Measuring steroids in hair opens up possibilities to identify congenital adrenal hyperplasia in developing countries.

OBJECTIVE: Patients with congenital adrenal hyperplasia (CAH) in developing countries have limited access to appropriate laboratory facilities for diagnosis and follow-up. The aim of this study is to evaluate steroid measurement in hair as a diagnostic tool to identify and monitor CAH in these patients. DESIGN: A method was developed to measure steroids in hair, the stability of steroids in hair was assessed, and the concentration range in healthy volunteers was determined. Hair samples of patients, before and after starting therapy, were transported at ambient temperature to The Netherlands for analysis. PATIENTS: Twenty-two Indonesian CAH patients and 84 healthy volunteers participated. MEASUREMENTS: Cortisol, 17-hydroxyprogesterone (17OHP), androstenedione, and testosterone in hair were measured by liquid chromatography with tandem mass spectrometry. RESULTS: Steroids in hair could be measured and remained stable (<4.9% deviation) for at least 3 weeks at 4°C and 30°C. In each of the untreated patients, hair concentrations of 17OHP (9.43-1135 pmol/g), androstenedione (36.1-432 pmol/g), and testosterone (2.85-69.2 pmol/g) were all above the upper limit of the corresponding range in healthy volunteers; 5.5 pmol/g, 13 pmol/g, and 1.8 pmol/g, respectively. After starting glucocorticoid treatment, the steroid concentrations in the hair of CAH patients decreased significantly for androstenedione (73%) and testosterone (59%) after 6 months. CONCLUSIONS: CAH could be confirmed in Indonesian patients based on the concentration of 17OHP, androstenedione, and testosterone in hair, and a treatment effect was observed. These findings open up opportunities to diagnose and/or monitor CAH in developing countries with a simple noninvasive technique.

Diurnal salivary androstenedione and 17-hydroxyprogesterone levels in healthy volunteers for monitoring treatment efficacy of patients with congenital adrenal hyperplasia.

OBJECTIVE: Treatment of congenital adrenal hyperplasia (CAH) patients with glucocorticoids is often challenging since there is a delicate balance between over- and undertreatment. Treatment can be monitored noninvasively by measuring salivary androstenedione (A4) and 17-hydroxyprogesterone (17-OHP). Optimal treatment monitoring requires the establishment of reference values in saliva. DESIGN: A descriptive study. PATIENTS: For this study saliva of 255 healthy paediatric and adult volunteers with an age range of 4-75 years old was used. MEASUREMENTS: We developed a sensitive liquid chromatography-tandem mass spectrometry method, assessed salivary A4 and 17-OHP stability, and measured A4 and 17-OHP concentrations in saliva collected in the morning, afternoon, and evening. RESULTS: We quantified A4 and 17-OHP concentrations in the morning, afternoon, and evening and demonstrated that there is a significant rhythm with the highest levels in the morning and decreasing levels over the day. A4 and 17-OHP concentrations display an age-dependent pattern. These steroids remain stable in saliva at ambient temperature for up to 5 days. CONCLUSIONS: Good stability of the steroids in saliva enables saliva collection by the patient at home. Since salivary A4 and 17-OHP display a diurnal rhythm and age-dependent pattern, we established reference values for both children and adults at three time points during the day. These reference values support treatment monitoring of children and adults with CAH.

Novel treatments for congenital adrenal hyperplasia.

Patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) need life-long medical treatment to replace the lacking glucocorticoids and potentially lacking mineralocorticoids and to lower elevated adrenal androgens. Long-term complications are common, including gonadal dysfunction, infertility, and cardiovascular and metabolic co-morbidity with reduced quality of life. These complications can be attributed to the exposure of supraphysiological dosages of glucocorticoids and the longstanding exposure to elevated adrenal androgens. Development of novel therapies is necessary to address the chronic glucocorticoid overexposure, lack of circadian rhythm in glucocorticoid replacement, and inefficient glucocorticoid delivery with concomitant periods of hyperandrogenism. In this review we aim to give an overview about the current treatment regimens and its limitations and describe novel therapies especially evaluated for 21OHD patients.

