The child with cryptorchidism or an "empty scrotum" represents one of the most common problems referred to the pediatric urologist or surgeon. The disorder occurs in approximately 0.08% to 1.0% of male children, although the incidence may be increasing. Despite this relatively high rate of occurrence, very little is known about the etiology of the disorder. Surgery continues to be the cornerstone of therapy for the correction of cryptorchidism.
The purpose of this review is to acquaint the reader with a basic understanding of the pathogenesis, pathophysiology, and complications associated with the undescended testis and to discuss the treatment methods used at our institution.
The incidence of testicular maldescent is directly related to the maturity and the birth weight of the infant (Table I).1 In the full-term male with a birth weight ≥ 2,500 g, the incidence of cryptorchidism is between 3% and 4%, while in the premature it approaches 30%. As the weight of these infants approaches 2,500 g, the majority of previously undescended testes have reached the scrotum spontaneously. By 1 year of age, virtually all testes that might be expected to descend spontaneously will have done so.
Recent data have suggested that the incidence of cryptorchidism may have doubled over the past 20 years, but this may be simply due to either greater awareness of cryptorchidism by the practicing physician or to diagnostic confusion with a more common anomaly, the retractile testis.2 In 10% of patients with cryptorchidism, the anomaly is bilateral. Unilateral or bilateral anorchism is found in approximately 4% of patients with cryptorchidism.
EMBRYOLOGY AND MECHANISM OF TESTICULAR DESCENT
In the human, by the sixth week of gestation the primordial germ cells have made their way from the yolk sac to the genital ridges. The gubernaculum appears at this time as a ridge of mesenchyme extending from the genital ridge to the site of the future scrotum, the genital swellings. The indifferent gonad begins its differentiation into the testis during the seventh week of gestation, and müllerian inhibiting factor (MIF) and testosterone (T) are secreted by the fetal testis during the eighth week of gestation. MIF, secreted by the Sertoli's cells, induces regression of the müllerian ducts, whereas T, secreted by the fetal Leydig's cells under maternal human chorionic gonadotropin hormone regulation (HCG), induces development of the epididymis and vas deferens (wolffian duct structures). From the ninth to the 15th weeks, the external genitalia develop; at this time the fetal testis lies in an intraabdominal position, proximal to the internal inguinal ring.
Between the 12th week and seventh month of gestation, a peritoneal out-pouching, the processus vaginalis, reaches the scrotum. At the seventh month of gestation, just prior to testicular descent, there is a rapid increase in the size of the vasa deferentia and spermatic vessels, and the gubernaculum swells. The swollen gubernaculum stretches the inguinal canal and scrotum, thus allowing free descent of the testis. The processus vaginalis obliterates and the gubernaculum atrophies after testicular descent is complete.
Incidence of Cryptorchidism in Relation to Age1
Many theories have been proposed to explain the mechanism of testicular descent. The traction theory suggests that the testis is pulled into the scrotum by the gubernaculum. * The theory of differential growth promotes the concept that there is rapid growth of the body wall when compared to that of the relatively immobile gubernaculum.4 Gier and Marion suggested that intraabdominal pressure is the primary force in testicular descent. Experimental evidence in the rabbit and rat support this suggestion. 5-7
The endocrine system has been proposed to play a major role in testicular descent, perhaps in concert with one or more of the aforementioned mechanisms. It was shown in monkeys and in humans that either T or HCG could induce testicular descent.8,9 More recently it has been shown in the rat and rabbit that dihydrotestosterone is actively involved in testicular descent. Indeed, abnormalities of gonadotropin and androgen metabolism, such as occurring in disease states affecting various levels of the hypothalamicpituitary-testicular axis, are associated with a high incidence of cryptorchidism (Table 2).10,11
The exact role of androgens in promoting testicular descent remains uncertain and controversial. Walsh et al found no difference between cryptorchid and normal males in HCG stimulation as a marker of the integrity of the hypothalamic-pituitary-testicular axis.12 In contrast, Cacciari et al found a subnormal testosterone response to HCG stimulation in cryptorchid males. ' * There are also conflicting data regarding LH and FSH secretion as well as LH and testosterone response to GnRH stimulation in cryptorchid and normal children.14-17
The cryptorchid testis may be categorized, based on its location, as:
* abdominal, that is proximal to the internal inguinal ring;
Hormonal Abnormalities Associated with Cryptorchidism10
* canalicular, located between the internal and external inguinal rings; or
* ectopic, located outside the normal pathways of descent between the abdominal cavity and the scrotum (Figure).
