Complete Androgen Insensitivity Research Articles

056 Gonadal tissue preservation for a girl with complete androgen insensitivity syndrome

Objectives: To present a case of gonadal tissue cryopreservation in a patient with Complete Androgen Insensitivity Syndrome (CAIS).

053 Totally extraperitoneal approach (TEP) for gonadectomy for differences in sex development (DSD): Report of 2 cases

Introduction: 17-β-hydroxysteroid dehydrogenase type-3 deficiency (17βHSD-3) is a rare cause of 46XY DSD. Gonadectomy is often offered to prevent further virilization and to continue living in a female gender role [ [1] Chuang J. Vallerie A. Breech L. Saal H.M. Alam S. Crawford P. Rutter M.M. Complexities of gender assignment in 17β-hydroxysteroid dehydrogenase type 3 deficiency: is there a role for early orchiectomy?. Int J Pediatr Endocrinol. 2013; 12: 15 Crossref Google Scholar ]. Both laparotomic and laparoscopic approaches to gonadectomy had been described for DSDs [ [2] Dellaportas D. Chatzipapas I. Pandraklakis A. Michala L. Laparoscopic bilateral gonadectomy and inguinal hernia repair with mesh for complete androgen insensitivity syndrome: A case report. J Pediatr Adolesc Gynecol. 2019; 32 (Epub 2019 Feb 27): 443-445 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ]. Retrieval and removal of testes located in the inguinal canal can be technically challenging and requires collaboration with surgical colleagues. Cases: We present 2 cases of DSD with 17βHSD-3. One of them is 16 years old, while the other one is 20 years old. Both cases presented with amenorrhea and clitoral enlargement, whereas the second case also had deepening of voice. Blood tests for both revealed elevated testosterone and androstenedione. MRI findings were similar showing bilateral gonads located in the inguinal canals. Genetic tests revealed 46 XY karyotype and HSD17B3 gene mutation. Both subjects opted to continue with a female gender role and opted for gonadectomy to prevent further virilization. Gonadectomy was performed with a totally extraperitoneal laparoscopic approach. An infraumbilical incision was made and care was taken to enter the potential space above the rectus sheath. Then a balloon was placed via the port to distend the extraperitoneal space and then the laparoscope was inserted. Secondary ports at the suprapubic region and the left lower quadrant were placed. The gonads were mobilized and gonadectomy performed. Gonadectomy was successfully performed for the first case, but for the second case, there was failure to mobilize the gonad and operation was completed with inguinal incisions. Conclusion: Totally extraperitoneal laparoscopic approach for hernia repair is a well-established technique familiar to surgeons [ [3] McKernan J.B. Laws H.L. Laparoscopic repair of inguinal hernias using a totally extraperitoneal prosthetic approach. Surg Endosc. 1993; 7: 26-28 Crossref PubMed Scopus (264) Google Scholar ]. This was the first time the TEP approach has been described for gonadectomy for DSD. By cooperating with surgeons who has abundant experience in operating in this region, one can allow utilization of techniques which were already commonly used. It raises the importance as gynecologists, we should be mindful of technological advances in other specialties as with other aspects of DSD, collaboration with other specialties may lead to advances in patient management.

Oocyte Donation and Surrogate Pregnancy-Fertility Options and Challenges, Possibilities and Opportunities for a Patient with Complete Androgen Insensitivity Syndrome

We wish to present a very unusual case of an interesting fertility in a known case of complete androgen insensitive syndrome.

Attitudes toward fertility-related care and education of adolescents and young adults with differences of sex development: Informing future care models

