Vol. 115, June Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1976 by The Williams & Wilkins Co.
THE VANISHING TESTIS SYNDROME: INDICATIONS FOR CONSERVATIVE THERAPY STEPHEN E. TOSI*
AND
LAWRENCE J. MORIN
From the Section of Urology, Dartmouth-Hitchcock Medical Center, Hanover, New Hampshire
ABSTRACT
Bilateral anorchism is a rare condition. In the past almost all of these patients have undergone surgical exploration. With modern laboratory determinations of serum gonadotropin and testosterone it is now possible to avoid operation in a large number of these cases. A case is presented that illustrates this point and a protocol is established for the treatment of bilateral anorchism, including indications for operation and conservative management. Bilateral anorchism is a rare condition, with a reported frequency of 1 in 20,000 male subjects. 1 About 81 cases have been reported in the literature. 2 • 3 Recent publications have advocated surgical exploration in all cases of bilateral cryptorchidism. • Other studies have suggested testicular artery angiography as a method of preoperative localization of intraabdominal testes. 5 Our experience with a case of anorchism in an otherwise normal young boy prompted a review of the subject. Herein we present what we believe is a reasonable alternative to surgical exploration in selected cases of anorchism. EMBRYOLOGY
The embryology of the male genitourinary tract must be understood in order to appreciate the term vanishing testis. The male gonad develops from the medial aspect of the urogenital ridge and first appears during the fifth and sixth weeks of fetal life. Simultaneously, male and female sex ducts develop. During the fifth week the wolffian and miillerian ducts transverse the germinal ridge. The wolffian duct eventually becomes the vas deferens and the epididymis. Union between the rete tubules of the testis and the wolffian duct is complete at 6 months. In the normal male subject the miillerian duct degenerates, leaving only vestigial remnants (appendix testis and prostatic utricle). The fetal testis is of primary importance in the development of the wolffian duct (male) system and the degeneration of the miillerian duct (female) system. In the absence of testes the female system will develop and the wolffian duct will degenerate. If testes are present but disappear or are removed early in fetal development a female system will develop. If testes are present but disappear after a critical amount of time (16 weeks of development)• a male system will develop. Therefore, in a phenotypic male subject with proved bilateral anorchism it must be hypothesized that testes were present through 16 weeks of embryologic development and then disappeared. Numerous hypotheses, including trauma, torsion and infection, have been advanced to account for the disappearance. CASE REPORT
An 11 ¼-year-old boy was referred because of absent testicles. The patient was the product of a completely normal birth and delivery. No testes were noted at birth. The patient was given anterior pituitary-like hormone when he was 5 years old but no testicular descent occurred. At age 6 years he underwent Accepted for publication November 14, 1975.
* Requests for reprints: 2 Maynard St., Hanover, New Hampshire 03755. 758
bilateral groin, retroperitoneal and intraperitoneal exploration. No cord structures were found on the left side and a rudimentary vas was found on the right side. The patient had a relatively normal childhood, did well in school and was active in athletics. He was admitted to our institution for further evaluation in February 1975. Physical examination revealed an eunuchoid body habitus with an arm span exceeding height by 4 cm. There was absence of facial, axillary, pubic and leg hair. The penis was small (3 cm. in length) and the scrotum was empty with no rugae. The patient was in the third percentile for height and fortieth percentile for weight. An excretory urogram was normal. Serum testosterone was 0.01 mg. per dl. (normal 0.3 to 0.10 mg. per dl.). Serum luteinizing hormone was 38.0 mlU. per ml. (normal 0.6 to 3.0 mlU. per ml.) and follicle stimulating hormone was 95.0 mlU. per ml. (normal 3.0 to 18.0 mIU. per ml.). A buccal smear showed absent Barr bodies. Bone age was 10 years. A flush aortogram revealed no evidence of testicular arteries. The patient was believed to have the vanishing testis syndrome and was discharged from the hospital on 2.5 mg. anavar per day, a mild androgenic steroid. After 2 months of therapy the patient noticed beginning pubic hair and an increased penile size (3.7 cm.). DISCUSSION
Some secondary sexual characteristics have developed at puberty in occasional patients with· anorchism. Serum testosterone has been elevated in these patients. 7 It has been hypothesized that the testosterone may be secreted by extragonadal Leydig cells, which may be found along the pathway of normal testicular descent. It also could be hypothesized that gonadal tissue was missed at the time of surgical exploration. The incidence of testicular tumors in undescended testes is 3.6 per cent or 14 times more than in normally located testes. 8 It has been reported that 1 in 20 abdominal testes will become malignant.• Because of these statistics there has been an understandable tendency to explore surgically all patients with cryptorchidism and anorchism. However, if the same information can be obtained without the risks of operation it would seem reasonable that a conservative course should be followed. Our patient falls into the category of individuals who do not need an operation. Since the follicle stimulating hormone and luteinizing hormone are exceedingly high and the serum testosterone is barely assayable it is obvious that no Leydig cells exist. Surgical exploration would be fruitless in such a patient. Similar information can be obtained in a young phenotypic male subject with low gonadotropin levels. Serum testosterone
VANISHING TESTIS SYNDROME PHENOTYPIC
MALE
with no clinically evident gonads
~
SERUM TESTOSTERONE
NORMAL
or
LOW
HIGH
!
