Androgen Insensitivity Syndrome: A Case Report

Background: Androgen insensitivity syndrome refers to an inability of the body to respond properly to male sex hormones (androgens) produced during pregnancy. This occurs because of a change (mutation) in a gene involved in the production of the protein inside cells that receives the androgen hormone and instructs the cells in how to use it. This is a genetic disorder that makes XY foetuses insensitive (unresponsive) to androgens, they are born looking externally like normal girls and Internally, there is a short blind pouch vagina and no uterus, fallopian tube or ovaries. There are testes in the abdomen or in the inguinal canal. The CAIS is usually detected at puberty when a girl should but does not begin to menstruate. They are at high risk of osteoporosis so should take oestrogen replacement therapy. Case Report: PAIS results in micropenis with hypospadias and gynaecomastia. We report this rare case of 18yr old female patient with primary amenorrhea. Subsequent investigation including karyotyping revealed that the patient is phenotypically female but genotypically male with testes. Gonadectomy was done with proper counselling and patient was put on hormonal replacement replacement therapy.

Male pseudohermaphroditism with os clitoris in three dogs

Two American Cocker Spaniels and one Bichon Frise were presented to our veterinary teaching hospital with an enlarged clitoris. Diagnostic imaging showed that the structure was composed of bony material. Exploratory laparotomy revealed uterine-like structures and testes which had an epididymis unilaterally. Surgical removal of internal genitalia, gonads and protruded clitoris were performed well. Histological evaluation revealed; inactive testes, female internal genital tracts with ambisexual ductal remnants, and prominent ossification in the clitoris. All 3 cases were diagnosed with male pseudohermaphroditism. In author's knowledge, this is the first report in Bichon Frise dog with os clitoris and also, it describes not common cases in small dog breeds with os clitoris.

Hiperplasia adrenal congénita. Presentación de caso / Congenital adrenal hyperplasia. Case presentation

Fundamento: La hiperplasia adrenal congénita es el desorden adrenal más común en niños, causa frecuente de seudohermafroditismo femenino y de ambigüedad sexual. La deficiencia de la enzima 21 hidroxilasa es la causa más común, ocurre entre un 90 y 95 % de los casos. La incidencia de la enfermedad es de 1:14 000 nacimientos. La determinación de hormona 17 hidroxiprogesterona al quinto día de nacido, facilita el diagnóstico y el adecuado tratamiento. Presentación de caso: Se describe el diagnóstico de un recién nacido femenino, de nueve días, con antecedentes prenatales de alto riesgo obstétrico, sin manifestaciones clínicas de pérdida adrenal, al examen físico discreto grado de virilización (moderada hipertrofia del clítoris) y niveles elevados de 17 hidroxiprogesterona, al cual se le realizó confirmatorio de 17 hidroxiprogesterona en suero a los nueve días, resultó positivo y ante los antecedentes prenatales, se decidió su diagnóstico y tratamiento oportuno. Conclusiones: Se realizó el diagnóstico de una hiperplasia adrenal congénita, en recién nacido femenino de nueve días, se brindó asesoría a sus familiares, se indicó tratamiento médico con hidrocortisona y fluorhidrocortizona, se le siguió por consulta del programa de hiperplasia adrenal congénita y se realizó estudio molecular para precisar déficit enzimático.

Background: Adrenal hyperplasia, congenital is the most common adrenal disorder in children, a frequent cause of femenine pseudohermaphroditism and sexual ambiguity. The deficiency of the 21 hydroxylase enzyme is the most common cause, occurs between 90 and 95 % of the cases. The incidence of the disease is at about 1:14 000 births. The determination of hormone 17 hydroxyprogesterone on the fifth day of birth facilitates diagnosis and adequate treatment. Case report: We describe the diagnosis of a 9 days old femenine infant with a prenatal history of high obstetric risk, with no clinical manifestations of adrenal loss, a discrete physical examination of virilization (moderate clitoris hypertrophy) and elevated levels of 17 hydroxyprogesterone, which was confirmed with serum hydroxyprogesterone at 9 days, was positive and before the prenatal history, the diagnosis and timely treatment was decided. Conclusion: Adrenal hyperplasia, congenital was diagnosed in a 9-day-old femenine newborn, counseling was given to her relatives, medical treatment with hydrocortisone and fluorhydrocortisone was indicated, followed by consult with the adrenal hyperplasia, congenital program and molecular study was made to determine enzymatic deficit.

