Author Information
Swaminathan G*, Parulekar SV**.
(* Specialty Medical Officer, ** Professor and Head, Department of Obstetrics and Gynecology, Seth G S Medical College & K E M Hospital, Mumbai, India.)
Abstract
Androgen insensitivity syndrome(AIS), previously known as testicular feminization syndrome, is an X-linked recessive disorder of sexual development due to a mutation of androgen receptor coding gene at locus Xq11-12. It is the most common cause of male pseudohermaphroditism. Patients usually have a female phenotype with a karyotype of 46XY and primary amenorrhea. We present a case of 17 year old girl who presented with primary amenorrhea. She had sufficient breast development but scanty pubic and axillary hair. On gynecological examination, she had a blind vaginal pouch of length around 5 cm. On ultrasonography, the uterus was hypoplastic and bilateral around 3 cm size gonads were present. Her karyotype was 46XY. Laparoscopy was performed which revealed no internal genitalia except bilateral gonads. A small low transverse incision was taken and open Bilateral gonadectomy was done in our case.
Introduction
Androgen insensitivity syndrome, which was previously known as testicular feminization syndrome is an X-linked recessive disorder of sexual development due to a mutation of androgen receptor coding gene at locus Xq11- q12.[1] It is the most common cause of male pseudohermaphroditism. Patients usually have a female phenotype with a karyotype of 46XY and primary amenorrhea.[2[ The prevalence of this syndrome is estimated to be about 1 in 20000 births.[3] The complete form is a more common, occurring in 1 in 20,000 to 64,000 male births. The importance of this syndrome is the development of testicular tumors, especially seminomas after puberty.[1] Gonadal malignancies like yolk sac tumor, Sertoli cell tumor, unclassified sex cord stromal tumors and embryonic teratomas are rare in these patients.[1,4) The risk of the occurrence of gonadal tumors is rare before the age of 25.[5] The risk of developing testicular tumors is 3.6% at an age of 25 years and 33% at 50 years of age.[4] The diagnosis is often based on the absence of a cervix, uterus and fallopian tubes, presence of nondysgenetic testes and a vagina of variable length.[6] In this report we present and discuss a case of androgen insensitivity syndrome who underwent bilateral gonadectomy.
Case Report
A 17-year old girl came to our outpatient department with the complaint of primary amenorrhea. Her height was 160 cm and weight 50 kg. Her breast development was Tanner stage 5. Pubic and axillary hair were scanty. She had no abnormal finding in her general and systemic examination. Gynecological examination showed normal perineum and vulva and a blind vaginal pouch of length around 5 cm. Rectal examination did not show any palpable uterus or pelvic mass. A transabdominal pelvic ultrasonography (USG) was suggestive of a hypoplastic uterus measuring 2.1x0.7x1.3 cm. Bilateral gonads were present measuring around 3 cm each, located in the position of ovaries. She had no other abnormal finding in her abdominal USG. The hormonal analysis were as follows: serum FSH:16.88 mIU/ml, LH:28.81 mIU/ml, prolactin 14.17 ng/ml, free testosterone 15 pg/ml which was consistent with normal male values. In cytogenetic examination, karyotype was determined to be 46XY. After preoperative preparations and anesthesia fitness, a diagnostic laparoscopy was performed under general anesthesia. Pelvic and abdominal inspection revealed the presence of bilateral gonads with some intervening tissue which could be the suspected hypoplastic uterus which was reported on ultrasonography. On the right side, the gonad was elongated and extending up to the lateral pelvic wall, passing very close to and under the appendix and cecum. Bilateral gonadectomy was done along with removal of intervening tissue, through a small abdominal infraumbilical incision. The patient made an uneventful recovery. The histopathologic report revealed a testicle on the left measuring 2.5x1.5x0.5 cm, with a cyst identified at one pole measuring 1.8x1.8 cm (possibly epididymal). The right testicle measured 3x2.5x0.5 cm. It had a tubular structure, possibly epididymis, measuring 1.5x1.5 cm. Both testes showed immature seminiferous tubules with immature Sertoli cells. There were prominent Leydig cell micronodules in the interstitium of the testes. No spermatogenesis seen. Histopathological diagnosis was bilateral gonads showing bilateral immature testis with Sertoli cells.
Figure 1. Left testis (T). G: Gubernaculum.
Figure 2. Relations of left testis: cecum (C), appendix (white arrow) and right testis (green arrows) are seen.
Figure 3. Right testis.
Figure 4. Surgical specimen.
