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Benefits of Thymus Irradiation:   Delusion or Reality?

Part 1.   The Pancoast "Imperative" of 1930:   Diagnostic Fluoroscopy

          Professor Henry Pancoast, another of the grand men of roentgenology, entered this entire fray, particularly with respect to the question of an adequate examination of the chest in seeking a diagnosis in suspected cases of enlarged thymus. Dr. Pancoast laid out the criteria for an adequate roentgenologic examination. His recommendations meant a large radiation dose to the chest and breasts, due to extensive use of fluoroscopy (examination of the patient while the x-ray beam is still "on"). We quote Dr. Pancoast in 1930 (at pages 747-748):

          "Every roentgenologic investigation of the respiratory tract in infancy and early childhood for any purpose should include a collective study of the nasopharynx, oropharynx, the neck, and the chest. Thymic cases are obviously referred for examination because of obstructive symptoms, and experience has taught us that obstructions anywhere in the upper passages may produce phenomena simulating those due to thymic enlargement." And (p.748):

          "A preliminary fluoroscopic study is always imperative." And:   "At any rate, the patients must be fluoroscoped in both the sagittal [front to back], and lateral directions. The neck must be included with the chest. The observer's eyes must be well accommodated before beginning fluoroscopy, and in emergency cases one must wait until the proper time arrives for perfect vision. The child must be crying in a regular manner, or at least, deductions must be based upon such crying, and not on sobbing or irregular or jerky respirations. One looks, of course, for any obviously intrathoracic lesions. The movements of the diaphragm domes must be carefully observed and the relations of the mediastinal shadows to these and any abnormalities at the two phases of respiration carefully noted. One should carefully observe the appearances of the pharynx, larynx and trachea and their relations, especially during the two respiratory phases."

          And, of course, Dr. Pancoast wanted a number of roentgenographic exposures (x-ray photographs), both lateral and sagittal.

          For the purposes of our study, we must take careful note of the fact that these Pancoast recommendations made the radiation dose to the child at least 10 times the dose from actual roentgen films, and it could be a much higher ratio than 10 between the fluoroscopy and the roentgenograms. This will weigh heavily in our assessment of radiation doses to infants and children.

          First of all, it can be commented that Dr. Pancoast was a man of very high repute, and his recommendations for technic were likely to be adopted by the best radiologists. Yet when we consider the comments of Dr. Leddy (1934) about fluoroscopists at the Mayo Clinic counting on speed ("celerity") to keep the radiation dose down, we wonder about doses to doctor and patient in those attempting to follow the Pancoast recommendations in cases of possible thymus enlargement.

          One might even wonder if a harried, not-too-competent fluoroscopist --- intimidated by the complexity of the Pancoast requirements --- might take the easy way out and simply give thymus therapy without even attempting the rigorous Pancoast technic. After all, there were all kinds of authorities (we have named some and shall name others) who attested to the "harmlessness" of a few hundred roentgens. And there were recommendations of a "therapeutic trial."

Part 2.   "Thymus Phobia":   Public Concern over Sudden Death in Infants

          We think the practice of medicine, especially with children, was not easy in the first half and more of the 20th century. The phenomenon of sudden infant death without explanation (which is still with us, as this century draws to a close) is no small matter. Families were terrified on hearing of sudden deaths with anesthesia, and of sudden deaths with what seemed to be nothing at all going on adverse to the child's health. Necessarily, that spilled over into physician practice, with justifiable concern over both the tragedy of losing a patient seemingly well and the jeopardy of lawsuits for negligence. So, when the public was "thymus conscious" as a part of the general fear of the sudden infant death syndrome, it was quite trying for physician and families.

          This situation helps account for the following kinds of comments from two physicians at a major medical center ---- 37 years after Lange's initial recommendations in 1911 for action.

