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Molecular genetic characterization of mutations in SRD5A2 gene is used as an essential procedure for the final diagnosis of 5alpha-reductase deficiency. Here, we report a novel homozygous point mutation of SRD5A2 gene at codon 65 in exon 1, due to a proline for alanine substitution in a Turkish family whose proband has severe undervirilization. This mutation has not been reported up to date in association with 5alpha-reductase deficiency in various ethnic groups. We discussed some questions about gender assignment in addition to the molecular and clinical characteristics of the disease.

Molecular genetic characterization of mutations in SRD5A2 gene is used as an essential procedure for the final diagnosis of 5alpha-reductase deficiency. Here, we report a novel homozygous point mutation of SRD5A2 gene at codon 65 in exon 1, due to a proline for alanine substitution in a Turkish family whose proband has severe undervirilization. This mutation has not been reported up to date in association with 5alpha-reductase deficiency in various ethnic groups. We discussed some questions about gender assignment in addition to the molecular and clinical characteristics of the disease. [ABSTRACT FROM AUTHOR]

Introduction: The conversion of testosterone into dihydrotestosterone is catalyzed by the 5α-reductase type 2 enzyme which plays a crucial role in the external genitalia virilization. It is encoded by the SRD5A2 gene. Allelic variants in this gene cause a 46,XY DSD with no genotype–phenotype relationship. It was firstly reported in the early 70s from isolated clusters. Since then, several cases have been reported. Putting together, it will expand the knowledge on the molecular bases of androgen milieu. Methods: We searched for SRD5A2 allelic variants (AV) in the literature (PubMed, Embase, MEDLINE) and websites (ensembl, HGMD, ClinVar). Only cases with AV in both alleles, either in homozygous or compound heterozygous were included. The included cases were analyzed according to ethnicity, exon, domain, aminoacid (aa) conservation, age at diagnosis, sex assignment, gender reassignment, external genitalia virilization and functional studies. External genitalia virilization was scored using Sinnecker scale. Conservation analysis was carried out using the CONSURF platform. For categorical variables, we used X2 test and Cramer's V. Continuous variables were analyzed by t test or ANOVA. Concordance was estimated by Kappa. Results: We identified 434 cases of 5ARD2 deficiencies from 44 countries. Most came from Turkey (23%), China (17%), Italy (9%), and Brazil (7%). Sixty-nine percent were assigned as female. There were 70% of homozygous allelic variants and 30% compound heterozygous. Most were missense variants (76%). However, small indels (11%), splicing (5%) and large deletions (4%) were all reported. They were distributed along with all exons with exon 1 (33%) and exon 4 (25%) predominance. Allelic variants in the exon 4 (NADPH-binding domain) resulted in lower virilization (p< 0.0001). The codons 55, 65, 196, 235 and 246 are hotspots making up 25% of all allelic variants. Most of them (76%) were located at conserved aa. However, allelic variants at non-conserved aa were more frequently indels (28% vs 6%; p< 0.01). The overall rate of gender change from female to male ranged from 16% to 70%. The lowest rate of gender change from female to male occurred in Turkey and the highest in Brazil. External genitalia virilization was similar between those who changed and those who kept their assigned gender. The gender change rate was significantly different across the countries (V=0.44; p< 0.001) even with similar virilization scores. Conclusion: 5ARD2 deficiency has a worldwide distribution. Allelic variants at the NADPH-ligand region cause lower virilization. Genitalia virilization influenced sex assignment but not gender change which was influenced by cultural aspects across the countries. Molecular diagnosis influenced on sex assignment, favoring male sex assignment in newborns with 5α-reductase type 2 deficiency. [ABSTRACT FROM AUTHOR]