Clinical characteristics and genetic analysis in two patients with 3β-hydroxysteroid dehydrogenase deficiency / 中华内分泌代谢杂志

Objective To analyze the clinical characteristics of two patients with 3β-hydroxysteroid dehydrogenase deficiency and to explore their molecular genetic defects.Methods The clinical features and laboratory data of two patients were collected.The exons of HSD3B2 gene were amplified by PCR and sequenced by Sanger sequencing.Results Patient 1, aged 5 yrs old, was raised as a girl with 46, XY karyotype, presented with hyperpigmentation, female infant vulva, clitoral hypertrophy, and bilateral cryptorchidism;Patient 2, aged 11 yrs old, was raised as a girl at birth but as a boy after 1 yr old for known 46, XY karyotype, presented with hyperpigmentation, micropenis and severe hypospadias.Both patients had markedly elevated adrenocorticotropin and decreased cortisol.Two homozygous missense mutations in HSD3B2 gene were identified:conversions of codon Pro155 toLeu(p.P155L)inpatient1,andcodonAla82toThr(p.A82T)inpatient2,bothofwhichwerereportedforthe first time in China.Conclusion The patients with 3β-hydroxysteroid dehydrogenase deficiency in 46,XY karyotype mainly present with male pseudohermaphroditism and adrenocortical deficiency, and the diagnosis should rely on the steroids detection and HSD3B2 gene screening.

Acute urinary retention caused by seminoma in a case of persistent Mullerian duct syndrome.

Urinary symptoms have been described secondary to a pelvic mass originating from the ovary, uterus, cervix, prostate, or rectum. Persistent Mullerian duct syndrome is a rare form of intersex disorder, characterized by the presence of uterus and fallopian tubes in an otherwise 46 XY male. We report an adult male with bilateral cryptorchidism and a pelvic mass, who presented with acute urinary retention, and was diagnosed with a seminoma of the right testis, intratubular germ cell neoplasia of the left testis with the presence of Mullerian remnants. Pelvic mass was caused due to seminoma is a rare cause of urinary retention.

Male pseudohermaphroditism in a Maltese/poodle mixed dog / 동물의과학연구지

Male pseudohermaphroditism is not commonly reported in veterinary medicine. Here, a 3-year-old Maltese/poodle mixed dog presented with malformed external genitalia and episodic hematuria. Inspection and palpation of the external genitals showed a malformed penis, shortened prepuce, external urethral orifice, and cryptorchidism. There was no urethral meatus at the tip of the penis. The urethral opening was situated between the prepuce and the penis. The anterior half of the prepuce was absent, and the penis was free and exposed to both trauma and licking. Plain radiographic examination showed absence of an os penis in the penis. A double-contrast cystograph showed the suspected uterus as well as the cystic calculi. A hypoechoic space was seen at the dorsal portion of the urinary bladder. The space was suspected to be the uterus. A sagital ultrasonograph showed cystic calculi in the urinary bladder. During surgery to remove cystic calculi, hypoplastic testes as well as the uterus were observed. Histological examination of the testes showed the seminiferous tubules and interstitial cells. The sertoli cells and spermatogonia were adjacent to the basement membrane. No evidence of spermatogenesis was found. Striated squamous epithelial cells and smooth muscle cells were found in the uterus. This dog had vestigial oviducts as well as a uterus with male-appearing external genitals.

Persistent mullerian duct syndrome.

Persistent mullerian duct syndrome is a rare form of internal male pseudohermaphroditism in which mullerian duct derivatives are present in a genotypic (46XY) and phenotypic male. We report a rare case of persistent mullerian duct syndrome in an adult fertile male in whom mullerian duct derivatives (uterus and fallopian tubes) were found in the right hernia sac at herniotomy.

Male Pseudohermaphroditism Presented with Sudden Cardiac Arrest

Torsades de Pointes is a life-threatening arrhythmia associated with a number of causes, but is very rare among endocrinologic disorders. We report a case of male pseudohermaphroditism with hyperaldosteronism due to a 17alpha-hydroxylase deficiency presented with sudden cardiac arrest.

Clinical effect of clitoroplasty with preservation of glans clitoris and dorsal neurovascular pedicle / 中华医学美学美容杂志

Objective To evaluate the clinical effect of clitoroplasty with preservation of the glans clitoris and the dorsal neurovascular pedicle in patients with clitoral hypertrophy. Methods From July 2003 to June 2009, cunnus feminization operations with preservation of the glans clitoris and the dorsal neurovascular pedicle and labioplasty were performed on 8 patients with female pseudohermaphroditism. Results All 8 cases were primary healing. The shaping glans of clitoris was completely viable with satisfactory size, location, contour and touching sensitivity, and the cunnuses presented the appearances of female external genital organs. Conclusions Clitoroplasty with preservation of the glans clitoris and the dorsal neurovascular can improve the appearance of clitoris and labia, preserving the functions of sensation and erection, reconstruting a new clitoris which is aesthetically appealing and functional, and it is suitable for various kinds of cunnus feminization operations.