Adolescents and young adults (AYA) with differences of sex development (DSD) face many challenging healthcare decisions. Fertility preservation is an emerging but experimental option for AYA with DSD. Optimal counseling regarding future fertility options has not yet been defined for this population. To examine the fertility-related attitudes and experiences of AYA with DSD to inform future care needs. Semi-structured interviews were conducted from 2015 to 2018 with AYA with a DSD diagnosis who were seen in our multidisciplinary clinic. Topics covered included attitudes toward fertility and family building, fertility-related communication, and perspectives on fertility-related education and decision-making. Qualitative content analysis was performed using an inductive and deductive approach. Eight AYA (median age 17 years, range 14-28) with various DSD diagnoses (Mayer-Rokitansky-Küster-Hauser syndrome, complete androgen insensitivity syndrome, congenital adrenal hyperplasia, and 46, XY DSD unspecified) participated. AYA were open to many options related to family building and fertility preservation, desired full disclosure of information, and recognized the importance of an age-related progression to autonomy in decision-making. Spanning all topics, the following were salient: 1) diversity of attitudes and care preferences amongst participants, 2) evolution of these attitudes and preferences over time, and 3) an emphasis on individualization of education and care (Fig.1). This qualitative study provided information on the fertility-related experiences and attitudes of AYA with DSD. Prior studies have shown a diversity of patient and parent preferences in many aspects of DSD research as well as low rates of fertility-related education and satisfaction therefrom. The knowledge gained from this study can be used to guide individualized and compassionate education and care surrounding the complex and evolving topic of fertility. This study is limited by interviews being conducted prior to the implementation of our DSD-specific gonadal tissue cryopreservation protocol. Despite this, the fertility-related patient experiences and attitudes prior to protocol implementation are important to present. The results from the preliminary analysis of these data were used to inform a new, ongoing qualitative study to explore the patient experience with fertility preservation in a more targeted fashion. The perspectives on fertility and related healthcare experiences of AYA with DSD demonstrated openness to many family-building options, a desire for full disclosure of information, care needs that evolved over time, and a recognition of the importance of eventual autonomy in decision-making. A flexible and individualized approach by the provider can optimize fertility-related healthcare experiences for AYA with DSD.

A Case of Familial Complete Androgen Insensitivity Syndrome- Baby with Three Mothers and the Daughter shows the Mother - Challenges and Threats in Advanced Assisted Reproduction Technology

We wish to present a very unusual case of an inheritance of a very rare disease, familial complete androgen insensitivity syndrome, in a baby girl with three mothers and the mother being a known case of complete androgen insensitive syndrome.

Management of Retained Intraabdominal Gonads in Complete Androgen Insensitivity

A 22 year-old 46XY patient raised female diagnosed with complete androgen insensitivity (CAIS) at adolescence, after workup for amenorrhea, presented for routine care. Intraabdominal gonads were retained at patient and family choice at diagnosis.

PD02-12 THE RISK OF GONADAL MALIGNANCY IN PATIENTS WITH ANDROGEN INSENSITIVITY SYNDROME

You have accessJournal of UrologyCME1 May 2022PD02-12 THE RISK OF GONADAL MALIGNANCY IN PATIENTS WITH ANDROGEN INSENSITIVITY SYNDROME Pratik Kanabur, Soo Jeong Kim, Sagar Patel, Lefkothea Karaviti, and Paul F. Austin Pratik KanaburPratik Kanabur More articles by this author , Soo Jeong KimSoo Jeong Kim More articles by this author , Sagar PatelSagar Patel More articles by this author , Lefkothea KaravitiLefkothea Karaviti More articles by this author , and Paul F. AustinPaul F. Austin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002517.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Androgen Insensitivity Syndrome (AIS) is a rare condition caused by a mutated androgen receptor, with varying penetrance levels. Patients often have undescended gonads, and thus an increased risk for developing germ cell tumors. Optimal gonad management in these patients is controversial. We aim to review the outcomes of gonad management in a large series of AIS patients at a single center. METHODS: A retrospective review was performed of patients with a diagnosis of AIS seen at a freestanding children’s hospital (2010-2020). Various patient factors including age at presentation, phenotypic gender, and subtype of AIS were collected. Management strategies including presence of imaging and tumor markers (AFP, HCG, LDH), surgical intervention, and length of follow-up were also evaluated. We also determined the rate of malignancy in gonadectomy specimens. RESULTS: 24 patients were included, 6 (25%) with partial AIS (PAIS) and 18 (75%) with complete AIS (CAIS). Age at evaluation ranged from 0 to 22 years. Of patients with PAIS, median age at presentation was 15 years. 3 (50%) had imaging of gonads and 2 (33%) had tumor markers obtained, all of which was negative for malignancy. 3 patients (50%) had surgical intervention (1 gonadopexy and 2 bilateral gonadectomy). One patient who underwent bilateral gonadectomy at 15 years of age was diagnosed with T1 dysgerminoma; there was no recurrence or progression of disease after 5 years of follow-up. Average length of follow-up was 2.9 years. Of patients with CAIS, median age at evaluation was 10.5 years. 12 (75%) had imaging of gonads and 3 (16.7%) had tumor markers obtained, all of which was negative for malignancy. 15 patients (83%) had surgical intervention (1 gonadopexy, 4 unilateral gonadectomy, 10 bilateral gonadectomy). One patient who underwent bilateral gonadectomy at 22 years of age had germ cell neoplasia in situ. She did not develop recurrence or progression after 6 years of follow-up. Average length of follow-up was 2.8 years. CONCLUSIONS: The majority of patients with CAIS and PAIS underwent surgical gonadectomy, and at younger ages (<5). In patients who had a gonadectomy after 12 years of age, over 25% of patients had a malignancy in the specimen, but were able to be treated with surgery alone. Imaging and tumor markers did not diagnose any malignancies. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e40 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Pratik Kanabur More articles by this author Soo Jeong Kim More articles by this author Sagar Patel More articles by this author Lefkothea Karaviti More articles by this author Paul F. Austin More articles by this author Expand All Advertisement PDF DownloadLoading ...

