have observed very little subsequent change in the thymus shadow.

It occasionally happens that radiograms made to show the thymus uncover other information of value to the clinician. In the course of these studies a-small number of cases were found which exhibited other pathological processes, included in which were one case of congenital heart disease, four of moderate atelectasis, two of bronchopneumonia and one case of congenital diaphragmatic hernia. Minute areas of atelectasis are of fairly frequent occurrence in the newborn, as shown by post-mortem examination,

pec / fa te


Autopsy specimen from case quoted in text, showing a cervico-thoracie type of thymus with two thick tongue-like processes reaching the inferior border of the thyroid.


but only areas of size sufficient to produce clinical signs and symptoms are in general demonstrable in a radiogram. The relationship of atelectasis to large thymus has been noted above. In the newborn we have. occasionally observed consolidation of one or both bases with coincident atelectasis of the upper portion of the lungs. This may be only a chance relationship or may result from tracheostenosis. In this connection the following case is of interest:

A male child, delivered of an easy labour, premature, 8 mos., weight 5 lbs. 4 oz., was referred for examination of the thymus. Respiration had been started with difficulty. Cyanosis was deep, but cleared up in a few hours, recurring at intervals for short periods. A peculiar high pitched note accompanied inspiration. The temperature at no time during the child’s illness rose above 98.3°. A slight convulsive attack occurred ten hours after birth. Physical examination also roused suspicions of actelectasis in the upper lobes. The bases were clear, breath sounds normal. When brought to the x-ray department the child was held in the arms and the head hyperextended. Cyanosis became deep and breathing promptly ceased and was restored only by artificial respiration. Radiograms showed the thymus shadow to be larger than the average, the thymus chest ratio being 1:1.6 There were minute areas in both uppers thought to be due to atelectasis. Radiation treatment was promptly administered. After a few hours improvement in breathing and colour were evident and the child became practically symptom free for twelve hours. Cyanosis then returned, respirations increased and death occurred on the third day. At autopsy pneumonic consolidation of both lower lobes was found. Minute areas of atelectasis were present in both uppers. The thymus was relatively large and presented two thick tongue-like processes, extending upward along the trachea through the superior thoracic inlet to the lower border of the thyroid gland.



CasE 1.—No. 1.—Baby A.—Age 3 hours. The transverse diameter of the thymus at the level of the third dorsal vertebra measures 3.8 cm.



CasE 2.—No. 1.—Baby W.—Age 5 hours. transverse diameter of the thymus measures 4 em.


The immediate cause of death in this case was evidently a pneumonia which developed apparently during the second day. The réle played by the thymus is thereby obscured, but it is certain that the cervico-thoracic type of gland found at autopsy lent colour to the clinical picture of large thymus. In the newborn the cervico-thoracic type has been reported in over 80 per cent of cases (Noback). It is possible that under aeration from tracheostenosis was the initial factor in the production of the pneumonic process observed in this instance.



Case 1—No. 2—Baby A—Age 3 days. The transverse diameter of the thymus at the level of the third dorsal has decreased to 2.6 cm., a diminution of 1.2 em.




CASE 2.—No. 2.—Baby W.—Age 6 days. The transverse diameter of the thymus shows a decrease to 3.6 cm., a difference of 0.4 cm. June 1930] SHANNON :


RADIOGRAPHIC DIAGNOSIS

There is comparatively little difficulty attending the recognition of the thymus shadow in plates of the infant chest. The so-called pedicle type, in which the thymus shadow merges with that of the heart, may be missed or interpreted as due to cardiac enlargement. The superior vena cava is. said at times to complicate the picture by causing broadening of the median shadow to the right, especially in young infants, during crying or struggling. We have experienced no difficulty in this way. Atelectasis is usually easily recognized. Enlarged mediastinal glands are not encountered in very young infants and in older children cast a shadow easily differentiated from that of the thymus. In this connection an observation by Mosher, MacMillan, and Motley is worthy of note. In a series of 90 children examined in the Peabody Home for Crippled Children, a tuberculosis sanatorium, only 7 per cent showed a broad mediastinal shadow. A series of routine examinations conducted by the same authors elsewhere established 7 per cent as their average incidence of enlarged thymus, by which they mean a gland larger than the vertebra lying behind it. The children in their series ranged from a few months to 16 years of age.






