Dr. James Findling

ℹ️ Basics: Testing: Inferior Petrosal Sinus Sampling

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Personal Stories:

From MaryO’s bio:  (At the NIH in October 1987) The MRI still showed nothing, so they did a Petrosal Sinus Sampling Test. That scared me more than the prospect of surgery. (This test carries the risk of stroke and uncontrollable bleeding from the incision points.)

Catheters were fed from my groin area to my pituitary gland and dye was injected. I could watch the whole procedure on monitors. I could not move during this test or for several hours afterwards to prevent uncontrollable bleeding from a major artery.

The test did show where the tumor probably was located.

Also done were more sophisticated dexamethasone suppression tests where drugs were administered by IV and blood was drawn every hour (they put a heplock in my arm so they don’t have to keep sticking me). I got to go home for a weekend and then went back for the surgery…

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From Karen’s Story: https://cushingsbios.com/2016/11/18/doc-karen-pituitary-and-bla-bio/

At that time, there was evidence of a pit tumor but it wasn’t showing up on an MRI. So, I had my IPSS scheduled. An IPSS stands for Inferior Petrosal Sinus Sampling. It is done because 60 % of Cushing’s based pituitary tumors are so small that they do not show up on an MRI. Non Cushing’s experts do not know this so they often blow patients off, even after the labs show a high level of ACTH in the brain through blood work. An overproduction of the hormone ACTH from the pituitary communicates to the adrenal glands to overproduce cortisol. Well, the IPSS procedure is where they put catheters up through your groin through your body up into your head to draw samples to basically see which side of your pituitary the extra hormone is coming from, thus indicating where the tumor is. U of C is the only place in IL that does it.

…

I was scheduled to get an IPSS at U of C on June 28th, 2011 to locate the tumor. Two days after the IPSS, I began having spontaneous blackouts and ended up in the hospital for 6 days. The docs out here had no clue what was happening and I was having between 4-7 blackouts a day! My life was in danger and they were not helping me! We don’t know why, but the IPSS triggered something! But, no one wanted to be accountable so they told me the passing out, which I was not doing before, was all in my head being triggered by psychological issues. They did run many tests. But, they were all the wrong tests. I say all the time; it’s like going into Subway and ordering a turkey sandwich and giving them money and getting a tuna sandwich. You would be mad! What if they told you, “We gave you a sandwich!” Even if they were to give you a dozen sandwiches; if it wasn’t turkey, it wouldn’t be the right one. This is how I feel about these tests that they ran and said were all “normal”. The doctors kept telling us that they ran all of these tests so they could cover themselves. Yet, they were not looking at the right things, even though, I (the patient) kept telling them that this was an endocrine issue and had something to do with my tumor! Well, guess how good God is?!!!!

…

Fast forward, I ended up in the hospital with these blackouts after my IPSS. The doctors, including MY local endocrinologist told me there was no medical evidence for my blackouts. In fact, he told the entire treatment team that he even doubted if I even had a tumor! However, this is the same man who referred me for the IPSS in the first place! I was literally dying and no one was helping me! We reached out to Dr. Ludlam in Seattle and told him of the situation. He told me he knew exactly what was going on. For some reason, there was a change in my brain tumor activity that happened after my IPSS. No one, to this day, has been able to answer the question as to whether the IPSS caused the change in tumor activity. The tumor, for some reason, began shutting itself on and off. When it would shut off, my cortisol would drop and would put me in a state of adrenal insufficiency, causing these blackouts!

Dr. Ludlam said as soon as we were discharged, we needed to fly out to Seattle so that he could help me! The hospital discharged me in worse condition then when I came in. I had a blackout an hour after discharge! But get this…The DAY the hospital sent me home saying that I did not have a pit tumor, my IPSS results were waiting for me! EVIDENCE OF TUMOR ON THE LEFT SIDE OF MY PITUITARY GLAND!!!

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From Kirsty: https://cushingsbios.com/2013/06/25/kirsty-kirstymnz-ectopic-adrenal-bio/

The hardest of all these was what they call a petrusal vein sampling (this is where they insert a catheter into the groin through the femoral vein which goes up to the base of the brain to look at the pituitary, they do this while awake – I could actually feel them moving around in my head.)

