Congenital Adrenal Hyperplasia
Congenital adrenal hyperplasia (CAH) refers to a group of genetic conditions that result in an enzyme deficiency that alters the production of adrenal hormones. Approximately 95% of CAH cases are caused by a mutation that leads to deficiency of the enzyme 21-hydroxylase. In classic CAH, severe deficiency of this enzyme leads to an inability of the adrenal glands to produce cortisol and, in approximately 75% of cases, aldosterone.
If left untreated, classic CAH can result in salt wasting, dehydration, and even death. Even with cortisol replacement, high levels of adrenocorticotropic hormone (ACTH) from the pituitary gland result in excess androgen production leading to virilization and menstrual irregularities in females. Both males and females with classic CAH can experience problems with growth and development in childhood including early puberty, short stature or height below genetic potential, and fertility problems in adulthood.
Classic CAH is estimated to affect up to approximately 30,000 people in the U.S. and 50,000 people in Europe.
There are currently no nonsteroidal treatments approved by the U.S. Food and Drug Administration (FDA) for classic CAH. Glucocorticoids, the current standard of care, are used to correct the endogenous cortisol deficiency and to try to reduce the high ACTH levels and androgen excess. However, the dose and duration of steroid use required to try to control androgen excess is generally well above the normal physiological level of cortisol, which can result in serious and common complications of steroid excess, including metabolic abnormalities, bone loss, growth impairment, and iatrogenic Cushing’s syndrome.