Gonadal Function in Boys with Bilateral Undescended Testes.

Background: Bilateral undescended testes (BUDT) may be a marker of an underlying condition that affects sex development or maturation. Aims: To describe the extent of gonadal dysfunction in cases of BUDT who had systematic endocrine and genetic evaluation at a single tertiary pediatric center. Methods: A retrospective review was conducted of all boys with BUDT who had endocrine evaluation between 2008 and 2021 at the Royal Hospital for Children, Glasgow (RHCG). Continuous variables were analyzed using Mann-Whitney U and non-continuous variables using Fisher's exact, via Graphpad Prism v 8.0. Multivariable logistic regression was used to identify any associations between groups. A P < .05 was considered statistically significant. Results: A total of 243 bilateral orchidopexies were performed at RHCG between 2008 and 2021. Of these 130 (53%) boys were seen by the endocrine team. The median (range) age at first orchidopexy was 1 year (0.2, 18.0) with 16 (12%) requiring re-do orchidopexy. The median External Masculinization Score of the group was 10 (2, 11) with 33 (25%) having additional genital features. Of the 130 boys, 71 (55%) had extragenital anomalies. Of the 70 who were tested, a genetic abnormality was detected in 38 (54%), most commonly a chromosomal variant in 16 (40%). Of the 100 who were tested, endocrine dysfunction was identified in 38 (38%). Conclusion: Genetic findings and evidence of gonadal dysfunction are common in boys who are investigated secondary to presentation with BUDT. Endocrine and genetic evaluation should be part of routine clinical management of all cases of BUDT.

Effects of Sex Hormones on Vascular Reactivity in Boys With Hypospadias.

BACKGROUND: Arteries from boys with hypospadias demonstrate hypercontractility and impaired vasorelaxation. The role of sex hormones in these responses in unclear. AIMS: We compared effects of sex steroids on vascular reactivity in healthy boys and boys with hypospadias. METHODS: Excess foreskin tissue was obtained from 11 boys undergoing hypospadias repair (cases) and 12 undergoing routine circumcision (controls) (median age [range], 1.5 [1.2-2.7] years) and small resistance arteries were isolated. Vessels were mounted on wire myographs and vascular reactivity was assessed in the absence/presence of 17ß-estradiol, dihydrotestosterone (DHT), and testosterone. RESULTS: In controls, testosterone and 17ß-estradiol increased contraction (percent of maximum contraction [Emax]: 83.74 basal vs 125.4 after testosterone, P < .0002; and 83.74 vs 110.2 after estradiol, P = .02). 17ß-estradiol reduced vasorelaxation in arteries from controls (Emax: 10.6 vs 15.6 to acetylcholine, P < .0001; and Emax: 14.6 vs 20.5 to sodium nitroprusside, P < .0001). In hypospadias, testosterone (Emax: 137.9 vs 107.2, P = .01) and 17ß-estradiol (Emax: 156.9 vs 23.6, P < .0001) reduced contraction. Androgens, but not 17ß-estradiol, increased endothelium-dependent and endothelium-independent vasorelaxation in cases (Emax: 77.3 vs 51.7 with testosterone, P = .02; and vs 48.2 with DHT to acetylcholine, P = .0001; Emax: 43.0 vs 39.5 with testosterone, P = .02; and 39.6 vs 37.5 with DHT to sodium nitroprusside, P = .04). CONCLUSION: In healthy boys, testosterone and 17ß-estradiol promote a vasoconstrictor phenotype, whereas in boys with hypospadias, these sex hormones reduce vasoconstriction, with androgens promoting vasorelaxation. Differences in baseline artery function may therefore be sex hormone-independent and the impact of early-life variations in androgen exposure on vascular function needs further study.

Predictors of surgical complications in boys with hypospadias: data from an internationa registry.

