Page 769 - Robbins Basic Pathology by Vinay Kumar, Abul K. Abbas, Jon C. Aster

Adrenocortical Hyperfunction (Hyperadrenalism) 755
Figure 19–38 A patient with Cushing syndrome. Characteristic features
include central obesity, “moon facies,” and abdominal striae.
(Reproduced with permission from Lloyd RV, et al: Atlas of Nontumor Pathology: Endocrine related conditions characterized by chronic excess aldos­
Diseases. Washington, DC, American Registry of Pathology, 2002.)
back (“buffalo hump”) (Fig. 19–38). Hypercortisolism
causes selective atrophy of fast-twitch (type II) myofibers,
with resultant decreased muscle mass and proximal limb
weakness. Glucocorticoids induce gluconeogenesis and
inhibit the uptake of glucose by cells, with resultant hyper-
glycemia, glucosuria, and polydipsia, mimicking diabetes
mellitus. The catabolic effects on proteins cause loss of col-
lagen and resorption of bone. Thus, the skin is thin, fragile,
and easily bruised; cutaneous striae are particularly common
in the abdominal area. Bone resorption results in the devel-
opment of osteoporosis, with consequent increased suscep-
tibility to fractures. Because glucocorticoids suppress the
immune response, patients with Cushing syndrome also
are at increased risk for a variety of infections. Additional
manifestations include hirsutism and menstrual abnormali-
ties, as well as a number of mental disturbances, including
mood swings, depression, and frank psychosis. Extra­
adrenal Cushing syndrome caused by pituitary or ectopic
ACTH secretion usually is associated with increased skin
pigmentation secondary to melanocyte-stimulating activ-
ity in the ACTH precursor molecule.
S U M M A RY
Hypercortisolism (Cushing Syndrome)
• The most common cause of hypercortisolism is exo­g­
enous administration of steroids.
• Endogenous hypercortisolism most often is secondary to
an ACTH-producing pituitary microadenoma (Cushing
disease), followed by primary adrenal neoplasms
(ACTH-independent hypercortisolism) and paraneoplastic
ACTH production by tumors (e.g., small cell lung cancer).
• The morphologic features in the adrenal include bilateral
cortical atrophy (in exogenous steroid-induced disease),
bilateral diffuse or nodular hyperplasia (most common
finding in endogenous Cushing syndrome), or an adreno­
cortical neoplasm.
Hyperaldosteronism
Hyperaldosteronism is the generic term for a group of closely
terone secretion. Hyperaldosteronism may be primary, or
it may be secondary to an extraadrenal cause. In secondary
hyperaldosteronism, aldosterone release occurs in response
to activation of the renin-angiotensin system. This condi-
tion is characterized by increased levels of plasma renin and
is encountered in association with
• Decreased renal perfusion (arteriolar nephrosclerosis,
renal artery stenosis)
• Arterial hypovolemia and edema (congestive heart
failure, cirrhosis, nephrotic syndrome)
• Pregnancy (caused by estrogen-induced increases in
plasma renin substrate)
Primary hyperaldosteronism, by contrast, indicates a primary,
autonomous overproduction of aldosterone, with resultant
suppression of the renin-angiotensin system and decreased
plasma renin activity. The potential causes of primary hyper-
aldosteronism are:
• Bilateral idiopathic hyperaldosteronism, characterized by
bilateral nodular hyperplasia of the adrenal glands. This
mechanism is the most common underlying cause of
primary hyperaldosteronism, accounting for about 60%
of cases. The pathogenesis is unclear.
• Adrenocortical neoplasm, either an aldosterone-producing
adenoma (the most common cause) or, rarely, an adre-
nocortical carcinoma. In approximately 35% of cases,
primary hyperaldosteronism is caused by a solitary
aldosterone-secreting adenoma, a condition referred to
as Conn syndrome.
• Rarely, familial hyperaldosteronism may result from a
genetic defect that leads to overactivity of the aldosterone
synthase gene, CYP11B2.
MORPHOLOGY
Aldosterone-producing adenomas are almost always
solitary, small (less than 2 cm in diameter), well-circumscribed
lesions. They are bright yellow on cut section and, surpris-
ingly, are composed of lipid-laden cortical cells more closely
resembling fasciculata cells than glomerulosa cells (the normal
source of aldosterone). In general, the cells tend to be
uniform in size and shape; occasionally there is some nuclear
and cellular pleomorphism. A characteristic feature of
aldosterone-producing adenomas is the presence of eosino-
philic, laminated cytoplasmic inclusions, known as spirono-
lactone bodies. These typically are found after treatment
with the antihypertensive agent spironolactone, which is the