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True Hermaphrodite Siblings
THE .JOURNAL O.F UROLOUY
·vol. 79, No. 0, .June 1958 P,n:nred [-.S.A.
TRC1'~ IIER:\IAPHRODITE SIBLI~GS VV A. J\IIL:'.\'ER, vV. B. GARLICK, A. J. FINK
AND
A. A. STEIN
From the Departments of -Crology and Pathology, Albany Hospital, Albany, N.
In a da;c:sical treatise on genital anonmlies, Young laid the foundation of aC·· ceptable criteria for the diagnosis of true herma,phroditism. He Rtated it to be the presence in the same individual of both microscopic ovarian and testicular ti:c;sues. From the first acceptable report of Salen in 1900, to l9SG, there have been recently collected and re-1·icwecl 68 proven case8. Undoubtedly, thiH reported num-· bcr reflects only a small part of the actual incidence. To date, there have been no reported instances of true hemmphroditism oecurring in siblings. The recent exarnination of two "brothers" for treatment of genital anomalies, ,d10 11·en: proven to be true hermaphrodites, is considered sufficicutly rare and of potential etiological implication to geneticists -working in this field to ,n1xmnt publicaticn1. Hermaphroditism is most often su8pectcd when there an, con1bined genital aberrnncies, but it is not usually considered in the differential diagno::,is of testicular nodules. The following caRe of the older Ribling, hovrnn1r, is an example of a testicular nodule which proved to be an
Case J. G. B., a 13-ycar-old white boy, was admitted to the Albany Hm,pitnl on Augu:-;t 2D, 19[55, with an undescended left testis. Past history revealed a full term, spoutaneous deli-rnry with normal feeding, scholastic and social developrncnt. He had measles, mumps and chicken pox in early childhood without sequelae. The patient was active in contact sport::; and considered to be masculine in gender and orientation There was one older male sibling, age 17, considered to be normal, and a 12·-year-old brother and 5-year-old sister also without genital anomalies. A one-year-old brother, however, was stated to have a marked penoscrotal hypospadias and unde8cended right testicle. PhyHieal examination disclosed a tall, slender, well-developed youth, with an early pubertal male hair escutcheon and android type pelvis. Slight breast enlargement was present, A small testis was palpable in the left inguinal cannl, but it was not possible to bring it dmn1 to the scrotum manually. The right testis was in the serotum and presented a pea-::Jized nodule, palpable on the upper The penis was of normal size and presented a balanitic one degree hypospadias 1Yith a narrow scrotal rnphe band extending to the base of the penile shaft, Ree figure 1 The lower pole of the left testis ,Yas also biopsied. On rectal examination, the prostate gland was identified. The next clay, a left orchiopexy and hernia repair with the scrotal placement of a normal-appearing testis and epididyn1is were performed. DiYision of the rudimentary chordee was likmvise accomplished. right scrotal exploration then revealed a 2.5 by 1.5 by 1.5 cm. brown, abnormal Read at annual meeting of Northeastern Section of American Urological Association, Whiteface, N_ Y., September 12-15, 1957. 1003
1004
MILNER, GARLICK, FINK AXD STEI;,,
Fw. 1. Case 1. Examination disclosed first degree hypospadias with narrow scrotal raphe band extending to base of penile shaft. Lower pole of left testis also biopsied.
