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Cushing Syndrome
Cushing Syndrome
Cushing Syndrome
Cushing syndrome is a disorder that occurs when your body has a high level of the
hormone cortisol.
Cushing syndrome is caused by prolonged exposure to elevated levels of either
endogenous glucocorticoids or exogenous glucocorticoids.
Individuals with Cushing syndrome can develop moon facies, facial plethora,
supraclavicular fat pads, buffalo hump, truncal obesity, and purple striae, as shown in
the image below.
Weight gain with fat accumulation on the trunk, but fat loss from the arms, legs, and
buttocks (central obesity)
Skin infections
Purple marks (1/2 inch or more wide) called striae on the skin of the abdomen, thighs,
and breasts
Excess hair growth on the face, neck, chest, abdomen, and thighs
Impotence
Other symptoms that may occur with this disease:
CAUSES
1. Exogenous steroid administration
Urinary free cortisol (UFC) determination has been widely used as an initial screening
tool for Cushing syndrome because it provides measurement of cortisol over a 24-hour
period. A valid result depends on adequate collection of the specimen.
Urinary creatinine excretion can be used to assess the reliability of the collection. Urine
free cortisol values higher than 3-4 times the upper limit of normal are highly suggestive
of Cushing syndrome.
Values higher than the normal reference range but less than 3-4 times the upper limit of
normal are inconclusive. Values that fall within this range may indicate pseudo–Cushing
syndrome or Cushing syndrome and require further testing. Multiple collections are
necessary because patients with disease may have values that fall within the normal
range. Three urine free cortisol levels in the normal range exclude the diagnosis of
endogenous Cushing syndrome.
The rationale for the dexamethasone suppression tests is based on the normal
physiology of the hypothalamic-pituitary-adrenal axis; glucocorticoids inhibit secretion of
hypothalamic CRH and pituitary ACTH but do not directly affect adrenal cortisol
production. Since cortisol production is controlled by ACTH, decreases in ACTH lead to
decreases in plasma and urine cortisol. The overnight 1-mg dexamethasone
suppression test requires administration of 1 mg of dexamethasone at 11 PM with
subsequent measurement of cortisol level at 8 am.
In healthy individuals, the serum cortisol level should be less than 2-3 mcg/dL. To
enhance the sensitivity of the test, a cutoff value of less than 1.8 mcg/dL (50 nmol/L)
excludes Cushing syndrome. Its ease of administration makes the 1-mg
dexamethasone suppression test a widely used screening tool.
Late-night serum and salivary cortisol levels take advantage of the alterations in
circadian rhythm of cortisol secretion in patients with Cushing syndrome. Normally,
cortisol values are at their lowest level late at night. In patients with Cushing syndrome,
an elevated serum cortisol at 11 PM can be an early, but not definitive, finding.
Measuring serum cortisol levels requires hospitalization, with blood samples obtained
within 5-10 minutes of waking a patient, and is not a practical test. Measuring salivary
cortisol level has gained interest, as it is a simple and convenient way of obtaining a
nighttime sample. This measurement allows patients to collect their own samples at
home. With repeated measurements, levels less than 1.3 ng/mL (radioimmunoassay) or
1.5 ng/mL (competitive protein-binding assay) exclude Cushing syndrome.
Less experience has been gathered for this assay, and it is expensive. Most physicians
who do use this test obtain readings over several evenings to increase accuracy.
Results from a meta-analysis of 7 studies relating to late-night salivary cortisol testing in
the diagnosis of Cushing syndrome (947 patients aged >18 years, including 339
persons with Cushing syndrome) indicated that such testing has a sensitivity of 92%, a
specificity of 96%, and a diagnostic odds ratio of 311. The report's authors concluded
that late-night salivary cortisol measurement "is a robust, convenient test for screening
and diagnosis of Cushing syndrome."
Hyperthyroidism
Pregnancy
Once the diagnosis is established, the next step requires determining the etiology of
Cushing syndrome. See the flow chart below. The logical first step involves identifying if
the hypercortisolism is an ACTH-dependent or ACTH-independent disorder
Treatment
If you cannot stop taking the medicine because of disease, your high blood sugar, high
cholesterol levels, and bone thinning or osteoporosis should be closely monitored.
With Cushing syndrome caused by a pituitary or a tumor that releases ACTH (Cushing
disease), you may need:
Cortisol replacement therapy after surgery and possibly for the rest of your life.
If the tumor cannot be removed, you may need medicines to help block the release of
cortisol.
References