Steroid disorders in children: Congenital adrenal hyperplasia and apparentmineralocorticoid excess

Our research team and laboratories have concentrated an two inherited endoc rine disorders, congenital adrenal hyperplasia (CAH) and apparent mineraloc orticoid excess, in thier investigations of the pathophysiology of adrenal steroid hormone disorders in children. CAH refers to a family of inherited disorders in which defects occur in one of the enzymatic: steps required to synthesize cortisol from cholesterol in the adrenal gland. Because of the impaired cortisol secretion, adrenocorticotropic hormone levels rise due to impairment of a negative feedback system, which results in hyperplasia of the adrenal cortex. The majority of cases is due to 21-hydroxylase deficien cy (21-OHD). Owing to the blocked enzymatic step, cortisol precursors accum ulate in excess and are converted to potent androgens, which are secreted a nd cause in utero virilization of the affected female fetus genitalia in th e classical form of CAH. A mild form of the 21-OHD, termed nonclassical 21- OHD, is the most common autosomal recessive disorder in humans, and occurs in 1/27 Ashkenazic Jews. Mutations in the CYP21 gene have been identified t hat cause both classical and nonclassical CAH. Apparent mineralocorticoid e xcess is a potentially fatal genetic disorder causing severe juvenile hyper tension, pre- and postnatal growth failure, and low to undetectable levels of potassium, renin, and aldosterone. It is caused by autosomal recessive m utations in the HSD11B2 gene, which result in a deficiency of 11 beta-hydro xysteroid dehydrogenase type 2. In 1998, we reported a mild form of this di sease, which may represent an important cause of low-renin hypertension.