A rare case of congenital heart disease with ambiguous genitalia.

Birth defects have become the important cause of mortality and morbidity in the perinatal period. Congenital heart disease (CHD) is the most common birth defect which includes the varying forms of cardiac abnormalities and occurs with an incidence of 1 per 100 live births. In most of the cases, CHD is an isolated malformation, but about 33% have associated anomalies. Ambiguous genitalia are one such rare anomaly that is associated with CHD among other genital abnormalities. The possible causes for this association could be pseudohermaphroditism, which in turn, may be due to congenital adrenal hyperplasia. The government of any country should consider providing for its people a free prenatal diagnosis for susceptible disorders.

Problemática jurídica de los estados intersexuales: el caso colombiano / Legal problematic of intersexual states: the Colombian case

En este artículo de reflexión, basado en una investigación, se describe la problemática jurídica planteada por los estados intersexuales en los menores de edad, y cómo la misma centra su discusión en la teoría del consentimiento informado, punto nodal en el que convergen, por un lado, la existencia de un sujeto titular de derechos, y por el otro, el modo en que debe darse la autorización para ciertos tratamientos médicos o quirúrgicos, así como para algunas intervenciones preventivas. Igualmente, se plantea la necesidad de articular el saber jurídico con el de otros campos como la medicina y la bioética, a fin de construir un marco teórico, analítico y práctico que aporte nuevas herramientas e instrumentos para resolver esta problemática. La Corte Constitucional Colombiana, como máximo órgano jurisdiccional, estableció algunos parámetros jurídicos para adoptar decisiones en estos casos pero cada uno de ellos plantea matices y opciones diferentes, y la solución que se pretenda adoptar debe ir dirigida a optimizar el bienestar del paciente.

This is a reflection article based on research. In it, we describe the legal issues raised by intersexual states in minors. Individual rights and the way in which authorization should be given for certain medical and surgical treatments are analyzed in the perspective of the informed consent theory. We emphasize on the need to combine legal, medical, and bioethical knowledge with the aim of building a theoretical and practical framework for approaching this problematic. The Colombian Constitutional Court established certain legal parameters for reaching decisions in cases of children with intersexual states. However, each case poses different challenges and should be approached with the aim of optimizing benefits for the patient.

Meta-analysis of 342 Female Pseudohermaphroditism / 中国医科大学学报

Objective To summarize the clinical characteristics of female pseudohermaphroditism (FPH) in the publication from 1994 to 2009 and the cases diagnosed and treated in our hospital from 2000.Methods We employed Chinese and English name of female pseudohermaphroditism as a key word separately to retrieve published articles of FPH during 1994 to 2009.A meta-analysis was performed together with the ten cases in our hospital.Results Among 342 cases involved in this study,only twenty-seven children were diagnosed immediately after birth and the other 315 cases at the age of 1 month to 59 years with median age of 29.54 years.The etiological factors were mostly congenital adrenal hyperplasia (70.47%).Clinical manifestations were advanced bone age (95.52%),clitoromegaly (84.14%) and early virilization (77.24%).The treatment mainly included drug and operation.Early diagnosis and available therapy were very important for the prognosis.Conclusion FPH is not rare,so we should improve our knowledge for its early diagnosis,good intervention and final better prognosis.

Study on a pedigree with Leydig cell hypoplasia caused by novel mutation of luteinizing hormone receptor / 中华内分泌代谢杂志

Objective To investigate a Chinese pedigree suffering from Leydig cell hypoplasia ( LCH) based on clinical data and genetic diagnosis. Methods The patient was diagnosed by means of clinical data, hormone profiles, and human chorionic gonadotropin ( hCC) test. The luteinizing hormone/chorionic gonadotropin receptor(LHCGR) gene of the patient and family members was amplified and sequenced. Results The patient presented with male pseudohermaphroditism, low level of testosterone, which did not respond to hCG. Genetic analysis of the LHCGR revealed two novel mutations: a missense mutation located in exon 5, resulting in Ile replaced by Thr in the extracellular domain; and a splice site mutation in the 3' terminal of intron 6( IVS6-3 C→A). Proband's sister (46, XX) who lacked clinical manifestations showed the identical genotype with the patient. Conclusions A mutation in the consensus sequence of 3' splice site, in addition to a missense mutation (Ile 152Thr)in the extracellular ligand-binding domain is the cause of inactivation of the LHCGR gene in patient with Leydig cell hypoplasia.