Discussion
Androgen insensitivity syndrome is the most frequent cause of the male pseudohermaphrotidism and the third most frequent cause of primary amenorrhea (approximately 10% of the primary amenorrhea). [2,7] Three different types of AIS have been reported. [2,7] The three AIS phenotype classifications are: complete androgen insensitivity syndrome (CAIS), also called as testicular feminization syndrome, partial androgen insensitivity syndrome (PAIS), and mild androgen insensitivity syndrome (MAIS) also called as under-virilized male syndrome.[8] CAIS, the typical mode of presentation is in an adolescent female who has well developed breasts with a pubertal growth spurt but has no menarche and no or scanty growth of axillary and pubic hair. CAIS may also present in early infancy with the appearance of bilateral labial or inguinal swellings. Bilateral inguinal hernias are rare in girls and it has been estimated that 1-2% of such cases actually have CAIS. On the other hand if a female child shows inguinal hernia, then CAIS must be suspected every time.[6] PAIS is one category of intersex. The prototypic phenotype for PAIS is characterized by micropenis, perineo-scrotal hypospadias and a bifid scrotum. The testes may also remain undescended. The most severe form of PAIS usually presents as isolated clitoromegaly.[8] MAIS as a category of AIS was first diagnosed following investigations for male factor infertility which suggested a defect in androgen action with oligospermia and a normal level of testosterone. Diagnosis of CAIS is usually with the absence of the female internal genital organs on physical examination and pelvic ultrasonography, karyotyping, molecular genetic testing of the androgen receptor gene mutations (chromosomal locus Xq11-q12), and elevated levels of testosterone and luteinizing hormone.[6,9] In our case the diagnosis of AIS was made based on history, physical and gynecologic examination, ultrasonography, the karyotype and laparoscopy. Gonadal tissue may be located in the inguinal canal or anywhere in the abdomen. Magnetic resonance imaging and laparoscopic examination have proven value for localizing nonpalpable undescended testes.[10,11].There is an increased risk of malignancy in dysgenetic gonads which can be as high as 30%. In contrast to the other forms of gonadal dysgenesis, the incidence of malignant tumors in AIS cases is rare before puberty and significantly higher after the age of 35 years.[2,8] Kriplani et al reported that two out of seven male pseudohermaprodite cases (28.6%) who underwent laparoscopic gonadectomy had gonadal malignancies (12). For patients with AIS, prophylactic gonadectomy is necessary in the post pubertal period for the risk of malignancy of the gonads. Gonadectomy is performed after puberty, to allow the development of the secondary sex characteristics during puberty.[1,4] The laparoscopic gonadectomy has many advantages compared to laparotomy i.e minimal blood loss, rapid recovery and shorter hospital stay. Laparoscopy also has a better visualization of abdomen and pelvis compared to the laparotomy.[12] The operational time is similar in laparoscopy and laparotomy, but the recovery time and the duration of the hospital stay is much less with laparoscopy as compared with laparotomy.[13,14] In our case, there was a need for laparotomy as the right gonad was very close to the appendix and cecum and partially adherent to it. The patients with AIS need to be treated with long term hormonal replacement therapy mainly estrogen after gonadectomy.[2,7] The androgen supplementation treatment will not be beneficial in these patients due to the absence of functional androgen receptors.[15]
Conclusion
In conclusion androgen insensitivity syndrome should be suspected in cases with primary amenorrhea, confirmed by genetic studies and gonadectomy should be performed after puberty due to the risk of development of gonadal malignancy in future.
Acknowledgment
We thank Dr. Ashwini Desai for taking surgical photographs.
References
Swaminathan G*, Parulekar SV**.
(* Specialty Medical Officer, ** Professor and Head, Department of Obstetrics and Gynecology, Seth G S Medical College & K E M Hospital, Mumbai, India.)
Abstract
Androgen insensitivity syndrome(AIS), previously known as testicular feminization syndrome, is an X-linked recessive disorder of sexual development due to a mutation of androgen receptor coding gene at locus Xq11-12. It is the most common cause of male pseudohermaphroditism. Patients usually have a female phenotype with a karyotype of 46XY and primary amenorrhea. We present a case of 17 year old girl who presented with primary amenorrhea. She had sufficient breast development but scanty pubic and axillary hair. On gynecological examination, she had a blind vaginal pouch of length around 5 cm. On ultrasonography, the uterus was hypoplastic and bilateral around 3 cm size gonads were present. Her karyotype was 46XY. Laparoscopy was performed which revealed no internal genitalia except bilateral gonads. A small low transverse incision was taken and open Bilateral gonadectomy was done in our case.
