[4]. The prevalence of nonclassic CAH is estimated as 1 in 1,000 births but can be higher (1–2%) in some ethnic groups [5]. The lives of patients with CAH have improved greatly since the discovery that cortisone is an effective treatment for the disorder in the 1950s. Neonatal screening is being done in several countries, and DNA-based prenatal diagnosis is feasible.
Fig. 1. Steroidogenesis in patients with CAH due to 21-hydroxylase deficiency.
Clinical management involves adrenal insufficiency treatment by cortisol and, when necessary, aldosterone substitution. Its role is to reduce the excessive ACTH production and consequently to suppress adrenal androgen production. Achieving and maintaining adrenal androgen suppression is far more challenging than preventing adrenal crises, and in some patients it is difficult to control adrenal androgen production without employing supraphysiological doses of GC [1, 2].
Therapeutic Managements during Transition between Pediatric and Adult Health Care
Contrarily to primary adrenal insufficiency, the aim of GC treatment is not only to compensate for the deficient hormone, but also to blunt the nocturnal ACTH secretion, which is the major driver of adrenal androgen production.
Management problems of CAH differ depending on patient age and sex. During childhood, the main aims of the medical treatment of CAH due to 21-OHD are to prevent salt loss, to achieve normal stature and to undergo normal puberty [2]. Once growth is complete, the management goals change, therefore the GC regimen should be reassessed. 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 GC use on bone, metabolism, and cardiovascular (CV) risk [6]. Indeed, overtreatment has been shown to result in growth suppression, obesity, and decreased bone mineral density (BMD), through the effects of steroids on growth hormone secretion and bone metabolism [6–8]. On the other hand, absence of adequate androgen suppression exposes the patient to the risk of adrenal crisis, early puberty, advancement of bone age and loss of growth potential in childhood, and to adrenal crisis and infertility in adulthood. In such an intervention, there is a narrow therapeutic window through which the intended results can be achieved [9].
Management of CAH during adolescence and the transition from pediatric to adult health care are challenging tasks because profound hormonal changes occur during this period, which can lead to inadequate suppression of adrenal androgens [10]. Moreover, this happens at a time when psychosocial issues often affect adherence to medical therapy [2]. Therefore, treatment regimens should be reassessed during adolescence and adulthood. In a prospective, cross-sectional study, the pharmacokinetic parameters of total and free cortisol in subjects with classic SW CAH have been determined [11]. The clearance of total and free cortisol was significantly higher in the pubertal than the prepubertal and postpubertal CAH patients. The volume of distribution of total and free cortisol was significantly higher in the pubertal and postpubertal than in prepubertal patients. No difference in the half-life of total or free cortisol was observed between groups. This was thought to be due to the concomitant rise in cortisol clearance and volume of distribution, both important determinants of the elimination of a drug from the body and, hence, its half-life. Comparison of the pharmacokinetic parameters of free cortisol between males and females in each separate group of patients (prepubertal, pubertal, and postpubertal) revealed a significantly shorter half-life of free cortisol in pubertal females than in pubertal males. The net effect of these changes in cortisol pharmacokinetics, if the administration schedule of hydrocortisone remains unchanged, will be a loss of control of the hypothalamic-pituitary-adrenal axis, inadequate suppression of the adrenal cortex, and excessive production of adrenal androgens and steroid precursors [11].
In children, hydrocortisone is the GC of choice because longer-acting GCs are more likely to impair growth [1, 12, 13]. Most oral GC regimens are proposed with at least half or 2/3 of the global dose in the morning [6, 14].Cross-sectional studies from France, the UK, and the USA show the use of varied GC regimens in adults, with some adult CAH patients given hydrocortisone and some given long-acting GC preparations such as dexamethasone, prednisone, or prednisolone [15–17]. No randomized controlled trials have assessed these varied regimens. There is no established cutoff of 17-hydroxyprogesterone levels in adults, and probably the optimal dose of GCs is that which fails to fully suppress 17-hydroxyprogesterone and maintains androgens in the mid-normal range [18]. The dose of mineralocorticoid (MC) treatment required for adults is generally lower than that required for infants and children. The dose should be adjusted to avoid hypertension and to maintain plasma renin activity in the upper normal range, although there is no consensus on the exact therapeutic goal of this treatment in adult patients [18]. The use of fludrocortisone therapy in patients with the SV form of CAH should be recommended in some patients because it might allow management with lower doses of GC [2]. Ideally, the treatment should be monitored in order to avoid iatrogenic comorbidities and to enable a good quality of life (QoL) [19]. However, this goal has not been reached up to now, since increased comorbidities and mortality are reported in patients with CAH [20, 21]. A recent study has shown that, at the time of transition between pediatric and adult care, the health status of young people with CAH was less than ideal with significant numbers having poor biochemical control, reduced final height, increased CV risk with elevated body mass index and blood pressure (BP), and reduced reproductive health [22]. These results were comparable to the recent UK study of adults with CAH [15]. These current data suggest that poor health status is likely to begin in adolescence and persist into adulthood, highlighting the importance of this time period in a patient’s endocrine care.
Management of Classic CAH in Adolescents and Adults
Female-Specific Issues
Sexuality and fertility in women with classic CAH have been described for many years as impaired, especially