!
SURGICAL EXPLORATION FOR GONADS
(
SERUM
FSH + LH
pre op les!iculor artery) arleriogroms opliona I
~
LOW or
HIGH
MORMAL
i
j
NO SURGERY INDICATED
COURSE OF GONADOTROPHIN
4
;::::)°"~ SERUM
TESTOSTERONE
LOW
ELEVATION
l
SURGICAL EXPLORATION FOR GONADS
!
NO SURGERY INDICATED
(pre op testicular artery orteriogroms optional)
can be measured before and after a brief parenteral course of chorionic gonadotropin. If there is no testosterone response it can be surmised that no gonadal tissue exists and, therefore, surgical exploration is unwarranted. If there is a testosterone response surgical exploration should be done. Testicular arteriography may serve as a useful adjunct in these cases and should be considered as a means of localizing gonadal tissue preoperatively so that it may be more easily located at the time of operation. The following regimen has been suggested. 10 Plasma testosterone is initially determined. The patient then receives 5,000 units of gonadotropin intramuscularly daily for 4 days. Plasma testosterone is measured on the day following cessation of gonadotropin administration. The principles outlined in the aforementioned paragraphs are then applied. The approach to patients with bilateral cryptorchidism is summarized schematically in the figure.
5. Ben-Menachem, Y., deBerardinis, M. C. and Salinas, R.: Localization of intra-abdominal testes by selective testicular arteriography: a case report. J. Urol., H2: 493, 1974. 6. Federman, D. D.: Abnormal Sexual Development: A Genetic and Endocrine Approach to Differential Diagnosis. Philadelphia: W. B. Saunders Co., p. 87, 1967. 7. Kirschner, M. A., Jacobs, J. B. and Fraley, E. E.: Bilateral anorchia with persistent testosterone production. New Engl. J. Med., 282: 240, 1970. 8. Mostofi, F. K.: Testicular tumors. Epidemiologic, etiologic, and pathologic features. Cancer, 32: 1186, 1973. 9. Sauer, H. R., Watson, E. M. and Burke, E. M.: Tumors of the testicle. Surg., Gynec. & Obst., 86: 591, 1948. 10. Federman, D. D.: Abnormal Sexual Development: A Genetic and Endocrine Approach to Differential Diagnosis. Philadelphia: W. B. Saunders Co., p. 32, 1967.
COMMENT REFERENCES 1. Borrow, M. and Gough, M. H.: Bilateral absence of testes. Lancet,
l: 366, 1970. 2. Glenn, J. R. and McPherson, H. T.: Anorchism: definition of a clinical entity. J. Urol., Hl5: 265, 1971. 3. Goldberg, L. M., Skaist, L. B. and Morrow, J. W.: Congenital absence of testes: anarchism and monarchism. J. Urol., Hl: 840, 1974. 4. Reckler, J. M., Rose, L. I. and Harrison, J. H.: Bilateral anorchism. J. Urol., U3: 869, 1975.
The authors have outlined a logical approach for the evaluation of boys with non-palpable testes. The presence of high gonadotropins in postpuberal boys with anorchia is well recognized but prepuberal boys also may have elevated gonadotropins. Consequently, in prepuberal patients the measurement of serum luteinizing hormone and follicle stimulating hormone may be all that is necessary to document the absence of testicular tissue. However, if serum gonadotropin levels are low human chorionic gonadotropin stimulation should be done.
P.C.W.