          In 1948, Conti and Patton wrote the following about therapeutic treatment of some cases, for the purpose of alleviating the parents' worry (p.892):

          "Diagnostic roentgenograms offer some reassurance to patients who are thymus conscious. This is not an undesirable effect. The alleviation of anxiety is a commendable medical achievement." And:   "The obstetrician or pediatrician should accede to the wishes of parents who want neonatal roentgenograms of their children. It might even be wise to administer therapeutic dosage over the thymus. Whatever assurance is gained by this apparently harmless and perhaps beneficial procedure will aid in alleviating an anxiety which occasionally becomes a thymus phobia."

          And the breast dose grows. And the breast dose grew in another way. Why wait for cyanosis, stridor, anxiety of parents? It became a practice in some hospitals to do roentgenograms in the nursery on every consecutive child to try to detect asymptomatic thymus enlargement, and if found, to treat such "enlargement" with therapeutic radiation. For example:  

          The non-believers stated that they had never observed the findings of enlarged thymus and had never seen any favorable results. Their position was largely that the reason why sudden death victims might tend to have larger thymus glands than those who died after a lingering illness is that thymus glands shrink markedly in lingering illnesses. Boyd (1932) did a large number of measurements and sponsored this point of view.

          The believers continued to find excellent results in their diagnosis and therapy of enlarged thymus glands. They claimed success rates at the 90 % level and were adamantly in favor of the diagnosis and treatment of thymic enlargement.

          It is indicative of the tenor of the times to examine what the textbooks are saying. Textbooks can be very wrong on many issues. Nonetheless, there is generally widespread support for a diagnostic or therapeutic approach when the textbooks "glow" about an issue in medical management.

The Work and Position of C. Winfield Perkins in the 1920s. Perkins (1925).

          Let us listen to some of his comments (1925 p.216):

          "The modern indiscriminate method of operating on children of all ages for adenoids and tonsils without preliminary roentgen-ray exploration of the chest for possible enlarged thymus and other chest pathology seems to be unwarranted. How frequently we hear of a sudden death of a child, either in a physician's office or in a hospital during an operation or even several days after operative procedure, the death having occurred without known cause in an apparently healthy child. Post mortem examination reveals an enlarged thymic gland even though the patient may not have presented previous clinical symptoms of this condition. That the life of an apparently normal child can be suddenly snuffed out without known cause is alarming and of grave professional concern."

          These are very strong words, and it is hard to mistake what Dr. Perkins thinks of any medical colleagues who are so callous as to permit these deaths to go on occurring. Dr. Perkins goes further (p.217):

          "During the past five summers, [at Seaside Hospital of St. Johns' Guild of New York City] 1,000 cardiac roentgen-ray examinations have been made for the cardiac clinic, and 500 examinations have been made to detect possible thymic enlargement in tonsil and adenoid patients. As a result of our investigations a standard rule is posted that no tonsil and adenoid cases shall be operated upon, or any child be operated upon, unless prior to such operation the chest is examined for cardiac, thymic or chest pathology [emphasis added]."

          And let us see how Dr. Perkins calls upon the textbook (p.217):

          "The fact that a child may have an enlarged thymus, which is not accompanied by the characteristic symptoms of stridor, cyanosis, unconsciousness, asthma, and respiratory difficulties is fraught with grave consequences, especially when operative proceedings are contemplated, for such patients are prone to sudden death under anesthesia. Kerley and Graves in their recent textbook, [Practice of Pediatrics, 1924] state:   `It is well proved by a long series of cases carefully studied, by competent observers, that the condition known as status lymphaticus is an entity and is characterized clinically by a lowered vitality or unstable equilibrium of the vital forces, so that accidents or disturbances, otherwise unimportant, such as some slight injury or a light anesthesia, may precipitate failure of the heart and respiration ... Autopsy findings in these subjects usually show a general lymphatic enlargement of the tonsils and follicles at the base of the tongue and in the intestine, and swelling and enlargement of the thymus, especially at an age when it has generally disappeared ... Many of the sudden deaths, occurring during chloroform and ether anaesthesia have proved to be due to status lymphaticus.' "

          When I was a medical student, such material in a textbook of Pediatrics would look quite acceptable to me ---- if I had not investigated to realize that a boiling controversy was going on in the nation between those who agreed with this "textbook wisdom" and those who accepted none of it at all. Words such as "well proved," and "a long series of cases" are potent expressions in a textbook. And so is a warning:   "Many of the sudden deaths occurring during chloroform and ether anaesthesia have proved to be due to status lymphaticus."

