Psychosoziale Determinanten von Körperakzeptanz und Lebensqualität bei Frauen mit Adrenogenitalem Syndrom

Beim Adrenogenitalen Syndrom (AGS) handelt es sich um eine der häufigsten autosomal-rezessiv vererbten Erkrankungen, welche durch Enzymdefekte zu einer Störung der Steroidsynthese führt. Das AGS ist charakterisiert durch einen Cortisol- und in schweren Fällen auch Aldosteronmangel, sowie einen ACTH vermittelten Androgenexzess. Die Erkrankung hat durch den Androgenexzess insbesondere für betroffene Frauen weitreichende Konsequenzen. So kommt es durch den pränatalen Androgenexzess in der embryonalen Entwicklung zur Virilisierung der äußeren Genitale, was häufig operative Eingriffe notwendig macht. Zudem leiden die Patientinnen häufiger unter Hirsutismus, Akne, Zyklusstörungen und auch Infertilität. Auch zeigt sich ein deutlicher psychosozialer Einfluss. Frauen mit AGS sind häufiger bi- oder homosexuell, befinden sich seltener in Partnerschaften, äußern häufiger Bedenken bezüglich Sexualität und sind unzufriedener mit ihrem Sexualleben. Außerdem berichten sie häufiger von erlebter Stigmatisierung in Bezug auf ihr Geschlecht und ihr körperliches Erscheinungsbild und zeigen häufiger Geschlechts-untypisches Verhalten. Die oben aufgeführten Gründe legen nahe, dass es bei betroffenen Frauen mit AGS zu einer Beeinträchtigung der Lebensqualität als auch der Körperakzeptanz kommen kann. Für die Therapie und Betreuung dieser Patientinnen sollten jedoch sowohl einzelne positive als auch negative Einflussfaktoren auf das Outcome der Patientinnen identifiziert werden, sodass diese gezielt verstärkt oder behoben werden können. Die Datenerhebung dieser klinischen, retrospektiven Studie erfolgte im Rahmen der dsd-LIFE Studie zu Varianten der Geschlechtsdifferenzierung in 14 spezialisierten Zentren in Europa und ermöglichte somit eine große Stichprobengröße von 203 Patientinnen mit AGS. Die Datenerhebung erfolgte mithilfe eines Fragebogens und einer optionalen körperlichen Untersuchung. Die Lebensqualität wurde anhand des WHOQOL-BREF erhoben, welcher die Domänen der physischen, psychischen, umweltbezogenen und sozialen Lebensqualität umfasst. Die Körperakzeptanz wurde anhand der Body-image Skala erhoben. Zusätzlich wurde die Zufriedenheit der Betroffenen mit der professionellen Betreuung und der sozialen Unterstützung in verschiedenen Lebensphasen abgefragt. Unserer Ergebnisse zeigten eine verminderte Körperakzeptanz bei Frauen mit AGS im Vergleich zu einer gesunden Kontrollgruppe. Außerdem fanden wir eine verminderte Lebensqualität in Bezug auf die physische, psychologische und soziale Lebensqualität im Vergleich zu einer gesunden Kontrollkohorte. Des Weiteren konnten wichtige psychosoziale Einflussfaktoren auf die Lebensqualität und Körperakzeptanz für Frauen mit AGS nachgewiesen werden. So konnte die Zufriedenheit mit der professionellen Betreuung in den letzten 12 Monaten als signifikant positiver Prädiktor für die Lebensqualität identifiziert werden. Unzufriedenheit mit der Betreuung im Kindes- und Jugendalter und mit der allgemeinen Unterstützung in verschiedenen Lebensphasen erwies sich als signifikant negativer Prädiktor für die Lebensqualität als auch Körperakzeptanz. Bezüglich psychologischer Betreuung zeigte sich, dass mit etwa 18% der befragten Patientinnen nur ein geringer Anteil eine solche psychologische Betreuung in der Kindheit und Jugend, sowie im Erwachsenenalter erhalten hatten. Zusammenfassend fanden wir in unserer Kohorte eine verminderte Lebensqualität und Körperakzeptanz bei Frauen mit AGS. Beide Endpunkte dieser Studie scheinen maßgeblich durch die Zufriedenheit der Patientinnen mit der erhaltenen professionellen Betreuung und sozialen Unterstützung über die Lebensspanne beeinflusst zu sein. Für eine optimale Betreuung dieser Patientinnen über die gesamte Lebensspanne sollte eine Anbindung an ein spezialisiertes Zentrum mit einem multidisziplinären Therapiekonzept erfolgen. Insbesondere die Schulung für sensible Themen, sowie die Sensibilisierung des sozialen Umfelds und der Angehörigen sollte hierbei berücksichtigt werden. Zudem zeigen unsere Daten einen deutlichen Mangel an psychologischer Betreuung der Patientinnen. Sowohl Betroffenen als auch Angehörigen sollte wiederholt psychologische Unterstützung angeboten werden