This test concluded that my Cushing’s was being caused by a tumor somewhere other than the pituitary (this only happens in 1% of cases, and there is about a 1 in 10 million chance of getting it). The question now was “where is the tumor?”

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Find other bios with which mention this test at https://cushingsbios.com/tag/ipss/

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This topic on these message boards:  https://cushings.invisionzone.com/forum/54-css-ct-ipss-ivp-mri-np-59-scan-octreoscan-pss-sonogram-ultrasound/

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Thoughts from Dr. James Findling: https://cushieblogger.com/2019/03/24/cushings-syndrome-expert-a-standout-in-clinical-practice/

Another defining moment in my career from a research perspective was when I was a fellow, I had to do a project. We were seeing a lot of patients with Cushing’s — of course, that’s why I went there — and in those days we had no good imaging. There were no CT scans, no MRI, there was no way to image the pituitary gland to find out whether there was a tumor. By the late ’70s it became obvious that some patients with Cushing’s syndrome didn’t have pituitary tumors. They had tumors in their lungs and other places, and there was no good way of sorting these patients from the pituitary patients.

My mentor at UCSF, Blake Tyrrell, MD, had the idea of sampling from the jugular vein to see if there was a gradient across the pituitary. I took the project up because I didn’t think this is going to be helpful due to there being too much venous admixture in the jugular vein from other sources of cerebral venous drainage. We went into the radiology suite to do the first patient. As I was sampling blood from the peripheral veins, the interventional radiologist, David Norman, MD, says, “Would you like to sample the inferior petrosal sinus?” I said, “Why not? It sounds like a good idea to me.” That turned out to be helpful. We then studied several patients, and it eventually went to publication. Now everybody acknowledges it is necessary, maybe not in all patients with Cushing’s, but in many patients with Cushing’s to separate pituitary from nonpituitary Cushing’s syndrome.

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Official information

Patient information from Canterbury Health Limited Endocrine Services

INFERIOR PETROSAL SINUS SAMPLING WITH CRH STIMULATION

Introduction

You have been diagnosed with Cushing’s syndrome which results from excessive production of the hormone cortisol, made by the adrenal glands. In your case, the adrenal glands are being driven by excessive amounts of another hormone called ACTH. This test is to determine where that ACTH is coming from. Constant high levels of ACTH are usually caused by a tumor. Approximately 80% of cases are tumors of the pituitary gland while the remainder may occur in the lung, pancreas and other sites (known as “ectopic” sites).

This test relies on the fact that if the source of your high ACTH is the pituitary gland blood levels taken from very near the gland will be higher than the blood level in an arm vein. Pituitary gland tumors are often tiny and can’t be seen even with the most modern scanners. This test will help your endocrinologist to know with almost 100% certainty whether the pituitary gland is the source or if a search is needed elsewhere (for example in the lungs or abdomen). This guides treatment, for example the recommendation for Pituitary surgery.

Procedure

You are allowed water only from midnight the night before (nothing else to eat or drink). You will be given a light sedative, but will be awake during the procedure. You will be taken to the Radiology Department where the procedure will take place. The radiologist will place some local anesthetic into the groin on each side over the main vein that drains blood from each leg. Then a fine bore catheter will be passed up the vein, past the heart and into the major vein in the neck (the jugular vein). From there it is passed into a smaller vein that drains blood directly from the pituitary gland, known as the inferior petrosal sinus. The procedure is repeated for the other side. X-ray screening guides the radiologist to know where the catheters are positioned. A small butterfly needle is inserted into an arm vein.

Once the catheters are in place, blood samples will be taken from the right and left petrosal sinus, and an arm vein at exactly the same time. After two baseline samples, a hormone called CRH is injected into the arm vein. This increases ACTH when a pituitary gland tumor is present, but has no effect on ectopic ACTH production. Further blood samples are taken for another 10 to 15 minutes, then the catheters are withdrawn. Pressure is applied to the groins to minimize bruising. Often sampling is continued from the arm vein only, for a total of 90 minutes. You will have to remain lying on your back for at least 2 hours afterwards.

Risks

This procedure is very safe when performed by an experienced radiologist. Rarely, there have been reports of people having a stroke at the time of this procedure but this was related to a catheter of faulty design which is now no longer used. Bruising, which is common in Cushing’s syndrome, may occur after the catheters are pulled out. Some people notice flushing of the face after the CRH and rarely it can result in a fall in blood pressure.

