Surgery in disorders of sex development (DSD) with a gender issue: If (why), when, and how?

Ten years after the consensus meeting on disorders of sex development (DSD), genital surgery continues to raise questions and criticisms concerning its indications, its technical aspects, timing and evaluation. This standpoint details each distinct situation and its possible management in 5 main groups of DSD patients with atypical genitalia: the 46,XX DSD group (congenital adrenal hyperplasia); the heterogeneous 46,XY DSD group (gonadal dysgenesis, disorders of steroidogenesis, target tissues impairments …); gonosomic mosaicisms (45,X/46,XY patients); ovo-testicular DSD; and "non-hormonal/non chromosomal" DSD. Questions are summarized for each DSD group with the support of literature and the feed-back of several world experts. Given the complexity and heterogeneity of presentation there is no consensus regarding the indications, the timing, the procedure nor the evaluation of outcome of DSD surgery. There are, however, some issues on which most experts would agree: 1) The need for identifying centres of expertise with a multidisciplinary approach; 2) A conservative management of the gonads in complete androgen insensitivity syndrome at least until puberty although some studies expressed concerns about the heightened tumour risk in this group; 3) To avoid vaginal dilatation in children after surgical reconstruction; 4) To keep asymptomatic mullerian remnants during childhood; 5) To remove confirmed streak gonads when Y material is present; 6) It is likely that 46,XY cloacal exstrophy, aphallia and severe micropenis would do best raised as male although this is based on limited outcome data. There is general acknowledgement among experts that timing, the choice of the individual and irreversibility of surgical procedures are sources of concerns. There is, however, little evidence provided regarding the impact of non-treated DSD during childhood for the individual development, the parents, society and the risk of stigmatization. The low level of evidence should lead to design collaborative prospective studies involving all parties and using consensual protocols of evaluation.

Enterocystoplasty: The long-term effects on bone mineral density.

BACKGROUND: Studies show that enterocystoplasty has a negative effect on bone mineral density (BMD). The aim of this study was to investigate the long-term impact of enterocystoplasty on BMD. We used dual energy x-ray absorptiometry (DEXA) scans to determine BMD and identify patients with osteopenia and osteoporosis who are at potential long-term risk for fracture. MATERIALS AND METHODS: We reviewed our database of >200 individuals, who had undergone enterocystoplasty or continent diversion for both neurogenic and non-neurogenic reasons during childhood. We chose to study the non-neurogenic group first for a number of technical reasons, and identified 24 individuals who had undergone the procedure for non-neurogenic reasons, and had more than 15 years of follow-up. In addition we had a control group of 10 individuals born with bladder exstrophy, who had undergone primary closure before the year 2000, without enterocystoplasty. We used DEXA scan T- and Z-scores to identify patients with osteopenia and osteoporosis. RESULTS: Eleven of 24 patients had normal DEXA scans with normal T- and Z-scores; seven had identifiable osteopenia and increased long-term risk for fracture. Six had osteoporosis; three of whom had reduced glomerular filtration rate (GFR). Eight of the 10 individuals in the control group had a normal DEXA scan. CONCLUSIONS: Enterocystoplasty during childhood can lead to loss of BMD. This does not seem to be related to the enterocystoplasty alone. It is more pronounced in individuals who have other risk factors, such as reduced GFR. The identification of BMD loss makes it possible to intervene before osteoporosis occurs and leads to pathologic fracture.

Metabolic bone loss after urinary diversion in children.

PURPOSE OF REVIEW: It has been widely known for some time that bone loss can be seen in certain subpopulations of children undergoing urinary diversion and/or enterocystoplasty. This review will hopefully look at the recent evidence in the field and help understand the multifactorial cause of bone loss in this group of individuals, as well as look at evidence for this phenomenon in growth retardation in certain groups of these individuals. RECENT FINDINGS: Most of the recent publications indicate that in normal individuals, decreased bone mineralization does not appear to affect final growth or adult height. It would appear that over time, demineralization allows compensation of the acidosis. However, it should be noted that it does lead to an increase in both osteoclastic and osteoblastic activity. SUMMARY: It is very likely that enterocystoplasty in childhood can lead to significant metabolic acidosis and that compensation with bone buffering does take place. It would appear that the bone demineralization secondary to increased osteoblastic and osteoclastic activity is the price paid for metabolic compensation and continued normal and near normal linear growth.