The most common site of testicular ectopia is the superficial inguinal pouch of Dennis Browne, although ectopic testes may also be found in suprapubic, femoral, and even perineal sites.18
It is of utmost importance to differentiate the true undescended testis from the more common retractile testis. This may be a difficult differentiation, particularly in the child over 5 years old. The retractile testis is a benign disorder due to a hyperactive cremasteric reflex; it does not require intervention. It is helpful to review old medical records to determine whether the testes have ever been present in the scrotum. One or more visits to the physician's office may be necessary to differentiate a retractile from a cryptorchid testis. In a relaxed child, a retractile testis usually can be manipulated or milked into the scrotum using gentle traction.
Once a testis is thought to be truly cryptorchid, it is important to verify its position. When located at the superficial inguinal pouch or near the external ring, the testis is usually palpable. When the testis is not palpable, it is usually intracanalicular or intraabdominal.' With the finding of bilateral nonpalpable testes, it is important to rule out bilateral anorchia. This differentiation can usually be made using a threeday course of HCG (2000 IU daily x 3).19 In the anorchid state, basal gonadotropin levels are extremely high and there is no increase in testosterone levels following exogenous HCG administration.
A unique dilemma is that of the unilateral impalpable testis. It is important to establish its presence so that appropriate management may be undertaken either to put it in a palpable position surgically or to remove it. Ultrasound, CT scanning, MRI, herniography, and testiculat angiography and venography have been used with variable results. More recently the use of the laparoscope has been popularized to locate these testes. 20,2' Regardless of the diagnostic test chosen, it is reasonable to assume that all patients with unilateral impalpable testis will require an exploration to determine whether the testis is present or not.
Figure. Sites of ectopic testes. (Reprinted by permission of Williams and Wilkins Company, Baltimore. From Rajfer J. Frey H: Cryptorchidism, in Resnick Ml fed): Current Trends in Urology, Vol 2, 1982.)
There is much theoretical and practical rationale for correcting the undescended testis, including: 1) the correction of a cosmetic defect; 2) the potential for psychologic maladjustment that might be prevented or reversed by bringing the testis into the scrotum; 3) an increased susceptibility of the undescended testis to malignant degeneration (if not removed it is certainly wise to place it in a site where it can be palpated with ease); and 4) the potential for improvement of fertility.
It is our policy to surgically place the testis within the scrotum at or around the end of the first year of life. In all prepubertal children, we attempt to salvage all testes if possible and try to place them in a site where they can be easily palpated. If this is not possible, an orchiectomy is performed. Orchiectomy should also be considered for the late postpubertal male and in patients with intersex syndromes in which the testes might be dysgenetic and prone to malignant degeneration.
In most cases, orchiopexy can be performed in an outpatient setting. In unilateral situations, we prefer a standard inguinal incision, whereas in the case of the nonpalpable testis, it may be necessary to enter the peritoneum to search for the organs. For bilateral nonpalpable testes, we prefer a midline transabdominal approach.
At times, the testes cannot be placed easily within the scrotum. Staged operations or actual transection of the cord relying on accessory blood vessels (FowlerStephens technique) with or without microsurgical reanastomosis have been used with mixed results to bring such high undescended testes down to the scrotum. 22
Hormonal therapy (HCG and GnRH) has been used for the treatment of undescended testes. HCG administration was proposed under the premise that it would stimulate the Leydig's cells, resulting in an increase in plasma testosterone and thus promoting testicular descent. The results, however, have been less than ideal.23,24 The results with GnRH are controversial,25 but in our hands have been very disappointing.26 In our opinion, the value of hormonal therapy in treating cryptorchidism is still an unresolved issue requiring additional controlled studies. In any event, early therapy (at or before the first birthday) is advocated.
Virtually all undescended cryptorchid testes are associated with an indirect hernia. This is due to persistence of the processus vaginalis.
