Pseudohermaphroditism Research Articles

Summary of surgical experience of 14 cases hermaphroditism

Objective To evaluate the surgical therapy for hermaphrodites.Methods Retrospective analysis the clinical data of 14 cases of different types of hermaphrodites treated in our hospital from Jan.1995 to Dec.2012,including 4 cases of female pseudohermaphrodite,2 cases of male sex reversal syndrome,3 cases of male pseudohermaphrodite and 5 cases of true hermaphrodites.The gender selection and the following surgical treatment were provided according to patients' protopathy,age,social gender,their desires and their parents' wishes.Results Out of 14 cases,10 cases were operated to women (4 cases of female pseudohermaphrodite,1 case of male pseudohermaphrodite,5 cases of true hermaphrodites),4 patients were operated to men (2 cases of male sex reversal syndrome,2 cases of male pseudohermaphrodite).The operation is relatively easy for the patients who are operated to female,and they all have well developed secondary sexual characteristics and satisfied sexual function after 3 to l0 years of follow-up.For the 4 patients who were operated to male,their penis and testicles are well developed,and 1 case had already entered adolescent period,whose morning erection can be seen normally but no spermatorrhea detected.Further observation is necessary to decide whether he has reproductive function.Conclusions The diagnosis and treatment for children external genitalia malformations should be taken as early as possible.A reasonable choice of gender,the appropriate surgical correction,and hormone replacement therapy in some cases,are feasible treatment with satisfactory effect. Key words: Hermaphroditism; Surgical procedures, elective

PSEUDOHERMAFRODITISMO CANINO: DESCRIPCIÓN DE UN CASO

The case of an 8 month-old crossbred dog with evidences of impaired sexual differentiation is described. There was an incomplete foreskin development, micropenis without urethral opening, bifid scrotum, and pseudovagina with urethral opening. The findings are discussed and a possible testicular feminization syndrome is assumed that resulted in a male pseudohermaphroditism.

Hermaphroditism in two dogs - pathological and cytogenetic studies: a case report

A Pit-bull and a Beagle, both one-year-old, with complaints of an enlarged clitoris were clinically suspected for hermaphroditism. The enlarged clitoris, the uteri and the gonads were removed surgically from each animal and submitted to our department for histopathological evaluation. Tissue samples were fixed with 10% buffered formalin solution and processed routinely, after which paraffin sections were obtained and stained with H&E. A blood sample was taken from the Beagle dog and a peripheral lymphocyte culture was prepared. While the clitoris and uteri were confirmed histopathologically, the gonads were detected as a testis instead of an ovary for both dogs. Additionally, cytogenetic evaluation revealed a normal female chromosome complement, 78, XX for the Beagle dog. According to the gonadal and phenotypic sexes, both cases were first determined as ‘male pseudohermaphroditism’, a phenotypic sex disorder. However, after karyotyping analysis, we concluded that the 78, XX Beagle dog should be defined as suffering from XX sex reversal syndrome, a gonadal sex disorder.  

Laparoscopic inguinal hernia repair in children using the percutaneous internal ring suturing technique - own experience.

IntroductionPercutaneous internal ring suturing (PIRS) is a method of laparoscopic herniorrhaphy, i.e. percutaneous closure of the internal inguinal ring under the control of a telescope placed in the umbilicus.AimTo evaluate the usefulness of the PIRS technique.Material and methodsFifty-five children (39 girls and 16 boys) underwent surgery using this method in our institution between 2008 and 2010.ResultsIn 10 cases the presence of an open inguinal canal on the opposite side was also noted during surgery, and umbilical hernia was recognized in 2 patients. In 5 cases it was necessary to convert to the open surgery because of the inability to continue the laparoscopic procedure. In 1 case, male pseudohermaphroditism was diagnosed during surgery. Recurrent inguinal hernia required a conventional method of surgery in 1 child. Other children did not exhibit the characteristics of hernia recurrence. The inguinal canals were followed up with postoperative ultrasound examination in 29 children. In 23 children, the ultrasound examination showed no dilatation of the inguinal canal. In the other 6 children dilatation of the inguinal canal or the presence of fluid within the inguinal canal was observed during ultrasound. In 6 children symptoms such as swelling and soreness around the inguinal canal developed within 3 to 6 months after surgery.ConclusionsInguinal hernia surgery using the PIRS procedure is an alternative, effective, minimally invasive method of surgery. Visualization of the peritoneal cavity allows for detection of other abnormalities, as well as for performing other procedures during the same session (such as closing the contralateral inguinal canal or umbilical hernia surgery).

