JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION

JANUARY, 1945

* VOL. XXXVII * No.

ORIGINAL COMMUNICATIONS
Cryptorchidism *
CLAUDE P. CARMICHAEL, M.D., Washington, D.C.
INTRODUCTION
EMBRYOLOGY

CRYPTORCHIDISM, by its very nature connotes its origin, life, and life history as being in darkness, hence the purport of the paper is not to shed light on a condition so conceived but rather to review the literature on the subject. The beginning of life itself is a matter of controversy with those who lean toward a divinely conceived beginning as set forth in Genesis and others who accept the biologic concept. It is the biologic concept woven for modern adaptation with which we have to deal as the beginning of matter itself. In the great maternity room of space an immense swirling mass of flaming gases were undergoing labor pains. The Virgin Mother of our universe was about to give birth to a brood of planets. This event did not take place unattended for a celestial vagabond, a passing star aided in the accouchment. Having delivered the planetary brood, the celestial vagabond, the accoucher-inchief, departed, leaving the planetary infants attached to the Virgin Mother by apron-strings of gravitation. One of these planetary infants, the earth, on whose surface the phenomenon of life as such, has in eons of light years gone from a simple, homogenous, unicellular state with powers of absorption, expansion and self-division to the complex, heterogenous, as exemplified by the primate vertebrate-Homo Sapiens-with the powers of reproduction invested in the reproductive organs; the testis in the male, and the ovary in the female. It is an anomaly of this male member of the reproductive team with which we have to deal. In order to better understand this anomaly we will briefly review the embryology, anatomy, histology and physiology of this organ.
* Read before the Scientific Session of Third Medical Reading Club, April 14, 1943.

In the first-third of fetal life the testicle begins to develop. Each testis appears first as a genital ridge upon the ventro-mesial border of each Wolffian body. Peritoneal infoldings give rise to solid cords of cells which extend inward from the peritoneal border of the genital ridges, connecting with glomerular capsules of some Wolffian tubules. Before doing so, however, these coils anastomose forming the rete testes. The Glomeruli atrophy, their canals become coiled, forming the Ducti-Efferentes in the Globus Major of the epididymis. They empty into the Wolffian duct which persists as the Ductus Epididymus and its continuation, the Vas Deferens. The Paradidymus is also a remnant of the Wolffian tubule; the Hydatid of Morgagni is a remnant of the Duct of Muller. As the testicles take definite shape a fold of peritoneum develops extending from the lower pole of the testes downward and outward across the iliac fossae. In the free border of this fold develops the Gubernaculum, a cord of connective tissue which has attachments in the Scarpas Triangle, Pouparts Ligament, the pubic bone, root of the penis, to the perineal fascia and the bottom of the scrotum. The testicles develop below the kidney by the lumbar spine. As the spine grows, the testicle is left behind and thus begins its descent. Whether that causes further descent or whether the Gubernaculum contracts and exercises a guiding pull is not known. However, by the sixth month of fetal life the testis is at the internal abdominal ring, drawn down by the gubernaculum and connected to its place of origin

by the spermatic vessels. During its descent the testicle and epididymis have received their peritoneal investures. Entering the inguinal canal and passing out through the external ring, the testis

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at birth or shortly thereafter reaches its position in the scrotum. The peritoneal canal as such becomes obliterated in its upper part leaving the lower part to form a serous sac for the testicle.
ANATOMY

The testis is a gland of oval form, with flattened sides and variable dimensions, but commonly is one and one-half inches by one inch by one-quarter inch, weighing one ounce more or less. The left side is somewhat larger than the right. The testes have two coverings, one the serous coat. derived from its peritoneal relationship during its descent in fetal life. The true capsule of the testicle is the tunica albuginea. This capsule composed of interlacing bundles of white fibrous tissue is inverted at the posterior portion of the gland forming an imperfect septum, the mediastinum. From it trabeculae radiate dividing the interior into many spaces. The trabeculae serve to maintain the shape of the organ, convey the blood vessels that ramify the interior, support the glandular portions which are made up of lobes. These lobes are cone-shaped. Some two hundred or more in number, each of these contains three or four seminiferous tubules. They unite to form a smaller number of tubules, the tubuli recti. These in turn open into the rete testes, a complicated network of canals occupying the mediastinum; from the rete testes some fifteen or twenty canals so curled as to present cone-shaped masses with their apices toward the testicle. These ducts, the vasa efferentia-and the single duct, the ductus epididymis -which is twenty feet long when unravelled-comprise the body and tail of the epididymis. Its continuation is the Vas Deferens.
HISTOLOGY

