The paired adrenal glands are situated in the retroperitoneum above the kidneys. They are variably shaped and irregularly folded, flattened structures whose cut surface reveals an outer yellow cortex and an inner gray medulla. The normal adrenals have an aggregate weight of about 6 g (upper limit, 8 g).
The adrenal cortex is derived from the mesoderm of the urogenital ridge. Its origin is independent of that of the adrenal medulla, which is derived from the neural crest.
The cortex is composed of the subcapsular zona glomerulosa (10–15%), the zona fasciculata (80%), and the zona reticularis (5–10%). The zona glomerulosa secretes aldosterone and is controlled by the renin–angiotensin mechanism, which is independent of the pituitary. The zona fasciculata and reticularis secrete cortisol and androgenic hormones, respectively, and are under the regulatory control of the pituitary via corticotropin adrenocorticotropic hormone (ACTH). ACTH secretion by the pituitary is under the control of (1) hypothalamic corticotropin-releasing factor (Chapter 57: The Pituitary Gland) and (2) the feedback inhibitory effect of serum cortisol.
Adrenocortical hormones are synthesized from cholesterol (Figure 60-1) by a series of enzyme-directed reactions.
Simplified pathways of steroid synthesis in the different zones of the adrenal cortex. Note the differences in the types of enzyme necessary and the different order of enzymatic reactions in the different zones.
Congenital Adrenal Hyperplasia
Congenital adrenal hyperplasia (adrenogenital syndrome) is a group of uncommon diseases that result from inherited deficiency of one of the several enzymes in the cortisol synthetic pathway (Figure 60-1). They have an autosomal recessive pattern of inheritance, and the genetic abnormality is on the short arm of chromosome 6. Decreased secretion of the end product (cortisol) stimulates, via the feedback mechanism, pituitary ACTH secretion. This in turn stimulates the zona fasciculata and reticularis to undergo bilateral hyperplasia and to secrete excessive amounts of precursor hormones. The clinical effects depend on the enzyme that is deficient and upon the products that accumulate prior to the block induced by the deficiency.
Complete 21-hydroxylase deficiency (30%) is a severe disease manifested by failure of cortisol and aldosterone secretion (Figure 60-2). Death usually occurs in infancy.
Partial 21-hydroxylase deficiency (60%) is the commonest of the group. 21-Hydroxylase levels are adequate to maintain normal aldosterone secretion under the renin–angiotensin stimulus so there is no sodium loss. Cortisol levels are also normal, the tendency to hypocortisolism having been compensated by adrenal hyperplasia via increased pituitary ACTH levels.
The main effects of partial 21-hydroxylase deficiency are (1) adrenal hyperplasia; (2) high serum ACTH levels; and (3) increased secretion of androgens by the overstimulated zona reticularis, producing virilism in the female and precocious puberty in the male. Serum levels of 17-hydroxyprogesterone and dehydroepiandrosterone are increased....