Background: Complications are frequently reported after hypospadias repair and there is a need to understand the factors that influence their occurrence. Methods: Data from boys with hypospadias born between 2000 and 2020 were obtained from the International Disorders of Sex Development (I-DSD) Registry. Logistic regressions, fisher's exact tests and spearman's correlation tests were performed on the data to assess associations between clinical factors and complication rates. Results: Of the 551 eligible boys, data were available on 160 (29%). Within the cohort, the median (range) External Masculinization Score (EMS) was 6 (2, 9). All presented with one or more additional genital malformation and 61 (38%) presented with additional extragenital malformations. Disorders of androgen action, androgen synthesis and gonadal development were diagnosed in 28 (18%), 22 (14%) and 9 (6%) boys, respectively. The remaining 101 (62%) patients were diagnosed as having non-specific 46,XY Disorders of Sex Development. Eighty (50%) boys had evidence of abnormal biochemistry, and gene variants were identified in 42 (26%). Median age at first hypospadias surgery was 2 years (0, 9), and median length of follow-up was 5 years (0, 17). Postsurgical complications were noted in 102 (64%) boys. There were no significant associations with postsurgical complications. Conclusions: Boys with proximal hypospadias in the I-DSD Registry have high rates of additional comorbidities and a high risk of postoperative complications. No clinical factors were significantly associated with complication rates. High complication rates with no observable cause suggest the involvement of other factors which need investigation.

Vascular dysfunction and increased cardiovascular risk in hypospadias.

AIMS: Hypogonadism is associated with cardiovascular disease. However, the cardiovascular impact of hypogonadism during development is unknown. Using hypospadias as a surrogate of hypogonadism, we investigated whether hypospadias is associated with vascular dysfunction and is a risk factor for cardiovascular disease. METHODS AND RESULTS: Our human study spanned molecular mechanistic to epidemiological investigations. Clinical vascular phenotyping was performed in adolescents with hypospadias and controls. Small subcutaneous arteries from penile skin from boys undergoing hypospadias repair and controls were isolated and functional studies were assessed by myography. Vascular smooth muscle cells were used to assess: Rho kinase, reactive oxygen species (ROS), nitric oxide synthase/nitric oxide, and DNA damage. Systemic oxidative stress was assessed in plasma and urine. Hospital episode data compared men with a history of hypospadias vs. controls. In adolescents with hypospadias, systolic blood pressure (P = 0.005), pulse pressure (P = 0.03), and carotid intima-media thickness standard deviation scores (P = 0.01) were increased. Arteries from boys with hypospadias demonstrated increased U46619-induced vasoconstriction (P = 0.009) and reduced acetylcholine-induced endothelium-dependent (P < 0.0001) and sodium nitroprusside-induced endothelium-independent vasorelaxation (P < 0.0001). Men born with hypospadias were at increased risk of arrhythmia [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.4-5.6, P = 0.003]; hypertension (OR 4.2, 95% CI 1.5-11.9, P = 0.04); and heart failure (OR 1.9, 95% CI 1.7-114.3, P = 0.02). CONCLUSION: Hypospadias is associated with vascular dysfunction and predisposes to hypertension and cardiovascular disease in adulthood. Underlying mechanisms involve perturbed Rho kinase- and Nox5/ROS-dependent signalling. Our novel findings delineate molecular mechanisms of vascular injury in hypogonadism, and identify hypospadias as a cardiovascular risk factor in males.

Congenital Micropenis: Etiology And Management.

In the newborn, penile length is determined by a number of androgen dependent and independent factors. The current literature suggests that there are interracial differences in stretched penile length in the newborn and although congenital micropenis should be defined as a stretched penile length of less than 2.5 SDS of the mean for the corresponding population and gestation, a pragmatic approach would be to evaluate all boys with a stretched penile length below 2 cm, as congenital micropenis can be a marker for a wide range of endocrine conditions. However, it remains unclear as to whether the state of micropenis, itself, is associated with any long-term consequences. There is a lack of systematic studies comparing the impact of different therapeutic options on long-term outcomes, in terms of genital appearance, quality of life, and sexual satisfaction. To date, research has been hampered by a small sample size and inclusion of a wide range of heterogeneous diagnoses; for these reasons, condition-specific outcomes have been difficult to compare between studies. Lastly, there is a need for a greater collaborative effort in collecting standardized data so that all real-world or experimental interventions performed at an early age can be studied systematically into adulthood.

Society for Endocrinology UK Guidance on the initial evaluation of a suspected difference or disorder of sex development (Revised 2021).

