The I-CAH Registry: A platform for international collaboration for improving knowledge and clinical care in congenital adrenal hyperplasia.

To provide an overview of the I-CAH Registry. Following the successful roll-out of the I-DSD Registry in the 2000s, it was felt that there was a need for a registry for congenital adrenal hyperplasia (CAH) and this was launched in 2014 as a dedicated module within the original registry. In addition to supporting and promoting research, the I-CAH Registry acts as an international tool for benchmarking of clinical care and it does this through the collection of standardised data for specific projects. Surveillance of novel therapies in the field of CAH can also be achieved via global collaborations. Its robust governance ensures adherence to the international standards for rare disease registries. Rare disease registries such as the I-CAH Registry are important tools for all stakeholders involved in the care of people with CAH.

A realist evaluation of an enhanced court-based liaison and diversion service for defendants with neurodevelopmental disorders.

BACKGROUND: In England, court-based mental health liaison and diversion (L&D) services work across courts and police stations to support those with severe mental illness and other vulnerabilities. However, the evidence around how such services support those with neurodevelopmental disorders (NDs) is limited. AIMS: This study aimed to evaluate, through the lens of court and clinical staff, the introduction of a L&D service for defendants with NDs, designed to complement the existing L&D service. METHODS: A realist evaluation was undertaken involving multiple agencies based within an inner-city Magistrates' Court in London, England. We developed a logic model based on the initial programme theory focusing on component parts of the new enhanced service, specifically training, screening, signposting and interventions. We conducted semi-structured interviews with the court staff, judiciary and clinicians from the L&D service. RESULTS: The L&D service for defendants with NDs was successful in identifying and supporting the needs of those defendants. Benefits of this service included knowledge sharing, awareness raising and promoting good practice such as making reasonable adjustments. However, there were challenges for the court practitioners and clinicians in finding and accessing local specialist community services. CONCLUSION: A L&D service developed for defendants with NDs is feasible and beneficial to staff and clinicians who worked in the court setting leading to good practice being in place for the defendants. Going forward, a local care pathway would need to be agreed between commissioners and stakeholders including the judiciary to ensure timely and equitable access to local services by both defendants and practitioners working across diversion services for individuals with NDs.

Analysis of therapy monitoring in the International Congenital Adrenal Hyperplasia Registry.

OBJECTIVE: Congenital adrenal hyperplasia (CAH) requires exogenous steroid replacement. Treatment is commonly monitored by measuring 17-OH progesterone (17OHP) and androstenedione (D4). DESIGN: Retrospective cohort study using real-world data to evaluate 17OHP and D4 in relation to hydrocortisone (HC) dose in CAH patients treated in 14 countries. PATIENTS: Pseudonymized data from children with 21-hydroxylase deficiency (21OHD) recorded in the International CAH Registry. MEASUREMENTS: Assessments between January 2000 and October 2020 in patients prescribed HC were reviewed to summarise biomarkers 17OHP and D4 and HC dose. Longitudinal assessment of measures was carried out using linear mixed-effects models (LMEM). RESULTS: Cohort of 345 patients, 52.2% female, median age 4.3 years (interquartile range: 3.1-9.2) were taking a median 11.3 mg/m2 /day (8.6-14.4) of HC. Median 17OHP was 35.7 nmol/l (3.0-104.0). Median D4 under 12 years was 0 nmol/L (0-2.0) and above 12 years was 10.5 nmol/L (3.9-21.0). There were significant differences in biomarker values between centres (p < 0.05). Correlation between D4 and 17OHP was good in multiple regression with age (p < 0.001, R2 = 0.29). In longitudinal assessment, 17OHP levels did not change with age, whereas D4 levels increased with age (p < 0.001, R2 = 0.08). Neither biomarker varied directly with dose or weight (p > 0.05). Multivariate LMEM showed HC dose decreasing by 1.0 mg/m2 /day for every 1 point increase in weight standard deviation score. DISCUSSION: Registry data show large variability in 17OHP and D4 between centres. 17OHP correlates with D4 well when accounting for age. Prescribed HC dose per body surface area decreased with weight gain.

