Bilateral Gonadectomy Research Articles

Efficacy of domestic single-hole robotic surgery system in the treatment of pediatric urological diseases

To explore the efficacy of domestic single-hole robotic surgery system in the treatment of pediatric urological diseases. A prospective review of clinical data of children who underwent laparoscopic surgery in the Department of Urology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, was conducted from July to November 2023. All surgeries were performed using the sharp single-port serpentine arm robotic surgery system, with an umbilical access route. All surgeries are performed by the same chief physician. Operative time, intraoperative blood loss, incision size, and postoperative complications were recorded. A total of 12 patients were included, consisting of 8 males and 4 females, aged 8.0-17.0 (13.5±2.7) years. The procedures included 5 pyeloplasties (1 case of bilateral pyeloplasty), with a unilateral operative time [M (Q1, Q3) ]of 180 (145, 200) minutes and a blood loss of 5 (5, 10) ml. Oral mucosa ureteroplasty was performed in 1 patient, taking 3 hours and 52 minutes with a blood loss of 10 ml. Renal cyst decortication was conducted in 1 case in 85 minutes with a blood loss of 20 ml. High ligation of the spermatic vein was conducted in 3 patients, with an average operative time of 97 minutes and no intraoperative blood loss. Bilateral gonadectomy was completed in 80 minutes with a blood loss of 5 ml. Ovarian cystectomy (1 case) was performed in 69 minutes with a blood loss of 5 ml. All surgeries were successfully completed without conversion to open surgery. Except for the oral mucosa ureteroplasty, which required an additional 5 mm auxiliary port, all procedures were performed through a 3 cm umbilical incision. Among the patients who underwent pyeloplasty, 1 case of urinary leak was identified and successfully treated conservatively with adequate drainage over 25 days. Re-stenosis was experienced by 1 patient with a long segment ureteral stricture postoperatively, while no Clavien-Dindo grade≥2 complications were observed in other patients. All umbilical wounds were concealed, and satisfactory postoperative appearances were noted. The domestic single-hole robotic surgery system is effective in treating pediatric urological diseases.

7756 Gonadectomy in Individuals with Differences of Sex Development - A Prospective I-DSD Registry Study

Abstract Disclosure: M.A. O'Connell: None. A.K. Lucas-Herald: None. J. Bryce: None. M. Chen: None. J.H. Davies: None. M. Shnorhavorian: None. N. Atapattu: None. I. Bachynska: None. N. Birkebaek: None. M. Cools: None. K. Demir: None. L. de Vries: None. H. Elsedfy: None. M.A. Fahmy: None. E. Globa: None. R. Grinspon: None. G. Guaragna-Filho: None. G. Guerra-Junior: None. D. Janus: None. Z. Kolesinska: None. I. Mazen: None. S.M. O'Connell: None. S.N. Seneviratne: None. M. Stancampiano: None. G. Verkauskas: None. S.F. Ahmed: None. O. i-DSD gonadectomy surveillance consortium: None. Introduction: Gonadectomy may be indicated in people with differences of sex development (DSD), but variation in practice is reported. This study aims to determine, through prospective surveillance, the frequency of gonadectomy and associated care pathways in individuals with DSD internationally. Methods: All I-DSD centres were invited to participate; the study commenced in December 2022. Participating centres receive a monthly email asking whether a gonadectomy has been performed in an individual with DSD. Where informed consent for inclusion in the I-DSD Registry has been obtained in a reported case, a secondary survey captures additional clinical information. Results: Of 208 centres invited, 74 have responded to monthly email surveys. Over the first 12 months of surveillance, gonadectomies were reported in 71 individuals from 34 centres in 19 countries (median [range]: 1[1, 5]); 40 centres reported no gonadectomy. Secondary survey data are available for 30/65 (46%) of reported cases to date. Twenty-four (80%) individuals are female; median (range) age at gonadectomy was 9.2 (2.1,20.0) years. All had specialist multidisciplinary team involvement prior to gonadectomy: endocrinology (97%), genetics (77%) and psychology (67%) were most frequently involved. Gonads were intra-abdominal in 25/30 (83%). Differences of gonadal development (13/30 [43%]) and Turner syndrome (8/30 [27%]) were the most frequent underlying DSD. Pre-gonadectomy investigations included: hormonal testing (28/30 [93%]), imaging (23/30 [77%] - US alone n=14; US + MRI n=7; MRI alone n=2), direct visualisation at laparoscopy (7/30 [23%]) and gonadal biopsy (2/30 [7%]). Bilateral gonadectomy was undertaken in 25/30 (83%). Mitigation of future malignancy risk in the context of gonadal insufficiency was the most common primary indication for gonadectomy (19/30, [63%]); additional indications were concerning changes on biopsy/imaging (3/30 [10%]), hormone production incongruent with sex assigned (4/30 [13%]) or gender identity (2/30 [7%]) and parental choice (2/30 [7%]). Histopathology confirmed neoplastic change in 7 individuals (23%). Gonadectomy was intentionally deferred in 8/30 (27%) individuals, most commonly to allow their involvement in decision making. Twelve individuals (40%) were 12yrs or older at gonadectomy; all were involved in the pre-operative decision-making process. Conclusions: This study offers important contemporary insights into the practice of gonadectomy in individuals with DSD internationally. Multidisciplinary care provision prior to gonadectomy is standard; however, management pathways vary, likely reflecting diversity of clinical presentations and lack of consensus regarding optimal approach. The I-DSD platform shows clear utility for performing prospective surveillance of rare procedures; such studies are essential for care quality improvement. Presentation: 6/2/2024