A connective tissue, framework and three kinds of cells: Two are found in seminiferous tubules. They are sustenacular or cells of Sertoli, and sexual cells. The third kind of cell-the interstitial cell, or cell of Leydig, occurring in the loose connective tissue. The descent of the testicle may be halted at any point. Retention in the abdomen is the least common variety as it is hidden from view. The condition is called cryptorchidism. This term has been

generaly applied to others of this anomaly wherever located. Causes of non-descent: Eccles' mentions any number of conditions which may be factors in producing this anomaly. Factors are: 1. A mesorchium that is too long. 2. Adhesions between the mesorchium and the adjoining peritoneum 3. The testicle may be abnormal in size as compared with its passage of exit 4. The vas deferens may be too short 5. The spermatic cord of insufficient length 6. An ill-developed inguinal canal 7. An ill-developed superficial abdominal ring, a mal-development of one-half of the scrotum 8. Endo-crinal insufficiency a. Thyroid b. Pituitary c. Primary gonadal d. A combination of any of these endocrinal disturbances or all of them Weisman2 observes, "The reasons for non-descent will be more easily understood when the true mechanism of descent is discovered." For the present endocrine dysfunction, pituitary, thyroid or gonadal, coupled with some individual anatomical defect are the only explanations temporarily acceptable. The classification of retained testes is based on the anatomical location. Campbell's classification is as follows: D. Pubic A. Abdominal B. Inguinal E. Femoral F. Crural C. Upper scrotal G. Perineal In man, at birth normally, the testes are located' in the scrotum. During the prepubertal years they grow in size and prepare for the production of spermatozoa as well as an increased hormonal secretion. At puberty the testicles are mature, spermatozoa are formed and ready and capable of being ejaculated. The internal secretion3 of the gonads3 give to the human body its male configuration, pubic escutcheon and the power of restless. combativeness. The physiology of the normal testes and bilateral ectopic testes is the same up to the time of puberty,4 that is, no histological difference up to this time. The gonads are the same. They do not produce spermatozoa. The male hormonal output

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is probably less in the extopic testicles. At puberty infection, penis small, scrotum poorly developed, the normal testes attain maturity, the cryptorchid pubic escutcheon spare. Early treatment for these begins to degenerate. This degeneration is gradual cases with endocrine therapy is highly beneficial but definite, the internal secretion of the cryptorwhile untreated cases grow worse and eunuchoid chid is probably deficient resulting in spermato- characteristics develop. genic and endo-crinal functional impairment. The fertility of the cryptorchid, that is the biMtore, Crew, Phillips and Andrews, et al, have lateral cryptorchid, is a moot question, one on reported that spermatogenesis of the ectopic testes which the investigators are at wide variance. Meyer5 in animals is progressively lessened owing to the reviewing this subject in 1927 reports that 19 temperature of the inguinal canal and pressure authors agree that cryptorchidism and spermatoatrophy. In the ingui4al canal and in the abdomen genesis were consistent while 12 authors denied the temperature is much higher than in the scro- that spermatogenesis of any practical value could tum and the formation of spermatozoa and their exist. However, all investigators agree that spermaviability are hindered by elevation of temperatures. togenesis may continue, but fecundation is doubtful. Nature's mechanism and timing of descent are The true test of fertility is the production of so well ordered that they are not subjected to offspring, among those patients with undescended testes sterility is the rule. Fertility is the exception body temperatures which would inhibit development as well as function. whether or not spermatogenesis is present. A norThis process of tubular damage by heat and mal spermatozoal count is about 120 million sperpressure fortunately is slow and in many cases matozoa per cubic centimeter of semen. Counts below 60 million are not conducive to fertility function, even under the abnormal conditions, is retained for years. according to Meaker.6 MacComber and Saunders report fertility from 25 million per cubic centiAbsence, non-descent or atrophy2 of one testicle with its fellow testicle normal and functioning is meter. MacCollum reports proved pregnancy with counts of 16 million and 26 million in 1939. not noted by the individual in his endocrine balance and physical make-up. The normal testis as Rea7 reported two cases of pregnancy with is the case with the remaining kidney in nephrecone spermatozoal count of 500 thousand per cubic tomy assumes the secretory functions of both centimeter and another with 1 to 3 to a high power field. These men were young. However, the organs. But in the case of bilateral cryptorchidism many test does not stand on the count alone but upon external changes are commonly observed; if, howthe morphology and the number of normal sperm ever, the cryptorchidism is purely resultant from in the counted field. On the basis of our present anatomical causes no changes may be noted either knowledge of fertility of cryptorchids, young men pre-pubertal, at puberty or during adolescence or between 18 and 25 exhibit the highest degree of early manhood. It is only during a later period fecundity, after 30 years sterility is practically when the testis is atrophied and the power of incomplete, after 40 years it is absolute. ternal secretion is lost that the individual shows At this point it would not be amiss to enter signs of gonadal disfunction. some observations by Rea8 of the University of Some manifestations of disfunction in case of Minnesota on the histologic character of undesrapid atrophy at puberty are gain in weight around cended testes after puberty. breast and hips, growth in size and height, sparseForty-six testes were available in an age group ness of pubic hirsutiae, under-development of the from 15-73 biopsied before orcho-pexy. Histologipenis. If, however, the testes continue to maintain cally, atrophy, usually progressive with age was their endocrine function until 25 years or more observed in all specimens. Spermatogonia was obthe only manifestation of slow atrophy is a gradual served in 17, primary spermatocytes in 13, secgain in weight with typical fat distribution. If the ondary spermatocytes in 13 and spermatids in 3, testes are undescended owing to primary pituitary spermatozoa in none, spermatids were seen in or thyroid deficiency early in childhood, outward persons in third, fourth and seventh decades; lomanifestations are observed early: child overlarge cation abdominal, inguinal near external ring. Gerfor his weight, girdle adiposity, low resistance to minal epithelium was fairly well preserved in two