It is paramount that any child or adolescent with a suspected difference or disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD and is discussed with the regional DSD service. In most cases, the paediatric endocrinologist within this service acts as the first point of contact but involvement of the regional multidisciplinary service will also ensure prompt access to specialist psychology and nursing care. The underlying pathophysiology of DSD and the process of delineating this should be discussed with the parents and affected young person with all diagnostic tests undertaken in a timely fashion. Finally, for rare conditions such as these, it is imperative that clinical experience is shared through national and international clinical and research collaborations.

Why adolescents delay with presentation to hospital with acute testicular pain: A qualitative study.

BACKGROUND/PURPOSE: Adolescents have poor outcomes following testicular torsion directly attributable to delay from onset of symptoms to presentation to hospital. The aim of this study was to investigate the barriers to urgent presentation in young men. METHODS: Semistructured interviews were undertaken with young men (11-19 years), using a topic guide exploring issues surrounding testicular pain and health. Thematic analysis was undertaken using a framework approach. RESULTS: Twenty-seven adolescents were recruited, data saturation was reached at sixteen participants, and median age was 13.5 years (range 11-18). The process by which an adolescent gets to hospital with testicular pain is slow. They must recognize the problem and alert their parents, who then use a 'watch and wait' policy to assess need for medical review, often leaving it 'a day' or overnight. Adolescent males do not engage with healthcare services independently of their parents. Additional factors preventing early presentation include: absence of knowledge about testicular pathology from adolescents and their parents; concern from the young people about raising a false alarm and family concerns about burdening healthcare services. CONCLUSIONS: Recommendations include designing a testicular health education campaign for young men and educating parents regarding the medical conditions where a 'watch and wait' policy may be harmful to their child. LEVEL OF EVIDENCE: VI.

Data and data illustrations supporting the analysis of transcripts from interviews exploring the views and experiences of young men and their parents/guardians regarding testicular health.

Evidence shows young men have poor outcomes from testicular torsion directly attributable to delay in presentation to hospital [1]. Only a third to a half of adolescents present within 6 h with testicular pain, [2,3] There is poor understanding of why adolescents delay in presenting with testicular pain. The authors started without an a-priori hypothesis and designed a thematic qualitative research protocol to explore the phenomena is a naturalistic setting [4,5] . Sixteen young men (11-19 years) and their parents or guardians underwent semi-structured interviews, directed by a topic guide which evolved with subsequent interview findings. Young men were recruited from out of school clubs to minimise the bias associated with schools or hospital recruitment, and were naïve to testicular disease. Verbatim transcriptions were coded, categories and themes formed and final concepts derived utilising a framework methodology. The figure included shows the initial topic guide. The data tables presented show the emergent themes and the final code book. The authors have utilised the analysis to explore the factors impeding young men in presenting early to hospital with testicular pain [6]. The authors feel the data tables and raw data will be of interest to other researchers interested in adolescent health, health access, public health, linguistics and healthcare qualitative methodology.

PUVs are more common in boys with hypospadias.

INTRODUCTION: The association between posterior urethral valves (PUVs) and hypospadias has previously been reported in case reports. After the identification of this twin pathology in a number of patients, a national retrospective review of all patients with this dual diagnosis was performed. PATIENTS AND METHODS: All patients were identified in each centre from surgical databases of prospectively collated information on all surgical procedures. The medical notes were reviewed to ascertain demographics, the type of hypospadias, the mode of presentation of the valves and the outcome. RESULTS: Twenty-eight patients who had the dual diagnosis of hypospadias and PUV between 2002 and 2017 in the four tertiary paediatric centres where specialist paediatric urology is undertaken in our country were identified. Most patients (n = 24) had the valves diagnosed after hypospadias surgery. The median age at the time of hypospadias surgery was 1.4 years (range 1-4 years). There were 12 proximal and 16 mid or distal hypospadias. The commonest presentation was with problems voiding after surgery in 14 cases with a further seven boys who had urinary tract infections. Four patients had a urethro-cutaneous fistula after repair that initiated further assessment. Two boys had distal dehiscence of their repair. There was one boy presented with new onset daytime incontinence. The median time of follow-up after valve incision surgery was 4.9 years (range 0.1-12.3 years). Twenty-two patients (three pre toilet training) had no ongoing urinary symptoms. Twenty-one boys have normal renal function with one patient in stage 3b chronic kidney disease. The incidence of this dual diagnosis in Scotland is estimated at one in 100 cases of hypospadias in the paediatric population. CONCLUSION: The incidence of PUV in boys with hypospadias is estimated at 1% patients.

