Syndrome, Serum Screening Test
Cushing's work up
|Endogenous Cushing's syndrome affects an
estimated 13 to 15 cases per million people in the USA...70% by
pituitary lesion, 15% from ectopic lesions, and 15% from adrenal
lesions. Cushing's is an increased concentration of glucocorticoid
hormone in the bloodstream. The earliest
clues are emotional & historical. One common presentation
is that of poor glycemic control in obese (BMI >25) diabetics.
Ectopic Cushing syndrome refers to the production of ACTH or glucocorticoid
hormone in a location other than the pituitary gland or adrenal
gland. Examples of ectopic sites include thymoma, medullary carcinoma
of the thyroid, pheochromocytoma, islet
cell tumors of the pancreas, and oat cell carcinoma of the lung.
On the other hand, some prefer that "Cushing's disease" specify
the disorder of the pituitary gland in the head wherein too much
pituitary ACTH is produced. Even if no masses or nodules are found in the pituitary, adrenals, or ectopic sites, there is the possible situation of supranormal adrenal steroidogenesis.
polycystic ovary (PCOS)
|Signs and symptoms include the "buffalo
hump" (a 'hump" of fat on the back between the
shoulders at the base of the neck (dorsicocervical fat pad over
C7), supraclavicular fat pad enlargement, large violaceous (purple)
stretch marks, a moon (wide & round) face, and being fat
in the trunk but not as much in the limbs, and cortisol induced
acne. If it is due to a pituitary tumor, there could be associated headaches due
to increased intra-sellar pressure and flushing as
the LH and FSH gland areas atrophy and cause menopausal symptoms.
Various...often highly precise...lab tests may be
needed to distinguish Cushing's & pseudo-Cushing's states from
In normals, the serum cortisol level regularly fluctuates
(diurnal variation), being highest at about 8AM (=/> 18 micro/dl)
and nearly undetectable at midnight. So, a midnight level > 5
micro/dl is suspicious for Cushing's.
with the overnight 1 mg low dose Dexamethasone Suppression
||This test is a
reasonable screening test for Cushing's
syndrome. Dexamethasone 1.0 mg should be taken by mouth at 11:00 PM.
A snack can be consumed with the medication. Report to the specified
laboratory or physician's office so that a sample
of blood can be obtained for determination of the serum cortisol
level at 8:00 AM the very next morning.
False positives causes:
- Dexa is rapidly metabolized, by: (a)
Stress, Depression and other psychiatric disorders.
When the distinction between hypercortisolism and deppression cannot
be made on clinical grounds alone, endocrine tests are abnormal,
an Insuline Tolerance Test may help distinguish them.
(b) Drugs: Phenytoins, phenobarbital, carbamazepine, Tyreotoxicose & likely others.
- Serum CBG (cortisol binding globulin)
is elevated: High estrogen
states: (oral estrogen replacement, oral contraceptives,
PCOS, ovarian tumors). About 50% of normal women taking these
pills could lack suppression. In order to improve the accuracy,
oral estrogens pills must be discontinued for 6 weeks and
the test repeated.
- Dexa is poorly absorbed: Renal
failure & alcoholism:
False negative causes:
Rare cases of only periodic hormonogenesis or
patients who metabolize dexa slowly.
Gold standard Screening Test
Urine from 24 hours is collected and urinary free cortisol (UFC)
is determined. If it is higher than 100mg/day, hypercortisolism
is present. Thus, the daily UFC measurement emerges as a very simple,
cost effective and accurate assessment confirming or not the presence
of Cushing syndrome. A result above 3 times the upper limit of
normal is nearly diagnostic of Cushing's; but, there are some surgically
proven Cushing's cases with normal UFC3.
For less than 5% of obese patients, the UFC measurements may be
above the normal range; however, as many as 10-15% will have elevations
in urinary 17OHCS excretion (derived from the metabolism of cortisol).
The diagnostic sensitivity and specificity of UFC values were 100%
and 98%, compared to only 73% and 94%, respectively for 17OHCS.
So, UFC determination, will usually provide clearcut distinction
between patients with hypercortisolism and obese non-cushing’s
patients. As discussed above, in obese patients the CBG increases,
giving us a false positive Dexa diagnosis.
UFC is considered the "gold-standard" of the screening
tests, since it excludes many of false positives and negatives.
Adrenals are commonly nonfunctionally enlarged
(9% of autopsies have a nodule 2mm or larger & 1.5% have 1CM
or larger) or nodular (too many false positive images). About 50%
of pituitary tumors are imaging occult (too many false negatives).
If an adrenal mass is found, >4CM cutoff is useful: for the
large masses, only 1 in 9 will be malignant.
(posted 28 February 2004; update 1 March 2004)
Pituitary Center DST protocols
William H. Ludlam, M.D., Ph.D., in web
file of Oregon Health & Science U., Portland.
Gail Alder, M.D., et. al., E-Medicine website
other web sources
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