What is the key difference in presentation between classic congenital adrenal hyperplasia (CAH) and late-onset CAH?

In classic congenital adrenal hyperplasia (CAH), the enzyme deficiency, most commonly 21-hydroxylase deficiency, leads to a significant impairment in cortisol synthesis. Consequently, the adrenal glands hyperproduce androgens, resulting in several clinical manifestations. One of the hallmark characteristics of classic CAH is the occurrence of salt-wasting crises due to a lack of adequate aldosterone production. This results in hyponatremia, hyperkalemia, and dehydration, often requiring urgent medical intervention in infants.

In contrast, late-onset CAH tends to present later in life, often after the neonatal period, and is typically associated with milder enzyme deficiencies. Patients with late-onset CAH may present with precocious puberty or other signs of androgen excess but do not generally experience the severe electrolyte imbalances seen in classic CAH. Neonatal screening programs help identify classic CAH promptly, preventing the severe consequences associated with salt-wasting and adrenal insufficiency, which is why recognizing that classic CAH includes these critical features is essential.