Monkeypox Case Investigation - Cook County Jail, Chicago, Illinois, July-August 2022.

Knowledge about monkeypox transmission risk in congregate settings is limited. In July 2022, the Chicago Department of Public Health (CDPH) confirmed a case of monkeypox in a person detained in Cook County Jail (CCJ) in Chicago, Illinois. This case was the first identified in a correctional setting in the United States and reported to CDC during the 2022 multinational monkeypox outbreak. CDPH collaborated with CCJ, the Illinois Department of Public Health (IDPH), and CDC to evaluate transmission risk within the facility. Fifty-seven residents were classified as having intermediate-risk exposures to the patient with monkeypox during the 7-day interval between the patient's symptom onset and his isolation. (Intermediate-risk exposure was defined as potentially being within 6 ft of the patient with monkeypox for a total of ≥3 hours cumulatively, without wearing a surgical mask or respirator, or potentially having contact between their own intact skin or clothing and the skin lesions or body fluids from the patient or with materials that were in contact with the patient's skin lesions or body fluids.) No secondary cases were identified among a subset of 62% of these potentially exposed residents who received symptom monitoring, serologic testing, or both. Thirteen residents accepted postexposure prophylaxis (PEP), with higher acceptance among those who were offered counseling individually or in small groups than among those who were offered PEP together in a large group. Monkeypox virus (MPXV) DNA, but no viable virus, was detected on one surface in a dormitory where the patient had been housed with other residents before he was isolated. Although monkeypox transmission might be limited in similar congregate settings in the absence of higher-risk exposures, congregate facilities should maintain recommended infection control practices in response to monkeypox cases, including placing the person with monkeypox in medical isolation and promptly and thoroughly cleaning and disinfecting spaces where the person has spent time. In addition, officials should provide information to residents and staff members about monkeypox symptoms and transmission modes, facilitate confidential monkeypox risk and symptom disclosure and prompt medical evaluation for symptoms that are reported, and provide PEP counseling in a private setting.

Severe mental illness, common mental disorders, and neurodevelopmental conditions amongst 9088 lower court attendees in London, UK.

BACKGROUND: Court Mental Health Liaison and Diversion Services (CMHLDS) have developed in some countries as a response to the over-representation of mental illness and other vulnerabilities amongst defendants presenting to criminal justice (or correctional) systems. This study examined the characteristics and rates of mental disorder of 9088 defendants referred to CMHLDS. METHOD: The study analysed service level data, obtained from the National Health Service's mental health data set, to examine characteristics relating to gender, ethnicity and comorbidity of common mental and neurodevelopmental disorders at five CMHLDS across London between September 2015 and April 2017. RESULTS: The sample included 7186 males (79.1%) and 1719 females (18.9%), the gender of 183 (2%) were not recorded. Of those referred, 6616 (72.8%) presented with an identifiable mental disorder and 503 (5.5%) with a neurodevelopmental disorder (NDD). Significantly higher rates of schizophrenia were reported amongst Black defendants (n = 681; 37.2%) and Asian defendants (n = 315; 29%), while higher rates of depression were found amongst White defendants (n = 1007; 22.1%). Substance misuse was reported amongst 2813 defendants (31%), and alcohol misuse amongst 2111 (23.2%), with significantly high rates of substance and alcohol misuse amongst defendants presenting with schizophrenia or personality disorder. CONCLUSIONS: This is one of the largest studies to examine mental health needs and vulnerabilities amongst defendants presenting to CMHLDS. It will enable an improved understanding of the required service designs and resources required to manage the healthcare pathways for people attending CMHLDS.

The Role of International Databases in Understanding the Aetiology and Consequences of Differences/Disorders of Sex Development.

The International Disorders of Sex Development (I-DSD) and International Congenital AdrenalHyperplasia registry (I-CAH) Registries were originally developed over 10 years ago and have since supported several strands of research and led to approximately 20 peer-reviewed publications. In addition to acting as an indispensable tool for monitoring clinical and patient-centered outcomes for improving clinical practice, the registries can support a wide nature of primary and secondary research and can also act as a platform for pharmacovigilance, given their ability to collect real world patient data within a secure, ethics approved virtual research environment. The challenge for the future is to ensure that the research community continues to use the registries to improve our understanding of Disorders of Sex Development (DSD).