Transverse testicular ectopia with persistent Mullerian duct syndrome: a rare anomaly

Persistent Mullerian duct syndrome is a disorder of male pseudo-hermaphroditism characterized by persistence of uterus, fallopian tubes and upper two third of vagina in otherwise normally virilized phenotypically and genotypically male (46XY). Aim of study was to create an awareness among the surgeons about the pathophysiological, morphological and clinical presentations of this rare entity along with its management. Between 2009 to 2013 we came across 5 boys with Persistent Mullerian Duct Syndrome (PMDS) with varied clinical spectrum in each, viz hernia, hydrocele, right sided Un-Descended Testis (UDT), left sided UDT and bilateral UDT. All were diagnosed intra-operatively and managed accordingly, 4 by Open Orchidopexy (OP) with 1 requiring midline splitting of the uterus and 1 laparoscopic orchidopexy. Awareness of this rare anomaly associated with inguinal hernia or undescended testis and also diagnostic laparoscopy for impalpable testis helps in appropriate management.

English

Testicular feminization syndrome or androgen insensitivity syndrome is a rare inherited form of male pseudohermaphroditism that occurs in phenotypically normal woman with male karyotype (XY), with an incidence of 1:20,000-64,000 male births. The individual with complete form of this syndrome have female external genitalia while those with partial form have variable ambiguity of genitalia. The undescended testis may go into malignant transformation. The androgen insensitivity syndrome with malignant testicular disorder is very rare. A twenty-eight year old female was admitted to the hospital with the complaint of primary amenorrhea. Clinical and laboratory investigation revealed testicular feminization syndrome with seminoma developed from intraabdominal undescended testis. Primary removal of the mass and postoperative chemotherapy was treatment of choice for the patient.

Ancient Healing Arts

In their article “Urethral Stricture: Etiology, Investigation and Treatments”, the authors mention that endourological procedures were undertaken as early as in antiquity. Since no further explanation was offered in the article, some additional details may not be altogether unwelcome. Heliodorus, a surgeon in the 1st/2nd century AD undertook the following procedure to remove proliferation related urethral obstructions—so-called synsarcoses (1): he used a thin, pointed instrument, the “skolops,” which was sharpenedbehind the tip. In order to avoid hemorrhage, the penis was compressed behind the stenosis, stretched, and then the instrument was inserted. As soon as the tip had penetrated past the stenosis, circular movements were used to eliminate the stenosing membranes and, where these did not pass of their own account, they were removed by using a tweezer-like instrument, the “mydion.” Postoperative care consisted mainly of inserting bougies fashioned from papyrus and metal probes, often made from tin or the tube of a bird’s feather. In such cases, a probe was inserted first, so as to avoid snapping. On the one hand, such hollow probes made for uninhibited urination, while the papyrus, tightly wound around the probe and previously soaked in water, absorbed the wound secretions. The historian Diodorus (first century BC) reported another type of endourethral procedure (2). In this case, the glans penis was incised in a male pseudohermaphrodite with atresia of the urethral opening, and a connection to the urethra was created by inserting a silver tube. For the treatment of hypospadias of the urethra, a pseudo-Galenian text recommends (3): “Therapy consists primarily of an incision into the tip of the glans and insertion of a cannula.”