From: http://www.pituitarycenter.com/html/article1.html

INFERIOR PETROSAL SINUS SAMPLING

Patients who are suspected of having a pituitary tumor resulting in Cushing’s syndrome may be referred for inferior petrosal sinus sampling if findings on MRI examination of the pituitary did not reveal a tumor or are inconclusive.

The inferior petrosal sinus sampling procedure is performed in the radiology department. With the patient on the angiography table both groin regions are partially shaved, sterilized, and a local anesthetic is injected into the skin to provide pain relief. A tiny incision is made within the skin and a needle is inserted to puncture the femoral vein which drains blood from the leg. A small catheter is then inserted into the vein and flushed with an intravenous solution. Longer catheters are passed into the shorter catheters and advanced through the large veins traversing the torso into the neck and then into the base of the skull. Thereafter, a microcatheter is advanced through each of these larger guiding catheters and threaded into the inferior petrosal sinuses which lie along the internal aspect of the skull base and drain blood from the pituitary gland. Once these microcatheters have been positioned, contrast dye is injected and X-rays are taken to verify their position in the inferior petrosal sinuses. Next, blood samples are collected from both catheters in the inferior petrosal sinuses and from a peripheral (usually arm) vein. Thereafter, corticotropin-releasing hormone is administered through the peripheral vein. Repeat blood samples are drawn 2, 5, and 10 minutes after the injection. Additional X-rays are taken to confirm that the catheters were not dislodged from their site during the sampling procedure. Thereafter, the catheters are removed and direct pressure is applied to the groin region to decrease the likelihood of bruising. Patients are observed for 4 hours following the procedure to ensure that no bleeding from the femoral vein puncture sites will occur. Normal non-strenuous activity may be resumed 48 hours after the procedure.

Sedatives and pain relievers may be administered during the procedure as necessary. A blood thinner might be used depending on the patient’s anatomy and the clinical suspicion of developing a blood clot. If a blood thinner is used, this may be counteracted with medication at the conclusion of the procedure to ensure that normal blood clotting resumes while removing the catheters. Overall, the inferior petrosal sinus sampling procedure involves minimal discomfort. The risks of the procedure are small. X-rays are used but the radiation doses are minimized. Infection is controlled by using sterile technique. Some patients might have an unexpected allergic reaction to the dye used during the study. A bruise may develop within the groin. Although rare, blood clots have developed in the groin veins following this procedure. Again, steps are taken to minimize the likelihood of each and every one of these complications.

ACTH levels are measured in each of the blood samples obtained during the procedure. The ratios between the petrosal sinus sampling and the peripheral vein samples are compared. The results are used to determine whether ACTH production is due to either a pituitary or a non-pituitary source.

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From: http://www.mc.vanderbilt.edu/pituitarycenter/html/article1.html

Patients who are suspected of having a pituitary tumor resulting in Cushing’s syndrome may be referred for inferior petrosal sinus sampling if findings on MRI examination of the pituitary did not reveal a tumor or are inconclusive.

The inferior petrosal sinus sampling procedure is performed in the radiology department. With the patient on the angiography table both groin regions are partially shaved, sterilized, and a local anesthetic is injected into the skin to provide pain relief. A tiny incision is made within the skin and a needle is inserted to puncture the femoral vein which drains blood from the leg. A small catheter is then inserted into the vein and flushed with an intravenous solution. Longer catheters are passed into the shorter catheters and advanced through the large veins traversing the torso into the neck and then into the base of the skull. Thereafter, a microcatheter is advanced through each of these larger guiding catheters and threaded into the inferior petrosal sinuses which lie along the internal aspect of the skull base and drain blood from the pituitary gland. Once these microcatheters have been positioned, contrast dye is injected and X-rays are taken to verify their position in the inferior petrosal sinuses. Next, blood samples are collected from both catheters in the inferior petrosal sinuses and from a peripheral (usually arm) vein. Thereafter, corticotropin-releasing hormone is administered through the peripheral vein. Repeat blood samples are drawn 2, 5, and 10 minutes after the injection. Additional X-rays are taken to confirm that the catheters were not dislodged from their site during the sampling procedure. Thereafter, the catheters are removed and direct pressure is applied to the groin region to decrease the likelihood of bruising. Patients are observed for 4 hours following the procedure to ensure that no bleeding from the femoral vein puncture sites will occur. Normal non-strenuous activity may be resumed 48 hours after the procedure.