Karyotype - Phenotype Associations in Patients with Turner Syndrome.

Variation in karyotype may be associated with the phenotype of patients with Turner syndrome (TS). Our objective was to identify these associations between karyotype and phenotype in TS patients. This study was part of the European multicentre dsd-LIFE study. We evaluated the associations between different karyotypes of TS patients and age at diagnosis, Turner stigmata, cardiac/renal involvement and gonadal function. Information was available for 328 TS patients. Participants had a monosomy 45,X (46%), mosaicism 45,X/46,XX (10%), karyotype with isochromosome (18%), or other karyotype (26%). The clinical signs of TS were the most severe in patients with monosomy 45,X and the least severe in patients with mosaicism 45,X/46,XX. Patients with isochromosome and y-material showed an intermediate phenotype. Despite the more severe features in patients with monosomy 45,X, the median age at diagnosis was only slightly lower compared to patients with other karyotypes, which suggests opportunities for improvement of knowledge and diagnostics.

Cardiac function in paediatric patients with congenital adrenal hyperplasia due to 21 hydroxylase deficiency.

BACKGROUND: Hyperandrogenism and exogenous glucocorticoid excess may cause unfavourable changes in the cardiovascular risk profile of patients with congenital adrenal hyperplasia (CAH). OBJECTIVE: To evaluate the cardiac function in paediatric patients with CAH. PATIENTS AND METHODS: Twenty-seven paediatric patients with CAH, aged 8-16 years, were evaluated by physical examination, electrocardiogram (ECG), conventional echocardiography, tissue Doppler imaging and two-dimensional (2D) myocardial strain (rate) imaging. Results were compared to 27 age- and gender- matched healthy controls. RESULTS: No signs of left ventricular hypertrophy or dilatation were detected on echocardiography. ECG revealed a high prevalence (25.9%) of incomplete right bundle branch block. Left ventricular posterior wall thickness in diastole (LVPWd) was significantly lower in patients with CAH compared to controls (5.55 vs 6.53 mm; P = .009). The LVPWd Z-score was significantly lower in patients with CAH yet within the normal range (-1.12 vs -0.35; P = .002). Isovolumetric relaxation time was significantly lower in patients with CAH (49 vs 62 ms; P = .003). Global longitudinal, radial and circumferential strain was not significantly different compared to controls. Global radial strain rate was significantly higher compared to healthy controls (2.58 vs 2.06 1/s; P = .046). Global longitudinal strain was negatively correlated with 24-hour blood pressure parameters. CONCLUSION: Cardiac evaluation of paediatric patients with CAH showed no signs of left ventricular hypertrophy or ventricular dilatation. LVPWd was lower in patients with CAH than in controls but within the normal range. A shorter isovolumetric relaxation time in patients with CAH may be a sign of mild left ventricular diastolic dysfunction.

Prenatal Treatment with Dexamethasone in Suspected Congenital Adrenal Hyperplasia and Orofacial Cleft: a Case Report and Review of the Literature.

Congenital adrenal hyperplasia (CAH) due to 21 hydroxylase deficiency is a genetic disorder that leads to hypocortisolism, hyperandrogenism and, in the most severe forms, also to hypoaldosteronism. Girls with classic CAH are born with virilized external genitalia. Prenatal dexamethasone (DXM) treatment can reduce virilization but may have side effects for mother and fetus. We present the first case of a girl who was born with CAH and an orofacial cleft. She was treated with prenatal DXM to prevent virilization. Oral clefts have to be considered as a potential side effect of prenatal DXM treatment.

Disorders of Adrenal Steroidogenesis: Impact on Gonadal Function and Sex Development.