Clinical and Biochemical Profile of Patients with 46, XY Disorders of Sex Development

Abstract Background Disorders of sex development (DSD) comprise a wide range of conditions with varying features and pathophysiology that most often present in the newborn or the adolescent. Affected newborns are born with ambiguous genitalia, whereas adolescents present with atypical sexual development during the pubertal years. Aim of the Work To study the clinical and biochemical profile of patients with 46, XY disorders of sex development. Patients and Methods This was a descriptive study, conducted on 50 patients with 46, XY DSD attending the Pediatric Endocrinology clinic, Children's Hospital, Ain Shams University were recruited from April 2019 till April 2020. Results In our study 88% of cases were reared as males, while 12% were reared as females. The mean age at diagnosis was 2.48 ± 1.33 years with a range of 1-7 years. Parental consanguinity was present in 28 (56.0%) patients and a positive family history in 10 (20.0%). Mean external masculinization score (EMS) in our study was 3.30 ± 1.81 and ranged from 0 to 9 with a median of 3. The mean of stimulated Testosterone / Dihydrotestosterone (T/DHT) ratio was 17.5 (7.8-26) and ranged between 1.5 and 66.6. The median of Anti Mullerian Hormone (AMH) was 56 ng/ml and ranged between 19.08 and 105 ng/ml. There was correlation between EMS final score and stimulated DHT (r = 0.54, P = 0.000). Of note 6 (12.0%) patients had reconstruction of scrotum, 7 (14%) had undergone inguinal hernia repair, 12 (24%) had undergone correction of hypospadias, 6 (12.0%) bilateral gonadectomy,6 (12.0%) left orchiopexy, 3 (6.0%) right orchiopexy and 10 (20%) bilateral orchiopexy. Conclusion Due to the overlapping clinical and biochemical parameters in various subsets of DSD, only a preliminary etiological diagnosis can be made in some cases. Genetic examination with long-term follow-up are needed for a precise diagnosis. Management of these patients is multidisciplinary which needs an endocrinologist, gynecologist, psychologist, pediatrician, and clinical geneticist.

A Case Report of 46 XY Partial Gonadal Dysgenesis with Dual Gonadal Tumours

46XY gonadal dysgenesis is known as a disorder of sex development (DSD) that occurs due to abnormality in gonadal development. There is a conflict between one’s genotype, phenotype, and gonadal development, which influences the wide range of presentation and clinical appearance of 46XY females. This was a case of a 46XY female who presented with primary amenorrhea with delayed puberty at the age of 18 years old. She had ambiguous genitalia. Her breast and pubic hair were at Tanner Stage 2. Transabdominal ultrasound found a small uterus with a vagina; however, the gonads were not seen. A magnetic resonance imaging (MRI) showed a 20mm right gonad located extra-pelvis near the right iliac vessels while the 9mm streak left gonad was at the usual location next to the sigmoid colon. All her tumour markers were normal except lactate dehydrogenase (LDH) was elevated. She was given estrogen therapy for pubertal induction and underwent laparoscopy prophylactic bilateral gonadectomy. The intraoperative findings were similar to the MRI findings, and the histopathology examination (HPE) results showed left gonadoblastoma and right dysgerminoma FIGO stage 1A. She continued taking estrogen therapy until she had withdrawal bleeding, and oral progesterone was added. 46XY-DSD has high risk of developing germ cell tumour and requires prophylactic gonadectomy as soon as the diagnosis is established. However, delay in presentation and surgery may affect the outcomes and prognosis.

