survive the journey

Korlym: New drug to treat Cushing's Disease

survivethejourney@gmail.com (RobinS) — Fri, 18 May 2012 07:12:20 PDT

I know several folks who have recently started taking the new FDA-approved drug, Korlym, to treat Cushing's Disease. Korlym is a new name for the "old" drug mifepristone and was developed by Corcept Therapeutics Incorporated.

Korlym blocks the activity of cortisol and is proven to reduce high blood sugar (hyperglycemia), a key symptom of Cushing's. Korlym has a unique way of working. Instead of reducing cortisol levels, it blocks the action of cortisol, thus preventing the effects of excess cortisol.¹

Korlym has many side effects and cannot be taken by everyone. Once the patient stops taking Korlym, she will continue to have Cushing's. The biologic half-life of Korlym is approximately 85 hours. If a patient suffers adrenal insufficiency or crisis, massive amounts of hydrocortisone or dexamethasone are needed to alleviate these and will have to be continued for the duration of the drug in his system.

To follow a patient who has just started taking Korlym, you will find her blog here: Cushing's Disease

Day 29 of the Cushing's Awareness Challenge: Life goes on

survivethejourney@gmail.com (RobinS) — Fri, 18 May 2012 06:36:58 PDT

Life goes on...

Life doesn't stop because one gets a rare illness or is diagnosed with a disease. However, mine seems to be delineated by before Cushings, after Cushing's, before BLA and after BLA. Before Cushing's is a gray area. I'm not sure exactly when I started getting symptoms. Some of my symptoms went as far back as childhood but others were more recent when I realized what was wrong with me. I was 47-48 at that time. I'm sure I had symptoms of Cushing's (verified by my photo evidence) from the age of 24.

Skipping ahead past those years between ages 47 and 52 when I was going through testing, diagnosis, pituitary surgery to remove the tumor, recurrence, and re-testing/diagnosis though my BLA, I am in the after BLA era. Does anyone else see her life this way? I know most folks look at graduation, job, marriage, children, etc. as the defining moments of their lives. And my children, plus my grand-child, are definitely more important to me, but I still categorize them in the pre-BLA/post-BLA eras.

Isn't it crazy that one event can be so momentous in one's life? I sit here typing this after a day of being lonely and wishing I was closer to my family and my grandson. Part of me wants to make the big leap and just "do it". Life is short. Just do it. The other, conservative part of me says, "You have to make it to retirement. You have to have something to live on and you don't want to lose this money." And once I do this, which I will someday, I know it will be a defining moment and I'll classify it post-move. I think that's a good thing. I'm tired of living my life around a disease.

Day 28 of the Cushing's Awareness Challenge: Getting it right...

survivethejourney@gmail.com (RobinS) — Sat, 28 Apr 2012 11:38:11 PDT

The Cushing's Awareness Challenge is winding down, and I haven't posted every day. I have tried to post at least twice a week. I have been so busy with work plus dealing with allergies I haven't had time or felt like posting when I have time.

I do believe my allergies are worse since my BLA. Perhaps the high cortisol treated them? I don't know. I do know this spring allergens are worse in my area than they usually are. Everything seemed to bloom and spout pollen all at once.

Someone asked me the other day why we are so concerned about awareness for Cushing's. "Isn't is a really rare disease?"

"No", I said, "It's just rarely diagnosed."

And there is research to back up my statement. One recent research article is one you should take to your doctor if you believe you have Cushing's. It talks about the reality of testing for Cushing's Disease/Syndrome and that it requires a lot of testing. One can have a lot of normal tests and still have Cushing's.

As I go through my daily life, I see a lot of people who have the signs of Cushing's. It's a daily conundrum deciding whether to approach a person about it or not. Many times when I have, I've been met with cynicism or been ignored totally. Other times, folks want information. A few times, I've been contacted by these saying either a) my doctor thinks I'm full of it or b) my doctor thinks you may be right but doesn't know what to do from here. It's tough, having this disease. Although there are a lot of textbooks for doctors describing how to test and diagnose, so many of us aren't truly textbook cases. That's the problem with textbooks. They are a "one size fits all" type of diagnosis/testing. We come in all sizes, shapes, and genders. We don't fit the textbook mold. Slowly, the textbooks are changing. Recent research is changing how doctors test and diagnose. In my opinion, it's going to take another generation or two of doctors to really get it right. Until then, many people won't be diagnosed and treated.

Day 24 of the Cushing's Challenge: When the "gold standard" becomes tarnished....

survivethejourney@gmail.com (RobinS) — Tue, 24 Apr 2012 17:18:19 PDT

Urinary Free Cortisol (UFC) testing has long been the "gold standard" for determining the need for more evaluation in the diagnosis of Cushing's Disease/Syndrome (CS). However, recent research belies the paradigm, especially with cyclic/episodic and mild/subclinical CS.

A fairly recent testing protocol, late-night salivary cortisol (NSC), is often touted as a replacement for the late-night serum cortisol. The ease of use at home has made it a practical application for testing cortisol levels. It, too, has limitations in testing for cyclic and/or mild CS.

A third application, the dexamethasone suppression test (DST), is another standard by which practioners evaluate their patients for CS. Again, there are limitations when evaluating cyclic/mild CS.

In a recent study, the full text article examines the three tests mentioned above. They found UFC's were of limited value whe diagnosing "mild" CS.

However, UFC may not accurately reflect the cortisol secretory state in patients with even the modest impairment of renal function (8). In addition, most of the cortisol secreted during a 24-h period is between 0400 h and 1600 h. Subtle increases in nighttime secretion, as may be seen in mild CS, may not be detected or only intermittently detected in a 24-h urine collection.

Notice the majority of the tests fell below the "normal" line on the graph.

In turn, the NSC was more accurate, but there were many "normals" in the results, with multiple repeats with several patients before obtaining a "high" result. The authors speculate this is due to cyclic CS or a "variability around a mildly elevated set point."

Of the 11 patients evaluated, all had surgery, and 10 of the 11 had pathology proven CS. (Sometimes it is hard to get enough sample tissue for a decent pathology with pituitary surgery.)

The DST was evaluated in this same study with those patients who were tested via that means, but not all patients were. However, in another study, the use of the DST was found to be of limited value for those patients with cyclic/mild CS.

These results demonstrate that the great majority of patients with mild and/or periodic Cushing's syndrome suppress to overnight dexamethasone. Since patients with mild and/or periodic Cushing's syndrome are the patients in whom the identification of hypercortisolism is difficult, our results from this relatively small study suggest that this test should no longer be used to exclude these patients from further workup for Cushing's syndrome.

It is important to remember that no one test adequately evaluates a patient for Cushing's. Even more important, multiple tests may have to be repeated multiple times. The authors in the first article emphasize this when they say, "Obviously [NSC and UFC ] may need to be performed several times before the suspected diagnosis of endogenous hypercortisolism can be correctly identified."

Still a third study (Findling, et al) says, "Even more problematic is the interpretation of the results of these tests, particularly if they are not in agreement with each other. This is particularly so in mild Cushing's syndrome; if the symptoms are subtle, the biochemical abnormalities are likely to be subtle as well." This is a very long article, chock full of information.

How important is it to screen for "mild" CS? "Mild" is a misleading term, sometimes more appropriately called subclinical CS. Findling, et al, point out a huge population where CS is generally overlooked and the depressing mortality for those same folks.

Dr. Theodore Friedman, et al, , in their research High Prevalence of Normal Tests Assessing Hypercortisolism in Subjects with Mild and Episodic Cushing’s Syndrome Suggests that the Paradigm for Diagnosis and Exclusion of Cushing ’ s Syndrome Requires Multiple Testing point out no one test is conclusive for testing for Cushing's Disease/Syndrome:

The probability of having Cushing’s syndrome when one test was negative was 92 % for 23:00 h salivary cortisol, 88 % for 24-h UFC, 86 % for 24-h 17OHS, and 54 % for nighttime plasma cortisol. These results demonstrated that episodic hypercortisolism is highly prevalent in subjects with mild Cushing’s syndrome and no single test was eﬀective in conclusively diagnosing or excluding the condition.

Why is CS generally overlooked, then? Findling lists many reasons, including a study done by Cartagi, et al, where an extraordinarily large percentage of diabetic patients actually had CS. It is often too easy to pin a diagnosis of diabetes or hypertension without realizing it is a symptom.

