Androgen receptors in boys with isolated bilateral cryptorchidism

A study was conducted in boys with bilateral cryptorchidism, who were to undergo surgical orchiopexy, to determine if target-organ androgen insensitivity might play a role in the failure of the testes to descend into the scrotum. Nine boys older than 1 year in whom bilateral undescended testes was the only genitourinary abnormality were evaluated. Each subject was administered a six-week course of human chorionic gonadotropin (hCG), 3000 U/m2 of body surface area, intramuscularly injected daily for five days and then twice per week. Basal and hCG-stimulated levels of testosterone were normal. However, hCG administration failed to induce testicular descent in all cases. At the time of surgery, scrotal skin and testicular biopsy specimens were obtained for propagation of cells in tissue culture. Androgen receptor levels and binding affinity were normal for the androgen-specific ligands dihydrotestosterone and metribolone in both skin fibroblasts and testicular cells. In addition, 5 alpha-reductase activity was normal in scrotal skin fibroblasts. Nine boys with bilateral cryptorchidism and normal testicular androgen biosynthesis had normal androgen receptor-binding activity and 5 alpha-reductase activity in cultured scrotal skin fibroblasts and testicular cells. Therefore, bilateral maldescent of the testes in these boys with cryptorchidism was not due to androgen insensitivity.     

Semen quality and gonadotropin levels in patients operated upon for cryptorchidism

In a long-term follow-up study we compared preoperative testicular position, age at orchiopexy, and morphology of testicular biopsies investigated at orchiopexy to sperm analysis results, testicular volume, and serum follicle-stimulating hormone and luteinizing hormone levels at follow-up in 46 men with a history of surgical correction of cryptorchidism in childhood. They had undergone orchiopexy at age 1.5–12.0 years, 24 for unilateral and 22 for bilateral cryptorchidism. Eleven (46%) of the 24 patients with unilateral and 7 (32%) of the 22 with bilateral undescended testes had a normal sperm analysis, whereas in men with impaired spermiogenesis oligo-asthenozoospermia was the predominant feature. Three (13.6%) patients with bilateral cryptorchidism showed azoospermia, but none of the patients with unilateral cryptorchidism did. Neither the age at orchiopexy nor the average germ-cell count per cross-sectioned seminiferous tubule of testicular biopsies examined at orchiopexy correlated significantly with subsequent sperm analysis results or gonadotropin levels at follow-up. The pretreatment testicular position (testicular position value) has a high prognostic value for prediction of subsequent sperm analysis results and serum gonadotropin levels.     

Management of undescended testis

The term cryptorchidism indicates a testis, which has failed to descend to the scrotum and is located at any point along the normal path of descent or at an ectopic site. Hormones play a pivotal role in testicular descent except during the migration to the level of internal inguinal ring. Cryptorchidism is present in about 4.5% of newborns with a higher incidence in preterms. The incidence decreases to 1.2% by the first year. It is classified as palpable and impalpable. The most common site of an ectopic testis is superficial inguinal pouch. Retractile testis is often bilateral and most common in boys between 5 and 6 years of age. Hypospadias and inguinal hernias are the most common associated anomalies seen with undescended testis. A thorough clinical examination helps in arriving at the etiology. A short hCG stimulation test helps to exclude anorchia. Different imaging techniques are of little help in diagnosis and require the help of an experienced radiologist. Laparoscopy has an important role in the diagnosis and management of undescended testis. The common complications include torsion and atrophy of testis. Infertility is seen in about 40% of unilateral and 70% of bilateral cryptorchidism. Undescended testis is 20 to 40 times more likely to undergo malignant transformation than normal testis. Both hCG and GnRH have been used with limited success in these children. All boys with cryptorchidism should be referred to a pediatric surgeon before 2 years of age. These children should be followed up every year after surgery to identify testicular tumors.     

