Bone Health Should Be an Important Concern in the Care of Patients Affected by 21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH, MIM 201910) describes a group of inherited autosomal recessive disorders characterized by enzyme defects in the steroidogenic pathways that lead to the biosynthesis of cortisol, aldosterone, and androgens. Many different mutations of the CYP21 gene have been identified causing varying degrees of impairment of 21-hydroxylase activity that result in a spectrum of disease expression [1]. Most patients are compound heterozygotes, and the clinical phenotype is generally related to the less severely mutated allele and, consequently, to the residual 21 hydroxylase activity.Indeed, CAH is classified according to symptoms and signs and to age of presentation. The clinical phenotype is typically classified as classic for the severe form, or non-classic (NCF) for the mild or late-onset form. Classic CAH is subclassified as salt-wasting (SW) or simple-virilizing (SV) forms, reflecting the degree of aldosterone deficiency. Current treatment is intended to reduce excessive ACTH and consequent increase in androgen production by substituting for deficient cortisol synthesis and, when necessary, mineralocorticoid substitution. During childhood, the main aims of the medical treatment of CAH secondary to 21-hydroxylase are to prevent salt loss and virilization, to achieve normal stature, and to undergo normal puberty [2]. Undertreatment exposes the patient to the risk of adrenal crisis and allows increased adrenal androgen production, with consequent advancement of bone age and loss of growth potential. Overtreatment, however, results in growth retardation, truncal obesity, and osteopaenia, through the effects of steroids on growth hormone secretion and bone metabolism. In adulthood, the aims of the medical treatment are to substitute cortisol and, when necessary, aldosterone deficiency, to ensure normal fertility, and to avoid the long-term consequences of glucocorticoid use. In such an intervention, there is a narrow therapeutic window through wh