Clinical characteristics and surgical treatment of children with 45, X/46, XY differences of sex development

This study retrospectively analyzes the clinical data of 18 children with 45,X/46,XY differences of sex development (DSD), summarizes their clinical features and explores gonadal and Müllerian duct remnants surgical treatment methods. The clinical data of 18 children with karyotype 45,X/46,XY diagnosed in the Department of Urology of Hunan Children's Hospital from March 2011 to October 2021 were collected. All children underwent HCG stimulation testing, laparoscopic exploration, urethroscopy and bilateral gonadal biopsy. After DSD multidisciplinary team (MDT) meeting, some children underwent gonadectomy and genitalia reconstructive surgeries. The median age at first diagnosis was 1 year and 4 months (range: 10 months ∼ 16 years and 3 months). 5 children presented with female gender; they all maintained their gender assignment. The external masculinisation score (EMS) of patients raised as female was 1 (0∼3) [median (range)]. 13 children presented with male gender, 10 maintained a male gender, 3 were assigned a neutral gender. The EMS of the children raised as male was 5 (2-8) [median (range)], the EMS of the children raised as neutral gender was 4 (3.5-9.5) [median (range)]. The HCG stimulation test was positive in 11 cases, partially positive in 2 case, and negative in 5 cases. There was no relationship between the percentage of chimerism (45X ratio) and the appearance and severity of genital abnormalities. (t=-1.08, P=0.298). There was 1 case of complete gonadal dysgenesis (CGD), 10 cases of mixed gonadal dysgenesis (MGD), 5 cases of partial gonadal dysgenesis (PGD), 1 case of bilateral normal testes and 1 case of ovotesticular DSD (split-lateral type). No gonadal specimen showed germ cell tumor changes. Five cases selected to maintain the female gender, among which 3 cases underwent bilateral gonadectomy and genitalia reconstructive surgeries. Among the 10 children who chose to maintain the male gender, unilateral streak gonadectomy was performed in 4 (57.1%) with MGD, unilateral dysgenetic orchiectomy in 1 (25%) with PGD, and right ovariectomy in 1 with OTDSD. Nine of them underwent genitalia reconstructive surgeries. Four of them preserved their uterus and vagina did not have any complications during the follow-up period. Hypospadias combined with cryptorchidism and residual Müllerian duct structures is the most common phenotype of children with 45, X/46, XY DSD. Mixed gonadal dysgenesis (MGD) is the most common gonadal type. Gender assignment should be carefully selected after a thorough evaluation, while genitalia reconstructive surgery can be considered in selected patients. In children who choose the male gender, the Müllerian duct can be preserved.

Laparoscopic Hysterectomy with Bilateral Gonadectomy in True Hermaphroditism: A Case Report

Laparoscopic Hysterectomy with Bilateral Gonadectomy in True Hermaphroditism: A Case Report

Pre-germ cell neoplasia in-situ in a patient with complete androgen insensitivity syndrome

Abstract Introduction/Objective Complete androgen insensitivity syndrome is a disorder of sex development in 46, XY individuals with external female genitalia and undescended testes, often presenting with inguinal hernia in infancy and/or primary amenorrhea in adolescents. Given the increased risk for the development of germ cell neoplasms in the ectopic testis, early gonadectomy or orchidopexy may be indicated. Methods/Case Report We report a 21-year-old patient assigned female at birth (46, XY) with a history of bilateral inguinal hernia repairs (age 2) and later with lack of menarche (age 16). Additional work-up showed an elevated testosterone level (394 ng/mL) and normal luteinizing and follicle stimulating hormone values. On pelvic ultrasound, retained intraabdominal gonads were identified, but female sex organs were absent. During a gonadal relocation procedure, the gonads appeared irregular in shape with multiple cysts and small nodules, and bilateral gonadectomy was performed. Grossly, the gonads measured 4.9 and 4.3 cm with a smooth external surface and a lobulated cut surface with multiple cysts, up to 1.6 cm, containing clear, serous fluid. Histologic sections showed most seminiferous tubules were lined only by Sertoli cells with only occasional spermatogonia. Leydig cell hyperplasia and areas of ovarian-like stroma were seen. OCT4 immunostain highlighted the nuclei of individually disposed germ cells in the base of tubules (singly dispersed, non-linear pattern), raising concern for germ-cell neoplasia in-situ (GCNIS). However, the histology and staining pattern were better interpreted as diagnostic of germ cells with delayed maturation and pre-GCNIS. Additionally, OCT4 showed rare single cells within the stroma and considered to represent residual undifferentiated gonadal tissue. After gonadectomy, the patient was started on hormone replacement therapy. Results (if a Case Study enter NA) NA Conclusion This case highlights the potential pitfalls in the interpretation of OCT4 immunostain to avoid misdiagnosis of germ cell neoplasia.

Germ Cell Tumors in 46, XY Gonadal Dysgenesis.