appearing testis, seemingly enclosed in a translucent serous membrane with a normal, loosely attached epididymis. The upper pole of the testis consisted of a firm, rubbery, brown nodule which shelled out easily from its testicular bed. Frozen section revealed sclerosed testis containing a few small cystic spaces. However, permanent sections showed atrophic sclerosed testis surrounded by dense fibrous tissue I to 2 mm. in thickness which merged into typical ovarian tissue containing multiple graafian follicles. See figure 2, A. On October 7, cystoscopy revealed the presence of a normal prostate and bladder with a bifid verumontanum. There was no visible vaginal communication ·with the utricle. By rectal examination under anesthesia, no uterus ,ms palpable. A skin biopsy taken for chromosomal sex determination was interpreted as consistent with the male sex. There were no characteristic dumb-bell nuclei present in a count of 250 polymorphonuclear neutrophilic leukocytes, implying a male type of blood smear. Since the parents wished to defer further diagnostic procedures, the patient was discharged on October 8, with the advice that no reference to his sexual anomaly be made and that he continue to be reared as a normal male. The discharge diagnosis was true hermaphroditism, type indeterminate (i.e., ovotestis on one side and the other not examined). The patient was readmitted on April 4, 1957, complaining of progressive breast enlargement and monthly recurring breast tenderness. His mother stated that almost simultaneously with the onset of her menstrual symptoms, the patient would likewise have anorexia and "take to his room." On examination bilateral breast enlargement and a definite female mons pubis were noted. The scrotum
TRUE HERMAPHRODITE SIBLINGS
1005
Frn. 2. Case 1. A, biopsy of upper pole of testis revealed typical ovarian stroma containing numbers of ova and developing graffian follicles merging with well-developed testicular tissue. X 120. B, biopsy of lower pole of left gonad disclosed ovarian stroma adjacent to testicular tissue. X 120.
and penis appeared as normal for a pubertal male except for a first-degree glans hypospadias. The right testis was small and smooth. However, the left one, equally small, now felt nodular. Cord structures and the prostate on rectal examination were small but intact.
1006
MILNER, GARLICK, FINK AND STEIN
The need for further laboratory and surgical measures was stressed to the parents and with two instances of sexual aberrancy in the family they readily agreed. Laboratory measures were then performed and their results were as follows: F.S.H. levels showed 16-64 mouse uterine units (normal 8-24 m.u.u.), 17 ketosteroids of 8.2 mg. per 24 hours, 17-hydroxy-corticosteroid level of 2.5 mg. per 24 hours (normal 4-10 mg. per 24 hours), pregnandial less than 1 mg. per 24 hours (normal 5 trace amounts) and protein-bound-iodine showed 5.5 micrograms per cent (normal 4-10 mcg. per cent). On April 26, 1957, laparotomy and bilateral scrotal explorations were performed. Examination of the pelvis did not reveal any female structures and exposure of each vas deferens to the internal inguinal ring was also normal. The pelvic outlet was androgynoid. The right gonad and spermatic cord were mobilized through a low inguinal incision. This right greyish-white, smooth, ovoid gonad was then subject to bipolar biopsy and frozen section interpretation. The upper pole revealed a focally sclerosed and inflamed epididymis. The inferior pole showed testis displaying inactive spermatogenesis with moderate interstitial cell hyperplasia. Attention was then directed to the left gonad which was exposed with its cord attachment through a similar incision. The epididymis on the left was noted to be loosely attached to the testis, whereas the cord structures otherwise were normal-appearing on both sides. The left gonad appeared rudimentary with a thin translucent-like tunica albuginea and slightly nodular in its superior pole. It was felt that the upper pole represented an ovarian segment of an ovotestis. On frozen section examination, this tissue was again reported as showing inactive spermatogenesis and interstitial cell hyperplasia. This finding quickly led to biopsy of the lower pole and a report of ovarian tissue containing numerous ova and some follicular cysts (fig. 2, B). A total excision of the left gonad was then performed. Convalescence was uneventful and the patient was discharged on metandren linguets 10 mg. b.i.d. with a final diagnosis of true hermaphroditism, bilateral type (i.e., bilateral ovotestes). Case 2. T. G., a 13-month-old male child, was admitted on November 27, 1955, for correction of anomalous-appearing external genitalia. Birth history revealed a full term, normal spontaneous delivery. Other than frequent colds and measles at 5 months, there were no significant medical complaints or prior illnesses. Interrogation of the mother indicated that there had not been any known gestational nutritional deficiency, medical illnesses or exposure to x-ray in either pregnancy. Both parents stated they had no awareness of similar genital deformities in their respective families. With the exception of the genitalia, the physical examination was within normal limits. The scrotum was small and illdefined and contained on the left a small, retractile testis. On the right, there was, in addition to a palpable gonad, a communicating hydrocele and indirect inguinal hernia. The penis was small with a severe chordee and a hypospadiac urethra existing at the penoscrotal angle. The next day, excision lysis of the chordee and transplantation of the urethra to the perineum were performed. In addition, a right hydrocelectomy and hernia
TRUE HERMAPHRODITE SIBLINGS
1007
FIG. 3. Case 2. A, nodule from upper pole of right testis composed of ovarian stroma with large numbers of ova. X 120. B, nodule excised from upper pole of left testis showed both typical ovarian parenchyma and immature testicular tissue. X 120.
