What is the most common form of congenital adrenal hyperplasia (CAH) affecting cortisol synthesis?

The most common form of congenital adrenal hyperplasia (CAH) affecting cortisol synthesis is due to 21-hydroxylase deficiency. This enzymatic deficiency is critical because 21-hydroxylase is a key enzyme in the adrenal steroidogenesis pathway responsible for the conversion of progesterone to 11-deoxycortisol and 17-hydroxyprogesterone to 11-deoxycorticosterone. When there is a deficiency, there is an accumulation of steroid precursors, which can lead to decreased cortisol synthesis.

The lack of adequate cortisol leads to an increase in adrenocorticotropic hormone (ACTH) secretion from the pituitary gland due to a lack of negative feedback. This results in adrenal hyperplasia as the adrenal glands attempt to compensate for insufficient cortisol levels. Additionally, with insufficient cortisol, there is often increased production of androgens, which can lead to a range of clinical manifestations, including virilization in females and precocious puberty in males.

While other forms of CAH, such as 11-hydroxylase deficiency, 3-beta-hydroxysteroid dehydrogenase deficiency, and 17-alpha-hydroxylase deficiency do exist, they are less common and involve