Robert Debré et Pitié-Salpétrière
Ecole des Psychologues Praticiens
Rue du Montparnasse
FR–75006 Paris (France)
Karinne Gueniche, Psychologist PhD
Service Endocrinologie, Gynécologie et Diabétologie Pédiatrique
Hôpital Necker Enfants Malades
149, rue de Sèvres
FR–75015 Paris (France)
E-Mail [email protected]
Specific Illnesses
Polak M, Touraine P (eds): Transition of Care: From Childhood to Adulthood in Endocrinology, Gynecology, and Diabetes. Endocr Dev. Basel, Karger, 2018, vol 33, pp 17–33 (DOI: 10.1159/000487523)
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Transition of Care from Childhood to Adulthood: Congenital Adrenal Hyperplasia
Anne Bachelot
Centre de Référence des Pathologies Gynécologiques Rares, ICAN, Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Department of Endocrinology and Reproductive Medicine, AP–HP, IE3M, Hôpital Pitié-Salpêtrière, Paris, France
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Abstract
Deficiency of the 21-hydroxylase enzyme is the most common form of congenital adrenal hyperplasia (CAH), accounting for more than 95% of the cases. With the advent of newborn screening and hormone replacement therapy, most children with CAH survive into adulthood. Adolescents and adults with CAH experience a number of complications, including short stature, obesity, infertility, impaired bone mineral density, and reduced quality of life. Transition from pediatric to adult care and management of long-term complications are challenging for both patients and practitioners. 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 on bone, metabolism, and cardiovascular risk. Recent 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. During transition from pediatric to adult specific care, a shift in treatment goals is thus needed. Successful transition from pediatric to adult health care requires a regular follow-up of patients by a multidisciplinary team including pediatric endocrinologists, urologists, gynecologists, psychiatrists, and adult endocrinologists. All of this could be included in a specific therapeutic education program regarding transition and/or CAH.
© 2018 S. Karger AG, Basel
Congenital adrenal hyperplasia (CAH, MIM 201910) corresponds to a group of inherited autosomal recessive disorders that arise from defective steroidogenesis and result from a deficiency in one or several of the enzymes of cortisol biosynthesis. Deficiency of the 21-hydroxylase enzyme is the most common form of CAH, accounting for more than 95% of the cases (Fig. 1) [1]. The impaired glucocorticoid (GC) feedback inhibition via the classic negative feedback loop leads to increased secretion of adrenocorticotropic hormone (ACTH) and to subsequent adrenal hyperplasia and increased production of adrenal androgens and steroid precursors prior to the enzymatic defect (Fig. 1) [1]. CAH due to 21-hydroxylase deficiency (21-OHD) is the result of deletions or deleterious mutations in the CYP21A2 gene [1]. There are many mutations of the CYP21A2 gene identified so far, which cause varying degrees of impairment of 21-hydroxylase activity, with a good genotype/phenotype correlation [1–3]. Most patients are compound heterozygotes. The clinical phenotype, related to the less severe mutated allele, is classified as classic for the severe form, or nonclassic for the mild form. Classic CAH has an estimated prevalence of 1 in 15,000 births and encompasses in 75% the salt-wasting (SW) form and in 25% the simple virilizing (SV) form, depending on the degree of aldosterone deficiency [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].