W235 A 31-year-old woman with complete androgen insensitivity syndrome

W235 A 31-year-old woman with complete androgen insensitivity syndrome

COMPLETE ANDROGEN INSENSITIVITY SYNDROME : A CASE REPPORT AND REVIEW OF LITERATURE

Complete androgen insensitivity syndrome or testicular feminization syndrome is the most common form of male pseudohermaphrodism, caused by a failure of androgen receptor binding. Patient with male genotype 46 XY, has a female morphotype with well developed external sexual organs. We report the case of two young patients aged 23 and 21 with a TF syndrome discovered during the exploration of primary amenorrhea. A bilateral orchiectomy was performed with institution of estrogen-progestogen hormone treatment.

Complete androgen insensitivity syndrome caused by a novel mutation in the androgen receptor gene and its mechanism

Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic disease characterized by disorders of sex development, commonly caused by mutations of the androgen receptor (AR) gene. Herein, we identified a novel hemizygous mutation (c.2118T > A, p. Asn706Lys) of AR resulting in complete androgen insensitivity syndrome (CAIS) in twins. This missense mutation contributed to significantly decreased mRNA transcription and protein expression. In addition, structure model analysis showed that Asn706Lys resulted in loss of hydrogen bond with Asp891 and reduced protein stability. Furthermore, the mutant AR failed to bind to ligand due to the loss of hydrogen bond with dihydrotestosterone (DHT). This disrupted the translocation of AR protein from cytoplasm to nucleus after hormone stimulation. Our findings firstly demonstrated the novel mutation of c.2118T > A in AR directly caused CAIS. This contributed to expanding the AR mutational spectrum and revealed the pathogenic mechanism of AIS, as well as facilitating precise diagnosis and genetic counseling.

Management of large gonadal cyst at diagnosis of complete androgen insensitivity syndrome (CAIS)

Background: Recent clinical practice for management of complete androgen insensitivity syndrome (CAIS) has shifted away from strict recommendations for gonadectomy following puberty, and now emphasizes shared decision-making including risk/benefit discussion of deferred gonadectomy with surveillance. However, there are no clearly defined guidelines for optimal surveillance or timing of gonadectomy. Biopsy or gonadectomy is recommended if imaging reveals abnormalities with a retained gonad.

Metabolic effects of estradiol versus testosterone in complete androgen insensitivity syndrome

PurposeTo study differences in metabolic outcomes between testosterone and estradiol replacement in probands with complete androgen insensitivity syndrome (CAIS).MethodsIn this multicentre, double-blind, randomized crossover trial, 26 women with CAIS were included of whom 17 completed the study. After a two-months run in phase with estradiol, probands either received transdermal estradiol followed by crossover to transdermal testosterone or vice versa. After six months, differences in lipids, fasting glucose, insulin, hematocrit, liver parameters and blood pressure between the treatment phases were investigated.ResultsLinear mixed models adjusted for period and sequence did not reveal major group differences according to treatment for the investigated outcomes. In each treatment group, there were however significant uniform changes in BMI and cholesterol. BMI increased significantly, following six months of estradiol ( + 2.7%; p = 0.036) as well as testosterone treatment ( + 2.8%; p = 0.036). There was also a significant increase in total ( + 10.4%; p = 0.001) and LDL-cholesterol ( + 29.2%; p = 0.049) and a decrease in HDL-cholesterol (−15.8%; p < 0.001) following six months of estradiol as well as six months of testosterone treatment (total cholesterol: + 14.6%; p = 0.008; LDL-cholesterol: + 39.1%; p = 0.005, HDL-cholesterol: −15.8%; p = 0.004). Other parameters remained unchanged.ConclusionTransdermal estradiol as well as testosterone treatment in women with CAIS results in worsening in lipid profiles. Given the relatively small sample size, subtle group differences in other metabolic parameters may have remained undetected.