Intelligent spectrophotometric resolution platforms for the challenging spectra of ipratropium and fenoterol in their combination inhaler with ecological friendliness assessment.

Asthma and chronic obstructive pulmonary disease (COPD) are the most common diagnoses for adults and children with respiratory tract inflammation. Recently, a novel fixed dose combination consisting of Ipratropium and Fenoterol has been released for the management and control of the symptoms of such disorders. The current research has newly developed and optimized three smart, accurate, simple, cost-effective, and eco-friendly spectrophotometric methods that enabled the simultaneous determination of the drugs under study in their combined inhaler dosage form, without the need for any previous separation steps, using water as a green solvent. The strategy employed was based on calculating one or two factors as a numerical spectrum or constant, which provided the complete removal of any component in the mixture that might overlap and the mathematical filtration of the targeted analyte. The methods developed could be classified into two types of spectrophotometric windows. Window I; involved absorption spectrum in their original zero-order forms (°D), which included recently designed methods named induced concentration subtraction (ICS) and induced dual wavelength (IDW). While window III focused on the ratio spectrum as the induced amplitude modulation (IAM) method. The extremely low absorptivity and lack of distinct absorption maximum in the zero-order absorption spectrum of Ipratropium were two intrinsic challenges that were better overcome by the proposed spectrophotometric methods than by the conventionally used ones. According to ICH guidelines, the proposed methods were validated using unified regression over range 2.0-40.0 µg/mL in the ICS method, while the linearity ranges for the IDW and IAM methods were 5.0-40.0 µg/mL of Ipratropium and 2.0-40.0 µg/mL of Fenoterol. Moreover, the three proposed methods were effectively used to assay the co-formulated marketed inhaler and further expanded to confirm the delivered dose uniformity in compliance with the USP guidelines. Finally, the established methods were evaluated for their greenness and blueness, in comparison to the official and reported analysis methods, using advanced cutting edge software metrics. Furthermore, the suggested techniques adhered well to the white analytical chemistry postulates that were recently published.

Chromatographic fingerprinting of ipratropium and fenoterol in their novel co-formulated inhaler treating major respiratory disorders; application to delivered dose uniformity testing along with greenness and whiteness assessment.

Ipratropium bromide (IPR) and fenoterol hydrobromide (FEN) have recently been combined in a promising inhaler to treat two prevalent inflammatory illnesses of the airways: bronchial asthma and chronic obstructive pulmonary disease (COPD). The necessity for a single, sensitive, and trustworthy analytical approach to cover the diverse and necessary tests of in-vitro and in-vivo studies is greatly grown with the rising production of new fixed combinations. Two novel, selective and environmentally friendly LC techniques were developed in order to guarantee precise measurement of IPR and FEN in their challenging formulation. The initial technique involved high-performance thin-layer chromatography (HPTLC) in conjunction with densitometric quantification. Chromatographic separation was attained on HPTLC plates utilizing ethyl acetate - ethanol - acetic acid (5.0:5.0:0.1, by volume) as a developing system. Densitometric quantification of the separated bands was carried out at 220.0 nm over concentration ranges of 0.50-15.0 µg/band for IPR and 0.50-12.0 µg/band for FEN. High-performance liquid chromatography (HPLC) paired with diode array detection (DAD) was the core of the second technique. The optimized separation was achieved on a Zorbax SB C18 (150 × 4.6 mm, 5 µm) column with a combination of 10.0 mM potassium dihydrogen orthophosphate, pH 5.0 ± 0.1, adjusted with o-phosphoric acid and methanol (70:30, v/v) as the mobile phase and pumped at flow rate of 1.0 mL/min. The peaks were monitored at 220.0 nm using diode array detection, achieving linearity range of 5.0-200.0 µg/mL for both drugs. The ICH criteria have been verified and both methods have been confirmed to be valid, and successfully applied for assay the cited drugs in the Atrovent® comp HFA metered dose inhaler as well as delivered dose uniformity testing of the final product. Finally, whiteness appraisal and several state-of-the-art green evaluation metrics were applied to evaluate the sustainability of the proposed methods. The suggested approaches produced promising results and are the first simple and sustainable methodologies for the simultaneous quantification of both drugs in different real samples, all of which strongly suggest their application in quality control laboratories.