English

BACKGROUND: Ambiguous genitalia are currently defined as disorders of sexual development (DSD) and constitute a complex, major social and medical emergency which is fortunately very rare. In developed countries, abnormalities of external genitalia occur in 1.7% of new born. Worldwide, approximately 1 in 2000 children are born with disorders of sexual development. Of all the causes, congenital adrenal hyperplasia remains the most common Aetiology. AIMS AND OBJECTIVES: The present study aims to analyse the various disorders of sexual development, their clinical presentation, histopathological findings and their treatment modalities. MATERIAL AND METHODS: The present study was undertaken at the Department of Pathology, Paediatric referral Hospital, Hyderabad from June 2004 to May 2009, eleven specimens were from children who presented with disorders of sexual development. Detailed case history was taken and all the results were reviewed. The specimens received included Gonadectomies and biopsies from gonads. The Haematoxylin and eosin stained slides were histologically evaluated. RESULTS: This study included a total of 11 children with disorders of sexual development, aged between 1 day and 9 years. Among them 7 were being reared as males, 3 as females, 1 as ambiguous. Out of 11 cases studied, 3 were diagnosed as male pseudo hermaphroditism, 1 female pseudo hermaphroditism, 1 male gonadal dysgenesis, 3 True hermaphroditism and 3 abnormal gonadal development. CONCLUSION: Histopathological confirmation of the gonadal sex plays an important role in the management of these children .There should be no change in sex beyond the second year of life. In the gender assignment, the gold standard is that genetic females should be reared as females. In genetic males, gender assignment is based on size of phallus. Early gender assignment & precise diagnosis in disorders of sexual development is important. Surgical correction, hormonal supplementation and psychosocial management are the various treatment options available.

Imaging of disorder of sex development

BACKGROUND AND OBJECTIVESDisorders of sex development (DSDs), formerly termed ambiguous genitalia, are a group of conditions where the external genitalia appear abnormal. It represents a true medical and social emergency that needs a multidisciplinary team approach for elucidation. The pediatric radiologist plays an important role in defining the genital anatomy that remains one of the most important factors in sex determination, in addition to chromosomal analysis.DESIGN AND SETTINGSA retrospective study, conducted between January 1995 and December 2010.MATERIALS AND METHODSImaging studies (ultrasound, genitogram, and/or magnetic resonance imaging) were performed in patients with ambiguous genitalia, confirmed by chromosomal analysis and appropriate hormonal investigations.RESULTSThe sensitivity of ultrasound is 89.5%, while its specificity reaches 100%. Retrograde genitogram is more invasive and less sensitive, as the yield of determining the presence of a uterus ± vagina is 84.2%. However, magnetic resonance imaging (MRI) is more sensitive for gonadal tissue identification. Its specificity reaches up to 100% and can provide detailed internal structures (uterus, fallopian tubes, and gonads).CONCLUSIONUltrasound examination is still the main modality of choice for screening patients with ambiguous genitalia. It is cheap and readily available everywhere. In addition to elucidating the uterus in 89.5%, it can also give more information on the adrenal glands. However, genitography is good—84.2% in elucidating genital anatomy—but it gives no information of the gonads and it is time consuming and invasive. MRI is helpful in cases with equivocal ultrasound, reaches 100% in elucidating internal extractor, and therefore could be reserved for that.

Wilms Tumor

Wilms Tumor

A familial WT1 mutation associated with incomplete Denys–Drash syndrome

Denys-Drash syndrome (DDS) is a rare disorder characterized by nephropathy, male pseudohermaphroditism, and wilms tumor. Cases are thought to arise sporadically through a de novo mutation in the wilms tumor suppressor gene (WT1), which encodes a zinc finger protein that not only acts as a tumor suppressor but is essential for normal gonadogenesis, nephrogenesis, and development of the urogenital tract. In this report, we describe a family with the well-known missense mutation in exon 9 of the WT1 gene, 1180C>T (R394W), causing incomplete DDS and no symptoms in their father. The proband, a boy with 46, XY karyotype, was born with ambiguous genitalia, penoscrotal hypospadias, and bilateral inguinal hernias. At 2 years of age, he has proteinuria and diffuse mesangial sclerosis, but no wilms tumor has been detected. The elder sister of the proband, at 3 years of age, has normal genitalia, proteinuria, focal mesangial sclerosis but no wilms tumor. The WT1 mutation was detected in both patients, who have suspected DDS, and their father, who is phenotypically normal. This case is unusual in that the 1180C>T mutation, which has been found in approximately 50 % of patients with complete DDS, has been inherited and is causing mild or no symptoms of DDS.