Evaluating complete androgen insensitivity syndrome with a multimodal sonography system.

Evaluating complete androgen insensitivity syndrome with a multimodal sonography system.

Androgen Insensitivity Syndrome with Bilateral Cryptorchidism and Seminoma in Tibet:Report of One Case

Androgen insensitivity syndrome(AIS)with bilateral testicular malignant transformation is very rare,and its diagnosis should be based on clinical manifestations,physical examination,serological findings,karyotype analysis,and pathological findings.This study reported a case of complete androgen insensitivity syndrome among Tibetan in Tibet.It took 17 years from the discovery of congenital absence of uterus to bilateral pelvic mass resection.Pathological examination confirmed that bilateral pelvic space occupying lesions were dysplastic testicular tissue with seminoma and sertoli cell adenoma-like nodules.This study summarized the clinicopathological features to deepen the understanding of the disease.

Complete Androgen Insensitivity Syndrome: A Case Report and Literature Review

Background: Androgen insensitivity syndrome (AIS) is a rare disease caused by mutations in the AR gene. This results in resistance to the actions of androgen as well as a female karyotype with 46 XY. Anatomically, individuals with AIS lack both a uterus and ovaries. Patients and clinical data: In this case report, we detail a 32-year-old patient with complete AIS (CAIS). This female patient with 46 XY genotype came to our hospital seeking surgical removal of bilateral testis. The subsequent medical history, clinical examination, imaging, and endocrine outcomes from this patient were collected and are presented here. Conclusion: Individuals with CAIS need appropriate care from doctors and support from their families. The diagnosis, treatment, and management of CAIS also require a multidisciplinary approach.

Whole exome sequencing reveals copy number variants in individuals with disorders of sex development

Complete androgen insensitivity syndrome (CAIS), where 46,XY individuals present as female, is caused by variants in the androgen receptor gene (AR). We analyzed the DNA of a patient with suspected CAIS using a targeted gene sequencing panel and whole exome sequencing (WES) but did not detect any small nucleotide variants in AR. Analysis of WES data using our bioinformatics pipeline designed to detect copy number variations (CNV) uncovered a rare duplication of exon 2 of AR. Using array comparative genomic hybridization, the duplication was found to span 43.6 kb and is predicted to cause a frameshift and loss of AR protein. We confirmed the power of our WES-CNV detection protocol by identifying pathogenic CNVs in FSHR and NR5A1 in previously undiagnosed patients with disorders of sex development. Our findings illustrate the usefulness of CNV analysis in WES data to detect pathogenic genomic changes that may go undetected using only standard analysis protocols.

Parents of Children With Newly Diagnosed Disorders of Sex Development Identify Major Concerns: A Qualitative Study

ObjectivesTo develop a conceptual framework to understand and define the impact of DSD diagnosis and management from the perspective of parents of recently diagnosed children. MethodsSemi-structured interviews were conducted with parents of children diagnosed with 46 XX, 46 XY, or chromosomal DSD including complete or partial androgen insensitivity, congenital adrenal hyperplasia, or 5-alpha reductase deficiency. Analysis was completed using content analysis with an inductive approach by three coders. ResultsParents of 6 patients agreed to be interviewed, consistent with saturation points for prior similar studies; a total of 16 recurring themes were identified which were further grouped by similarity and categorized into 1 of 3 meta-themes: a) personal impact (effect of diagnosis on parents psyche, happiness, gender/sexual identity, anatomic function, mental health), b) family impact (relationships with parents/siblings, parental guilt); and c) societal impact (bullying, need for secrecy, future desirability, societal openness to DSD individuals). ConclusionsPersonal, family, and societal concerns amongst parents following a DSD diagnosis have significant potential psychosocial impacts for both parents as well children. The nexus between these categories provides a framework for approaching diagnosis and management of DSD and has implications for patients, families, and clinicians. Improved resource allocation, education, and clinical tools conceived through this framework may considerably alleviate potent psychosocial stressors for parents of children born with DSD.