Germ cell tumor in an adolescent with extensive testicular microlithiasis: concerns regarding future management.

We report on a 14-year-old boy with bilateral testicular microlithiasis and a right-sided testicular tumor. Tumor markers alpha-fetoprotein (AFP) and ß-human chorionic gonadrotropin (ß-hCG) levels were elevated and orchiectomy revealed a mixed germ cell tumor consisting of embryonal carcinoma, yolk sac tumor, choriocarcinoma, and mature teratoma. The patient had no evidence of metastatic disease. Although there is a strong association between testicular microlithiasis and testicular tumor, the pediatric literature is varying in the recommended surveillance of these patients. The literature and management of pediatric patients with testicular microlithiasis is herein reviewed.

An unusual presentation of uterine didelphys and obstructed hemivagina.

BACKGROUND: Congenital disorders of the genitourinary system can be unpredictable. There are both medical and surgical interventions that can help manage symptoms. CASE: A 10-year-old girl was evaluated 6 months post-menarche with dysuria and pelvic pain. Her symptoms were not relieved with menstrual suppression. Evaluation revealed a probable ectopic ureter versus ureterocele and uterine didelphys with suspicion for obstructed hemivagina and hematocolpos. Surgical exploration revealed an obstructed hemivagina with a high vaginal septum. When resection failed, she ultimately underwent a robot-assisted hemihysterectomy, with resolution of her symptoms. SUMMARY AND CONCLUSIONS: In this case presentation, a surgical approach was necessary to adequately make a diagnosis. When vaginal septum resection failed, robot-assisted laparoscopic hemi-hysterectomy and resection of a vaginal pouch led to symptom resolution in this pediatric patient with a complex anomaly.

Colovaginoplasty using the Yang-Monti modification.

OBJECTIVE: Bowel vaginoplasty is particularly difficult in patients who are extremely obese or those with an android pelvis. This report evaluates the use of the Yang-Monti principle as a viable alternative in the reconstruction of these patients. METHODS: Upon retrospective chart review of patients who underwent bowel replacement vaginoplasty between 1980 and 2008, 4/60 were identified who underwent the Yang-Monti modification. The neovagina was created with an 8‒10-cm segment of descending colon which was detubularized and then retubularized using the Yang-Monti principle. This was sewn in place in the perineum. Outcome was evaluated by physical examination data and clinical information on postoperative sexual function. RESULTS: Three of the four patients had an XY karyotype and an android pelvis, and of these two were failures of previous ileovaginoplasties and one was a failed colovaginoplasty. The fourth was a case of primary mullerian failure (XX) in a morbidly obese individual. All four were discharged without complication following surgery. With a median follow-up of 6 years (range 4-9), none showed evidence of introital stenosis or required dilation. Two were engaged in vaginal intercourse at last consultation, and they reported vaginal length was adequate. No further procedures were required in any of the patients at the end of the follow-up period. CONCLUSION: The Yang-Monti modification, when used as an adjunct to colovaginoplasty, can be an effective reconstructive technique in this subset of patients. It allows for lengthening of the neovagina, without perpetuating tension on the vascular pedicle.

Adult male health risks associated with congenital abnormalities.

Congenital abnormalities of the genitourinary system have a definable durable impact on the adult lives of those individuals affected, despite prompt and appropriate surgical and medical intervention during infancy and childhood. Three abnormalities are described, including relatively common problems of the newborn male, such as hypospadias and cryptorchidism, as well as a less common issue, posterior urethral valves. An understanding and awareness of the consequences of these 3 congenital abnormalities is paramount for the long-term care of the pediatric patient as he transitions to adolescence and adulthood.

Endoscopic management of vesicoureteral reflux in adult women.