A case of complete androgen insensitivity syndrome: genetic analysis of the family.

Besides many other factors, androgens play a role in expression of male phenotype. Androgen activity is mediated by androgen receptor (AR). After binding to androgen, AR translocates to nucleus and adheres to the regulatory regions of specific chromosomal DNA sequences (androgen response elements/ARE), to activate androgen dependent genes. The AR is encoded by the AR gene (Xq11–12). The gene is formed by 8 exons and 7 introns, spanning more than 90 kb. The functional domains are (a) exon 1 encoding the N-terminal domain (NTD) (1,586 bp); (b) exons 2 and 3 encode the DNA-binding domain (DBD) (152 and 117 bp); (c) the “hinge” region which binds the NTD and DBD consists of residues 628–669; (d) exons 4–8 encode the C-terminal ligand-binding domain (LBD), (131–288 bp). The C-terminus of the LBD mediates the hormone-dependent transcription. Mutations in the LBD region of AR perturb the conformation of the helix. The mutant AR is unable to efficiently bind to dihydrotestosterone (DHT) and to transactivate AREs [1]. Mutations in the AR gene leading to disordered AR function results in different forms of X-linked male pseudohermaphroditism, known as androgen insensitivity syndrome (AIS). This affects XY female individuals with normal androgen production and metabolism. AIS is present in 1:20,000–64,000 male births. The presence of variable phenotypic expression allows for the classification of AIS into complete androgen insensitivity (CAIS), partial androgen insensitivity (PAIS), and mild androgen insensitivity (MAIS). Approximately, 90 % of molecular defects in AR gene are single base point mutations, mostly missense mutations [2]. Here, we describe a familial case of CAIS presenting with similar mutations described across three generations. To the best of our knowledge and belief, ours is first such report citing this mutation in an Indian family.

WT1 microdeletion and slowly progressing focal glomerulosclerosis in a patient with male pseudohermaphroditism, childhood leukemia, Wilms tumor and cerebellar angioblastoma

The Wilms tumor 1 (WT1) gene is currently in focus by pediatric nephrologists as its mutations are associated with nephrotic syndrome, especially as part of complex clinical entities like Denys-Drash or Frasier syndrome. Renal failure may also develop in young WAGR patients, whose condition is attributed to a deletion at chromosomal region 11p13. However, only limited data exist on WT1 microdeletions. A 30-year-old male patient, with a history of genital malformations, a Wilms tumor manifested during the treatment of acute lymphoid leukemia (ALL) at the age of 4, and a cerebellar angioblastoma, was referred with proteinuria and a reduced glomerular filtration rate (GFR). Kidney biopsy revealed FSGS. Although all WT1 exons were amplified with polymerase chain reaction (PCR) and sequenced, none of them showed a mutation. However, an formalin-fixed, paraffin- embedded (FFPE) tissue sample of the patient's childhood Wilms tumor showed WT1- positivity restricted to the renal tumor cells, so the WT1 gene was investigated further. Using quantitative reverse transcription PCR (qRT-PCR), the gene was found to be present in only one copy in the patient's genomic DNA sample, while both copies were detected in both parents. In the patient's sister, the proximal region of WT1 was shown to have an extra copy. Evidence suggests that a heterozygous microdeletion of the gene WT1 is responsible for the patient's disease. It seems reasonable to assume a possible abnormality affecting meiotic crossing over at the WT1 locus in one of the parents.