Context: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) is characterized by decreased sex steroids and cortisol synthesis, as well as an increased mineralocorticoid effect. Aim: This study aimed to evaluate the clinical, biochemical, and molecular characteristics of patients with 17OHD and to discuss the diagnosis, treatment, and follow-up process. Methods: Age, symptoms, anthropometric measurements, blood pressure, and hormonal, biochemical, and chromosomal analysis results of 13 patients diagnosed with 17OHD between 2003 and 2022 were recorded at admission and during follow-up. Whole gene next-generation sequencing was performed for the CYP17A1 gene. Multiplex ligation-dependent probe amplification was used to detect deletions in patients without point mutations in CYP17A1. Results: The median age at diagnosis was 14.0 (3.5–16.8) years. Nine of 13 patients (69.2%) had 46,XY karyotypes. All patients were phenotypically female and were raised as girls. The most common reasons for admission were the absence of puberty and amenorrhea (n = 8, 61.5%), followed by hypertension (n = 3, 23.0%), and family screening (n = 2, 15.3%). At the time of diagnosis, hypertension was detected in 10 (76.9%) patients, and 11 (84.6%) patients had hypokalemia. Conclusions: 17OHD should be considered in patients with pubertal delay/primary amenorrhea, hypertension, and hypokalemia. Adrenal function should be included in the clinical study of hypergonadotropic hypogonadism, after excluding Turner syndrome, in all 46,XX females. Deletion in the CYP17A1 gene, including exons 1–6, is the founder mutation for Turkey's east and southeast regions. [ABSTRACT FROM AUTHOR]

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Objective: Standard short adrenocorticotropic hormone (ACTH) stimulation test (SST) has traditionally been used for assessing adrenal gland fuction by intravenous (iv) application. However the iv form is not readily available in all countries, including Turkey. The aim of this study was to evaluate the effectiveness of the intramuscular (im) SST. Methods: Patients underwent im SST with suspected adrenal insufficiency (AI) and hyperandrogenism. The SSTs were done with 250 mcg ACTH (Synacthen Depot ampul, concentration 1 mg/mL). The cases were divided into two groups: suspected AI (group 1 n=87); and hyperandrogenism group (group 2 n=124). Definite AI was defined as peak cortisol <18 µg/dL, suspected AI as a peak cortisol of 18-21 µg/dL and normal result was defined as a peak cortisol =22 µg/dL. Results: The mean age of the patients was 11.7±5.2 years. In 164 patients (78%) all of the peak cortisol tests were normal (=22 mcg/dL). The rates were 64% and 88% in group 1 and 2, respectively. Only 8.5% (n=18) of all cases had an inadequate peak cortisol response of <18 mcg/dL. On follow up, 15 patients whose peak cortisol was <18 mcg/dL needed cortisol therapy. Of all cases 3.3% (n=8) had 17-OHP =10 ng/dL. Clinical findings suggestive of non-classical congenital adrenal hyperplasia and/or mutation were found in six of these cases (75%). No local and systemic side effects or allergic reactions were observed in any patient. Conclusion: IM ACTH SST is a safe, effective and reliable test in children with suspected AI. There were no local or systemic side effects, supporting the reliability of the im ACTH test. [ABSTRACT FROM AUTHOR]

The article focuses on the 14th World Congress of Perinatal Medicine (WCPM) that was held at Istanbul Lütfi Kırdar Convention and Exhibition Centre, Turkey. on 11-14 September, 2019. It mentions that patients with adherent placenta carry many life-threatening risks. It also mentions that preparing the proper environment for the fetus to grow in, could help prevent the number of perinatal diseases.

