This page is under construction, more information will be added, rearranged, consolidated, and edited as I have the time to do so...
Uncontrolled Cushing’s syndrome is among the most morbid and life-threatening diseases.
Daniel M. Prevedello, MD, Department of Neurosurgery at the University of Pittsburgh School of Medicine and with UPMC Presbyterian. http://brainsurgery.upmc.com/_pdf/Review-of-Endocrin-Cushings.pdf
One of the health problems I'm being tested for is called Cushing's Disease. Cushings Disease is part of the greater Cushing's Syndrome, which is usually caused by taking steroid medications and afflicts roughly 10-15/million. I don't take any form of steroid, but my endocrinologist felt that I had enough signs and symptoms that we needed to rule it our. Cushings Disease is usually caused by a benign tumor on your pituitary that increases your body's natural steroid production and it occurs in roughly 1-2/million. Three of the tests for this, a 24 hour Urinary Free Cortisol (UFC) and 2 8am serum free cortisols, have come back high and are indicative of the over-production of cortisol Cushings causes. I have 2 more 24 hr UFC's pending and one of 3 salivary cortisols still needing to be completed (tonight!) before I send those back. None of them appear to be crazy high, but they are out of range and atleast "agreeing" with eachother, so if more of these tests come back high I will likely be diagnosed with Cushing's Disease.
What is Cushing's Disease?
However, too much cortisol in the body can lead to such problems as:
- Cognitive dysfunction
- Cushingoid appearance
- Skin changes
- Severe fatigue
- Weak muscles
- First, a part of the brain called the hypothalamus sends corticotropin-releasing hormone (CRH) to the pituitary gland, which is located at the base of the brain.
- The pituitary gland then secretes another hormone called adrenocorticotropin hormone (ACTH).
- ACTH stimulates the adrenal glands, which are located on top of the kidneys, to release cortisol into the bloodstream.
- When there is an adequate amount of cortisol in the blood, less CRH and ACTH are released. This process ensures that the adrenal glands release just the right amount of cortisol to meet the body's needs.
Classifying Cushing's syndromeThere are two types of Cushing's syndrome.
The first type, endogenous Cushing's, occurs when tumors in the body cause the production of high levels of cortisol. These tumors are typically classified based on their location in the body:
- Cushing's Disease. Caused by tumors in the pituitary gland, Cushing's disease accounts for approximately 70% of all Cushing's syndrome cases.
- Ectopic Cushing's. Ectopic Cushing's is caused by tumors outside of the pituitary gland. These tumors can be either benign or malignant.
- Adrenal Cushing's. Adrenal Cushing's is caused by tumors or abnormalities in the adrenal glands. These tumors can be either benign or malignant.
What are the signs and symptoms?
Although essential to mammalian life, cortisol at supraphysiologic doses provokes symptoms and signs such as decreased libido (100%), weight gain (90%), moon facies (88%), hypertension (85%), glucose intolerance, plethoric facies (80%), reddish striae (65%), hirsutism (65%), among others. Growth retardation is frequently seen in children. On routine screening, Cushing’s syndrome is found in 2% to 5% of patients with poorly controlled type 2 diabetes.
Drawing is reproduced from Mayo Clinic Family Health Book, 2nd Edition, 1996
Below are pictures from my photo album showing what would be my before/after (in a max of 1.5 year span) if I do indeed have this disease:
Notice my super-thick hair.
This was about a year ago. I don't seem to have many more recent pictures...I'm usually the one with the camera.
My "buffalo hump" when I'm just standing normally. I had assumed it was due to slumping and being overweight, yet I looked around in a crowded room of around 150 yesterday and even in overweight or those who share poor-posture with me, I didn't see a single hump in the room.
This is me trying to straighten my back/neck as much as possible lest "slumping" make it worse...it appears to be the opposite!
What testing is required for diagnosis?
