Complete Androgen Insensitivity Research Articles

Congenital uterovaginal abnormalities, it's embryogenesis, surgical management and clinical implications.

ObjectiveCongenital Mullerian duct malformations are a challenging group of conditions for surgeons and need surgical experience and skill. Accordingly, the aim of this study is to present the diagnosis, surgical management, and clinical implications of congenital uterovaginal abnormalities.MethodsBetween 1980 and 2015, 8 patients with congenital uterovaginal abnormalities were diagnosed. In one patient a unique case of an unusual horseshoe shaped double uterus communicating via a transverse canal along with agenesis of the cervix and vagina was noted, and utero-vaginal agenesis was diagnosed in 6 patients. Complete androgen insensitivity syndrome with its female phenotype associated with bilateral testicular tissue in the inguinal canal with an accompanying absence of the ovaries, uterus, uterine tubes, vagina, and an imperforate hymen, was diagnosed in one patient. Clinical examination of all the patients revealed well-developed secondary sexual characteristics. A modified McIndoe vaginoplasty procedure was the surgical treatment common to all patients to treat vaginal agenesis. The surgery was performed by a consultant (Dr. K.G. Paul) using the standardized surgical technique.ResultsAn unusual Mullerian duct anomaly, uterus bicornisacollis, was successfully corrected by uteroplasty and a new cervix was constructed. Complete vaginal agenesis was corrected by a modified McIndoe vaginoplasty technique. None of the patients had any significant post-operative complications.ConclusionKnowledge of congenital uterovaginal abnormalities diagnosed in this study is essential for surgeons, clinical anatomists, radiologists, and morphologists who may increase the success of their diagnostic evaluations and surgical approaches to the region.

Computational analysis of androgen receptor (AR) variants to decipher the relationship between protein stability and related-diseases

Although more than 1,000 androgen receptor (AR) mutations have been identified and these mutants are pathologically important, few theoretical studies have investigated the role of AR protein folding stability in disease and its relationship with the phenotype of the patients. Here, we extracted AR variant data from four databases: ARDB, HGMD, Cosmic, and 1,000 genome. 905 androgen insensitivity syndrome (AIS)-associated loss-of-function mutants and 168 prostate cancer-associated gain-of-function mutants in AR were found. We analyzed the effect of single-residue variation on the folding stability of AR by FoldX and guanidine hydrochloride denaturation experiment, and found that genetic disease-associated mutations tend to have a significantly greater effect on protein stability than gene polymorphisms. Moreover, AR mutants in complete androgen insensitivity syndrome (CAIS) tend to have a greater effect on protein stability than in partial androgen insensitive syndrome (PAIS). This study, by linking disease phenotypes to changes in AR stability, demonstrates the importance of protein stability in the pathogenesis of hereditary disease.

A non-surgical approach to 46,XY differences in sex development through hormonal suppression at puberty: a single-center case series study.

We aim to report outcomes and safety with hormonal suppression to facilitate gonadal preservation in a select group of patients with 46,XY differences in sex development (DSD) who are raised and identify as female yet have diagnoses with potential for androgenization at puberty. We performed a retrospective review of the past 10 years of DSD patients treated by a multidisciplinary program. Inclusion criteria were 46,XY DSD, female sex of rearing, risk of androgenization at puberty, and plan for hormonal suppression at puberty. Patients on hormonal suppression had at least 6 months of follow-up from initiation. We excluded those with complete gonadal dysgenesis or complete androgen insensitivity. Four patients met inclusion criteria. Initial evaluation by DSD team was at a mean age of 6.6 years (3 weeks-16 years). All patients were evaluated in a coordinated multidisciplinary clinic. The diagnoses are listed in Table 1. Mean follow-up was 5.7 years (1.2-10.9 years). One patient presented as an infant, and is being monitored until Tanner stage 2 and/or serum hormonal evidence to initiate hormonal suppression. Three patients have been receiving hormonal suppression for 1.4 years (1.1-1.9 years) without side effects or complication. Three patients were initiated with estrogen replacement to promote desired breast development. At last follow-up, all patients had retained their gonads, all have female gender identity with no reported gender dysphoria, and no progression of androgenization. In our initial experience, gonadal preservation with hormonal suppression is a tool in multidisciplinary management of select DSD patients with female gender identity with conditions associated with androgenization at puberty. Patients' growth, bone health, and overall psychosocial well-being will need to be monitored closely.

