5α-reductase Deficiency Research Articles

Expert consensus for the management of 5α-reductase deficiency (2024)

Expert consensus for the management of 5α-reductase deficiency (2024)

Long-term outcome of gender assignment in individuals with 46, XY DSD assigned female sex in multicultural society

The decision regarding sex rearing in patients with Disorders of Sex Development (DSD) is heavily connected to the shared decision-making model within multidisciplinary team. Some of these patients might develop gender dysphoria, when they become adults. We have aimed to evaluate the long-term outcomes of patients with XY DSD who underwent female gender assignment at our center. We have conducted a retrospective study of all 46, XY DSD patients who underwent female assignment in our institution over the last 30 years. we have found 25 46, XY patients who were raised as a female after birth. After excluding the Androgen insensitivity syndrome (AIS) patients we have identified 15 patients who have matched study criteria. The decision on gender rearing was made by the parents in 11(74%) and by the surgical team 2(13%) during hernia repair/inguinal exploration. In 2(13%) cases, the patients opted to continue identifying as women after learning about the pathology during adolescence. Nine (60%) out of 15 patients (age17.9±4.7 years (mean±SD)) agreed to answer questionnaires regarding sexual function and satisfaction from gender assignment. Mean follow up was 11.1±8.2 years (mean±SD). only one participant consented to respond to a questionnaire regarding sexual intercourse (homosexual). The overall FSFI score was 24 which included the scores 4, 4, 3, 4, 3, 2 in the categories desire, arousal, lubrication, orgasm, satisfaction, and pain respectively. Two patients regretted the decision of female gender assignment. The first with 5α-reductase deficiency, he made the decision for assignment himself as an adult and the other (3β-hydroxysteroid dehydrogenase) who underwent gonadectomy during inguinal exploration as a child. The rest of the patients were satisfied with the choice of gender, 2 need psychological support on the daily basis. In the study group, relationship and cohabitation were significantly later in life compared to the general population. Despite the sensitivity of the subject and cultural differences, most patients (78%) were satisfied with the decision to undergo female gender assignment. Over the years, patients require meticulous follow-up in order to consider additional interventions, and mental support if it is necessary. The two cases of later regret highlight the importance of proper education of patients, their families and medical providers upon decision on gender assignment.

Characteristic external genitalia in male neonates with 5α-reductase deficiency.

There have been no reports comparing neonatal external genitalia of 5α-reductase deficiency (5αRD) with those of other 46,XY differences of sex differentiation (DSD). This study enrolled 31 Japanese cases of 46,XY DSD whose external genitalia was examined during the neonatal period; four were diagnosed as 5αRD and 15 were defined as non-5αRD by genetic analysis of SRD5A2 or urinary steroid metabolites. We compared the following characteristics between 5αRD and non-5αRD groups, adjusting the severity of undermasculinization of the external genitalia: stretched penile length (SPL), glans width, location of the external urethral opening, and proportion of undescended testis. The external genitalia of all the 5αRD cases were Quigley classification grade 2 or 3. We compared the phenotypes between the four 5αRD cases and 11 non-5αRD cases with grade 2 or 3. The median (range) of SPL in the 5αRD group (14 mm [11-16]) was significantly lower than that in the non-5αRD group (22 mm [15-29]) (p = 0.003). An SPL cut-off value of <15 mm yielded a sensitivity of 50% (95% confidence interval [CI]; 7-93%) and specificity of 100% (95% CI, 72-100%) for discriminating between the groups. The median glans width, location of the external urethral opening, and proportion of undescended testis were not significantly different between the groups. The SPL of 5αRD in Quigley classification grade 2 or 3 was significantly shorter than that of other 46,XY DSDs with the equivalent grade.

Dermatologic care of patients with differences of sex development.

Differences of sex development (DSD or disorders of sex development) are uncommon congenital conditions, characterized by atypical development of chromosomal, gonadal, or anatomic sex. Dermatologic care is an important component of the multidisciplinary care needed for individuals with DSD. This article discusses the most common primary dermatologic manifestations of DSD in addition to the cutaneous manifestations of hormonal and surgical therapies in individuals with DSD. Published articles including case series and case reports on PubMed. Selection was conducted by examining existing literature with a team of multidisciplinary specialists. Narrative review. This article was not conducted as a systematic review. In Klinefelter syndrome, refractory leg ulcers and incontinentia pigmenti have been described. Turner syndrome is associated with lymphatic malformations, halo nevi, dermatitis, and psoriasis. Virilization can be seen in some forms of congenital adrenal hyperplasia, where acne and hirsutism are common. Dermatologists should consider teratogenic risk for treatments of skin conditions in DSD depending on pregnancy potential. Testosterone replacement, commonly used for Klinefelter syndrome, androgen insensitivity syndrome, 5-alpha reductase deficiency, gonadal dysgenesis, or ovotesticular DSD, may cause acne.