The recognition of mild/subclinical and cyclic CS has changed the diagnostic approach. Sadly, too many patients are never seen by those who know that. And most of all, there really is no such thing as "mild" Cushing's. It damages the body just as much as "florid".

~~~~~~~~~~~~~~~~~~~~~~

(For more information on how these tests are done, see Testing 101: Biochemical analysis.

For problems/errors to watch for when testing, see When lab tests don't rate an A+, or even a C-..... )

Kidambi, S., Raff, H., Findling, J.W. (2007). Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis of mild Cushing's syndrome. European Journal of Endocrinology, 157(6), 725-731. DOI: 10.1530/EJE-07-0424

Day 23 in the Cushing's Awareness Challenge: Why do we overeat? Underexercise? Is it a matter of willpower?

survivethejourney@gmail.com (RobinS) — Mon, 23 Apr 2012 18:37:17 PDT

I'd like to talk to you a bit about what it is like with Cushing's high cortisol surging through one's system and the hunger it brings.

Have you ever been on steroids for anything? Do you remember the hunger you felt on them? That's all I remember feeling in my life prior to my bilateral adrenalectomy. I have always been hungry. Ok, let me clarify "always". Let's say 80% of my life I was hungry. Between the flu and what I now know were "lows*", I had periods of no hunger. But for the most part, I was somewhere between stomach-growling hungry to ravenous, bite-my-arm-off hungry.

Does that mean I had no willpower? No. I managed, with the help of my very nutritionally wise mother, to stay at a normal weight even through college. I did put on the freshman 15 in my sophomore year of college, but also managed to lose it by essentially living on caffeine and a diet of books. (Study, that is.) Labs are not good places to eat, and I basically lived in one.

Was that easy? NO! I confess to binge eating at times. I don't think I ever purged. I don't remember doing that. I was so absolutely hungry and nothing would sate my appetite. Nothing. I know my mother knew it, too. I remember slipping into the kitchen when I was small and "stealing" bread or crackers hoping she wouldn't notice. She never mentioned it, but she was sharp. She knew. I would panic at the thought of not being able to have food even at a young age.

Snacks were forbidden when I grew up unless we picked an apple off the tree or a tomato out of the garden. We ate three nutritional meals a day, drank skim milk, and lived outside. Yes, I exercised. Only we called it "play", then. Bicycles were star ships and swings were space stations. Lightening bugs were made by God to be chased. Dusk was a time for hide-and-seek. But I digress...

After college and graduate school, I got married. Had babies. Couldn't lose weight. You can read all about that in Metamorphosis. The thing is, I was hungry all the time. But I DID NOT EAT all the time. Sure, it absolutely possessed my every thought, my every action and my every plan. I had to know food was available even if I didn't eat it. And yes, sometimes I lost control and I overate. I wanted so much to be free of that obsession with food.

I managed to lose that obsession one time on phentermine. However, I started gaining weight even then. I was in a "low*", either induced by the phentermine or just coincidentally, prior to that gain. I vote for the latter.

My disease accelerated. I became "florid" or "classical" as my neurosurgeon coined it. I daily went from periods of nausea in the morning to periods of starvation by afternoon. Ok...it felt that way. I WANTED FOOD! I wanted to EAT! But did I? Most of the time, no. I counted calories, I measured food, I watched my carbs, I measured fat grams, I ate high fiber, I tried to exercise.

Let me emphasize: I TRIED to exercise. Have you ever walked through mud? How about walking in the waves in the ocean? That's how my legs felt when I tried to do anything. That started a long time ago, but I persisted in trying to build them up. Even when I was at my worst before my first surgery to remove my pituitary surgery, I did water aerobics and/or swam several times a week. I did that until the pain became unbearable. I even hired a trainer who eventually told me something was very wrong with me because I could not build muscle.

Did I lack willpower? I don't think so. Only a few people know the magnitude of the will it took to find someone to help me, understand me, diagnose me and get me on the road to recovery. I fought hard every day to lose weight. I fought hard to get well. I fought hard to live! To work! To be here for my daughters, my grandson, my brother, and my parents. I fought the "establishment" called medicine, too. And I still fight for all that. And I am not alone. Zebras do exist.

I am no longer hungry for food. Since my BLA in June 2010, I can exercise plus I am seldom starving. I often have to remind myself to eat. I am hungry for understanding, however. Not just for me, but for all who fight as I do for others to see beyond the obesity to the true problem of Cushing's Disease/Syndrome.

*"lows": periods in the cycle of cyclic/intermittent/episodic Cushing's where cortisol is low.

Day 21 of the Cushing's Awareness Challenge: eHow doesn't know how...

survivethejourney@gmail.com (RobinS) — Sat, 21 Apr 2012 11:11:19 PDT

A must read on another blog, Brain Tumors can make you Fat!, points out the problem with eHow's information on Cushing's Disease/Syndrome.

The title of your article is "How to Avoid Cushing's Disease." So, in your expert opinion, how does reducing your salt intake prevent a disease that is caused by an overproduction of cortisol? Could you please cite your source for your readers on what tells you avoiding salt will help a person avoid hypercortisolemia?

You don't want to miss this.

Day 18 of the Cushing's Awareness Challenge: Fiona Apple may just have it right...

survivethejourney@gmail.com (RobinS) — Wed, 18 Apr 2012 19:05:06 PDT

He said 'It's all in your head' and I said 'So's everything' but he didn't get it --Fiona Apple in "Paperbag".

Pituitary tumors have a large spectrum pathology. These "little buggers" may cause large problems, also. Dr. Shereen Ezzat of the Toronto Cancer Institute has been studying pituitary tumors for several years, and presents the case for epigenetic disruption of gene expression which causes alterations of normal pituitary cells. Using the information he and others have gathered, he is hopeful treatments for these lesions/tumors can be developed. Since the morbidity/mortality of most with pituitary tumors is greatly increased, and the only long-term therapies so far are surgical or radioactive, improved treatment is anxiously sought by those of us with Cushing's or presently in remission.
According to Dr. Ezzat, pituitary tumors comprise 10% of the tumors surgically removed intercranially with increased morbidity due to invasion of surrounding structures. As a Cushie community, we know this only too well first-hand. All too often the only recourse for the hypercortisolemia due to ACTH producing tumor cells is a bilateral adrenalectomy. Radiation is often a secondary treatment to decrease tumor growth or Nelson's syndrome.
In another article, Dr. Ezzat says, "Some pituitary adenomas grow rapidly, producing symptoms of an intracranial mass, loss of normal anterior pituitary hormone production, and visual-field disturbances due to stretching of the overlying optic chiasm. They can invade downward into paranasal sinuses, laterally into the cavernous sinuses (thereby disrupting coordinated eye movement) and upwards into the brain. They can cause death by invasion of the brain."
But size does NOT always matter with these tumors. Dr. Ezzat also says "they can cause mood disorders, sexual dysfunction, infertility, obesity and disfigurement, hypertension, diabetes mellitus and accelerated heart disease. If untreated, hormone-excess syndromes can be lethal."
In the pre-print, recent article, Epigenetic Control in Pituitary Tumors , Dr. Ezzat discusses epigenetically-mediated gene dysregulation as a cause for the production of pituitary tumors. He explores the role of fibroblast growth factors and histone gene silencing and discusses the implications of the need to find the process or mechanism involved in order to develop new therapies.

Shereen Ezzat, M.D. (2008). Epigenetic Control in Pituitary Tumors Endocrinology Journal DOI: http://dx.doi.org/http://www.jstage.jst.go.jp/article/endocrj/advpub/0/0804240101/_pdf

Day 17 of the Cushing's Awareness Challenge: Adrenalectomy Improves Quality of Life for Cushing's Patients Although It May Take Years

survivethejourney@gmail.com (RobinS) — Tue, 17 Apr 2012 14:52:20 PDT

Although adrenalectomies are only a first-line treatment for those with ACTH-independent tumors in Cushing's Syndrome (ectopic and adrenal tumors, benign and malignant), they are also often a treatment for those with Cushing's Disease when pituitary surgery fails to totally remove the source of excess ACTH.

Hypercortisolemia, the result of excess ACTH from the pituitary or from overproduction in ectopic or adrenal tumors, is very debilitating for those who suffer from CS/CD. According to the authors, "Untreated Cushing’s syndrome can cause significant physical and mental morbidity and mortality, with a mortality rate in untreated that is 4 times greater than the baseline population."

This study looked at the outcomes of 60 patients who underwent either a unilateral (53%) or bilateral adrenalectomy (47%) to treat their Cushing's. Except for one patient, all adrenalectomies were done laproscopically. The median follow-up time was 41.4 months. At that median time, 9 patients had died. 4 patients had died from the progression of malignant disease, 2 from unknown causes, 1 from pulmonary embolus 2 months after surgery, and 2 five months post-op from severe complications due to pituitary (ACTH-dependent) Cushing's Disease.

Around 75% of the common physical signs/symptoms of Cushing's resolved after surgery, but the central obesity only had a resolution rate of 57%. Diabetes was cured in 79%, hypertension "improved dramatically or was cured in 67%."