A defect in adrenal steroidogenesis may cause a disorder of sex development (DSD). Importantly, DSD of adrenal origin is not restricted to a genital phenotype but is in most cases accompanied by mild to severe impairment in glucocorticoid and/or mineralocorticoid synthesis. If a patient is suspected of DSD of adrenal origin evaluation of glucocorticoid and mineralocorticoid metabolism is therefore essential to provide adequate medical care in the case of a severe and potentially life-threatening insufficiency. The adrenal steroidogenic defects causing DSD, their clinical features and diagnostic work-up are discussed. In this review we provide an overview of defects in the adrenal steroidogenesis and its impact on gonadal function and sex development.

Salivary morning androstenedione and 17α-OH progesterone levels in childhood and puberty in patients with classic congenital adrenal hyperplasia.

BACKGROUND: Treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency can be monitored by salivary androstenedione (A-dione) and 17α-hydroxyprogesterone (17OHP) levels. There are no objective criteria for setting relevant target values or data on changes of 17OHP and A-dione during monitoring. METHODS: We evaluated A-dione and 17OHP levels in nearly 2000 salivary samples collected during long-term treatment of 84 paediatric patients with classic 21-hydroxylase deficiency. RESULTS: A-dione and 17OHP levels and its ratio 17OHP/A-dione remained constant from 4 to 11 years with no sex-related differences. During puberty, A-dione and 17OHP levels both increased, starting at earlier age in girls than in boys. The ratio 17OHP/A-dione declined. Normalised A-dione concomitant with elevated 17OHP [1.43 nmol/L (0.46-4.41) during prepuberty; 2.36 nmol/L (0.63-8.89) for boys and 1.99 nmol/L (0.32-6.98) for girls during puberty] could be obtained with overall median glucocorticoid doses of 11-15 mg/m2/day. A-dione levels above the upper reference limit (URL), suggesting undertreatment, coincided with 17OHP levels ≥10 times URL. The percentage of A-dione levels above URL was 16% at ages 4-8 years, but increased to 31% for girls at 16 years and 46% for boys at 17 years. CONCLUSIONS: Normalised A-dione consistent with 17OHP three times URL during prepuberty and normalised A-dione consistent with 4-6 times URL during puberty could be obtained by moderate glucocorticoid dosages. A constant 17OHP/A-dione ratio during prepuberty suggested absence of adrenarche. During puberty, a higher percentage of samples met the criteria for undertreatment, especially of boys.

Cardiometabolic Aspects of Congenital Adrenal Hyperplasia.

Treatment of classic congenital adrenal hyperplasia (CAH) is directed at replacing deficient hormones and reducing androgen excess. However, even in the era of early diagnosis and lifelong hormonal substitution, the presence of CAH is still associated with numerous complications and also with increased mortality. The aim of this article was to create an authoritative and balanced review concerning cardiometabolic risk in patients with CAH. The authors searched all major databases and scanned reference lists of all potentially eligible articles to find relevant articles. The risk was compared with that in other forms of adrenal insufficiency. The reviewed articles, most of which were published recently, provided conflicting results, which can be partially explained by differences in the inclusion criteria and treatment, small sample sizes and gene-environmental interactions. However, many studies showed that the presence of CAH is associated with an increased risk of weight gain, worsening of insulin sensitivity, high blood pressure, endothelial dysfunction, early atherosclerotic changes in the vascular wall and left ventricular diastolic dysfunction. These complications were more consistently reported in patients with classic than non-classic CAH and were in part related to hormonal and functional abnormalities associated with this disorder and/or to the impact of over- and undertreatment. An analysis of available studies suggests that individuals with classic CAH are at increased cardiometabolic risk. Excess cardiovascular and metabolic morbidity is likely multifactorial, related to glucocorticoid overtreatment, imperfect adrenal hormone replacement therapy, androgen excess and adrenomedullary failure. Cardiometabolic effects of new therapeutic approaches require future targeted studies.

Reference intervals for serum 11-oxygenated androgens in children.

