Beta-hydroxysteroid Dehydrogenase Deficiency Research Articles

Four novel mutations identification in 17 beta-hydroxysteroid dehydrogenase-3 deficiency and our clinical experience: possible benefits of early treatment.

Individuals with 17-beta-hydroxysteroid dehydrogenase type 3 (17β-HSD3) deficiency face a multitude of challenges, primarily concerning genital appearance, potential malignancy risks, and fertility issues. This study reports our findings from an investigation involving five individuals affected by 17β-HSD3 deficiency, ranging in age from pre-adolescence to adolescence. Notably, we identified four previously unreported mutations in these subjects. Our study included a comprehensive evaluation to determine the potential occurrence of testicular tumors. The methods involved clinical examinations, genetic testing, hormone profiling, and patient history assessments. We closely monitored the progress of the study subjects throughout their treatment. The results of this evaluation conclusively ruled out the presence of testicular tumors among our study subjects. Moreover, four of these individuals successfully underwent gender transition. Furthermore, we observed significant improvements in genital appearance following testosterone treatment, particularly among patients in the younger age groups who received appropriate treatment interventions. These findings underscore the critical importance of early intervention in addressing concerns related to genital appearance, based on our extensive clinical experience and assessments. In summary, our study provides insights into the clinical aspects of 17β-HSD3 deficiency, emphasizing the vital significance of early intervention in addressing genital appearance concerns. This recommendation is supported by our comprehensive clinical assessments and experience.

A rare case report of ambiguous genitalia

An ambiguous genitalia is a commonly referred clinical scenario to endocrinology outpatient department. Accurate diagnosis is paramount to prevent associated salt-wasting crisis, direct the gender of rearing in the short-term, and monitoring for the development of malignancy in the gonads in the long-term. 17 beta-hydroxysteroid dehydrogenase 3 deficiency (17 β HSD 3) is one of the causes of defective testosterone biosynthesis. 17β-HSD3 deficiency should be suspected in children with female external genitalia with inguinal hernias or mild clitoromegaly; as well as males with ambiguous genitalia who develop virilization and gynecomastia at puberty. A hormonal evaluation may not always be diagnostic which makes genetic confirmation essential.

THU210 A Single-center Retrospective Study Of Brazilian Subjects With Differences In Sex Development (DSD) From Infancy To Adulthood

Abstract Disclosure: R.L. Batista: None. N.L. Gomes: None. T.A. Bachega: None. G. Madureira: None. M.C. Miranda: None. R.T. dallago: None. M.M. Ferrari: None. L.M. Lousada: None. F.L. Craveiro: None. J.P. Batatinha: None. R.D. Scalco: None. E.F. Costa: None. M.P. Sircili: None. F.T. Denes: None. M. Inacio: None. M.Y. Nishi: None. S. Domenice: None. B.B. Mendonca: None. Context: DSD represent a wide range of conditions presenting at different ages to many health professionals with several backgrounds. Establishing a correct diagnosis is essential for appropriate management. Objective: To amplify the understanding of the first clinical presentation, prevalence, and gender change of Brazilian DSD subjects. Design: A retrospective, observational cohort study of all DSD subjects referred to a DSD multi-professional team over 41 years (from 1980 to 2021). Participants: 696 subjects.Outcome Measures: Data included DSD diagnosis, sex assignment, age at diagnosis, gender change, clinical presentation, and phenotypic features. Results: Subjects presented at prepubertal, post-pubertal, and adult age, usually with atypical genitalia, undescended testes, or primary amenorrhea. Amongst the three major DSD categories, sex chromosome DSD was diagnosed in 264 subjects (135 with 45,X karyotype); 101 are mosaics (45,X/46,Xi(Xq) and three chimerism (all ovotesticular DSD). Among the 4 ovotesticular DSD subjects, 3 were raised as females and 1 as male, no gender changes occurred in this group. Thirteen chromosome DSD patients with Y material were assigned as male and two female-assigned patients changed their gender. 258 subjects have 46,XY DSD (69 unknown DSD, 64 gonadal dysgenesis, 36 5-αRD2 deficiency, 18 17β-HSD3 deficiency, 11 17α-hydroxylase deficiency, 9 Leydig cell hypoplasia, 25 CAIS, 18 PAIS, 8 AMH defects). Among the 192 XY subjects with atypical genitalia, the sex of rearing was female in 89 (46%) and gender change from female to male occurred in 13%, most in 5 αRD2 (45%) followed by 17β-HSD3 (33%) deficiency. Among those reared as male, only 2.9% changed their gender. 46,XX DSD was diagnosed in 178 patients. Congenital adrenal hyperplasia-CAH (most 21-hydroxylase deficiency) was diagnosed in 123 (115 female-assigned). Among CAH, gender change from female to male occurred in 6 cases, of which most have VS form (5/6; p=.004), a late beginning of treatment (>2 ys old), and poor compliance. In the remaining 55 with 46,XX DSD, 24 have ovotesticular DSD (all with atypical genitalia), 16 have 46,XX testicular DSD (seven with atypical genitalia). Among the ovotesticular subjects, 14 were reared as male and ten as female, and gender change occurred in 4 cases (3 from female to male). The diagnosis was not established in twelve 46,XX DSD patients (all with atypical genitalia, three with syndromic features). One patient has aromatase deficiency, one POR deficiency, and one glucocorticoid resistance syndrome. Conclusion: gender change from female to male mainly occurred among subjects with 46,XY DSD, particularly in those with 5 αRD2 and 17β-HSD3 deficiency, suggesting that male sex assignment is desirable in patients with these diagnoses. Among 46,XX DSD, the VS form of CAH, a late start of treatment, and poor compliance were implicated in female-to-male gender change. Presentation: Thursday, June 15, 2023