          After all these forceful words, it is no surprise that the following conclusions are presented in the close of Dr. Perkins' 1925 article:  

          The reader might be surprised to learn there was a countervailing medical opinion that none of this was true. But that countervailing opinion was far from strong enough to prevent a great deal of ionizing radiation exposure to the breasts of female infants and children.

          How Did Dr. Perkins look at this issue four years later (Perkins, 1929)? We shall quote some of his conclusions (1929 p.261):

          "Therefore, a preliminary roentgen examination of chests in children in order to find possible thymic enlargement is in the field of prophylactic [preventive] medicine and should be done when possible at all times. If in a thousand operative cases in children, 50 show definite roentgen evidence of thymic hypertrophy, there is always the chance of postponement of operation, and the institution of roentgen therapy will probably save some lives. According to other observers and reports, 50 cases of thymic enlargement in 1000 cases is a conservative figure. Some of these cases may be status lymphaticus, but there is very little difference as to the question of a possible fatality as the result of shock, either surgical or otherwise. A thymic death is a surgical tragedy and anything that can be done to avert such an outcome should be done immediately and not questioned. I have good reason to believe that there will soon be a demand for a roentgen examination of a child's chest prior to operation and if this is neglected, the physician or surgeon will be held responsible as is now the case in fractures. Into the difficulties of universal preoperative roentgen examination of the thymus as a measure of safety in pediatric surgery, one need not go. The practicability of this step has been I believe proven in many instances. The added advantage of heart and lung examination is without question. It has always followed that when something could be done for the better protection of the patient, it would in the end be demanded and thereby become routine."

          Clearly, Dr. Perkins has not changed his opinion. He may even be more forceful than he was four years earlier.

The Work of Drs. Conti and Patton of Pittsburgh, 1948

          Thirty-seven years after the publication of the 1911 Lange paper, not only was the issue of "enlarged thymus" by no means settled, a gigantic increment in radiation exposure of human breasts in infants and children had been created, and Conti and Patton reported the following in a paper entitled "Study of the Thymus in 7,400 Consecutive Newborn Infants," American Journal of Obstetrics and Gynecology 56:   884-892, November 1948 (p.884):

          "The thymus problem presents today as it has for many decades, a challenge to the physician. Most thoughtful investigators believe that definitions and clarification of the physiology of this gland must precede any stable and scientifically sound solution. Controversy has been the keynote of thymus discussion since 1889."

          "At present there seem to be a few points upon which there is agreement."

          1.   A competent radiologist experienced in thymus interpretation will usually be able to determine whether the gland is enlarged. [Note that 37 years later, there is still a discussion of how to find out whether thymic enlargement is even present.]

          2.   Many obstetricians and pediatricians believe that respiratory symptoms in the presence of thymic enlargement justify therapeutic irradiation.

          3.   In the majority of cases where no other pathology is demonstrable the respiratory symptoms will improve with the rapid thymus atrophy which follows roentgen therapy.

          4.   There has been no positive proof adduced that sudden death in infants can be due to tracheal compression or bilateral recurrent laryngeal nerve paralysis from enlarged thymus. However, many reliable authorities attest to this possibility and submit autopsy proof of cases which showed no postmortem findings except the presence of an enlarged thymus gland.

          5.   The general public is thymus conscious and has what is possibly unjustified confidence in the efficacy of roentgen diagnosis and treatment.