repair were done. Upon opening the hydrocele sac, a very small nubbin of greyishwhite tissue, measuring 0.2 cm. in its greatest dimension, was excised from the upper pole of the normal-appearing right testis. The histological report on the permanent section stated "ovarian tissue in which definite primordial follicles are numerous and characteristic ovarian stroma is present. No testicular elements are present (fig. 3, A)."
1008
MILNER, GARLICK, FINK AND STEIN
The patient, now 18 months old, was readmitted on June 11, 1956. Exploratory laparotomy the next day did not visualize the presence of any internal female sex organs. Left high scrotal exploration mobilized a normal-appearing testis with a pearly-white tunica albuginea. At the upper pole there was a palpable sensation of a nodule beneath the tunica. The tunica was incised, expressing from the upper pole a small, firm, greyish-yellow, ovoid structure, measuring 0.8 by 0.4 by 0.4 cm., covered with a semitranslucent fibrous membrane. This nodule was excised. An additional biopsy from the bed of the excised nodule revealed the presence of junctional ovarian and testicular tissue (fig. 3, B). Skin biopsy for sex chromatin pattern was negative (i.e., male). Final diagnosis, in view of a proven ovotestis only on the left side, was true hermaphroditism, unilateral type. It is considered probable that the remaining portion of the right gonad was testis and that this case also is representative of the bilateral type of true hermaphroditism. Hypospadias repair is planned in a few years and androgen supplement will be used, if needed, at puberty or earlier. DISCUSSION
By definition, an ovotestis is the unilateral histologically proven presence of testicular and ovarian tissues occurring as a single mass or as adjacent anatomically separate nodules. In our two cases of true hermaphroditism, it is likely that we have selectively enucleated the ovarian portion of the ovotestis. Although Mclver stated that only rarely can this be surgically accomplished, more recent studies indicate that bisexual gonad division is feasible and often surgically simple. It is worth emphasizing that an estimated 80 per cent of the ovotestes in the reported cases of true hermaphroditism have lent themselves readily towards selective unisexual gonadal enucleation. However, bipolar gonad biopsy and microscopic examination of all discrete nodules must be employed before removal, for gross interpretations frequently prove unreliable. Actually not more than 20 per cent of ovotestes showed inseparable mixing of ovarian and testicular tissues, usually evidenced by juxtaposition blending or, rarely, a central core of of either ovarian or testicular substance. The association of the combination of hypospadias and cryptorchidism present in almost all the previously reported instances of true hermaphroditism was similarly noted in these two cases. Assembled under the entity of true hermaphroditism are congenital anomalies of the gonads and the primary sex characteristics. These genitourinary anomalies are due to arrested or defective prenatal development. Considerable controversy exists between geneticists and environmentalists as to the factors of major importance in the creation of this form of teratism. That a persistent abnormal uterine environment was probably not responsible may be inferred from the fact that there were two normal siblings intermediate in age between these two cases. The occurrence of two similar type (bilateral ovotestes) true hermaphrodites in the same family lends additional support to the hereditary concept of defective germ plasm. More vital in its implications have been the findings and beliefs of the en-
TRUE HERMAPHRODITE SIBLINGS
1009
vironmentalists. Most prominently, Jost has expounded on the ability of fetal gonadal hormones to produce the changes seen in hermaphroditism. Also noted has been the hermaphroditic tendency of the retained genital ducts in vitamin A deficient rats during gestation. The field of experimental teratogenesis has shed further light on this obtuse problem by implicating not only specific time periods in the life of the developing embryo when teratogenic stimuli m::iy cause selective types of congenital anomalies, but also agent specificity wherein these stimuli, varying in quality and quantity, achieve the same anomalous result irrespective of time. SUMMARY
The first reported cases of true hermaphrodite siblings, bilateral type, have been presented. The presence of a testicular nodule combined with an external genital defect should suggest the diagnosis of true hermaphroditism and indicate the need for surgical exploration. Surgical sexual gonadal separation in the majority of ovotestes is feasible and histologically complete. The finding of true hermaphrodite siblings has given indirect support to the geneticists in their controversy concerning the etiology of this condition.
