Benign tumors in the pituitary or adrenal glands can lead to excess release of
ACTH or cortisol into the blood, causing the symptoms of Cushing syndrome.
Typically, excess levels of endogenous cortisol—not synthetic forms of
cortisol—can cause hypertension, most likely because of its weak binding capac-
ity with mineralocorticoid receptors (i.e., aldosterone receptors).
Typically, hypercortisolism comes from: (1) A pituitary adenoma, which
secretes excess ACTH, thus causing release of cortisol from the adrenals;
(2) an adrenal adenoma, which secretes excess cortisol; (3) a lung tumor, which
secretes excess ACTH; or (4) administration of synthetic forms of cortisol
(i.e., dexamethasone, prednisone, etc.) due to previously diagnosed diseases,
such as rheumatoid arthritis. In the case of a pituitary adenoma, the location of
the adenoma makes the pituitary gland insensitive to the negative feedback
mechanism brought on by excess cortisol in the blood. Sixty-six percent of all
cases of Cushing syndrome are derived from pituitary adenomas. When hyper-
cortisolism is due to exogenous administration of steroids it is referred to as
iatrogenic Cushing syndrome.
Also, because cortisol is a stress hormone, people who suffer a great deal
of stress, such as athletes, alcoholics, and pregnant women may have high
blood cortisol levels and exhibit symptoms of Cushing syndrome (also known
as pseudo-Cushing syndrome).
Treatment of Cushing syndrome is intended to return cortisol levels back to
normal and usually occurs through surgery. In some cases medications, such
as mitotane, which lower blood and urine cortisol levels, can be used alone or
in combination with radiation therapy.
C O M P R E H E N SIO N Q U E ST IO N S
A 45-year-old female patient presents with hirsutism, striae, bruising, acne,
and hyperpigmentation of the skin. After a thorough physical examination the
physician notes that she also suffers from hypertension and shows signs of a “buf-
falo hump” on her back between the shoulders. Cushing syndrome is suspected
and after laboratory tests show elevated blood cortisol levels she is given a
dexamethasone suppression test. Her results are positive.
[50.1] Following administration of dexamethasone, this patient exhibits ele-
vated cortisol levels (a positive result) because of which of the
A. The humoral stress pathway can no longer regulate cortisol levels
via a negative feedback loop.
B. There is a deficiency in the enzyme that breaks down dexametha-
sone, leading to excess amounts of glucocorticoid in the blood
C. The anterior pituitary is nonresponsive to excess cortisol and is
aberrantly producing excess CRH
D. A CRH-secreting tumor of the adrenal glands is stimulating cortisol
synthesis and is no longer responding to the negative feedback loop