Complete Androgen Insensitivity Syndrome Presenting as Inguinal Hernia—a Diagnostic Dilemma

Inguinal hernia is the most common type of groin hernia in females. In comparison, complete androgen insensitivity syndrome (CAIS) is a rare genetic disease that can present with an inguinal swelling containing testis in a female. We report a case of a 42-year-old phenotypic female who presented with swelling in the right inguinal region and primary amenorrhea. The swelling showed impulse on coughing, and working diagnosis of incarcerated hernia was made. Investigations revealed the absence of uterus, cervix, and fallopian tube with presence of right ovary in right inguinal canal and left ovary in intra-abdominal region. Chromosome analysis revealed XY karyotype, thereby confirming the diagnosis of CAIS. On exploration, firm testis-like structure was detected in the right inguinal canal, and gonadectomy with herniotomy was done. However, opposite side gonadectomy was refused by the patient. Histopathologically, excised mass showed atrophic testis with sertoli cell adenoma.

Generation of human induced pluripotent stem cell (SKLRMi001-A) from a patient with partial androgen insensitivity syndrome (PAIS).

Androgen receptor (AR) is essential for maintaining normal spermatogenesis and male fertility, and its mutation can cause complete or partial androgen insensitivity syndrome (CAIS or PAIS) in patients. We established an induced pluripotent stem cell line (SKLRMi001-A) from a PAIS patient with AR mutation (c.2710G>A; p. V904M). The iPSC line expressed pluripotency markers, retained normal karyotype, carried the mutation, showed capability of differentiating into three germ layers and was absence of mycoplasma infection. The iPSC line will help to further elucidate the pathogenic mechanisms of AR mutation, and benefit treatment for PAIS in the future.

Genital Ambiguity and Challenges in Gender Assignment

This is a case presentation involving two siblings of four and six years of age with female gender identity from a neighboring country with 46,XY DSD and a 20 years old youngster from Northwest Ethiopia with an alleged male sex but with a 46,XX DSD; but definitely all the three with obvious ambiguous external genitalia. The 46XX, DSD with Congenital Adrenal Hyperplasia (CAH) generated more challenges as opposed to the siblings who were diagnosed to have Complete Androgen Insensitivity Syndrome (CAIS). The case presentations are unique as they were referred for sex identification by physicians unlike the usual late complaints of patients with primary amenorrhea or absence of menarche, failure to attain penetrative vaginal sexual intercourse or primary infertility. It was evident that the role of the parents, grandparents, relatives and the healthcare professionals is very much impacting in the sex assignment of the clients, although the final preferential gender choice is made by the individual himself. The atypical external genitalia, contrary to the sex of rearing so far, are the hallmark of the abnormality and source of confusion of the clients under investigations. An early and thorough neonatal physical examination and random checkups of pediatric age groups underscores the complex issues of the subsequent multidisciplinary approach towards the sex assignment. The situations glare the psychosexual and physical development of those involved and the undesirable consequences in their respective families, relatives and their respective societies where beliefs, religion and culture play significant role in the social upbringing of the individual. The main objective of the presentation is to increase the degree of awareness among healthcare professionals of the existence of such congenital anomalies in the communities and is also intended to contribute to the national and world literature.

OR27-02 An Exploration of Novel Clinical Benchmarks for Assessing the Practice of Gonadectomy in Conditions Affecting Sex Development - on Behalf of the I-DSD Consortium