Eight-year follow-up on postoperative improvement protocol in extensive metoidioplasty transgenders: A case series

BackgroundThis study aimed to evaluate the long-term penile size among patients who underwent extensive metoidioplasty. MethodsAn evaluation was conducted on 7 out of 14 patients (mean age: 29.71 ​± ​13.76 years) who participated in a 2015 study that introduced a postoperative protocol to improve penile size after extensive metoidioplasty. Five transsexual females (46XX karyotype) and two patients with 5-alpha reductase deficiency were retrospectively followed up in 2023 to assess the long-term efficacy of the protocol at a specialized clinic in a general hospital in Tehran, Iran. All participants were informed about the study and consented to participate. ResultsFive patients achieved increased penile size from their 2015 measurements (mean, 29.00 ​± ​13.34 ​mm). Five patients requested a larger sized penile traction device to continue the protocol. ConclusionThe long-term implementation of this protocol can result in increased penile size. We advise highly motivated patients to continue practicing the protocol to achieve better results.

Genetic Variants in SRD5A2 in a Spectrum of DSD Patients from Australian Clinics Highlight Importance of Genetic Testing alongside Typical First-Line Investigations

Introduction: Steroid 5-alpha reductase deficiency (5α-R2D) is a rare condition caused by genetic variants that reduce the activity of the enzyme that converts testosterone into dihydrotestosterone. The clinical spectrum of 5α-R2D is known to overlap with other 46,XY differences of sex development (DSD) such as androgen insensitivity or gonadal dysgenesis. However, the clinical trajectories of the aetiologies can differ, with 5α-R2D presenting its own challenges. Methods: In this study, we have collated clinical information for five individuals with variants in SRD5A2 identified using research genetic testing in an Australian paediatric setting. Results: We describe how a genetic finding resolved or confirmed a diagnosis for these individuals and how it guided clinical management and family counselling. Conclusion: This work highlights the importance of early genetic testing in children born with 46,XY DSD where it complements traditional first-line testing.

Effect of Preoperative Androgen Stimulation on Penile Size and Postoperative Complication Rate in Patients with Hypospadias: A Systematic Review and Meta-Analysis.

To systematically review and evaluate the beneficial effects of preoperative androgen stimulation (PAS) on penile length, glans width, and postoperative complications in patients with hypospadias using meta-analysis. A comprehensive search of the published literature between 1980 and 2022 was done on PubMed, Embase, Google Scholar, Scopus, Web of Science, and Proquest. Studies of patients with 5-alpha reductase deficiency, differentiation sex disorder, or micro-penis without hypospadias were excluded. The full-text screening, quality assessment, and data acquisition were done independently by two reviewers. Meta-analysis was done to quantify the penile growth and postoperative complications. The initial literature search yielded 2,389 records, wherein 32 studies were eligible for the systematic review and meta-analysis. Preoperative testosterone stimulation increased the penile length and glans width by 9.34 mm (95% CI: 6.71-11.97) and 3.26 mm (95% CI: 2.50-4.02), respectively. A longer penis at the baseline led to greater length gain following treatment (1 mm longer at the baseline was likely to gain 0.5 mm more). However, the increase in penile length was not associated with the severity of hypospadias. While the treatment did not affect the overall complication rate, the postoperative fistula risk was lower in those receiving PAS (RR=0.52, 95% CI: 0.30-0.91, p=0.02). The beneficial effects of PAS on increasing the penile length and glans width were again confirmed. More gain of penile length was expected in the larger penis at baseline. There are no reported increased postoperative complications in association with PAS.

A 10-YEAR STUDY OF CHILDREN WITH GONADAL TUMORS AND DISORDERS OF SEX DIFFERENTIATION, IN ROMANIA.