Genotype, mortality, morbidity, and outcomes of 3β-hydroxysteroid dehydrogenase deficiency in Algeria

Genotype, mortality, morbidity, and outcomes of 3β-hydroxysteroid dehydrogenase deficiency in Algeria

High carrier frequency of a nonsense p.Trp230* variant in HSD3B2 gene in Ossetians.

Congenital adrenal hyperplasia (CAH) caused by 3β-HSD deficiency is a rare form of congenital adrenal deficiency with an autosomal recessive type of inheritance. Previously we have demonstrated that a single nucleotide variant (SNV) p.Trp230* in the homozygous state is a frequent cause of CAH among the indigenous population of North Ossetia-Alania represented by Ossetians. Genotyping of the NM_000198.3:c.690G>A p.Trp230* variant was performed by Real-time PCR. 339 healthy individuals of Ossetian origin were included in the study. Allele frequencies, Fisher's confidence intervals (CI) were calculated using the WinPepi v. 11.65 software. Comparison of allele frequencies was performed with the z-score test for two proportions. Eight heterozygous carriers of c.690G>A variant in HSD3B2 gene were detected in 339 samples investigated. The total allele frequency of p.Trp230* variant was 0.0118 (n=8/678, 95% CI=0.0051-0.0231). Accordingly, the heterozygous carrier rate was 0.0236 (n=8/339). The frequency of CAH caused by p.Trp230* variant in HSD3B2 in Ossetian population was 1:7183 or 13.9 per 100,000 (95% CI: 1:1874-1:38447 or 3-53 per 100,000). The results demonstrate high frequency of p.Trp230* variant in Ossetians, which is most likely attributed to a founder effect.

Molecular mechanisms underlying the defects of two novel mutations in the HSD17B3 gene found in the Tunisian population

17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) converts Δ4-androstene-3,17-dione (androstenedione) to testosterone. It is expressed almost exclusively in the testes and is essential for appropriate male sexual development. More than 70 mutations in the HSD17B3 gene that cause 17β-HSD3 deficiency and result in 46,XY Disorders of Sex Development (46,XY DSD) have been reported. This study describes three novel Tunisian cases with mutations in HSD17B3. The first patient is homozygous for the previously reported mutation p.C206X. The inheritance of this mutation seemed to be independent of consanguineous marriage, which can be explained by its high frequency in the Tunisian population. The second patient has a novel splice site mutation in intron 6 at position c.490 -6 T > C. A splicing assay revealed a complete omission of exon 7 in the resulting HSD17B3 mRNA transcript. Skipping of exon 7 in HSD17B3 is predicted to cause a frame shift in exon 8 that affects the catalytic site and results in a truncation in exon 9, leading to an inactive enzyme. The third patient is homozygous for the novel missense mutation p.K202M, representing the first mutation identified in the catalytic tetrad of 17β-HSD3. Site-directed mutagenesis and enzyme activity measurements revealed a completely abolished 17β-HSD3 activity of the p.K202M mutant, despite unaffected protein expression, compared to the wild-type enzyme. Furthermore, the present study emphasizes the importance of genetic counselling, detabooization of 46,XY DSD, and a sensitization of the Tunisian population for the risks of consanguineous marriage.