Introduction: Although the practice of gonadectomy in the field of differences/disorders of sex development (DSD) has undergone intense scrutiny, objective knowledge regarding current practice of gonadectomy is lacking in conditions affecting sex development. Methods: The International DSD Registry (www.I-DSD.org) was examined for clinical information reported by the DSD specialist centre on age at presentation, year of birth, diagnosis, karyotype, sex of rearing and age at gonadectomy in all cases over the age of 16 years at the time of search and who had a disorder of androgen action or synthesis, gonadal dysgenesis or a non-specific DSD.Results: Of the 3,618 cases available in the registry, 757 (21%) met the inclusion criteria and data regarding gonadectomy status were available in 668 (88%) from 44 participating centres. Of these, 248 (37%) with a median age of 24 years (range 17, 75) were registered as male and 420 (63%) with a median age of 26 years (16, 86) were registered as female. Gonadectomy was reported from 36 centres in 351 of these 668 cases (53%) of whom 302 (86%) had a 46 XY karyotype. Females were more likely to undergo gonadectomy (n=311, p<0.0001) and the most common diagnoses were complete androgen insensitivity syndrome (n=161, 24%) and partial gonadal dysgenesis (n=94, 14%). Of the 351 cases, the primary indication for gonadectomy was reported in 268 (76%) cases and included mitigation of tumourigenesis risk in 172 (64%), conformity to sex assignment in 74 (28%) and another indication in 22 (8%). Gonadectomy was bilateral in 295 (84%), unilateral in 16 (5%) and unknown in 40 (11%). The median ratio for age at first presentation to age at gonadectomy in those who presented before the age of 5 years and those who presented after the age of 10 years was 0.1 (range) and 0.9 (range), respectively (p<0.0001). Of the 351 cases, 17 (5%) had undergone a gonadectomy before their first presentation to the specialist centre and these cases were distributed across 9 of the 36 centres. Conclusions: Not only does the rate of gonadectomy vary according to underlying diagnosis and sex of rearing, it also seems that there is a variable discrepancy between the age at presentation and age at gonadectomy. The use of this objective marker to identify trends in practice may improve our understanding of the causes of variation.

SUN-038 Social and Psychological Aspects of Partial Androgen Insensitivity Syndrome, Therapeutic Challenges

Background: Partial Androgen Insensitivity Syndrome (PAIS) is a rare congenital condition with incongruence of chromosomal, gonadal and phenotypic sex and classified as differences of sex development. Distinct from complete Androgen Insensitivity by the presence of ambiguous genitals in a 46, XY individual with normal testis development and partial responsiveness to androgens. Clinical Case: 18 years phenotypic female presented with primary amenorrhea and ambiguous genitalia with poor secondary sexual characteristics after puberty. Born out of a consanguineous marriage, normal vaginal delivery conducted by midwife at home in a small village, who informed a female with ambiguous genital though. Since childhood she uses to dress up in female attire. She has 5 siblings, two brothers and three sisters, one year back she got engaged to her distant cousin and was about to get married when one of her younger sister now 8 years having similar problem alarmed family to report before the wedlock.Vitals:Weight 55kg,Height 167cm,Physical, biochemical, chromosomal testing and imaging revealed:micropenis 3cm(N=8cm) with hypospadias, a small blind vaginal orifice, hormones within normal male ranges, Karyotype: XY, MRI revealed no female internal organs or prostate gland, left testis seen in partly formed scrotal sac (4.6x2.5cm) right in superficial inguinal region (2.7x1.9cm),normal testes size(4x3cm), bilateral cavernous tissue,respectively. Findings suggested phenotypic female with PAIS. Further investigations could not be carried out due to poor affordability and non-availability of Genetic testing facility. Management: Male gender was preferred (after discussion with urologist and consent of the patient and the family) Assigning the gender, health-related quality of life (QoL), social and psychological well-being, and affective disorders, like fertility and sexual functions in PAIS were discussed. Psychometric data was obtained through psychological questionnaires: Beck Depression Inventory & Hospital Anxiety and Depression Scale revealed moderate depression. An important pre-decision analysis regarding the potential impact of clinical decisions such as the type and timing of genital surgeries on patient’s life is missing due to absence of a multidisciplinary team for counseling and decision making. Conclusion: After spending 18.yrs as a phenotypic female the patient and her family experienced considerable emotional distress. In our culture and society these types of cases are seldom reported. We as medical professionals need to be sensitive to the social and psychological wellbeing of patients so that they can be settled and acceptable in their part of the world.

MON-066 17B-hydroxysteroid dehydrogenase Type 3 Deficiency: An Under-Recognized Cause of 46,XY DSD in the United States?