It takes numerous tests to diagnose Cushing's disease or to differentiate it from other forms of Cushing's Syndrome and Pseudo-Cushings' states. Cushie-Wiki gives a really simple flow chart followed by explanations of each type of test used, I will include just the flow chart and the link to view the rest: http://www.cushiewiki.com/index.php?title=Diagnostic_Testing
How is Cushing's Disease Treated?
What does recovery entail?
Is there a cure?
For around 40-50% of those with pituitary adenomas, transphenoidal surgery is a "cure", for the rest it either had little effect or causes a remission for a brief period of time, sometimes lasting a few years. Many in this group go on to have another transphenoidal surgery, many opt for a bilateral adrenalectomy (removal of both adrenal glands, trading untreatable Cushing's Disease for treatable Addison's disease, meaning their life literally now depends on medications they must take multiple times a day). Some choose a sepcialized kind of radiation when certain parameters are met.
Here is a link to a page listing just a sampling of Cushing's patients and their various treatments (with dates) in honor of Cushing's Awareness Day (April 8th): http://www.cushiewiki.com/index.php?title=Cushie_Warriors
Stuff I've posted elsewhere but haven't edited and consolidated for this page yet:
I actually haven't been able to figure it out...gut-feeling-wise...between the AI/Sheehan's and the Cushings that Dr. F is testing for. I've been feeling for a while like it was somehow both, but knew that in all reality the chances of that were next to nothing (I mean, pituitary adenomas are 1-2/million, Sheehan's around 5/100K...so the chances of having both?). I was pretty confused but didn't want to sound crazy by saying what I thought. Both fit so well in so many ways, though not completely. So maybe this is exactly what it is and why both sounded so right? Dr. F did say that if I had Cushing's (or Sheehan's for that matter) that I would be an atypical case.
It would explain why at times I gain weight for no apparent reason, and why at other times I lose weight for no apparent reason (and I don't mean a few pounds here or there, but 1-4 lbs/week for multiple weeks or months)...it could have been up and down cycles messing with my metabolism. I've always accepted that my weight was my fault, but was always irritated that everyone assumed I ate poorly or was totally inactive (okay, well that part is true now!) when I stayed active and ate better than most people I knew, ESPECIALLY the twigy ones!
If I have Cushings, it'd probably be "episodic" (meaning at various times, days, weeks, months or years I'm high, and at various times I'm low...kind of random) or possibly cyclic (which from what I gather generally means high cortisol at night and low during the day), I'd assume mild most of the time (or how else could it have gone on this long, right, either that or my younger body has handled the high periods better?), and started about 15-16 years ago when I was in high school. I fit the Cushings scenario perfectly at that time, but it was a chicken vs. egg thing with the weight, depression, etc and being a teenager I accepted the blame from parents and doctors. About 9 years ago now Britton and I read up on Cushings (his mother died from it because she'd refused all treatment) and SO much of it fit, it is just that it wasn't an exact match at the time (mostly because my sex hormone-related functions weren't affected --and for the most part still aren't) so I read a bit but didn't ever see a doctor about it.
I've learned you can have false positives on high UFC's, though false "negatives" are very common if you have cyclical or episodic cushings. And thing also said that people wiith AI can frequently fall in the normal ranges despite proven dx, fyi. I don't have any known reason for a false high, though. Unless you have a REALLY high number, they want other highs as well before diagnosis...preferably in another form of test, but a good endo will continue testing till highs are proven, disproven over a long time (like a year!), or another diagnosis is made. Once you're dx'd, they move onto other testing (like supression tests, etc) to find where it is coming from (adrenal, pituitary, ectopic) and that further confirms the dx. Some 50% of tumors found via pit surgery weren't visualized on MRI. In those cases they get sufficient lab testing to show it's hypercortisol and the likely source and then move forward.
I've also learned that episodic or cyclic cushings can cause hypo-pit or AI symptoms in a low. It's pretty interesting stuff. For one, the hypercortisolemia affects the metabolism, production, absorption, etc of other hormones and can throw them off. But, in episodic/cyclic cushings disease (ACTH producing tumor) the tumor produces excess from time to time, and that supresses the pituitary's own ACTH production much the way inappropriate replacement can, and then when the tumor production cycles back down (not sure the mechanisms at play there yet), your pit is suppressed and you can have low cortisol (not just "normal") before your pituitary kicks back into gear sufficiently. That makes a lot of sense and could explain a great deal.
