What condition is indicated by increased plasma ACTH levels?

Increased plasma ACTH levels typically occur in the context of adrenal insufficiency or conditions where the feedback mechanism regulating cortisol production is disrupted. In the case of adrenal enzyme deficiencies, such as 11-hydroxylase, 17-hydroxylase, or 21-hydroxylase deficiencies, the adrenal cortex is unable to produce adequate levels of cortisol. As a result, the hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the anterior pituitary to release more ACTH in an attempt to stimulate cortisol production from the adrenal glands.

When any of these enzymatic pathways are deficient, especially in 21-hydroxylase deficiency, cortisol levels drop, leading to increased ACTH production. This is a common finding in congenital adrenal hyperplasia (CAH) conditions.

In contrast, conditions such as primary adrenal insufficiency would lead to elevated ACTH due to low cortisol levels. However, the specific mention of multiple pathway deficiencies—11, 17, and 21-hydroxylase—highlights a broader context where ACTH levels can also be elevated due to reduced feedback inhibition on the pituitary gland from the adrenal cortex, which is consistent across these different enzymatic deficiencies