Children having gonadal tumors and disorder of sex differentiation (DSD) are rare. To investigate the presentation of DSD children with malignant gonadal tumors. A retrospective study from 2010-2020, that evaluated 17 children with DSD, including 13 females, eight months to 16 years, with congenital adrenal hyperplasia, 5-alpha reductase deficiency, androgen insensitivity syndrome, Turner, Sywer, and Klinefelter syndromes. Ten children had malignant gonadal tumor; nine had germ cell tumors and one person granulosa cell tumors, while seven children with non-malignant tumor had gonadoblastoma, cystadenoma (five children), and cysts. Systemic malformations, obesity, elevated tumor markers, and psychosocial issues were observed in 90%, 90%, 70%, and 50% of children with malignancy unlike 28.6%, 42.9%, 14.35%, and 57.1% children without malignancy respectively. Most (9/10) children >12 years, had psychosocial issues, unlike 0/7 children ≤12 years. From 8/17 children presenting with symptoms suggestive of tumor, 75% had malignancy, while from 9/17 children with DSD presentation, 44% had malignant tumors. Malignancy was observed in 3/10 children between eight months to age six, while 7/10 children had stage 1-2 tumors. We reported a child, identified as female, aged 13 years, with partial androgen insensivity syndrome (PAIS) 46,XY, and testicular papillary serous cystadenoma with genomic variant AR NM_000044.4:c.2750del. p.(F917Sfs*27) chromosome Xq12, never published in people with PAIS nor population databases (GnomAD). DSD diagnosis raises numerous challenges. People with DSD have increased risk of malignancy, especially when obesity and, systemic malformations are present; also, psychosocial issues in these children are associated with postpubertal age.

A role for steroid 5 alpha-reductase 1 in vascular remodeling during endometrial decidualization.

Decidualization is the hormone-dependent process of endometrial remodeling that is essential for fertility and reproductive health. It is characterized by dynamic changes in the endometrial stromal compartment including differentiation of fibroblasts, immune cell trafficking and vascular remodeling. Deficits in decidualization are implicated in disorders of pregnancy such as implantation failure, intra-uterine growth restriction, and pre-eclampsia. Androgens are key regulators of decidualization that promote optimal differentiation of stromal fibroblasts and activation of downstream signaling pathways required for endometrial remodeling. We have shown that androgen biosynthesis, via 5α-reductase-dependent production of dihydrotestosterone, is required for optimal decidualization of human stromal fibroblasts in vitro, but whether this is required for decidualization in vivo has not been tested. In the current study we used steroid 5α-reductase type 1 (SRD5A1) deficient mice (Srd5a1-/- mice) and a validated model of induced decidualization to investigate the role of SRD5A1 and intracrine androgen signaling in endometrial decidualization. We measured decidualization response (weight/proportion), transcriptomic changes, and morphological and functional parameters of vascular development. These investigations revealed a striking effect of 5α-reductase deficiency on the decidualization response. Furthermore, vessel permeability and transcriptional regulation of angiogenesis signaling pathways, particularly those that involved vascular endothelial growth factor (VEGF), were disrupted in the absence of 5α-reductase. In Srd5a1-/- mice, injection of dihydrotestosterone co-incident with decidualization restored decidualization responses, vessel permeability, and expression of angiogenesis genes to wild type levels. Androgen availability declines with age which may contribute to age-related risk of pregnancy disorders. These findings show that intracrine androgen signaling is required for optimal decidualization in vivo and confirm a major role for androgens in the development of the vasculature during decidualization through regulation of the VEGF pathway. These findings highlight new opportunities for improving age-related deficits in fertility and pregnancy health by targeting androgen-dependent signaling in the endometrium.

From Conception to Adulthood: The Impact of Androgens on Abnormalities of Male Genital Development and Size

Androgens play a critical role in male development starting in utero. In a 46XY male patient, testosterone plays a significant role in the development of the internal genitalia while external genitalia formation is largely dependent on the conversion of testosterone to dihydrotestosterone (DHT). Testosterone is important for testicular descent and later, the onset of puberty. Defects in the production of testosterone, the conversion of testosterone to DHT, or within the androgen receptor can lead to a variety of pediatric urological conditions including micropenis, cryptorchidism, hypospadias, and disorders of sexual differentiation. Supplementation with testosterone is the standard of care for the treatment of micropenis and is used to increase glans size and reduce complications before hypospadias repair. Unfortunately, patients with a 5-alpha reductase deficiency will respond sub-optimally to testosterone supplementation and instead may benefit from DHT supplementation.

Genotype-Phenotype Correlation Analysis and Identification of a Novel SRD5A2 Mutation in Four Unrelated Chinese Patients with 5α-Reductase Deficiency.