A Systematic Review of Core Outcomes for Hypospadias Surgery.

Although the outcome of hypospadias surgery requires careful scrutiny, there is little consensus on what clinical outcome parameters should be considered essential as part of routine clinical practice. To understand the extent of variation in reported outcome measures, Pubmed was searched to identify outcomes in boys with hypospadias published in the English language from 2008 to 2017. Eligibility criteria were met in 268 publications. Outcomes were inconsistently reported and only 9 (13%) were reported in more than 25% of papers. Outcome studies describing younger boys were overrepresented. Urethrocutaneous fistula was reported in about 90% of publications that included boys aged <16 years. Among younger boys meatal stenosis, dehiscence, and urethral strictures were next most frequent. In the older age groups, an increasing frequency of cosmesis, meatal shape/location, and genital skin changes was described. Outcomes reflecting sexual health, erection, and relationship status including paternity were reported in those aged >16 years. The current study identifies the range of parameters that are measured to assess outcome after hypospadias surgery. The results can be used to promote the development of an age-specific core outcome set that can be applied as a standardized assessment tool in future routine clinical settings.

Association Between Extra-Genital Congenital Anomalies and Hypospadias Outcome.

Extra-genital congenital anomalies are often present in cases of hypospadias, but it is unclear whether they have an association with the outcome of hypospadias surgery. The aim of this study was to review all hypospadias cases that had surgery between 2009 and 2015 at a single centre and identify clinical determinants of the surgical outcome. An extra-genital congenital anomaly was reported in 139 (22%) boys and 62 (10%) had more than 1 anomaly. Of the 626 boys, 54 (9%), including 44 with proximal hypospadias, had endocrine as well as limited genetic evaluation. Of these, 10 (19%) had a biochemical evidence of hypogonadism and 5 (9%) had a molecular genetic abnormality. At least 1 complication was reported in 167 (27%) patients, with 20% of complications (most frequently fistula) occurring after 2 years of surgery. The severity of hypospadias and the existence of other anomalies were clinical factors that were independently associated with an increased risk of complications (p < 0.001). In conclusion, complications following surgery are more likely in those cases that are proximal or who have additional extra-genital anomalies. To understand the biological basis of these complications, there is a greater need to understand the aetiology of such cases.

Predictors of complications following retroperitoneoscopic total and partial nephrectomy.

INTRODUCTION: Recent reports in the literature suggest an increased risk of complications with retroperitoneal as opposed to transperitoneal approach to partial nephrectomy (PN) and total nephrectomy (TN). We are a large unit performing predominantly retroperitoneoscopic PN and TN. We aim to review our outcomes and perform analysis to elucidate the predictors of complications following the retroperitoneal approach for extirpative kidney surgery. METHODS: We performed a single center retrospective review of children undergoing MIMS TN and PN between 2005 and 2015. Variables were tested for association with outcomes using Chi2 and Spearman's Rho correlation. RESULTS: We performed 173 MIMS nephrectomies, 119 total and 54 partial. Median age and weight were 5 years (6 months to 18 years) and 24.9 kg (7.7 to 85 kg) and operative time 147 min. There were 4 conversions and 17 postoperative complications. 19.6% children required further surgery, including 8 completion stumpectomies. Retroperitoneal approach did not have increased risk compared to transperitoneal for need of further surgery. Partial nephrectomy was not associated with higher rate of intraoperative complication or LOS. Predictors of intraoperative complication were vessel closure technique. Associations with need for further surgery were: ESRF, contralateral disease, bladder dysfunction, presence of PD catheter, and need for concomitant procedure. CONCLUSION: Our conversion rate (1.9%) and need for further surgery (13.1%) following the retroperitoneal approach to the kidney are favorable to the literature. Need for reoperation is often associated with the underlying diagnosis and the natural sequelae of the disease process. LEVEL OF EVIDENCE: IV.

Society for Endocrinology UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development (Revised 2015).