The increased susceptibility of the undescended testis to undergo torsion is due to an anatomic discrepancy between the testis and its mesentery. 1 Torsion is most likely to occur in the postpubertal male, when there is a gross increase in testicular size relative to the mesentery.
To produce viable and mature spermatozoa, the testis must descend from the warm intraabdominal environment to that of the cool intrascrotal compartment.27 Even a rise of 1. 5° to 2° C greater than that of the scrotum will inhibit spermatogenesis, although the function of the Leydig's cells (testosterone synthesis) is not affected. The further the testes are away from the bottom of the scrotum the greater the likelihood of damage to the seminiferous tubules. Of interest is the fact that the defect in spermatogenic activity of the contralateral scrotal testis may also be present in the patient with unilateral cryptorchidism.28,29 Lipschultz et al discovered that the unilateral cryptorchids had much lower than expected sperm counts when compared with normal adult patients. 30
The association between neoplasia and cryptorchidism is controversial. Approximately 10% of testicular tumors arise in undescended testes.31 The chance of an undescended testis undergoing malignant degeneration is approximately 1 in 4,000 (2.2 per 8,000) each year. Thus the risk of an undescended testis undergoing malignant degeneration is small; however, an abdominal testis is four times more likely to undergo malignant degeneration than an inguinal testis.
Because testicular tumors have occurred in patients who have undergone orchiopexies as early as 5 years of age, we recommend surgical correction around the first year of age, since there is little likelihood of descent beyond this age and ultrastructural changes (abnormalities) begin to occur during the second year of life. 32 Whether early surgical correction will deter the potential for development of neoplasms remains to be seen.
Johnson et al have shown that testicular tumors can also occur in the contralateral scrotal testis of the patient with unilateral cryptorchidism.33 In bilateral cryptorchidism there is a 15% chance of developing a tumor in the contralateral testis, should one testis become involved with tumor. 34 If both testes are intraabdominal and one testis becomes malignant, there is approximately a 30% chance that the other testis will become malignant. The most common form of tumor in this group is seminoma, followed by nonseminomatous germ cell tumors. In the intersex disorders associated with cryptorchidism, gonadoblastoma is the most common tumor seen. 35
Cryptorchidism is a frequently neglected problem seen by the practitioner. Early diagnosis and the institution of therapy for this disorder are to be encouraged. Until large controlled studies can substantiate a role for hormonal therapy, surgery remains the treatment of choice in the management of the child with cryptorchidism.
1. Scorer CG, Farrington GH: Congénital Deformities of the Testis imj Epididymis. New York, Appleton-Century-Cnifts, 1971.
2. John Radclirfc Hospital Cryptorchidism Study Group: Cryptorchidism: An apparent substantial increase since I960. Br Med J 1986; 293:1401.
3. Rajfer J: Morphological study of testicular descent in the rabbit. Investigative UWogy 1981; 18:295.
4. McMurrich J: The Development«/ the Human Body, A Manual of Human Embryology, ed 7. Philadelphia, P. Blaskisttm's Son and Company, 1923, ? 374.
5. Gier HT, Marion GB: Development of the mammalian testis, in Johnson AD, Gomez WR. Vandmark NL (eds): The Testis. New York. Academic Press. 1970.
6. Elder JS, Isaac JT, Walsh PC: Androgenic sensitivity of the gubernaculum testis: Evidence for humoral/mechanical interaction in testicular descent. Abstract 117. Presented at the American Urological Association Meeting, Boston, May 1981.
7. Frey H, Peng S. Rajfer J: Synergy between abdominal pressure and androgens in testicular descent. Biol Reprod 1983; 29:1233.
8. Engle ET: Experimentally induced descent of the testis in the Macacus monkey by hormones lrom the anterior pituitary and pregnancy urine. EnaV-rinolugy 1932; 16.513.
9. Hamilton JB: The effect ot male hormone upon the descent of the testes. Anuí Ree 193«: 70:533.
10. Rajfer J. Walsh PC: Hormonal regulation of testicular descent: Experimental and clinical observations. J IAuI 1977; 118:985.