THE JOURNAL OF UROLOGY
Copyright© 1976 by The Williams & Wilkins Co.
THE VANISHING TESTIS SYNDROME: INDICATIONS FOR CONSERVATIVE THERAPY STEPHEN E. TOSI*
AND
LAWRENCE J. MORIN
From the Section of Urology, Dartmouth-Hitchcock Medical Center, Hanover, New Hampshire
ABSTRACT
Bilateral anorchism is a rare condition. In the past almost all of these patients have undergone surgical exploration. With modern laboratory determinations of serum gonadotropin and testosterone it is now possible to avoid operation in a large number of these cases. A case is presented that illustrates this point and a protocol is established for the treatment of bilateral anorchism, including indications for operation and conservative management. Bilateral anorchism is a rare condition, with a reported frequency of 1 in 20,000 male subjects. 1 About 81 cases have been reported in the literature. 2 • 3 Recent publications have advocated surgical exploration in all cases of bilateral cryptorchidism. • Other studies have suggested testicular artery angiography as a method of preoperative localization of intraabdominal testes. 5 Our experience with a case of anorchism in an otherwise normal young boy prompted a review of the subject. Herein we present what we believe is a reasonable alternative to surgical exploration in selected cases of anorchism. EMBRYOLOGY
The embryology of the male genitourinary tract must be understood in order to appreciate the term vanishing testis. The male gonad develops from the medial aspect of the urogenital ridge and first appears during the fifth and sixth weeks of fetal life. Simultaneously, male and female sex ducts develop. During the fifth week the wolffian and miillerian ducts transverse the germinal ridge. The wolffian duct eventually becomes the vas deferens and the epididymis. Union between the rete tubules of the testis and the wolffian duct is complete at 6 months. In the normal male subject the miillerian duct degenerates, leaving only vestigial remnants (appendix testis and prostatic utricle). The fetal testis is of primary importance in the development of the wolffian duct (male) system and the degeneration of the miillerian duct (female) system. In the absence of testes the female system will develop and the wolffian duct will degenerate. If testes are present but disappear or are removed early in fetal development a female system will develop. If testes are present but disappear after a critical amount of time (16 weeks of development)• a male system will develop. Therefore, in a phenotypic male subject with proved bilateral anorchism it must be hypothesized that testes were present through 16 weeks of embryologic development and then disappeared. Numerous hypotheses, including trauma, torsion and infection, have been advanced to account for the disappearance. CASE REPORT
An 11 ¼-year-old boy was referred because of absent testicles. The patient was the product of a completely normal birth and delivery. No testes were noted at birth. The patient was given anterior pituitary-like hormone when he was 5 years old but no testicular descent occurred. At age 6 years he underwent Accepted for publication November 14, 1975.
* Requests for reprints: 2 Maynard St., Hanover, New Hampshire 03755. 758
bilateral groin, retroperitoneal and intraperitoneal exploration. No cord structures were found on the left side and a rudimentary vas was found on the right side. The patient had a relatively normal childhood, did well in school and was active in athletics. He was admitted to our institution for further evaluation in February 1975. Physical examination revealed an eunuchoid body habitus with an arm span exceeding height by 4 cm. There was absence of facial, axillary, pubic and leg hair. The penis was small (3 cm. in length) and the scrotum was empty with no rugae. The patient was in the third percentile for height and fortieth percentile for weight. An excretory urogram was normal. Serum testosterone was 0.01 mg. per dl. (normal 0.3 to 0.10 mg. per dl.). Serum luteinizing hormone was 38.0 mlU. per ml. (normal 0.6 to 3.0 mlU. per ml.) and follicle stimulating hormone was 95.0 mlU. per ml. (normal 3.0 to 18.0 mIU. per ml.). A buccal smear showed absent Barr bodies. Bone age was 10 years. A flush aortogram revealed no evidence of testicular arteries. The patient was believed to have the vanishing testis syndrome and was discharged from the hospital on 2.5 mg. anavar per day, a mild androgenic steroid. After 2 months of therapy the patient noticed beginning pubic hair and an increased penile size (3.7 cm.). DISCUSSION
Some secondary sexual characteristics have developed at puberty in occasional patients with· anorchism. Serum testosterone has been elevated in these patients. 7 It has been hypothesized that the testosterone may be secreted by extragonadal Leydig cells, which may be found along the pathway of normal testicular descent. It also could be hypothesized that gonadal tissue was missed at the time of surgical exploration. The incidence of testicular tumors in undescended testes is 3.6 per cent or 14 times more than in normally located testes. 8 It has been reported that 1 in 20 abdominal testes will become malignant.• Because of these statistics there has been an understandable tendency to explore surgically all patients with cryptorchidism and anorchism. However, if the same information can be obtained without the risks of operation it would seem reasonable that a conservative course should be followed. Our patient falls into the category of individuals who do not need an operation. Since the follicle stimulating hormone and luteinizing hormone are exceedingly high and the serum testosterone is barely assayable it is obvious that no Leydig cells exist. Surgical exploration would be fruitless in such a patient. Similar information can be obtained in a young phenotypic male subject with low gonadotropin levels. Serum testosterone
VANISHING TESTIS SYNDROME PHENOTYPIC
MALE
with no clinically evident gonads
~
SERUM TESTOSTERONE
NORMAL
or
LOW
HIGH
!
