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Internal Jugular Vein Sampling for ACTH Levels for the Differential Diagnosis of Cushing Syndrome

18 Years
75 Years
Open (Enrolling)
Cushing's Syndrome

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Trial Information

Internal Jugular Vein Sampling for ACTH Levels for the Differential 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.


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.

Type of Study:


Study Design:


Principal Investigator

Lynnette K Nieman, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)


United States: Federal Government

Study ID:




Start Date:

April 1995

Completion Date:

Related Keywords:

  • Cushing's Syndrome
  • Petrosal Sinus Sampling
  • Corticotropin Releasing Hormone
  • Cushing Syndrome
  • Internal Jugular Vein Sampling
  • Corticotropin Releasing Hormone Stimulation
  • Cushing Syndrome



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