Copyright of Turkish Journal of Endocrinology & Metabolism is the property of Aves Yayincilik Ltd. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: A comprehensive survey was conducted to evaluate the shortcomings of clinical care in patients with Turner syndrome (TS) in Turkey. Methods: A structured questionnaire prepared by the Turner study group in Turkey, which covered relevant aspects of patient care in TS was sent to 44 pediatric endocrinology centers. Results: Eighteen centers (41%) responded to the questionnaire. In the majority of the centers, diagnostic genetic testing, screening for Y chromosomal material, protocols regarding the timing and posology of growth hormone (GH) and estrogen, thrombophilia screening, fertility information and screening for glucose intolerance, thyroid, and coeliac diseases in patients with TS were in line with the current consensus. Thirteen centers (72.2%) performed GH stimulation tests. Only four centers (22.2%) used oxandrolone in patients with TS with very short stature. The majority of the centers relied on bone age and breast development to assess estrogen adequacy, though together with variable combinations of oestrogen surrogates. Two centers (11.1%) reported performing serum estradiol measurements. Eight centers (44.4%) routinely conducted cardiac/thoracic aorta magnetic resonance imaging. Screening for hearing, dental and ophthalmologic problems were performed by thirteen (72.2%), six (33.3%) and ten (55.6%) centers, respectively. Psychiatric assessments were made by four centers (22.2%) at diagnosis, with only one center (5.6%) requiring annual reassessments. Conclusion: Although we found some conformity between the current consensus and practice of the participating centers in Turkey regarding TS, further improvements are mandatory in the multi-disciplinary approach to address co-morbidities, which if unrecognized, may be associated with reduced quality of life and even mortality. [ABSTRACT FROM AUTHOR]

Background/purpose: Although it is known that there is generally a good correlation between genotypes and phenotypes, the number of studies reporting discrepancies has recently increased, exclusively between milder genotypes and their phenotypes due to the complex nature of the CYP21A2 gene and methodological pitfalls. This study aimed to assess CYP21A2 genotyping in children with 21-hydroxylase deficiency (21-OHD) and establish their predictive genotype-phenotype correlation features using a large cohort in Southeastern Anatolia's ethnically diverse population., Methods: The patients were classified into three groups: salt-wasting (SW), simple virilizing (SV) and non-classical (NC). The genotypes were categorized into six groups due to residual enzyme activity: null-A-B-C-D-E. CYP21A2 genotyping was performed by sequence-specific primer and sequenced with next generation sequencing (NGS), and the expected phenotypes were compared to the observed phenotypes., Results: A total of 118 unrelated children with 21-OHD were included in this study (61% SW, 24.5% SV and 14.5% NC). The pathogenic variants were found in 79.5% of 171 mutated alleles (60.2%, 22.2%, and 17.6% in SW, SV and NC, respectively). Patient distribution based on genotype groups was as follows: null-16.1%, A-41.4%, B-6.0%, C-14.4%, E-22%). In2G was the most common pathogenic variant (33.9% of all alleles) and the most common variant in the three phenotype groups (SW-38.8%, SV-22.2% and NC-23.3%). The total genotype-phenotype correlation was 81.5%. The correlations of the null and A groups were 100% and 76.1%, respectively, while it was lower in group B and poor in group C (71.4% and 23.5%, respectively)., Conclusion: This study revealed that the concordance rates of the severe genotypes with their phenotypes were good, while those of the milder genotypes were poor. The discrepancies could have resulted from the complex characteristics of 21-OHD genotyping and the limitations of using NGS alone without integrating with other comprehensive methods., (© 2021. Italian Society of Endocrinology (SIE).)

The article presents a two case study related to 53-years-old post-menopausal woman was referred to our out-patient clinic due to bilateral surrenal adenoma, and 7-year-old girl was referred to our clinic for hypertrichosis and dysmorphic facial appearance. Topics include the hormonal function tests for Cushing's syndrome, pheochromocytoma, and Conn's syndrome were negative, and the patient have two sons after spontaneous pregnancy.