OBJECTIVE: Classic androgens such as dehydroepiandrosterone, androstenedione, and testosterone are generally measured for diagnosis and treatment monitoring in children and adolescents with hyperandrogenism, as can occur in congenital adrenal hyperplasia, premature pubarche, or polycystic ovarian syndrome. However, adrenally-derived 11-oxygenated androgens also contribute to the androgen pool and should therefore be considered in clinical management. Nevertheless, paediatric reference intervals are lacking. Therefore, we developed a serum assay to establish reference intervals for four 11-oxygenated androgens in addition to four classic androgens. DESIGN: Reference interval study for serum 11-oxygenated androgens in children. METHODS: We developed and validated a sensitive LC-MS/MS assay and quantified eight serum androgens, including four 11-oxygenated androgens, in serum of 256 healthy children (aged 0-17 years old). An age-dependency for all androgens was observed, and therefore we divided the cohort based on age (prepubertal (n=133; 94 boys, 39 girls) and pubertal (n=123; 52 boys, 71 girls)) to compute reference intervals (2.5th - 97.5th percentiles). RESULTS: In the prepubertal group, there was no significant sex-difference for any of the measured androgens. In the pubertal group, androstenedione, testosterone, and dihydrotestosterone showed a significant difference between boys and girls. In contrast, adrenal androgens dehydroepiandrosterone, 11-hydroxyandrostenedione, 11-ketoandrostenedione, 11-hydroxytestosterone, and 11-ketotestosterone did not. CONCLUSIONS: We developed and validated an assay for 11-oxygenated androgens, in addition to four classic androgens and established reference intervals. This enables a comprehensive evaluation of serum androgen status in children with clinical symptoms of hyperandrogenism.

Experience in a PHTS Expertise Centre: Yield of Thyroid Ultrasound Surveillance in Children with PTEN Hamartoma Tumor Syndrome.

Objective: Children with PTEN hamartoma tumor syndrome (PHTS) are at increased risk for developing thyroid abnormalities, including differentiated thyroid carcinoma (DTC). The Dutch PHTS guideline recommends ultrasound surveillance starting from age 18. Since the literature describes PHTS patients who developed DTC before age 18, the Dutch PHTS expertise centre has initiated annual ultrasound surveillance starting from age 12. The purpose of this study was to identify the yield of thyroid ultrasound surveillance in children. Methods: A retrospective single centre cohort study was conducted. Pediatric PHTS patients who received thyroid ultrasound surveillance before age 18 between 2016-2023 were included. Patients' medical records have been reviewed. Primary outcomes included prevalence and time to develop thyroid nodules ≥10mm, nodular growth, goiter, thyroiditis and DTC. Descriptive statistics and Kaplan-Meier analyses were performed. Results: Forty-three patients were included. Two patients (5%) were diagnosed with DTC at ages 12 and 17. Both DTCs were identified as minimally invasive follicular carcinoma at stages pT3NxMx and pT1NxMx respectively. A total of 84% were diagnosed with thyroid abnormalities at a median age of 12 years (range 9-18). Most common findings were benign, including nodular disease (74%), goiter (30%) and autoimmune thyroiditis (12%). Nodular growth was observed in 14 patients (33%) resulting in (hemi)thyroidectomy in 7 patients (16%). Conclusion: Thyroid ultrasound surveillance resulted in the detection of DTC in 2/43 PHTS patients before age 18. These findings support the recommendation to initiate thyroid ultrasound surveillance in children at least from age 12, preferably within an expertise centre.

46,XX males with congenital adrenal hyperplasia: a clinical and biochemical description.

