Yolk sac tumor and dysgerminoma in the left gonad following gonadoblastoma in the right gonad in a 46,XY DSD with a novel SRY missense mutation: a case report.

BACKGROUND: Approximately 10-15% of 46,XY disorders of sex development (DSDs) have an SRY mutation residing in the high mobility group (HMG) domain. Here, we present a case of 46,XY DSD caused by a novel missense mutation in the HMG region of SRY rapidly progressing to germ cell tumors (GCTs). CASE PRESENTATION: An adolescent female (15 years old) exhibiting primary amenorrhea was later diagnosed as a 46,XY female with bilateral gonadal dysplasia on the basis of peripheral lymphocyte karyotype 46,XY and a novel missense mutation in SRY (c.281 T > G, p.L94R). The novel missense mutation (c.281 T > G, p.L94R) and its adjacent region were conserved. Protein structure analysis showed that the mutant site was located in the middle of the HMG domain, and the mutant protein had a diminished ability to bind to DNA. Imaging examination revealed an adolescent female with a naive uterus. Laparoscopy and initial pathological examination revealed left gonadal dysplasia and right gonadal dysplasia with gonadoblastoma (GB). Right gonadectomy by laparoscopy was performed upon consent from the patient's parents. Less than 1 year postoperatively, the left gonadal gland deteriorated as observed by the findings of a mass in the left adnexal region by pelvic MRI and serum AFP > 1000 ng/ml by serological tests, and then total hysterectomy and adnexal and left gonadectomy by laparoscopy were performed. The GCT stage was classified as stage Ic according to FIGO. At this time, pathologic examination showed that the left gonad had progressed to yolk sac tumor and dysgerminoma. The patient underwent chemotherapy post-operatively but developed type III myelosuppression and tumor recurrence several months later. CONCLUSIONS: The patient initially presented with right gonadoblastoma but chose only right gonadectomy by laparoscopy to preserve the female sex characteristics, which resulted in rapid deterioration of the left gonad and poor treatment outcomes. This case demonstrates the importance of early genetic diagnosis and treatment of 46,XY female DSD.

GPR109A gene deletion ameliorates gonadectomy-induced bone loss in mice.

Sex steroid deficiency plays critical roles in the pathophysiology of bone as the result of uncertain bone remodeling, i.e., increased bone resorption with equivocal bone formation. We have previously shown that GPR109A, a G protein coupled receptor, controls osteoclastogenesis and bone resorption, where global GPR109A deletion decreased osteoclast bone resorption and increased bone mass. Here, we used global GPR109A gene deletion, ovariectomized (OVX) and orchidectomized (ORX) mouse models to probe the role of GPR109A in gonadectomy-induced bone loss in female and male mice. Six months old GPR109A-/- mice and their wild type littermates were allocated to Sham or gonadectomized groups for six weeks. Using densitometric micro-CT confirmed by peripheral quantitative CT (pQCT) scans on tibia and spine, and three-point bending test on femur ex vivo, we found the bone volume, trabecular number, as well as bone mineral density and content in both trabecular and cortical sites were significantly decreased in wild type OVX and ORX compared with respective Sham groups. While bone mass in both male and female GPR109A-/- Sham groups were significantly higher compared with their respective wild type Sham groups, global GPR109A gene deletion ameliorated gonadectomy-induced bone loss. In GPR109A-/- females, most of bone mass and strength parameters measured by micro-CT, pQCT and three-point bending test were not different between Sham and OVX groups. In wild type but not in GPR109-/- mice, bone remodeling marker measurements indicated that both bone resorption (Cathepsin K) and bone formation (osteocalcin) markers were increased in gonadectomized mice compared to sham, with the exception of bone specific ALP, which was decreased in gonadectomized mice. Expression of bone resorption markers (Cathepsin K) were significantly lower, but ß-catenin expression was higher in GPR109A-/- mice compared with their wild type littermates. Collectively, these data indicate that global GPR109A deletion ameliorates gonadectomy-induced bone loss through suppression of bone resorption.

Prophylactic gonadectomy in 46 XY females; why, where and when?