OBJECTIVE: • To describe our endoscopic management of adult women with vesicoureteral reflux (VUR) and associated outcomes. PATIENTS AND METHODS: • We retrospectively identified 19 adult women who presented for the endoscopic treatment of VUR from November 2001 to January 2008. • Each patient was diagnosed with VUR by voiding cystourethrogram or nuclear cystourethrogram after an episode of pyelonephritis or recurrent urinary tract infections with renal scarring on ultrasound. • A dimercaptosuccinic acid renal scan was performed prior to treatment. All patients underwent endoscopic treatment with dextranomer/hyaluronic acid copolymer (Deflux). Patients with bilateral VUR received bilateral injections during the same procedure. • Follow-up imaging was obtained and success was strictly defined as no degree of VUR. Patients with residual VUR received repeat endoscopic treatment. RESULTS: • Nineteen patients with a mean age of 22 years old (range 18-33 years old) underwent endoscopic treatment for VUR. A total of 79% (15/19) had pre-existing risk factors for VUR, including prior open anti-reflux surgery (26%), family history of VUR (26%) and childhood diagnosis of VUR (26%). • Imaging revealed that 47% (9/19) had renal scarring and 26% (5/19) had bilateral VUR. The success rate was 79% (19/24) after one treatment, 92% (22/24) after 5 patients received a second treatment, and 96% (23/24) after 2 patients received a third treatment. There were no perioperative complications. CONCLUSION: • Endoscopic management of VUR is both safe and effective in adult women.

The psychosexual aspects of hypospadias repair: A review.

OBJECTIVE: To review the psychosexual effects on men after hypospadias repair. METHODS: We reviewed all English-language publications in the MEDLINE database from the US National Library of Medicine with the search terms 'hypospadias adult', 'psychosexual hypospadias', 'psychosocial hypospadias', and 'social hypospadias'. Each term returned 1036, 35, 19 and 68 results, respectively, which were reviewed. RESULTS: While improvements in surgical techniques have improved function, the abnormality and repair still causes a disruption in perceived quality of life for many men. After repair, many men suffer from a negative view of their genitals and some degree of sexual inhibition. However, they still maintain a satisfactory sex life. CONCLUSIONS: Psychosexual effects of hypospadias repair they endure in adulthood, although affected men maintain satisfaction with their sexual life.

A Summary of the Endocrine Society Clinical Practice Guidelines on Congenital Adrenal Hyperplasia due to Steroid 21-Hydroxylase Deficiency.

Steroid 21-hydroxylase deficiency accounts for about 95% of cases of congenital adrenal hyperplasia (CAH). Newborns are currently being screened for the classical forms of this disease throughout the United States and in 12 other countries. As such, it seems important to develop the best practice guidelines for treating not only infants and children, but affected adults as well. This report gives a brief overview of the most recent expert opinion and clinical practice guidelines for CAH as formulated by The Endocrine Society Task Force.

Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline.

OBJECTIVE: We developed clinical practice guidelines for congenital adrenal hyperplasia (CAH). PARTICIPANTS: The Task Force included a chair, selected by The Endocrine Society Clinical Guidelines Subcommittee (CGS), ten additional clinicians experienced in treating CAH, a methodologist, and a medical writer. Additional experts were also consulted. The authors received no corporate funding or remuneration. CONSENSUS PROCESS: Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. CONCLUSIONS: We recommend universal newborn screening for severe steroid 21-hydroxylase deficiency followed by confirmatory tests. We recommend that prenatal treatment of CAH continue to be regarded as experimental. The diagnosis rests on clinical and hormonal data; genotyping is reserved for equivocal cases and genetic counseling. Glucocorticoid dosage should be minimized to avoid iatrogenic Cushing's syndrome. Mineralocorticoids and, in infants, supplemental sodium are recommended in classic CAH patients. We recommend against the routine use of experimental therapies to promote growth and delay puberty; we suggest patients avoid adrenalectomy. Surgical guidelines emphasize early single-stage genital repair for severely virilized girls, performed by experienced surgeons. Clinicians should consider patients' quality of life, consulting mental health professionals as appropriate. At the transition to adulthood, we recommend monitoring for potential complications of CAH. Finally, we recommend judicious use of medication during pregnancy and in symptomatic patients with nonclassic CAH.