Diagnosis and treatment of female pseudohermaphroditism / 中国医师进修杂志

Objective To discuss the etiology,clinical features,diagnosis and treatment measures of female pseudohermaphroditism.Methods Five Cases,of female pseudohermaphroditism were collected.The etiology,clinical features,diagnosis and treatment measures were discussed.Results One case induced by exogenous androgenic hormones,4 cases induced by congenital adrenal hyperplasia.All the 5 cases presented with abnormal development of vulva and the sex chromosomes karyotype of 46XX.The combined treatment ofreconstructive surgery (5 cases)and supplementary glucocorticoid (4 cases)wefe performed.After 3months,the levels of adrenocorticotrophic hormone and virosterone were normal.Followed up for 1-10 years,The postoperative appearance of external genitalia was similar to the normal.The secondary sex characters were improved obviously,3 cases were mainly feminilism,2 cases existed different degree of psychologic obstacle.Conclusions The diagnosis and treatment in the early stage are very important.The combination treatment of surgery and medicine for the patients with female pseudohermaphroditism is satisfied.

Disorder of Sex Development with 5alpha-reductase Deficiency in Identical Twins / 대한소아내분비학회지

Children with abnormal sex development may present with ambiguous genitalia in the newborn period or lacking of secondary sexual characteristics in puberty. Clinicians should make a prompt and accurate diagnosis and counsel parents on therapeutic options to minimize or avoid medical and psychological complications. 5alpha-reductase deficiency is a rare autosomal recessive disorder of sex development caused by a mutation of the 5alpha-reductase type 2 gene. As a result, there is an abnormality in conversion of testosterone (T) to dihydrotestosterone (DHT) and children with 5alpha-reductase deficiency are born with ambiguous genitalia. Here, we report identical twins who presented with ambiguous genitalia with a 46,XY karyotype and were diagnosed as 5alpha-reductase deficiency.

Male pseudohermaphroditism due to 17β-hydroxysteroid dehydrogenase 3 deficiency / 中华内分泌代谢杂志

Objective To investigate the clinical and genetic characteristics in a patient with 17β-hydroxy-steroid dehydrogenase (17β-HSD) 3 deficiency, regarding its pathophysiology and pathogenesis. Methods Clinical features and laboratory data were analyzed in a pedigree of 17β-HSD3 deficiency. Blood samples from the patient and his parents were collected. HSD17B3 gene was screened for mutations by PCR and subclone sequencing. Results The patient presented with pubertal virilization and gynecomastia. The physical examination showed female external genitalia and testes in inguinal canals. The chromosome karyotype was 46, XY. Serum FSH, LH, dehydroepiandrosterone sulfate, androstenedione and 17-OH-progesterone levels were raised, whereas plasma testosterone was lowered. Sequencing analysis revealed 4 nucleotide deletion (172-175del) of HSD17B3 gene. Conclusion Virilization and gynecomastia in puberty suggest the probability of 17β-HSD deficiency. It may be verified clinically by hCG-stimulating test and confirmed by gene diagnosis.

Etiology analysis of male pseudohermaphroditism / 中华泌尿外科杂志

Objective To discuss the etiology of male pseudohermaphroditism. Methods The clinical data of 42 male pseudohermaphroditisms were retrospectively analyzed.Among the 42 cases (mean age of 10 years,range from 8 to 19 years),39 caseg social gender were female sex and 3 were male.Physical examination indicated abnormal external genitalia,cryptorchidism,hypospadias and mass of pelvis or inguinal.Chromosome examination showed that 39 cases were 46,XY,2 cases of 45,X/46.XY and 1 case of 45,X/47,XXY.Etiology analyses were established in 42 cases by eytogeneties,endocrinology,B-ultrasound or CT examination,celiac exploration and pathology examination.Results All the 42 cases received operation.All cases were treated by hormone replacement according to the social gender which they selected.Thirty-three cases were followed up for 7 to 10 years. Conclmion The etiology of male pseudohermaphroditism includes anti-androgen syndrome,testosterone synthetase deficiency,resistant LH/hCG by testis,simple gonadal dysgenesis,mixed gonadal dysgenesis and resistant mullerian duct syndrome.