Effectiveness of Telemedicine in Managing Health-Related Issues in the Pediatric Population: A Systematic Review.

Healthcare delivery is made more convenient and effective via telemedicine, which enables physicians to conduct virtual consultations and evaluations with pediatric patients. The purpose of this systematic review was to evaluate the efficacy of telemedicine as compared to physical appointments in the pediatric population. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to search for the available literature using pre-specified inclusion and exclusion criteria. These databases provided 968 relevant research articles, which Endnote software screened for duplicates. Fourteen studies were considered relevant for full-text evaluation. After complete text evaluation, only 11 of these articles were found to be relevant. The Newcastle-Ottawa Scale (NOS) was used for the risk of bias assessment of all included studies. Eleven articles in all satisfied the requirements for inclusion and were added to the review. Every study was classified as either a cluster randomized trial (27%) or a randomized controlled trial (RCT) (73%). There were between 22 and 400 participants in each trial. Medical conditions evaluated included obesity (27%), mental health disorders (9%), asthma (18%), otitis media (9%), skin disorders (9%), type 1 diabetes (9%), attention deficit hyperactivity disorder (ADHD) (9%), and pancreatic insufficiency associated with cystic fibrosis (1/11). Telemedicine strategies employed included telemedicine-based screening visits (9%), smartphone-based therapies (27%), phone counseling (18%), and videoconferencing visits between patients and doctors (45%). The outcomes of the telemedicine procedures in every included study were on par with or superior to those of the control groups. Medication adherence, appointment completion rates, life satisfaction, symptom management, and disease progression were all outcomes associated with these findings. Although more research is needed, the evidence from this review suggests that telemedicine services for the general public and pediatric care are comparable to or better than in-person services. Patients, healthcare professionals, and caregivers may benefit from using both telemedicine services and traditional in-person healthcare services. To maximize the potential of telemedicine, future research should focus on improving patients' access to care, increasing the cost-effectiveness of telemedicine services, and eliminating barriers to telemedicine use.

Development and validation of a short version of the quality of life-DSD questionnaire for parents of young children with conditions affecting sex development.

Background: There is a paucity of information on health-related quality of life (HRQoL) outcomes in parents and children with conditions affecting sex development. The objective of this study was to develop short forms of HRQoL questionnaires which consist of a 63-item and 25-item parent self-report (PSR) and parent proxy-report (PPR), respectively, optimizing use in routine clinical settings. Methods: Short questionnaires were developed following exploratory factor analysis using raw data from 132 parents. Long and short PSRs were completed by 24 parents of children with conditions affecting sex development, with a median age of 3.6 years (range 0.1, 6.6); 21 (88%) were boys, and 11 (46%) had proximal hypospadias. A subset of 19 parents completed both long and short PPRs. Results: Item selection, based on factor loadings of >0.8 and expert consultation, produced short PSRs and PPRs containing 16 and 7 items, respectively. There was no statistically significant difference in 11 out of 12 (92%) scales on the PSR and 4 out of 5 (80%) scales on the PPR when comparing short and long questionnaire scores. The short and long questionnaires took <1 min and 5 min to complete, respectively. Eighteen parents (75%) reported that the time taken to complete the short questionnaires was acceptable; 10 (42%) preferred short questionnaires. Ten (42%) versus 6 (25%) stated a preference for completing the short versus long questionnaires. Conclusion: The short versions were largely representative of the long questionnaires and are acceptable for evaluating psychosocial distress in young children and their caregivers. Further psychometric validation of the short forms is warranted.

Cross-sectional study on urinary metal concentrations in young adult residents of Emirate of Sharjah, United Arab Emirates.