青春期前隐睾患儿手术前后抗精子抗体检测的意义

目的检测青春期前隐睾患儿手术前后血清抗精子抗体（AsAb），探讨AsAb与睾丸位置、手术、单／双侧和伴输精管／附睾畸形等因素的关系。方法收集隐睾患儿,50例，取腹股沟斜疝患儿和腹股沟区正常儿童各50例作为对照组。分别抽取患儿术前及术后6个月血清，采用AsAb金标免疫斑点法检测其血清AsAb IgG、IgM水平。结果隐睾组术前及行睾丸下降固定术后AsAb的阳性率分别明显高于腹股沟斜疝组术前及术后和健康对照组（Pa〈0．01）。睾丸下降固定术、单／双侧隐睾、术前睾丸位置及伴输精管和（或）附睾畸形均与AsAb无显著相关（Pa〉0．05）。结论青春期前隐睾患儿血清AsAb阳性率显著升高，与手术、术前睾丸位置、单／双侧隐睾及是否伴输精管／附睾畸形无显著关系。     

Unsuspected urological anomalies in asymptomatic cryptorchild boys

In a period of 6 years 144 asymptomatic boys with cryptorchidism, of mean age 7±SD 3.5 years, underwent orchiopexy. None of these boys referred to a history of a known urological anomaly, urinary tract infection, haematuria, palpable mass in the renal region, bladder extrophy, epispadias, hypospadias or anorectal malformation. On the third day after orchiopexy an intravenous pyelography was done in every boy following testicular protection against irradiation. Ultrasonic investigation was not available at that time. There were minor urological abnormalities in 36 (25%) boys and major ones in 8 (5.5%) boys. A major anomaly is defined as one resulting in significant loss of renal substance (one case of single kidney and three cases of unilateral renal hypoplasia), or requiring surgical correction for conservation of the renal substance (one case of ureterocele, two cases of pelviureteric stenosis and one case of vesicoureteric stenosis with ipsilateral hydronephrosis). The unsuspected major urological abnormalities are usually ipsilateral to the more undescended testis. They may be associated with a hernia and are more frequent in bilateral cryptorchidism. In conclusion we encourage the routine use of IVP, or ultrasonic investigation or dynamic renal scanning (99^mTc-DTPA), if it is possible, in all patients undergoing orchiopexy for the detection of an unsuspected major renal anomaly. Presented at the VIIIth Meeting of the Hungarian Association of Paediatric Surgeons, Miskolc, 22–24 July 1985     

Hormonal treatment of cryptorchidism—hCG or GnRH—a multicentre study

In a modified, double-blind controlled study, 163 prepubertal boys (aged 1.8-13.0 years) with bilateral and 94 (aged 1.5-13.1 years) with unilateral cryptorchidism were allocated to treatment with either human chorionic gonadotrophin (im), gonadotrophin releasing hormone (intranasally) or placebo (intranasally). In individuals with the bilateral condition treatment with human chorionic gonadotrophin resulted in complete descent of both testes in 23% of patients. Treatment with human chorionic gonadotrophin in unilateral cryptorchidism resulted in complete descent in 19% of patients; all results were significantly better than those obtained with gonadotrophin releasing hormone or placebo. Linear and logistic regression analysis of the results obtained by treatment of bilateral disease showed that all treatments were more successful the younger the age of the boys. The data indicated that bilateral and unilateral cryptorchidism respond differently to hormonal treatment. We suggest that human chorionic gonadotrophin should be the first choice of treatment for prepubertal boys older than one year.     

The relation of germ cells per tubule in testes,serum inhibin B and FSH in cryptorchid boys

At bilateral orchiopexy bilateral biopsies may be indicated to determine fertility potential. It is currently unknown if the serum inhibin B levels at time of orchiopexy reflect the testicular status of the bilaterally cryptorchid child. The aim of this study was to relate the results of inhibin B and FSH measurements with testicular biopsy parameters in bilateral cryptorchid boys. Included were 25 boys with bilateral cryptorchidism, median 2.5 years (9 months to 5.5 years) at surgery for bilateral cryptorchidism with simultaneous testicular biopsies, and blood sample for inhibin B and FSH. The number of spermatogonia and gonocytes was measured in 100 tubular transverse sections, the S/T and the mean-S/T of the patient was found, and expressed as percent of lowest normal value. Inhibin B and FSH were measured and related to age-specific values. Forty percent (10/25) of the patients had very low mean-S/T (mean-S/T < 10% of lowest normal-value). Inhibin B was decreased in 24% (6/25) of the patients, all with decreased mean-S/T, predominantly with a mean-S/T < 10% of lowest normal-value (p < 0.05). There was a negative correlation between inhibin B and FSH (p < 0.05). In cases of mean-S/T<10% of lowest normal-value and decreased inhibin B, we found increased FSH in 9% (2/22) of the patients and hypergonadotropic hypogonadism was suspected. Low FSH was found in 5% (1/22) of the patients and hypogonadotropic hypogonadism was suspected. Low inhibin B predicts a serious condition in respect of infertility. Low FSH and inhibin B indicates examination for hypogonadotropic hypogonadism. In bilateral cryptorchid boys inhibin B levels correlated negatively to FSH.     