Not that I want a brain tumor, but hopefully I'll get confirming results instead of conflicting ones so we can start getting some answers instead of more confusion. If it is cushings, I'd definitely be in a high right now so testing should show it (sudden insatiable appetite, 12lb weight gain in last 4 weeks despite no changees in diet and doing more physically than the weeks before, harder time staying asleep, higher bp, etc). I was really worried they left the urine sitting on the counter with the first UFC after I left and it should be refridgerated...the gal told me she was the only one at the lab that day. That would cause a false low though, so at worst it could have been higher and doesn't negate the results. Guess we'll see what the others all say...
Britt and I went through my photo albums the other night and it is a very drastic change between my 14 1/2 y/o pictures and my 16 y/o pictures. I can't really find any pictures that I know for sure are from when I was 15 y/o, but if pictures in the albums are of that age, then it just shortens the timespan that I made that drastic change as we can't see any between look that would suggest a slower transition. I went from about a size 11/12 to a size 18/20 and gained about 60lbs sometime within those 1 1/2 years. My face changed (red, round, acne, didn't have that for the 3+ years before when AF had started), my hair went from super-thick to thin and frizzy, I became depressed/anxious, I started having trouble sleeping, I stopped sports (used to be in softball, competetive jumprope on a state level, played almost the entire game of basketball in my league, swam in front of the house all summer long, etc) and took up music instead and I stopped doing things outside the house. I have the huge stretch marks (silvery now, not red) that go from almost my knees to my elbows and around my back. Britton says I had them when we got married (ie, not from pregnancy). I even have a fat pad that looks similar to the "buffalo hump", but I don't know if normal overweight people get those. Dr. F noted thin skin on the top of my hands in my charting, and apparently high cortisol is about the only thing that does that to young women. What I don't have is facial hair, menstruation issues (aside from maybe a heavier flow, so backwards), infertility, diabetes (though I will with time if I can't get healthy), chronic hypertension, and joint pain.
Britton thinks it can't be a fluke that this disease has been brought up twice for me now, and says the above pictures are not normal for a year and a half's time, even if I was depressed...
Anyway, if more of my current cortisol tests come back high (still waiting on 2 more UFC's, I'm doing my last salivary tonight then will send those 3 in, and the serum one), then Dr. F will probably order more labwork. Either more of the same in the hopes of just getting sufficient lab confirmation (don't know what he requires, especially since that first high was only a little high), or he'll move forward with testing like Dex suppresion tests (basically the opposite of the Stim tests), of which there are various types, or a petrosal sinus sampling, or more CT's/MRI's (to check adrenals or for ectopic tumors --though those are really rare) in an effort to figure out where this pesky tumor might be. Then I'd get approved for surgery. Chances are it is pituitary (some 80% of the 1-2/million), especially since my ACTH has been above 15 twice now...atleast that is what one study said.
Sorry, I don't know if I explained that "Cushing's Syndrome" is 10-15/million and the majority of those have steroid-induced cushings, meaning over-replacement or often from treating autoimmune disorders. "Cushing's Disease" is caused by tumors, is found in 1-2/million, and some 80% of those are pituitary adenomas (benign). The rest are either adrenal tumors or ectopic tumors (meaning anywhere else in the body) and can be malignant or benign...seems like they said usually found in the kidneys or lungs. It is my understanding that that minority often have severe disease, though, and are more likely to get a quick diagnosis with very high lab results.
So, anyway, they would do a trans-sphenoidal surgery where they go in through your nose, through the sinuses, and remove a part of the bone around the pituitary to gain access. They remove whatever tumor(s) they find there (apparently 50% aren't seen prior to surgery by MRI, but their tissue is easily distinguishable to the naked eye) and hopefully don't remove too much of the pituitary tissue. That is a definite risk, though treatable. There is also a moderate risk of a CFS leak, though I forget the stats. They re-seal the area around the pituitary with a fat plug from your own body, I think, and the bone re-grows.
