In which condition is the plasma or 24-hour urinary cortisol inconsistent with the clinical picture?

Congenital adrenal hyperplasia (CAH) is a group of genetic disorders affecting adrenal steroidogenesis, which often leads to imbalances in hormone production, particularly an excess of adrenal androgens. In classical forms of CAH, such as 21-hydroxylase deficiency, cortisol production is typically impaired due to enzymatic blockages. As a result, there is often an issue with the feedback mechanism, causing the body to release more adrenocorticotropic hormone (ACTH) in an effort to stimulate cortisol synthesis.

In patients with CAH, plasma or urinary cortisol levels may not accurately reflect the patient's clinical state. For example, despite high levels of ACTH, patients can have low or normal cortisol, especially in acute adrenal crises or certain situations where the adrenal glands cannot produce sufficient cortisol, leading to an inconsistent picture when serum or urinary cortisol measurements are assessed. Thus, this inconsistency between the clinical presentation and cortisol levels makes CAH a notable exception.

In contrast, other options such as pregnancy or ectopic ACTH syndrome present more predictable alterations in cortisol levels relative to clinical observations. During pregnancy, cortisol levels typically rise due to increased production by the placenta, and in conditions like ectopic ACTH syndrome, high cortisol