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.

Management of Acute Adrenal Insufficiency-Related Adverse Events in Children with Congenital Adrenal Hyperplasia: Results of an International Survey of Specialist Centres.

INTRODUCTION: There is wide variation in reported rates of acute adrenal insufficiency (AI)-related adverse events (sick day episodes and adrenal crises) between centres. This study aimed to evaluate the level of consensus on criteria considered essential for defining and managing these events in children with Congenital Adrenal Hyperplasia. METHODS: Active users of the International Congenital Adrenal Hyperplasia and International Disorders of Sex Development (I-CAH/I-DSD) Registries (n = 66), non-active users of I-CAH/I-DSD (n = 35), and the EuRRECa e-Reporting Registry (n = 10) were approached to complete an online survey. RESULTS: Fifty-six centres from 27 countries responded to the survey; the response rates for the three groups were 42 (65%), 11 (31%), and 3 (30%), respectively. Steroid management plans, one to one patient education, and contact details of health care staff were provided by over 90% of centres in high-income countries. All 56 centres advised glucocorticoid stress dosing in the event of fever. Less common indications for sick day dosing included vaccination and mild afebrile intercurrent illness, recommended by 17 (30%) and 9 (16%) centres, respectively. The most frequently reported stress dosing regimens were tripling the total daily dose of hydrocortisone and administering 3 times daily and doubling or tripling the largest daily hydrocortisone dose depending on the nature of the trigger and administering 3 times daily, recommended by 24 (43%) and 21 (38%) centres, respectively. Vomiting was the most common indication for intramuscular hydrocortisone injection, reported by 34 (61%) centres. Over 50% of respondents indicated that essential clinical criteria for adrenal crisis should include fatigue and nausea or vomiting and over 60% indicated that hypotension, hyponatraemia, hyperkalaemia, and clinical improvement following parenteral glucocorticoids were essential criteria. In the event of an adrenal crisis, 47 (84%) reported that the majority of patients were admitted to hospital. For the management of an adrenal crisis, a bolus parenteral injection of hydrocortisone was the most frequently administered medication, reported by 50 (89%) centres. CONCLUSION: Although there is variation in the definition and management of AI-related adverse events in children amongst centres, there is also a good level of consensus on specific aspects that can lead to greater benchmarking of care.

The Quality Evaluation of Rare Disease Registries-An Assessment of the Essential Features of a Disease Registry.

Rare disease (RD) registries aim to promote data collection and sharing, and facilitate multidisciplinary collaboration with the overall aim of improving patient care. Recommendations relating to the minimum standards necessary to develop and maintain high quality registries are essential to ensure high quality data and sustainability of registries. The aim of this international study was to survey RD registry leaders to ascertain the level of consensus amongst the RD community regarding the quality criteria that should be considered essential features of a disease registry. Of 35 respondents representing 40 RD registries, over 95% indicated that essential quality criteria should include establishment of a good governance system (ethics approval, registry management team, standard operating protocol and long-term sustainability plan), data quality (personnel responsible for data entry and procedures for checking data quality) and construction of an IT infrastructure complying with Findable, Accessible, Interoperable and Reusable (FAIR) principles to maintain registries of high quality, with procedures for authorized user access, erasing personal data, data breach procedures and a web interface. Of the 22 registries that performed a self-assessment, over 80% stated that their registry had a leader, project management group, steering committee, active funding stream, website, and user access policies. This survey has acceptability amongst the RD community for the self-quality evaluation of RD registries with high levels of consensus for the proposed quality criteria.

International practice of corticosteroid replacement therapy in congenital adrenal hyperplasia: data from the I-CAH registry.

OBJECTIVE: Despite published guidelines no unified approach to hormone replacement in congenital adrenal hyperplasia (CAH) exists. We aimed to explore geographical and temporal variations in the treatment with glucocorticoids and mineralocorticoids in CAH. DESIGN: This retrospective multi-center study, including 31 centers (16 countries), analyzed data from the International-CAH Registry. METHODS: Data were collected from 461 patients aged 0-18 years with classic 21-hydroxylase deficiency (54.9% females) under follow-up between 1982 and 2018. Type, dose and timing of glucocorticoid and mineralocorticoid replacement were analyzed from 4174 patient visits. RESULTS: The most frequently used glucocorticoid was hydrocortisone (87.6%). Overall, there were significant differences between age groups with regards to daily hydrocortisone-equivalent dose for body surface, with the lowest dose (median with interquartile range) of 12.0 (10.0-14.5) mg/m2/day at age 1-8 years and the highest dose of 14.0 (11.6-17.4) mg/m2/day at age 12-18 years. Glucocorticoid doses decreased after 2010 in patients 0-8 years (P < 0.001) and remained unchanged in patients aged 8-18 years. Fludrocortisone was used in 92% of patients, with relative doses decreasing with age. A wide variation was observed among countries with regards to all aspects of steroid hormone replacement. CONCLUSIONS: Data from the I-CAH Registry suggests international variations in hormone replacement therapy, with a tendency to treatment with high doses in children.

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).