Symptoms took anywhere from a few weeks to 4 years to resolve with most of the physical changes resolving in a mean of 7-9 months. There was a great variability with no good predictor of this variability.

The remark that I find so telling is this:

In fact, we had several patients with ‘‘subclinical’’ Cushing’s who took over 2 years for their symptoms to resolve.

Too often those of us who suffer with Cushing's are told to wait until the disease "gets worse" before being diagnosed/treated.

The authors point out the complication rates which are typically higher for Cushing's patients than for others who undergo adrenalectomies for whatever reason. Immunosuppression leads to greater risk of infection. Addisonian crisis is another prevalent complication. However, overall they conclude that adrenalectomies are a safe and effective treatment option, but both physicians and patients must not expect overnight improvements. This is another case of where slow and steady wins the race.

R SIPPEL, D ELARAJ, E KEBEBEW, S LINDSAY, J TYRRELL, Q DUH (2008). Waiting for change: Symptom resolution after adrenalectomy for Cushing's syndrome Surgery, 144 (6), 1054-1061 DOI: 10.1016/j.surg.2008.08.024

Day 16 of the Cushing's Awareness Challenge: When lab tests don't rate an A+, or even a C-.....

survivethejourney@gmail.com (RobinS) — Mon, 16 Apr 2012 19:17:08 PDT

When testing for Cushing's, there are some standard tests that most up-to-date, in-the-know endocrine centers/doctors abide by. Of course, when one gets into the current research, combines the complexities of mild/episodic/cyclic Cushing's with florid/classical (you know...the CIA operative "thang" I've mentioned before), and then adds a ~~dash~~ ton of no-one-uses-the-same-protocols, no wonder it gets confusing.

The Urinary Free Cortisol (UFC) test has long been touted as the "gold standard". The current concensus among those who test episodic (et al) Cushing's the most is that it is NOT, but for the sake of argument and time, let's go with it. Everyone being tested for Cushing's will have to do UFC's. You are a rare one if not.

The UFC is a 24-hour collection of urine. That part is pretty easy. You discard the first void, start timing from there and collect every single pee-pickin' drop (I know...it's "pea"...couldn't resist) for those 24 hours, ending at the same time you started. What happens to that urine is the big debate, both before and after collection. My endocrinologist and at least two other major endocrinologists who are experts in the field recommend refrigeration if it's not going to the lab immediately (and possibly even then) but NO PRESERVATIVE.

Well, getting labs to agree to that is like the debacle in D.C. right now over Medicare. It ain't gonna happen. The absolute no-no that I've been told over and over is hydrochloric acid (HCl) as a preservative. Boric acid is accepted by most labs. Acetic acid is mentioned occasionally. In a study done by ARUP Institute, they found "Cortisol concentrations in samples stored with the acids were higher by 30% than in samples stored without acid, possibly as a result of partial hydrolysis of sulfate and glucuronide conjugates. " Esoterix, the diamond of endocrine labs, prefers no preservative at all.

What is a UFC measuring anyway? Well, "free" cortisol is used by the body for various functions, but the thought behind the test is that this free cortisol is spilled into the urine if there is excess. One can get into the effect of cortisol binding globulin (CBG) and all sorts of other scenarios which make that not true for many folks, but I won't in this post. So, if there is excess free cortisol spilled into the urine, an average can be measured for a 24-hour period.

UFC's are not just used to measure cortisol, though. Most endocrinologists also want to test the amount of creatinine in the urine, and many want to also test 17-hydroxycorticosteriods (17-OHC's). When that is the case, now the lab protocol must include them and determine if a preservative and which preservative is necessary or optional.

Also, the type of testing determines preservative use. Radioactive immunoassay (RIA) is now outdated, but is still being used. HPLC Tandem Mass Spectrometry is the most current, with Liquid Chromatography Tandem Mass Spectrometry (LCMSMS) running a close second.

I can tell tales about labs and how they handle this urine. Bacteria degrade the cortisol quickly at room temperature, and getting a lab to refrigerate it is a crap shoot (pee shoot?). You hope they will but often they don't. Measure/aliquoting a correct sample is another problem if there is more than one jug for a collection. I often collected more than one jug when my cortisol was high. The aliquot must be a mix of all samples so there is a proper average and the TOTAL volume for all jugs used in the 24-hour collection has to be recorded.

Some won't accept the collection if it doesn't have the what the person who is working at that time thinks is the correct preservative. I've been known to leave with my jugs in tow, call the lab manager, and go back when s/he is there. God forbid my hard work is wasted. Sadly, I have many friends with Cushing's who have had collections wasted due to inadequacy and nonunderstanding of proper protocols. Not MISunderstanding, mind you. NONunderststanding.

From experience and observation, I offer my humble opinion: Find a lab which will use one of the preferred methods above (not RIA), will refrigerate the urine until tested, will not add a preservative, and which understands all must be THAWED and MIXED before aliquoting it. If the urine aliquot/sample is sent elsewhere, it needs to be sent FROZEN to be thawed before measured, and the total amount of urine that was presented needs to be recorded.

Another test that is used extensively for the measurement of cortisol, especially with diurnal variation or lack of, is serum cortisol. This one is pretty straight forward as long as the person reading the lab results understands what they really mean.

The article, "Cushing's Syndrome" by John Newell-Price, Xavier Bertagna, Ashley B Grossman, Lynnette K Nieman, Lancet 2006; 367: 1605–17,Division of Clinical Sciences, University of Sheffi eld, Northern General Hospital, Sheffi eld, UK (J Newell-Price FRCP); says

An awake midnight concentration of cortisol in plasma of more than 207
nmol/L differentiates between Cushing’s syndrome and other causes of
hypercortisolaemia but can miss mild disease diagnosis in about 7% of cases.
(The conversion factor of μg/dL x 27.6 = nmol/L)

Essentially, serum cortisols only have valid ranges for the 8 a.m. and 4 p.m. time periods in most labs. The research and leading endocrinologists acknowledge the validity of midnight serum cortisols, also. So, as I said before, the 8 a.m. should be the highest of the three, with the 4 p.m. about half of the 8 a.m. value. The midnight value should be close to zero.

The problem is that the labs don't know about the midnight range (uh...zero), so IF one can find a lab willing to draw a midnight serum cortisol fairly frequently for testing, they won't know to put "zero" on the range and flag it as high if it's above that. 7.5 μg/dL (207 nmol/L) is diagnostically high. If you have someone ordering tests for you who does not understand this, you may get a call saying "it was normal". Ask for the actual report.

As for the bloodwork itself, it should be drawn into a red-top or green-top tube. However, all is not lost if another tube is used. Most of the time, it can be used anyhow for this test. Temperature really isn't a factor if the test is run in a timely manner. The serum needs to be separated from the cells and the sample cannot be anticoagulated. If it's not run within an hour, this should be done and the serum refrigerated up to 24 hours or frozen if longer.

A third test that is important in the diagnosing of Cushing's and differentiating between types is Adrenocorticotropic Hormone (ACTH). The lab technician must use an EDTA (lavender top) plasma tube only! Collection in nonsiliconized tubes can result in falsely low results as ACTH adheres to glass. It needs to be mixed by inversion and centrifuged immediately after collection. IT MUST NOT GET WARM. The tubes should be on ice prior to drawing the blood, and put immediately back in the ice until it is separated and then frozen. The plasma must be separated and frozen immediately. If it is shipped, it should be shipped on dry ice while still frozen. ACTH breaks down easily in heat, and if not collected and preserved on ice, proteolysis (degradation of proteins by cellular enzymes) can reduce the plasma concentration.

The salivary cortisol test is another test used very similarly to the serum cortisol tests. It, too, can help show diurnal rhythm (or lack thereof). The protocol is pretty simple and straight-forward regardless of the lab. There are only a few labs who use an FDA approved test for these salivary cortisol levels. The labs are Esoterix, ACL Laboratories, LabCorp (who now owns Esoterix), and Quest. It is very easy for a doctor to set up an account with any of these and order the testing kits for patients. The patient simply collects "spit" until s/he gathers enough for the container or "salivette". Some of the labs use a tampon-like material (salivette) for the patient to soak with saliva and place in the tube. Both methods of collection are reliable. However, it is important that one does not touch the salivette with hands and should not eat, drink or rinse the mouth for thirty minutes prior to collection.

A word of caution. Although the cortisol supposedly does not break down very quickly, a number of us got much higher results when we first froze the samples, then shipped them overnight. Since bacteria will break down cortisol, it stands to reason this can happen with the salivary test, too.

Another inconsistency with salivary cortisols that many of us have observed is that we have had high serum cortisols the same nights we have done salivary cortisols. I did several while sitting and having blood drawn. My serum cortisol was high. My salivary cortisol was "normal". Only when my serum cortisol (at midnight) was around 16 μg/dL or higher did my salivary cortisol show high levels, too. The clearance is different, thus the outcomes can vary.