75 Willett St., Albany, N. Y. REFERENCES ANDERSON, R. C.: Causative factors underlying congenital heart malformations. Pediatrics, 14: 143-152, 1954. BREWER, J. L., JONES, H. 0. AND CuLVER, H.: True hermaphroditism. J.A.M.A., 148: 431-435, 1952. CECIL, A. B.: A true hermaphrodite. J. Urol., 72: 534-540, 1954. DoGRAMACI, I. AND GREEN, H.: Factors in etiology of congenital heart anomalies. J. Pediat., 30: 295-301, 1947. Doss, A. K. AND PRIESTLEY, J. T.: True hermaphroditism, report of a case. J. Urol., 43: 859-863, 1940. FINK, A. J.: True hermaphroditism: Review and analysis of 68 cases. Pending publication. JosT, A.: Problems of fetal endocrinology: The gonadal and hypophyseal hormones. Recent Prog. Hormone Research, 8: 379-418, 1953. MclvER, R. B., SEABAUGH, D.R. AND MANGELS, M. P.: True hermaphroditism: A report of two cases. J. Urol., 52: 67, 1944. WILSON, J. G., ROTH, C. B. AND WARKANY, J.: An analysis of syndrome of malformation induced by maternal vitamin A deficiency. Effects of restoration of vitamin A at various times during gestation. Am. J. Anat., 92: 189, 1953. WILSON, J. G.: Is there specificity of action in experimental teratogenesis? Pediatrics Supplem., 19: 755-763, 1957. YouNG, H. H.: Genital Abnormalities, Hermaphroditism and Related Adrenal Diseases. Baltimore: Williams & Wilkins Co., 1937.
·vol. 79, No. 0, .June 1958 P,n:nred [-.S.A.
TRC1'~ IIER:\IAPHRODITE SIBLI~GS VV A. J\IIL:'.\'ER, vV. B. GARLICK, A. J. FINK
AND
A. A. STEIN
From the Departments of -Crology and Pathology, Albany Hospital, Albany, N.
In a da;c:sical treatise on genital anonmlies, Young laid the foundation of aC·· ceptable criteria for the diagnosis of true herma,phroditism. He Rtated it to be the presence in the same individual of both microscopic ovarian and testicular ti:c;sues. From the first acceptable report of Salen in 1900, to l9SG, there have been recently collected and re-1·icwecl 68 proven case8. Undoubtedly, thiH reported num-· bcr reflects only a small part of the actual incidence. To date, there have been no reported instances of true hemmphroditism oecurring in siblings. The recent exarnination of two "brothers" for treatment of genital anomalies, ,d10 11·en: proven to be true hermaphrodites, is considered sufficicutly rare and of potential etiological implication to geneticists -working in this field to ,n1xmnt publicaticn1. Hermaphroditism is most often su8pectcd when there an, con1bined genital aberrnncies, but it is not usually considered in the differential diagno::,is of testicular nodules. The following caRe of the older Ribling, hovrnn1r, is an example of a testicular nodule which proved to be an
Case J. G. B., a 13-ycar-old white boy, was admitted to the Albany Hm,pitnl on Augu:-;t 2D, 19[55, with an undescended left testis. Past history revealed a full term, spoutaneous deli-rnry with normal feeding, scholastic and social developrncnt. He had measles, mumps and chicken pox in early childhood without sequelae. The patient was active in contact sport::; and considered to be masculine in gender and orientation There was one older male sibling, age 17, considered to be normal, and a 12·-year-old brother and 5-year-old sister also without genital anomalies. A one-year-old brother, however, was stated to have a marked penoscrotal hypospadias and unde8cended right testicle. PhyHieal examination disclosed a tall, slender, well-developed youth, with an early pubertal male hair escutcheon and android type pelvis. Slight breast enlargement was present, A small testis was palpable in the left inguinal cannl, but it was not possible to bring it dmn1 to the scrotum manually. The right testis was in the serotum and presented a pea-::Jized nodule, palpable on the upper The penis was of normal size and presented a balanitic one degree hypospadias 1Yith a narrow scrotal rnphe band extending to the base of the penile shaft, Ree figure 1 The lower pole of the left testis ,Yas also biopsied. On rectal examination, the prostate gland was identified. The next clay, a left orchiopexy and hernia repair with the scrotal placement of a normal-appearing testis and epididyn1is were performed. DiYision of the rudimentary chordee was likmvise accomplished. right scrotal exploration then revealed a 2.5 by 1.5 by 1.5 cm. brown, abnormal Read at annual meeting of Northeastern Section of American Urological Association, Whiteface, N_ Y., September 12-15, 1957. 1003
1004
MILNER, GARLICK, FINK AXD STEI;,,
Fw. 1. Case 1. Examination disclosed first degree hypospadias with narrow scrotal raphe band extending to base of penile shaft. Lower pole of left testis also biopsied.
