Case Of Androgen Insensitivity Syndrome Research Articles

Complete Androgen Insensitivity Syndrome (AIS) in a young female: A rare form of sexual development disorder

Androgen Insensitivity Syndrome (AIS) is a rare genetic condition affecting individuals with 46 XY genotypes. We present a case of Complete AIS (CAIS) in a 16-year-old phenotypically female patient with primary amenorrhea and bilateral inguinal masses. Despite male karyotype (46XY), physical examination and imaging revealed the absence of Müllerian structures and the presence of testes-like structures. The diagnosis was confirmed through hormone profiling and karyotyping. Management involved multidisciplinary collaboration, including surgical interventions (gonadectomy) and counseling. Early recognition and intervention in CAIS can mitigate psychological distress and optimize outcomes. This case also highlighted the importance of considering AIS in the differential diagnosis of primary amenorrhea, particularly in the presence of inguinal hernias.

A Gly684Ala substitution in the androgen receptor is the cause for azoospermia in a Chinese family with mild androgen insensitivity syndrome and normal hormone levels.

Androgen receptor gene (AR) is essential for male growth and fertility. Its mutations are responsible for androgen insensitivity syndrome (AIS) that usually shows the phenotype of azoospermia resulting in male infertility. This study reported the first case of mild AIS with complete normal serum hormones in a Chinese family. The proband referred for infertility because of azoospermia. His uncle and two cousins are both infertile and have azoospermia. Whole-exome sequencing in the genetic analyses showed that the proband carries a novel hemizygous AR missense mutation, NM_000044.6: c.2051G>C (p.Gly684Ala), in exon four within the ligand-binding domain. His mother and maternal aunt are heterozygous carriers, while his father and brother are wildtype, indicating that the mutation in the proband was inherited from his mother. This pattern is consistent with the genetic model of the X-linked recessive inheritance of AR in AIS pathogenesis. HOPE predicts that p.Gly684Ala increases the hydrophobicity of AR but does not change the AR conformation. PolyPhen-2 predicts that p.Gly684Ala is harmful. This study provides the new knowledge to understand the AR gene mutations in MAIS.

Ventral clitoroplasty preserves dorsal nerves in case of partial androgen insensitivity syndrome: 4 years follow‐up

Androgen insensitivity syndrome (AIS) causes feminization of the external genitalia, in 46XY individuals. We report a notable case of partial AIS (PAIS), which was treated with ventral clitoroplasty and vaginal dilatation. The patient is a 17-year-old phenotypically female, presented with primary amenorrhea, infantile vagina, clitoromegaly, and presence of testes. Feminizing genitoplasty was done in form of ventral clitoroplasty with gonadectomy and was put on hormone replacement therapy and advised regular use of vaginal dilators to improve vaginal length. In ventral approach, the erectile tissues are excised without disturbing the neurovascular structure. Vibratory threshold perception of clitoris assessed by biothesiometer was normal 4 years after the surgery. Vaginal corrective surgery is not required when presentation is at later stage and has some vaginal depth to work out with vaginal dilators. Regular psychiatric consultations and support are needed in patients with PAIS to develop their confidence in gender identity and sexual orientation.

Endocrine and Cytogenetic Profile of Variations in Genital Development: Series of 9 Cases at the Mali Hospital

We carried out a retrospective and descriptive study in the Medicine and Endocrinology service of the Mali Hospital from January 2015 to December 2018. Nine cases of anomalies in sexual differentiation were referred for pubertal delay, growth retardation, gynecomastia, micropenis or infertility. Outcomes: The average age was 14 years; 5 patients were declared female at birth; 2 were married without children; 7 patients came from the region of Kayes; 8 patients consulted for pubertal delay; 1 patient presented with association of a blind vagina and 2 bilateral inguinal gonads. 3 of 4 patients declared male at birth had a micropenis; 2 patients had gynecomastia with a history of hypospadias. Ultrasound and biological data showed a clinical-hormonal picture of hypergonadotropic hypogonadism in 6 patients, 1 case of hypogonadotropic hypogonadism with hypercorticism and 2 cases with normal gonadotropic axis; two cases of azoospermia. Karyotypic analysis showed: 3 cases of SK, 2 cases of Klinefelter Syndrome, 2 cases of Androgen Insensitivity Syndrome and 2 cases of male 46 XX syndrome including one with sry negative. Conclusion: The precise diagnosis of anomalies in sexual differentiation remains complicated in Mali, due to the inadequacy of the technical platform. Diagnosis must be made at an early stage to allow normal growth, puberty and satisfactory fertility. Taking charge of the medical treatment possibly associated with plastic surgery could give good results.

A case of androgen insensitivity syndrome treated with laparoscopic gonadectomy

A case of androgen insensitivity syndrome treated with laparoscopic gonadectomy

Two Korean girls with complete androgen insensitivity syndrome diagnosed in infancy.