What advice do I have for testing? You must be proactive in your testing process.

Know the proper protocols

Take print-outs of the proper protocols with you. You can find them for just about any lab. If you can't, the Mayo site and ARUP labs have great details. Labcorp and Esoterix also have may good, informative articles.

If your doctor wants it done a certain way, get him/her to put that in writing

Insist on the proper protocol. This is YOUR TIME and YOUR MONEY (even with insurance) that is paying for a service to be done right. You may need to catch that high and you don't want anyone to mess it up.

Call the lab ahead of time and speak with the lab manager. Explain your situation courteously and ask if they are familiar with the tests and protocols. Go over them together, talk about when you will be in, and what you need to do to make sure those protocols are followed. This will save you many headaches down the road. A good relationship with your lab will go a LONG way.

Call the lab manager again if you do encounter problems and discuss the issues. Courtesy still goes further than anger. However, I've been known to use some of that southern "charm" my mother taught me. Ahem...

For midnight serums, it is difficult to find a lab, other than the local hospital lab, open late at night. Again, call them ahead of time, explain the testing protocol and why you need to come in at midnight. Get the paperwork done ahead of time so you can go in and get it done quickly once you are there.

A little kindness goes a long way. A treat, some cookies, a gift basket or something simple as a cake shared with the lab folks occasionally will brighten their day. The late-night lab I used was full of readers. I saw good books everywhere, so I took in a stack every now and then after I'd finished them along with some candy or something.

Say thank-you when it is done right. Again, that goes a long way.

Don't be surprised if drawing blood is difficult. If you are one of the Cushies who has issues with that due to the affect of the cortisol on the veins, try to keep your arms warm and stay hydrated. My blood draws were very difficult on the best of days, and I was prepared for that. Warm bags of rice, a warm fleece jacket, or whatever it takes to keep those arms warm are helpful.
Well, the report card isn't in on the labs, yet, because the rubric hasn't been standardized, but you get an A for effort!!!

I apologize for missing a few days. I was just too busy, which is a delight unto itself.

Day 13 in the Cushing's Awareness Challenge: Central Hypothyroidism--A Cushing's Disease Problem, too

survivethejourney@gmail.com (RobinS) — Fri, 13 Apr 2012 05:50:53 PDT

Since approximately 80% of Cushing's Disease/Syndrome is caused by a pituitary adenoma, other hormones produced by the interaction of the hypothalamic-pituitary-adrenal (HPA) axis are often deficient. This includes thyroid-stimulating hormone (TSH).

Primary hypothyroidism is often detected by elevated TSH values. This is due to the normal feedback-loop of the HPA axis. Central hypothyroidism (CH), however, is not typically detected by measuring TSH which is low due to a disruption of the pituitary's stimulus and is not produced as needed. The most common cause is a pituitary adenoma.

In Mechanisms Related to the Pathophysiology and Management of Central Hypothyroidism, the authors state, "Given that the prevalence of pituitary adenomas in the general population is greater than 10%, the true prevalence of CH might be much higher than that reported". When speaking of the method of measuring TSH levels alone, they say this "approach works, however, only if the hypothalamic-pituitary-thyroid axis is normal. Conversely, the strategy of first-line TSH measurement can miss patients with CH."

The authors give a very nice synopsis of the HPA axis' role in thyroid regulation and function. The diagrams are well-done, also. In Table 1, the causes of CH are listed:

Table 1. Causes of Central Hypothyroidism

Cause Congenital Acquired

Classic causes

Space-occupying lesions (brain or pituitary; pituitary adenoma, craniopharygioma, etc.) Yes Yes

Radiation No Yes

Vascular disease (Sheehan syndrome, etc.) Yes Yes

Nonclassic causes

Traumatic brain injury or subarachnoid hemorrhage No Yes

Drug-induced (bexarotene, carbemazepine, etc.) No Yes

Growth hormone therapy No Yes

Infection (lymphocytic adenohypophysitis, lymphocytic hypophysitis) No Yes

Set point diseases (infant's born to mothers with inadequately controlled Graves disease, etc.) Yes No

Genetic mutations Yes No

Idiopathic Yes Yes

Cause	Congenital	Acquired
Classic causes
Space-occupying lesions (brain or pituitary; pituitary adenoma, craniopharygioma, etc.)	Yes	Yes
Radiation	No	Yes
Vascular disease (Sheehan syndrome, etc.)	Yes	Yes
Nonclassic causes
Traumatic brain injury or subarachnoid hemorrhage	No	Yes
Drug-induced (bexarotene, carbemazepine, etc.)	No	Yes
Growth hormone therapy	No	Yes
Infection (lymphocytic adenohypophysitis, lymphocytic hypophysitis)	No	Yes
Set point diseases (infant's born to mothers with inadequately controlled Graves disease, etc.)	Yes	No
Genetic mutations	Yes	No
Idiopathic	Yes	Yes

CH usually appears concurrently with other hormone deficiencies. "Hormone deficiencies were seen for luteinizing hormone/follicle-stimulating hormone (LH/FSH) in 85% of patients, growth hormone in 65%, adrenocorticotropic hormone (ACTH) in 62%, TSH in 60%, antidiuretic hormone in 23% and prolactin in 15%."

The authors also detail non-classic causes of CH, including genetic mutations. With one familial case inheritance was determined to be autosomal recessive. Interestingly, the values of TSH measured varied by assay with one mutation.

The researchers make a case for using free T4 and free T3 to determine CH while levels of TSH have no diagnostic value. They also indicate that although the "nocturnal surge of serum TSH level has been used to assess CH, this approach is still controversial. MRI could be required for most suspected cases of CH to detect origin of hypothalamic or pituitary disorders."

Treatment is much the same as for any hypothyroidism. Levoxythyroxine is the first line of treatment. They also carefully point out the following:

Deficiencies of hormones other than TSH should be considered before starting
treatment. When ACTH deficiency is also present, glucocorticoid therapy should
be started at least 1 week before initiation of levothyroxine to avoid increased
consumption of cortisol and worsening of the ACTH deficiency, which can
induce crisis. (emphasis mine)

An algorithm was developed for treating CH sufferers. Interestingly, this does not show using any form of T3, although there are folks who do not convert forms of T4 to the needed T3. They do empasize, however, the importance of achieving "free T4 in the upper end of the normal range rather than within the middle or lower values".

On a positive note for those who have or will undergo pituitary surgery, they authors conclude, "Surgery is reported to lead to an improvement in anterior pituitary function in approximately 35% of patients with pituitary adenoma and CH."

Masanobu Yamada, Masatomo Mori (2008). Mechanisms related to the pathophysiology and management of central hypothyroidism Nature Clinical Practice Endocrinology & Metabolism, 4 (12), 683-694 DOI: 10.1038/ncpendmet0995

Day 12 of the Cushing's Awareness Challenge: The Multiple Aliases of Cushing's

survivethejourney@gmail.com (RobinS) — Fri, 13 Apr 2012 06:36:10 PDT

Episodic/intermittent/cylical/mild Cushing's has more aliases than a CIA operative. And I'm sure there are some I've left out. Since this form of Cushing's seems to be so elusive to the medical community, the analogy works extremely well. Episodic Cushing’s syndrome (CS) is a rare disorder, characterized by repeated episodes of cortisol excess interspersed by periods of normal cortisol secretion. The so-called cycles of hypercortisolism can occur regularly or irregularly with the phases ranging from days to years.

In comparison, "florid" or "classical" Cushing's shows evidence of continual or almost continual hypercortisolism. There is a school of thought which says these are really very rapidly cycling forms of Cushing's. However, there does not seem to be a concensus on that in the literature and in the research. Frankly, I don't know if anyone has done enough testing daily to figure it out.

According to some research done in the Netherlands, "As with classic hypercortisolism, cyclic CS is found more commonly among women than men, with a female to male ratio of 3:1 (Table 2). The disorder usually becomes manifest in the fifth decade, but may present from early infancy until older age (highest reported age at presentation being 72 years)."

Other clinical studies say, "The features of endogenous hypercortisolism (especially, when mild) are protean and coincide with many common clinical conditions like the dysmetabolic syndrome (1, 2). Screening studies in high-risk populations have discovered unsuspected CS in as many as 2–5% of patients with diabetes mellitus (3–7) and suggest that mild CS is more common than
previously appreciated."

In Cyclical Cushing's syndrome: an update the full text article says, "Cyclical Cushing's syndrome is a pattern of hypercortisolism in which the biochemistry of cortisol production fluctuates rhythmically. This syndrome is often associated with fluctuating symptoms and signs. This type of case was initially thought to be rare. It has, however, recently been recognized as occurring much more frequently. The phenomenon is important because it can, if not recognized, lead to errors in diagnosis and differential diagnosis of the syndrome and in assessment of therapeutic outcomes. All of these can have very serious clinical consequences."

In High Prevalence of Normal Tests Assessing Hypercortisolism in Subjects with Mild and Episodic Cushing’s Syndrome Suggests that the Paradigm for Diagnosis and Exclusion of Cushing’s Syndrome Requires Multiple Testing, "episodic hypercortisolism is highly prevalent in subjects with mild Cushing’s syndrome and no single test was effective in conclusively diagnosing or excluding the condition."

