Mineralocorticoid Deficiency and Treatment in Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) is a disorder of steroidogenesis in which cortisol metabolism primarily is impaired. Mineralocorticoid deficiency in CAH is a feature of 21-Hydroxylase (21-OHD), 3-Hydroxysteroid dehydrogenase (3-HSD) deficiencies and lipoid adrenal hyperplasia. Deficiency of 21-OHD accounts for 90% of cases of CAH [1] while deficiency of 3-HSD, and lipoid adrenal hyperplasia are rare causes of CAH. Approximately 75% of cases of 21-OHD [1] and 60%–70% of cases of 3-HSD deficiency [2] cannot synthesise sufficient aldosterone and are classed as "salt wasters."Several studies have demonstrated strong genetic association between the degree of mineralocorticoid and glucocorticoid deficiency in 21-OHD CAH and abnormalities in the CYP21 gene [3–6]. Large gene deletions and point mutations which are expected to produce no measurable enzyme activity are associated with aldosterone deficiency and salt-wasting 21-OHD [7]. Exceptions however exist and a similar mutation can be associated with more than one phenotype giving rise to genotype-phenotype discordance [5]. The I172N CYP21 mutation is mainly associated with simple virilizing CAH but can also cause salt wasting CAH [8]. A significant difference exists between the degree of genotype-phenotype correlation demonstrated in relation to the concentration of aldosterone and that of genital phenotype [9]. The relationship with degree of virilization with genotype and aldosterone concentration is less predictable as various genetic factors regulate androgen biosynthesis and sensitivity or the ability to retain sodium through extra-adrenal mechanisms [9, 10]. A degree and spectrum of aldosterone deficiency and salt loss exists in all forms of CAH including those with simple virilising and nonclassical forms of CAH [2, 11, 12]. In clinical practice this is only relevant in very hot countries where extreme salt deprivation can manifest.Glucocorticoids are essential for development and function of adrenal medulla