Androgen insensitivity syndrome (AIS) is a rare genetic disease caused by various abnormalities in the androgen receptor (AR). The AR is an essential steroid hormone receptor that plays a critical role in male sexual differentiation and development and preservation of the male phenotype. Mutations in the AR gene on the X chromosome cause malfunction of the AR so that a 46,XY karyotype male has some physical characteristics of a woman or a full female phenotype. Depending on the phenotype, AIS can be classified as complete, partial or mild. Here, we report 2 cases of complete AIS in young children who showed complete sex reversal from male to female as a result of AR mutations. They had palpable inguinal masses and normal female external genitalia, a blind-end vagina and absent Müllerian duct derivatives. They were both 46,XY karyotype and AR gene analysis demonstrated pathologic mutations in both. Because AIS is inherited in an X-linked recessive manner, we performed genetic analysis of the female family members of each patient and found the same mutation in the mothers of both patients and in the female sibling of case 2. Gonadectomy was performed in both patients to avoid the risk of malignancy in the undescended testicles, and estrogen replacement therapy is planned for their adolescence. Individuals with complete AIS are usually raised as females and need appropriate care.

Etiology and management of primary amenorrhoea: A study of 102 cases at tertiary centre

ObjectiveTo determine the prevalence of etiologic causes of primary amenorrhea in Indian population. Materials and methodsA retrospective study was performed using 102 complete medical records of women with primary amenorrhea who attended the Gynaecologic Endocrinology Clinic, Department of Obstetrics and Gynaecology, AIIMS, New Delhi from September 2012 to September 2015. Cases were analysed according to clinical profile, development of secondary sexual characteristics, physical examination, pelvic and rectal examination, X-ray of chest and lumbo-sacral spine, hormone profile, pelvic USG, MRI, and cytogenetic study including karyotype. ResultsThe three most common causes of primary amenorrhea were Mullerian anomalies (47%), gonadal dysgenesis (20.5%), and hypogonadotropic hypogonadism (14.7%) in the present study. There were 3 cases of Turner syndrome (45,XO), 5 cases of Swyer's syndrome (46,XY) and 2 cases of Androgen insensitivity syndrome (46,XY). One case had pituitary macroadenoma and eight cases (7.8%) were of genital tuberculosis. ConclusionsThe present study has currently been the largest case series of primary amenorrhea from North India. Mullerian anomaly is the most prevalent etiological factor leading to amenorrhoea followed by gonadal dysgenesis in our study. Racial, genetic and environmental factors could play role in the cause of primary amenorrhea.

Prenatal Diagnosis of Twin Fetuses with a Novel AR Gene Mutation in a Chinese Family of Complete Androgen Insensitivity Syndrome

ABSTRACTIntroduction and aims: Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic disorder caused by mutations in the androgen receptor (AR) gene. Only a few cases of AIS with AR gene mutations have been diagnosed prenatally. This study aimed to investigate the gene mutation in a Chinese complete androgen insensitivity syndrome family and perform prenatal diagnosis for twin fetuses. Case report: We evaluated the AR gene of the child proband in a Chinese CAIS family, and detected a novel mutation c.3864T>C (p. Phe917Leu). Amniocentesis was performed when the mother presented to our hospital with a subsequent twin pregnancy. Mutation analysis revealed that both fetuses were hemizygous for this mutation. The aborted fetuses had typical female external genitalia and bilateral testes in abdomen. Conclusion: The c.3864T>C AR novel mutation is responsible for complete androgen insensitivity syndrome, and its identification was subsequently used for a subsequent successful prenatal diagnosis.

Müllerian Anomalies: A Cause for Primary Amenorrhea

ABSTRACT Introduction Primary amenorrhea is a challenging entity as it affects the reproductive outcome. Primary amenorrhea is an absence of secondary sexual characters until 14 years of age or absence of menstruation with secondary sexual characters until 16 years of age. Aim The aim of this article is to study the frequency, etiologic causes, presentation, diagnosis, and optimal mode of management of primary amenorrhea. Materials and methods All girls who had not attained menarche until 16 years of age in the absence of secondary sexual characters and until 14 years, if no secondary sexual characters, and were willing for follow-up were subjected to investigations and were treated as per the etiology. Results Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome was the most common cause of primary amenorrhea (42.85%) followed by imperforate hymen (28.57%) and transverse vaginal septum (21.42%), one each of low, mid, and high varieties. There was one case of androgen insensitivity syndrome. Conclusion Establishing correct diagnosis is essential for planning treatment and management strategies in primary amenorrhea as treatment goals are preservation of fertility and progression of normal development. How to cite this article Bhalerao AV, Garg R. Müllerian Anomalies: A Cause for Primary Amenorrhea. J South Asian Feder Obst Gynae 2017;9(3):221-224.