Title: 17β-hydroxysteroid dehydrogenase type 3 deficiency: An under-recognized cause of 46,XY DSD in the United States? Introduction: The 17β-hydroxysteroid dehydrogenase type 3 (17BHSD3) enzyme, expressed in the testes, converts androstenedione (A) to testosterone (T). 17BHSD3 deficiency causes a 46,XY difference of sex development (DSD), or intersex condition, characterized by lack of prenatal virilization followed by marked virilization at puberty due to peripheral conversation of A to T by other 17BHSD isoenzymes. Diagnosis is suspected with an abnormal T:A ratio of <0.8 and confirmed by HSD17B3 sequencing and deletion/duplication analysis. 17BHSD3 deficiency may present similarly to complete or partial androgen insensitivity syndrome (CAIS, PAIS) due to undervirilization in infancy, and to 5α-reductase deficiency due to virilization during puberty. Previously, only 12 cases of this autosomal recessive disorder have been reported in the US. We report 3 cases of 17BHSD3 deficiency diagnosed at a single pediatric center in the US. Clinical Cases: Patient A had atypical genitalia at birth and a presumed diagnosis of PAIS though sequencing of AR was normal. He underwent multiple genital surgeries throughout childhood, had significant psychiatric and behavioral concerns, and was referred to our multidisciplinary clinic at age 16 years. Additional diagnostic testing revealed a T:A ratio of 0.29 consistent with 17BHSD3 deficiency; confirmatory genetic testing was deferred per family preference.Patient B was noted to have testicular tissue present at age 3 years during an inguinal hernia repair and was diagnosed with CAIS. She presented to our institution at age 14 years with clitoromegaly. T:A ratio was 0.29 and genetic testing revealed a pathogenic splice site variant in HSD17B3. She requested gonadectomy due to unwanted virilization inconsistent with her female gender identity. Following gonadectomy at age 16 years, she began estrogen treatment and vaginal dilations.Patient C presented to our institution at age 18 years with pubertal delay and primary amenorrhea. She was noted to have palpable gonads and clitoromegaly. Evaluation revealed a 46,XY karyotype and a T:A ratio of 0.32. She was raised as a girl and identified as female. She requested gonadectomy to avoid further virilization, after which she began estrogen for pubertal induction. She deferred confirmatory genetic testing. Conclusions: Previous studies noted 17BHSD3 deficiency to be rare in the US, but the presence of 2 suspected and 1 confirmed diagnoses at a single US institution suggests it is likely more common and may be misdiagnosed as other types of DSD. Differentiating 17BHSD3 deficiency from other causes of 46,XY DSD is essential to inform accurate counseling about sex designation, gender identity, gonadal function, malignancy risk, potential fertility and heritability.

SUN-036 Evaluation of Gender Experience Among Individuals with Isolated GnRH Deficiency Compared to Controls

Background: Sex hormones play a role in gender identity development. For example, 46,XY individuals with complete androgen insensitivity typically have a female gender identity. Isolated GnRH deficiency (IGD) leads to hypogonadism due to decreased GnRH-induced gonadotropin production. It is unknown if decreased sex hormone exposure leads to differences in gender identity among individuals with IGD compared with the general population. Our objective was to determine if the gender identity in subjects with IGD differs from controls.Methods: We distributed a validated questionnaire; the Gender Identity/Gender Dysphoria Questionnaire for Adults and Adolescents (GIDYQ-AA) (1), to IGD participants who previously enrolled in a phenotyping study. Subjects also provided their age, sex assigned at birth (SAAB), gender and information about their condition and treatment. Group survey scores are expressed as mean ± SD. IGD subject scores were compared with control data (Student’s t-test) obtained from a validation study for the GIDYQ-AA (2).Results: Out of 79 subjects who were contacted, 8 males (M) assigned at birth and 7 females (F) assigned at birth chose to participate and one person actively declined. Average age was 30 y for F and 28 y for M. At the time of the study, all subjects were on hormone supplementation except for one F. A score of 5 indicates a gender identity congruent with SAAB. Among F, mean scaled IGD score was 4.73 ± 0.29 vs. controls (4.8 ± 0.28, n=57; not significant (ns)), and for M it was 4.62 ± 0.52 vs. controls (4.82 ± 0.24, n=37; ns). One female identified as “non-gendered”, one male identified as “intersex/DSD” (14% of respondents), one female did not respond and gender was congruent with SAAB in the remainder. The lowest mean score for an individual question for the IGD F group was in response to whether they felt satisfied being a woman and for the IGD M group, it was in response to whether they felt they were a real man.Conclusions: Men and women with IGD did not show a significant difference in their gender identity compared with controls, and gender was found to be congruent with SAAB for the majority. However, the individual question responses and the self-described gender in this small cohort may suggest that there are differences in how some individuals with IGD experience their gender development. We speculate that this may be related to how they perceive the differences in physical development that they experienced related to their condition. Larger studies in participants with IGD and other disorders that alter sex hormone production/effect are necessary to further understand the relationship between decreased sex hormone exposure during critical developmental periods and gender identity development.