The present study’s purpose was to determine the size and morphometric development of the female external genital organs on foetal cadavers. Dimensions of labia majora, labia minora and clitoris, bilabial diameter, vertical and horizontal diameters of hymenal opening, distance between the external urethral orifice and hymenal opening, distance between the clitoris and external urethral orifice and anogenital distance were measured. The hymenal types were determined. Mean values of parameters according to gestational weeks, months and trimesters were calculated. Imperforate hymen were determined in the first trimester. Twenty-eight foetuses with annular hymen, 25 foetuses with imperforate hymen, and 1 foetus with septated hymen were determined in the second trimester. Twenty-four foetuses with annular hymen, 3 foetuses with imperforate hymen, 1 foetus with fimbriated hymen, and 1 foetus with hymenal tag were determined in the third trimester. All foetuses in the full term were determined with annular hymen. [ABSTRACT FROM PUBLISHER]

Objective: Deficiency of steroid 5-alpha reductase type 2 (5αRD2) is a rare autosomal recessive disorder caused by mutations in the SRD5A2 gene. A defect in the 5-alpha reductase enzyme, which ensures conversion of testosterone into dihydrotestosterone, leads to disorders of sex development. This study presents the clinical and genetic results of patients with 5αRD2 deficiency. Methods: 5αRD2 deficiency was detected in 6 different patients from 3 unrelated families. All patients were reared as girls. Two of the patients presented with primary amenorrhea, one with primary amenorrhea and rejection of female gender, and the others with masses in their inguinal canals. Chromosome and sex-determining region Y (SRY) gene analyses were performed in all patients. Additionally, five exons of the SRD5A2 gene were amplified with polymerase chain reaction in the obtained DNA samples and evaluated. Results: While 46,XY was identified in 5 patients, 47,XXY was detected in one patient. The SRY gene was positive in all patients. The p.Ala65Pro (c193G>C) mutation and V89L polymorphism were observed in exon 1 of the SRD5A2 gene in all patients. Conclusion: Identification of this mutation and polymorphism is a significant indicator of presence of 5αRD2 deficiency in Southeastern Turkey, a geographical region where consanguineous marriages are also highly common. [ABSTRACT FROM AUTHOR]

Objective: The CYP19A1 gene product aromatase is responsible for estrogen synthesis and androgen/estrogen equilibrium in many tissues, particularly in the placenta and gonads. Aromatase deficiency can cause various clinical phenotypes resulting from excessive androgen accumulation and insufficient estrogen synthesis during the pre- and postnatal periods. In this study, our aim was to determine the clinical characteristics and CYP19A1 mutations in three patients from a large Turkish pedigree. Methods: The cases were the newborns referred to our clinic for clitoromegaly and labial fusion. Virilizing signs such as severe acne formation, voice deepening, and clitoromegaly were noted in the mothers during pregnancy. Preliminary diagnosis was aromatase deficiency. Therefore, direct DNA sequencing of CYP19A1 was performed in samples from parents (n=5) and patients (n=3). Results: In all patients, a novel homozygous insertion mutation in the fifth exon (568insC) was found to cause a frameshift in the open reading frame and to truncate the protein prior to the heme-binding region which is crucial for enzymatic activity. The parents were found to be heterozygous for this mutation. Additionally, all patients had hypoplastic ovaries instead of cystic and enlarged ovaries. Conclusion: A novel 568C insertion mutation in CYP19A1 can lead to severe aromatase deficiency. Homozygosity for this mutation is associated with the development of hypoplastic ovaries. This finding provides an important genetic marker for understanding the physiological function of aromatase in fetal ovarian development. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Medical Sciences is the property of Scientific and Technical Research Council of Turkey and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The prevalence of non-classic adrenal hyperplasia (NCAH) among Turkish women with hirsutism has not been established so far. Thus, we aimed to evaluate the prevalence of 21-hydroxylase (21-OH) deficiency by ACTH stimulation test among hirsute women. The study population consisted of 285 premenopousal women, aged 16–46 years (mean: 23.2 ± 0.3). All were hirsute and hyperandrogenic. Androgen secreting tumors of the ovaries and the adrenal glands were excluded as well as thyroid dysfunction and hyperprolactinemia. All the patients were evaluated by 0.25 mg (i.v.) ACTH stimulation test and 17-OHP responses were obtained at 30 and 60 min. The diagnosis of NCAH due to 21-OH deficiency was considered in patients with the poststimulation 17-OHP level exceed 10 ng/ml. Six (2.1%) of the patients had NCAH due to 21-OH deficiency confirmed by genotyping. The rest of the patients were polycystic ovary syndrome ( n = 166, 58.2%) and idiopathic hyperandrogenemia ( n = 113, 39.7%). There were no patients with idiopathic hirsutism because patients with normal serum androgen levels were excluded. This first and most extensive national study investigating NCAH prevalence among Turkish population showed that NCAH is not prevalent in this population. [ABSTRACT FROM AUTHOR]