ODP035 Congenital Adrenal Hyperplasia secondary to 3 beta hydroxydehydrogenase deficiency: Case study and review of literature

Abstract Introduction Congenital Adrenal Hyperplasia (CAH) results from one of the five steroidogenic hormonal deficiencies in adrenal steroid synthesis pathway, most commonly caused by 21-hydroxylase deficiency (21-OHD). 3β-hydroxysteroid dehydrogenase (3βHSD) deficiency (def) is very rare cause of CAH, accounting for less than 0.5% of the CAH cases, associated with disorder of sexual development (DSD) and steroidogenesis. We present a case of salt wasting CAH secondary to 3βHSD-def with focus on the management compared with 21-OHD. Case 53yr white female who was diagnosed with salt wasting CAH at birth, started on hydrocortisone replacement. She had oophorectomy at age of 11 due to hemorrhagic changes in ovaries. She was placed on oral contraceptives for most of her life. Her family history is significant for CAH in all of her 3 sisters, with oldest sister having pubic hair at age of 2 with frequent illnesses, triggering extensive workup and was subsequently diagnosed with CAH. Two brothers were also diagnosed with CAH with complete scrotum bifurcation at birth. Her family was subsequently diagnosed with 3βHSD deficiency. Patient's ACTH, Renin, 17-Hydroxyprogesterone (17-OHP) levels have been fluctuating due to skipping of hydrocortisone doses on occasions. Her sleep pattern remains disturbed, going to bed 3-4 AM and waking up at 2-3 PM. Discussion 3βHSD deficiency is very rare cause of CAH with prevalence less than 1 in million cases at birth. First cases were reported by Bongiovanni in 1962. It is autosomal recessive disorder affecting both the sexes. 3βHSD is expressed in adrenal glands and gonadal tissues, where it catalyzes conversion of pregnenolone, 17-hydroxypregnenolone (17OHPreg) and dehydroepiandrosterone (DHEA) into aldosterone, cortisol and androstenedione respectively. Patient with salt-wasting 3βHSD def need mineralocorticoids, glucocorticoids along with sex steroid replacements. Clinical presentation varies with different degrees of salt wasting, incomplete masculinization in males and virilization in females, depending on the severity of the gene mutation. Elevated 17-OHPreg and its ratio with cortisol along with elevated Δ-5 steroids is used for diagnosis with confirmation through genetic testing, compared with 17-OHP levels which are mainly used for 21-OHD diagnosis. Management is challenging with glucocorticoid and mineralocorticoid replacement therapy with risk of under-/over-replacement, some requiring higher doses compared with other forms of CAH. There is higher risk of long term complication such as obesity, reduced adult height, infertility, osteoporosis, TARTs. Compared with 21-OHD, patients with complete 3βHSD def may need sex steroid replacement at puberty including testosterone (males) and cyclic estrogen-progesterone therapy (females). Timing of hydrocortisone should be individualized as higher doses in the morning or evening showed no substantial differences affecting sleep rating, daily activity score, nocturnal BP. DHEA is a useful marker for the adequacy of the therapy along with clinical monitoring. Presentation: No date and time listed

OR18-3 Case Series of 16 Patients With 17β-Hydroxysteroid Dehydrogenase Type 3 Deficiency at Five Children's Hospitals in the United States

