Jugular Vein Sampling for Hormone Levels for the Diagnosis of Cushing Syndrome
Condition: Cushing's Syndrome
MeSH terms: Cushing Syndrome; Syndrome
Study type: Observational

Summary: 
      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
      sinuses.

      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>
    

Detailed description: 
      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.
    

Keywords: Petrosal Sinus Sampling; Corticotropin Releasing Hormone; Cushing Syndrome; Internal Jugular Vein Sampling; Corticotropin Releasing Hormone Stimulation