Patients with Cushing disease have hormone producing tumors in their pituitary gland. Often
these tumors are so small they cannot be detected by magnetic resonance imaging (MRI). The
inferior petrosal sinuses are small veins that drain the blood from the pituitary gland. By
taking a small sample of blood from these sinuses, doctors can differentiate a small tumor
in the pituitary gland from other tumors in the body producing the hormone. Patients with
Cushing disease have high levels of the hormone ACTH in the petrosal sinuses. Patients with
other causes of Cushing syndrome do not have increased levels of ACTH in the petrosal
The procedure to collect blood from the petrosal sinus is called Inferior Petrosal Sinus
Sampling (IPSS). The technique is very sensitive and can tell the difference between a
pituitary tumor and other causes of Cushing syndrome nearly 100% of the time. However, IPSS
is very difficult to perform and is only available in a few hospitals. Therefore,
researchers are looking for another possible way to diagnose Cushing syndrome that would be
less technically difficult and more readily available to patients.
ACTH is produced in the pituitary gland as a response to the production of
Corticotropin-Releasing Hormone (CRH) in the brain (hypothalamus). This study will compare
ACTH levels in the internal jugular veins before and after CRH stimulation with those
obtained by conventional IPSS from patients with Cushing's syndrome.
Obtaining blood from the jugular veins is a simple, practically risk free procedure that
could be done easily in a community hospital on an out patient basis. Researchers believe
that CRH stimulation will increase ACTH production from tumors of the pituitary gland
(corticotroph adenomas) so that the diagnostic information from jugular venous sampling
would be equivalent to that of IPSS.
This proposal to develop jugular venous sampling (JVS) with CRH stimulation as a test for
the differential diagnosis of Cushing Syndrome would potentially contribute greatly to the
medical care of patients with Cushing syndrome, as a less costly, safer and more widely
available alternative to IPSS.<TAB>
Sampling from the inferior petrosal sinuses for ACTH levels differentiates Cushing disease
from the ectopic ACTH syndrome in nearly all patients. Patients with corticotroph tumors
have a petrosal-to-peripheral ACTH gradient of 2 or more, while patients with other causes
of Cushing syndrome have lower gradients. Bilateral petrosal sinus sampling also often
provides useful information on lateralization of the adenoma for the neurosurgeon. The
widespread application of inferior petrosal sinus sampling has been limited by concerns
about potential complications and by technical failures in the hands of less experienced
radiologists. In this protocol, we compare ACTH levels in the internal jugular veins before
and after CRH stimulation with those obtained by conventional inferior petrosal sinus
sampling from patients with Cushing's syndrome. Obtaining blood from the jugular veins is a
simple, practically risk-free procedure that could be accomplished easily in community
hospitals on an outpatient basis. We hypothesize that corticotropin-releasing hormone (CRH)
stimulation will increase ACTH production from corticotroph adenomas so that the diagnostic
information from jugular venous sampling would be equivalent to that obtained by
catheterization of the petrosal sinuses.
Currently fewer than ten centers in the United States have sufficient technical expertise
with inferior petrosal sinus sampling (IPSS) to ensure reliable results. This proposal to
develop jugular venous sampling (JVS) with CRH stimulation as a test for the differential
diagnosis of Cushing syndrome would potentially contribute greatly to the medical care of
patients with Cushing syndrome, as a less costly, safer and more widely available
alternative to inferior petrosal sinus sampling. Initial data from 35 patients undergoing
both JVS and IPSS revealed no technical problems with either procedure. IPSS correctly
identified 28/31 patients with Cushing disease, while JVS correctly identified 23 of these
patients using conventional criteria (petrosal:peripheral greater than 2 before or 3 after
CRH administration). Thus, JVS may be a useful initial procedure at institutions where IPSS
is not available. However, since it is likely that jugular:peripheral ratios will be lower
in patients with ectopic ACTH secretion (so far, 1.2 - 2.04), the protocol evaluates also
the performance of JVS in patients with ectopic ACTH secretion to determine whether the
criteria for interpretation of JVS should be different than those used for IPSS.
- INCLUSION CRITERIA:
Patients with the following characteristics may be included in the protocol:
Age 18-75 years.
Evidence of Cushing syndrome. Evidence to suggest overactivity of the
hypothalamic-pituitary-adrenal axis, such as increased urinary excretion of
glucocorticoids or lack of suppressibility with low doses of dexamethasone in conjunction
with clinical features, will be sought prior to admission.
Patients will be excluded from entry to the protocol if:
A clear-cut pituitary tumor is present on T1-weighted conventional pituitary MR scan.
There is any contraindication to catheterization. Patients with known reaction to contrast
material will be excluded from this elective study if they have a strong history of
previous contrast media reaction and cannot be studied safely by giving medical
prophylaxis before the procedure.
The patient is pregnant.
Combined blood withdrawal during the six weeks preceding the study exceeds 450 ml, or if
hematocrit at entry is less than 33%.
Because of the increased risk of morbidity caused by contrast dyes in patients with a
renal dysfunction, patients with a creatinine greater than 1.3 mg/dl will be excluded.
Patients with a diastolic blood pressure persistently greater than 100 mm Hg (with or
without medication) will be excluded from sampling procedures.
They have had radiation exposure during the previous year that represents a significant
additive risk in combination with the expected doses in this protocol. Patients and their
doctors will be questioned about their exposure to radiation before they are accepted into
For the questionnaire only, patients who do not speak and read English will be excluded.
This instrument has not been validated in non-English speakers.