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JANUARY, 1945

in the sixth and seventh decades. All were near external ring; only 5 per cent of patients past 30 showed any degree of germinal epithelial retention, hence they are not good operative timber. Heckel and Thompson stress the differentiation of cryptorchidism from pseudo-cryptorchidism, emphasizing the fact that the diagnosis of cryptorchidism should never be made by examination of a patient in a recumbent position, but, that the patient should be examined in a standing position as well, also after exercise. Cognizance must be taken of so-called migratory testes which are not true cryptorchids. Finally the diagnosis can be confirmed by finding the testicle absent from the scrotum, and noting its presence elsewhere if possible. Other differentials are anorchism, monorchism and pseudo-hermaphroditism.
INCIDENCE

Nowhere in all medical literature are the writers on the subject of so contrariwise opinions than they are on the incidence of retained testes. It is possible that this diversity of opinion is due to the fact that some observers include in the group, pseudo-cryptorchidism, and different interpretations have been placed in defining the words cryptorchidism, ectopy, anorchism and monorchism, thus leading to false analyses. Rea reviewing the literature on cryptorchidism and finding the incidence to be 0.1 per cent to 0.31 per cent in adults, stated that only 20 per cent were bilateral with non-descent more common on the right than the left side. McCutcheon studied 3,197 boys of school age and reported a greater prevalence in that of undescended testes but observed further that in growing children this condition was frequently self-corrected, brought in position by the urologic surgeon or endocrine therapy. Hence, the percent of nondescent in children is higher than in adults; or less permanent unless corrected by operative procedure which is probably done only for corrective reasons since undescended testes late in life are apt to be atrophic. There is no useful purpose to be gained by operating on an atrophic testis. They are usually func-

tionless.9 Some observations on incidence of cryptorchidism: Incidence of 1 to 500 in examination of 7,000,000 Austrian recruits; 1 to 150 in 57,000 surgical admissions (Manchester Infirmary); 1 to

300 in the American Army; 1 to 150 in American recruits of World War I; 1 to 200 in 10,000 Scottish recruits; 1 to 200 in 12,500 admissions to Brady Urological Institute; 1 to 50 in 48,000 hernia cases (Eccles). Hinman states that one in every 25 or 30 boys under 14 years and one in every 250 men over 25 years have undescended testes. The condition is usually unilateral and found more often on the right than left. Examination of one thousand boys for Camp Litchman's summer camp for the years 1939 through 1942 inclusive reveals the following findings:10 Youngest age- 51/2 years; oldest-17 years; average age-12. Number of cryptorchids in the group examined was 10; youngest cryptorchid in the group 7 years; oldest in the group-14 years. Location of retained testes, right side7-11-12 years; left side-13-19-14 years; bilateral 10-11 years; perineal-lO years. Average age of cryptorchid group, 10. Incidence 1-100. The retained testes is subject to the same diseases as is the normally placed organ. Many times one is not aware of the anomaly until the patient has an epididymitis of the retained member secondary to his urethritis. Secondary inguinally retained testes are subjected to infections and trauma, the abdominally retained testes is subjected to torsion. It has been almost an accepted fact that a cryptorchid testes was a precancerous testes and should be so treated but the truth of the matter is that a cryptorchid testes is not a great deal more cancerous than its normal brother. Hinman reports an incidence of 2 per cent.11 H. E. Campbell of Denver12 enumerates six reasons why these facts have been unappreciated: 1. Drawing the wrong conclusion from statistics. 2. Errors in misquoting authors. 3. Differing definitions of the words cryptorchidism, crystorchid, ectopy, anorchism, monarchism, etc. 4. Reporting from hospital practice but not from private practice. 5. Disproportionate incidence occurrences as between the abdominal and inguinal; this no longer exists because of the frequency of the abdominal explorations. 6. Computation of incidence on basis of