Abstract Objectives The 17β-hydroxysteroid dehydrogenase type 3 (17βHSD3) enzyme, expressed in the testes, converts androstenedione to testosterone. Deficiency of 17βHSD3 causes a 46,XY difference of sex development (DSD). Until recently, just 12 cases of 17βHSD3 deficiency had been reported in the literature in the United States. We report a series of 16 patients diagnosed at five children's hospitals in the United States. Methods We performed a multi-center chart review of patients with 17βHSD3 deficiency diagnosed based on hormone values and/or sequencing and deletion/duplication analysis of the HSD17B3 gene. Results Sixteen patients were identified, ranging in age at diagnosis from birth to 22.3 years (average age 9.5 years). One patient, assigned female at birth, was diagnosed due to a positive family history of the condition. Three patients underwent testing due to discordance between the sex predicted by prenatal cell-free DNA testing and the external genital appearance on prenatal ultrasound or at birth (two were assigned female, one was assigned male). An additional four patients had non-binary (atypical) appearing external genitalia at birth (two assigned female, two assigned male). Two children assigned female at birth were diagnosed after undescended testes were identified during hernia repair in early childhood. Six patients who were assigned female at birth came to medical attention peri-pubertally due to signs of excess/undesired androgen effects and/or primary amenorrhea. Data on gender identity is limited by the current age of many of the patients, but as of most recent follow-up, one patient assigned male and one assigned female are reported to be exploring their gender identities. Four patients had a prior diagnosis of complete or partial androgen insensitivity syndrome and 8 had a prior diagnosis of 46,XY DSD of unknown etiology. Eleven patients had genetic testing confirming pathogenic or likely pathogenic variants in the HSD17B3 gene (two identified on whole exome, one on a DSD-specific multi-gene panel, and the remaining 8 on single gene testing). Of the patients without genetically confirmed 17βHSD3 deficiency, one had a clinical diagnosis due to a genetically-confirmed diagnosis in a sibling. The remaining four declined or have not completed genetic testing, but had hormonal testing consistent with the diagnosis. Conclusions 17βHSD3 deficiency is likely much more common in the US than previously appreciated, and can present at any age with a range of physical findings. Accurate diagnosis is important, as the broad category of 46,XY DSD encompasses a wide spectrum of gonadal malignancy risk, potential for pubertal hormone function and fertility, and gender identity outcomes. We suggest evaluating for this potential diagnosis with genetic and/or hormonal testing in cases of 46,XY DSD with absent uterus. Presentation: Monday, June 13, 2022 11:30 a.m. - 11:45 a.m.

Lessons from 17β-HSD3 deficiency: Clinical spectrum and complex molecular basis in Chinese patients

17β-Hydroxysteroid dehydrogenase type 3 (17β-HSD3) deficiency is rarely reported in Chinese patients with 46, XY disorders of sexual development (DSD). Seven subjects with 17β-HSD3 deficiency were identified from 206 Chinese 46, XY DSD patients using targeted next-generation sequencing (NGS). Serum AD and T levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In silico and functional studies were performed to evaluate the enzymatic activity impairment of HSD17B3 variants. A minigene assay was performed in an exonic splicing variant. Our results showed that four novel and five reported HSD17B3 variants were identified in 7 unrelated patients. The patients showed cryptic presentation during childhood and classical virilization after puberty with T/AD ratio< 0.4. A heterozygous large deletion from the 5’UTR to exon 1 was identified in a patient with a monoallelic variant of p.N130S. Although predicted to be ‘likely pathogenic’, only p. S232P and p. S160F drastically reduced the enzymatic activity of 17β-HSD3. A previously reported ‘missense’ variant c 0.277 G>A (p. E93K) was revealed to have no impact on enzyme activity but resulted in aberrant splicing of exon 3 and was reclassified as an exonic splicing variant. In our study, one nonsense, one exonic splicing, one deletion, one large deletion and five missense variants were detected in patients with 17β-HSD3 deficiency, expanding the clinical and molecular profile of this disorder. In silico analysis should be cautiously interpreted when the heredity pattern and functional study are inconsistent.

Genotype, Mortality, Morbidity, and Outcomes of 3β-Hydroxysteroid Dehydrogenase Deficiency in Algeria.

