Approach to the Child and Adolescent With Adrenal Insufficiency.

Abstract

The management of adrenal insufficiency (AI) is challenging, and the overall goals of treatment are to prevent life-threatening adrenal crises, to optimize linear growth, to control androgen levels without overdosing in patients with congenital adrenal hyperplasia (CAH), and to improve quality of life in affected individuals. Standard glucocorticoid formulations fail to replicate the circadian rhythm of cortisol and control the adrenal androgen production driven by adrenocorticotropin. To personalize and tailor glucocorticoid therapy and to improve patient outcomes, new pharmacological strategies have been developed that best mimic physiological cortisol secretion. Novel therapeutic approaches in the management of AI include new ways to deliver circadian cortisol replacement as well as various adjunctive therapies to reduce androgen production and/or androgen action/effects. Preclinical studies are exploring the role of restorative cell-based therapies, and a first recombinant adeno-associated virus-based gene therapy is also being developed in humans with CAH. In this article, we present 3 illustrative cases of AI with different underlying etiologies and times of presentation. Diagnostic and management processes are discussed with an emphasis on treatment and outcomes. We have also provided the most up-to-date evidence for the tailored management of children and adolescents with AI.