Most people go home from the hospital within a few days. You can't bend over for some 6 wks due to pressure increases, and there is some funky "blow your nose/nose picking" stuff as you could imagine. If you feel worse after surgery (being hit by a truck is the general description), then you know you're in remission. A cortisol of 2 is considered good news after surgery (I'm assuming immediately after, and serum). You go home with AI and on HC. Within 6 months -2 years you gradually wean yourself off the HC as your pituitary starts to kick back in. Some never do, but most are weaned by 12 months post-op. I was reading recovery info last night, and it sounds like it is a long road. Many have emotional symptom improvement immediately, though struggles with the recovery itself, which is understandable. You're weaning yourself from steroids, and apparently it is like being an addict deprived of drugs...the high cortisol has masked the pain of joints, injuries, and even muscle wasting and there can be a fair amount of pain involved (makes me think of Dr. House, though that's necrosis). Some people recovery physically rather quickly, most have to work hard to gain muscle strength back...and take it slowly in the process, doing things like swimming and yoga. I wonder if I could try karate again for the tai-chi like parts and just forgo the actual sparring for a while? I did enjoy that and it is GREAT for working various muscle groups and burning calories.
Few report making it back to "normal", but just about everyone is happy they did it and has major improvements. Some have to diet, some don't. The majority of the weight is lost in the first 12 months (with the average gain from cushings being 55lbs, say you lose the first 35 in 12 months, then 10 the next year, and 5 the year after that and so on till you're stabilized).
The mental issues (memory, etc) generally take years to resolve and some never do. I read articles about that last night, apparently with hypercortisolemia your brain actually shrinks and it lessens the synapses (think my brain hit overload by that point in my reading so I can't explain it better). The shrinking recovers over time but sometimes the synapses stuff doesn't...all depends and hasn't been studied too much if I remember right.
Remission is considered a "cure" after a few years. Sometimes the tumor regrows, or the disease comes back for whatever reason (an ectopic or adrenal tumor, they didn't get all the tumor tissue, they missed a tumor on another part of the pituitary, etc) or it just wasn't successful in the first place. The stats are all over the place on this one. Some say 90% cure rate, some say 40%, my guess is it depends on what you consider a "cure." If the tumor can be identified the majority of people go in for another pit surgery. Some opt for gamma knife radiation, though it sounds as though it is VERY few and has some really specific requirements for where the tumor is in relation to vessels, brain, etc. Some opt for a bilateral adrenalectomy at that point, chosing addisons over cushings. That sounds fairly common, and is the first choice doctor recommendation should a 2nd pit surgery fail, it seems. There is controversy over using a BLA for the 2nd surgery, though seems pretty evenly split among the doctors depends more on the patient and their understanding of what they're chosing.
Medical treatment for cushings is not used long-term and is only for those who cannot undergo surgery, and only if you have type 1 diabetes (cushings causes it) as well, due to the large numbers of high-risk side effects involved with the medications (I think only one is FDA approved, and there are two more, one not available in the states). So, surgery really is the only option and it explains more why people for whom surgery has failed move on to chosing a BLA and addisons. The mortality rate untreated is somewhere around 5 fold, whereas treated it is closer to the norm. It is still slightly elevated, but that is all individual based on how much damage the disease has done to your cardiovascular system already.
I don't have chronic hypertension, diabetes, or joint pain, and I'm young. While they say the same thing as you do with AI "takes as long to get better as you've been sick", I can't imagine it would be 15 years! The younger patients generally recover faster and easier (and 31 is young-ish), and because I don't have a lot of the complications if I do have Cushing's, I should do fairly well.
So, it appears that the norm is to start getting positive test results about 3-5 months before surgery is scheduled...so it'd be fall/winter before we got that far (IF we do).