appearing testis, seemingly enclosed in a translucent serous membrane with a normal, loosely attached epididymis. The upper pole of the testis consisted of a firm, rubbery, brown nodule which shelled out easily from its testicular bed. Frozen section revealed sclerosed testis containing a few small cystic spaces. However, permanent sections showed atrophic sclerosed testis surrounded by dense fibrous tissue I to 2 mm. in thickness which merged into typical ovarian tissue containing multiple graafian follicles. See figure 2, A. On October 7, cystoscopy revealed the presence of a normal prostate and bladder with a bifid verumontanum. There was no visible vaginal communication ·with the utricle. By rectal examination under anesthesia, no uterus ,ms palpable. A skin biopsy taken for chromosomal sex determination was interpreted as consistent with the male sex. There were no characteristic dumb-bell nuclei present in a count of 250 polymorphonuclear neutrophilic leukocytes, implying a male type of blood smear. Since the parents wished to defer further diagnostic procedures, the patient was discharged on October 8, with the advice that no reference to his sexual anomaly be made and that he continue to be reared as a normal male. The discharge diagnosis was true hermaphroditism, type indeterminate (i.e., ovotestis on one side and the other not examined). The patient was readmitted on April 4, 1957, complaining of progressive breast enlargement and monthly recurring breast tenderness. His mother stated that almost simultaneously with the onset of her menstrual symptoms, the patient would likewise have anorexia and "take to his room." On examination bilateral breast enlargement and a definite female mons pubis were noted. The scrotum
TRUE HERMAPHRODITE SIBLINGS
1005
Frn. 2. Case 1. A, biopsy of upper pole of testis revealed typical ovarian stroma containing numbers of ova and developing graffian follicles merging with well-developed testicular tissue. X 120. B, biopsy of lower pole of left gonad disclosed ovarian stroma adjacent to testicular tissue. X 120.
and penis appeared as normal for a pubertal male except for a first-degree glans hypospadias. The right testis was small and smooth. However, the left one, equally small, now felt nodular. Cord structures and the prostate on rectal examination were small but intact.
