C h a p t e r 3 2
Disorders of Endocrine Control of Growth and Metabolism
789
is the adrenal form, caused by a benign or malignant
adrenal tumor. The third form is ectopic Cushing syn-
drome, caused by a nonpituitary ACTH-secreting tumor.
Certain extrapituitary malignant tumors such as small
cell carcinoma of the lung may secrete ACTH or, rarely,
CRH and produce Cushing syndrome. Cushing syn-
drome also can result from long-term therapy with one
of the potent pharmacologic preparations of glucocorti-
coids; this form is called
iatrogenic Cushing syndrome.
The major manifestations of Cushing syndrome rep-
resent an exaggeration of the many actions of cortisol.
Altered fat metabolism causes a peculiar deposition of
fat characterized by a protruding abdomen; subclavicu-
lar fat pads or “buffalo hump” on the back; and a round,
plethoric “moon face” (Fig. 32-16). There is muscle
weakness, and the extremities are thin because of protein
breakdown and muscle wasting. In advanced cases, the
skin over the forearms and legs becomes thin, having
the appearance of parchment. Purple striae, or stretch
marks, from stretching of the catabolically weakened
skin and subcutaneous tissues are distributed over the
breast, thighs, and abdomen. Osteoporosis may develop
because of destruction of bone proteins and alterations
in calcium metabolism, resulting in back pain, compres-
sion fractures of the vertebrae, and rib fractures. As cal-
cium is mobilized from bone, renal calculi may develop.
Derangements in glucose metabolism are found in
approximately 75% of patients, with clinically overt
diabetes mellitus occurring in approximately 20%. The
glucocorticoids possess mineralocorticoid properties;
this causes hypokalemia as a result of excessive potas-
sium excretion and hypertension resulting from sodium
retention. Inflammatory and immune responses are
inhibited, resulting in increased susceptibility to infec-
tion. Cortisol increases gastric acid secretion, which may
provoke gastric ulceration and bleeding. An accompany-
ing increase in androgen levels causes hirsutism (facial
hair), mild acne, and thinning of the hair, along with
menstrual irregularities in women (Fig. 32-17). Excess
levels of the glucocorticoids may give rise to extreme
emotional lability, ranging from mild euphoria and
absence of normal fatigue to grossly psychotic behavior.
Diagnosis of Cushing syndrome depends on the find-
ing of cortisol hypersecretion.
39,40,47,48
The determination of
24-hour excretion of cortisol in urine provides a reliable
and practical index of cortisol secretions. One of the promi-
nent features of Cushing syndrome is loss of the diurnal
pattern of cortisol secretion. This is why late-night (between
11
pm
and midnight) serum or salivary cortisol levels can be
inappropriately elevated, aiding in the diagnosis of Cushing
syndrome. The overnight dexamethasone suppression test
is also used as a screening tool for Cushing syndrome.
Emotional
disturbance
Moon facies
Osteoporosis
Cardiac
hypertrophy
(hypertension)
Pendulous
abdomen
Thin, wrinkled
skin
Abdominal striae
Amenorrhea
Fat pads
(buffalo hump)
Purpura
Ecchymosis
Poor wound
healing
Muscle wasting
and weakness
FIGURE 32-16.
Clinical features of Cushing syndrome.
FIGURE 32-17.
Cushing syndrome. A woman who suffered
from a pituitary adenoma that produced adrenocorticotropic
hormone exhibits a moon face, buffalo hump, increased facial
hair, and thinning of scalp hair (From: Merino MJ, Quezado M.
The endocrine system. In: Rubin R, Strayer DS, eds. Rubin’s
Pathology: Clinicopathologic Foundations of Medicine. 6th ed.
Philadelphia, PA: Wolters Kluwer Health/Lippincott Williams &
Wilkins; 2012:1073.)