11. Rajfer J: An endocrinological study of testicular descent in the rabbit: Preliminary observations. Abstract 176. Presented at the American Urological Association Meeting. San Francisco. May 1980.
12. Walsh PC. Curry N, Mills RC, et al: Plasma androgen response to HCG stimulation in prepubertal boys with hypospadias and cryptorchidism. J Clin Endocrinol Metob 1976; 42:52.
13. Cacciari E, Cicognani A, Pirazzoli P, et al: Hypophyso-gonadal function in the cryptorchid child: Differences between unilateral and bilateral cryptorchids. Actu Endi<crmol 1976; 83:182.
14. Hadziselimovic F: Pathogenesis of cryptorchidism, in Kogan SJ. Hate: ESE (eds): Clinics in Androloge. !Winnie Andnilogy. The Hague, Mantinius NijofF, vol 7. 1981.
15. Von Vliet Ci. Gavfric2 A. Robyn C. et al: Plasma gonadotropin values in prepubertal cryptorchid hoys: Similar increase of FSH in uni- and bilateral cases. I Feduirr 1980; 97:253.
16. Job JC, GendrelD. Sarar A, et al: Pituitary LH and FSH and testosterone secretion in infants with undescended testes. Acta Endocrinol 1977; 85:644.
17. Gendrel D, Ruber M. Chaussain JL, et al: Correlation of pituitary and testicular responses to stimulation tests in cryptorchid children. Actu Endocrinol 1977; 86:641.
18. Brown D: Treatment ut the undescended testis. Proceeding of the KuW Society uf Mediane 1949; 42:643.
19. Winter JSD. Tarasha S. Faiman C: The hormonal response to HCG stimulation in male children and adolescents. J Clin Endocrinol Metab 1972; 34:348.
20. Hamidimia A, NoId S, Amankwah KS: Localization and treatment ol nonpalpable testes. Surg Gynecol Ofestet 1984; 159:439.
21. Maone PS, Gumey EJ: A comparison between ultrasonography and laparoscopy in localizing the impalpable undescended testis. HrJ Unii 1985: 57:f#í.
22. Fowler R, Stephens FD: The role of testicular vascular anatomy in the salvage of high undescended testes. Aust NZJ Surg 1959; 29:92.
23. Bigler JA. Hardy LM, Scott HV: Cryptorchidism treated with gonadotropic principle. Am J Dis Child 1938; 55:273.
24. Job JC. Canlorbe P. Garagorri JM, et al: Hormonal therapy of cryptorchidism with human chorionic gonadotropin (HCG). Unii Clin North Am 1982; 9:405.
25. Hadzisclimuvic F: Treatment of cryptorchidism with GnRH. Urol Clin North Am 1982; 9:413.
26. Rajfer J. Handelsman DJ. Swcrdloff RS. et al: Hormonal therapy of cryptorchidism. N Engl J.Med 1986; 314:166.
27. Mixwe CR, Quick WJ: The scrotum as a temperature regulator lor the testes. Am J Physiol 1924: 68:70.
28. Hecker W, Hein: HA: Cryptorchidism and fertility. J Pediair Surg 1967: 2:513.
29. Wnxlhead DM. Pohl DR. Johnson DE: Fertility of patients with solitary testes. J LW 1973; 100:66.
30. Lipschultz Ll. Caminos-Torres R. Greenspan CS. et al: Testicular function after orchidopexy tiir unilaterally descended testis. N Engl J Med 1976; 295:15.
31. Gordon-Taylor Ci, Wynbon NR: On malignant tumors of the testis, fir J Surg 1947; 35:6.
32. Airman BL, Malament M: Carcinoma of the testis following orchidopexy. J Urti 1967; 97:498.
33.Johnson DE. Woodhead DM, Pohl DR, er al: Cryptorchidism and testicular rumorigencsis. Surgery 1968: 63:919.
34. Gilbert JB. Hamilton JB: Incidence and nature of tumors in ectopic testes. Sutg Gynecol Ohstef 1970; 71:731.
35. Scully RE: Gonadoblastoma: A review of 74 cases. Cancer 1970; 25:1340.
Incidence of Cryptorchidism in Relation to Age1
Hormonal Abnormalities Associated with Cryptorchidism10