Sedatives and pain relievers may be administered during the procedure as necessary. A blood thinner might be used depending on the patient’s anatomy and the clinical suspicion of developing a blood clot. If a blood thinner is used, this may be counteracted with medication at the conclusion of the procedure to ensure that normal blood clotting resumes while removing the catheters. Overall, the inferior petrosal sinus sampling procedure involves minimal discomfort. The risks of the procedure are small. X-rays are used but the radiation doses are minimized. Infection is controlled by using sterile technique. Some patients might have an unexpected allergic reaction to the dye used during the study. A bruise may develop within the groin. Although rare, blood clots have developed in the groin veins following this procedure. Again, steps are taken to minimize the likelihood of each and every one of these complications.

ACTH levels are measured in each of the blood samples obtained during the procedure. The ratios between the petrosal sinus sampling and the peripheral vein samples are compared. The results are used to determine whether ACTH production is due to either a pituitary or a non-pituitary source.

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From https://www.uclahealth.org/radiology/interventional-neuroradiology/inferior-petrosal-sinus-sampling

The IPSS test is done in some patients to identify if there is too much ACTH is causing the excess production of cortisol, and where it is coming from.

How do we do an IPSS procedure?

Typically under general anesthesia, we place small tubes (catheters) into the femoral veins (the main vein draining the legs) at the level of the groin. From there, under X-ray guidance, we navigate those catheters to the main veins which drain the Pituitary gland. These are the inferior petrosal sinuses (right and left). We then draw samples from those veins and the main vein of the abdomen and test those samples for ACTH. We also take timed samples after giving a dose of medication which would normally stimulate the production of ACTH to improve the sensitivity of the test.

When we get the results, the different levels of ACTH may help the endocrinologist determine where the tumor is located that is causing the adrenal gland to produce the excess cortisol. If it is from the Pituitary gland, any difference between the right and left samples may help the surgeon determine the surgical plan to remove the tumor yet preserve the normal Pituitary gland.

Example of testing results:

Time Right IPS Left IPS Inf Vena Cava Cortisol
Baseline 1    09:32 40 pg/ml 17 18 25 mcg/dl
Baseline 2    09:34 45 18 15 24
DDAVP inj     09:38
Post 2min    09:40 72 21 18
Post 5min    09:43 157 20 19
Post 10min  09:48 161 30 25
Post 15min  09:53 162 33 26
Post 30min  10:08 124 32 29 30

This example shows elevation of ACTH in the right inferior petrosal sinus, likely indicating a tumor in the right side of the pituitary gland causing Cushing’s Disease.

Picture of contrast injection of the inferior petrosal sinuses:

Picture of contrast injection of the inferior petrosal sinuses

Tips of the catheters in the inferior petrosal sinuses.

💉 Cushing’s syndrome expert a standout in clinical practice

MaryO Helpful Doctors , , , , , , , ,

James Findling, MD, is a veteran of the endocrinology field, a clinical practitioner and a Cushing’s syndrome expert. For his efforts in these areas, particularly clinical practice, the Endocrine Society is honoring him with its Outstanding Clinical Practitioner Award at ENDO 2019 in New Orleans.

James Findling

Findling, who currently serves as director of community endocrinology services and clinical professor of medicine at the Medical College of Wisconsin in Milwaukee, has made his clinical practice a national one as, according to the Endocrine Society, he receives referrals from across the U.S. In addition, he has played an important role in Cushing’s syndrome research, including breakthroughs that the Endocrine Society has incorporated into its own clinical practice guidelines.

In a conversation with Endocrine Today, Findling discussed his serendipitous entrance into endocrinology, his own experience with medical history and his dream of playing golf with Barack Obama.

What was the defining moment that led you to your field?

Findling: In 1977, I was a resident in internal medicine at what was then the Milwaukee County General Hospital, which doesn’t exist anymore. I did an endocrinology rotation, and my attending physician was James Cerletty, MD. Endocrinology was the farthest thing from my mind as something I would be interested in, but I was assigned to do this rotation and it changed my life. I thought, “Oh my goodness. This is fascinating.” Dr. Cerletty was a fabulous teacher and great mentor. The reason I chose endocrinology was because of that 1-month rotation. I had never done it previously, and I just fell in love with it. It was primarily because of this one man, who just died recently. He changed my life.