不同日龄隐睾复位大鼠睾丸组织结构观察

目的 观察不同13龄隐睾复位大鼠睾丸组织结构的变化.方法 72只21 d雄性SD大鼠随机分为单侧隐睾组、双侧隐睾组、假手术对照组各24只.建立单、双侧隐睾动物模型.2周后行隐睾大鼠睾丸下降固定术,于日龄40、60 d处死取睾丸,采用苏木素.伊红染色光镜下观察各组大鼠精曲小管生育力指数(TFI)和平均精曲小管直径(MTD);生物素-dUTP/酶标亲和素法(TUNEL法)检测睾丸生殖细胞凋亡情况.结果 隐睾侧睾丸MTD、TFI显著低于阴囊内睾丸,而隐睾生殖细胞凋亡指数(AI)明显增高于阴囊内睾丸(P＜0.05);单侧隐睾组阴囊内睾丸TFI低于相应日龄的假手术对照组,但无统计学意义(P＞0.05).40 d时单侧隐睾组隐睾侧睾丸生殖细胞AI较双侧隐睾组低(P＜0.05),日龄60 d,各组隐睾侧睾丸AI较40 d时明显降低(P＜0.05),但单侧隐睾和双侧隐睾AI比较无统计学差异(P＞0.05).结论 实验隐睾复位大鼠睾丸AI升高,同时单侧隐睾鼠对侧睾丸组织存在不同程度的损害.随着复位时间的延长,隐睾组织的病理损害有恢复的趋势.     

Practice variation and clinical confusion regarding undescended testes and retractile testes among primary care respondents: a multi-regional survey study in the United States

Purpose

Although previous studies have looked at referral patterns and indications for orchiopexy, this is the first attempt at quantifying the primary care provider knowledge base of cryptorchidism and its implications in a large multi-state setting in the United States.

Methods

Primary care providers (PCPs) (n?=?3,000) were invited to complete a web-based survey regarding cryptorchidism. We evaluated: practice setting; training; knowledge of cryptorchidism; relationship to pediatric urologists and surgeons; understanding of the relationship between cryptorchidism, infertility and testis cancer.

Results

Seventeen percent (n?=?453) of PCPs responded to the survey. Fifty-three percent indicated that they had minimal to no exposure to pediatric urology during training. Two-thirds refer patients with retractile testes to surgical specialists. Practice setting was associated with the type of information families received about the impact of UDT on fertility and malignancy with rural practices being more likely to counsel that unilateral UDT imparted a high risk of malignancy (RR 1.5; 95?% CI 1.2, 1.9) and bilateral UDT resulted in likely infertility (RR 2.1; 95?% CI 1.5, 2.8).

Conclusions

This study underscores the need for increased evidence-based recommendations, as well as improved training and education of PCPs in the US who deal with disorders of testicular descent.     