Background3β-hydroxysteroid dehydrogenase 2 (3βHSD2) deficiency is a rare form of congenital adrenal hyperplasia (CAH), with fewer than 200 cases reported in the world literature and few data on outcomes.Patients and MethodsWe report a mixed longitudinal and cross-sectional study from a single Algerian center between 2007 and 2021. Virilization and under-masculinization were assessed using Prader staging and the external masculinization score (EMS), pubertal development staged according to the system of Tanner. Adrenal steroids were measured using mass spectrophotometry (LC-MS/MS). A genetic analysis of HSD3B2 was performed using Sanger sequencing.ResultsA 3βHSD2 defect was confirmed in 6 males and 8 females from 10 families (8 consanguineous), with p.Pro222Gln mutation in all but two siblings with a novel deletion: c.453_464del or p.(Thr152_Pro155del). Probable 3βHSD2 deficiency was diagnosed retrospectively in a further 6 siblings who died, and in two patients from two other centers. In the genetically confirmed patients, the median (range) age at presentation was 20 (0–390) days, with salt-wasting (n = 14) and genital anomaly (n = 10). The Prader stage for female patients was 2 (1–2) with no posterior fusion of the labia. The EMS for males was 6 (3–9). Median (range) values at diagnosis for 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEA-S), and 17-hydroxypregnenolone (17OHPreg) were elevated: 73.7 (0.37–164.3) nmol/L; 501.2(9.4–5441.3) nmol/L, and 139.7 (10.9–1500) nmol/l (NB >90 nmol/L diagnostic of 3βHSD2 defect). Premature pubarche was observed in four patients (3F:1M). Six patients (5F:1M) entered puberty spontaneously, aged 11 (5–13) years in 5 girls and 11.5 years in one boy. Testicular adrenal rest tumors were found in three boys. Four girls reached menarche at 14.3 (11–14.5) years, with three developing adrenal masses (surgically excised in two) and polycystic ovary syndrome (PCOS), with radiological evidence of ovarian adrenal rest tumor in one. The median IQ was 90 (43–105), >100 in only two patients and <70 in three.ConclusionsThe prevalence of 3βHSD2 deficiency in Algeria appears high, with p.Pro222Gln being the most frequent mutation. Mortality is also high, with significant morbidity from adrenal tumors and PCOS in adolescence and an increased risk of learning disability. The finding of adrenal tumors in older patients with 3βHSD2 indicates under-replacement, requiring effective hydrocortisone and fludrocortisone treatment rather than surgical removal.

Decision-making Regarding Orchiectomy in Patients with 17β-Hydroxysteroid Dehydrogenase Type 3 Deficiency: Clinical Considerations

Background: Patients with 46,XY differences of sex development (DSD) due to 17β-hydroxysteroid dehydrogenase type 3 (17βHSD3) deficiency are generally assigned female at birth. With known future virilizing puberty, orchiectomy is often discussed with patients and their families. Decision-making and factors to consider around orchiectomy are complex and challenging. We report two patients who presented at different ages to highlight the considerations and complexities surrounding gonad management, including the likelihood of gonadal malignancy, the possibility of fertility and options for preservation, and the current knowledge of gender identity outcomes.

17β hydroxysteroid dehydrogenase 3 deficiency in 46,XY disorders of sex development: Our experience and a gender role-focused systematic review.

To describe Asian Indian patients with 17β hydroxysteroid dehydrogenase 3 (17βHSD3) deficiency and to perform a systematic review to determine the factors influencing gender role in 46,XY disorder of sex development (DSD) due to 17βHSD3 deficiency. We present the phenotypic and genotypic data of 10 patients (9 probands and 1 affected family member) with 17βHSD3 deficiency from our 46,XY DSD cohort (N = 150; Western India) and a systematic review of 152 probands with genetically proven, index 17βHSD3 deficiency patients from the world literature to identify the determinants of gender role. 17βHSD3 deficiency was the third most common (6%) cause of non-dysgenetic 46,XY DSD in our cohort. Five patients each had prepubertal (atypical genitalia) and pubertal (primary amenorrhoea) presentations. Six patients were initially reared as female of whom two (one each in prepubertal and pubertal age) changed their gender role. Ten pathogenic molecular variants (six novel) were observed. In the systematic review, initial male sex of rearing was uncommon (10.5%) and was associated with atypical genitalia, higher testosterone/androstenedione (T/A) ratioand Asian origin. Gender role change to male was seen in 10.3% of patients with initial female sex of rearing and was associated with Asian origin but unrelated to pubertal androgens or molecular variant severity. It has not been reported in patients of European origin. We report the first Indian case series of 17βHSD3 deficiency, the third most common cause of 46,XY DSD, with six novel molecular variants. Distinct geographical differences in the frequency of initial male sex of rearing and gender role change to male in those initially reared as females in 17βHSD3 deficiency were noted which needs further evaluation for the underlying molecular mechanisms.