I was told by a prominent endocrinologist at a prominent teaching hospital that "cyclical Cushing's does not exist" and that I was "reading too much" when I was trying to get someone to help me. I hope this person is doing some more reading. S/he is not reading enough.

Day 11 of the Cushing's Awareness Challenge: Bilateral Adrenalectomy and Change

survivethejourney@gmail.com (RobinS) — Wed, 11 Apr 2012 07:23:15 PDT

I had a bilateral adrenalectomy to control my Cushing's Disease on June 14, 2010. Although adrenalectomies are only a first-line treatment for those with ACTH-independent tumors in Cushing's Syndrome (ectopic and adrenal tumors, benign and malignant), they are also often a treatment for those with Cushing's Disease when pituitary surgery fails to totally remove the source of excess ACTH, which was the case for me.

Hypercortisolemia, the result of excess ACTH from the pituitary or from overproduction in ectopic or adrenal tumors, is very debilitating for those who suffer from CS/CD. According to the authors, "Untreated Cushing’s syndrome can cause significant physical and mental morbidity and mortality, with a mortality rate in untreated that is 4 times greater than the baseline population."

This study looked at the outcomes of 60 patients who underwent either a unilateral (53%) or bilateral adrenalectomy (47%) to treat their Cushing's. Except for one patient, all adrenalectomies were done laproscopically. The median follow-up time was 41.4 months. At that median time, 9 patients had died. 4 patients had died from the progression of malignant disease, 2 from unknown causes, 1 from pulmonary embolus 2 months after surgery, and 2 five months post-op from severe complications due to pituitary (ACTH-dependent) Cushing's Disease.

Around 75% of the common physical signs/symptoms of Cushing's resolved after surgery, but the central obesity only had a resolution rate of 57%. Diabetes was cured in 79%, hypertension "improved dramatically or was cured in 67%."

Symptoms took anywhere from a few weeks to 4 years to resolve with most of the physical changes resolving in a mean of 7-9 months. There was a great variability with no good predictor of this variability.

The remark that I find so telling is this:

In fact, we had several patients with ‘‘subclinical’’ Cushing’s who took over 2 years for their symptoms to resolve.

Day 10 of the Cushing's Awareness Challenge: What I Have Learned the Hard Way

survivethejourney@gmail.com (RobinS) — Tue, 10 Apr 2012 17:18:29 PDT

When I first realized I might have Cushing's Disease, I thought it would be easy to get help. After umpteen dozen doctors, endocrinologists, bariatric surgeons, and neurosurgeons, I found out otherwise. While many things are diagnosed fairly quickly, it took years to be diagnosed even with conclusive tests to prove I had Cushing's.

I learned the hard way that I had to be my own advocate. I started researching in reputable places such as medical journals all I could learn about Cushing's Disease/Syndrome. I found knowledgeable doctors/endocrinologists/neurosurgeons to test, look at tests already done, and read MRI's. Only have I expended that effort by traveling all over the country was I diagnosed for the first time preceding surgery to remove my pituitary tumor.

Even after that, when I had a recurrence, I had to choose to travel to a renowned endocrinologist again. There aren't many out there who really understand the disease. Those who research and study it are more prone to understand it. Now, I know that with any disease, finding the doctors who are most knowledgeable can save my life. I went through almost 30 years of Cushing's before my remission due to a bilateral adrenalectomy. I wish I'd know at the beginning what I know now.

Day 9 of the Cushing's Awareness Challenge: Repost of "We Need An Elephant Specialist"

survivethejourney@gmail.com (RobinS) — Mon, 09 Apr 2012 04:35:00 PDT

This is a special story written on the Cushings Help support boards. The author gave me permission to post it here on my blog. No matter how good our doctors are, if someone doesn't put it all together, no one sees the whole picture. Most of the time we, the patients, are the ones who put it all together.

Kim's story:

He walked into the exam room, introduced himself, and as he sat down, he asked, "Has anyone ever suggested you might have Cushing's disease or Cushing's syndrome?"

My name's Kim, and I'm 49 years old. I have two children, two grandchildren, and two full-time jobs. On the weekdays, I'm a writer and editor specializing in education issues; evenings and weekends, I'm marketing director at an international and arthouse movie theater. I had to pick up this second job to pay for the medical expenses not covered by my health insurance. And, as you may know, there are a lot of medical expenses involved in this disease/syndrome.

Until three years ago, I was also a marathon walker and a racewalking coach for an organization that trains endurance athletes who raise funds to fight blood cancers. For ten years, I walked between 35 and 50 miles every week. It was nothing for me to wake up on any given morning and decide to walk 10 miles. Saturdays I would racewalk between 12 and 18 miles with my group, and then Sunday mornings I met with some friends to bicycle 10 miles and then walk four miles. I bicycled or walked to and from my weekend job even after walking and cycling for hours earlier in the day. When I traveled, I walked everywhere: once I walked the entire length of Manhattan just to see what it would be like. Four years ago, I was sitting in a coffeehouse in mountainous Sarajevo, Bosnia, and noticed a passel of runners with race tags on their shirts. I was curious to know which race was going on, as I hadn't heard of any big events, so I walked down along the lines of runners back to where the slower runners and walkers were, and then walked alongside them for the rest of the 10-mile race. Up mountains and hills and down them, talking and listening all along the way. Just on the force of a whim.

In September 2006, I walked two half-marathons and kept up with my regular training besides. But a few weeks later, I came down with a bad flu, which quickly spiraled down to bronchitis and pneumonia. I was sick for weeks. So sick that an alarmed marathoning friend called his brother-in-law, a renowned pulmonologist, and asked a favor: would he come home from vacation immediately and see me at Duke University Hospitals and Clinics? His brother-in-law did indeed drop everything and met me at the hospital during his vacation time so that he could figure out what was wrong. Himself a marathon runner, he asked me to walk with him down the hallway to check my tolerance for exercise; I couldn't walk even five minutes at a brisk walking pace. I was "deconditioning" before his eyes. I was so exhausted I cried. I slept in the exam room between tests; I even fell asleep during a CT scan.

I never got better. I never walked another half-marathon. I never got back to my daily routines. I never felt healthy again.

Recently I sat at my table staring at an information sheet for the referral to an endocrinologist. I was so exhausted with the task of listing out all my surgeries, procedures, and diagnoses. I flipped through the contact list on my iPhone to help me remember which doctors I'd seen in the past three years. Almost every alphabetical category on my contact list contains a specialist. Each one of them is at the top of his or her field. Each one of them is terrific. Each one of them solved seemingly impossible medical riddles. Each one had valid points in believing that solving the mystery within his or her field would make me better. But which one was right?

I spun through my contact list, A-Z.

Would all be revealed by the bariatric surgeon who performed the LapBand surgery after I'd gained 70 pounds in 2007? Well, it must not be him; despite a very successful first couple of months post-Band surgery in 2008, I began to put on ounces rather than lose pounds -- even while on a strict diet that was assiduously journaled. He was frustrated, I was frustrated. Why on earth wasn't I losing weight and feeling better? I was clearly committed to compliance, and he was clearly committed to having a successful patient outcome. What was wrong?

There was the cardiologist who warned me that my heart is "practically dissolving." Maybe fixing that would solve the puzzle and make me healthier. Well, we tried that, but the slow slide continued. And what was the deal with this hypertension? Before 2006, my blood pressure was fine. Now it was so high that I was at risk for stroke.

My dentist was concerned about the mouth sores that never seemed to heal properly. And my mouth was so dry.

A dermatologist was amused by my response when I was referred to her and diagnosed with a pyogenic granuloma on my hand: I just couldn't stop laughing. My hand was bleeding spontaneously from this spot on the palm of my hand -- just like I had stigmata! Who could have kept themselves from laughing at that? While she was repairing the exposed vein, she commented on my dry skin and the vertical split in two of my fingernails (one of them quite severe). Also, where did I get all those bruises? Do I bruise often? Have I had a recent blood count?

Then there was the forensic psychiatrist who specializes in treating patients with posttraumatic stress disorder and said that I was the highest-functioning victim of childhood trauma and domestic abuse she'd ever met, but that I was so medically fragile since getting sick in 2006 that she was seriously worried about my living through 2007. The anti-depressants prescribed didn't seem to help with the insomnia I was suffering, so she kindly offered Ambien as well.

And the gastroenterologist who was intrigued by the various symptoms I presented -- not merely the GERD, Schatzki ring, difficulty processing and storing iron taken orally (attempts to keep my iron levels up failed so miserably that the only way I could keep my gums from remaining permanently white was to go back to the hematology-oncologist for IV infusions of iron), and esophageal ulcers and lesions that never healed ... but also the various other ways my body was failing. CREST syndrome seemed likely, but ....

