[Congenital disorders of gonadal differentiation: clinico-morphological variants and surgical treatment].

The article presents the results of examination and surgical treatment of 25 patients with congenital disorders of gonadal differentiation. Survey plan included an assessment of the external genitalia, karyotyping and molecular analysis of Y-chromosome, determination of serum gonadotropins and testosterone levels, visualization of the gonads using ultrasound and laparoscopy methods, and intraoperative morphological examination of the material. Based on the results of a comprehensive survey, mixed testicular dysgenesis was identified in 25% of patients, complete testicular dysgenesis--in 16%, partial gonadal dysgenesis--in 44%, ovotesticular violation of sexualization--in 16% of patients. Clinical, macroscopic and morphological characteristics of each of these options are defined. The choice of sexual identity and tactics of surgical treatment are explained.

Mutation of the MIF type II receptor in two brothers.

The Müllerian inhibiting factor (MIF) is responsible for regression of Müllerian ducts during male sexual differentiation. Mutations in MIF or its type II receptor lead to persistence of the uterus and Fallopian tubes in male children--i.e., persistent Müllerian duct syndrome (PMDS). Both are rare autosomal recessive disorders. We report a 7-month-old male infant who underwent inguinal herniorrhaphy. Remnants of vas deferens and gonads with macroscopic characteristics of ovaries, along with Fallopian tubes and a rudimentary uterus, were found. Karyotype confirmed male sex. Molecular genetics revealed the most frequent MIF type II receptor gene mutation--27 bp deletion. Investigation of the older brother presenting bilateral cryptorchidism at 7 years of age led to similar clinical findings and the same mutation. We report here an MIF type II receptor mutation in two brothers, with the particularity that the surgical findings in the younger son initiated the diagnostic process in both children.

Laparoscopic gonadectomy in a kidney transplant patient with pure gonadal dysgenesis: a case report.

BACKGROUND: Laparoscopy has been successfully used following renal transplantation for many procedures, including native kidney nephrectomy, revision of transplant ureters and cholecystectomy. Laparoscopic surgery has also been used recently to treat pelvic disorders in patients after renal transplantation, such as removal of endometriotic cyst and hysterectomy. In such cases, we must pay special attention to the anatomy of the renal graft transplanted into the pelvic cavity. CASE: A woman received a kidney transplant at 7 years old, with her mother as the donor. At 19 years old, she was diagnosed with pure gonadal dysgenesis and began hormone replacement therapy and monitoring of tumor markers. At 23 years old, laparoscopic gonadectomy was performed under general anesthesia. Bilateral atrophic gonads were removed without any complications. The renal graft in the right hemipelvis did not obstruct the operation. CONCLUSION: To our knowledge, this case is the first published report of laparoscopic castration in a patient with a sexual differentiation disorder and prior renal transplantation.

[Identification of potential neoplastic risk in gonadal development abnormality with Y chromosome of 79 cases].

OBJECTIVE: To identify the potential neoplastic risk in gonadal development abnormality with Y chromosome. METHODS: Inquiries about the illness history were made. Lymphocyte chromosomal karyotype of peripheral blood was analyzed. Sex determining region Y gene and relative steroids and enzymes were detected. Gonadal site was examined through medical imaging. Gonadal excision was performed by laparotomy or laparoscopy. Pathological examinations were done on all of the specimens. RESULTS: Among 41 cases of androgen insensitive syndrome, spermatogenic cell neoplasm occurred in 1 patient, sertoli cell tumor in 2, and interstitial cell hyperplasia in 5. Among 14 cases of 17 alpha-hydroxylase deficiency (XY) syndrome, one was sertoli cell tumor, and one was sertoli cell hyperplasia. In 4 cases of XY pure gonadal dysgenesis, one was gonadoblastoma with dysgerminoma. One of 16 cases of XO/XY gonadal dysgenesis was spermatogenic cell neoplasm with agenda cell tumor. Four cases of testes degeneration were all with dysgenetic testes. All of the gonadoblastoma and germ-cell tumor were located in the pelvis. Tumors occurred mostly during 15 years of age to 32 years. CONCLUSIONS: The gonads of XY pure gonadal dysgenesis has high risks of gonadoblastoma and germ-cell tumor. The older the onset age after puberty, the higher the malignancy risk is. Once diagnosed, bilateral gonads should be excised as soon as possible.