Introduction: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) or 11-hydroxylase deficiency (11OHD) is characterized by underproduction of cortisol and overproduction of adrenal androgens. These androgens lead to a variable degree of virilization of the female external genitalia in 46,XX individuals. Especially in developing countries, diagnosis is often delayed and 46,XX patients might be assigned as males. This study aims to describe the clinical and biochemical characteristics of a unique cohort of untreated male-reared 46,XX classic CAH patients from Indonesia and discusses treatment challenges. Methods: Nine untreated classic CAH patients with 46,XX genotype and 21OHD (n=6) or 11OHD (n=3), aged 3-46 years old, were included. Biometrical parameters, clinical characteristics, and biochemical measurements including glucocorticoids, renin, androgens, and the pituitary-gonadal axis were evaluated. Results: All patients had low early morning serum cortisol concentrations (median 89 nmol/L) without significant increase after ACTH stimulation. Three patients with salt wasting 21OHD reported one or more periods with seizures and/or vomiting in their past until the age of 6, but not thereafter. The remaining patients reported no severe illness or hospitalization episodes, despite their decreased capacity to produce cortisol. In the 21OHD patients, plasma renin levels were elevated compared to the reference range, and in 11OHD patients renin levels were in the low-normal range. All adult patients had serum testosterone concentrations within the normal male reference range. In 21OHD patients, serum 11-oxygenated androgens comprised 41-60% of the total serum androgen concentrations. Glucocorticoid treatment was offered to all patients, but they refused after counseling as this would reduce their endogenous androgen production and they did not report complaints of their low cortisol levels. Discussion: We describe a unique cohort of untreated classic 46,XX male CAH patients without overt clinical signs of cortisol deficiency despite their cortisol underproduction and incapacity to increase cortisol levels after ACTH stimulation. The described adolescent and adult patients produce androgen levels within or above the normal male reference range. Glucocorticoid treatment will lower these adrenal androgen concentrations. Therefore, in 46,XX CAH patients reared as males an individual treatment approach with careful counseling and clear instructions is needed.

Free cortisol and free 21-deoxycortisol in the clinical evaluation of congenital adrenal hyperplasia.

CONTEXT: Some patients with classic congenital adrenal hyperplasia (CAH) survive without glucocorticoid treatment. Increased precursor concentrations in these patients might lead to higher free (biological active) cortisol concentrations by influencing the cortisol-protein binding. In 21-hydroxylase deficiency (21OHD), the most common CAH form, accumulated 21-deoxycortisol (21DF) may further increase glucocorticoid activity. Both mechanisms could explain the low occurrence of symptoms in some untreated classic CAH patients. OBJECTIVE: Develop and validate an LC-MS/MS method for free cortisol and free 21DF to quantify these steroids in untreated patients with classic CAH (n=29), non-classic CAH (NCCAH, n=5), other forms of adrenal insufficiency (AI, n=3), and controls (n=11) before and 60 minutes after Synacthen® administration. RESULTS: Unstimulated total cortisol concentrations of untreated classic CAH patients (median 109 nmol/L) were lower than in untreated NCCAH patients (249 nmol/L, p=0.010) and controls (202 nmol/L, p=0.016), but free cortisol concentrations were similar. Basal free 21DF concentrations were high in 21OHD patients (median 5.32 nmol/L) and undetectable in AI patients and controls (<0.19 nmol/L). After Synacthen® administration, free 21DF concentrations increased in 21OHD patients, while free cortisol concentrations did not change. CONCLUSIONS: Free cortisol concentrations in classic CAH patients were similar to those in controls and NCCAH patients, indicating comparable cortisol availability. Additionally, 21OHD patients produce high concentrations of 21DF, possibly explaining the low occurrence of symptoms in some classic 21OHD patients. Free cortisol and 21DF levels should be considered in evaluating adrenal insufficiency in patients with CAH.

Monochorionic dizygous twins presenting with blood chimerism and discordant sex.

Monochorionic dizygous twins are probably more frequent than considered previously as many cases remain unrecognized, especially when the children have the same sex. Here we present a pair of dizygous, sex-discordant monochorionic twins who were conceived after artificial insemination. Histological examination of the placenta and extensive genetic studies of the healthy boy and girl clearly proved that they indeed were monochorionic dizygous twins with a fully joined blood circulation. We conclude that when counseling parents expecting monochorionic twins of discordant sex, not only a disorder of sexual differentiation in one of the twins should be addressed but also the possibility of dizygosity with a completely normal (sexual) development of both children.

Novel likely pathogenic variant in NR5A1 gene in a Tanzanian child with 46,XY differences of sex development, inherited from the mosaic father.