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number of patients seen, instead of number of cases, thus the true incidence of malignant changes in bilateral undescended testes has not been determined. From the literature since 1900 a group of 1,413 cases of undescended testes with a known incidence of malignant change has been collected, a group of 2,119 cases of undescended testes in which the relative incidence of abdominal and inguinal non-descent is known, and 672 cases of malignant growth in the testes in which the relative frequency of abdominal and inguinal nondescent is known. One in 20 abdominal testo6 shows a malignant change as against 1 in 80 in inguinal growths. This is because the proportion of inguinal to abdominal is 4-1 and that of cancerous inguinal to cancerous abdominal testes is 1-4.
TREATMENT

The treatment of undescended testes falls in three stages: 1. Expectant. 2. Endocrine. 3. Endocrine followed by operative procedure. Einhorn and Rowntree13 enumerate four main concerns in treatment of cryptorchidism. They are: 1. Anatomic restitution of the testicles to a normal position in the scrotum. 2. Proper development of the affected organs. 3. Normal functional results insuring both fertility and elaboration of the sex hormone. 4. The possibility of degeneration and malignancy occuring in the restored testes.
EXPECTANT TREATMENT

As has been stated previously deterioration does not commence in the cryptorchid testes until after puberty sets in so King's obstetrical dictum"masterly inactivity"-could be applied to this condition without endangering any patient. Carefully observing and only instituting therapeutic procedures when definite signs of endocrine inadequacy are noted.
ENDROCRINE THERAPEUTICS

Thyroid: Prior to 1930 thyroid substances were widely acclaimed and prescribed in pre-adolescence, with enthusiastic reports by the experimenters. Conservative investigators decried the indiscriminate use and went so far as to say that untold damage could be wrought by giving large doses so early in life. Englebach and his followers obtained satisfactory results without ill effects

from this therapeutic modality and there are many today who prescribe this substance in small doses with no apparent ill effects. Gonadotropic Hormones :14,15 There are two gonadotropic substances13 in use for the treatment of undescended testes; anterior pituitary-like hormone derived from pregnancy urine and placental tissue, and anterior pituitary hormone. Synthetic male hormone or testosterone propionate is used. In 1936 Thompson, Heckel, McCarthy and Thompson reviewed the literature published up to that time dealing with the treatment of undescended testes with anterior pituitary-like hormone, reported the rate of successful outcome in a large series was 61 per cent. Thompson and Heckel16 reporting on their own cases were successful in 27 per cent of them. Many clinicians now use anterior pituitary-like substance as a preliminary to operative intervention. Successful results are in proportion to those cases in which there is endocrine dysfunction. Those are the ones that are benefited by same. Here again we have dissenters. Eisensteadt, Appel and Frankel 18 have reported that hormones in this condition does not assist in the descent but makes operative interference more difficult on account of adhesions caused by therapy and in fact causes testicular atrophy. They advocate surgery only and claim 87 per cent success. Complications which may follow anterior pituitary-like hormone therapy are signs of precocity in children. This is however problematic and close observance of the therapeutic effect as well as careful selection of cases will obviate this seeming obstacle. Bauer and Koch advocate use of testosterone propionate (synthetic male hormone). Zelson and Steintz17 suggest the treatment with the A.P.L. hormone-causes direct stimulation of the testicle as produced; whereas with testosterone propionate the hormone itself supplants the action of the testicle and in doing so probably inhibits its internal secretion. Therefore, one must, if this is true, use it cautiously. Talbot and Talbot suggest in reviewing gonadal disorders in children that A.P.L. hormone is the treatment of choice in undescended testes.
SURGICAL TREATMENT

Brunzema in 1929 compiled upwards of eighty operations for this condition. Many observers