Evaluation of low-dose hCG treatment for cryptorchidism

The aim of this study was to evaluate the efficiency of low-dose hCG (human chorionic gonadotropin) (500 IU/week for 3 weeks) in the treatment of cryptorchidism and in the assessment of Leydig cell functions. We include 35 male patients who had been diagnosed with cryptorchidism by the pediatric endocrinology specialist in the study. Twenty-one cases (Group I) received 500 IU/week of hCG while 14 patients (Group II) received 1500 IU/m2 three times a week, both for three weeks. The percentage of testis descent was calculated for both groups for the right and left testes. Leydig cell functions were evaluated by the pre- and post-treatment measurement of plasma testosterone level in all cases. A delta testosterone greater than 100 was considered to be a sufficient response. Among our patients, 77% had unilateral and 23% bilateral cryptorchidism. Unilateral cryptorchidism was detected in 80.9% of Group I patients and 71.4% of Group II patients. The pre-treatment percentages for Group I of right- and left-sided cryptorchidism were 81% and 38.1%, respectively, which decreased to 23.8% and 9.5% after treatment. The pre-treatment percentages for Group II of right- and left-sided cryptorchidism were 57.1% and 71.4%, respectively, which decreased to 14.3% and 35.7% after treatment. The success rate of hCG treatment, as defined by the testis descending into the scrotum, was 66.7% for Group I and 57.1% for Group II (p > 0.05). There was no significant difference between the two groups when Leydig cell functions were assessed. In conclusion, it is possible to use low-dose hCG for the treatment of cryptorchidism and the assessment of Leydig cell functions.     

Cryptorchidism: isolated and associated with other genitourinary defects

Cryptorchidism is the most common disorder of sexual differentiation in male children, with an incidence of 3.4 per cent in the term newborn, decreasing to 0.8 per cent at 1 year of age. The mechanisms of normal testicular descent are multifactorial and include an intact hypothalamic-pituitary-testicular axis, as well as a normal gubernaculum and epididymis. In boys with cryptorchidism, the testes demonstrate degenerative changes histologically as early as 1 to 2 years of age. Both testes may be affected, even with a unilateral undescended testis. The most important long-term complications of cryptorchidism include infertility and testicular cancer. The risk of malignancy is approximately 40 times higher in male subjects with cryptorchidism than in normal men, and is highest in male subjects who have had an intra-abdominal testis and in certain intersex conditions. Orchiopexy does not appear to lessen this risk. Hormonal therapy with HCG or LH-RH has remained unproven in clinical trials in the United States; therefore, orchiopexy remains standard treatment. HCG is recommended if the clinician suspects that a testis is retractile, however. Orchiopexy should be performed between 12 and 18 months of age to prevent the degenerative changes that are demonstrable by 2 years.     

Cryptorchidism: a prospective study of 7500 consecutive male births, 1984-8. John Radcliffe Hospital Cryptorchidism Study Group.

A total of 7441 boys were examined for cryptorchidism at birth and, if present, again at 3 months of age. After excluding boys with severe congenital malformations noted at birth, the cryptorchidism rates at 3 months in babies weighing less than 2000 g, 2000-2499 g, and greater than or equal to 2500 g were 7.7%, 2.5%, and 1.41% respectively. The overall rate was 1.55%. The cryptorchidism rate at birth had increased by 35.1% and at 3 months by 92.7%, over Scorer''s rates in the 1950s. Part of these increases may be attributable to differences in neonatal mortality, but the increases in babies weighing 2500 g or more of 50.2% at birth and 77.4% at 3 months are unlikely to be overestimates. At birth 1.92% of boys had bilateral cryptorchidism and 3.0% unilateral cryptorchidism. Boys with cryptorchidism at 3 months were more likely to have hypospadias, a small scrotum, and poor scrotal rugation compared with boys having normally descended testes at birth. Factors predicting descent by 3 months in babies cryptorchid at birth are birth weight, laterality and scrotal size, babies with low birth weight, bilateral cryptorchidism, and normal scrotal size being more likely to have normally descended testes by 3 months. Descent by 3 months was more likely the lower the testis along the normal pathway of descent. The orchidopexy rate at an average age of 3 years was 1.24%. This is substantially lower than in other series and lower than our estimated rate of 2.9% using Hospital In-Patient Enquiry data for England and Wales.     

Efficacy and safety of hormonal treatment of cryptorchidism: current state of the art

Meta-analyses of randomised trials using hCG or GnRH for treatment on testicular descent show in most studies overall efficacy of about 20%, less if retractile testes were excluded. In recent years a number of potentially serious side effects have been reported. Conclusion: Considering the efficacy and the possible side effects of the hormonal treatment, the general use of hCG and GnRH in the treatment of cryptorchidism cannot be further recommended.     