Ectopic Prostate Tissue in the Uterine Cervix of a Female with Non-Classic Congenital Adrenal Hyperplasia-A Case Report

Introduction: The occurrence of ectopic prostate tissue in the female genital tract is rare and has only been described sporadically. The origin of these lesions is unclear, but their appearance seems to be associated with various forms of androgen excess, including androgen therapy for transgender treatment or disorders of sex development, such as classic congenital adrenal hyperplasia (CAH). This is the first described case of ectopic prostate tissue in the cervix uteri of a 46,XX patient with a confirmed diagnosis of non-classic CAH due to 21-OHD and a history of mild adrenal androgen excess. Case presentation: We describe a 34-year-old patient with a genetic diagnosis of non-classic CAH due to 21-hydroxylase deficiency (21-OHD) with a female karyo- and phenotype and a history of mild adrenal androgen excess. Due to dysplasia in the cervical smear, conization had to be performed, revealing ectopic prostate tissue in the cervix uteri of the patient. Conclusions: An association between androgen excess and the occurrence of prostate tissue is likely and should therefore be considered as a differential diagnosis for atypical tissue in the female genital tract

Major immunophenotypic abnormalities in patients with primary adrenal insufficiency of different etiology

INTRODUCTION Patients with primary adrenal insufficiency (PAI) suffer from increased risk of infection, adrenal crises and have a higher mortality rate. Such dismal outcomes have been inferred to immune cell dysregulation because of unphysiological cortisol replacement. As the immune landscape of patients with different types of PAI has not been systematically explored, we set out to immunophenotype PAI patients with different causes of glucocorticoid (GC) deficiency. METHODS This cross-sectional single center study includes 28 patients with congenital adrenal hyperplasia (CAH), 27 after bilateral adrenalectomy due to Cushing's syndrome (BADx), 21 with Addison's disease (AD) and 52 healthy controls. All patients with PAI were on a stable GC replacement regimen with a median dose of 25 mg hydrocortisone per day. Peripheral blood mononuclear cells were isolated from heparinized blood samples. Immune cell subsets were analyzed using multicolor flow cytometry after four-hour stimulation with phorbol myristate acetate and ionomycin. Natural killer (NK-) cell cytotoxicity and clock gene expression were investigated. RESULTS The percentage of T helper cell subsets was downregulated in AD patients (Th1 p = 0.0024, Th2 p = 0.0157, Th17 p < 0.0001) compared to controls. Cytotoxic T cell subsets were reduced in AD (Tc1 p = 0.0075, Tc2 p = 0.0154) and CAH patients (Tc1 p = 0.0055, Tc2 p = 0.0012) compared to controls. NKCC was reduced in all subsets of PAI patients, with smallest changes in CAH. Degranulation marker CD107a expression was upregulated in BADx and AD, not in CAH patients compared to controls (BADx p < 0.0001; AD p = 0.0002). In contrast to NK cell activating receptors, NK cell inhibiting receptor CD94 was upregulated in BADx and AD, but not in CAH patients (p < 0.0001). Although modulation in clock gene expression could be confirmed in our patient subgroups, major interindividual-intergroup dissimilarities were not detected. DISCUSSION In patients with different etiologies of PAI, distinct differences in T and NK cell-phenotypes became apparent despite the use of same GC preparation and dose. Our results highlight unsuspected differences in immune cell composition and function in PAI patients of different causes and suggest disease-specific alterations that might necessitate disease-specific treatment

An update on the long-term outcomes of prenatal dexamethasone treatment in congenital adrenal hyperplasia

