Which enzyme deficiency might result in both ambiguous genitalia and adrenal insufficiency?

The correct choice relates to 21-hydroxylase deficiency, which is associated with both ambiguous genitalia and adrenal insufficiency due to its role in steroidogenesis. This enzyme is critical in the synthesis of cortisol and aldosterone from progesterone and 17-hydroxyprogesterone. When there is a deficiency in 21-hydroxylase, there is a reduced conversion of these precursors, leading to decreased production of cortisol and aldosterone.

The lack of cortisol leads to adrenal insufficiency, marked by symptoms such as fatigue, weight loss, and potentially life-threatening adrenal crisis. In addition, the diminished feedback inhibition caused by low cortisol levels prompts increased ACTH (adrenocorticotropic hormone) secretion, which results in the accumulation of steroid precursors like 17-hydroxyprogesterone. The excess androgens produced from the shunted pathway can lead to virilization in genetic females (XX individuals), causing ambiguous genitalia at birth.

In contrast, 11-hydroxylase deficiency primarily presents with hypertension due to accumulation of 11-deoxycorticosterone, and while it can also cause mild virilization, it does not typically lead to ambiguous genitalia to the same extent as