Undescended testes: Treatment with gonadotropin

The therapeutic success of treatment of testicular maldescent must be judged according to 2 parameters,-I. occurrence of descent, II. fertility. Ad I. Indication for hCG-treatment is always given unless an unequivocal indication for operation exists, i.e. ectopias, accompanying hernias, retention after herniotomy and advanced puberty. The optimal time for treatment is the second year of life. The large European statistics which include the prescrotal but not the retractile testes, unanimously show success rates of 50–55%. In the largest American series which does not include prescrotal testicles, descent was observed in 40% of the bilateral and in 30% of the unilateral cases. Analyzing those cases which did not respond to hormones but had to be operated, in the majority of cases ectopic, not dystopic gonads were found. Ad II. Infertility in testicular maldescent can have two reasons, 1. congenital anomalies of the primordium, 2. acquired damages due to the malposition. The few large prospective studies at hand show fertility in the majority of cases with descent after hCG, but in the minority of those coming down only after additional operation. Obviously the latter group represents a negative selection. Unilateral cases had a higher fertility rate than bilateral ones.     

微型腹腔镜下睾丸下降固定术40例

目的 探讨微型腹腔镜下睾丸下降固定术在儿童隐睾中的应用.方法 2010年6月至2011年6月,我们对40例隐睾患儿施行微型腹腔镜睾丸下降固定术.术中行单侧睾丸下降固定术33例,双侧5例,一期Fowler-Stephens手术4例.术中见睾丸萎缩2例,除2例睾丸萎缩病例外,其余病例均行患侧疝囊高位结扎术,对侧疝囊高位结扎术7例.结果 40例患儿均顺利完成手术,无中转开放手术.单侧手术时间30~45 min,平均38 min,双侧手术时间54~78 min,平均64 min.随访12～24个月,平均18个月,无睾丸回缩、睾丸萎缩、腹股沟疝等并发症.结论 微型腹腔镜下睾丸下降固定术治疗儿童隐睾创伤小,睾丸下降完全,安全有效,并发症少,可作临床推广应用.     

Clinical spectrum of steroid sulfatase deficiency: X-linked recessive ichthyosis,birth complications and cryptorchidism

When boys affected with steroid sulfatase deficiency are delivered, the lack of the enzyme in the placenta may cause birth complications. In postnatal life this gene defect gives rise to X-linked recessive ichthyosis. In a series of 25 patients birth complications were reported in 9 cases. Of these boys, 4 displayed bilateral inguinal cryptorchidism and one was affected unilaterally. In a further boy we observed unilateral inguinal cryptorchidism without a history of birth complications. In one patient who had been delivered by forceps, abdominal bilateral cryptorchidism resulted in severe hypogenitalism. A review of the literature revealed 30 cases with X-linked recessive ichthyosis displaying hypogenitalism or cryptorchidism or both. In conclusion, cryptorchidism should be considered as a further clinical manifestation of steroid sulfatase deficiency.     

Evaluation of orchiopexy practice patterns in patients with cryptorchidism: A single-centre study

ObjectiveA retrospective study was conducted to determine the age at which orchiopexy was performed, and the laterality and anatomic location of undescended testes (UDTs) or non-palpable testes (NPTs). All documented orchiopexies performed in a large referral centre of Qom province, Qom, Iran during a 5 year period were evaluated.Materials and methodsA total of 324 patients admitted for surgical correction of cryptorchidism from 2005 to 2009 were eligible for inclusion in our study. The patients were divided into two groups: group A paediatric orchiopexy, and group B adult orchiopexy.ResultsThere were 252 paediatric patients (78%), with a mean age of 4.44 years, and 72 adult patients (22%). Forty-three patients (17%) were under 2 years of age and 59 patients (23.5%) were between 2 and 3 years. Right-side involvement was seen in 126 patients (50%), left-side in 91 patients (36%), and bilateral involvement in 35 patients (14%). Unilateral cryptorchidism was seen in 217 patients (85%). Regarding the anatomical location of the testes in unilateral cryptorchidism, superficial inguinal testis was seen in 117 patients (54%).ConclusionThe higher age of orchiopexies determined from this study compared with the recommended age for surgery, indicates that active interventions are necessary with public health education programs for patients, parents, midwives and general practitioners.     