I was a chemistry major in college, and I enjoyed the pathophysiology and the biochemistry of it. I remember in those days, it was a little bit more complicated and convoluted to assess thyroid function, and it was never something I appreciated or understood. The concepts like T3 resin uptake I didn’t quite understand. Jim Cerletty made me understand how to interpret thyroid function studies, how they were done, how T3 resin uptake was measured, and it made all the difference in the world; a light bulb went off.

What area of research in endocrinology most interests you right now and why?

Findling: Pituitary-adrenal disorders. How I got interested in that, it’s kind of an interesting story in itself. After I did the month with Dr. Cerletty, I got interested in endocrinology, and 6 months later, I was in a general medical clinic seeing a woman with obesity, hypertension and diabetes. I went in and said to the attending physician at the time, “Well, maybe she has Cushing’s syndrome,” and I got kind of reamed out. “That’s rare. Nobody has that. It’s a stupid thing to think about.” He was trying to embarrass me and it upset me. I said, “How do you know she doesn’t have Cushing’s if you don’t do the testing?”

So, I started looking into it and realized nobody knows. Maybe some of these people with obesity and hypertension do have Cushing’s syndrome, but the testing was cumbersome and stupid and didn’t make any sense to me. About that time there was an article in The New England Journal of Medicine about pituitary surgery for Cushing’s disease from UCSF. I read that and said, “That’s where I’m going. I’m going there to learn about Cushing’s.” I applied and, fortunately, I got in and the rest is history. It’s because some attending physician embarrassed me by saying, “That’s stupid. Nobody could have Cushing’s syndrome,” and I’ve spent the rest of my life trying to figure that out. It’s been my passion for the last 40 years.

What advice would you offer a student in medical school today?

Findling: You need to find something that you’re passionate about in medicine. For many young people, that requires specialization into a relatively focused area so that they can develop a higher level of expertise. For some, that may be a more general area, and for some it may be based on location. For example, they might like to be a family physician in a small town where they can do a great deal of good. Either way, you must find something that you’re passionate about within our field, because if you’re not, you’re going to be unhappy. This is hard work and you’re going to spend many hours doing this, so you better find something you enjoy doing, whatever it is. There are so many different aspects from psychiatry to surgery to hospitals. There are so many different things you can do, but you have to find something that you like.

I hear a lot about work-life balance, and I understand that particularly in young physicians, this is a critically important part of being a doctor. The problem is if you’re going to be a physician, there’s going to be a lot of work. Half of your time or more is going to be working. You better enjoy that part of it because if you don’t enjoy the work part of it, you’re not going to enjoy the life part of it.

Have you ever been fortunate enough to witness or to have been part of medical history in the making?

Findling: I was lucky to go to University of California, San Francisco. Shortly after I got there, there were several people cloning the growth hormone gene and the insulin gene. The foundation of Genentech and the idea of making growth hormone was just fermenting at UCSF when I was there. In one of the labs was Herb Boyer, PhD, who was one of the first people to clone growth hormone, and he was on the cover of Time magazine. The head of the metabolic research unit and my boss was John Baxter, MD, who was president of the Endocrine Society years ago. There is now a prize named after him; he was on the cover of The New York Times magazine. So, here I am at UCSF and somebody in the lab down the hall is on the cover of Time magazine and my boss was on the cover of The New York Times magazine, so it was an exciting time to be at UCSF in the late ’70s and early ’80s.

Another defining moment in my career from a research perspective was when I was a fellow, I had to do a project. We were seeing a lot of patients with Cushing’s — of course, that’s why I went there — and in those days we had no good imaging. There were no CT scans, no MRI, there was no way to image the pituitary gland to find out whether there was a tumor. By the late ’70s it became obvious that some patients with Cushing’s syndrome didn’t have pituitary tumors. They had tumors in their lungs and other places, and there was no good way of sorting these patients from the pituitary patients.