Could the answer lie with the general practitioner who steadfastly maintained that if I would just fecking lose weight that I'd feel better? When I was too exhausted to see the cardiologist he referred me to, he called me at the office and ordered me to leave my desk right then and there and get my butt to the cardiology office, and then to call him when I was finished. And he was a pitbull when it came to my meeting with other specialists. It was his recommendation that I have weight-loss surgery, because he was sure it would reduce the strain on my heart, fix my pulmonology issues, and get me back on track with my marathoning.

My hematology-oncologist was convinced the issue was a leukemoid disorder consequent to chronic illness. She could treat that. But which chronic illness was causing it? After months and months of testing (including one test that required me to be helicoptered to the testing facility), bone-marrow biopsies (ouch!), and endless rounds of hours-long IV infusions of iron, enzymes, vitamins, and mildly chemotherapeutic agents, she admitted she was stumped.

An amazing opthalmologist spent hours and hours and hours trying to figure out why my vision would go blurry and I suffered endless headaches. Retinal tumor, possibly? CREST syndrome would explain the dry eyes, of course. But not even tear replacement helped with the blurriness.

There was also my fantastic orthopaedic surgeon who did a meniscus repair after I injured my knees through repeated stumbling. He told me he was concerned about how long it took me to recover and the fact that I hadn't seemed to heal well from a previous surgical repair of an ankle injury also caused by instability. He's a very good surgeon, he said: why was there so much scarring, and why was it taking so long for his work to heal? And what was up with all the inflammation in my knees, calves, and ankles?

What about the pulmonologist who was investigating the possibility of pulmonary hypertension? He seemed buoyed by his success in most of the investigative work but simply could not track down the reasons the condition of my lungs and heart made me a possible candidate for a heart-lung transplant a few years down the road. My blood pressure was so high at the time of my initial appointment that he was concerned I would have (or perhaps had had) a stroke. Why was my throat chronically sore? Why did I have such severe laryngitis for so many weeks on end -- so persistent and severe that he considered referring me to an ENT surgeon to repair what might be a malfunctioning larynx?

Maybe the rheumatologist seeing me for fibromyalgia and a strange pattern of diffuse inflammations throughout the body? We never got very far getting to the bottom of that, either. But we did get a lot of test results flowing.

Finally, I'd completed the medical history form and my list of medications. It was my bariatric surgeon who called my primary-care physician (the mean, crabby one who insisted I was fat, not sick) and asked him to have my cortisol levels tested. He was just so frustrated that the LapBand surgery didn't work as well as he was sure it would. There was clearly some underlying cause impeding success -- because it wasn't his surgical skills!

And that's how I ended up in the office of my endocrinologist last week. With my chart of lab results and my medical history in his hand, he walked into the exam room and introduced himself. As he sat down, he asked, "Has anyone ever suggested you might have Cushing's disease or Cushing's syndrome?"

I thought I'd had a lot of testing done by other specialists, but I was a mere wee, green lassie inexperienced in the ways of testing before this past week! To be honest, I can't really tell you all the results of all the tests right now, but as things come in, I'll be documenting them and perhaps sharing some of them here. (Robin's note: "here" is on the cushings-help.com message/support boards.)

I want to repeat that, with the possible exception of my primary-care physician (who's a pitbull when it comes to medical case management but ... um ... well ... lacks certain people skills that ordinary mortals have), I have had the most amazing doctors in the entire known and unknown universes. But my endocrinologist is probably the most amazing I've ever had. Compassionate, holistic, and knowledgeable. When he learned I was working two full-time jobs and still wouldn't be able to afford more testing and medical costs until my new insurance year starts in January, he referred me right there and then to HealthWell Foundation, which offers financial assistance for medication copays for certain illnesses and conditions. He was astonished that I was still working full-time, much less working two jobs seven days a week. "You're just not well enough to keep that up," he said, "and I am not going to let money keep you from getting a diagnosis and treatment." And 20 hours later, I had an email from HealthWell Foundation saying that I was preliminarily approved, pending verification of a couple documents.

I'm exhausted. And I'm broke. And I want to feel better. And I don't know whether I'm resilient enough to make it through this.

But there's a saying in Bosnian: "Novi dan, nova nafaka." It means something like "With every new day dawns a new chance." Giving my medical history to this incredible endocrinologist was one dawn. I just have to hang in there for another. And another. And as many anothers as it takes.

Novi dan. Nova nafaka. I believe in that chance.

After I asked Kim if I could post her story here, she responded in part with this: "Robin, thank you so much! I don't mind sharing my story at all. It's a perfect demonstration of the "four blind men and the elephant" story: every single one of my doctors over the years has been excellent, and I wouldn't want anyone else to have dealt with my leukemoid disorder, my knee meniscus tear, my therapy needs, my eye problems, my asthma, my heart and blood pressure issues, etc. .... but what resulted was that I had an ear specialist, a trunk specialist, a tail specialist, and a foot specialist all entirely missing the need for an elephant specialist."

I would have used the analogy of hearing hooves but not seeing the stripes. Elephant or zebra, the point is well made. Thank you, Kim.

Day 8 of the Cushing's Awareness Challenge: Cushing's Awareness Day!

survivethejourney@gmail.com (RobinS) — Sun, 08 Apr 2012 04:38:00 PDT

Dr. Harvey Williams Cushing (April 8, 1869 - October 7, 1939) was a neurosurgeon who pioneered many techniques of neurosurgery. Cushing's Disease gets its name from him because he discovered a malfunction of the pituitary gland which he termed "polyglandular syndrome." He published his findings in 1932 as "The Basophil Adenomas of the Pituitary Body and Their Clinical Manifestations: pituitary Basophilism".

Dr. Ashley B. Grossman has published an excellent "Case Report" about Dr. Cushing, "Harvey Cushing and Cushing's Syndrome". His modern take on the early diagnosis and treatment is very interesting.

Day 7 of the Cushing's Awareness Challenge: Wordle

survivethejourney@gmail.com (RobinS) — Sat, 07 Apr 2012 04:15:07 PDT

Day 6 of the Cushing's Awareness Challenge: 10 Things I Can't Live Without

survivethejourney@gmail.com (RobinS) — Fri, 06 Apr 2012 09:15:14 PDT

Cortef/Hydrocortisone: Without adrenal glands which were removed to control my Cushing's Disease, I must replace cortisol at a normal level. I take it early in the morning and again early in the afternoon. If I have an infection or have a major stresser, I must take extra. Sometimes that is a lot extra!
Fludrocortisone: Again, since I have no adrenal glands, I must replace aldosterone. This medication does that for me.
Solu-Cortef Act-o-Vial: If I have severe adrenal insufficiency or am having a crisis, I must have an emergency injection of this immediately. I carry one at all times, keep one beside my bed, have one at work, and there is one on my refrigerator.
Crisis letter from my endocrinologist: With each of my emergency injections is a letter from my endocrinologist explaining my condition, how to treat me, and where to reach him.
Medic-Alert bracelet: My bracelet tells my name, my Medic-alert number with phone number where they have all my details, says I have no adrenal glands, gives my medical allergies. It also says, "Give 100 mg Solu-Cortef, Check Electrolytes."
Sugar-free sports drink with salt: I drink a lot of this. I crave salt now, and I often make my own mixture that is similar to the "store-bought" variety.
Wristlet: I carry this everywhere. If I carry a purse, I put this in it. It contains a few pills of all my medicines, my small "wonder wallet" with identification, a syringe, a Solu-cortef Act-o-Vial, and my cell phone. I made this myself with a hint of zebra print on it. See yesterday's post for the meaning of that.
Cell phone: It is my lifeline when I need help, support, people, information, whatever. It contains emergency numbers, the folks who know what to tell caregivers about me, and much more.
"Darth": This is the nickname of my CPAP. I have central sleep apnea and was diagnosed with that long before I was diagnosed with Cushing's. Both problems started about the same time, but no one realized the Cushing's part for many years.
Support: Last, but definitely not least, support is so necessary with this disease. Those who have been through what I have been and know what I deal with are vital to functioning well. We have a fount of knowledge with our combined experience, and talking/sharing among ourselves is often better than a visit to our doctors. We tend to figure things out because of the knowledge base we have between us. (We still see our doctors, though.) My daughters (with their families) and my parents have been a tremendous support for me during all of my diagnoses and treatments. I couldn't have done it without them. My endocrinologist is a huge supporter and tremendous help. He's a gem among endos. Most of all, the Cushing's Help website and message/support boards have saved my life. This site led me to the right folks for diagnosis and treatment. It lead me to the wonderful people who help each other through thick and thin. And I must mention my grandson here. I can't live without him, either!