To present the clinical data, investigative profile, management, and follow-up of patients with 46, XY gonadal dysgenesis with germ cell tumors from the endocrine unit of a tertiary care university hospital. This retrospective study included 3 cases of 46, XY gonadal dysgenesis with germ cell tumors evaluated and managed at the Department of Endocrinology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, over a period of 13 years from (September 2008 to December 2021). Over a period of 13 years, we diagnosed and managed 7 patients with 46, XY gonadal dysgenesis. This included 4 patients with pure gonadal dysgenesis (PGD; Swyer syndrome), 2 patients with mixed gonadal dysgenesis (MGD), and one patient with partial gonadal dysgenesis. Out of these 7 patients, three patients developed germ cell tumors, one patient with MGD, and two patients with pure PGD (Swyer syndrome). In all three patients, germ cell tumor was the first presentation of DSD. The patient with MGD presented with primary amenorrhea and virilization, while the two patients with PGD presented as phenotypic females with primary amenorrhea and pelvic mass. All three patients developed seminomatous cancers. Patient with MGD developed seminoma and the two patients with PGD (Swyer syndrome) developed dysgerminoma. The patients were managed with bilateral gonadectomy with removal of the tumor. In addition, the 2 patients with PGD (Swyer syndrome) received combined chemotherapy. On a follow up ranging from 1 to 10 years, all three patients are disease free. we conclude that germ cell tumors may be the first presentation of 46, XY gonadal dysgenesis. In all phenotypic females with primary amenorrhea and dysgerminoma, karyotype is a must to uncover the diagnosis of PGD. In addition virilization may be clue to the presence of germ cell tumor in a patient with 46, XY gonadal dysgenesis.

Workflow for Management of Gonadal Neoplasm in 2 Patients with Differences of Sex Development Enrolled in an Experimental Gonadal Tissue Cryopreservation Protocol

To outline our experimental gonadal tissue cryopreservation (GTC) protocol that does not disrupt standard of care in medically-indicated gonadectomy for patients with differences of sex development (DSD), including highlighting the multidisciplinary collaborative protocol for when neoplasm is discovered in these cases. Two patients with complete gonadal dysgenesis (CGD) who were undergoing medically-indicated prophylactic bilateral gonadectomy elected to pursue GTC. Both were found to have germ cell neoplasia in situ (GCNIS) on initial pathologic analysis, requiring recall of the gonadal tissue, which had been cryopreserved. Cryopreserved gonadal tissue was successfully thawed and transferred to pathology for complete analysis. No germ cells were identified in either patient nor were found to have malignancy, so further treatment beyond gonadectomy was not indicated. Pathologic information was communicated to each family, including that long-term GTC was no longer possible. Organizational planning and coordination between the clinical care teams, GTC laboratory and pathology were key to handling these cases with neoplasia. Processes that anticipated the possibility of discovering neoplasia within tissue sent to pathology and the potential need to recall GTC tissue to complete staging included: (1) documenting the orientation and anatomical position of tissue processed for GTC, (2) defining parameters in which tissue will be recalled, (3) efficiently thawing and transferring GTC tissue to pathology, and (4) coordinating release of pathology results with verbal communication from the clinician to provide context. GTC is desired by many families and at the time of gonadectomy and is: (1) feasible for patients with DSD and (2) did not inhibit patient care in two patients with GCNIS.

Undetectable anti-Mullerian hormone and inhibin B do not preclude the presence of germ cell tumours in 45,X/46,XY or 46,XY gonadal dysgenesis.

Individuals with 45,X/46,XYor 46,XYgonadal dysgenesis are at increased risk of germ cell malignancies. Therefore, prophylactic bilateral gonadectomy is advised in girls and considered in boys with atypical genitalia for undescended, macroscopically abnormal gonads. However, severely dysgenetic gonads may not contain germ cells rendering gonadectomy unnecessary. Therefore, we investigate if undetectable preoperative serum anti-Müllerian hormone(AMH) and inhibin B can predict the absence of germ cells, (pre)malignant or otherwise. Individuals who had undergone bilateral gonadal biopsy and/or gonadectomy because of suspected gonadal dysgenesis in 1999-2019 were included in this retrospective study if preoperative AMH and/or inhibin B were available. Histological material was reviewed by an experienced pathologist. Haematoxylin and eosin and immunohistochemical stainings for SOX9, OCT4, TSPY and SCF (KITL) were used. Thirteen males and 16 females were included, 20 with 46,XYand 9 with 45,X/46,XY DSD. Threefemales had dysgerminoma alongside gonadoblastoma; twogonadoblastoma, one germ cell neoplasia in situ (GCNIS) and three males had pre-GCNIS and/or pre-gonadoblastoma. Gonadoblastoma and/or dysgerminoma were present in 3/11 individuals with undetectable AMH and inhibin B, one of whom also had non-(pre)malignant germ cells. Of the other 18, in whom AMH and/or inhibin B were detectable, only one had no germ cells. Undetectable serum AMH and inhibin B cannot reliably predict the absence of germ cells and germ cell tumours in individuals with 45,X/46,XYor 46,XYgonadal dysgenesis. This information should help in counselling about prophylactic gonadectomy, taking into account both the germ cell cancer risk and potential for gonadal function.