Normal pelvic ultrasound or MRI does not rule out neoplasm in patients with gonadal dysgenesis and Y chromosome material.

INTRODUCTION: Patients with gonadal dysgenesis (GD) with a Y chromosome have an increased risk of gonadal neoplasm. Few data exist on the ability of imaging to detect malignancy in intra-abdominal gonads in these patients. OBJECTIVE: We aimed to determine the correlation between preoperative imaging findings and gonadal pathology in GD patients with Y chromosome material. METHODS: A retrospective review was performed of patients with XY or XO/XY GD who underwent gonadectomy at our institution from 2003 to 2017. Patients were assessed preoperatively with ultrasonography; some additionally underwent MRI. RESULTS: The series consisted of 10 patients, all with female gender and non-palpable gonads. Median age was 13.1 years (range 2.4-18.3 years). Overall, four of the ten patients (40%) had a tumor (gonadoblastoma or dysgerminoma) on final pathology. Four patients had a gonad or gonads that were definitively seen on ultrasonography. All visualized gonads were described as "normal" or "small" with the exception of one patient, who had a normal MRI. Three of the four patients in this group had a tumor on final pathology. The remaining six patients had a gonad or gonads that were not definitively visualized on ultrasound; one patient in this group had a tumor on final pathology. Overall, five of seven gonads (71%) definitively visualized on ultrasound had tumor on final pathology, and two of thirteen gonads (15%) not visualized on ultrasound had tumor on final pathology; this difference was statistically significant (p = 0.012). Three patients were imaged with MRI. Of the gonads that could be visualized on MRI, no definitive abnormalities were seen. All patients imaged with MRI had tumors on final pathology. DISCUSSION: Both ultrasound and MRI are relatively poor at identifying and characterizing intra-abdominal gonads in GD patients. The majority of patients who had a neoplasm had normal imaging findings. Gonads that were definitively visualized on ultrasound were more likely to contain neoplasms that could not be visualized, which perhaps because of tumor growth. No other consistent imaging findings of malignancy were found. Our study included ultrasound evaluations that were completed over 10 years ago and not performed by pediatric ultrasonographers, which may have biased the results. However, results suggest that when discussing gonadectomy with GD patients, one should not be reassured by "normal" imaging findings. Neither ultrasound nor MRI should be relied on for surveillance in GD patients who decide against gonadectomy. CONCLUSION: A normal ultrasound or MRI does not rule out neoplasm in GD patients with intra-abdominal gonads.

Persistent mullerian duct syndrome with transverse testicular ectopia.

A 15-month-old boy was discovered to have internal female genitalia during an operation for bilateral inguinal hernia. The biopsies showed normal testicular tissue and the karyotyping result was 46XY, so the diagnosis of persistent mullerian duct syndrome (PMDS) was made. At the second operation, the uterine fundus and fallopian tubes were excised. Then, he underwent bilateral orchiopexy. We discuss a rare presentation of this disorder, its management, and genetic implications together with a review of the literature.

Surgical, medical and psychological dilemmas of sex reassignment: report of a 46,XY patient assigned female at birth.

This is a report of a 16 year-old 46,XY male who was reassigned female and had feminizing surgery during infancy because of what was judged to be inadequate genital masculinization. This patient had a dysgenetic testis that was shown to be producing testosterone during infancy. Although initially the reassignment appeared to be successful, psychological problems became progressively more severe during childhood to incapacitation by age 10 years. After it was verified that he had a male sexual identity, reassignment as male began, initially by living as a boy, then with testosterone therapy. Staged phalloplasty surgery was begun at age 16 years. Currently he has an adult-sized penis, although its function is not yet clear. Sadly, none of the steps to align his sex assignment to his perception as male has significantly alleviated his psychological issues and he continues to be severely impaired and socially compromised. Major issues include the crippling psychiatric disease that is resistant to psychotherapy and surgical problems with phalloplasty after surgery at infancy that involved reduction of the phallus with recession of the glans to the typical clitoral location. The glans was left intact at the anterior base of the phallus. Genital responsiveness during sexual activity and satisfaction are as yet unknown.