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advise surgical treatment after endocrine therapy has failed to yield results after 6 months or a year's trial. It is agreed if used prior to operation if it does not facilitate descent it will aid the subsequent surgery and for that reason it should be used as routine preoperative procedure. However, Frankel, Eisensteadt and Appel disagree with this procedure. Orchidectomy is reserved for cases of unilateral nondescent in which all methods to induce descent have failed. The testis is removed in order to keep it from being traumatized or cause the patient discomfort. The Torek operation and its modifications are now in use for successful relief of ectopic retention. Rea-For an orchopexy to be successful one has to take in consideration; the age of the patient to be operated on, the location of the retained testicle, the adequacy of the blood supply of the transplanted testes, the testis must be placed securely in the scrotum without encroachment, look out for signs of atrophy afterwards, watch out for malignant changes. MacCollum suggests that the ejaculate be studied from the standpoint of count and morphology. Man in the second decade of life with inguinal retained testes offer best chance for successfully functioning testes. Afterward men in the third decade may be offered a chance if the testis is in the inguinal region. Men in the 4th, 5th, 6th, 7th decade are without hope as study shows that germinal epithelium lessens with increasing age.
SUMMARY

decade and is almost nil in the 4th decade. The true test of fecundity is the ability to beget children. An ejaculate with I count from 60,000,000 to 120,000,000 spermatozoa per cubic centimeter with a normal morphology may be considered ample for impregnation. The treatment is expectant, endocrine and surgical.
REFERENCES

The exact etiological factor is not known; the ot opinion is that there are either endocrinologic or anatomic factors, mayhaps both. The bilaterally cryptorchid is the cryptorchid presenting a symptom-complex. The incidence of cryptorchidism varies with the age group studied. It is apt to be temporary, in the young, in the adult cryptorchidism unless corrected by therapeutic modalities is apt to be permanent. Bilateral cryptorchidism occurs in about 20 per cent of cryptorchids. Malignancy is not necessarily a sequelae or accompaniment of cryptorchids. Hinman reports an incidence of 2 per cent. Fertility may be retained 25 years in the cryptorchid but decreases rapidly with each succeeding

consensus

1. Eccles: The Imperfectly Descended Testis. N. Y. Med. J., 1903. Pp. 10-12. 2. Weisman, A. T.: Spermatazoa and Sterility. Hoeber 1941, Vol. 1, pg. 220. .3. Martin, Thomas and Moorhead: Genito-Urinary Surgery and Venereal Diseases. J. B. Lippincott. Vol. 12, pg. 297. 4. Vines: Urology. See Keyes and Ferguson. Appleton-Century (N. Y.) 5. Meyer, A. W.: The Discovery and Earliest Representations of Spermatazoa Hist. Med. 1938, Vol. 6, pg. 89. 6. Meaker, S. R.: Human Sterility. T. H. Williams and Williams (Balt. Md.) 1934. 7. Rea, C. E.: Functional Capacity of Undescended Testes. Arch. of Surg., Jan., 1942, Vol. 44, pages 27-3 1. 9. Curling, Martin, Thomas and Moorhead: GenitoUrinary Surgery and Venereal Diseases. J. B. Lippincott (Phila.) Vol. 12, pg. 304. 10. Combined Examination Records, Litchman's Summer Camp. Washington, D. C., 1939-1942. 11. Rea, C. E.: An Evaluation of Treatment for Cryptorchidism. Surg., Gyn. & Obst. May 1941. Vol. 72, pages 940-941. 12. Campbell, H. E.: Arch. of Surg. (Denver) 1942 Vol. 44, pgs. 353-369. 13. Einhorn, Nathan H.; and Rowntree, Leonard G.: Jour. Clin. Endo. 1941. Vol. 1, Aug. pgs. 649-655. 14. Davis, C. D.; Pullen, R. L.; Madden, J. H. M. and Hamblen, E. C.: Therapy of Seminal Inadequacy. Jour. Clin. Endo. May 1943. Vol. 13. pg. 268. 15. Pullen, R. L.; Wilson, J. A.; Hamblen, E. C. and Cuyler, W. R.: Clinical Rev. in Andrologic Endo. Dec. 1942. Vol. 2, pg. 730. 16. Thompson, Williard D. and Heckel, Norris: Jour.

Clin. Endo., Dec. 6, 1941. Pgs. 1953-1956. 17. Zelson, C. and Steintz, E.: Treatment of Cryptorchidism with Male Sex Hormones. Jour. Ped. 1937. Vol. 15. Pg. 522. 18. Eisensteadt, J. S.: Appel, M. and Frankel: The Effects of Hormones on Indescended Testes. J.A.M.A. Vol. 115, pg. 200. 19. Campbell, M. F.: Perineal Testicle. 1936. Vol. 106, pg. 222. 20. McCutcheon, H. B.: Delayed Tests, Further Observations. Med. Jour. Australia 1938. Vol. 1, pg. 654. 21. Weisman, A. T.: Spermatazoa and Sterility. Hoeber 1941, Vol. 1, pg. 222.