Prognosis and clinical characteristics of patients with 3β-hydroxy-Δ5-C27-steroid dehydrogenase deficiency diagnosed in childhood: A systematic review of the literature.

Objectives:3β-hydroxy-Δ5-C27-steroid dehydrogenase deficiency is a rare autosomal recessive condition. So far fewer than 100 cases have been reported and the factors affecting the prognosis are not yet established. The objective of this study is to explore a possible prediction of the outcome of this rare condition.Methods:This review was undertaken and reported in accordance with the preferred reporting items for systematic review and meta-analyses guidelines. Demographics, clinical features, gene data, treatment strategies and prognoses at the last follow-up were extracted and summarized. Patients were divided into 2 groups (alive with native liver and liver transplantation/died). Risk factors for the different clinical features were identified.Results:87 patients that were taken from 7 case reports and 9 case series were included. 38 (38/63, 63.0%) of them presented initial symptoms when they were younger than 1 month and 55 (55/63, 87.3%) less than 1 year. There is a larger proportion of patients younger than 1 month or 1 year at the age of symptom onset in the liver transplantation /died group than patients in alive with the native liver group. The majority of patients (53/62, 85.5%) were diagnosed before the age of 5 year. In all cases, 65 (predicted) pathogenic variants have been identified. Over 70% of patients carried an HSD3B7 variant on exon 1, 4, 5 or 6. 71 (81.6%) were alive at the last follow-up, 16 (18.4%) underwent liver transplantation or died. No significance was found between the group alive with native liver and group liver transplantation /died.Conclusion:Age of onset of the symptoms may be a potential factor that determines the outcome of patients with 3β-HSD deficiency, patients presented with symptoms and signs at an age younger than 1 month or even 1 year may have a worse prognosis. Since there is no difference between clinical outcome and zygosity of gene mutation, we recommend a further study about any possible relationship between mutation site and clinical characteristics or prognosis.

A Case of Congenital Adrenal Hyperplasia due to 3-Beta-Hydroxysteroid Dehydrogenase Deficiency Presented With Acute Liver Failure

Congenital adrenal hyperplasia (CAH) is a group of rare autosomal disorders characterized by a variety of defects in adrenal steroidogenesis. Most cases of CAH are due to an enzyme deficiency in either 21-hydroxylase or 11-beta-hydroxylase. A much rarer form of CAH due to 3-betahydroxysteroid dehydrogenase (3B-HSD) deficiency results in impaired synthesis of all steroid hormones. The clinical presentation of undervirilization in 46 XY patients, hyponatremia, hyperkalemia, and recurrent hypoglycemia in 3B-HSD deficiency cases is well described in the literature. We describe a neonate with 3B-HSD deficiency that presented with ambiguous genitalia and hypoglycemia and was found to have comorbid coagulopathy, cholestasis, and direct hyperbilirubinemia with liver failure that resolved with glucocorticoid and mineralocorticoid treatment. Prompt recognition of this disease is imperative for timely intervention.

Screening for testicular adrenal rest tumors among children with congenital adrenal hyperplasia at King Fahad Medical City, Saudi Arabia.