Gonadal dysgenesis in disorders of sex development: Diagnosis and surgical management.

Recent studies on gonadal histology have improved the understanding of germ cell malignancy risk in patients with disorders of sex development (DSD), and evidence-based gonadal management strategies are gradually emerging. Especially in 46,XY DSD and 45,X/46,XY DSD, which are characterized by gonadal dysgenesis, the risk of germ cell malignancy is significantly increased. This paper summarized the progress over the past 10 years in malignancy risk assessment in patients with DSD, and its implications for optimal surgical handling of the involved gonads.

[Diagnostic principles of gonadal dysgenesis in adolescents].

103 patients aged 11-20 with short stature and/or with delayed puberty were studied. Among all patients classical form of gonadal dysgenesis was diagnosed in 31 patients (karyotype 45,X- 17 patients, 45,X/46,XX- 14), "mixed" gonadal dysgenesis in one patient (karyotype 45,X/46,XY)-, "pure" gonadal dysgenesis- in 5 cases (karyotype 46,XY-in 4 , 45,X -- in one). The majority of cases (66) were diagnosed as ovarian dysgenesis with the mosaic karyotype- 46,XX/45,X. In the clinical diagnostics of ovarian dysgenesis some difficulties were aroused because of slight reduction of height and delayed sexual development, mild appearance absence or somatic anomalies. The main diagnostic criteria for the various forms of gonadal dysgenesis are detection of characteristic karyotype and hypogonadotropic hypogonadism. Characteristic phenotype is more informative in the cases of classical and "mixed" forms of gonadal dysgenesis. Early diagnosis of gonadal dysgenesis is very important for effective correction of height and sexual development. Timely begin hormonal therapy may avoid complications induced bihypoestrogenia, such are: osteoporosis, cardiovascular diseases and etc. Karyotype investigation and in the cases of revealing Y chromosome material, and therefore gonadectomy must precede the beginning of hormonal therapy.

Disorders of sexual differentiation.

An infant born with ambiguous genitalia requires an accurate and prompt diagnosis so that a management plan can be formulated. This article discusses the signaling cascade of genes that controls sexual differentiation. Clinical disorders involving sex reversal or ambiguous genitalia are discussed in relation to the genes regulating sexual development. An approach to the treatment of these disorders is outlined.

Multifetal pregnancy in a gonadal dysgenesis mosaic.

A successful triplet gestation in a 45,X/46,XY woman is presented. A previously hypoplastic uterus was prepared for implantation by exogenous hormone replacement. Conception was achieved through in vitro fertilization of donor oocytes and transfer of four embryos into a hormonally primed endometrium. This case illustrates that some women with 45,X/46,XY karyotype can have a successful triplet pregnancy. Therefore, a conservative approach during gonadectomy in patients with a Y chromosome may be warranted.

Vaginal construction.

Construction of the vagina was performed in 5 46 XY, phenotypic female children, by utilizing a vascularized segment of ileum, which is folded and converted into a pouch, then placed between the rectum and bladder, and transplanted to the perineum. The neovaginal opening remained patent in all, mucus discharge decreased with time, and one teenager experienced a satisfactory sexual relationship.

Polyorchidism and testicular torsion.

Presented is a case of a young man with polyorchidism and traumatic testicular torsion.

Dysgerminoma of the ovary in association with XY gonadal dysgenesis.

A case is reported of an adolescent presenting with primary amenorrhea. On pelvic examination a large unilateral ovarian tumor was palpated. Microscopic examination of the tumor removed at laparotomy revealed a pure dysgerminoma. Further gynecological-endocrinological investigations and chromosome analysis showed an XY gonadal dysgenesis. A review of current approaches to diagnosis, prognosis and especially to the controversial therapeutic modalities is presented.

Laparoscopic gonadectomy in male pseudohermaphrodites.