Deferring gonadectomy in patients with turner syndrome with a genetic Y component is not a safe practice

Patients with Turner syndrome who harbor Y chromosome material are known to be at increased risk of developing germ cell neoplasms. The optimal timing to perform gonadectomy to reduce the risk of cancer development in these patients is not well defined. We present outcomes of Turner with a Y component (TSY) patients who underwent gonadectomy at our institution. We hypothesized that tumors could occur in a significant portion of TSY patients at any age and gonadectomy can be safely performed at diagnosis rather than deferred. We performed an IRB-approved retrospective single center study in which we queried our institutions electronic health record to identify all patients with TSY who underwent gonadectomy at our institution from 2012 to 2021. In our series of 18 consecutive TSY patients, a tumor was identified in 6 patients (33.3%): 4 (22.2%) with dysgerminoma (DG) [Fig.1] and 2 (11.1%) with gonadoblastoma (GB). Our cohort of 18 consecutive TSY who underwent gonadectomy over a 9-year period is the largest published single site cohort to date. Additionally, our patient who was found to have GB at 40 days is to our knowledge the youngest TSY patient to be diagnosed with GB in the literature. This patient's remarkably early incidence of tumor occurrence illustrates the urgency of protective gonadectomy. Given the high incidence of tumor formation in this population and the minimal morbidity associated with gonadectomy, we do not recommend delaying gonadectomy in this population for any reason. Our study is vulnerable to selection bias and confounding innate to any retrospective study. There was variation with respect to the frequency and timing of pre-operative imaging as a strict preoperative imaging protocol with sequential studies was not in place at our institution. Additionally, we do not have a comparison cohort of patients who are being followed without operative intervention as all TSY patients at our institution have undergone gonadectomy. TSY patients cannot be safely observed for tumor formation based on clinical factors such as imaging or age. Gonadectomy is safe with a low complication rate and without tumor recurrence during three-year follow-up. We continue to recommend bilateral gonadectomy in this patient population at the time of diagnosis.

8732 Laparoscopic Bilateral Gonadectomy in a Patient with Mosaic 45,X/46,XY Turner Syndrome

<h3>Study Objective</h3> To demonstrate a laparoscopic technique for prophylactic bilateral gonadectomy in a patient with mosaic 45,X/46,XY Turner syndrome. <h3>Design</h3> We present a stepwise, narrated demonstration of our technique for risk reducing bilateral gonadectomy. We highlight key anatomy, and place special attention on techniques to permit excision of at least 2 cm of the gonadal vessels with the specimen. <h3>Setting</h3> Referral center in Upstate New York. <h3>Patients or Participants</h3> 27-yo G1P1 diagnosed with mosaic Turner syndrome (45,X/46,XY) <h3>Interventions</h3> Visual inspection of the pelvis was performed, and pelvic washings were obtained. The course of the ureter was dissected out within the retroperitoneal space, developing a window between the ureter and gonadal vessels. The peritoneum was opened medial and lateral to the streak gonad to ensure removal of all tissue with potential for malignancy. The infundibulopelvic ligament (IP) was skeletonized and gonadectomy was performed transecting the IP 3-4 cm cephalad to the streak gonad. The same procedure was completed on the opposite side. <h3>Measurements and Main Results</h3> Successful laparoscopic bilateral gonadectomy was performed with an estimated blood loss of 5mL. Pathology demonstrated bilateral streak gonads without evidence of germ cell tumor. <h3>Conclusion</h3> Given the inability to reliably diagnose the presence of germ cell tumors in streak gonads preoperatively, the use of wide dissection at the time of laparoscopic bilateral gonadectomy for risk reduction in mosaic Turner Syndrome patients with Y-chromosome material is an important consideration.

PMON312 A De Novo Heterozygous Nonsense Variant In The SEC31A Gene Associated With Pituitary Hormone Deficiency And Disorders Of Sex Development.