To assess the incidence of testicular adrenal rest tumors (TARTs) among male children with congenital adrenal hyperplasia (CAH) in tertiary care centers. All male children aged 1-14 years diagnosed with CAH due to 21-hydroxylase deficiency (21 HOD), 11β-hydroxylase deficiency, and 3β-hydroxysteroid dehydrogenase deficiency, confirmed by biochemical and/or genetic testing, underwent scrotal ultrasound examination to identify TARTs. After receiving the diagnosed patients' data, patients' electronic medical records were accessed to collect demographic data and scrotal ultrasound results, along with growth parameters and specific biochemical test results within 2months of the ultrasound. TARTs were observed in 5 (10.9%) of 46 male children with CAH. Four patients with positive findings had 21 HOD classical CAH with salt loss and one had 21 HOD simple virilizing classical CAH. All patients had poor compliance and stage 2 bilateral TARTs. Three TART-positive patients (60.0%) had high ACTH levels, 5 patients (100%) had elevated 17-OHP levels, and 5 patients (100%) had advanced bone age. The youngest patient with positive findings was 4years old. The prevalence of TARTs increases with age and can be present in young males with classical CAH with 21 HOD. It is associated with elevated 17-hydroxyprogesterone (17-OHP) and advanced bone age SDS. TARTs are less likely to be associated with nonclassical CAH with 21 HOD or other less common CAHs due to 11β-hydroxylase deficiencies and 3β-hydroxysteroid dehydrogenase deficiencies in children. Our study recommends early and routine screening of TARTs in children with CAH.

Successful Management of Significant Maternal 3 Beta-Hydroxysteroid Dehydrogenase Deficiency

We report a case of successful management of pregnancy in a patient with significant 3beta-hydroxysteroid dehydrogenase (3beta-HSD) deficiency. A 25-year-old female presented for interfertility evaluation after failure to conceive for 8 months. The patient began full menses each month at the time of ovulation. Her unique clinical presentation led to the diagnosis of a significant 3beta-HSD deficiency. Treatment for infertility with clomiphene citrate, gonadotropins, dexamethasone and human chorionic gonadotropin trigger was unsuccessful. The patient conceived spontaneously while taking continuous combination oral contraceptive pills. Due to her history of instability and full menses in the luteal phase, oral estrogen and progesterone in oil were administered to support the early pregnancy. The results of elevated 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), and ratio of 17 OH-pregnenolone to 17-OHP were consistent with diagnosis of significant 3beta-HSD deficiency. Successful pregnancy was achieved after exogenous hormone supplementation. Fertility in 3beta-HSD deficiency, a rare form of congenital adrenal hyperplasia, has not been extensively studied. Varying phenotype can make the diagnosis challenging. Heightened suspicion in patients with reported bleeding at ovulation or breakthrough bleeding on oral contraceptive pills could aid in the diagnosis. Successful pregnancy in these patients is possible. J Clin Gynecol Obstet. 2021;10(2):51-54 doi: https://doi.org/10.14740/jcgo730

Successful Management of Significant Maternal 3 Beta-Hydroxysteroid Dehydrogenase Deficiency

Successful Management of Significant Maternal 3 Beta-Hydroxysteroid Dehydrogenase Deficiency

Abstract #1003768: Non Classic Congenital Adrenal Hyperplasia Due to Late Onset 3 Beta-Hydroxysteroid Dehydrogenase Deficiency Diagnosed as a Work Up of Infertility and Adrenal Adenoma

3 Beta-Hydroxysteroid Dehydrogenase (3B-HSD) deficiency is a rare form of Congenital Adrenal Hyperplasia (CAH). It is an autosomal recessive disease leading to varying degrees of enzymatic defects. Presented is a case of late onset type 2 3B-HSD deficiency, diagnosed as a work up of infertility, adrenal adenoma, and high dehydroepiandrosterone sulfate (DHEA-S) levels.

Congenital adrenal hyperplasia due to 3 beta hydroxysteroid dehydrogenase deficiency About two cases

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

46, XY Disorder of Sexual Development with Ambiguous Female External Genitalia: A Case Report

Disorder of Sexual Development (DSD) is a group of congenital conditions with atypical development of sex at chromosomal, gonadal or anatomic level. Genetic males with DSD (46 XY DSD) can present with female external genital phenotype, ambiguous, or a micropenis. It is caused by incomplete intrauterine masculinization with or without the presence of Müllerian structures. It results either from decreased synthesis of testosterone or DHT or from impairment of androgen action. Herein, we report a case of a 13-year child raised as female with hoarseness of voice and gradual enlargement of clitoris with hormonal assessment not suggestive of either 5 Alfa Reductase deficiency, Congenital Adrenal Insufficiency Syndrome or 17β-Hydroxysteroid Dehydrogenase deficiency