Dr. Henry Pancoast Speaks on the Thymus Issue, 1930

          Henry K. Pancoast, M.D., Professor of Roentgenology, wrote an influential paper, "Roentgenology of the Thymus in Infancy and Differential Diagnosis of Enlarged Thymus and Its Treatment." This paper appeared in December 1930 in the American Journal of the Medical Sciences. Professor Pancoast, highly regarded in roentgenological circles, was then Professor of Roentgenology, University of Pennsylvania, and Roentgenologist to the Hospital of the University of Pennsylvania.

          We single this paper out because Professor Pancoast (one of two enormously influential voices during years of the debate) wrote in no uncertain terms about a proper roentgenological examination to study the thymus and to differentiate thymic enlargement from other intrathoracic entities (Part 1). We can be sure that nationwide and worldwide his advice was respected and commonly followed by many radiologists and other physicians.

          Concerning his views on how the roentgenologist should proceed in problems for the individual presenting clinical evidence of thymic enlargement and upper respiratory tract obstruction, we have the following (p.746):

          "The vigorous controversy regarding the exact cause of death in cases of supposed status lymphaticus or enlarged thymus has been waged for well nigh a century. The so-called thymic death has been ascribed to a variety of causes ... The one theory which seems to be most popular at the present time regards the calamity or potential danger as due to the pressure of an enlarged thymus upon the trachea, blood vessels or nerve trunks. A second theory ascribes death to a constitutional defect manifesting itself through an injurious raising of the vagus [nerve] tone, together with a deficiency of the chromaffin system and weakness of the sympathetic system. Another cause of death that has been stressed is a hypersusceptibility to physical and chemical agents. A fourth theory is anaphylaxis. Finally, a fifth ascribes death to an abnormal thymic secretion of a general lymphotoxemia." And (p.746):

          "Personally, as previously stated elsewhere [citing two prior papers], we have followed the trend of most roentgenologists and pediatrists who have seen the wisdom of being on the safe side in the thymic controversy and of recognizing the condition of enlarged thymus as an entity. Our views have been greatly strengthened by the observations and statements of Jackson [the Chevalier Jackson, regarded as "Dr. Bronchoscopy" in that period]. We believe, therefore, that the potential danger in the infantile thymus lies in its ability to enlarge further and to compress the trachea and the recurrent laryngeal nerves, and to cause other phenomena due to respiratory obstruction. We have observed all of these occurrences roentgenographically and fluoroscopically in the living infant and we have the statements of Jackson upon observation made directly in the respiratory passages during life. Our beliefs and our remarks do not in any way apply to the cause of supposed thymic deaths in adults. We do not believe that compression is a possible cause of death during adult life."

          [We insert here the fact that many observers in that era pooh-poohed the idea of tracheal compression in the infants or the adults. But the experience and capabilities of those critics hardly stood up against the views of two highly respected physicians, Henry Pancoast and Chevalier Jackson.]

          Back to Dr. Pancoast:   At page 746:  

          "Jackson in 1907 made the following statement:   `It has been my privilege with the aid of the bronchoscope, to demonstrate beyond all doubt on the living patient the purely mechanical nature of thymic asthma in one instance. This, of course, does not prove that every case has this same pathological mechanism, but it does prove the occurrence of that which many ... have denied, namely, that a hypertrophic thymus can compress the trachea sufficiently to obliterate its lumen ... it would seem more accurate to call it thymic tracheostenosis.'" And:   "Jackson, in 1915, made the following statement, based upon further observations:   `Thymic deaths under anesthesia attributed to `status lymphaticus' and `hyperthymization of the blood' are nothing more or less than arrested respiration due to obstructive pressure of the engorged thymus. Artificial respiration is useless, as air cannot be drawn into the lungs, although it can be forced out. After death the engorgement factor is not evident.' In a recent personal communication [to Pancoast], Jackson stated that `over 300 cases since that time have been observed bronchoscopically, showing compression and the purely mechanical character of wheezing, dyspnea, and the impending asphyxia from thymic pressure.' `The upper orifice of the thorax is a rigid ring, and coughing, choking, and hard breathing jam the large thymus into this ring and compress the trachea. After asphyxia the thymus shrinks because engorgement is depleted, and at autopsy the thymus is no long compressing the trachea.'

