21-hydroxylase deficiency is the most common form of adrenogenital syndrome (congenital adrenal hyperplasia) and presents with precocious puberty, virilization, and accelerated linear growth. Hypotension and hyperkalemia may also be present due to a decrease in mineralocorticoids, with corresponding elevation in plasma renin levels.
21-hydroxylase deficiency is an autosomal recessive disorder where increased 17-hydroxyprogesterone and androgens occur as corticosteroid precursors are shunted to the androgenic synthesis pathways. Synthesis of cortisol and aldosterone are markedly decreased, which can result in hyperkalemia and hypotension and a compensatory increase in renin. Afflicted females present with pseudohermaphrodism due to virilization from elevated androgen production. Treatment includes exogenous glucocorticoids and mineralocorticoids.
Deaton et al. state that mild congenital adrenal hyperplasia (CAH) affects up to 1:100 persons in the US and is grossly underdiagnosed. They conclude that the diagnosis can be made in fetuses via HLA haplotype or demonstration of excess cortisol in the amniotic fluid.
Nimkarn et al. review 21-hydroxylase deficiency in CAH. This deficiency is the most common form of CAH. Disease severity depends on several factors,including the extent of impaired enzymatic activity, which is caused by different mutations of the 21-hydroxylase gene. Treatment centers around correcting the deficiency in cortisol secretion and suppressing the excess of androgens.
Illustration A diagrams steroidogenesis. Note the role of 21-hydroxylase (21a-hydroxylase in image) in the production of aldosterone and cortisol. Also note that 11ß-hydroxylase deficiency allows for production of 11-deoxycorticosterone, which acts as a mineralocorticoid when secreted in excess. Plasma renin and potassium levels are low in this disorder.
Answer 1: Increased mineralocorticoid production and an absence of androgens characterize 17a-hydroxylase deficiency. Afflicted males present with pseudohermaphroditism due to an absence of dihydrotestosterone (DHT). Afflicted females lack secondary sex characteristics.
Answer 2: 11ß-hydroxylase deficiency differs symptomatically from 21-hydroxylase deficiency due to the presence of hypertension in afflicted patients with low renin and potassium levels.
Answer 4: Aromatase converts testosterone to estrogen. Its activity is low in males.
Answer 5: 5a-reductase converts testosterone to DHT. Enzyme deficiency results in male pseudohermaphroditism including female phenotype and lack of internal reproductive structures.
Nimkarn S, Lin-Su K, New MI. Steroid 21 hydroxylase deficiency congenital adrenal hyperplasia. Pediatr Clin North Am. 2011 Oct;58(5):1281-300, xii. Review
PMID:21981961 (Link to Abstract)
Deaton MA, Glorioso JE, McLean DB. Congenital adrenal hyperplasia: not really a zebra. Am Fam Physician. 1999 Mar 1;59(5):1190-6, 1172.
USMLE World Step 1 QBank Question #2080. Copyright © USMLEWorld, LLC 2012