!
SURGICAL EXPLORATION FOR GONADS
(
SERUM
FSH + LH
pre op les!iculor artery) arleriogroms opliona I
~
LOW or
HIGH
MORMAL
i
j
NO SURGERY INDICATED
COURSE OF GONADOTROPHIN
4
;::::)°"~ SERUM
TESTOSTERONE
LOW
ELEVATION
l
SURGICAL EXPLORATION FOR GONADS
!
NO SURGERY INDICATED
(pre op testicular artery orteriogroms optional)
can be measured before and after a brief parenteral course of chorionic gonadotropin. If there is no testosterone response it can be surmised that no gonadal tissue exists and, therefore, surgical exploration is unwarranted. If there is a testosterone response surgical exploration should be done. Testicular arteriography may serve as a useful adjunct in these cases and should be considered as a means of localizing gonadal tissue preoperatively so that it may be more easily located at the time of operation. The following regimen has been suggested. 10 Plasma testosterone is initially determined. The patient then receives 5,000 units of gonadotropin intramuscularly daily for 4 days. Plasma testosterone is measured on the day following cessation of gonadotropin administration. The principles outlined in the aforementioned paragraphs are then applied. The approach to patients with bilateral cryptorchidism is summarized schematically in the figure.
5. Ben-Menachem, Y., deBerardinis, M. C. and Salinas, R.: Localization of intra-abdominal testes by selective testicular arteriography: a case report. J. Urol., H2: 493, 1974. 6. Federman, D. D.: Abnormal Sexual Development: A Genetic and Endocrine Approach to Differential Diagnosis. Philadelphia: W. B. Saunders Co., p. 87, 1967. 7. Kirschner, M. A., Jacobs, J. B. and Fraley, E. E.: Bilateral anorchia with persistent testosterone production. New Engl. J. Med., 282: 240, 1970. 8. Mostofi, F. K.: Testicular tumors. Epidemiologic, etiologic, and pathologic features. Cancer, 32: 1186, 1973. 9. Sauer, H. R., Watson, E. M. and Burke, E. M.: Tumors of the testicle. Surg., Gynec. & Obst., 86: 591, 1948. 10. Federman, D. D.: Abnormal Sexual Development: A Genetic and Endocrine Approach to Differential Diagnosis. Philadelphia: W. B. Saunders Co., p. 32, 1967.
COMMENT REFERENCES 1. Borrow, M. and Gough, M. H.: Bilateral absence of testes. Lancet,
l: 366, 1970. 2. Glenn, J. R. and McPherson, H. T.: Anorchism: definition of a clinical entity. J. Urol., Hl5: 265, 1971. 3. Goldberg, L. M., Skaist, L. B. and Morrow, J. W.: Congenital absence of testes: anarchism and monarchism. J. Urol., Hl: 840, 1974. 4. Reckler, J. M., Rose, L. I. and Harrison, J. H.: Bilateral anorchism. J. Urol., U3: 869, 1975.
The authors have outlined a logical approach for the evaluation of boys with non-palpable testes. The presence of high gonadotropins in postpuberal boys with anorchia is well recognized but prepuberal boys also may have elevated gonadotropins. Consequently, in prepuberal patients the measurement of serum luteinizing hormone and follicle stimulating hormone may be all that is necessary to document the absence of testicular tissue. However, if serum gonadotropin levels are low human chorionic gonadotropin stimulation should be done.
P.C.W.