ObjectiveThe 5α-reductase type 2 deficiency is mainly caused by mutations in the SRD5A2 gene. Our study aims to investigate the SRD5A2 gene mutations and their corresponding manifestations.MethodsFour unrelated Chinese patients with 46, XY ambiguous genitalia were studied. Molecular genetic alterations and clinical presentations were analyzed.ResultsFive variants in the SRD5A2 gene were identified, all highly conserved in vertebrate orthologs. The p.P251A was a novel variant, predicted to “Affect protein function” and to be “probably damaging”. Combining patients’ gene mutations with their external genitalia and male sexual characteristics, we found that three variants, p.Q6X, p.N193S, and p.H90Y, were associated with severe undervirilization of external genitalia, and the other two, p.G203S and p.P251A, probably retained part of the enzyme activity.ConclusionMutation analysis of SRD5A2 gene is crucial for differential diagnosis in patients with 5α-reductase type 2 deficiency. Patients’ variable manifestations depend on the mutation type and residual enzyme activity. The novel variant p.P251A enlarges the spectrum of SRD5A2 mutations.

Etiological Classification of Patients with Ambiguous Genitalia: A Cross-Sectional Study

Background: Disorder of sex development (DSD) is one of the most serious problems encountered at birth. DSD is a heterogeneous group of rare conditions wherein chromosomal, gonadal, or anatomical sex is atypical. The aim of this study was to define the classification and etiological distribution of patients presented with ambiguous genitalia&#x0D; Methods: This study was a cross-sectional study conducted in the department of Pediatric and Endocrinology and Surgery at Shahid Sadoughi Hospital in Yazd from March 2016 to March 2020. All patients with genital ambiguity were included in the study with the exception of five patients since they did not have a final diagnosis of ambiguous genitalia.&#x0D; Results: Out of 50 patients, thirty-one (62 %) patients were diagnosed with 46, XXDSD, fifteen (30%) patients with 46, XYDSD, while four (8%) patients with ovotesticular DSD. Congenital adrenal hyperplasia (CAH) was the common cause in 46, XXDSD with majority due to deficiency of 21 hydroxylase enzyme. Three (6%) patients with 46, XXDSD were diagnosed with genital ambiguity as part of syndrome. Out of patients with 46, XYDSD, CAH observed in two (4%) patients, severe hypospadias in nine (18%) patients and 5-alpha reductase deficiency in two (4%) patients and one (2%) patient with syndrome. Four (8%) patients were diagnosed with ovoteticular DSD.&#x0D; Conclusion: Our study revealed that 46, XXDSD was the most frequent DSD etiological diagnosis. CAH was the commonest cause in 46, XXDSD and severe hypospadias were the underlying cause of 46, XYDSD.

Mutations in AR or SRD5A2 Genes: Clinical Findings, Endocrine Pitfalls, and Genetic Features of Children with 46,XY DSD

Objective:Androgen insensivity syndrome (AIS) and 5α-reductase deficiency (5α-RD) present with indistinguishable phenotypes among the 46,XY disorders of sexual development (DSD) that usually necessitate molecular analyses for the definitive diagnosis in the prepubertal period. The aim was to evaluate the clinical, hormonal and genetic findings of 46,XY DSD patients who were diagnosed as AIS or 5α-RD.Methods:Patients diagnosed as AIS or 5α-RD according to clinical and hormonal evaluations were investigated. Sequence variants of steroid 5-α-reductase type 2 were analyzed in cases with testosterone/dihydrotestosterone (T/DHT) ratio of ≥20, whereas the androgen receptor (AR) gene was screened when the ratio was <20. Stepwise analysis of other associated genes were screened in cases with no causative variant found in initial analysis. For statistical comparisons, the group was divided into three main groups and subgroups according to their genetic diagnosis and T/DHT ratios.Results:A total of 128 DSD patients from 125 non-related families were enrolled. Birth weight SDS and gestational weeks were significantly higher in 5α-RD group than in AIS and undiagnosed groups. Completely female phenotype was higher in all subgroups of both AIS and 5α-RD patients than in the undiagnosed subgroups. In those patients with stimulated T/DHT <20 in the prepubertal period, stimulated T/DHT ratio was significantly lower in AIS than in the undiagnosed group, and higher in 5α-RD. Phenotype associated variants were detected in 24% (n=18 AIS, n=14 5α-RD) of the patients, revealing four novel AR variants (c.94G>T, p.Glu32*, c.330G>C, p.Leu110=; c.2084C>T, p.Pro695Leu, c.2585_2592delAGCTCCTG, p.(Lys862Argfs*16), of these c.330G>C with silent status remained undefined in terms of its causative effects.Conclusion:T/DHT ratio is an important hormonal criterion, but in some cases, T/DHT ratio may lead to diagnostic confusion. Molecular diagnosis is important for the robust diagnosis of 46,XY DSD patients. Four novel AR variants were identified in our study.