First-trimester prenatal treatment with glucocorticoid (GC) dexamethasone (DEX) in pregnancies at risk for classic congenital adrenal hyperplasia (CAH) is associated with ethical dilemmas. Though effective in reducing virilisation in g irls with CAH, it entails exposure to high doses of GC in fetuses that do not benefit from the treatment. The current paper provides an update on the literature on outcomes of prenatal DEX treatment in CAH cases and unaffected subjects. Long-term follow-up resear ch is still needed to determine treatment safety. In addition, advances in early prenatal diagnostics for CAH and sex-typing as well as studies assessing dosing effects of DE X may avoid unnecessary treatment and improve treatment safety

Integration of clinical parameters and CT-based radiomics improves machine learning assisted subtyping of primary hyperaldosteronism

ObjectivesThe aim of this study was to investigate an integrated diagnostics approach for prediction of the source of aldosterone overproduction in primary hyperaldosteronism (PA).Methods269 patients from the prospective German Conn Registry with PA were included in this study. After segmentation of adrenal glands in native CT images, radiomic features were calculated. The study population consisted of a training (n = 215) and a validation (n = 54) cohort. The k = 25 best radiomic features, selected using maximum-relevance minimum-redundancy (MRMR) feature selection, were used to train a baseline random forest model to predict the result of AVS from imaging alone. In a second step, clinical parameters were integrated. Model performance was assessed via area under the receiver operating characteristic curve (ROC AUC). Permutation feature importance was used to assess the predictive value of selected features.ResultsRadiomics features alone allowed only for moderate discrimination of the location of aldosterone overproduction with a ROC AUC of 0.57 for unilateral left (UL), 0.61 for unilateral right (UR), and 0.50 for bilateral (BI) aldosterone overproduction (total 0.56, 95% CI: 0.45-0.65). Integration of clinical parameters into the model substantially improved ROC AUC values (0.61 UL, 0.68 UR, and 0.73 for BI, total 0.67, 95% CI: 0.57-0.77). According to permutation feature importance, lowest potassium value at baseline and saline infusion test (SIT) were the two most important features.ConclusionIntegration of clinical parameters into a radiomics machine learning model improves prediction of the source of aldosterone overproduction and subtyping in patients with PA

Modified-release hydrocortisone is associated with lower plasma renin activity in patients with salt-wasting congenital adrenal hyperplasia

OBJECTIVE: Poorly controlled salt-wasting (SW) congenital adrenal hyperplasia (CAH) patients often require high 9α-fluorocortisol doses as they show high levels of 17-hydroxyprogesterone (17OHP), which is a mineralocorticoid (MC)-receptor antagonist. DESIGN: We investigated the renin-angiotensin-aldosterone system in patients with SW-CAH receiving twice daily modified-release hydrocortisone (MR-HC, Efmody) compared with standard glucocorticoid (GC) therapy. METHODS: Data were analyzed from the 6-month, phase 3 study of MR-HC (n = 42) versus standard GC therapy (n = 41). MC replacement therapy remained unchanged throughout the study. Blood pressure, serum potassium, serum sodium, plasma renin activity (PRA), and serum 17OHP and androstenedione concentrations were analyzed at baseline, 4, 12, and 24 weeks. RESULTS: The median serum 17OHP in the morning was significantly lower on MR-HC compared with standard GC at 24 weeks (2.5 nmol L-1 (IQR 8.3) versus 10.5 nmol L-1 (IQR 55.2), P = .001). PRA decreased significantly from baseline to 24 weeks in patients on MR-HC (0.83 ng L-1 s-1 (IQR 1.0) to 0.48 ng L-1 s-1 (IQR 0.61), P = .012) but not in patients on standard GC (0.53 ng L-1 s-1 (IQR 0.66) to 0.52 ng L-1 s-1 (IQR 0.78), P = .613). Serum sodium concentrations increased from baseline to 24 weeks in patients on MR-HC (138.8 ± 1.9 mmol L-1 to 139.3 ± 1.8 mmol L-1, P = .047), but remained unchanged on standard GC (139.8 ± 1.6 mmol L-1 to 139.3 ± 1.9 mmol L-1, P = .135). No significant changes were seen in systolic and diastolic blood pressure and serum potassium levels. CONCLUSION: 6 months of MR-HC therapy decreased PRA and increased sodium levels indicating a greater agonist action of the 9α-fluorocortisol dose, which may be due to the decreased levels of the MC-receptor antagonist 17OHP