          Professor Chevalier Jackson is very clear concerning his interpretation of what is happening.

          Professor Pancoast says at p. 747:   "Our roentgenological studies made during two phases of respiration have proven that the thymus is pushed upward during expiration, and it is easy to understand how the apex of the wedge jams up into the narrow, rigid, bony thoracic inlet and compresses other yielding structures such as the trachea, vessels, and recurrent laryngeal nerves." And:  

          "In view of these observations of an eye witness of actual conditions during life, of the post-mortem findings of the character of the gland which readily lends itself to causing pressure, and the confirmation of both by roentgenologic studies, we, who have almost an equal opportunity to confirm these findings in the living, cannot do otherwise than take the stand that the danger in the thymus lies in the possibility of its causing pressure stenoses under certain circumstances. Even if it cannot be proven that actual death results from thymic compression, we have sufficient evidence to lead us to believe that obstructive phenomena and cyanosis can result. It may be that another factor is essential in the causation of asphyxia and death. We know from experience that at least one such factor is possible, namely, recurrent laryngeal [nerve] paralysis, which is a complication of thymic enlargement, to be discussed later."

Part 4.   Was There Really No Way
             to Tell Whether a Thymus Was Enlarged?

          Drs. Jackson and Pancoast have made their positions crystal-clear, in support of tracheal compression by the thymus, and their prestige made a great deal of difference. Many physicians, radiologists and others believed passionately in x-ray therapy of enlarged thymus. Their numerous papers, over several decades, are filled with evaluations of "90% cured," "95% cured," "almost all favorable results." And many of these super-optimistic reports came from very prestigious institutions on the medical scene in the USA.

          But it is also true that there was a series of investigators who denied that thymic enlargement ever existed as a pathological-clinical entity. Boyd (1932) was certainly one such investigator. The basis for the argument centered around what the expected weight of a normal thymus gland must be. Those who agreed with Boyd believed that in deaths which followed a lingering or wasting illness, the thymus gland was very, very small. However, in those who died suddenly, in accidental circumstances, with no prior wasting disease, the thymus was not small. So, the controversy centered in a large measure around what the true normal size of a thymus gland should be. Obviously, since pathological material was the source of thymuses, there was real room for differences among pathologists on this issue. There seemed to exist no way to stop the bitter debates about whether a certain size was normal for the thymus gland or whether that size represented enlargement.

          Professor Pancoast certainly seemed to practice what he preached. He indicated (Pancoast 1930, p.762) that "We have treated 315 cases of enlarged thymus from 1912 up to April, 1930. Of these 271 have been treated since 1924."

          Are roentgenologists today suggesting that Dr. Pancoast consistently deceived himself about what he saw in roentgen studies from 1912 to 1930? Dr. Pancoast is in the top echelons of the famous American roentgenologists.

Part 5.   A Pathologist-Coroner
             with Enthusiasm for "Enlarged Thymus Disease"

          I was a student at UCSF Medical School at the time that Jesse Carr was one of our professors of pathology. He was also the coroner for San Francisco. Professor Carr was a flamboyant, enthusiastic lecturer who certainly had his pathology well in hand. He was very popular with the medical students.

          In 1945, some 34 years after the 1911 paper by Lange, Professor Carr wrote an extensive (43 page) paper in the Journal of Pediatrics, Vol.27, No.1, July 1945, pp. 1-43, in which he was scathing in his comments about those who denied the existence of thymic enlargement as a real pathological entity.

