people taking long-term corticosteroid therapy to
suppress the IMMUNE RESPONSEsuch as following
ORGAN TRANSPLANTATION(to prevent GRAFT VS. HOST
DISEASEand organ rejection) or to treat chronic
inflammatory conditions such as ASTHMA, SYSTEMIC
LUPUS ERYTHEMATOSUS(SLE), RHEUMATOID ARTHRITIS,
SARCOIDOSIS, andINFLAMMATORY BOWEL DISEASE(IBD).
Occasionally multiple corticosteroid injections into
inflamed joints can also produce exogenous Cush-
ing’s syndrome.
Endogenous Cushing’s SyndromeCushing’s disease is an older term for endogenous
Cushing’s syndrome, which most commonly
occurs as a result of adrenal or pituitary ADENOMA
(noncancerous tumor) that increases cortisol
secretion. A pituitary adenoma causes the anterior
lobe of the PITUITARY GLANDto produce excessive
ADRENOCORTICOTROPIC HORMONE(ACTH). The ACTH
stimulates the adrenal cortex of the ADRENAL
GLANDS to secrete cortisol. An adrenal adenoma
develops in the adrenal cortex and itself secretes
cortisol independent of ACTH stimulation.
Other causes of endogenous Cushing’s syn-
drome include adrenal hypertrophy (enlargement
of the adrenal glands), which increases cortisol
secretion, and ACTH-secreting tumors located
elsewhere in the body such as some cancers of the
lung, PANCREAS, and BREAST. As with pituitary ade-
noma, the ACTH secretion stimulates the adrenal
cortex to increase cortisol production. Cushing’s
syndrome is sometimes one of the earliest indica-
tions of small-cell LUNG CANCER(SCLC), the tumors
of which are characteristically ACTH secreting.
Symptoms and Diagnostic PathThe symptoms and signs of Cushing’s syndrome
are the same regardless of the condition’s cause
and typically include
- a rounded, flushed face (“moon face”)
- transition to an “apple” body shape: thickened
trunk due to accumulated abdominal fat and
thinned arms and legs due to MUSCLEatrophy
(wasting) - accumulation of fat in a “hump” between the
shoulder blades - HIRSUTISM(increased body HAIR) and ACNE
- HYPERTENSION(high blood pressure)
- delayed wound HEALINGand decreased resist-
ance to INFECTION - irritability, DEPRESSION, mood swings, and diffi-
culty concentrating
The diagnostic path begins with BLOOD and
URINEtests to measure the body’s levels and excre-
tion of cortisol. When the endocrinologist suspects
exogenous Cushing’s syndrome due to cortico-
steroid therapy, these tests are often conclusive for
the diagnosis. The endocrinologist may conduct
additional tests to assess the body’s response to
dexamethasone (a corticosteroid) and ACTH (dex-
amethasone test and ACTH-stimulation test,
respectively) when endogenous Cushing’s syn-
drome is likely. Imaging procedures such as
COMPUTED TOMOGRAPHY (CT) SCAN or MAGNETIC
RESONANCE IMAGING (MRI) can reveal structural
abnormalities, including tumors, of the pituitary
gland and the adrenal glands.Treatment Options and Outlook
Treatment targets reducing the amount of cortisol
in the blood circulation. With exogenous Cush-
ing’s syndrome, treatment usually means transi-
tioning to noncorticosteroid medications to
manage the underlying condition and its symp-
toms. Treatment in endogenous Cushing’s syn-
drome may be surgery to remove or RADIATION
THERAPYto shrink a pituitary or adrenal adenoma,
appropriate treatment for an ACTH-secreting
tumor located elsewhere in the body, or medica-
tions such as ketoconazole or mitotane to suppress
ACTH or cortisol synthesis. Some people require
HORMONE THERAPY(sometimes long-term) to sup-
plement or replace adrenal or pituitary hormones
after treatments that target the gland directly.Risk Factors and Preventive Measures
The primary risk factor for exogenous Cushing’s
syndrome is corticosteroid therapy. Transitioning
to noncorticosteroid medications generally relieves
Cushing’s syndrome symptoms and often prevents
the condition from developing. However, noncor-
ticosteroid medications may have undesired side
effects or be less effective in controlling the under-
lying condition for which the doctor prescribesCushing’s syndrome 117