CAsE 3.—No. 1.—Baby M.—Age 5 hours. The transtransverse diameter of the thymus is 3.9 em.



. CASE 4.—No. 1.—Baby N.—Age 10 hours. The diameter of the thymus is 3.4 em.





CasE 3.—No. 2.—Baby M.—Age 3 days. The transverse diameter of the thymus has diminished to 2.6 cm.



Case 4.—No. 2.—Baby N.—Age 4 days. meter of the thymus has decreased to 2.6 em.


TREATMENT

The actual technique of radiation does not materially matter so long as it is efficient in reducing the size of the thymus and is not unnecessarily heavy. The field should be as restricted as possible, in order to avoid injury to the surrounding lung tissue, though positive evidence of any such untoward reaction resulting from radiation of the thymus has never, we believe, been produced. ,

We have found it convenient to tape to the skin a small protective rubber with cut-out aperture, with a cradle-like rest to support additional protective material. We employ a target skin distance of 10 inches at 90 K.V., 5 M.A., using a filtration of 4 M.M. aluminum. Treatments are given alternately anteriorly and posteriorly over the chest for four doses, at weekly intervals. In one month plates are made and the thymus, in about 90 per cent of eases, is sufficiently reduced in size to make further treatment unnecessary.

It has been our experience, in common with that of many observers, to note a marked improvement in symptoms even a few hours following radiation, though decrease in the size of the gland may not be measurable for days, a fact difficult to explain on the basis of the pressure theory of symptom production. Our records show some cases requiring two or even three series of treatments.

In a small percentage of cases the gland has become large again after having been reduced in size by radiation and further treatment has usually been again successful in controlling this regeneration. As a rule, irrespective of the size of the thymus, radiation has been continued till symptoms have disappeared or have been modified to a satisfactory degree from the standpoint of the clinician. We do not hesitate to treat a thymus well within normal limits as to size, for, as has been frequently mentioned, we are not certain that symptoms may not result from a dysfunction of some type, or from antero-posterior enlargement not demon strable radiographically. In either case radiation is justifiable. Moreover, the radiation of itself constitutes a therapeutic test, and we may, I believe, conclude definitely that if symptoms do not clear up after adequate treatment by radiation the thymus gland is not the causative factor in their production.

Late Results of Treatment

Barnes, in a recent article, has carefully analyzed the result of treatment in a group of 63 children who had received fairly heavy radiation for definitely ‘‘enlarged’’ thymus from three and a half to eight years previously. He reports that the study of this group of cases ‘‘fails to demonstrate any constant deviation from normal, in either the physical or mental spheres, which might be attributed to the treatment.’’ A survey of this kind has not been made by us, but is entirely in accord with our own experience.

Conclusions

1. Examination of 119 infants of varying ages, 76 of whom were under one day, 43 averaging slightly under 4 days old, showed a thymus chest ratio of 1:2.08, the ratio being between the transverse diameter of the thymus at the level of the third dorsal vertebra and the external transverse diameter of the chest at the same level.

2. Fifty infants of about the same average age, referred with clinical signs of thymic disease, showed a thymus chest ratio of 1:2.07.

3. Therefore we believe, that the presence of a large thymus shadow on the x-ray plate has no direet interpretation in terms of disease or clinical symptoms, and that clinical manifestations should be the sole index as to the advisability of treatment.

4. A study of 33 infants whose thymuses at. birth measured 3 cm. or more showed an average diminution in the transverse diameter of the gland of 0.55 ecm. in the first three and a half days of post-natal life. The most marked decrease in size observed was from 3.8 to 2.6 cm., within three days of birth.

5. Therefore the radiographic examination of the thymus in the newborn should be delayed, unless urgent symptoms are present, until the third or fourth day after birth.

6. A study of the chest films of 73 infants of from three to seven days of age, showed a thymus chest ratio of 1.2.5. This we believe to be the average in the normal infant over three days of age. We wish to emphasize, however, that the knowledge of this ratio is of very limited diagnostic value.

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Cite this page: Hill, M.A. (2020, March 28) Embryology Paper - Some observations on the thymus in early infancy (1930). Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Paper_-_Some_observations_on_the_thymus_in_early_infancy_(1930)

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