OBJECTIVES: We compared cases of phenotypic female patients who presented with male karyotype and underwent prophylactic gonadectomy. CASE PRESENTATION: Five patients with female phenotypes presented in early adulthood with primary amenorrhoea with varying degrees of puberty. One was tall with breast development. Another was very short with clitoromegaly and multiple co-morbidities. The other three had no secondary sexual characteristics. They were examined, after which hormonal profile, karyotyping, ultrasound examination and magnetic resonance imaging were done to assess the site of gonads. Gonadectomy was performed once their 46 XY karyotype was confirmed. Results of histopathological examination of their gonads ranged from dysgenetic gonads to having testicular tissues and malignancy. CONCLUSION: Female patients with 46 XY karyotypes require prophylactic gonadectomy performed at different timings depending on diagnosis due to the malignancy risk. Pre-operative assessment is essential to locate the gonads prior to surgery.

Gonadectomy and Blood Sampling Procedures in the Small Size Teleost Model Japanese Medaka (Oryzias latipes).

Sex steroids, produced by the gonads, play an essential role in brain and pituitary tissue plasticity and in the neuroendocrine control of reproduction in all vertebrates by providing feedback to the brain and pituitary. Teleost fishes possess a higher degree of tissue plasticity and variation in reproductive strategies compared to mammals and appear to be useful models to investigate the role of sex steroids and the mechanisms by which they act. The removal of the main source of sex steroid production using gonadectomy together with blood sampling to measure steroid levels has been well-established and fairly feasible in bigger fish and is a powerful technique to investigate the role and effects of sex steroids. However, these techniques raise challenges when implemented in small size teleost models. Here, we describe the step-by-step procedures of gonadectomy in both males and female Japanese medaka followed by blood sampling. These protocols are shown to be highly feasible in medaka indicated by a high survival rate, safety for the life span and phenotype of the fish, and reproducibility in terms of sex steroid clearance. The use of these procedures combined with the other advantages of using this small teleost model will greatly improve the understanding of feedback mechanisms in the neuroendocrine control of reproduction and tissue plasticity provided by sex steroids in vertebrates.

Clinical and Economic Value of Routine Pathological Examination of Hernia Sacs and Scheduled Clinic Follow-Ups After Inguinal Hernia and Hydrocele Repair in a Canadian Tertiary Care Children's Hospital.

BACKGROUND: The clinical and economical value of routine submission of hernia sacs for pathological examination and scheduled clinic follow-ups after inguinal hernia and hydrocele repair has been questioned. Herein, we assessed the institutional variability in these routine practices. METHODS: We retrospectively reviewed patients who underwent unilateral or bilateral inguinal hernia and/or hydrocele repair, open or laparoscopically, at our institution from 2015 to 2018. RESULTS: 1181 patients were included (1074 inguinal hernias and 157 hydroceles). Of 531 specimens obtained from 446 (38%) patients, 515 (97%) were normal. 16 (3%) abnormal pathological findings included 7 with mesothelial hyperplasia, 5 with nonfunctional genital ductal remnants, 3 with ectopic adrenal cortical tissues, and 1 epidydimal structure which was not recognized at the time of surgery. 418 (35%) patients had scheduled clinic follow-ups 65 (IQR 46-94) days postoperatively. 44 (4%) patients with unexpected postoperative Emergency Department visits within 30 days of surgery were identified. Only one patient required inpatient treatment, and the rest did not require intervention or admission. The total direct cost of analyzing specimens during the study period was $30,798 CAD ($10,266/year). The average cost to detect a potentially significant finding was $1924.88/specimen and $2053.20/patient. CONCLUSIONS: Routine pathological examination of hernia sacs and scheduled clinic follow-ups were associated with significant costs and predominantly nonsignificant findings. They should therefore be reserved for patients with a high clinical suspicion of injuries/abnormalities or risk factors for potential complications. LEVEL OF EVIDENCE: This is a level III evidence study.

Bone mineral density, body composition and metabolic profiles in adult women with complete androgen insensitivity syndrome and removed gonads using oral or transdermal estrogens.

