So, the big updates are that I had my post-op MRI and follow up appointment (though it did NOT go as planned). My MRI looks better post-op than it did before surgery (good news, right?!) I went from having what looked like a post-op MRI (chunk missing here, blob added there) to having what looks like a normal MRI (perfect little "u" shape). There is no surgical target on my MRI, which means unless something changes (ie, grows) between now and the time I'm finished with my re-diagnosis testing, I am not a candidate for further pit surgery nor either form of radiation therapy. With those MRI findings plus the thrice-repeated "hyperplasia" (in different forms/ways) on my pathology report, Dr. McC says bilateral adrenalectomy (BLA, removal of both adrenal glands) is the next course of treatment for me. I still need a great deal more testing before I have some life-giving glands permanently removed from my body, but now we know where we're headed, how many tests I'll need, and which surgeons to look into. So far I'm considering a surgeon close to home at Virginia Mason in Seattle or a more experienced (in BLA's specifically) surgeon in Wisconsin. It'll be a big change, with my life literally being dependent on the intake of medication throughout the day for survival and the constant risk of adrenal crisis, basically Addison's disease without ANY cushion of poorly-functioning adrenals (cause I won't have any!), but it should bring a lasting cure from Cushing's disease and even with the illness I'll be trading it for, my quality of life should improve dramatically.
On to MAGIC: How on earth do I sum up 3 days of learning, emotions, and fun!? I already had a basic understanding of the pituitary gland's feedback systems, hormones and functions, along with a decent understanding of my disease and it's treatments, but I did learn some new things along with some nuances and interesting points, for sure. I'll go through my notes and share what I learned and found most interesting.
- I learned that 15-30 minutes was NOT enough time for even 3 people to share their Cushing's stories.
- In endogenous Cushing's Syndrome (meaning, coming from within the body, not from taking medications), 70% is Cushing's Disease (pituitary tumor), 10% is ectopic, 15% is adrenal, and 5% are "other" --don't ask me?
- 50% of pathology-proven Cushing's Disease cases (ie, they have surgery and the tumor is found and tests positive as an ACTH producing adenoma) were not seen on MRI prior to surgery.
- Adrenals can become hypertrophied from long-term ACTH-driven Cushing's Disease...meaning, they've been forced to produce so much for so long that they kind of just kick into overdrive regardless of the current stimulating hormone production (ie, even after a tumor is removed from the pituitary, your adrenals might not slow down), though it isn't known how common/rare this is.
- Cardiovascular damage is the biggest concern, with 4 times the mortality rate in Cushing's Syndrome compared to the national average.
- Cushing's is really more like a state of Adrenal Insufficiency with Hypercortisolism superimposed upon it. IE, the pituitary's (and post-op, your adrenals') own ACTH/cortisol production is suppressed because of the tumor = adrenal insufficiency/Addison's disease. The tumor is causing excess production of ACTH/cortisol (ie, Cushing's) = hypercortisolism. So when the source of hypercortisolism is successfully removed/treated, your body is left in a state of adrenal insufficiency, requiring steroid replacement therapy and a slow weaning process to "wake" your pituitary and adrenals in the hopes of returning full function.
- It can take up to 5 years for your adrenals to fully wake up.
- Incidence (new cases) .7-2.4/million cases per year in Europe, looks to be higher in the US.
- Prevalence (number of cases, old or new, at any given time) is roughly 60-100/100,000.
- Some co-morbidities (couldn't take notes fast enough to get the whole list): carotid atherosclerosis, coronary artery disease, dyslipidemia, depression, hypertension, diabetes, obesity, etc.
- The pituitary is made from neuro-endocrine tissue with similar receptors.
- Diagnosis is a 3-step process. The first step is ALL-IMPORTANT, because getting the first step wrong can lead to falsely-concordant results in steps 2 and 3.
Step 1: Suspect Cushing's Syndrome without exogenous glucocorticoid use (steroid-based medication). Test for high cortisol, exclude other physiological causes = Cushing's Syndrome diagnosis.Step 2: Confirm high ACTH (helps differentiate causes of Cushing's Syndrome --ie, ectopic, adrenal, pituitary)
Step 3: Establish pituitary source of ACTH via MRI or IPSS = "Cushing's Disease" diagnosis.
- Cushing's diagnosis is like a justice scale -- you add weights for and against the diagnosis based on severity and likelihood. Some tests and symptoms carry more weight than others.
- UFC's that are 3+ times the normal limit are considered "pathogenic", ie, nothing else can really cause levels that high. Having results below that limit does not exclude Cushing's Syndrome, it just means further testing/investigation to be sure there are no other causes.
- Few people have truly cyclic disease, which is easily predictable in it's pattern of high and low/normal cortisol production, and a more preferable term might be "variable" disease or hypercortisolism, because it varies from person to person and day/week/month/year within the same person.
- ACTH has a 15 minute half-life, so samples can become degraded easily.
- Pituitary MRI contrast shows differences in blood flow and tissue density. ACTH-producing adenomas are very similar in tissue density and blood flow to that of healthy pituitary tissue, though not identical, so on a pre- and post-contrast MRI, pituitary adenomas are very, VERY easily missed. The biggest difference (often the only difference) is visible with "Dynamic" MRI protocols, as the contrast uptake (absorption of the dye) in adenoma's is just slightly delayed in comparison to that of normal pituitary tissues. So as the pituitary absorbs the dye and whitens, there might remain a slightly darker grey area (tumor tissue) for a few moments. If the MRI scan is not performed during that "uptake" time, it will eventually also absorb the dye so as to often look indistinguishable from the gland itself.