Day 5 of the Cushing's Awareness Challenge: Hoofbeats and Zebras

survivethejourney@gmail.com (RobinS) — Thu, 05 Apr 2012 03:47:17 PDT

Medical schools often teach doctors, "When you hear hoofbeats, think horses, not zebras", a form of Occam's Razor. This concept fails Cushing's patients more often than not. We are zebras. Most doctors see horses.

Cushing's patients are zebras in so many ways. My pretty little zebra is a reminder of those who suffer from this zebra disease. More than that, it is a symbol of our commonality, support for each other, and friendship.

Phil, who has Cushing's, and his wife, Rachel, made a very large, loving detour to meet me for dinner while on a trip from New Jersey. They brought me this zebra. Rachel has fought her own battle with another terrible disease. Phil and I have a bond from our common journey. So do so many of us who suffer from this disease and/or it's after-effects. This zebra symbolizes that bond and the love so many of us have come to share. So, with the bad comes the good. And I sure can appreciate the goodness.

Day 4 of the Cushing's Awareness Challenge: One for the money, two for the show, three to make ready....

survivethejourney@gmail.com (RobinS) — Wed, 04 Apr 2012 04:12:12 PDT

Just how many kinds of tumors are there associated with Cushing's? Wait, are we talking about pituitary tumors? Or adrenal tumors? How about ectopic tumors? Are you beginning to get the picture of why this illness is so hard to diagnose?

PITUITARY TUMORS/ADENOMAS:

So, let's talk about tumors. These are also sometimes called adenomas. Pituitary adenomas are classified several ways. They may be classified by pathology, by size, and by hormone production. I'm going to keep it simple here and list the basic types of tumors by the hormones they produce. Bear in mind that many pituitary adenomas produce more than one hormone. This production is not held in check by the body's normal feedback loops, thus they aren't controlled.

Corticotroph (ACTH-Producing) Adenomas :
The corticotroph adenoma secretes adrenocorticotropic hormone (ACTH), which results in Cushing Disease because it stimulates the adrenal glands to overproduce cortisol. These tumors are initially confined to the sella turcica, but they may enlarge and become invasive especially after bilateral adrenalectomy. This is called Nelson's Syndrome.
Somatotroph (GH-Producing) Adenomas:
Somatotroph adenomas produce growth hormone (GH), resulting in gigantism in younger patients and acromegaly in adults. These tumors may also extend beyond the sella.
Thyrotroph (TSH-Producing) Adenomas:
Thyrotroph adenomas secrete thyroid-stimulating hormone (TSH), also known as thyrotropin, which results in hyperthyroidism without TSH suppression. Many are large and invasive and typically have other types of adenoma cells included, such as ACTH and/or GH.
Lactotroph (PRL-Producing) Adenomas:
Lactotroph adenomas secrete prolactin (PRL) and are typically an intrasellar tumor. However, they can become large enough to enlarge the sella turcica.
Nonfunctioning (Endocrine-Inactive) Adenomas:
These tumors cause symptoms when they extend beyond the sella, which results in pressure on the surrounding structures such as optic nerves and carotid veins. They are not associated with clinical and biochemical evidence of hormone excess.
Carcinomas:Pituitary carcinomas, although extremely rare, are usually endocrinologically functional, and ACTH-producing and PRL-producing tumors are the most frequent.
Other Tumors:
Other tumors of the pituitary include craniopharyngiomas, meningiomas, and germ cell tumors. Even rarer are the granular cell tumors, pituicytomas, and gangliogliomas. Most rare include gangliocytomas, lymphomas, astrocytomas, and ependymomas.

ADRENAL TUMORS/ADENOMAS:

When a tumor in an adrenal gland overproduces hormones, the tumor is called a functioning tumor. A tumor in an adrenal gland that does not produce hormones is, understandably, called a nonfunctioning tumor. A tumor can start in an adrenal gland (called a primary adrenal tumor) or it can begin in another organ, such as the lungs, and then metastasize (spread) to the adrenal glands. I'm going to focus on primary adrenal gland tumors.

Adenoma:An adenoma is a benign nonfunctioning tumor of the adrenal cortex. Also called an adrenocortical adenoma, this tumor usually does not cause symptoms, and, if it is small, may not require any treatment. However, as it grows it can put pressure on parts of the gland causing it to under or overproduce hormones. The cause of adrenal adenomas is unknown, but the current accepted theory is that they arise because of mutations in certain genes. Adrenal adenomas are more common in some inherited diseases, including multiple endocrine neoplasia type I, Beckwith-Wiedemann syndrome and the Carney complex.

Chronic adrenal stimulation by ACTH leads to bilateral adrenocortical hyperplasia and, if long-standing, nodular transformation according to recent research. Thus, an ACTH producing tumor of the pituitary or ectopic tumor may stimulate the adrenals to form tumors or become hyperplastic (more about hyperplasia in a bit).
Adrenocortical carcinoma:Although exceedingly rare this is the most common type of malignant adrenal gland tumor, affecting the cortex, also called an adrenal cortical carcinoma. Adrenocortical carcinoma can be a functioning or nonfunctioning tumor. If the tumor is functioning, it may produce more than one hormone.
Pheochromocytoma:A pheochromocytoma is a rare tumor that develops in the core of an adrenal gland. It secretes excessive amounts of catecholamines, usually epinephrine and norepinephrine.
Neuroblastoma:
Neuroblastoma is a disease in which malignant cells form in nerve tissue of the adrenal gland. It is very rare.

If that isn't enough, there is another form of tumor that isn't a tumor. It's called hyperplasia. These tumor cells may invade the pituitary or the adrenals in nests throughout the gland. Rather than go in-depth right now, I'll post some links to articles so you can explore the topic:

Pituitary Hyperplasia: A Review
Adrenal Hyperplasia

This is just a basic, no-frills outline of various tumors/adenomas associated with Cushing's Disease. And now....four to go.....to work, that is....

Day 3 of the Cushing's Awareness Challenge: What is Cushing's Disease/Syndrome?

survivethejourney@gmail.com (RobinS) — Tue, 03 Apr 2012 04:17:01 PDT

I have been asked that umpteen times by folks who care about me. Other folks just look at me like I'm from an alien planet, and even others just nod and go on like they already know. I'm sure they go right home and google it. Ok, maybe some of them do.

When you get right down to it, I've become a walking library of sorts with facts and figures most medical students and doctors don't know. It's a matter of self-preservation, but you already know that if you are fighting any illness.

So, what is Cushing's? There are two terms used with Cushing's: Disease and Syndrome. They signify the source of the illness, although the presentation is pretty much the same with both. Cushing's Disease is hypercortisolism due to a pituitary source of stimulation. Cushing's Syndrome is hypercortisolism due to an ectopic or adrenal source. There really is a third type of Cushing's called iatrogenic Cushing's which results from the overuse of corticosteriod medications. And actually another type called pseudo-Cushing's.

I want to discuss Cushing's Disease/Syndrome (CD/CS). CD/CS is an endocrine disorder caused by chronic exposure of the body's tissues to excess levels of cortisol - a hormone naturally produced by the adrenal gland. Pituitary adenomas, usually benign, secrete increased amounts of ACTH (adrenocorticotropic hormone), a substance that controls the release of cortisol in that feedback loop I mentioned the other day. It typically causes an overproduction of cortisol. Tumors of the adrenal gland and ectopic ACTH producing tumors can cause similar problems with cortisol overproduction.

What are the symptoms? The most common symptoms are:

Striae
Buffalo hump
red-faced all the time
sweaty or hard to control body temp
High blood pressure (often hard to control even with medication)
High blood sugar and/or insulin resistance
Insomnia
Fatigue
Altered diurnal rhythm (See previous post)
Secondary hypothyroidism
Low hormones such as FH, LSH, testosterone, growth hormone
Low Vitamin D
Low ferritin
Unexplained muscle, bone, and joint pain
Easy bruising
Difficulty when drawing blood
Upper body obesity
Muscle weakness
Increased facial hair/body hair (hirsutism)
Loss of hair on head
Loss of menstrual cycle and/or ovulation
Loss of libido
galactorrhea

Not everyone has all the symptoms. And the weight gain can vary by individual. Some folks don't gain a lot. Others do.

Without prompt treatment for Cushing's syndrome, other complications may occur, such as:

Cardiovascular disease
Bone loss (osteoporosis), due to the damaging effects of excess cortisol
High blood pressure (hypertension)
Kidney stones
Diabetes
Unusual infections
Hypothyroidism

When the cause of Cushing's syndrome is a pituitary tumor (Cushing's disease), it can sometimes lead to other problems, such as interfering with the production of other hormones that the pituitary controls. It can also affect the optic nerves and carotid arteries if large. The majority of pituitary tumors that cause Cushing's disease are small (less than one cm in size).

Long-Term Remission Rates After Pituitary Surgery for Cushing's Disease: the Need for Long-Term Surveillance says:
Morbidity and mortality are higher in patients with Cushing's disease, with vascular disease a frequent cause of death.[2,32,33] Cardiovascular complications, including coronary heart disease, congestive heart disease and cerebrovascular events, contribute to the morbidity and mortality of patients with undiagnosed or untreated Cushing's disease.[34,35] Early diagnosis and successful treatment of Cushing's disease is therefore most important.