BACKGROUND: Human biomonitoring is crucial for regulatory toxicology, yet data on biomarker concentrations in the UAE are lacking. This study addresses this gap by analyzing urinary concentrations of 16 metals in UAE young adults, assessing correlations with personal characteristics, dietary patterns, and lifestyle habits. METHODS: A cross-sectional pilot study was conducted among 144 randomly selected young adults (71 males and 73 females) from Sharjah, UAE, between January and March 2023. Participants provided urine samples, which were analyzed for 16 heavy metals using ICP-OES, and completed detailed questionnaires covering sociodemographic factors, lifestyle, and dietary habits. Descriptive statistics were used to summarize participant characteristics, and linear regression analysis was applied to explore associations between metal concentrations and factors such as gender, dietary habits, and exposure to environmental risks. Non-parametric tests, including the Mann-Whitney test, were used to assess differences by gender. Statistical significance was set at p < 0.05. Ethical approval was obtained, and informed consent was secured before participation. RESULTS: Significant findings include dietary influences on metal exposure, with rice consumption linked to higher metal concentrations. Sex differences were significant, with females showing elevated levels of arsenic, lead, and cadmium. Lifestyle factors, such as smoking and incense use, were correlated with increased barium and boron levels. CONCLUSION: This study highlights the significant role of dietary habits, especially the consumption of rice, in metal exposure among young adults in Sharjah. The findings highlight the urgent need for comprehensive human biomonitoring to understand environmental exposures and reform public health policies. The gender-specific differences in metal distribution suggest the necessity for targeted public health strategies. The study, however, is limited by its cross-sectional nature and the focus on a specific geographic area, warranting further research for broader generalizability. Future investigations, particularly on the impact of incense exposure on metal levels, are essential for developing comprehensive health interventions and preventive strategies in the UAE.

Temporal Trends in Acute Adrenal Insufficiency Events in Children With Congenital Adrenal Hyperplasia During 2019-2022.

Background: It is unclear whether targeted monitoring of acute adrenal insufficiency (AI) related adverse events (AE) such as sick day episodes (SDEs) and hospitalization rate in congenital adrenal hyperplasia (CAH) is associated with a change in the occurrence of these events. Aim: Study temporal trends of AI related AE in the I-CAH Registry. Methods: In 2022, data on the occurrence of AI-related AE in children aged <18 years with 21-hydroxylase deficiency CAH were compared to data collected in 2019. Results: In 2022, a total of 513 children from 38 centers in 21 countries with a median of 8 children (range 1-58) per center had 2470 visits evaluated over a 3-year period (2019-2022). The median SDE per patient year in 2022 was 0 (0-2.5) compared to 0.3 (0-6) in 2019 (P = .01). Despite adjustment for age, CAH phenotype and duration of study period, a difference in SDE rate was still apparent between the 2 cohorts. Of the 38 centers in the 2022 cohort, 21 had also participated in 2019 and a reduction in SDE rate was noted in 13 (62%), an increase was noted in 3 (14%), and in 5 (24%) the rate remained the same. Of the 474 SDEs reported in the 2022 cohort, 103 (22%) led to hospitalization compared to 299 of 1099 SDEs (27%) in the 2019 cohort (P = .02). Conclusion: The I-CAH Registry can be used for targeted monitoring of important clinical benchmarks in CAH. However, changes in reported benchmarks need careful interpretation and longer-term monitoring.

Miscommunication influences how women act when fetal movements decrease an interview study with Swedish Somali migrant women.

OBJECTIVE: To explore how Swedish Somali migrant women perceive fetal movements, process information about fetal movements, and take actions if decreased fetal activity occurs. DESIGN: A qualitative study based on individual semi-structured interviews. The interviews were analysed using content analysis. SETTING: The study was conducted in Sweden. PARTICIPANTS: Swedish Somali migrant women (n=15) pregnant in their third trimester or recently given birth. FINDINGS: The analysis led to the main category: tailored information about fetal movements enhances the possibility to seek care if the movements decrease. The results are described in the generic categories: explanatory models determine action; and understand and interpret information. KEY CONCLUSIONS: Miscommunication on fetal movements can be a hurdle for Swedish Somali migrant women that may have impact on stillbirth prevention and the quality of care. Improved communication and information tailored to individual needs is essential to achieve equality for women and their newborns. IMPLICATIONS FOR PRACTICE: The midwife can be used as a hub for reassuring that adequate information about fetal movements reaches each individual woman in antenatal care. Individualised information on fetal movements based on the women's own understanding is suggested to increase the possibility that the pregnant woman will seek care if the movements decrease. Somali women's verbal communication can be used to spread accurate information in the Somali community on the importance of seeking care if fetal movements decrease.

