ACTH receptor blockade: a novel approach to treat congenital adrenal hyperplasia, or Cushing's disease.

It is hypothesized that blocking the adrenocorticotrophic hormone (ACTH) receptor, using either a blocking antibody or a drug will result in a medical cortical-adrenalectomy, with relative sparing of mineralocorticoid hormone production. This would be similar to the clinical findings in familial glucocorticoid deficiency type 1, an autosomal recessive condition due to inactivating mutations of the adrenal receptor for ACTH, also known as the melanocortin 2 receptor (MC2R). It is further hypothesized that MC2R blockade should allow using lower glucocorticoid doses to treat congenital adrenal hyperplasia (CAH) due to enzyme deficiency of either 21-hydroxylase (CYP21B) or 11-hydroxylase (CYP11B1), thus reaching a better final adult height than with current therapeutic strategies. Blocking the ACTH receptor can also be employed to medically treat Cushing's due to excess pituitary or ectopic ACTH production.