OBJECTIVES: To assess bone health in adult women with complete androgen insensitivity syndrome (CAIS) and removed gonads compared with age-matched healthy controls. To evaluate the effects of transdermal oestradiol 2 mg or oral estradiol valerate 2 mg on bone, biochemical and clinical characteristics. DESIGN: Cohort study. METHODS: Bone, body composition and anthropometric parameters were assessed in 32 adult CAIS and 32 healthy controls. In 28 cases, CAIS evaluations of metabolic, bone and body composition were performed also after a maximum of 6 years of therapy. RESULTS: Lumbar, femoral and total body bone mineral density (BMD) were significantly lower in those with CAIS when compared with controls. The prevalence of vertebral osteoporosis and osteopenia was significantly higher in the CAIS group (P = 0.038, OR = 9.67, 95% CI: 1.13-82.83 and P = 0.012, OR= 3.85, 95% CI: 1.34-11.16, respectively). Prevalence of femoral osteopenia was significantly higher in the CAIS group (P = 0.0012, OR = 7.93, 95% CI: 2.26-27.9). During follow-up, lumbar BMD significantly increased suggesting a significant effect of treatment on BMD (P = 0.0016), while femoral and total body BMD did not show any significant change. Total body BMD values were positively associated to the duration and route of oestrogen administration and to serum estradiol levels. Transdermal administration of estrogens was associated with better total body BMD in comparison to oral administration. CONCLUSIONS: Our results reinforce the importance of adequate hormonal treatment for women living with CAIS, suggesting a better effect from the transdermal route over the oral route.

Hyperandrogenism in a girl with Turner syndrome: A case report.

RATIONALE: The gonads of patients with Turner syndrome (TS) were previously thought to be funicular. There was no increase in androgen level. The gonad that is testis should be taken into account when the patient's serum testosterone level was abnormal and hypothalamic-pituitary-adrenal disease was excepted. PATIENT CONCERNS: A 16-year-old girl was admitted to our hospital because of chromosomal abnormalities and elevated androgen levels. DIAGNOSIS: Turner syndrome could be diagnosed since her chromosome karyotype was 45, XO. INTERVENTIONS: The patient was given bilateral gonadectomy and hormone replacement therapies. OUTCOME: The level of the patient's serum testosterone was <0.45 nmol/L 2 days after the operation. Postoperative pathology showed that her right gonad was testicular tissue. The patient's menstruation was normal after the treatment of hormone replacement therapy. LESSONS: All TS patients should get Y chromosome material screening. Gonadectomy could be done for Turner syndrome patients who have hyperandrogenism or Y chromosome material.

A Management Protocol for Gonad Preservation in Patients with Androgen Insensitivity Syndrome.

Historically, individuals with androgen insensitivity syndrome (AIS) were managed with removal of gonadal tissue at various ages to avert the risk of gonadal malignancy. Recently, clinical practice changed, with gonadectomy being postponed until late adolescence. Adolescents and adults with complete AIS have questioned this approach. Additionally, testicular germ cell tumors are increasingly believed to be quite rare with rates as low as 0% in molecularly confirmed individuals with AIS. Gonadectomy deprives patients of the benefits of their endogenous hormones and potential fertility. Furthermore, human rights organizations advocate for deferring irreversible surgery in conditions known as differences of sex development, which includes AIS, to allow patient autonomy in decision-making. Recent literature supports an approach that uses risk stratification to manage gonads in AIS. Herein we review what is known about malignancy risk in the different subtypes of AIS and propose a management protocol for gonad retention.

Role of HPA and the HPG Axis Interaction in Testosterone-Mediated Learned Helpless Behavior.

