What Is IPSS? Is Inferior Petrosal Sinus Sampling Painful?

If your doctor suspects you have Cushing disease (and has confirmed you have high, ACTH-dependent cortisol levels), but your MRI is normal, negative, or equivocal, they may recommend a procedure called Inferior Petrosal Sinus Sampling (IPSS) ^[1][2]. Sometimes a small spot on an MRI is just an incidental finding, so doctors need more evidence to be sure where the excess hormones are coming from.

The idea of catheters being threaded up toward your brain sounds terrifying, but IPSS is a specialized blood test, not a brain surgery. It does not enter your brain tissue at all.

Instead, IPSS measures the levels of adrenocorticotropic hormone (ACTH) directly in the veins that drain your pituitary gland, known as the inferior petrosal sinuses ^[1][3]. ACTH is the hormone that tells your body to make cortisol. By comparing the ACTH levels in these veins with the ACTH levels in your arm or leg (the peripheral sample), doctors look for a gradient. A significantly higher level of ACTH near the pituitary strongly supports a pituitary source of Cushing disease, whereas no gradient suggests the ACTH might be coming from an ectopic tumor elsewhere in the body ^[1][2].

Preparing for the Procedure

Before the day of your IPSS, your medical team will give you specific instructions. You will likely need to:

• Fast: Stop eating and drinking several hours beforehand.
• Review Medications: Tell your team about all medications you take, especially blood thinners, diabetes medicines, or blood pressure drugs, as you may need to pause them.
• Discuss Allergies and Health Conditions: Inform your doctor if you have kidney disease, could be pregnant, or have an allergy to contrast dye (iodine).
• Arrange a Ride: Because you will receive sedation, you must have an escort to drive you home. You will not be allowed to drive or make important decisions for a period specified by your center.

How the Procedure Works

IPSS is performed by a specialized, multidisciplinary team in an interventional neuroradiology suite ^[4][5]. The procedure typically takes a few hours from start to finish, including preparation and recovery.

• Anesthesia and Access: You will be given local anesthesia to numb the access site (usually the groin) and sedation to keep you relaxed ^[4][6].
• Threading the Catheters: The doctor will insert tiny, flexible tubes (catheters) into a vein in your groin and carefully guide them up to the inferior petrosal sinuses at the base of your skull ^[4][6]. They use real-time X-ray imaging and contrast dye to ensure perfect placement ^[4][5].
• Taking Samples: Once placed, the team draws simultaneous blood samples from the catheters and a peripheral vein ^[4].
• Stimulation: You will then receive an injection of a medication (like CRH or desmopressin) that stimulates ACTH production. Several more timed blood samples are drawn over the next 10 to 15 minutes ^[4][1].
• Completion: The catheters are removed, and firm pressure is applied to your groin to prevent bleeding ^[7].

Is it Painful?

Patients often worry that threading catheters to the head will be excruciating, but most people do not feel the catheters moving ^[4].

You will feel a pinch and some burning when the local numbing medication is injected into your groin. After that, you may feel some pressure or vague discomfort as the catheters are placed, but you should not feel sharp pain ^[4]. If you do feel uncomfortable, you should tell the team immediately so they can adjust your sedation or numbing medication.

During the procedure, you may experience brief sensations from the medications used. The contrast dye used for imaging often causes a warm flush or a metallic taste in your mouth. The stimulating medication (CRH or desmopressin) might cause temporary flushing, mild nausea, or a headache, but these pass quickly ^[8].

For many patients, the hardest part is simply having to lie perfectly still on the procedure table for a prolonged period while the timed blood samples are drawn ^[4][1].

Risks and Recovery

IPSS is an invasive test. While it has a high rate of technical success when performed by experienced teams at major centers, complications can occur ^[5][9].

The most common side effect is minor bruising or a small collection of blood (hematoma) at the groin puncture site ^[7][5]. Rare but serious risks include significant bleeding, blood clots (venous thrombosis), infection, allergic reactions to the contrast dye, or neurologic complications (such as stroke-like symptoms).

After the procedure, you will need to lie flat for several hours (often 2 to 6 hours, depending on the center’s protocol) to allow the groin puncture to seal and prevent bleeding ^[7].

When to Seek Immediate Medical Help:
Once you go home, you should monitor your puncture site and how you feel. Contact your clinic immediately or go to the emergency room if you experience:

• Bleeding or rapid, painful swelling at the groin puncture site
• A new, severe headache
• New weakness, numbness, vision changes, or trouble speaking
• Chest pain or shortness of breath
• Fainting or severe dizziness