Outcome of COVID-19 infections in patients with adrenal insufficiency and excess

Background: Information on clinical outcomes of coronavirus disease 19 (COVID-19) infection in patients with adrenal disorders is scarce. Methods: A collaboration between the European Society of Endocrinology (ESE) Rare Disease Committee and European Reference Network on Rare Endocrine Conditions via the European Registries for Rare Endocrine Conditions allowed the collection of data on 64 cases (57 adrenal insufficiency (AI), 7 Cushing’s syndrome) that had been reported by 12 centres in 8 European countries between January 2020 and December 2021. Results: Of all 64 patients, 23 were males and 41 females (13 of those children) with a median age of 37 and 51 years. In 45/57 (95%) AI cases, COVID-19 infection was confirmed by testing. Primary insufficiency was present in 45/57 patients; 19 were affected by Addison’s disease, 19 by congenital adrenal hyperplasia and 7 by primary AI (PAI) due to other causes. The most relevant comorbidities were hypertension (12%), obesity (n = 14%) and diabetes mellitus (9%). An increase by a median of 2.0 (IQR 1.4) times the daily replacement dose was reported in 42 (74%) patients. Two patients were administered i.m. injection of 100 mg hydrocortisone, and 11/64 were admitted to the hospital. Two patients had to be transferred to the intensive care unit, one with a fatal outcome. Four patients reported persistent SARS-CoV-2 infection, all others complete remission. Conclusion: This European multicentre questionnaire is the first to collect data on the outcome of COVID-19 infection in patients with adrenal gland disorders. It suggests good clinical outcomes in case of duly dose adjustments and emphasizes the importance of patient education on sick day rules

Body Image and Quality of Life in Women with Congenital Adrenal Hyperplasia

Objective: Women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) may have poor quality of life (QoL) and low satisfaction with body appearance. We investigated the influence of the patients’ satisfaction with their support on their QoL and body image. Design: Retrospective, comparative, Europe-wide study as part of the multicenter dsd-LIFE study. Methods: 203 women with CAH were included in this study. We investigated the patients’ QoL and body image compared to a healthy control group. The patients’ satisfaction with their treatment and support in childhood and adolescence as well as in adulthood was assessed by questionnaire and its influence on the patients’ body image and QoL was analyzed by multiple regression models. Results: Women with CAH showed worse body image and poorer physical, psychological and social QoL compared to a healthy reference population. The patients’ satisfaction with professional care in the last 12 months was a significant positive predictor for all four domains of QoL (psychological, physical, social, environmental). Dissatisfaction with care in childhood and adolescence and with general support through different stages of life was a significant negative predictor for QoL and body image. Conclusions: These results show that women with CAH have poor QoL and body image compared to a healthy reference population. Psychosocial factors such as general and family support, and social interactions with professionals have a substantial impact on QoL and body image in adult females with CAH. This should be taken into account regarding patient care and multimodal therapy

<b>Supplements for the manuscript: Women with congenital adrenal hyperplasia have favorable pregnancy outcomes but prolonged time to conceive irrespective of phenotype</b>

This study examined pregnancy outcomes in women with congenital adrenal hyperplasia (CAH) from a retrospective multicenter perspective, including participants from tertiary reference centers in Austria, Germany, Italy, Sweden, and the USA. It involved 72 adult women categorized into non-classic (NC, n=34), simple virilizing (SV, n=21), and salt-wasting (SW, n=17) phenotypes. The study documented 133 pregnancies, resulting in 112 live births and 25 abortions. Findings highlighted a prolonged latency to pregnancy, particularly in the SV group, and a relatively high use of fertility-enhancing medications or assisted reproductive technologies. Despite these challenges, the fertility rates of women with CAH matched those of the general population, and abortion rates did not increase. The average number of children per woman was similar across all CAH phenotypes. The study also reported high rates of cesarean sections but low complications during pregnancy, delivery, and postpartum. Overall, the pregnancy outcomes for women with CAH were favorable, suggesting effective management and adaptation despite the condition</p