Affective disorders show sex-specific differences in prevalence, symptoms, and complications. One hypothesis for this discrepancy is the interaction between the hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis. The present study investigates the influence of androgen on the behavioral phenotype and explores how it interacts with HPA axis genes. Gonadectomized (GDX) and GDX rats treated with testosterone propionate (T) were tested for learned helplessness (LH) behavior and compared with tested controls (TC). Prefrontal cortex was used for analyses of HPG- axis-related genes (androgen receptor, (Ar); estrogen receptor-ß (Er-ß)) and HPA axis-related genes (corticotropin-releasing hormone, (Crh); glucocorticoid receptor, (Nr3c1); corticotropin-releasing hormone receptor 1, (Crhr1); corticotropin-releasing hormone receptor 2, (Crhr2); FK506 binding protein 5, (Fkbp5)). Promoter-specific CpG methylation in the Crh gene was determined by bisulfite sequencing. Chromatin immunoprecipitation (ChIP) assay was used for determining ER-ß binding on the proximal promoter region of Crh gene. Serum testosterone levels confirmed a testosterone-depleted GDX group, a group with supraphysiological levels of testosterone (T) and another group with physiological levels of testosterone (control (C)). Unlike GDX rats, T group exhibited significantly higher LH score when compared with any other group. Crh and Fkbp5 genes were significantly upregulated in GDX group compared with controls, whereas Er-ß showed a significant downregulation in the same group. Methylation analysis showed no significant differences in-between groups. ChIP assay was unable to determine a significant change in ER-ß binding but revealed a notable contrast in Crh promoter occupancy between T and GDX groups. Altogether, the present study reveals an increased susceptibility to depression-like behavior due to chronic supraphysiological level of androgen via HPA axis inhibition.

The Mosaicism Ratio of 45,X May Explain the Phenotype in a Case of Mixed Gonadal Dysgenesis.

Some patients with mixed gonadal dysgenesis (MGD), whose prototypical karyotype is 45,X/46,XY, are known to manifest complications characteristic of Turner syndrome. We report a 16-year-old social male with MGD presenting with coarctation of the aorta, one of the common complications for Turner syndrome. At birth, the patient was found to have hypospadias, bifid scrotum, and cryptorchidism. Chromosomal analysis of his lymphocytes revealed the karyotype 45,X[7]/46,X,dic(Y;22)(p11.3;q13.3)[23] (named 45,X/46,X+Y fragment in this article). A left gonadectomy was performed at 1 year of age, and the histology showed a streak gonad with an epithelial cord-like structure compatible with MGD. At the age of 10 years, coarctation of the aorta was discovered by chance, for which the patient underwent surgical repair. The ratio of mosaicism in the gonad and aortic tissues was estimated by FISH with probes to identify the X centromere-specific repeat sequence and Yp11.2. The mosaicism ratio of 45,X/46,X+Y fragment varied among the tissues, with those having a higher ratio being more likely to exhibit the Turner syndrome phenotype. Some 90% of cells in the aortic tissues and 80% in the gonadal tissues lacked a Y chromosome. In conclusion, the mosaicism ratio in the different tissues may explain the phenotypes in MGD.

A propósito de un caso: disgenesia gonadal pura 46XY o síndrome de Swyer / On the subject of a case: 46XY pure gonadal dysgenesis or Swyer’s syndrome

La disgenesia gonadal es la primera causa de amenorrea primaria. Se define como una falta de correlación entre el fenotipo sexual manifestado y el genotipo. Las principales etiologías por su mayor frecuencia corresponden al síndrome de Turner y síndrome de Swyer. Se presenta el caso de una paciente que consulta por una amenorrea primaria a los 17 años. En primer lugar, se realiza una anamnesis descartando cuadros similares en su familia. A la exploración física destaca un aspecto femenino normal, aunque el desarrollo de los caracteres sexuales secundarios no es completo observándose unas mamas en estadio I de Tanner y escaso vello axilar y púbico. A la exploración ginecológica se observan genitales externos femeninos normales sin signos de hipoestrogenismo. Se realiza un tacto bimanual en el que impresiona que el útero está en anteversoflexión, de pequeño tamaño y no es posible tactar los ovarios en las zonas anexiales. Se realiza una ecografía transvaginal en la que se objetiva un útero pequeño y no se distinguen estructuras compatibles con ovarios en ambas zonas anexiales. Se solicita un cariotipo que es informado como 46XY. El juicio diagnóstico es síndrome de Swyer. Se realiza una gonadectomía profiláctica vía laparoscópica. Intraoperatoriamente se objetiva un útero de aspecto hipoplásico y los ovarios se encuentran sustituidos por cintillas fibrosas de color blanco nacarado. Histológicamente están compuestas por tejido similar a la cortical ovárica sin distinguirse folículos primordiales, datos característicos de la disgenesia gonadal. Tras la intervención la paciente ha recibido tratamiento con terapia de reemplazo hormonal (AU)