1006
MILNER, GARLICK, FINK AND STEIN
The need for further laboratory and surgical measures was stressed to the parents and with two instances of sexual aberrancy in the family they readily agreed. Laboratory measures were then performed and their results were as follows: F.S.H. levels showed 16-64 mouse uterine units (normal 8-24 m.u.u.), 17 ketosteroids of 8.2 mg. per 24 hours, 17-hydroxy-corticosteroid level of 2.5 mg. per 24 hours (normal 4-10 mg. per 24 hours), pregnandial less than 1 mg. per 24 hours (normal 5 trace amounts) and protein-bound-iodine showed 5.5 micrograms per cent (normal 4-10 mcg. per cent). On April 26, 1957, laparotomy and bilateral scrotal explorations were performed. Examination of the pelvis did not reveal any female structures and exposure of each vas deferens to the internal inguinal ring was also normal. The pelvic outlet was androgynoid. The right gonad and spermatic cord were mobilized through a low inguinal incision. This right greyish-white, smooth, ovoid gonad was then subject to bipolar biopsy and frozen section interpretation. The upper pole revealed a focally sclerosed and inflamed epididymis. The inferior pole showed testis displaying inactive spermatogenesis with moderate interstitial cell hyperplasia. Attention was then directed to the left gonad which was exposed with its cord attachment through a similar incision. The epididymis on the left was noted to be loosely attached to the testis, whereas the cord structures otherwise were normal-appearing on both sides. The left gonad appeared rudimentary with a thin translucent-like tunica albuginea and slightly nodular in its superior pole. It was felt that the upper pole represented an ovarian segment of an ovotestis. On frozen section examination, this tissue was again reported as showing inactive spermatogenesis and interstitial cell hyperplasia. This finding quickly led to biopsy of the lower pole and a report of ovarian tissue containing numerous ova and some follicular cysts (fig. 2, B). A total excision of the left gonad was then performed. Convalescence was uneventful and the patient was discharged on metandren linguets 10 mg. b.i.d. with a final diagnosis of true hermaphroditism, bilateral type (i.e., bilateral ovotestes). Case 2. T. G., a 13-month-old male child, was admitted on November 27, 1955, for correction of anomalous-appearing external genitalia. Birth history revealed a full term, normal spontaneous delivery. Other than frequent colds and measles at 5 months, there were no significant medical complaints or prior illnesses. Interrogation of the mother indicated that there had not been any known gestational nutritional deficiency, medical illnesses or exposure to x-ray in either pregnancy. Both parents stated they had no awareness of similar genital deformities in their respective families. With the exception of the genitalia, the physical examination was within normal limits. The scrotum was small and illdefined and contained on the left a small, retractile testis. On the right, there was, in addition to a palpable gonad, a communicating hydrocele and indirect inguinal hernia. The penis was small with a severe chordee and a hypospadiac urethra existing at the penoscrotal angle. The next day, excision lysis of the chordee and transplantation of the urethra to the perineum were performed. In addition, a right hydrocelectomy and hernia
TRUE HERMAPHRODITE SIBLINGS
1007
FIG. 3. Case 2. A, nodule from upper pole of right testis composed of ovarian stroma with large numbers of ova. X 120. B, nodule excised from upper pole of left testis showed both typical ovarian parenchyma and immature testicular tissue. X 120.
repair were done. Upon opening the hydrocele sac, a very small nubbin of greyishwhite tissue, measuring 0.2 cm. in its greatest dimension, was excised from the upper pole of the normal-appearing right testis. The histological report on the permanent section stated "ovarian tissue in which definite primordial follicles are numerous and characteristic ovarian stroma is present. No testicular elements are present (fig. 3, A)."
1008
MILNER, GARLICK, FINK AND STEIN
The patient, now 18 months old, was readmitted on June 11, 1956. Exploratory laparotomy the next day did not visualize the presence of any internal female sex organs. Left high scrotal exploration mobilized a normal-appearing testis with a pearly-white tunica albuginea. At the upper pole there was a palpable sensation of a nodule beneath the tunica. The tunica was incised, expressing from the upper pole a small, firm, greyish-yellow, ovoid structure, measuring 0.8 by 0.4 by 0.4 cm., covered with a semitranslucent fibrous membrane. This nodule was excised. An additional biopsy from the bed of the excised nodule revealed the presence of junctional ovarian and testicular tissue (fig. 3, B). Skin biopsy for sex chromatin pattern was negative (i.e., male). Final diagnosis, in view of a proven ovotestis only on the left side, was true hermaphroditism, unilateral type. It is considered probable that the remaining portion of the right gonad was testis and that this case also is representative of the bilateral type of true hermaphroditism. Hypospadias repair is planned in a few years and androgen supplement will be used, if needed, at puberty or earlier. DISCUSSION