An automated, low volume, and high-throughput analytical platform for aggregate quantitation from cell culture media.

High throughput screening methods have driven a paradigm shift in biopharmaceutical development by reducing the costs of good manufactured (COGM) and accelerate the launch to market of novel drug products. Scale-down cell culture systems such as shaken 24- and 96-deep-well plates (DWPs) are used for initial screening of hundreds of recombinant mammalian clonal cell lines to quickly and efficiently select the best producing strains expressing product quality attributes that fit to industry platform. A common modification monitored from early-stage product development is protein aggregation due to its impact on safety and efficacy. This study aims to integrate high-throughput analysis of aggregation-prone therapeutic proteins with 96-deep well plate screening to rank clones based on the aggregation levels of the expressed proteins. Here we present an automated, small-scale analytical platform workflow combining the purification and subsequent aggregation analysis of protein biopharmaceuticals expressed in 96-DWP cell cultures. Product purification was achieved by small-scale solid-phase extraction using dual flow chromatography (DFC) automated on a robotic liquid handler for the parallel processing of up to 96 samples at a time. At-line coupling of size-exclusion chromatography (SEC) using a 2.1 mm ID column enabled the detection of aggregates with sub-2 µg sensitivity and a 3.5 min run time. The entire workflow was designed as an application to aggregation-prone mAbs and "mAb-like" next generation biopharmaceuticals, such as bispecific antibodies (BsAbs). Application of the high-throughput analytical workflow to a shake plate overgrow (SPOG) screen, enabled the screening of 384 different clonal cell lines in 32 h, requiring < 2 µg of protein per sample. Aggregation levels expressed by the clones varied between 9 and 76%. This high-throughput analytical workflow allowed for the early elimination of clonal cell lines with high aggregation, demonstrating the advantage of integrating analytical testing for critical quality attributes (CQAs) earlier in product development to drive better decision making.

The latest perspectives of small molecules FMS kinase inhibitors.

FMS kinase is a type III tyrosine kinase receptor that plays a central role in the pathophysiology and management of several diseases, including a range of cancer types, inflammatory disorders, neurodegenerative disorders, and bone disorders among others. In this review, the pathophysiological pathways of FMS kinase in different diseases and the recent developments of its monoclonal antibodies and inhibitors during the last five years are discussed. The biological and biochemical features of these inhibitors, including binding interactions, structure-activity relationships (SAR), selectivity, and potencies are discussed. The focus of this article is on the compounds that are promising leads and undergoing advanced clinical investigations, as well as on those that received FDA approval. In this article, we attempt to classify the reviewed FMS inhibitors according to their core chemical structure including pyridine, pyrrolopyridine, pyrazolopyridine, quinoline, and pyrimidine derivatives.

I-DSD: The First 10 Years.

BACKGROUND: Research and audit are vital for the management of Differences/Disorders of Sex Development (DSD). Clinical networks have a strong potential to drive these activities with the development of care standards including patient experience data and peer-observation of clinical care provision. SUMMARY: Following the 2005 Consensus Workshop that stressed the need for the regular collection and sharing of data across geographical boundaries, the current I-DSD registry was initially launched in 2008. Over a decade later, this registry and its associated network play an increasingly important role in supporting research, training, and benchmarking of care and service. Patient registries can also facilitate the development of local circles of patients and parents with similar conditions who can support each other. KEY MESSAGES: The case for participating in standardized data collection and exchange for DSD has now been made and should be standard practice in centres that care for people with DSD.

Emergency and perioperative management of adrenal insufficiency in children and young people: British Society for Paediatric Endocrinology and Diabetes consensus guidance.

