Our research team and laboratories have concentrated on two inherited endocrine
disorders, congenital adrenal
hyperplasia (CAH) and apparent
mineralocorticoid 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 deficiency (21-OHD). Owing to the blocked enzymatic step,
cortisol precursors accumulate in excess and are converted to potent
androgens, which are secreted and cause in utero
virilization of the affected female fetus genitalia in the 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 that cause both classical and nonclassical CAH. Apparent
mineralocorticoid excess is a potentially fatal
genetic disorder causing severe juvenile
hypertension, pre- and postnatal growth failure, and low to undetectable levels of
potassium,
renin, and
aldosterone. It is caused by autosomal recessive mutations in the HSD11B2 gene, which result in a deficiency of
11beta-hydroxysteroid dehydrogenase type 2. In 1998, we reported a mild form of this disease, which may represent an important cause of low-
renin hypertension.