Sampling

In reaction to physiological stress, the hypothalamus secretes corticotropin-releasing hormone (CRH), which stimulates the anterior pituitary gland to release adrenocorticotropic hormone (ACTH). This, in turn, prompts the adrenal cortex to produce cortisol. Increased cortisol levels enhance gluconeogenesis, fat, and protein mobilization, which subsequently suppress further CRH and ACTH release.

Cushing Syndrome: This condition encompasses the signs and symptoms arising from prolonged elevated cortisol levels. Most instances stem from the exogenous use of steroid medications. Among the endogenous causes, ACTH-dependent conditions are prevalent, largely due to pituitary disorders (85%) and ectopic secretion (15%). Cushing syndrome caused by excessive secretion from the pituitary is known as Cushing disease, primarily linked to ACTH-secreting pituitary adenomas. These adenomas predominantly occur in young individuals, with a female-to-male ratio of 3.5:1.

Upon diagnosing Cushing syndrome, plasma ACTH levels are measured on multiple occasions to identify an ACTH-dependent cause of hypercortisolism. Distinguishing Cushing disease from ectopic ACTH secretion is initially performed using peripheral ovine or human sequence CRH stimulation, which has an overall sensitivity of 85%–90% and a specificity of 100%. The high-dose dexamethasone suppression test is less favored due to its lower sensitivity compared to the pretest probability in women with ACTH-dependent Cushing syndrome.

For imaging, a dedicated pituitary protocol using magnetic resonance (MR) imaging is employed. However, up to 40% of these scans can be falsely negative. Additionally, up to 10% of normal subjects may present a nonfunctioning pituitary tumor, or incidentaloma, on MR imaging. While newer imaging techniques improve sensitivity, they also increase the rate of false-positive results.

Presentation

Last updated:

Write your text here

	File Name	Type	Permissions	Changed Date	Date	Size

Anatomy

The normal anatomy and anatomical variants of cavernous sinus drainage are depicted in the picture shown. Shiu and colleagues developed a four-part anatomical classification system, which was later refined by Bonelli and associates. Typically, the inferior petrosal sinus (IPS) drains into the internal jugular vein (IJV) separately from the condylar vein. The second most frequent pattern is the convergence of the IPS and condylar vein, both draining into the IJV. Less common variations consist of multiple small venous channels comprising the IPS and drainage pathways outside the jugular system.

Indications

In some instances, when the drainage pattern cannot be discerned, even high spatial resolution imaging fails to depict the complex anatomy accurately. In these situations, inferior petrosal sinus sampling (IPSS) remains essential for differentiating Cushing's disease caused by a pituitary adenoma from ectopic ACTH secretion due to other tumors. As such, IPSS continues to be the gold standard for diagnosing ACTH-secreting pituitary adenomas.

No discrete pituitary lesion is identified on imaging, or results are equivocal
A discrete pituitary lesion is identified, but peripheral ACTH results are equivocal after CRH stimulation
Cushing syndrome persists after transsphenoidal surgery
There is clinical need to resolve discrepancy among clinical, biochemical, and imaging tests

Contra Indications

None specific

Workup

Write your text here

Preproduceral

DRUGS TO STOP

Discontinue 5-7 d before
Aspirin
Clopidogrel
Metyrapone
Ketoconazole
Fasting for at least 4 hours prior to the procedure

Material

Essentials

Labeled red Vacutainers
EDTA Vacutainers
oCRH (ovine corticotropin-releasing hormone)
hCRH (human corticotropin-releasing hormone)

Non Essentials

Write your text here

Positioning

Supine

Steps

Bilateral femoral vein access
4-F or 5-F angled catheter advanced into each IJV and positioned in bilateral inferior petrosal sinuses
Position confirmed with gentle digital subtraction angiography (DSA)
Baseline 5-mL blood samples collected from each bilateral IPS and peripheral locations at 5 minutes and 1 minute before stimulation
CRH administered through a peripheral intravenous line (1 mg/kg, up to 100 mg)
Bilateral peripheral and IPS samples obtained at 2, 5, and 10 minutes after stimulation
Positioning reverified with DSA to ensure no catheter migration into the IJV during sampling
Some authors advocate for central sampling in the cavernous sinus to potentially reduce the need for ovine CRH and improve lateralization, though it's technically challenging, time-consuming, and controversial
After labeling, plasma separated by centrifugation, placed in ice-cooled EDTA (lavender-top tube), and sent for chemiluminescence study

Tips & Tricks

When abnormal anatomy, such as an inferior vena cava filter or thrombosis, prevents bilateral inferior petrosal sinus sampling (BIPSS) via the femoral approach, direct access to the internal jugular vein (IJV) can be considered. If there is no communication between the IJV and the inferior petrosal sinus (IPS), catheters are placed at the C1-2 vertebral level for sampling. However, sampling at this level may lead to false results due to contamination from the transverse or sigmoid sinuses.