As novas definições e classificações dos estados intersexuais: o que o Consenso de Chicago contribui para o estado da arte? / New definitions and classifications of the intersexual states: in which the Chicago Consensus has contributed to the state of the art?

As anomalias da diferenciação sexual têm-se constituído em um formidável desafio quanto ao diagnóstico e à conduta, colocando o paciente, os familiares e os profissionais da equipe de saúde na difícil situação de definir a melhor opção quanto ao gênero de criação. Uma terminologia confusa e estigmatizante tem sido adotada e, nesse sentido, o Consenso de Chicago propõe várias modificações no sentido de minimizar os desconfortos graças a uma terminologia que nem sempre auxilia na solução de problemas. Os autores fazem uma análise crítica da classificação sugerida pelo Consenso, levantando a questão de que, na nova classificação, também não se resolvem certos problemas terminológicos e continua a se criar algum grau de estigmatização. Em primeiro lugar, a sugestão de se incluir o cariótipo no nome da doença supõe, erroneamente, que os pacientes não tenham conhecimento do que significa ser 46,XY ou 46,XX. Uma criança criada no sexo feminino com uma anomalia da diferenciação sexual (ADS) 46,XY não vai entender porque está no sexo feminino se seu cariótipo é "masculino". A substituição do termo hermafroditismo verdadeiro por ADS ovotesticular está longe de resolver o problema de estigmatização causado por "hermafroditismo". O termo ovotesticular é claramente entendido como uma fusão entre ovário e testículo e não será aceito com "naturalidade". Se, por um lado, é muito satisfatório que a questão da nomenclatura seja discutida, por outro lado devemos escolher termos alternativos que sejam realmente neutros e não tragam, em si, a conotação de um sexo que pode não condizer com o escolhido para aquele paciente em particular. Um ponto em que todos concordamos é que a substituição de intersexo por anomalia da diferenciação sexual (ADS) ou, disorder of sex development (DSD), na língua inglesa, cai muito melhor e não dá a conotação de um "sexo intermediário" como o nome antigo proporcionava.

Disorders of sex development have posed a tremendous challenge not only in the diagnosis but also in the treatment, placing the patient, the family members, and the health team in the difficult task of attributing the best sex of rearing for that specific patient. A confusing and stigmatizing nomenclature has been employed and the Chicago Consensus tried to minimize the discomfort with modifications of the current terminology. The authors perform a critical analysis of the Consensus, raising the question that the new terminology does not solve the problems and persist being stigmatizing to the patient and to the family. First of all, the inclusion of the karyotype in the name of the disease holds the false premise that the patients do not know the meaning of a 46,XY or a 46,XX karyotype. A child raised in the female sex will not understand that her disease holds a "male" karyotype in its name (46,XY DSD). The substitution of ovotesticular DSD for true hermaphroditism maintains the stigma of the name since ovotesticular is easily perceived as ovarian and testicular tissues. If, on one hand, the recognition of using terms like intersex and hermaphroditism are stigmatizing, on the other hand, we need terms that are really neutral to not create problems of sexual identification. One point in which there is consensus is that the change of the term "intersex" for "disorder of sex development" is highly desirable and eliminates the idea of an "intermediate sex".

A case of 5 alpha reductase deficiency / 대한산부인과학회지

5 alpha-reductase deficiency is a rare autosomal recessive disorder caused by mutations in the SRD5A2-gene, resulting in absent or diminished dihydrotestosterone (DHT) formation and, hence, in an underdevelopment of the external genitalia in patients with 46,XY karyotype. Recently we experienced a 17 years old patient with chief complaint of primary amenorrhea, who showed 46,XY karyotype, enlarged clitoris, virilization, undeveloped breast and palpable bilateral inguinal mass. We diagnosed it as 5 alpha?reductase deficiency and removed the bilateral gonads, so we report it with brief review of literature.

A Case of Male Pseudohermaphroditism due to 17alpha-Hydroxylase Deficiency / 대한불임학회지

Female phenotype of a 46,XY male may originates from male pseudohermaphroditism due to 17alpha-hydroxylase deficiency. Lack of cortisol increases adrenocorticotropic hormone (ACTH) and mineralocorticoid production, leading to low renin hypertention and hypokalemia. A 41-year-old phenotypic female presented primary amenorrhea and hypertension. In the hormonal profile, the levels of serum estradiol, testosterone, rennin, and cortisol were decreased and ACTH and deoxycorticosterone were increased. Laparoscopic bilateral gonadectomy was performed, and corticosteroid, antihypertensive drugs, and estrogen were administered. We report this case with a brief review of the literatures.