Immunophenotypic differences between neoplastic and non-neoplastic androgen-producing cells containing and lacking Reinke crystals.

We performed a detailed morphologic, immunophenotypic, and endocrine characterization of neoplastic and non-neoplastic lesions of androgen-producing cells known to harbor or lack Reinke crystals (RCs) with an aim to provide further insight into the nature of these cells and crystals. Study cases were selected from the files of participating hospitals and subclassified according to current classifications: 20 with Leydig cell tumors (LCTs), 2 with testicular adrenal rest tumors (TARTs), 2 with testicular tumors of adrenogenital syndrome (TTAGS), and 2 with androgen insensitivity syndrome (AIS). An extensive immunophenotypic panel including markers used in sex cord-stromal cell tumors, androgen hormones, enzymes, and receptors was applied to the cases and 10 non-tumoral adrenal glands. Non-tumoral tissues were scored separately. RCs were present in 90% of LCT cases and all cases with normal Leydig cells; RCs stained specifically with calretinin and 3β-hydroxysteroid dehydrogenase (3BHSD) and were present only in cells with high concomitant expression of both proteins, a phenotype unique to Leydig cells and LCTs. Leydig cells from AIS cases lack RCs due to decreased expression of 3BHSD. Calretinin is decreased in testicular adrenal-like tumors and absent in normal adrenocortical cells, which explain why they lack RCs. Calretinin expression in androgen-producing cells is independent from androgen receptors and androgen synthesis. RCs represent for the most part, if not exclusively, crystallized forms of a 3BHSD/calretinin complex. Androgen-producing cells containing and lacking RCs differ mainly in the level of expression of these proteins and androgen receptors.

Two cases of androgen insensitivity syndrome

Two cases of androgen insensitivity syndrome

Psychological Aspects of Androgen Insensitivity Syndrome- A Case Report

Introduction: Androgen insensitivity syndrome (AIS) is a condition that results in the partial or complete inability of the cell to respond to androgens. A person with androgen insensitivity syndrome can experience significant psychological distress secondary to the ambiguity concerning their sexual anatomy. Psychological evaluation and management of a case of Androgen insensitivity syndrome brought up as a female experiencing such distress is reported here. Case history: A 25 years aged female patient working as a police constable, was referred for psychiatric evaluation for repeated attempts to commit suicide secondary to depression and anxiety arising out of her sexual ambiguity . She had consulted a gynaecologist for not having attained menarche. Ultrasonography of abdomen showed aplastic uterus with streak ovaries. According to chromosome analysis, she was a phenotypic female with male karyotype-46, XY (sex reversal). Her testosterone levels were increased. She had undergone prophylactic laparoscopic gonadectomy . The impact of test results made her anxious and sad. Her sexual ambiguity resulted in worry about getting transformed into a hijda (Eunuch) which led to repeated attempts to commit suicide. Psychiatric intervention consisted of antidepressants and counselling sessions aimed at coming to terms with ambiguity about her gender. Conclusion: Androgen insensitivity syndrome, although very rare, can result in considerable psychiatric morbidity. Apart from gynaecological and endocrinal aspects , addressing associated psychological issues is essential to reduce psychiatric morbidity and increase quality of life.

Androgen Insensitivity Syndrome with Gynandroblastoma and Vulvar Leiomyoma

This study aimed to describe a rare case of androgen insensitivity syndrome (AIS) in association with gynandroblastoma and vulvar leiomyomata. The patient was a 64-year-old phenotypically female person with 46 XY chromosomal karyotypes who presented with a chief complaint of abdominal distension of 1-month duration. She had 2 vulvar masses for more than 20 years and had experienced life-long (untreated) amenorrhea. History and physical examination findings showed the patient to be 175 cm in height, with normal breast development, and a lack of pubic or axillary hair. Serum levels were as follows: testosterone, 1,980 ng/dL; estradiol, 1,380.8 pg/mL. In combination with clinical findings, a diagnosis of complete AIS was made. The patient subsequently underwent surgery, during which the bilateral vulvar masses and the rudimentary uterus, right sex gland, and left side of the tumor were resected. Histological examination of the tumor revealed a mass composed primarily of juvenile-type granulosa cells, admixed with a Sertoli cell component that comprised less than 50% of the tumor. The right side of the gonad had an ovarian-like cortex and was considered to be an undeveloped ovary. The left and right side of the vulvar masses were diagnosed with leiomyomas. Patients with AIS should be monitored closely because these patients may also experience gonadal tumors. When confronted with gynandroblastoma, close attention should be paid to the patient's endocrinologic status, and comprehensive endocrinologic analyses should be conducted to make correct treatment decisions.