Gonadal dysgenesis is the leading cause of primary amenorrhea. It is defined as a lack of correlation between the sexual phenotype and genotype said. The main etiologies for their most frequently correspond to Turner syndrome and Swyer syndrome. It is described the case of a patient who complains of primary amenorrhea at age 17. First, a thorough history is made by ruling similar pictures in your family. A physical examination revealed a normal female appearance, although the development of secondary sexual characteristics is not fully, observed a breast Tanner stage I and low axillary and pubic hair. A pelvic examination showed normal female external genitalia, no evidence of hypoestrogenism. A two-hand touch in which the uterus is impressive in anteversoflexión, is small and can not be tactar ovaries in adnexal areas is performed. Transvaginal ultrasound in which a small uterus objective and non-compatible structures with ovarian adnexal differ in both areas is performed. A karyotype which is reported as 46XY is requested. The diagnosis judgment is Swyer syndrome. Prophylactic gonadectomy performed laparoscopically. Intraoperatively was observed a hypoplastic uterus stayed in pelvis and ovaries are substituted by fibrous tracts of pearly white. From the histological point of view these slips are composed similar to the cortical tissue without distinguishing ovarian primordial follicles ovarian, data compatible with the characteristics of gonadal dysgenesis. After the intervention the patient has been treated with hormone replacement therapy (AU)

Luteinizing Hormone and GATA4 Action in the Adrenocortical Tumorigenesis of Gonadectomized Female Mice.

BACKGROUND/AIMS: Physiological role of luteinizing hormone (LH) and its receptor (LHCGR) in adrenal remains unknown. In inhibin-α/Simian Virus 40 T antigen (SV40Tag) (inhα/Tag) mice, gonadectomy-induced (OVX) elevated LH triggers the growth of transcription factor GATA4 (GATA4)-positive adrenocortical tumors in a hyperplasia-adenoma-adenocarcinoma sequence. METHODS: We investigated the role of LHCGR in tumor induction, by crossbreeding inhα/Tag with Lhcgr knockout (LuRKO) mice. By knocking out Lhcgr and Gata4 in Cα1 adrenocortical cells (Lhcgr-ko, Gata4-ko) we tested their role in tumor progression. RESULTS: Adrenal tumors of OVX inhα/Tag mice develop from the hyperplastic cells localized in the topmost layer of zona fasciculata. OVX inhα/Tag/LuRKO only developed SV40Tag positive hyperplastic cells that were GATA4 negative, cleaved caspase-3 positive and did not progress into adenoma. In contrast to Lhcgr-ko, Gata4-ko Cα1 cells presented decreased proliferation, increased apoptosis, decreased expression of Inha, SV40Tag and Lhcgr tumor markers, as well as up-regulated adrenal- and down-regulated sex steroid gene expression. Both Gata4-ko and Lhcgr-ko Cα1 cells had decreased expression of steroidogenic genes resulting in decreased basal progesterone production. CONCLUSION: Our data indicate that LH/LHCGR signaling is critical for the adrenal cell reprogramming by GATA4 induction prompting adenoma formation and gonadal-like phenotype of the adrenocortical tumors in inhα/Tag mice.

Kidney Transplantation Using Gonadal Vein for Venous Anastomosis in Patients With Iliac Vein Thrombosis or Stenosis: A Series of Cases.