          Professor Carr wrote, at page 2, "Young and Turnbull, in 1931, were sent into this confusing maze of theories by the Status Lymphaticus Committee working under the auspices of the National Research Council of Great Britain, but they emerged unfortunately with little more theory of acceptable character than was proposed before their work and established no new facts concerning the function or development of the gland. In fact, by their stated position, doubting the presence of such syndrome as status thymo-lymphaticus, they probably did more to confuse the issue than they did to clarify it." Real vintage Jesse!

          Concerning lymphatism, Carr wrote (p.8):

          "Part of the confusion existing in the literature and in the minds of doctors today is perhaps due to a futile ambition to ascribe all deaths in children with lymphatism to one cause. Certainly there is enough material available in the literature to certify that sudden death does occur in this condition with no cytological changes being demonstrable at autopsy other than hyperplasia of the lymphatic tissues and enlargement of the thymus. That not all of these cases point to a common cause of death is, however, equally true, which may mean that at least some and possibly all of the theories of death in lymphatism which we have enumerated are valuable and that the diagnosis of lymphatism should not only not be discarded as both a clinical and necropsy diagnosis but rather could with profit be broadened and extended with qualifications added covering the conditions which upon analysis prove to be more than pure theory."

          At the San Francisco coroner's office they had 520 cases of sudden death in children below 10 years of age. After eliminating many cases as being other than thymus-related, Carr says (p.9)"...of this total we can collect 49 cases dying of conditions arising from, or directly associated with, pathological changes in the thymus and lymphatic system. This group offers what we feel to be indisputable examples of death from asphyxia following tracheal compression from an enlarged thymus gland, deaths from partial obstruction by an enlarged thymus during or following anesthesia, cases showing a combination of thymic enlargement, lymphatism, and anaphylaxis, and substantiated cases of adrenal insufficiency associated with thymic hyperplasia."

          Then he introduced a new term, "Status Thymico-Asthmaticus." Dr. Carr said (p.9):

          "In addition to reporting a series of cases of each of these types, we wish to contribute a new descriptive term which denotes a disease entity frequently responsible for strangulation in the young, namely, status thymico-asthmaticus. Under this heading is presented a series of cases occurring in widely varying age groups where death has occurred from asphyxia and wherein the thymus is enlarged. This enlargement is of lesser degree than in cases dying with acute tracheal compression from an enlarged thymus and associated with it is an hyperplasia of the lymphoid system which instead of being generalized is limited largely to the bronchi and bronchioles. Because the lymphocytic infiltration is in the submucosa, and among the muscle fibrils as well as peribronchial, the term asthmaticus is included. This picture cytologically resembles a developing or existing asthma and the clinical course is differentiated with difficulty from true asthma excepting for the single but very important fact that the status thymico-asthmaticus group show no beneficial response to the injection of epinephrine."

          The clinicians and pathologists remained seriously divided on these issues of thymic involvement in illness and particularly in sudden deaths. However, it does appear clear that physicians feared malpractice suits if they failed to include thymic enlargement as a possible diagnosis and if they failed to treat with radiation. The studies were both large and plentiful from around the country reporting large series of cases of infants studied for thymic enlargement and treated for it --- in leading medical centers.

Part 6.   A Clinical Study of 2,000 Newborn Babies

The Donaldson Studies at Ann Arbor, Michigan, 1930 and 1938

          Some 27 years after Lange's paper, Dr. Sam W. Donaldson published a paper in the Ohio State Medical Journal, entitled "A Study of the Relation between Birth Weight and Size of the Thymus Shadow in 2000 Newborn" (Vol.34, No.5, pages 538-541). He had published a paper on "Hyperplasia of the Thymus" in 1930. That paper dealt with 1,045 patients.