OBJECTIVE: To study patients of male pseudohermaphroditism and establish the laparoscopic approach for gonadectomy in these cases. STUDY DESIGN: Seven phenotypic females with XY karyotype were evaluated through a diagnostic protocol which included clinical, cytogenetic, hormonal, endoscopic and histologic evaluation. The gonads were then removed by laparoscopic surgery. RESULTS: The seven patients included three patients of pure gonadal dysgenesis, two patients of testicular feminization and one patient each of mixed gonadal dysgenesis and dysgenetic male pseudohermaphroditism. Two of the seven patients (28.57%) had gonadal neoplasias on histopathology-one dysgerminoma and one occult seminoma. In all of these patients, removal of the gonads was accomplished laparoscopically. No complications occurred during any of the surgeries. CONCLUSION: Due to the reduced morbidity, shorter hospital stay and safety, laparoscopic gonadectomy can be considered the treatment of choice for the removal of gonads in male pseudohermaphrodites in the hands of experienced laparoscopic surgeons.

Genital ambiguity with a Y chromosome: does gender assignment matter?

Recommendations for sex of rearing in newborns with genital ambiguity, testicular differentiation and a Y chromosome continue to be challenging. Complaints from former patients have forced those providing the medical, surgical and psychological care for these individuals to reassess evaluation and treatment strategies. In this paper, the histories of six patients born with genital ambiguity and at least partial testicular differentiation with a karyotype containing a Y chromosome are presented. Three of these patients were assigned as males and three as females. The factors involved in these individuals' adaptation to the assigned gender and their subsequent quality of life are discussed. Factors needing further study, including the parents' ability to accept and support the sex of rearing, the child's temperament, associated psychological disorders, and other influences, such as masculinization of the central nervous system, are highlighted.

Importance of early diagnosis and gonadectomy in 46, XY females.

Gonadal neoplasms developed in three 46, XY females aged 3 yr and 10 mo, 15 yr, and 19 yr. One patient died from metastatic neoplasia. Early diagnosis of 46, XY gonadal dysgenesis is essential, and should be considered in female infants and children with any features of Turner's syndrome, ambiguous genitalia, phallic hypertrophy, excessive height, large hands and feet, failure of development of secondary sexual characteristics, primary amenorrhea, abdominal mass, or unexplained hypertension. Any female with gonadal dysgenesis and a Y chromosome in her karyotype should have prophylactic gonadectomy as soon as possible. The absence of Sertoli cells in these patients, causing lack of androgen binding protein with deficient local concentration of androgens and consequent failure of maturation of spermatogonia, may lead to unregulated proliferation of germ cells, and hence explain the frequency of gonadal neoplasia in the 46, XY female.

Preperitoneal ectopic testis: a case report.

We report a 5 1/2-year-old boy with preperitoneal ectopic testes. This condition has been reported only once before. Both testes were attached to the umbilicus and at operation were successfully placed in the scrotum.

Surgical treatment of intersex disorders.

Despite the progress made in understanding the factors regulating sexual differentiation, infants born with ambiguous genitalia face significant problems. The authors reviewed a group of 84 children with ambiguous genitalia managed surgically between 1986 and 1993. The most frequent condition was male pseudohermaphroditism (PM) (58%); 31% had female pseudohermaphroditism. Fifty-seven percent of patients were raised as males and 43% as females. In each group of patients, feminine and masculine reconstructive operations were performed. In only 31% of PM and 60% of PF cases was the diagnosis made within the first 2 months of life. In 41% of PF and 40% of PM patients, treatment was begun before the second year of life, which we consider an acceptable time. The timing and type of vaginoplasty were determined by the point of entry of the vagina into the urogenital sinus. Of the 29 patients reared as females, 22 required perineal vaginoplasty, had pull-through vaginoplasty, and 2 had colovaginoplasty. Since 1986, we have applied Mollard's clitoroplasty, which preserves the neurovascular bundle and is important for experiencing orgasm. Seventeen percent of patients with feminization procedures experienced complications. The optimal time for masculinization procedures is 2 years of age, after obligatory testosterone treatment. If there is utriculus prostaticus (UP) type II or III, it is removed before urethroplasty. This is not done for UP types 0 and 1. In PM cases, the number of feminization and masculinization operations was 2.1 and 4.05 per patient, respectively. It is easier to make a vagina than a phallus, not taking into consideration dimensions, aesthetics, or capability of erection of the phallus.(ABSTRACT TRUNCATED AT 250 WORDS)