It is paramount that any child or adolescent with a suspected disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD. If there is any doubt, the case should be discussed with the regional DSD team. In most cases, particularly in the case of the newborn, the paediatric endocrinologist within the regional team acts commonly as the first point of contact. This clinician should be part of a multidisciplinary team experienced in management of DSD and should ensure that the affected person and parents have access to specialist psychological support and that their information needs are comprehensively addressed. The underlying pathophysiology of DSD and the strengths and weaknesses of the tests that can be performed should be discussed with the parents and affected young person and tests undertaken in a timely fashion. Finally, in the field of rare conditions, it is imperative that the clinician shares the experience with others through national and international clinical and research collaboration.

The long-term outcome of patients diagnosed with sacrococcygeal teratoma in childhood. A study of a national cohort.

BACKGROUND/PURPOSE: The improved survival of sacrococcygeal teratoma (SCT) has led to increased awareness of its long-term sequelae. Our aim was to assess the long-term outcome of a national cohort using detailed questionnaires. METHODS: The three paediatric surgery centres in Scotland were contacted to identify all SCT patients ≥5 years of age. Case notes were reviewed. Detailed separate questionnaires were used to assess long-term bowel, urinary and obstetric outcomes and were completed during an arranged interview. Groups were statistically compared using Z-tests or Fisher's exact test. RESULTS: Overall, 48 patients were identified but only 31 were available for follow-up. Age ranged from 5-35 years (median 12 years and 8 months). There were 25 (81%) females and 5 (16%) patients had malignant disease. Abnormal bowel function was noted in 42% of patients, with constipation being the commonest complaint (39%) with no obvious predictive features at presentation. Urinary symptoms were reported in 55% of the patients. A total of nine (29%) patients suffered from urgency and/or wetting. Confirmed urinary tract infections (UTIs) were reported by nine patients. Successful pregnancies were reported by two females and neither of their children had SCT. CONCLUSIONS: This is one of the largest national studies assessing the long-term outcome of patients with SCT. It highlights the significant gastrointestinal and urological long-term morbidities of SCT patients, which is useful for counselling families.

Reverse Tissue Expansion in Gastroschisis: What to do if the Defect is too large to close after Silo Removal?

A female baby with an antenatal diagnosis of gastroschisis was transferred to our institution. The defect was large but the bowel was in good condition and a silo was placed. After successful reduction of the bowel the abdominal wall defect was too large to allow fascial or even skin closure. We utilised a Gore-tex patch with two prolene purse string sutures placed concentrically to enable the diameter of the patch to be sequentially reduced. This enabled gradual stretching of the tissues with a progressive reduction in the size of the defect. The patch was removed after 8 days and a delayed fascial closure was achieved.

Increased occurrence of disorders of sex development, prematurity and intrauterine growth restriction in children with proximal hypospadias associated with undescended testes.

PURPOSE: Proximal hypospadias represents 20% of hypospadias cases, which are considered to have a higher incidence of associated urological, nonurological, developmental and sexual development disorders, and chromosomal anomalies. We compared associated anomalies in boys with proximal hypospadias and undescended testis with those in boys with proximal hypospadias and descended testes. MATERIALS AND METHODS: We reviewed the medical records of 69 boys who underwent 2-stage hypospadias repair for proximal hypospadias at a single institution during the 11-year period of 2001 to 2011. Collected data included demographics, birth history, associated urological and extra-urological anomalies, karyotype analysis and gonad palpability. Patients were divided into group 1-those with proximal hypospadias and undescended testis, and group 2-those with proximal hypospadias and descended testes. Statistical analysis was performed using the 2-tailed Fisher exact test. RESULTS: There were 17 patients (25%) in group 1 with a median age of 2.2 years and 52 in group 2 (75%) with a median age of 2 years. Children in group 1 had a higher incidence of XY nondysgenetic testicular sexual development disorder (8 vs 11, p = 0.06), premature birth (9 vs 10, p = 0.01) and intrauterine growth restriction (8 each) than children in group 2 (p = 0.01). CONCLUSIONS: Prematurity and intrauterine growth restriction are significantly associated with proximal hypospadias and undescended testis. Also, due to the 28% incidence of an underlying sexual development disorder, male infants with proximal hypospadias should undergo multidisciplinary evaluation.