          In the second paper, not only did Dr. Donaldson present data on 2000 consecutive infants in the St. Joseph's Mercy Hospital, Ann Arbor, Michigan, but he showed the following. In the male newborns (examined 24 hours after birth), 19.3% of babies were regarded as borderline or positive for x-ray evidence of thymic enlargement;   in the female newborns, 17.5% were regarded as positive or borderline. This is a much higher incidence than that widely reported elsewhere.

          For the females (112 positive and 63 borderline), the following was the procedure:   The 112 positive cases were given from two to four treatments of 100 R each, the treatment being given at weekly intervals.

          The 63 with borderline positive thymic findings were given one treatment with 100 R --- stated by Donaldson to be a prophylactic measure.

          Altogether, about 18 % of all the children born in that hospital during the period of accumulation of 2000 births were given therapeutic doses of x-rays.

          Dr. Donaldson was by no means unaware of a deep split in the medical profession concerning whether enlarged thymus was a disease at all and whether it made any sense to treat it with radiation.

Awareness of the Controversy

          Dr. Donaldson wrote (p.538):

          "It has long been the opinion of many physicians that only those newborn who are above average weight should be examined roentgenologically for evidence of an enlarged thymus. Complicating the picture is the fact that there appear to be two separate and distinct schools of thought regarding the thymus problem. One group maintains vehemently that there is no such problem and that the danger from the existence of an enlarged thymus is negligible if it exists at all. The members of the other school of thought contend with equal firmness than an enlarged thymus is pathological, basing this contention on their experiences with sudden and unexplainable deaths in which the only finding was that of an enlarged thymus, or on their observation of the disappearance, following irradiation, of the classical symptoms attributed to the thymic syndrome."

          Donaldson pointed out that even though Lange's 1911 paper was one of the first to describe the effects of roentgen irradiation upon the thymus gland, the textbooks published as late as 1915 made no mention of the use of roentgen treatment of enlarged thymus gland. They simply ignored the subject, both with respect to therapy and with respect to prognostic significance of an enlarged thymus, according to Dr. Donaldson.

          In spite of this "textbook failure," Lange's work became applied early. Newborns whose x-ray exam showed a thymic shadow were subjected to x-ray treatment, and routine pre-operative irradiation of the gland with its subsequent reduction in size was a precaution taken by many surgeons, according to Dr. Donaldson (at p.540).

Results of the Treatments One Month Later

          As for Dr. Donaldson's own practice, the detailed observations are indeed fascinating. At page 540, Dr. Donaldson relates:  

          "All babies in this series with a borderline finding were given one treatment of 100 R, 130 P.K.V. [our kVp] filtered through 4 mm. of aluminum. This amount of radiation was considered to be sufficient to cause involution of the gland in a newborn infant and was given solely as a prophylactic measure. Those with a more marked finding of enlargement and with compression of the trachea were given from two to four treatments of 100 R each with the same factors. Treatments were administered at weekly intervals and checkup films were made 30 days following the last treatment to determine whether or not there had been a reduction in size of the shadow and expansion of the shadow of the trachea." And:  

          "In practically every case where a re-examination was made following treatment there was found to be a reduction in the size of the shadow of the thymus and an increase in the width of the shadow of the trachea to normal. In a very small percentage of the cases the thymus shadow had not receded to within normal limits, but had diminished in size and appeared denser, suggesting that fibrotic changes had occurred as a result of the radiation and induced involution. Up to the present time, although records are not complete on every child examined, in none of the children in either the treated or untreated group who have died has the death been attributed to a persistent thymus."

Part 7.   Delusion or Reality? An Enduring Enigma, in Our Opinion

          The reader has quite a platter to choose from concerning what one finds when searching for enlarged thymus glands, and what one finds when assessing the benefit of x-ray therapy of those thymuses found to be enlarged. It is a disturbing matter indeed to witness the disparities in reports on this issue. We go from the "observation" that there is no entity such as a pathologically enlarged thymus gland to the "observation" of marvelous results of the x-ray therapy itself. That is quite a range.