Disorders of sexual development with XY karyotype and female phenotype: clinical findings and genetic background in a cohort from a single centre.

46, XY disorders (or differences) of sex development (DSD) are a group of clinical conditions with variable genetic background; correct diagnosis is often difficult, but it permits to optimize the management. The aim of this study is to identify clinical and genetics features of a group of women with 46, XY DSD to define some issues characterizing people with 46, XY DSD in Italy. Retrospective analysis of girls and women with 46, XY DSD and female phenotype evaluated between year 2000 and 2016, performed by anonymised database, focusing on the clinical features and management, including presentation, first diagnostic suspect, gonadal surgery and molecular diagnostic delay. A total of 84 records were collected (mean age at clinical presentation: 9.1 ± 7.9years; mean age at definitive diagnosis: 20.1 ± 15.0years). Complete androgen insensitivity syndrome was the most common diagnosis (60%). Only 12 patients (14.3%) did not receive a molecular diagnosis. Early misdiagnoses frequently occurred; diagnostic delay was 10.2 ± 11.2years, being reduced in patients presenting from 2007 to 2016. The discordance between genotypic and phenotypic sex during pregnancy or at birth determined early reason for referral in a considerable percentage (4.9%). Misdiagnosis and long diagnostic delays are present in females with 46, XY DSD in Italy, but the new genetic techniques permit faster right diagnoses in the last years. The centralization in dedicated third level units permits to reduce the number of patients without a molecular diagnosis, allowing better clinical management and appropriate genetic counselling.

Newborn with incarcerated inguinal hernia and complete androgen insensitivity syndrome

Abstract Disorders of sex development represent a large and heterogeneous group of diseases that have an important impact on physical and mental well-being of patients and their families. An early diagnosis and a multidisciplinary approach are fundamental to guarantee the highest standard of care.

Clinical, hormonal and genetic characteristics of androgen insensitivity syndrome in 39 Chinese patients

BackgroundAbnormal androgen receptor (AR) genes can cause androgen insensitivity syndrome (AIS), and AIS can be classified into complete androgen insensitivity syndrome (CAIS), partial androgen insensitivity syndrome (PAIS) and mild AIS. We investigated the characteristics of clinical manifestations, serum sex hormone levels and AR gene mutations of 39 AIS patients, which provided deeper insight into this disease.MethodsWe prospectively evaluated 39 patients with 46, XY disorders of sex development (46, XY DSD) who were diagnosed with AIS at the Department of Endocrinology of Shanghai Children’s Hospital from 2014 to 2019. We analysed clinical data from the patients including hormone levels and AR gene sequences. Furthermore, we screened the AR gene sequences of the 39 AIS patients to identify probable mutations.ResultsThe 39 AIS patients came from 37 different families; 19 of the patients presented CAIS, and 20 of them presented PAIS. The CAIS patients exhibited a higher cryptorchidism rate than the PAIS (100 and 55%, P = 0.001). There were no significant difference between the CAIS and PAIS groups regarding the levels of inhibin B (INHB), sex hormone-binding globulin (SHBG), basal luteinizing hormone (LH), testosterone (T), or basal dihydrotestosterone (DHT), the T:DHT ratio, DHT levels after human chorionic gonadotropin (HCG) stimulation or T levels after HCG stimulation. However, the hormone levels of AMH (P = 0.010), peak LH (P = 0.033), basal FSH (P = 0.009) and peak FSH (P = 0.033) showed significant differences between the CAIS group and the PAIS group. Twenty-one reported pathogenic and 9 novel AR mutations were identified. Spontaneous AR mutations were found in 5 AIS patients, and 21 patients inherited mutations from their mothers, who carried heterozygous mutations.ConclusionsForty-six XY DSD patients with cryptorchidism and female phenotypes were highly suspected of having AIS. We demonstrated that CAIS patients could not be distinguished by their hormone levels alone. Compared with PAIS patients, CAIS patients exhibited higher basal FSH, peak FSH, and peak LH hormone levels but lower AMH expression. We identified 21 reported pathogenic AR mutations and 9 novel AR mutations that led to different types of AIS. Missense mutations were the major cause of AIS and mostly occurred in exon 7 of the AR gene. These findings provided deeper insight into the diagnosis and classification of AIS and will even contributed to its clinical assessment.