Malignant phyllodes with bilateral leydig cell hyperplasia of testes in a case of complete androgen insensitivity syndrome- A rare case report

Complete androgen insensitivity syndrome (CAIS) is an AIS condition that results in the complete inability of the cell to respond to androgens. Individuals with complete androgen insensitivity syndrome are born phenotypically female, without any signs of genital masculinization, despite having a 46,XY karyotype. Case report We present a case of a 66 year nulliparous female with primary amenorrhea with complaints of bilateral inguinal mass for 5 years and bilateral breast lump for 3 years. Patient developed a sudden increase in the size of left breast lump. An MRI chest revealed a large 15.4x11.5cm heterogeneous mass in the left breast and 9.9x6.1 cm lobulated mass in the right breast. MRI abdomen and pelvis revealed soft tissue structures in the bilateral inguinal region near the deep inguinal ring with blind ending vaginal tract and absent uterus and ovaries. karyotyping revealed 46XY. We received specimens of left MRM, right lumpectomy and bilateral inguinal mass. Left MRM measured 32x20x12cm. On the cut section showed a large tumor with variegated appearance. Right lumpectomy showed a tumor with leaf-like appearance was noted. Bilateral inguinal mass measured 5x3x3 cm each, cut section showed yellowish nodules. Histopathological examination reveals malignant phyllodes of left breast with benign phyllodes of the right breast and leydig cell hyperplasia of bilateral testes. Conclusion This is the first case reported of malignant phyllodes in a case of complete androgen insensitivity syndrome with bilateral leydig cell hyperplasia of testes.

Disorders of Sexual DevelopmentPathological Profile of 45 Cases at a Tertiary Care Centre

Disorders of Sexual Development (DSD) are rare syndromes, which show congenital discordance between chromosomal, gonadal and phenotypic sex. A retrospective analysis was performed to analyse the histopathological profile and spectrum of a large number of cases of DSD received at a tertiary care center. There were 45 cases of DSD encountered over a period of eight years, from January 2012 to December 2020. Detailed evaluation of each case with respect to demographic details, clinical features, imaging and pathology was done. All cases were classified as per Chicago Consensus Classification (2006) modified in 2010. The 46, XY DSD were the most common 26 (57.78%) cases, followed by sex chromosomal DSD 14 (31.1%) and 46,XX, DSD 5 (11.1%). Among 46, XY DSD, Complete Gonadal Dysgenesis (CGD) (Swyer syndrome) and Complete Androgen Insensitivity Syndrome (CAIS) had the highest number of cases, with 30.77% cases of each. Among 46XX, DSD, cases of ovotesticular DSD amounted to 80%. In sex chromosomal DSD, cases of Mixed Gonadal Dysgenesis (MGD) amounted to 78.57%. Out of 45 cases studied in this series, 20% cases showed neoplasms, of which 8.89% were malignancies. Nine out of 45 (20%) patients had neoplasms, out of which 5 (55.6%) had benign tumours while 4 (44.4%) had malignant tumours. Five patients had gonadoblastoma and three of these had coexistent dysgerminoma. Two patients had sertoli cell adenomas, one seminoma and one serous cystadenoma. Frequent clinical features noted were primary amenorrhea seen in 25 (55.5%) cases and ambiguous genitalia seen in 18 (40%) cases, while the most common location of gonad was intra-abdominal in 30 (66.6%) cases. Streak gonads were seen in CGD, MGD and Turner’s syndrome. Malignant germ cell tumours were seen in CGD and CAIS. Early diagnosis, good histopathology and follow-up are essential in the management of DSDs

A young infant with complete androgen insensitivity syndrome

Complete androgen insensitivity syndrome (CAIS) is a rare X-linked recessive disorder resulting from maternally inherited or de novo mutations involving the androgen receptor (AR) gene. The AR is a vital steroid hormone receptor that has a critical role in male sexual differentiation and development and preservation of the male phenotype. The diagnosis of CAIS is based on the presence of female external genitalia in an individual with 46, XY karyotype having normally developed but undescended testes and target tissue unresponsiveness to androgen. Our case presented at the age of 2 months with asymmetric labia majora with bilateral labial mass. Ultrasonography revealed absence of female internal genital organs and presence of testes at labial folds. The child was found to have 46, XY karyotype. BIRDEM Med J 2022; 12(1): 74-77