Abstract Introduction XYdisorders of sex development (DSD) result from variants in many different human genes but frequently have no detectable molecular cause. In approximately 25% of cases of XY DSD, the index case may have associated malformations. Genetic disorders of endoplasmic reticulum (ER) function are increasingly being recognised but have not been associated with DSD or pituitary disorders. Clinical case Three siblings (with unaffected non-consanguineous parents) were reviewed at the tertiary endocrine clinic. Child I was noted at birth to have cliteromegaly. Imaging and examination under anaesthetic revealed a normal vagina and uterus but gonads of indeterminate origin. She was 46,XY and basal endocrine investigations at the age of 4 years showed a low AMH for male but otherwise normal gonadal and thyroid function and normal IGF-1. She had a laparoscopic bilateral gonadectomy aged 5 years. Pathology demonstrated bilateral testicular tissue, with substantial fibrotic atrophic change and occasional placental alkaline phosphatase (PLAP) positive cells, suggestive of germ cell tumours. Aged 8 years she developed obesity and later hypertension. Child II was reviewed due to short stature and diagnosed with GH deficiency aged 2 years. She has normal adrenal and thyroid function and gonadotrophins. MRI demonstrated an ectopic posterior pituitary. Child III presented with perineal hypospadias, a small phallus, bilateral undescended testes and craniofacial abnormalities. Endocrine investigations revealed hypogonadotrophic hypogonadism, with no testosterone response to hCG stimulation, a low normal AMH and no response of LH or FSH on LHRH stimulation. He has panhypopituitarism with an ectopic posterior pituitary gland on MRI and is currently on treatment with GH, hydrocortisone and levothyroxine. His BP is on the 98th centile for age and height. Child I and Child III have mild developmental delay but are in mainstream school with additional educational support. High-throughput DNA sequencing revealed, in all three siblings, a heterozygous truncating variant in the SEC31A gene that encodes a component of the COPII-complex that coats the vesicles mediating ER to Golgi transport. CRISPR-Cas9 targeted knockout of the corresponding Sec31a region resulted in embryonic lethality in homozygous mice. mRNA phenotyping of ER-related genes demonstrated increased mRNA expression of ATF4 and CHOP in the affected children, genes encoding key ER stress-related proteins, associated with defective protein transport. Conclusions Dysregulation ofanterograde and retrograde COPII-coated-vesicle ER-Golgi transport is increasingly recognised to underlie human developmental disorders, including Craniolenticulosutural dysplasia (OMIM 607812) and Saul-Wilson syndrome (OMIM 618150). The de novo SEC31A nonsense variant in all three affected siblings, the ER stress response, plus reported developmental syndromes with dysfunction of this transport mechanism and evidence from the preclinical mouse model suggest that SEC31A might underlie a previously unrecognised clinical syndrome comprising DSD, endocrine abnormalities, dysmorphic features and developmental delay. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Gonadal tumor risk in pediatric and adolescent phenotypic females with disorders of sex development and Y chromosomal constitution with different genetic etiologies.

ObjectivesThis retrospective study sought to investigate the risk and proportion of gonadal neoplasms in phenotypic female pediatric patients with DSD and the presence of the Y chromosome and different genetic backgrounds in a single Chinese center.Materials and MethodsFrom January 2012 to December 2020, pediatric and adolescent patients with DSD and the presence of the Y chromosome who had unambiguous female genitalia and underwent bilateral gonadectomy or gonadal biopsy were included in this study. Patients’ demographics, karyotype, laboratory test results, gross pathology, and histology of gonadal tissue were all collected. The patients were divided into three groups based on their different genetic backgrounds, and the percentage of gonadal tumors was calculated to assess the risk of gonadal tumor and malignancy by etiology.ResultsA total of 22 patients with DSD and an unambiguous female phenotype with a Y chromosome were recruited. The mean age was 10.91 ± 4.99 years (9 months to 19 years). Gonadal neoplasia was confirmed in six (27.3%) cases by pathological examination of surgical gonadal tissue samples. Among 44 gonadal samples from these 22 patients, the following were identified: five gonadoblastomas, three dysgerminomas, and two Leydig cell tumors. The youngest patient with a tumor was a 2-year-old girl with 46,XY complete gonadal dysgenesis (46,XY CGD or Swyer syndrome) and bilateral gonadoblastoma. Patients with 46,XY complete gonadal dysgenesis (4/6; 66.7%) had the highest tumor occurrence rate. Among 10 patients with Turner syndrome with the presence of the Y chromosome, only one patient was diagnosed with a gonadal tumor. Leydig cell tumor was diagnosed in only one of six patients with 46,XY androgen synthesis/action disorders.ConclusionPediatric patients with 46,XY complete gonadal dysgenesis had a significantly increased risk of developing gonadal tumors and underwent prophylactic gonadectomy as soon as the diagnosis was confirmed, whereas those with Turner syndrome with Y chromosome and 46,XY androgen synthesis/action disorders had a relatively low risk. In view of the limited number of patients, a large multicenter study with close follow-ups is needed to support these conclusions.