          Some readers may be ready to assume that the marvelous results "observed" from radiation therapy were just "self-suggestion" by the physicians or the parents. And such readers may be correct. The phenomenon of self-suggestion in medicine is not limited to patients (or parents of very young patients). There is no doubt that physicians, too, sometimes "find" a positive outcome therapeutically for the patients they treat, when there is no such outcome.

          But were the immediate benefits of thymus irradiation really a delusion? We are not ready to say so. It seems hard enough for people to maintain their convictions about reality if the beliefs are under attack. The physicians who believed in roentgen therapy for alleged thymus disorders maintained the faith decade after decade, despite vigorous challenge, well-known to them. What were all those physicians "seeing" to sustain their faith in the 1920s, 1930s, 1940s, and 1950s, if not real benefits? The enigma remains, in our opinion.

          By contrast, there is no mystery about the public's enthusiasm for the thymus-explanation. When there were babies turning blue and having trouble breathing, parents were desperate for relief. When there were unexpected sudden deaths in young children without any evidence of pre-death illness, the public was primed to be responsive to something like the enlarged thymus concept --- especially with all the reports of favorable (even "brilliant") results from the roentgen irradiation of the thymus.

          Under these circumstances, parents did not want to hear from the skeptics. The parents wanted x-ray diagnosis and x-ray treatment for their children --- and they got them.

# # # # #

1925:   "... there is no doubt that a decided enlargement of the thymus exists in a large number of newborn babies and that while it causes no inconvenience in many of these, there are a few of them in whom it will cause serious trouble, or even prove fatal. The number of sudden deaths from enlarged thymus in babies supposedly healthy is sufficiently large to consider this condition a potentially serious one whenever found. Since we do not know which of these babies will develop trouble, or why some do and some do not, the only safe plan to follow is to treat all enlargements as pathological. Fortunately the treatment is simple and so far as we know harmless, both as to immediate and remote effects."

o - G.W. Grier, "Enlarged Thymus:   Differential Diagnosis and Radium Treatment," Atlantic Medical Journal pp.502-506. May 1925.

1927:   "... from the observation and treatment of a large number of cases, it may be confidently stated that the roentgen ray offers not only a highly satisfactory method of treatment of enlarged thymus, but, in practically all cases, a safe and certain cure."

o - John Remer and Webster W. Belden, "Roentgen Diagnosis and Therapy of the Thymus in Children," American Journal of Roentgenology and Radium Therapy Vol. 18:   119-124. August 1927.

"... the one real specific in pediatric medicine ..."


          "If there is one real specific in pediatric medicine, I feel it is the radiation treatment of thymic disease. The relief afforded sometimes by only one exposure is so marked that it verges on the dramatic. In a number of instances I have seen infants practically in extremis with stridor, dyspnea, and tetany, react miraculously within a few hours after a single roentgen treatment. The reduction in size of the enlarged thymus gland can be simultaneously followed by roentgenographic study." And:  

          "Two conclusions might be stated as almost axiomatic:   (1) That failure of symptomatic relief suggests an error in diagnosis, and (2) the effects of properly measured roentgen dosage on the thymus appears so definite that it might be applied as a diagnostic procedure in doubtful cases, much as the therapeutic test is employed in suspected syphilitic conditions." And:  

          "Empiricism is so contrary to modern scientific medicine that any therapeutic measure advanced at the present day not based upon experimental and laboratory research and data, must perforce lose much of its value. And yet clinical medicine has struggled through the ages and given birth to its most valuable healing agents purely upon empirical grounds. Assayed in the molten crucible of experience and withstanding every conceivable onslaught of criticism and trial, there have survived many of the most valuable therapeutic aids in medicine based upon what is the true and tried test --- the result achieved in the war against disease at the patient's bedside ... "

Mulford K. Fisher, M.D. "Roentgen-Ray Treatment of Chronic Cough in Children."
American Journal of Roentgenology and Radium Therapy Vol.14:   244-246. 1925.

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