By definition, an ovotestis is the unilateral histologically proven presence of testicular and ovarian tissues occurring as a single mass or as adjacent anatomically separate nodules. In our two cases of true hermaphroditism, it is likely that we have selectively enucleated the ovarian portion of the ovotestis. Although Mclver stated that only rarely can this be surgically accomplished, more recent studies indicate that bisexual gonad division is feasible and often surgically simple. It is worth emphasizing that an estimated 80 per cent of the ovotestes in the reported cases of true hermaphroditism have lent themselves readily towards selective unisexual gonadal enucleation. However, bipolar gonad biopsy and microscopic examination of all discrete nodules must be employed before removal, for gross interpretations frequently prove unreliable. Actually not more than 20 per cent of ovotestes showed inseparable mixing of ovarian and testicular tissues, usually evidenced by juxtaposition blending or, rarely, a central core of of either ovarian or testicular substance. The association of the combination of hypospadias and cryptorchidism present in almost all the previously reported instances of true hermaphroditism was similarly noted in these two cases. Assembled under the entity of true hermaphroditism are congenital anomalies of the gonads and the primary sex characteristics. These genitourinary anomalies are due to arrested or defective prenatal development. Considerable controversy exists between geneticists and environmentalists as to the factors of major importance in the creation of this form of teratism. That a persistent abnormal uterine environment was probably not responsible may be inferred from the fact that there were two normal siblings intermediate in age between these two cases. The occurrence of two similar type (bilateral ovotestes) true hermaphrodites in the same family lends additional support to the hereditary concept of defective germ plasm. More vital in its implications have been the findings and beliefs of the en-
TRUE HERMAPHRODITE SIBLINGS
1009
vironmentalists. Most prominently, Jost has expounded on the ability of fetal gonadal hormones to produce the changes seen in hermaphroditism. Also noted has been the hermaphroditic tendency of the retained genital ducts in vitamin A deficient rats during gestation. The field of experimental teratogenesis has shed further light on this obtuse problem by implicating not only specific time periods in the life of the developing embryo when teratogenic stimuli m::iy cause selective types of congenital anomalies, but also agent specificity wherein these stimuli, varying in quality and quantity, achieve the same anomalous result irrespective of time. SUMMARY
The first reported cases of true hermaphrodite siblings, bilateral type, have been presented. The presence of a testicular nodule combined with an external genital defect should suggest the diagnosis of true hermaphroditism and indicate the need for surgical exploration. Surgical sexual gonadal separation in the majority of ovotestes is feasible and histologically complete. The finding of true hermaphrodite siblings has given indirect support to the geneticists in their controversy concerning the etiology of this condition.
75 Willett St., Albany, N. Y. REFERENCES ANDERSON, R. C.: Causative factors underlying congenital heart malformations. Pediatrics, 14: 143-152, 1954. BREWER, J. L., JONES, H. 0. AND CuLVER, H.: True hermaphroditism. J.A.M.A., 148: 431-435, 1952. CECIL, A. B.: A true hermaphrodite. J. Urol., 72: 534-540, 1954. DoGRAMACI, I. AND GREEN, H.: Factors in etiology of congenital heart anomalies. J. Pediat., 30: 295-301, 1947. Doss, A. K. AND PRIESTLEY, J. T.: True hermaphroditism, report of a case. J. Urol., 43: 859-863, 1940. FINK, A. J.: True hermaphroditism: Review and analysis of 68 cases. Pending publication. JosT, A.: Problems of fetal endocrinology: The gonadal and hypophyseal hormones. Recent Prog. Hormone Research, 8: 379-418, 1953. MclvER, R. B., SEABAUGH, D.R. AND MANGELS, M. P.: True hermaphroditism: A report of two cases. J. Urol., 52: 67, 1944. WILSON, J. G., ROTH, C. B. AND WARKANY, J.: An analysis of syndrome of malformation induced by maternal vitamin A deficiency. Effects of restoration of vitamin A at various times during gestation. Am. J. Anat., 92: 189, 1953. WILSON, J. G.: Is there specificity of action in experimental teratogenesis? Pediatrics Supplem., 19: 755-763, 1957. YouNG, H. H.: Genital Abnormalities, Hermaphroditism and Related Adrenal Diseases. Baltimore: Williams & Wilkins Co., 1937.