Summary: Pathogenic variants in the nuclear receptor subfamily 5 group A member 1 gene (NR5A1), which encodes steroidogenic factor 1 (SF1), result in 46,XY and 46,XX differences of sex development (DSD). In 46,XY individuals with a pathogenic variant in the NR5A1 gene a variable phenotype ranging from mild to severe is seen, including adrenal failure, testis dysgenesis, androgen synthesis defects, hypospadias and anorchia with microphallus and infertility. We report the clinical, endocrinological and genetic characteristics of a patient with 46,XY DSD with a novel likely pathogenic missense variant in the NR5A1 gene. A retrospective evaluation of the medical history, physical examination, limited endocrinological laboratory analysis and genetic analysis with DSD gene panel testing was performed. A 1.5-month-old individual was referred with ambiguous genitalia. The karyotype was 46,XY. The endocrinological analyses were within normal male reference including a normal response of cortisol within an adrenocorticotropic hormone test. A novel heterozygous missense variant c.206G>C p.(Arg69Pro) in the NR5A1 gene was detected. This variant was present in mosaic form (~20%) in his unaffected father. Because another missense variant at the same position and other missense variants involving the same highly conserved codon have been reported, we consider this NR5A1 variant in this 46,XY DSD patient as likely pathogenic in accordance with the ACMG/AMP 2015 guidelines causing ambiguous genitalia but no adrenal insufficiency. This variant was inherited from the apparently unaffected mosaic father, which might have implications for the recurrence risk in this family. Learning points: The importance of performing trio (patient and parents) sequencing is crucial in pointing out the origin of inheritance. In a 46,XY differences of sex development patient, a normal adrenal function does not rule out an NR5A1 mutation. With the support of a dedicated overseas institute partnership, we could solve this complex clinical case by molecular diagnosis in a resource-limited setting.

[Children and adolescents with gender questions: dilemmas in the hormonal treatment by multidisciplinary teams]. / Jongeren met genderincongruentie.

In the Netherlands but also in many other countries, there is an increasing social discussion about gender identity and gender diversity, and an increasing number of children and adolescents are seeking medical help because of questions about their gender identity. The cause of this increase is still unknown. Gender questions are diverse and require an individual approach by a multidisciplinary team. A number of adolescents have additional problems such as mood problems, autistiform symptoms and systemic problems. Diagnosis and treatment takes place in accordance with the quality standard for transgender care somatic and psychological. Hormonal treatment can help to reduce gender dysphoria and improve mental health.

Evaluation of Ex Vivo Adrenocorticotropic Hormone Responsiveness of Human Fetal Testis.

Testicular adrenal rest tumors (TARTs), commonly occurring in males with congenital adrenal hyperplasia, may arise from chronic stimulation of adrenocorticotropic hormone (ACTH)-sensitive cells in the testes. It is not yet established whether the human fetal testis (HFT) is responsive to ACTH. To investigate this, we cultured HFT tissue with and without ACTH for up to 5 days, and quantified adrenal steroid hormones and expression of adrenal steroidogenic enzymes. Fetal testis and adrenal tissue produced high levels of testosterone and cortisol, respectively, indicating viability. In contrast to fetal adrenal tissues, the expression of ACTH receptor MC2R was either absent or expressed at extremely low levels in ex vivo HFT tissue and no clear response to ACTH in gene expression or steroid hormone production was observed. Altogether, this study suggests that the HFT is unresponsive to ACTH, which would indicate that a TART does not arise from fetal testicular cells chronically exposed to ACTH in utero.

Corrigendum: Challenges in the treatment of late-identified untreated congenital adrenal hyperplasia due to CYP11B1 deficiency: Lessons from a developing country.

[This corrects the article DOI: 10.3389/fendo.2022.1015973.].

Quality of life in men with Klinefelter syndrome: a multicentre study.