Malignant Testicular Germ Cell Tumor in Late Adolescent With Androgen Insensitivity Syndrome [26B

INTRODUCTION: Androgen receptor mutations located in the X chromosome may present as several clinical disorders. When total function of the androgen receptor is loss in a male, complete androgen insensitivity syndrome develops. A phenotypically normal appearing female develops without uterus, fallopian tubes, short vagina and bilateral intraperitoneal testes. Germ cell neoplasia may develop and the risk of developing malignant germ cell tumor is approximately a 5% that gradually increases after puberty. Although gonadectomy is the actual management, there is no consensus about the specific timing for gonadectomy or risk of developing malignant germ cell tumor by age. METHODS: IRB, Consent. RESULTS: 15-year-old girl with primary amenorrhea, no relevant medical history and Tanner stage four for breast and pubic hair. Complete androgen insensitivity syndrome was diagnosed by means of transabdominal ultrasound, normal male testosterone levels and karyotype 46XY. Laparoscopic gonadectomy was performed at 18-year-old due to loss of follow up. Pathology with immunohistochemistry reported bilateral germ cell neoplasia in situ and unilateral seminoma. CONCLUSION: This case presents with an early development of a seminoma and appoints to reconsider an earlier post pubertal gonadectomy. A 30% risk of developing malignant germ cell tumor in late adulthood also supports the decision for an earlier gonadectomy. This case challenges the typical presentation of a female patient with complete androgen insensitivity syndrome, due to a clinical presentation with adequate tanner stage development. Considerations must be taken into account when dealing with a non-compliant patient, addressing the traditional timeline management to a more individualized clinical evaluation and prompt management.

A young girl with right ovarian torsion and left ovarian ectopy

BackgroundMayer-Rokitansky-Küster-Hauser (MRKHS) syndrome refers to congenital hypoplasia/aplasia of the uterus, the cervix and the upper 2/3 of the vagina, in females with normal ovaries and fallopian tubes, secondary sexual characteristics and 46 XX karyotype. This condition originates from abnormal development of Müller’s paramesonephric ducts in the early stages of embryonic development. Kidney agenesis or malformations are the most commonly associated with unilateral kidney agenesis. Ovaries may be ectopic in 16–19% of MRKHS patients. Primary amenorrhoea, due to the absence of the uterus, is the most common presentation. Female karyotype confirmation is mandatory to differentiate it from complete androgen insensitivity syndrome and 17-alpha-hydroxylase deficiency. The management of MRKHS is multidisciplinary in order to encompass psychological, medical and surgical issues.Case presentationA four-year-old girl, presented to the emergency department complaining of left groin swelling noted 2 days earlier. The patient had recently been evaluated for an episode of acute abdominal pain and vomiting, with a final diagnosis of right ovarian torsion. At that time, the ultrasound imaging was not able to identify the left kidney, the left ovary and uterus. Surgical abdominal exploration confirmed the right ovarian torsion and was not able to identify the left kidney and the left ovary. Only a remnant of the uterus was present. Therefore, the right ovary was removed, and a diagnosis of MRKHS was made. Ultrasound imaging showed a left inguinal hernia. The hernial sac consisted of a solid oval vascularized formation suggestive of an annexe. The patient underwent a surgical procedure to correct the left inguinal hernia. In the operating setting, the presence of a vascularized, ectopic ovary carrying the tuba inside the hernial sac was observed.ConclusionsIn front of a patient with ovarian torsion and anatomical features suggestive of MRKHS, both the ovaries should always be searched for, with a high suspicion threshold for extrapelvic ovary. Identifying the ectopic ovary, in this case, helped to preserve patient fertility, avoiding a possible torsion.