Introduction
Androgen insensitivity syndrome, which was previously known as testicular feminization syndrome is an X-linked recessive disorder of sexual development due to a mutation of androgen receptor coding gene at locus Xq11- q12.[1] It is the most common cause of male pseudohermaphroditism. Patients usually have a female phenotype with a karyotype of 46XY and primary amenorrhea.[2[ The prevalence of this syndrome is estimated to be about 1 in 20000 births.[3] The complete form is a more common, occurring in 1 in 20,000 to 64,000 male births. The importance of this syndrome is the development of testicular tumors, especially seminomas after puberty.[1] Gonadal malignancies like yolk sac tumor, Sertoli cell tumor, unclassified sex cord stromal tumors and embryonic teratomas are rare in these patients.[1,4) The risk of the occurrence of gonadal tumors is rare before the age of 25.[5] The risk of developing testicular tumors is 3.6% at an age of 25 years and 33% at 50 years of age.[4] The diagnosis is often based on the absence of a cervix, uterus and fallopian tubes, presence of nondysgenetic testes and a vagina of variable length.[6] In this report we present and discuss a case of androgen insensitivity syndrome who underwent bilateral gonadectomy.
Case Report
A 17-year old girl came to our outpatient department with the complaint of primary amenorrhea. Her height was 160 cm and weight 50 kg. Her breast development was Tanner stage 5. Pubic and axillary hair were scanty. She had no abnormal finding in her general and systemic examination. Gynecological examination showed normal perineum and vulva and a blind vaginal pouch of length around 5 cm. Rectal examination did not show any palpable uterus or pelvic mass. A transabdominal pelvic ultrasonography (USG) was suggestive of a hypoplastic uterus measuring 2.1x0.7x1.3 cm. Bilateral gonads were present measuring around 3 cm each, located in the position of ovaries. She had no other abnormal finding in her abdominal USG. The hormonal analysis were as follows: serum FSH:16.88 mIU/ml, LH:28.81 mIU/ml, prolactin 14.17 ng/ml, free testosterone 15 pg/ml which was consistent with normal male values. In cytogenetic examination, karyotype was determined to be 46XY. After preoperative preparations and anesthesia fitness, a diagnostic laparoscopy was performed under general anesthesia. Pelvic and abdominal inspection revealed the presence of bilateral gonads with some intervening tissue which could be the suspected hypoplastic uterus which was reported on ultrasonography. On the right side, the gonad was elongated and extending up to the lateral pelvic wall, passing very close to and under the appendix and cecum. Bilateral gonadectomy was done along with removal of intervening tissue, through a small abdominal infraumbilical incision. The patient made an uneventful recovery. The histopathologic report revealed a testicle on the left measuring 2.5x1.5x0.5 cm, with a cyst identified at one pole measuring 1.8x1.8 cm (possibly epididymal). The right testicle measured 3x2.5x0.5 cm. It had a tubular structure, possibly epididymis, measuring 1.5x1.5 cm. Both testes showed immature seminiferous tubules with immature Sertoli cells. There were prominent Leydig cell micronodules in the interstitium of the testes. No spermatogenesis seen. Histopathological diagnosis was bilateral gonads showing bilateral immature testis with Sertoli cells.
Figure 1. Left testis (T). G: Gubernaculum.
Figure 2. Relations of left testis: cecum (C), appendix (white arrow) and right testis (green arrows) are seen.
Figure 3. Right testis.
Figure 4. Surgical specimen.
Discussion
Androgen insensitivity syndrome is the most frequent cause of the male pseudohermaphrotidism and the third most frequent cause of primary amenorrhea (approximately 10% of the primary amenorrhea). [2,7] Three different types of AIS have been reported. [2,7] The three AIS phenotype classifications are: complete androgen insensitivity syndrome (CAIS), also called as testicular feminization syndrome, partial androgen insensitivity syndrome (PAIS), and mild androgen insensitivity syndrome (MAIS) also called as under-virilized male syndrome.[8] CAIS, the typical mode of presentation is in an adolescent female who has well developed breasts with a pubertal growth spurt but has no menarche and no or scanty growth of axillary and pubic hair. CAIS may also present in early infancy with the appearance of bilateral labial or inguinal swellings. Bilateral inguinal hernias are rare in girls and it has been estimated that 1-2% of such cases actually have CAIS. On the other hand if a female child shows inguinal hernia, then CAIS must be suspected every time.[6] PAIS is one category of intersex. The prototypic phenotype for PAIS is characterized by micropenis, perineo-scrotal hypospadias and a bifid scrotum. The testes may also remain undescended. The most severe form of PAIS usually presents as isolated clitoromegaly.