Jugular Vein Sampling for Hormone Levels for the Diagnosis of Cushing Syndrome

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.

EXCLUSION CRITERIA:

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
the protocol.

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.