17β-hydroxysteroid dehydrogenase type 3 deficiency: female sex assignment and follow-up

Deficiency of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is a rare autosomal recessive 46,XY disorder of sex development (DSD). It is due to pathogenetic variants in the HSD17B3 gene. Mutated genes encode an abnormal enzyme with absent or reduced ability to convert Δ4-androstenedione (Δ4-A) to testosterone (T) in the fetal testis. Affected individuals are usually raised as females and diagnosis is made at puberty, when they show virilization. A girl with a presumptive diagnosis of complete androgen insensitivity syndrome underwent endocrine and genetic assessment. Long-term follow-up was reported. The diagnosis of 17β-HSD3 deficiency was made (stimulated T/Δ4-A ratio: 0.15; HSD17B3 gene analysis: c.277+4A>T in intron 3/c.640_645del (p.Glu214_Glu215del) in exon 9. After extensive information, parents decided to maintain female sex. Gonadal removal was performed and histological evaluation demonstrated deep fibrosis of testicular tissue. Follow-up till 8.5years of age showed somatic and neuro-psychological development fitting with the female sex. Management of a child with the rare 17β-HSD3 deficiency remains challenging. Any decision must be carefully evaluated with parents. Long-term follow-up must be warranted by a multidisciplinary DSD team to evaluate the adequacy of the choices made on quality of life in later life.

Mental health outcomes among individuals with 46,XY disorders of sex development: A systematic review.

This review summarizes research on the mental health outcomes of genetic males with a disorder of sex development (46,XY DSD). Databases were systematically searched, yielding 19 studies included in this review. Results varied widely, with mental health outcomes ranging from very poor to similar to comparison groups. A small number of studies demonstrated that patients with hypospadias or complete androgen insensitivity syndrome reported better mental health than patients with other 46,XY (DSD) diagnoses. Future studies should include larger samples of patients within a similar developmental stage, display results separately by DSD diagnosis and gender identity, and consider the potential impact of medical/surgical events on their mental health.

Induced Lactation in a Mother Through Surrogacy With Complete Androgen Insensitivity Syndrome (CAIS).

Breastfeeding offers the optimal feeding option for newborns in terms of nutritional content and reinforces mother-infant bonding. As a physiological process intrinsically linked to parturition, breastfeeding is no longer reserved for puerperal mothers. Progress in understanding the intricacies of lactogenesis and breastfeeding has further paved the way for artificially induced lactation in recent years. We describe the case of a mother through surrogacy with XY karyotype and complete androgen insensitivity syndrome who wished to breastfeed her child. Through a combination of estrogen therapy, galactagogues, and mechanical breast stimulation she was able to partially breastfeed her child for one month. This case further shifts the concept that breastfeeding is a physiological process confined to only puerperal mothers and offers an opportunity to a wider group of nontraditional mothers to take part in the unique experience of breastfeeding.

A Case of Hair Regrowth in a Patient with Complete Androgen Insensitivity Syndrome and Female Pattern Hair Loss

A Case of Hair Regrowth in a Patient with Complete Androgen Insensitivity Syndrome and Female Pattern Hair Loss

Bone mineral density, body composition and metabolic profiles in adult women with complete androgen insensitivity syndrome and removed gonads using oral or transdermal estrogens.

To assess bone health in adult women with complete androgen insensitivity syndrome (CAIS) and removed gonads compared with age-matched healthy controls. To evaluate the effects of transdermal oestradiol 2 mg or oral estradiol valerate 2 mg on bone, biochemical and clinical characteristics. Cohort study. Bone, body composition and anthropometric parameters were assessed in 32 adult CAIS and 32 healthy controls. In 28 cases, CAIS evaluations of metabolic, bone and body composition were performed also after a maximum of 6 years of therapy. Lumbar, femoral and total body bone mineral density (BMD) were significantly lower in those with CAIS when compared with controls. The prevalence of vertebral osteoporosis and osteopenia was significantly higher in the CAIS group (P = 0.038, OR = 9.67, 95% CI: 1.13-82.83 and P = 0.012, OR= 3.85, 95% CI: 1.34-11.16, respectively). Prevalence of femoral osteopenia was significantly higher in the CAIS group (P = 0.0012, OR = 7.93, 95% CI: 2.26-27.9). During follow-up, lumbar BMD significantly increased suggesting a significant effect of treatment on BMD (P = 0.0016), while femoral and total body BMD did not show any significant change. Total body BMD values were positively associated to the duration and route of oestrogen administration and to serum estradiol levels. Transdermal administration of estrogens was associated with better total body BMD in comparison to oral administration. Our results reinforce the importance of adequate hormonal treatment for women living with CAIS, suggesting a better effect from the transdermal route over the oral route.