[8] MAIS as a category of AIS was first diagnosed following investigations for male factor infertility which suggested a defect in androgen action with oligospermia and a normal level of testosterone. Diagnosis of CAIS is usually with the absence of the female internal genital organs on physical examination and pelvic ultrasonography, karyotyping, molecular genetic testing of the androgen receptor gene mutations (chromosomal locus Xq11-q12), and elevated levels of testosterone and luteinizing hormone.[6,9] In our case the diagnosis of AIS was made based on history, physical and gynecologic examination, ultrasonography, the karyotype and laparoscopy. Gonadal tissue may be located in the inguinal canal or anywhere in the abdomen. Magnetic resonance imaging and laparoscopic examination have proven value for localizing nonpalpable undescended testes.[10,11].There is an increased risk of malignancy in dysgenetic gonads which can be as high as 30%. In contrast to the other forms of gonadal dysgenesis, the incidence of malignant tumors in AIS cases is rare before puberty and significantly higher after the age of 35 years.[2,8] Kriplani et al reported that two out of seven male pseudohermaprodite cases (28.6%) who underwent laparoscopic gonadectomy had gonadal malignancies (12). For patients with AIS, prophylactic gonadectomy is necessary in the post pubertal period for the risk of malignancy of the gonads. Gonadectomy is performed after puberty, to allow the development of the secondary sex characteristics during puberty.[1,4] The laparoscopic gonadectomy has many advantages compared to laparotomy i.e minimal blood loss, rapid recovery and shorter hospital stay. Laparoscopy also has a better visualization of abdomen and pelvis compared to the laparotomy.[12] The operational time is similar in laparoscopy and laparotomy, but the recovery time and the duration of the hospital stay is much less with laparoscopy as compared with laparotomy.[13,14] In our case, there was a need for laparotomy as the right gonad was very close to the appendix and cecum and partially adherent to it. The patients with AIS need to be treated with long term hormonal replacement therapy mainly estrogen after gonadectomy.[2,7] The androgen supplementation treatment will not be beneficial in these patients due to the absence of functional androgen receptors.[15]
Conclusion
In conclusion androgen insensitivity syndrome should be suspected in cases with primary amenorrhea, confirmed by genetic studies and gonadectomy should be performed after puberty due to the risk of development of gonadal malignancy in future.
Acknowledgment
We thank Dr. Ashwini Desai for taking surgical photographs.
References
- Collins GM, Kim DU, Logrono R. Pure seminoma arising in androgen insensitivity syndrome (testicular Feminization syndrome): a case report and review of literature. Mod Pathol 1993;6(1):89-93.
- Creatsas GK. Hermaphroditism-Intersexual Disorders,Modern Obstetrics and Gynecology. Athens: Pashalidis Publishers, 1998;34-42.
- Barthold JS, Kumasi-Rivers K, Upadhyay J, Testicular position in the androgen insensitivity syndrome: implications for the role of androgens in testicular descent. J Urol 2000;164(2):497-501.
- Handa N, Nagasaki A, Tsunoda M. Yolk sac tumor in a case of testicular feminization syndrome. J Pediatr Surg 1995;30(9):1366-1368.
- Velidedeoglu HV, Coskunfirat OK, Bozdogan MN. The surgical management of incomplete testicular feminization syndrome in three sisters. British Journal of Plastic Surgery 1997;50(3):212-216.
- Solari A, Groisman B, Bidondo MP. Complete androgen insensitivity syndrome: diagnosis and clinical characteristics. Arch Argent Pediatr 2008;106(3):265-268.
- Speroff L, Fritz MA. Normal and abnormal sexual development in Clinical Gynecologic Endocrinology and Infertility. 7th ed. Philadelphia: Williams and Wilkins Publishers, 2005;319-359.
- Hughes IA, Deeb A. Androgen resistance. Best Pract Res Clin Endocrinol Metab 2006;20(4):577-598.
- Ahmed SF, Cheng A, Dovey L. Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome. J Clin Endocrinol Metab 2000;85:658-665.
- Christensen JD, Dogra VS. The undescended testis. Semin Ultrasound CT MR 2007;28(4):307-316.
- Ishida K, Harada Y, Tei K. Laparoscopic examination of the nonpalpable testis. Hinyokika Kiyo 2007;53(11):795-799.
- Kriplani A, Abbi M, Ammini AC. Laparoscopic gonadectomy in male pseudohermaphrodites. Eur J Obstet Gynecol Reprod Biol 1998;81(1):37-41.
- Kallipolitis GK, Milingos SD, Creatsas GK. Laparoscopic gonadectomy in a patient with testicular feminization syndrome. J Pediatr Adolesc Gynecol 2000;13(1):23-26.
- Chantilis SJ, Mc Quitty DA, Priminger GM. Laparoscopic removal of gonads containing an occult seminoma in a woman with complete androgen resistance. J Am Assoc Gynecol Laparosc 1994;1(3):277- 282.
- Slob AK, van der Werfften Bosch JJ, van Hall EV. Psychosexual functioning in women with complete testicular feminization: Is androgen replacement therapy preferable to estrogen? J Sex Marital Ther 1993;19(3):201-9.
Swaminathan G, Parulekar SV. Bilateral Gonadectomy In A Case Of Complete Androgen Insensitivity Syndrome. JPGO. 2018 Vol 5 No. 8. Available from: http://www.jpgo.org/2018/08/bilateral-gonadectomy-in-case-of.html