BACKGROUND: Kidney transplantation is the treatment of choice for patients with end-stage renal disease. The standard surgery uses the recipient's iliac vessels for vascular anastomosis. Thrombosis and/or stenosis of the iliac vein, which are possible complications of multiple vascular access points for dialysis, can be detected intraoperatively, constituting a surgical challenge. An infrequently reported option is the use of the gonadal vein. OBJECTIVES: This study aims to evaluate the outcomes of venous anastomosis in the gonadal vein in patients with iliac vein thrombosis and/or stenosis submitted to kidney transplantation. METHODS: We reviewed the records of five adult recipients with iliac vein thrombosis and/or stenosis detected intraoperatively during emergency kidney transplantation with deceased donor due to vascular access failure from February 2013 to December 2014. Antithrombotic prophylaxis was not performed. We evaluated the postoperative complications, length of stay, early graft echo-Doppler, and renal function during the first year postoperatively. RESULTS: Delayed graft function occurred in three cases. Two patients developed postoperative infection requiring antibiotics. One patient required reoperation due to post-renal biopsy complications. The mean length of stay was 31.2 days and the mean serum creatinine levels at discharge, at 6 months, and at 12 months postoperatively were 1.42 mg/dL, 0.86 mg/dL, and 0.82 mg/dL, respectively. All patients had normal ultrasonography. There were no losses of graft or deaths during follow-up. CONCLUSION: Venous anastomosis using the gonadal vein in kidney transplantation for patients with iliac vein thrombosis and/or stenosis showed good clinical and surgical results, showing this method to be a viable alternative to venous drainage in these complex patients.

Frequency of gonadal tumours in complete androgen insensitivity syndrome (CAIS): A retrospective case-series analysis.

BACKGROUND: Complete androgen insensitivity syndrome (CAIS) is an X-linked recessive disorder of sex development (DSD) where affected individuals are phenotypically female, but have an XY karyotype and testes. The risk of gonadal tumour development in CAIS may increase with age; incidence rates have been reported to be 0.8-22% in patients who have retained their gonads into adulthood. Consequently, gonadectomy has been recommended either during childhood or after puberty is complete, although there is no consensus on the optimal timing for this procedure. OBJECTIVE AND HYPOTHESES: To establish the frequency of histological abnormalities in CAIS in relation to the age at gonadectomy. METHOD: Data were collected from the Cambridge DSD database on patients with CAIS (n = 225; age range 3-88 years) who had undergone gonadectomy, and their age of gonadectomy, gonadal histology and immunohistochemistry. RESULTS: Evaluable data were obtained from 133 patients. Median age at gonadectomy was 14.0 years (range: 18 days-68 years). Pubertal status was: prepuberty, n = 62; postpuberty, n = 68. Thirteen cases were aged >20 years at gonadectomy. The pattern of histology is summarised in the Summary table. DISCUSSION: In this large case series of CAIS patients who had undergone gonadectomy, while the combined malignant and premalignant gonadal histology prevalence was 6.0%, the findings confirm the low occurrence of gonadal malignancy in CAIS, with a frequency of 1.5%. The two cases of malignancy were postpubertal. Germ cell neoplasia in situ (GCNIS) was observed in six cases, of which one occurred prepuberty and five postpuberty. The study highlighted difficulties in diagnosis of GCNIS and the need for histological analysis in expert centres. CONCLUSION: The results support the current recommendation that gonads in CAIS can be retained until early adulthood. The small number of individuals with gonadectomy after age 20 years do not allow firm conclusion regarding later adulthood. Therefore, it is recommended that the option of gonadectomy be discussed in adulthood. Some form of regular surveillance of the gonads is then recommended, although none of the available options are ideal.

Mosaicismo XYY/X0 / Mosaicism XXY/X0

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GLI1+ progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic gonadal-like tissue.

As certain strains of mice age, hyperplastic lesions resembling gonadal tissue accumulate beneath the adrenal capsule. Gonadectomy (GDX) accelerates this heterotopic differentiation, resulting in the formation of wedge-shaped adrenocortical neoplasms that produce sex steroids. Stem/progenitor cells that reside in the adrenal capsule and retain properties of the adrenogonadal primordium are thought to be the source of this heterotopic tissue. Here, we demonstrate that GLI1+ progenitors in the adrenal capsule give rise to gonadal-like cells that accumulate in the subcapsular region. A tamoxifen-inducible Cre driver (Gli1-creERT2) and two reporters (R26R-lacZ, R26R-confetti) were used to track the fate of GLI1+ cells in the adrenal glands of B6D2F2 mice, a strain that develops both GDX-induced adrenocortical neoplasms and age-dependent subcapsular cell hyperplasia. In gonadectomized B6D2F2 mice GLI1+ progenitors contributed to long-lived adrenal capsule cells and to adrenocortical neoplasms that expressed Gata4 and Foxl2, two prototypical gonadal markers. Pdgfra, a gene expressed in adrenocortical stromal cells, was upregulated in the GDX-induced neoplasms. In aged non-gonadectomized B6D2F2 mice GLI1+ progenitors gave rise to patches of subcapsular cell hyperplasia. Treatment with GANT61, a small-molecule GLI antagonist, attenuated the upregulation of gonadal-like markers (Gata4, Amhr2, Foxl2) in response to GDX. These findings support the premise that GLI1+ progenitor cells in the adrenal capsule of the adult mouse give rise to heterotopic tissue.

