section 32.1
Adrenal Cortex
This endothelial effect and the permissive effect of glu-
cocorticoids on catecholamine-induced vasoconstriction
inhibit edema and swelling. Use of glucocorticoids to re-
duce inflammation due to bacterial infection should not be
undertaken without concurrent use of antibiotics.
Adrenal Androgen,
Dehydroepiandrosterone (DHEA)
The zona reticularis is the innermost layer of the cor-
tex, about equal in size to the zona glomerulosa in the
adult. Although it shares similarities with the zona fascic-
ulata, both histologically and functionally the zona retic-
ularis should be regarded as a distinct entity because it
has certain features that are not found in the other zones.
One distinct feature is the relatively late appearance and
growth of this zone (“adrenarche”) and its functional de-
cline in late adulthood (“adrenopause”); another unique
feature is that the zona reticularis is the exclusive site of
DHEAS formation in the adult, owing to the presence of
a steroid sulfotransferase that attaches a sulfate to DHEA.
Although there is evidence that the zona fasciculata pro-
duces DHEA, no sulfate ester is formed at that site; and
although the zona reticularis contains cortisol-producing
cells from the zona fasciculata, the major steroid product
of this zone is DHEAS. This sulfated steroid is the most
abundant in circulation with basal plasma levels at least
1 0
times higher than peak levels of cortisol and about
1 0 0
times higher than that of DHEA. The levels are twice as
high in men as in women. The circulating level of DHEAS
increases at adrenarche, when the zona reticularis matures,
and it declines at adrenopause, when the zona reticularis
undergoes functional attenuation; in neither situation is
there any significant change in the circulating levels of
ACTH. However, the endocrine function of the zona retic-
ularis is known to be strongly influenced by ACTH. In
instances of ACTH deficiency, the level of DHEAS de-
clines, and the administration of ACTH provokes a rise
in plasma DHEAS levels. The physiological significance
of DHEAS in the adult is unclear. This sulfated steroid
is biologically inactive; however, cells that have steroid
sulfatase are capable of converting the steroid to its unes-
terified form (DHEA), which can then be transformed to
either estrone (El) in the presence of P450arom (CYP19)
or to DHT in the presence of 5a-reductase. The latter con-
version pathway explains why virilization can occur in
conditions of adrenal hyperactivity.
It has been suggested that the decline in DHEA and
DHEAS production after adrenopause may be causally
related to age-related health problems and that DHEA
replacement may reduce the aging process. Evidence to
date from animal and human studies that involved the
administration of DHEA appears to support the idea that
increasing or restoring the level of this steroid may be
beneficial in promoting protein anabolism and immune
function while decreasing body fat content, although the
evidence is not conclusive. However, the notion that this
steroid is a youth-promoting drug has led to successful
marketing of this preparation as a food supplement. Al-
though no known deleterious side effects of this steroid
have been reported, there is evidence from
in vitro
ies that high levels may cause convulsions by inhibiting
chloride currents in the CNS.
Disturbances in Adrenocortical Function
Primary adrenocortical insufficiency (Addison’s dis-
is a condition in which secretion of all adrenal
steroids diminishes or ceases owing to deterioration of
adrenocortical function. The adrenal cortex atrophies as
a result of an infectious disease or autoimmune reaction.
Circulating levels of aldosterone and cortisol decrease,
whereas those of renin and ACTH increase. ACTH lev-
els increase enough to produce darkening of the skin, a
hallmark of Addison’s disease. Aldosterone deficiency en-
courages potassium retention and sodium loss and leads
to hyperkalemia, hypovolemia, and hypotension. Defi-
ciency of cortisol renders the tissues more sensitive to
insulin; hence, hypoglycemia may develop. In addition,
cortisol deficiency diminishes responsiveness of tissues
to catecholamines, particularly in vascular smooth mus-
cles, which do not contract adequately in response to
adrenergic stimulation. All of these changes can lead to
circulatory collapse.
More specific adrenocortical deficiencies occur when
only specific steroidogenic enzymes are affected. If there
is deficient production of cortisol, which is the exclu-
sive feedback suppressor of ACTH release, hypersecte-
tion of ACTH with overstimulation of the adrenal cortex
(hyperplasia) results. This condition is called
tal adrenal hyperplasia.
The most common enzyme de-
ficiency is that of 21-hydroxylase (CYP21), and neonatal
diagnosis of this disorder is accomplished by measuring
17-hydroxyprogesterone. The incidence of 21-hydroxy-
lase deficiency varies from
1 0 , 0 0 0
to 1:18,000 live
births. The deficiency can be severe or mild, giving
rise to a continuum of clinical symptoms. Deficiency of
2 1
-hydroxylase causes a lack of production of both min-
eralocorticoids and glucocorticoids (Figure 30-2). Two
steroid precursors prior to the enzyme deficiency, namely,
progesterone and 17-hydroxyprogesterone, accumulate
and are diverted to the synthesis of androgens. The
decreased production of cortisol removes the negative
feedback on ACTH production by the pituitary, resulting
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