Adrenal insufficiency (AI) is characterised by lack of cortisol production from the adrenal glands. This can be a primary adrenal disorder or secondary to adrenocorticotropic hormone deficiency or suppression from exogenous glucocorticoids. Symptoms of AI in children may initially be non-specific and include growth faltering, lethargy, poor feeding, weight loss, abdominal pain, vomiting and lingering illnesses. AI is treated with replacement doses of hydrocortisone. At times of physiological stress such as illness, trauma or surgery, there is an increased requirement for exogenous glucocorticoids, which if untreated can lead to an adrenal crisis and death. There are no unified guidelines for those <18 years old in the UK, leading to substantial variation in the management of AI. This paper sets out guidance for intercurrent illness, medical, dental and surgical procedures to allow timely and appropriate recognition and treatment of AI and adrenal crisis for children and young people.

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.

Long-term cardiometabolic morbidity in young adults with classic 21-hydroxylase deficiency congenital adrenal hyperplasia.

PURPOSE: To study the current practice for assessing comorbidity in adults with 21-hydroxylase CAH and to assess the prevalence of comorbidity in these adults. METHODS: A structured questionnaire was sent to 46 expert centres managing adults with CAH. Information collected included current therapy and surveillance practice with a particular focus on osteoporosis/osteopaenia, hyperlipidaemia, type 2 diabetes/hyperinsulinaemia, hypertension, CV disease, obesity. RESULTS: Of the 31 (67%) centres from 15 countries that completed the survey, 30 (97%) screened for hypertension by measuring blood pressure, 30 (97%) screened for obesity, 26 (84%) screened for abnormal glucose homoeostasis mainly by using Hb1Ac (73%), 25 (81%) screened for osteoporosis mainly by DXA (92%), 20 (65%) screened for hyperlipidaemia and 6 (19%) screened for additional CV disease. Of the 31 centres, 13 provided further information on the six co-morbidities in 244 patients with a median age of 33 yrs (range 19, 94). Of these, 126 (52%) were females and 174 (71%) received fludrocortisone in addition to glucocorticoids. Of the 244 adults, 73 (30%) were treated for at least one comorbidity and 15 (21%) for more than 2 co-morbidities. Of 73, the patients who were treated for osteoporosis/osteopaenia, hyperlipidaemia, type 2 diabetes/hyperinsulinaemia, hypertension, CV disease, obesity were 43 (59%), 17 (23%), 16 (22%), 10 (14%), 8 (11), 3 (4%) respectively. CONCLUSION: Cardiometabolic and bone morbidities are not uncommon in adults with CAH. There is a need to standardise the screening for these morbidities from early adulthood and to explore optimal therapy through routine collection of standardised data.

Hormonal control during infancy and testicular adrenal rest tumor development in males with congenital adrenal hyperplasia: a retrospective multicenter cohort study.

IMPORTANCE: Testicular adrenal rest tumors (TARTs), often found in male patients with congenital adrenal hyperplasia (CAH), are benign lesions causing testicular damage and infertility. We hypothesize that chronically elevated adrenocorticotropic hormone exposure during early life may promote TART development. OBJECTIVE: This study aimed to examine the association between commencing adequate glucocorticoid treatment early after birth and TART development. DESIGN AND PARTICIPANTS: This retrospective multicenter (n = 22) open cohort study collected longitudinal clinical and biochemical data of the first 4 years of life using the I-CAH registry and included 188 male patients (median age 13 years; interquartile range: 10-17) with 21-hydroxylase deficiency (n = 181) or 11-hydroxylase deficiency (n = 7). All patients underwent at least 1 testicular ultrasound. RESULTS: TART was detected in 72 (38%) of the patients. Prevalence varied between centers. When adjusted for CAH phenotype, a delayed CAH diagnosis of >1 year, compared with a diagnosis within 1 month of life, was associated with a 2.6 times higher risk of TART diagnosis. TART onset was not predicted by biochemical disease control or bone age advancement in the first 4 years of life, but increased height standard deviation scores at the end of the 4-year study period were associated with a 27% higher risk of TART diagnosis. CONCLUSIONS AND RELEVANCE: A delayed CAH diagnosis of >1 year vs CAH diagnosis within 1 month after birth was associated with a higher risk of TART development, which may be attributed to poor disease control in early life.