激素治疗小儿隐睾的系统评价

目的评价激素治疗隐睾的效果,为进一步的临床研究与实践提供参考。方法制定原始文献的纳入标准、排除标准及检索策略,在美国医学索引MEDLINE(1966~2004)、荷兰医学文摘EMBASE(1974~2004)、Cochrane图书馆的图书馆临床对照试验资料库(2004年第4期)、中国生物医学文献光盘数据库CBMdisc(1978~2004)、中国期刊全文数据库(1994~2004)和万方数据库(1980~2004)内检索、收集激素治疗隐睾的相关随机对照试验(RCT),并手检相关参考文献,进行质量评价和资料提取。应用Rev Man 4.2版软件进行数据的Meta分析处理;本系统评价疗效资料均为分类变量,故以比数比或相对危险度(Peto OR或RR)及其95%可信区间(95%CI)表示效应量。结果共检索到相关文献500篇,其中RCT 29篇,排除18篇,符合纳入标准11篇进入Meta分析。结果2个研究组设立人绒毛膜促性腺激素(HCG)治疗组和对照组,其睾丸完全下降率分别为25.2%与5.48%,PetoOR值及其95%CI分别为4.67[2.94,7.43];10个随机化组比较促性腺激素释放激素(GnRH)治疗组和对照组的效果,其睾丸完全下降率分别是17.2%与3.04%,Peto OR值及其95%CI分别为4.73[3.34,6.68];3个组比较HCG治疗组和GnRH治疗组,其睾丸完全下降率分别为24.0%与13.1%,Peto OR值及其95%CI分别为2.11[1.38,3.21];两组比较HCG或GnRH治疗单侧隐睾和双侧隐睾的效果,其睾丸完全下降率分别为25.0%与20.9%,其RR值及其95%CI分别为1.16[0.69,1.95]。结论按照目前已有资料分析,HCG较GnRH治疗隐睾有效,GnRH较安慰剂有效;激素治疗双侧隐睾效果较单侧隐睾好。但由于这些试验RCT数量较少,且可能存在一定程度的偏倚,因此其结果只能供临床参考。     

The effects of orchiopexy on serum anti-Müllerian hormone levels in unilateral cryptorchid infants

Background/Purpose: In males, serum anti-Müllerian hormone (AMH) reflects Sertoli cell function and provides an estimate of seminiferous tubular integrity. It has been suggested that comparison of AMH levels before and after surgery could be useful to determine effectiveness of the treatment. In this study, we determined the serum AMH levels in infants with unilateral cryptorchidism before and after orchiopexy procedure and compared these data with the AMH values in age-matched controls. Methods: The study population was 20 cryptorchid children with unilateral palpable testes who underwent orchiopexy as a cryptorchid group, and 20 healthy children who underwent circumcision as a control group. All children are 12 months of age. Serum AMH levels were measured at just before surgery (at 12 month old) and 6 months after surgery (at 18 month old). Results and Conclusions: All undescended testes were found to be normal in size and in the superficial inguinal pouch or subcutaneous region of the groin at surgery. With regard to the preoperative serum AMH levels, there was a significant difference between the cryptorchid and the control groups (40.04±4.97 ng/ml versus 53.46±7.51 ng/ml) (P<0.05). Similarly, the postoperative serum AMH levels were lower in cryptorchid children than in controls (39.27±4.58 ng/ml versus 52.79±6.27 ng/ml) (P<0.05). In cryptorchid children, serum AMH levels measured at 6 months after orchiopexy were similar with preoperative basal levels (40.04±4.97 ng/ml versus 39.27±4.58 ng/ml) (P>0.05). AMH levels in children with unilateral palpable undescended testes remain unchanged 6 months after orchiopexy performed at 1 year of age. This is the first report in literature regarding the effect of orchiopexy on the serum AMH levels.     

Testicular undescent and torsion

The higher the testis resides above the scrotum, the more dysgenetic the morphology is likely to be. High testes are rarely responsive to HCG and should be treated by orchiopexy by the age of 2 to 3 years. The undescended testis does not mature normally after the age of 2 years and may produce adverse effects on the contralateral descended testis, possibly by an autoimmune mechanism. A course of HCG for boys with low-lying undescended testes, both unilateral and bilateral, may produce descent in as many as 15 per cent of patients and may make the technical aspects of orchiopexy easier in those who do not respond. Unilateral cryptorchid testes that are dysplastic or located high should generally be removed before adolescence.