Validation of steroid ratios for random urine by mass spectrometry to detect 5α-reductase deficiency in Vietnamese children.

The 5α-reductase-type-2 deficiency (5ARD2) is a rare autosomal recessive 46,XY disorder of sex development caused by the mutated 5α-reductase type 2 (SRD5A2) gene. In this disease, defective conversion of testosterone to dihydrotestosterone leads to variable presentations of male ambiguous genitalia during fetal development. We aimed to examine characteristics of patients presenting with 5ARD2 over a 4year period. Random urine samples of control and patients with suspected 5ARD2 were collected and urine steroidomic metabolites were measured by Gas chromatography-mass spectrometry (GC-MS) in the period from 2017 to 2021 at National Children's Hospital, Hanoi Vietnam. 5α- to 5β-reduced steroid metabolite ratio, 5a-tetrahydrocortisol to tetrahydrocortisol (5α-THF/THF), was reviewed by receive operator characteristics (ROC) curve analysis. Molecular testing was offered to 25 patients who were diagnosed with 5ARD2 by GC-MS urinary steroid analysis. Urine steroidomic profiling was conducted for 104 male controls and 25 patients between the ages of 6months and 13years old. Twelve of the twenty-five 5ARD2 patients agreed to undertake genetic analysis, and two mutations of the SRD5A2 gene were detected in each patient, confirming the diagnosis. All patients showed a characteristically low ratio of 5α-THF/THF. There was no overlap of 5α-THF/THF ratio values between control and 5ARD2 groups. The ROC of 5α-THF/THF ratio at 0.19 showed 100% sensitivity and 100% specificity for boys between 6months and 13years of age. Analysis of the urine steroid metabolome by GC-MS can be used to assist in the diagnosis of 5ARD2. We recommend consideration of random urine steroid analysis as a first-line test in the diagnosis of 5ARD2.

46, XY 5-Alpha Reductase Deficiency in a 36-Year-Old Phenotypic Female Patient

46, XY 5-Alpha Reductase Deficiency in a 36-Year-Old Phenotypic Female Patient

Abstract 107: Klinefelter's syndrome presenting with ambiguous genitalia

A first-born child born out of non-consanguinity, with term delivery and low birth weight was brought at 1 year 4 months of age with left undescended testis and ambiguity. Antenatal, perinatal and developmental history were uneventful. There was no h/o failure to thrive or generalized hyperpigmentation. On examination there was bifid scrotum with rugosities and palpable testis on the right with left testis in the inguinal canal. The shaft measured 2 cm with penoscrotal hypospadias. On evaluation the stimulated T: DHT was 127.3 and T: A was 13.42, suggestive of 5-alpha reductase deficiency. However, the karyotyping revealed 47XXY karyotype. Clinical exome sequencing did not reveal any mutations. Ambiguity is a rare presentation in patients with Klinefelter's syndrome.

COMPARISON OF SINGLE DOSE AND MULTI-DOSE hCG STIMULATION TESTS

Objective: The human chorionic gonadotropin (hCG) stimulation test is widely used to assess testicular steroidogenesis. This test evaluates Leydig cell function and helps to evaluate testosterone synthesis in testicular enzyme defects, hypogonadism, 46,XY sexual development disorders (DSD), and micropenis. This study will compare testosterone responses to a single dose of 5000 IU/m2 and three consecutive days of 1500 IU/m2 hCG regimens. Materials and Methods: The study evaluated 18 patients who were admitted with micropenis, hypospadias, or undescended testis (Group 1) and 18 patients with a molecular diagnosis of androgen receptor insensitivity (56%) or 5α reductase deficiency (44%) (Group 2). The median (interquartile range; IQR) age of the patients were 1.4 (0.8-4.2) years for Group 1 and 0.7 (0.3-0.8) years for Group 2. Baseline testosterone levels were checked and after a single dose of hCG 5000 IU/m2 injection into the first group, testosterone levels were observed on day one and day four. In the second group, after the injection of hCG 1500 IU/m2 for three days, testosterone levels were checked on the fourth day. Results: There was no significant difference in height, weight, BMI SDS, and baseline testosterone levels between groups. After hCG, stimulation testosterone responses did not vary among the groups. Testosterone levels were increased 40-fold and 40.1- fold on day four compared to the baseline in Group 1 and Group 2. In Group 1, testosterone response was significantly higher on day four compared to day one (p=0.001). Conclusions: The hCG tests performed with a single dose or multidoses showed that there was no difference between testosterone responses and these two tests were applicable the 5000 IU/m2 hCG test requires fewer injections and is easy to administer, this test may be preferred to an evaluation of the Leydig cell function. For an adequate testosterone response, the researchers suggest measuring testosterone levels on the fourth day after the single dose of 5000 IU/m2 .