- There is a 10-35% chance of surgery failure (meaning surgery doesn't lead to remission).
- 5 year recurrence rates in those who did receive surgical remission are as high as 25%.
- 10 year recurrence rates are as high as 44%
- It is said the longer you follow a patient in remission, the higher the rates of recurrence will go.
- Repeat pituitary surgeries (after the first whether successful or not) have a less than 50% remission rate, along with increased incidence of CSF leaks (cerebrospinal fluid) and loss of pituitary hormone production (hypo-pituitarism). 3rd + surgeries decrease/increase those odds, respectively.
- Radiotherapy (Radiation) has a mean reported remission time of 3 years.
- Radiotherapy leads to hypo-pituitarism in 50-60% of cases, with a risk of damage to surrounding structures.
- Bilateral Adrenalectomy (BLA, removal of both adrenal glands laparoscopically) has a risk of Nelson's Syndrome, corticoid deficiencies (Adrenal insufficiency/crisis), higher rate of ER trips.
- BLA-ers have a Quality Of Life (QOL) level that is VERY closely matched to that of Diabetes patients in terms of lifelong follow-up, testing, medications, etc. (As compared to Cushing's Disease which has a QOL lower than that of Cancer patients, with an average 5 year mortality rate untreated.)
- On Korlym, 60% of diabetic patients had a greater than or equal to 25% reduction in their glucose curve, and a 38% reduction in hypertension. Side affects of nausea, fatigue, low potassium, endometrial issues, etc...(Couldn't type fast enough again!)
- On Ketoconazole, roughly 40-50% had normalization of Urinary Free Cortisol labs (UFC's), though 19% of those still had no change in symptoms. Keto shuts off the production of cortisol (synthesis), though hopefully only partly! Side affects: nausea, diarrhea, low cortisol, increased liver enzymes, etc.
- On Cabergoline (used more often for prolactinomas than ACTH-producing adenomas), in studies with 12-30 patients there was UFC normalization in 25-36%, with a small increase in usefulness seen over time. (Works with Dopamine receptors) Side affects of GI issues and dizziness, etc.
- Signifor works on somatostatin receptors specific to pituitary ACTH tumors and not healthy pituitary tissue, so it allows your pituitary to "wake up" and function, though there are similar receptors found in the GI tract (diarrhea, etc as side effect) and pancreas. It causes diabetes because of it's affects on the pancreas, but that is easily treated with insulin and quickly stabilizes (doesn't continue to worsen). 29% initially mildly elevated LFT's that usually resolves itself. Side affects are basically those of steroid withdrawal. In one patient it did cause QT prolongation (heart rhythm changes), so monitoring is necessary to be sure you aren't that "one."
- Increased IGF-1 is seen in Acromegaly.
- Only 15 pituitary surgeries are required to complete a residency and become a Neurosurgeon. It takes MANY more than that to become proficient, and statistics are poor below 200 total.
- Cushing's tumors are often VERY different than other types of pituitary tumors (gooey, milky, etc) and surgeons inexperienced in Cushing's-Specific pituitary surgeries may miss the tumorous tissue completely, or even "scramble it like an egg" thus spreading the tumor tissue unknowingly. It is VERY important to see a Cushing's-experienced surgeon.
- GPS mapping can be used to locate tumors in the posterior-pituitary region during surgery (an instance in which the tumor isn't visible upon opening for surgery).
- Endoscopic dopplers (ultrasound on the end of what looks like a bent, stainless steel chopstick) can be used to locate the carotid arteries before and during removal of the sella turcica bones, dura, etc.
- The carotids sit as "goal posts" on either side of the pituitary gland with the optic nerves above.
- Cushing's patients CAN get pregnant.
- BLA/Addison's is not a reason to deny yourself a family (ie, pregnancy can be quite manageable)
Some great quotes from this weekend:
- "This is about the messiest disease out there." -Dr. Ludlam, Director of "all things pituitary" at Novartis Pharmaceuticals, and previous Chief of Endocrinology at Swedish in Seattle, known to many as the director of "Camp Cushie".
- "I've worked as a patient advocate for many different diseases before...Cancer, etc. You guys have it so much worse. I didn't hate doctors till I saw what you go through; their mindset and biases make it so much harder for you!" -Cushing's Patient Advocate
- "The Alamo has come to symbolize fighting a battle with impossible odds...which some of you do on a daily basis." -Dr. Heaney, Professor of Endocrinology, UCLA
- In speaking about post-op weaning from replacement medications and how awful it makes you feel, "You have to pay that piper." -Dr. Ludlam
- "My mother died of Cancer...and when she was diagnosed she said to me, 'At least I don't have Cushing's.' I'd talked to her about my work...She got it." Paraphrased from Kate, A Cushing's Support Advocate (Nurse) for Corcept Pharmaceuticals.
- "I was not ready to do pituitary surgery when I became a neurosurgeon." -Dr. Kelley,
Neurosurgeon at UCLA, paraphrased from him speaking of the requirements to graduate from residency and the amount really required to become proficient. Kudos to him for stating that the requirements (cases seen) are far too few, and that much more experience is required to become skilled...which he since has, to many patient's appreciation! **UPDATE - Dr. Daniel F Kelly is now the Director of the Brain Tumor Center at John Wayne Cancer Institute. firstname.lastname@example.org **
- "I've had other doctor's tell me that if they had to diagnose and treat Cushing's all day, they'd quit [or shoot themselves]!" -Dr. Ludlam, said jovially about the confusion and long process that is the diagnosis and treatment of Cushing's disease.
- "I haven't seen people suffer so much and be so misunderstood." Kate, Cushing's Patient Advocate