Wilms' tumour 1 gene mutations in south Indian children with steroid-resistant nephrotic syndrome.

BACKGROUND & OBJECTIVES: Clinically, nephrotic syndrome (NS) is a diverse group of symptoms; about 20 per cent of NS cases are resistant to steroid treatment, and within ten years they progress to end-stage renal disease. The present study was undertaken to identify the mutations of Wilms' tumour 1 (WT1) gene in steroid-resistant NS (SRNS) children. METHODS: A total of 173 children with SRNS and 100 children in the control group were enrolled in the study. DNA extraction was done, screened for WT1 (exons 8 and 9) gene amplified by polymerase chain reaction and direct sequencing. Karyotype analyses were done for WT1 mutation cases. RESULTS: WT1 mutations were found in three of 173 SRNS cases (2 girls, 1 boy). All of them had intron 9 (IVS 9 + 4 C>T, 2; IVS + 5 G>A, 1) mutation. Of these three cases, one had familial and another two had sporadic history. Renal histology analysis showed two cases with focal segmental glomerulosclerosis (FSGS) and they had external female genitalia but 46,XY karyotype. Both of them had streak gonads. Of the three cases, one expired. INTERPRETATION & CONCLUSIONS: The findings of the present study indicate that all females with SRNS-FSGS should be screened for WT1 gene mutation to diagnose whether they have FS for possible gonadectomy.

Laparoscopic Removal of Streak Gonads in Turner Syndrome.

STUDY OBJECTIVE: To demonstrate the skills necessary for complete resection of bilateral streak gonads in Turner syndrome. DESIGN: Video case presentation with narration highlighting the key techniques used. The video was deemed exempt from formal review by our institutional review board. SETTING: Turner syndrome is a form of gonadal dysgenesis that affects 1 in 2500 live births. Patients often have streak gonads and may present with primary amenorrhea or premature ovarian failure. Patients with a mosaic karyotype that includes a Y chromosome are at increased risk for gonadoblastoma and subsequent transformation into malignancy. Gonadectomy is recommended for these patients, typically at adolescence. Streak gonads can be difficult to identify, and tissue margins are often in close proximity to critical retroperitoneal structures. Resection can be technically challenging and requires a thorough understanding of retroperitoneal anatomy and precise dissection techniques to ensure complete removal. INTERVENTIONS: Laparoscopic approach to bilateral salpingo-oophorectomy of streak gonads. Retroperitoneal dissection and ureterolysis are performed, with the aid of the Ethicon Harmonic Ace, to ensure complete gonadectomy. CONCLUSION: Careful and complete resection of gonadal tissue in the hands of a skilled laparoscopic surgeon is key for effective cancer risk reduction surgery in Turner syndrome mosaics.

What do we do about women athletes with testes?

Elite sport and the measures imposed to prevent 'men' from 'cheating' by posing as women in women's events cast interesting light on notions of sex and gender. Some women have testes, organs that produce testosterone, because they are trans women or they have an intersex state. Testosterone is recognised as a performance-enhancing substance in at least some circumstances, and therefore, women with testes may possess an advantage when competing in some sport against women without testes, though this has never been subjected to rigorous scientific testing. The International Olympic Committee and the International Association of Athletics Federation have decreed that such individuals can compete only if they undergo medical and surgical treatment, which is likely to mean gonadectomy. This might be considered to impose an unethical demand on the individual concerned and constitute an infringement of bodily autonomy for that individual. It also suggests a binary view of sex/gender that is simplistic and not scientifically accurate. I discuss this approach and consider alternative methods of approaching the problem of women with testes in athletics.