Overnight urethral stenting after tubularized incised plate urethroplasty for distal hypospadias.

OBJECTIVES: The duration of urethral stenting after tubularized incised plate (TIP) urethroplasty for hypospadias varies among surgeons. Typically the catheter is left for up to 7 days with the goal of minimizing post-operative complications. We describe our experience with overnight stenting for distal TIP hypospadias repair. MATERIALS AND METHODS: A retrospective chart review was performed on patients who underwent TIP hypospadias repair from 2003 to 2008. Patients who had their urethral catheter overnight were included in this analysis. Outcomes analyzed were the rates of: urethrocutaneous fistula, meatal stenosis, urethral stricture and urinary tract infections. RESULTS: A total of 64 patients underwent outpatient TIP hypospadias repair. Forty-nine patients had overnight urethral stenting with at least 12 months follow-up and were included in the analysis. Five of the 49 patients (10.2%) developed urethrocutaneous fistula. Of these five patients, two had undergone re-do hypospadias repair. The fistula rate in primary repairs was 3/45 (6.7%). There were no incidences of meatal stenosis, urinary tract infections or urethral strictures. CONCLUSION: In our experience, overnight urethral stenting for TIP hypospadias repair does not significantly affect the rates of urethrocutaneous fistula, meatal stenosis and urinary tract infections. Patients who have had a primary TIP hypospadias repair may have their urethral catheter removed safely on post-operative day one.

Rising hypospadias rates: disproving a myth.

Hypospadias is one of the most common congenital abnormalities occurring in males. In recent years, the prevalence of hypospadias and whether that prevalence is rising or stable has become part of a larger debate over the potential effects of so-called 'endocrine disruptors', such as phthalates and bisphenol-A, on male reproductive health. This commentary critically examines allegations suggesting a worldwide increase in hypospadias rates. Despite the lack of scientific support for this hypothesis and for related claims that the disorders of male reproductive health are related to endocrine disruptors, these constructs remain firmly entrenched in popular literature, and are being used in part to justify litigation banning suspected endocrine disruptors such as phthalates and bisphenol-A. A review of the epidemiologic data on this issue amassed to date clearly demonstrates that the bulk of evidence refutes claims for an increase in hypospadias rates. This suggests that two of the three components of alleged testicular dysfunction syndrome, i.e. decline in sperm counts and rise in urogenital anomalies, lack clinical support. It further suggests that extrapolations from data derived in laboratory animal studies about alleged occult risks to humans of various candidate compounds are unwarranted at this time.

Hypospadias rates in new york state are not increasing.

PURPOSE: The testicular dysgenesis syndrome describes urogenital abnormalities associated with exposure to environmental endocrine disruptors such as phthalates, specifically decreased semen quality, and increased rates of testis cancer and hypospadias. Recently there has been concern that these abnormalities described in animal studies may also be present in humans. To determine if hypospadias rates are increasing, we retrospectively reviewed the total prevalence of hypospadias in New York State from 1992 to 2005, categorized by maternal age younger than 35 years and 35 years or older. MATERIALS AND METHODS: Hypospadias rates were obtained from the New York State Congenital Malformations Registry from 1992 to 2005. An analysis was also performed on the rates of children with hypospadias who had mothers younger than 35 years and mothers 35 years or older. This investigation was approved by the Columbia University internal review board. RESULTS: There was no statistical change in hypospadias rates in New York State from 1992 to 2005 (r = 0.127, p = 0.6). Overall the mean +/- SE prevalence rate was 34.9 +/- 0.36 per 10,000 live births. However, mean +/- SE hypospadias rates in children of mothers 35 years old or older (38.7 +/- 0.7) were significantly greater than those in children of mothers younger than 35 years (34.1 +/- 0.386, t test p <0.01). CONCLUSIONS: Hypospadias rates have not changed in New York State from 1992 to 2005. Additionally advanced maternal age continues to be a risk factor for hypospadias. Combined with previous studies that demonstrate sperm counts are not declining, these data suggest that the testicular dysgenesis syndrome described in animal models may not be evident in humans.