Management of adolescents with congenital adrenal hyperplasia

Summary

The management of congenital adrenal hyperplasia involves suppression of adrenal androgen production, in addition to treatment of adrenal insufficiency. Management of adolescents with congenital adrenal hyperplasia is especially challenging because changes in the hormonal milieu during puberty can lead to inadequate suppression of adrenal androgens, psychosocial issues often affect adherence to medical therapy, and sexual function plays a major part in adolescence and young adulthood. For these reasons, treatment regimen reassessment is indicated during adolescence. Patients with non-classic congenital adrenal hyperplasia require reassessment regarding the need for glucocorticoid drug treatment. No clinical trials have compared various regimens for classic congenital adrenal hyperplasia in adults, thus therapy is individualised and based on the prevention of adverse outcomes. Extensive patient education is key during transition from paediatric care to adult care and should include education of females with classic congenital adrenal hyperplasia regarding their genital anatomy and surgical history. Common issues for these patients include urinary incontinence, vaginal stenosis, clitoral pain, and cosmetic concerns; for males with classic congenital adrenal hyperplasia, common issues include testicular adrenal rest tumours. Transition from paediatric to adult care is most successful when phased over many years. Education of health-care providers on how to successfully transition patients is greatly needed.

Introduction

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is an autosomal recessive disease of the adrenal cortex caused by mutations in the CYP21A2 gene. Impairment of cortisol biosynthesis results in overstimulation of the adrenal glands and excessive androgen production. There is a wide range of disease severity with good genotype-phenotype correlation. Genetic mutations that significantly impair synthesis of the 21-hydroxylase enzyme result in the classic or severe form of congenital adrenal hyperplasia, whereas genetic mutations that mildly impair the 21-hydroxylase enzyme result in a mild non-classic form of the disease.¹ Classic congenital adrenal hyperplasia has an estimated worldwide prevalence of 1 in 16 000 births and presents in newborn girls as genital ambiguity.1, 2 About 75% of patients with classic congenital adrenal hyperplasia also have severe aldosterone deficiency, which can result in a life-threatening salt-wasting adrenal crisis in the neonate. Patients with the classic form of the disease who produce small amounts of aldosterone and therefore escape the neonatal adrenal crisis are termed classic simple virilising. The prevalence of non-classic congenital adrenal hyperplasia is estimated as 0·1%, but can be higher (1–2%) in some ethnic groups (eg, Ashkenazi Jewish, Hispanic, and Yugoslav ethnic groups).3, 4

The clinical management of congenital adrenal hyperplasia (CAH) involves suppression of adrenal androgen production, in addition to treatment of adrenal insufficiency. Supraphysiological doses of glucocorticoid drugs are often needed to adequately suppress adrenal androgens.⁵ However, glucocorticoid excess can result in obesity, growth suppression in children, decreased bone mineral density, cardiovascular risk, and adverse psychological effects.6, 7 Absence of adequate androgen suppression in congenital adrenal hyperplasia can result in early puberty, virilisation in females, infertility, adrenal and adrenal rest tumour formation (classic disease only), and potential adverse psychological effects. Patient management focuses on the control of excess androgen production, while avoiding the side-effects of hypercortisolism. Generally, clinicians need to provide individualised therapy because a standardised approach fails to account for individual variability in disease severity and response to treatment.

Management of adolescents with congenital adrenal hyperplasia presents unique challenges. Changes in the hormonal milieu during puberty can lead to inadequate suppression of adrenal androgens at a time when psychosocial issues often affect adherence to medical therapy. Once epiphyseal closure has occurred and growth regulation is no longer a concern, a shift in treatment goals from optimisation of growth and development to prevention of long-term adverse outcomes and optimisation of fertility and sexual function is needed. Sexual maturation occurs during adolescence, and clinicians caring for children with congenital adrenal hyperplasia play a major part in promoting a healthy self-image. For women with classic congenital adrenal hyperplasia, comprehension of their genital anatomy and surgical history is essential. Health professionals need to be educated about the unique needs of adolescents with congenital adrenal hyperplasia as they become increasingly independent from parental supervision and transfer from paediatric care to adult care (termed here transition). In this Review, we discuss several challenges faced by adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency, and provide guidance to health-care professionals in helping patients to navigate a path towards self-reliance and successful transfer of care to an adult practitioner.