My mentor at UCSF, Blake Tyrrell, MD, had the idea of sampling from the jugular vein to see if there was a gradient across the pituitary. I took the project up because I didn’t think this is going to be helpful due to there being too much venous admixture in the jugular vein from other sources of cerebral venous drainage. We went into the radiology suite to do the first patient. As I was sampling blood from the peripheral veins, the interventional radiologist, David Norman, MD, says, “Would you like to sample the inferior petrosal sinus?” I said, “Why not? It sounds like a good idea to me.” That turned out to be helpful. We then studied several patients, and it eventually went to publication. Now everybody acknowledges it is necessary, maybe not in all patients with Cushing’s, but in many patients with Cushing’s to separate pituitary from nonpituitary Cushing’s syndrome.

That was kind of a defining moment in terms of my research career because it was complete serendipity. I had never even heard of this vessel before. I went to the library to get a bunch of books to try to figure out what the venous drainage of the pituitary gland looked like. That was not easy to find. That was the defining moment of my research career as a postdoctoral fellow in endocrinology at UCSF. I was blessed because there were so many people smarter than me that it was a big help and an inspiration.

What do you think will have the greatest influence on your field in the next 10 years?

Findling: Most people would say genetics. The genetic diagnosis of so many disorders and the connection of disorders because of germline mutations or somatic mutations in tumors is just exploding. Whether you talk about pheochromocytomas, pituitary tumors in Cushing’s disease or adrenal tumors, you can go on and on and on.

Genetics wasn’t even on the radar screen when I was in training, so I feel a little bit lost because I’m behind the eight ball in terms of trying to keep up with that. Nobody was talking about that back in 1979, and I wish I understood it a lot better than I do. If I was going to think that there’s going to be anything that’s going to change the future of endocrinology it’s that, and not just for diagnosis but its potential applications for therapy.

What are your hobbies/interests outside of practicing medicine?

Findling: I’m an avid golfer. I live in Wisconsin, so right now it’s only 4° — so not too much golfing going on. I golf in the summer about once a week. I have a nice group of people I play with, and its one of my passions.

I run a lot. Not in 4° weather, but when the weather’s nice I run a lot and my goal is to run a half marathon this year. I’ve done one in the past, but it’s been many years since I’ve run one. I still enjoy running. Fortunately, my hips and knees and ankles and feet are capable of withstanding it. I don’t run very far. Maybe 8 to 10 miles per week.

I enjoy gardening. My wife and I, she loves flowers and I love vegetables, so we have a nice garden we put up every spring. So that’s another passion I have. We also love live theater, so we go to a lot of theater here in Milwaukee and all over Wisconsin.

Whom do you most admire and what would you ask that person if you had 5 minutes him/her?

Findling: The person I’d most like to meet is President Barack Obama. He’s one person I have a lot of admiration for. I would tell him I want more than 5 minutes. I’d want to play golf with him. I think his skill level is about the same as mine, so we’d have a competitive game. We’d probably do a lot of trash talking along the way.

I would ask him, “How did you stay so calm and have so much grace with all the criticism he got from so many people?” Some criticism is always a little bit justified, but a lot of it was so unjustified. How did he stay so calm and not raise his voice? Sometimes when you’re getting a lot of criticism and people are saying negative things about you, how do you stay professional and graceful? It’s not easy to do.

What was the last book you read , and what did you think of it?

Findling: The last one I finished was American Dervish. It’s a novel by Ayad Akhtar, who grew up in the suburbs of Milwaukee. His parents are from Pakistan, and he grew up as a Muslim. This young man is going to be a force in American literature.

This particular book is the story of a young Pakistani-American boy growing up in the American Midwest and a growing up story with the struggle of identity and religion. It’s a fascinating read.

In fact, Akhtar has won a Pulitzer Prize for one of his plays called Disgraced. He’s just had a play on Broadway that was nominated for a Tony Award called Junk, which the Milwaukee Repertory Theater just performed here. My wife and I saw it recently and it was entertaining

Much of what he’s written is regarding Muslims and the struggles they have living in the United States. If you haven’t seen one of his plays or read any of his stuff, I think he’s going to be a real force. He’s still a young man and he’s creative and provocative. This book, as I understand it, he’s going to make it into a play, and I wouldn’t be surprised if someday it might even be a movie. It’s an interesting perspective and I enjoyed it.

From https://www.healio.com/endocrinology/news/online/%7Baeddd4af-a2d1-430e-a421-ffa5c15dd732%7D/cushings-syndrome-expert-a-standout-in-clinical-practice