Male pseudo hermaphrodism due to the association of two very rare conditions: a deficit in 17β-hydroxysteroid dehydrogenase type 3, and a chimerism

Male pseudo hermaphrodism due to the association of two very rare conditions: a deficit in 17β-hydroxysteroid dehydrogenase type 3, and a chimerism

Male pseudohermaphroditism Leydig cell hypoplasia

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Vaginoplasty using the inner surface or mucosa of the prepuce in children with congenital adrenal hyperplasia

ObjectiveTo describe and present the results of the use of the inner surface or mucosa of the prepuce in vaginoplasty for ambiguous genitalia. Patients and MethodsThis technique can be used alone in low vaginal insertion or associated with a total urogenital mobilization in cases of high vagina. During the past 7 years, we have performed 18 vaginoplasties using the described technique in 46, XX DSD (female pseudohermaphroditism). All patients had 21-hydroxylase deficiency; four had the simple virilizing form and 14 had additional salt loss. The age of the patients at surgery varied from 4 to 28 months (average 11.2). ResultsThe final cosmetic results were considered good by the parents and surgeon for the majority of our patients, and satisfactory in three cases. Clinical examination revealed stenosis of vaginal introitus in only one patient (which responded very well to one dilatation) and one urethra-vaginal fistula. ConclusionThis technique of vaginoplasty, simple in its realization and answering the purpose of treatment with few complications, can be used in the feminizing genitoplasty of young children with 46,XX DSD, ovotesticular DSD (true hermaphroditism), mixed gonadal dysgenesis and dysgenetic male pseudohermaphroditism.

Indirect inguinal hernia with uterine tissue in a male: A case of persistent Mullerian duct syndrome and literature review

A 32-year-old male presenting with a direct inguinal hernia was found to have uterine tissue extending through the inguinal canal, warranting a diagnosis of persistent Mullerian duct syndrome (PMDS). PMDS is an extremely rare form of internal male pseudo-hermaphroditism in which female internal sex organs, including the uterus, cervix and proximal vagina, persist in a 46XY male with normal external genitalia. The condition results from a congenital insensitivity to anti-Mullerian hormone, or lack of anti-Mullerian hormone, leading to persistence of the female internal sex organs in a male. Clinically, this condition is associated with cryptochoridism. Controversy persists regarding the appropriate treatment of PMDS, since resection of the remnant structures is associated with potential morbidity, but retention risks development of occasional malignancies. We review the literature and discuss various aspects of pathophysiology, diagnosis, and management of PMDS.

Persistent Müllerian Duct Syndrome: a Case Report

Persistent Müllerian duct syndrome is a rare form of internal male pseudohermaphroditism caused by defects in synthesis or action of Müllerian-inhibiting factor, due to which Müllerian duct derivatives, such as uterus, fallopian tube, and upper vagina, are normally present in 46XY males. Here, we report a 26-year-old male with right-sided obstructed inguinal hernia with left undescended testis. On exploration, hernial sac containing bowel loops, uterus with fallopian tubes, upper vagina, and testes were present.

5-Alpha-Reductase 2 Deficiency in a Woman with Primary Amenorrhea

Steroid 5-alpha-reductase 2 deficiency is a rare disorder leading to male pseudohermaphroditism, a condition characterized by incomplete differentiation of male genitalia in 46,XY patients. Here, we report a case of a 21-year-old woman from Ardabil who presented with primary amenorrhea, ambiguous genitalia, and lack of breast development. All of the serum hormone profiles were normal except for raised serum total testosterone. Testosterone to DHT ratio (T/DHT) was elevated before (15.72) and further increased after hCG stimulation (32.46). A chromosomal study revealed a 46,XY karyotype. A bilateral gonadectomy, recessive cliteroplasty, urethroplasty, and vaginoplasty were performed and hormonal replacement therapy using estrogen was started. In conclusion, the diagnosis of 5-alpha-reductase 2 deficiency may be suspected in infants with ambiguous genitalia or in adolescents or young adults with the characteristic phenotype and serum hormone profiles.

XY Female with Complete Androgen Insensitivity Syndrome with Bilateral Inguinal Hernia

The complete androgen insensitivity syndrome, previously called testicular feminization syndrome, is an X-linked recessive rare disorder. The individual is phenotypically female and genotypically male: a male pseudohermaphrodite. The individuals are reared as girls and the condition is suspected when the individual is evaluated for primary amenorrhea, infertility, or when unilateral/bilateral inguinal hernia is diagnosed in girls.