053 Totally extraperitoneal approach (TEP) for gonadectomy for differences in sex development (DSD): Report of 2 cases

Introduction: 17-β-hydroxysteroid dehydrogenase type-3 deficiency (17βHSD-3) is a rare cause of 46XY DSD. Gonadectomy is often offered to prevent further virilization and to continue living in a female gender role [ [1] Chuang J. Vallerie A. Breech L. Saal H.M. Alam S. Crawford P. Rutter M.M. Complexities of gender assignment in 17β-hydroxysteroid dehydrogenase type 3 deficiency: is there a role for early orchiectomy?. Int J Pediatr Endocrinol. 2013; 12: 15 Crossref Google Scholar ]. Both laparotomic and laparoscopic approaches to gonadectomy had been described for DSDs [ [2] Dellaportas D. Chatzipapas I. Pandraklakis A. Michala L. Laparoscopic bilateral gonadectomy and inguinal hernia repair with mesh for complete androgen insensitivity syndrome: A case report. J Pediatr Adolesc Gynecol. 2019; 32 (Epub 2019 Feb 27): 443-445 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ]. Retrieval and removal of testes located in the inguinal canal can be technically challenging and requires collaboration with surgical colleagues. Cases: We present 2 cases of DSD with 17βHSD-3. One of them is 16 years old, while the other one is 20 years old. Both cases presented with amenorrhea and clitoral enlargement, whereas the second case also had deepening of voice. Blood tests for both revealed elevated testosterone and androstenedione. MRI findings were similar showing bilateral gonads located in the inguinal canals. Genetic tests revealed 46 XY karyotype and HSD17B3 gene mutation. Both subjects opted to continue with a female gender role and opted for gonadectomy to prevent further virilization. Gonadectomy was performed with a totally extraperitoneal laparoscopic approach. An infraumbilical incision was made and care was taken to enter the potential space above the rectus sheath. Then a balloon was placed via the port to distend the extraperitoneal space and then the laparoscope was inserted. Secondary ports at the suprapubic region and the left lower quadrant were placed. The gonads were mobilized and gonadectomy performed. Gonadectomy was successfully performed for the first case, but for the second case, there was failure to mobilize the gonad and operation was completed with inguinal incisions. Conclusion: Totally extraperitoneal laparoscopic approach for hernia repair is a well-established technique familiar to surgeons [ [3] McKernan J.B. Laws H.L. Laparoscopic repair of inguinal hernias using a totally extraperitoneal prosthetic approach. Surg Endosc. 1993; 7: 26-28 Crossref PubMed Scopus (264) Google Scholar ]. This was the first time the TEP approach has been described for gonadectomy for DSD. By cooperating with surgeons who has abundant experience in operating in this region, one can allow utilization of techniques which were already commonly used. It raises the importance as gynecologists, we should be mindful of technological advances in other specialties as with other aspects of DSD, collaboration with other specialties may lead to advances in patient management.

PD02-12 THE RISK OF GONADAL MALIGNANCY IN PATIENTS WITH ANDROGEN INSENSITIVITY SYNDROME

You have accessJournal of UrologyCME1 May 2022PD02-12 THE RISK OF GONADAL MALIGNANCY IN PATIENTS WITH ANDROGEN INSENSITIVITY SYNDROME Pratik Kanabur, Soo Jeong Kim, Sagar Patel, Lefkothea Karaviti, and Paul F. Austin Pratik KanaburPratik Kanabur More articles by this author , Soo Jeong KimSoo Jeong Kim More articles by this author , Sagar PatelSagar Patel More articles by this author , Lefkothea KaravitiLefkothea Karaviti More articles by this author , and Paul F. AustinPaul F. Austin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002517.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Androgen Insensitivity Syndrome (AIS) is a rare condition caused by a mutated androgen receptor, with varying penetrance levels. Patients often have undescended gonads, and thus an increased risk for developing germ cell tumors. Optimal gonad management in these patients is controversial. We aim to review the outcomes of gonad management in a large series of AIS patients at a single center. METHODS: A retrospective review was performed of patients with a diagnosis of AIS seen at a freestanding children’s hospital (2010-2020). Various patient factors including age at presentation, phenotypic gender, and subtype of AIS were collected. Management strategies including presence of imaging and tumor markers (AFP, HCG, LDH), surgical intervention, and length of follow-up were also evaluated. We also determined the rate of malignancy in gonadectomy specimens. RESULTS: 24 patients were included, 6 (25%) with partial AIS (PAIS) and 18 (75%) with complete AIS (CAIS). Age at evaluation ranged from 0 to 22 years. Of patients with PAIS, median age at presentation was 15 years. 3 (50%) had imaging of gonads and 2 (33%) had tumor markers obtained, all of which was negative for malignancy. 3 patients (50%) had surgical intervention (1 gonadopexy and 2 bilateral gonadectomy). One patient who underwent bilateral gonadectomy at 15 years of age was diagnosed with T1 dysgerminoma; there was no recurrence or progression of disease after 5 years of follow-up. Average length of follow-up was 2.9 years. Of patients with CAIS, median age at evaluation was 10.5 years. 12 (75%) had imaging of gonads and 3 (16.7%) had tumor markers obtained, all of which was negative for malignancy. 15 patients (83%) had surgical intervention (1 gonadopexy, 4 unilateral gonadectomy, 10 bilateral gonadectomy). One patient who underwent bilateral gonadectomy at 22 years of age had germ cell neoplasia in situ. She did not develop recurrence or progression after 6 years of follow-up. Average length of follow-up was 2.8 years. CONCLUSIONS: The majority of patients with CAIS and PAIS underwent surgical gonadectomy, and at younger ages (<5). In patients who had a gonadectomy after 12 years of age, over 25% of patients had a malignancy in the specimen, but were able to be treated with surgery alone. Imaging and tumor markers did not diagnose any malignancies. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e40 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pratik Kanabur More articles by this author Soo Jeong Kim More articles by this author Sagar Patel More articles by this author Lefkothea Karaviti More articles by this author Paul F. Austin More articles by this author Expand All Advertisement PDF DownloadLoading ...

