ESPE Abstracts

Primary adrenal insufficiency (PAI) is a rare, potentially life-threatening, condition due to abnormalities of steroid biosynthesis or of adrenal gland development and responsiveness. PAI is characterized by impaired secretion of glucocorticoids and can be accompanied by mineralocorticoid and adrenal androgens deficiency or excess, depending on the underlying cause. In adults, the most common etiology is represented by autoimmunity. In contrast, the disease in children is more frequently associated with inherited monogenic disorders either isolated or in the context of syndromes. The most common cause of PAI in children is represented by Congenital Adrenal Hyperplasia due to 21 OH deficiency. Prompt recognition is important since delayed treatment or more severe symptoms will increase mortality or morbidity. The diagnosis of PAI is challenging due to its insidious onset; clinical presentation in children is indeed related to the respective hormone deficiency and is highly variable, ranging from subtle and nonspecific symptomatology to acute onset with life-threatening adrenal crisis. The diagnostic process includes the demonstration of low cortisol concentrations along with high plasma ACTH. Plasma renin and aldosterone levels should be measured to determine the presence of mineralocorticoid deficiency. Once PAI has been confirmed, the etiology should be investigated. Establishing a diagnosis has great importance to patient care for the correct management, treatment, and monitoring as well as for counseling about inheritance patterns. The diagnostic workup should take into account detailed clinical and biochemical characterization of the subject. Although many forms of PAI do not have diagnostic specific features, in recent years the emergence of NGS approaches has extended the knowledge on the genetic background of childhood-onset PAI. The mainstay of treatment is glucocorticoid replacement. Oral hydrocortisone is the first choice treatment in children. In case of mineralocorticoid deficiency, replacement with fludrocortisone is needed. However, currently available glucocorticoid preparation fails to replicate the physiological cortisol circadian rythm and additional advances are needed to improve therapy and outcomes. In this session, the diagnostic approach and management of children with PAI will be discussed.