Background: Klinefelter syndrome (KS) is associated with an increased risk of lower socioeconomic status and a higher risk for morbidity and mortality, which may have a significant impact on quality of life (QOL). The objective of this study is to investigate QOL in a large European cohort of men with KS. Design: Cross-sectional multicentre study. Methods: Two-hundred-eighteen men with KS were recruited from 14 clinical study centres in 6 European countries which participated in the European dsd-LIFE study. Male normative data from a healthy and a psychiatric reference population were used for comparison. The validated World Health Organization (WHO) QOL (WHOQOL)-BREF questionnaire was used to investigate five main domains of quality of life (WHOQOL): global, physical, psychological, environment, and social. Results: The QOL physical domain score was lower for men with KS compared to the healthy reference population (KS: 66.9; s.d. 19.4, n = 193; healthy reference population: 76.5; s.d. 16.2, n = 1324, P < 0.001) but higher compared to the psychiatric reference population (54.6; s.d. 20.6; n = 77, P < 0.001). The WHOQOL-psychological domain score was lower for men with KS compared to the healthy reference population (KS: 63.6; s.d. 17.8, n = 193; healthy reference population: 67.8; s.d. 15.6, n = 1324, P < 0.05) but higher compared to the psychiatric reference population (45.9; s.d. 26.0), n = 77, P < 0.001). The social domain score on the WHOQOL questionnaire was found to be lower in men with Klinefelter syndrome (KS) compared to the healthy reference population (KS: 60.0; s.d. 21.6, n = 193; healthy reference population: 68.2; s.d. 13.8, n = 1324, P < 0.001). However, this score was similar to that of the psychiatric reference population (61.0; s.d. 17.0, n = 77, P = 0.5). The WHO environment domain score of men with KS (70.0; s.d. 15.0, n = 193) was similar to the healthy reference population (70.5; s.d. 20.7, n = 1324) but higher compared to the psychiatric reference population (61.9; s.d. 20.8, n = 77, P = 0.002). Experienced discrimination, less social activities, and the presence of chronic health problems were associated with significantly decreased QOL in men with KS. Conclusion: Overall QOL in European men with KS is significantly worse compared to a healthy European reference population. Especially, the presence of discrimination, less social activities, and chronic health problems is associated with lower physical, psychological, and social QOL. Further studies are necessary to investigate if a multidisciplinary approach may help to provide adequate counselling and psychosocial support to improve QOL.

The clinical characteristics and quality of life of 248 pediatric and adult patients with Congenital Adrenal Hyperplasia.

Background: Congenital Adrenal Hyperplasia (CAH) is a chronic disease that requires lifelong treatment. Patients may face stigmatization, which may affect their quality of life (QoL). Therefore, we assessed the clinical characteristics and QoL of patients with CAH in the Middle East. Methods: This case-control study included patients with CAH aged >5 years from two tertiary centers (2020-2021). The patients were matched to a healthy control group and were then divided into pediatric and adult groups. Data were collected from their electronic medical records. Additionally, the EQ-5D-5L QoL questionnaire was completed by both the patients and control group to assess five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Results: The study included 248 patients with CAH (females: 58.8%), with a family history of the condition (57.3%) and/or parental consanguinity (68.1%). The most frequently reported gene defect was CYP21A2, while the most commonly reported symptoms/signs were ambiguous genitalia and obesity. Almost all female patients had received corrective surgery. The questionnaire response rate was 86.3% (n=214/248). The CAH patient group's mean total QoL score was 85.2 compared with 99.8 in the control. Further, CAH patients had lower QoL scores in all domains compared to those in the control group (p ≤ 0.0001-0.0023). The pain/discomfort and anxiety/depression domains were affected significantly more than the other domains were, with 47.7% and 44.4% participants, respectively, p<0.0001. Additionally, obesity was found to be a predictor of reduced mobility following a logistic regression analysis (p ≤ 0.04, OR (0.18-0.98)). Conclusion: Patients with CAH reported lower QoL overall, particularly in the pain/discomfort and anxiety/depression domains. Based on this, we recommend the early involvement of psychologists in a multidisciplinary team approach, pre-marital screening, and the implementation of awareness programs for people diagnosed with CAH in communities with high consanguineous mating.