Leydig Cell Hypoplasia and Pituitary Stalk Agenesis: Genetic Link or Coincidence

Leydig cell hypoplasia illustrates a rare category of 46, XY DSD "disorders of sex development". We report a case of a patient assigned to the female sex carrying a DSD with 46 XY karyotype on Leydig cell hypoplasia associated with pituitary stalk agenesis. This association has not been described yet in the literature. The patient was first admitted at the age of five for failure to thrive (FTT) with an abnormality of sexual development. The FTT was related to complete GH deficiency on pituitary stalk agenesis. Upon investigation, the patient was diagnosed as carrying a DSD 46, XY. The endocrine evaluation revealed low testosterone, FSH, and LH levels with a negative HCG test. The abdominopelvic ultrasound objectified two testicles in the inguinal folds. ²After discussing the case in a multidisciplinary consultation meeting, and taking into account the wishes of the family and the psychiatric expertise, the selected sex that was assigned to the patient was female. At the age of 19, the patient underwent a bilateral gonadectomy and the anatomopathological examination confirmed the diagnosis of Leydig cell hypoplasia. Leydig cell hypoplasia is a rare autosomal recessive syndrome, diagnosed by clinical, biological, radiological, histological, and genetic evidence. Its association with pituitary stalk agenesis has not been described in the literature. This syndrome is characterized by the inability of the chorionic gonadotropin luteinizing hormone receptor in Leydig cells to respond to luteinizing hormone, thereby causing feminization of a male fetus. The treatment has three components: hormonal treatment, surgical treatment, and psychological care.

EP353: Testing for Y chromosome in Turner syndrome

Turner syndrome (TS) is a genetic condition where phenotypic females have a total or partial monosomy of the X chromosome. Approximately 12% of individuals with TS are mosaic for Y chromosome material (TS+Y). TS+Y individuals have an approximately 12% increased risk for gonadoblastoma, a germ cell neoplasm with malignant transformation potential. Current clinical management guidelines for TS+Y females recommends bilateral gonadectomy to eliminate future risk for malignant transformation. Therefore, detection of occult Y chromosome material is crucial when considering prophylactic surgery, as we well as potential for future fertility.

Identification of a Novel Mutation in an Iranian Family With 17-β Hydroxysteroid Dehydrogenase Type 3 Deficiency: A Case Series

Background: We presented the clinical and genetic features of a male ambiguity due to 17-beta-hydroxysteroid dehydrogenase 3 (17B-HSD3) deficiency. Methods: The proposita was an 11-year-old girl and the first child of a consanguineous family. The external genitalia were completely female and had a short vaginal pouch. She had palpable gonads in her inguinal area and underwent bilateral gonadectomy at the age of two. At the age of 10, she was referred to our clinic for more evaluation. In pelvic sonography, uterine and ovarian were not seen. Her karyotype was 46, XY, and her LH and FSH levels were elevated, and three of the patient’s aunts and one of the mother’s aunts had similar signs. Conclusions: We identified a novel homozygous missense variation (c.731T&gt;A, p. Ile244Lys) in the HSD17B3 gene. This alteration changes Isoleucine to Lysine in exon 10.

Prophylactic Laparoscopic Bilateral Gonadectomy for Complete Androgen Insensitivity Syndrome

Watch this full-length, narrated, surgical procedure of a prophylactic bilateral gonadectomy performed by Dr. Canon at the University of Arkansas for Medical Sciences on a 15-year-old patient with complete androgen insensitivity syndrome.