ESPE Abstracts

Primary adrenal insufficiency (PAI) is a potentially life-threatening condition that usually needs urgent diagnosis and treatment. Whilst autoimmune adrenal insufficiency (Addison disease) and other destructive causes are common in teenage years and adulthood, rare genetic forms of PAI are more common in infancy and childhood. Aside from congenital adrenal hyperplasia (CAH) (usually 21-hydroxylase deficiency, 1:10,000-15,000), other causes of early-onset PAI include developmental conditions (adrenal hypoplasia), ACTH-resistance conditions, oxidative stress/metabolic causes, and monogenic autoimmune dysfunction, as well as infective and destructive aetiologies (e.g., haemorrhage). More than 20 different genetic conditions have now been reported, with a range of different inheritance patterns (de novo dominant, recessive, X-linked, imprinted). Important associated features may be present, or may develop and need monitoring. Treatment approaches may vary, depending on the underlying cause. Thus, making a specific genetic diagnosis can have important implications for a child and their wider family. In recent years, several collaborative studies have used next-generation sequencing approaches to investigative the genetic basis of PAI, with diagnosis rates generally ranging from 75-85%, and even higher when classic CAH is included. Increasingly, clinical genetic testing is available. This symposium will provide an overview of genetic causes of PAI, the benefits of making a specific diagnosis, approaches to genetic analysis, and how this information relates to our understanding of human adrenal development and physiology of the HPA-axis.