Androgen insensitivity syndrome ten years of our experience

Abnormalities of secondary sexual differentiation manifest in varying degrees depending upon the severity of the underlying cause. Primary amenorrhea in phenotypic females is caused by several different factors, including hormonal imbalance, nutritional deficiency and sex differentiation abnormalities. Androgen insensitivity syndrome (AIS) accounts for a large proportion of such cases in phenotypic females but genetically male individuals. Over the past 10 years, we have collected data related to androgen insensitivity from more than 150 cases. The research identified several important but neglected facts about this syndrome; including the identification of mutations in 39% of the cases and the establishment of the cause of pathogenesis in 60% of them. The most intriguing facts were uncovered in relation to late presentation of the AIS cases, little awareness among patients and family members, no consensus on the age of performing gonadectomy, and reluctance of the patients to undergo recommended surgery. These issues need immediate attention to improve healthcare and management of AIS cases. This article summarizes our observations about AIS with an aim to spread awareness among patients and clinicians.

The Three Cases of AIS (Androgen Insensitivity Syndrome) Performed by Laparoscopic Gonadectomy

The Three Cases of AIS (Androgen Insensitivity Syndrome) Performed by Laparoscopic Gonadectomy

Androgen insensitivity syndrome in an Indian adult

In androgen insensitivity syndrome (AIS), the patients are phenotypically females with male karyotype. Affected persons present at puberty with primary amenorrhea with adequate breast development and normal external genitalia. The gonads may be found in lower abdomen, inguinal regions, or sometimes in the labia majora. Rarely, the testes may undergo malignant transformation. So, gonadectomy is indicated in these patients after they attain puberty. Here, we present a case of AIS with primary amenorrhea and bilateral inguinal swelling.

Rare cases of disorders of sex development (DSD) in adolescents with female phenotype

Disorders of sex development (DSD) belong to uncommon pathologies; in addition, there are especially rare forms, such are ovotesticular disorders (OT), Turner syndrome and early malignisation of intraabdominal located gonads in the cases of androgen insensitivity syndrome. In this article we present four rare cases of DSD in female phenotype adolescents: two cases of ovotesticular DSD with 46,XX and 46,XY karyotypes; one familial case of androgen insensitivity syndrome (AIS) with early malignancy (19-year-old) of intra-abdominally-located testicle in older siblings, and a case of spontaneous menstruation in a patient with Turner syndrome and mosaic karyotype 45,X/47,XXX. Rare cases of DSD are connected with diagnostic and management difficulties and so description of each such case and collection of data in this field is very important from a scientific, as well as a practical, point of view. Determination of prognosis and adequate management of each individual patient are also essential. Study of this issue is especially sensitive in the case of adolescent patients in order to avoid physiological stress, to reduce health risks and to improve quality of life.

Síndrome de insensibilidad a los andrógenos como causa de amenorrea primaria

Androgen insensitivity syndrome is characterized by the presence of external female phenotype, 46,XY karyotype and intraabdominal testes. This syndrome is the third most frequent cause of primary amenorrhea, after gonadal dysgenesis and congenital absence of the vagina (Mayer-Rokitansky-Küster-Hauser syndrome). Androgen insensitivity syndrome is of interest due to its role in sexual identification and its possible association with malignant tumors of the male gonads, which require an accurate diagnosis and surgical treatment. We present two cases of androgen insensitivity syndrome. The results of the clinical and genetic examinations, as well as the treatment and follow-up of these two patients, are discussed.

A case of complete androgen insensitivity syndrome with malignant mixed germ cell tumors

Androgen insensitivity syndrome cases have an increased risk of developing testicular cancer due to many factors such as mutations, hormonal disturbances involving gonadotropins and cryptorchidism. However, malignant germ cell tumor is relatively rarely found compared to those seen in other types of intersex. Recently, the authors experienced a case of malignant mixed germ cell tumor with lymph node metastasis and chemotherapy resistance which was developed in a 31-year-old patient with complete androgen insensitivity syndrome.

G708E Mutation in the Androgen Receptor Results in Complete Loss of Androgen Function

End-organ resistance to androgens, called androgen insensitivity syndrome (AIS), is a rare disorder. The most common cause of AIS is mutations(s) in the androgen receptor (AR) gene; however, a significant number of these mutations have not been functionally analyzed. In the present study, we analyzed a case of complete AIS for mutations in the AR gene. Sequencing of the entire coding region of the AR gene revealed a 2650G>A mutation (mRNA sequence reference) in exon 4 of the gene, resulting in replacement of glycine with glutamate at codon 708 in the ligand-binding domain of the AR protein. The mutation was absent in 200 normal male individuals analyzed to look at its occurrence in general population. In vitro androgen-binding and transactivation assays showed that the mutation resulted in approximately 65% loss of ligand binding and almost complete loss of transactivation function. Complete AIS in this individual was due to a G708E substitution in the AR protein.