Mutations in AR or SRD5A2 Genes: Clinical Findings, Endocrine Pitfalls, and Genetic Features of Children With 46,XY DSD

Androgen insensivity syndrome (AIS) and 5α-reductase deficiency (5α-RD) present indistinguishable phenotypes among the 46,XY disorders of sexual development (DSD) that usually necessitate molecular analyses for the definitive diagnosis in prepubertal period . The aim was to evaluate the clinical, hormonal and genetic findings of 46,XY DSD patients who were diagnosed as AIS or 5α-RD. Patients diagnosed as AIS or 5α-RD according to clinical and hormonal evaluations were investigated. Sequence variants of steroid 5-α-reductase type 2 (SRD5A2) were analyzed in cases with testostetone/dihydrotestosterone (T/DHT) ratio ≥ 20, whereas androgen receptor (AR) gene was screened when the ratio was below 20. Stepwise analysis of other associated genes were screened in cases with no causative variant found in previous analysis. For statistical comparisons, the group was divided into three main groups and subgroups according to their genetic diagnosis and T/DHT ratios. A total of 128 DSD patients from non-related 125 families were enrolled. Birth weight SDS and gestational weeks were significantly higher in 5α-RD patients than AIS and undiagnosed groups. Completely female phenotype was higher in all subgroups of both AIS and 5α-RD patients than in undiagnosed subgroups. In those patients with stimulated T/DHT lower than 20 in the prepubertal period, stimulated T/DHT ratio was significantly lower in AIS than in the undiagnosed group, and higher in 5α-RD. Phenotype associated variants were detected in 24% (n=18 AIS, n=14 5α-RD) of the patients, revealing four novel AR variants (c.94G>T, p.Glu32*, c.330G>C, p.Leu110=; c.2084C>T, p.Pro695Leu, c.2585_2592delAGCTCCTG, p.(Lys862Argfs*16), of those c. c.330G>C with silent status remained undefined in terms of its causative effects. T/DHT ratio is an important hormonal criterion, but in some cases, T/DHT ratio may lead to diagnostic confusion. Molecular diagnosis is important for the robust diagnosis of 46,XY DSD patients correctly. Four novel AR variants were identified in our study.

Leydig and Sertoli cell function in individuals with genital ambiguity, 46,XY karyotype, palpable gonads and normal testosterone secretion: a case-control study.

Because normal male sexual differentiation is more complex than normal female sexual differentiation, there are more cases of disorders of sex development (DSDs) with 46,XY karyotype that have unclear etiology. However, Leydig and Sertoli cell markers are rarely used in distinguishing such individuals. To evaluate the function of Leydig and Sertoli cells in individuals with genital ambiguity, 46,XY karyotype, palpable gonads and normal testosterone secretion. Case-control study with 77 patients, including eight with partial androgen insensitivity syndrome, eight with 5α-reductase deficiency type 2 (5ARD2) and 19 with idiopathic 46,XY DSD, and 42 healthy controls, from the Interdisciplinary Study Group for Sex Determination and Differentiation (GIEDDS), at the State University of Campinas (UNICAMP), Campinas, Brazil. Baseline levels of gonadotropins, anti-Müllerian hormone (AMH), inhibin B, insulin-like 3 (INSL3), testosterone and dihydrotestosterone in cases, and AMH, inhibin B, and INSL3 levels in controls, were assessed. There was no significant difference in age between cases and controls (P = 0.595). AMH and inhibin B levels were significantly lower in cases than in controls (P = 0.031 and P < 0.001, respectively). INSL3 levels were significantly higher in cases than in controls (P = 0.003). Inhibin B levels were lower in 5ARD2 patients (P = 0.045) and idiopathic patients (P = 0.001), in separate comparisons with the controls. According to our findings, we can speculate that inhibin B levels may be used to differentiate among DSD cases.

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.