Congenital Adrenal Hyperplasia

Classic congenital adrenal hyperplasia (CAH) is a genetic disorder that results in an enzyme deficiency that alters the production of adrenal steroids. Because of this deficiency, the adrenal glands have little to no cortisol biosynthesis, resulting in a potentially life-threatening condition. If left untreated, classic CAH can result in salt wasting, dehydration, and eventually death. Even with cortisol replacement, persistent elevation of adrenocorticotropic hormone (ACTH) from the pituitary gland results in excessive androgen levels leading to virilization and menstrual irregularities in females; both males and females may also experience precocious puberty, short stature, hirsutism, acne and fertility problems. Classic CAH is a disease that affects approximately 20,000 to 30,000 people in the United States.

There are currently no non-steroidal FDA-approved treatments for classic CAH. Corticosteroids, the current standard of care, are used to both correct the endogenous cortisol deficiency and reduce the excessive ACTH levels and androgen excess. However, the dose and duration of steroid use required to suppress ACTH is well above the normal physiological level of cortisol, which can result in serious and common complications, including metabolic syndrome, bone loss, growth impairment and iatrogenic Cushing’s syndrome.