BACKGROUND: In September 2002, an outbreak of toxoplasmosis was noted in a male boarding high school on the Aegean coast of Turkey. We have focused our efforts to investigate the sex hormones in this population. METHODS: Blood samples were collected from 40 male patients, 17–18 years old, who also had positive titres of antibody to Toxoplasma gondii. Serum FSH, LH, free testosterone (FT), total testosterone (TT), interferon‐γ (IFN‐γ), interleukin‐1β (IL‐1β) and macrophage‐inflammatory protein‐1α (MIP‐1α) concentrations were measured in all patients and 20 control subjects. Initially, the patients were divided on the basis of the levels of sex hormones into the following groups: patients who had normal sex hormone levels (n = 31) as group A and patients with low sex hormone levels (n = 9) as group B. RESULTS: IL‐1β levels were found to be higher in group B patients than group A. The levels of IL‐1β correlated significantly in a negative manner with FSH, LH, FT and TT in all patients with acute toxoplasmosis (n = 40). CONCLUSIONS: Acute toxoplasma infection may cause temporary hypogonadotrophic gonadal insufficiency regardless of the course of the disease. [ABSTRACT FROM AUTHOR]

Objectives: Lipoid congenital adrenal hyperplasia (LCAH) is a rare autosomal recessive disease caused by mutations in the steroidogenic acute regulatory protein ( STAR ) gene, expressed in the adrenal and gonadal tissues. In classical LCAH, individuals with 46, XY chromosomes present with a female appearance of the external genitalia due to insufficient androgen production. In the non-classical form, a milder phenotype is observed with male external genitalia. Here, we present a non-classical LCAH diagnosis with a newly identified c.266T>A (p.Ile89Asn) likely pathogenic homozygous variant in a 46, XY infant., Case Presentation: A three-month-and-thirteen-day-old male proband presented with clinical features of cortisol and mineralocorticoid deficiencies. The manifestation of salt-wasting syndrome occurred relatively late, and although the external genitalia appeared male, there was a mild virilization defect. The combination of mild impairment in androgen production and severe salt-wasting syndrome is an intriguing finding in our patient. Peripheral blood samples were obtained from the patient and his family. The newly identified variant, determined by next-generation sequencing analysis, was confirmed by segregation analysis showing carrier status in both parents., Conclusions: We aim to contribute to the literature by elucidating molecular mechanisms by presenting an atypical presentation and a newly identified variant., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Sex assignment decisions for children with disorders of sex development (DSD) should be based on integrative assessments of relevant biological and psychosocial characteristics., Aim: To investigate the factors that contributed to sex assignment decisions for children with 46,XY DSD., Patients: Sixty-one children recruited from a clinical sample were evaluated., Methods: Findings of endocrinological and psychiatric evaluations were entered into a logistic regression analysis., Results: Gender identity was the strongest correlate of assigned sex. External genital under-virilization, sex announced at birth and toy/ activity preferences were predominant predictors. Twelve children, six of whom were prepubertal, were reassigned to male sex., Conclusions: Psychological factors seem to be as influential on sex reassignment decisions as are endocrinological and social factors, especially if the disorder is diagnosed at an older age. Prepubertal gender conversion is possible, which implies the importance of follow-up during childhood.