Now, diagnosis....that's a whole 'nuther ballgame. To mix metaphors, it is no walk in the (ball)park.

Day 2 of the Cushing's Awareness Challenge: Vituperation

survivethejourney@gmail.com (RobinS) — Mon, 02 Apr 2012 07:28:03 PDT

I want to re-post something I wrote June 30, 2008. It is as true today as it was then. And I still feel as strongly about it as I did then.

Vituperation [vahy-too-puh-rey-shuhn, -tyoo-, vi-] is.......

...what I want to spew when I think about how long it took me to be treated by doctors for the Cushing's Disease I had for at least 25 years (probably more) before anyone even checked to see if I had it. My problem is I don't know to whom I should spew! Medical schools? Doctors? God?

I had problems keeping weight off even in college. Well, even before that, but college was the worst. I did gain the freshman 15 but waited 'til my sophomore year to do it. I was always a late-bloomer. ;) In my junior year, I started running daily during the week (5 times a week) with a group from my dorm. Why was it so hard for me and it got easier and easier for them? It never got easier for me. I followed this trend with exercise for many, many years. Periods of exercise followed by periods of pain. What I didn't know then but know now is that I probably had cyclical Cushing's even then. In case you don't know, high cortisol (which causes Cushing's Disease) also causes muscle wasting.

I got pregnant with my first daughter at the age of 24. In the 7th month of pregnancy, I had terrible pain and she quit moving. I had a non-stress test and was told she was "ok". At 7.5 months, I went into labor. My daughter was premature, but healthy. She got to come home at the huge size of 4 lbs. 15 oz.

After the birth of my daughter, I had a hard time losing the weight. No, I wasn't as active outside the home as I had been, but I sure was a lot more active inside. And I thought I was supposed to lose weight when I nursed. That didn't happen. I remember a period of time when food was actually abhorrent to me, too. Eventually, I tried every decent diet under the sun including counting calories. I went to a nutritionist. I went to Weight Watchers. Topps. Tried the Atkins diet.

I went to my doctor. He laughed at me and told me that was what happened when one had a baby. "Eat less and exercise more." Yes, I know...but.... And there were no "buts" as far as he was concerned. And I didn't know any better, so I figured it MUST be my fault. Doctors were always right, right?

I always had very prominent clavicles. That is, until I woke up one morning to realize there were two "lumps" where those clavicles used to be. That worried me. Because I'd had several pre-cancerous places removed from my back and neck area by the time I was 25, I thought the worst. At my next visit to my doctor, I pointed them out, anxiously I might add. He laughed. He laughed at me. He laughed about me to the nurse. He laughed, again. "Those are nothing but fat. Not to worry!! Lose the weight." And he was gone.

I had my second child at the age of 27. She was one month early. The funny thing with that pregnancy was that I actually lost weight for the first time since the birth of my first daughter. When my daughter number two was born, I actually weighed less than I did when I got pregnant. And I had no clue why. I didn't have morning sickness at all. Frankly, I'd had morning sickness when I wasn't pregnant.

But.....you guessed it....I started gaining weight after she was born. And I didn't eat differently, I was even more active with a baby and a three-year-old. I also breast-fed her.

I eventually weaned my younger daughter at 14 months. But my milk didn't dry up. It didn't dry up ever. It was less at times and more at other times, but it never totally stopped. So, when I pointed that out to my new doctor, she said that happened after having babies sometimes and not to worry about it. When I pointed out all the problems I was having with what I now know was a mild case of Hidradenitis suppurativa she told me to use a certain brand of antibacterial soap. When I asked about my increasing edema and joint problems, she tested me for lupus. With my increasing bouts of insomnia she told me to take benadryl.

Year after year, doctor after doctor did not believe me when I said I really did try to eat right and could not lose weight. Year after year I gained more and more weight. In 2004, in desperation I found a doctor who would prescribe phentermine for me. I did lose weight, for about 4 months. I ate next to nothing. I lost about 40 pounds, but felt terrible. Then, I started putting it back on. Still eating less than 800 calories a day, I gained weight. Swimming at the Y every single day and eating less than 800 calories a day, I gained weight. Fatigue overwhelmed me but I was not able to sleep at night.

It had to be my fault. Right? The doctors said so, even with all this.

I had no idea my red, "moon" face meant anything. That having babies prematurely was a symptom. Obviously those doctors didn't either. I didn't know my striae were possibly due to something other than pregnancies. Or that those fat pads were called supraclavicular fat pads. No, not then I didn't. Nor, obviously, did my doctors. Or they thought I didn't need to know.

I started having problems with a "lump" in my throat, pain in my flanks, and pressure that was unbearable in my "middle". My arms and legs were in constant pain, although varying. Sometimes it was joint pain, other times bone pain. Fatigue was my master. Insomnia was my burden. No one should have to live like that.

I ended up in the ER with some of that awful pain/pressure one day. My good friend from work took me. We were afraid it was heart related. No, they found nothing but kidney stones with all the testing, and those weren't moving. In desperation, my dear friend asked the attending who could help me. He said he couldn't answer that. She said, "Who would you recommend for your wife?" He did answer that. Dr. M.

I went to see Dr. M immediately. I really don't remember a lot from that first visit other than she said the word "endocrine" after expressing milk from my breasts to culture. Endocrine. A word. The queen of internet research came home to her throne and googled "endocrine", "galactorrhea", "obesity", "insomnia", "fatigue". Guess what came up? Cushing's. Yep, right there I was. There was a picture of my body as it had become. OMG, there I was! And all my other symptoms which I had no idea were related to the "endocrine" word.

When I went back to see Dr. M, I told her what I'd found. I'd also found the cushings-help.com website. I had read what tests to run. And when. Dr. M was actually a trooper because I inundated her with emails of articles, research, etc. I begged for certain tests and she complied. She wrote letters of reference to a major hospital/testing center for me. And I got my first high test almost immediately. But we didn't realize that until months later. No, she didn't know that midnight serum cortisols were supposed to be close to zero, and I took her word on it. That 9.6 ug/dl that was "in range" for an afternoon cortisol wasn't done in the afternoon. The labs didn't know how to label, so just left it as normal.

But I get ahead of myself. Dr. M asked me to go ahead and talk to a bariatric surgeon because I had mentioned that possibility myself when I first saw her. I hadn't done my googling then. And because she asked, I went. To make a long story short, he told me I had to lose 30 pounds to show my commitment before he'd do the surgery. I asked if I had an endocrine problem if the surgery would work. He wouldn't say. I then said, "If I could lose 30 pounds, I wouldn't be here." He told me, and I'll never forget this, "You can't put on what you don't put in." When I tried to explain how I'd tried to lose weight, he walked out on me. Left me. DISMISSED ME.

That was probably the most demeaning, devastating visit with a doctor I have ever had. There is no way I can sit and type about all the visits with all the diatribes, but this one tops them all. There is no way I can get across the nature of this visit, my last hope, and how much I really did want to lose the weight. I was sincere, I was concerned, and I knew I had a problem. Why else would I put myself through that? And there is no way to show the snide, arrogant way this doctor talked to me.

I admit, I'm not a doctor. But, I do have an IQ that's up there, I can read, and I darn well know my body. I can hold an intelligent conversation, and I can look anyone in the eye when I do it. I expect that from my doctor. At least that. And I expect RESPECT.

I haven't told even half of my story. Not by a long-shot. The kidney stones, the ovarian cysts, and more. But I have told enough to maybe enlighten you why I am angry. I had Cushing's Disease for almost 30 years. If even one doctor had known the symptoms and had tested me for it back when it started, I may have never gotten so heavy. I might have had a more "normal" life. I might have had a lot less pain. I might have actually been able to walk and run like a normal person. I could have had that.

If just one doctor reads this, please hear one thing. You need to listen to your patients. I know you get some wacky ones. But you know, it's sad that your diagnoses and evaluations are colored by that. We are real people wanting to live real lives. Your profession took that away from me because no one would listen. No one would put it all together. No one took the time or cared. And I tried. I tried so hard.

Yes, I'm angry.

Be sure to check out all the other great blog posts: Click here

Kick-Off of the Cushing's Awareness Challenge

survivethejourney@gmail.com (RobinS) — Sat, 31 Mar 2012 21:00:04 PDT

I was telling someone the other day about this challenge. She doesn't have Cushing's so she was a bit perplexed about the reason for it. I told her to just read the comments on my blog, and that alone should give her some understanding. For as many comments that I get, I get many more emails.

"OMG, that is ME!"

"I am terrified and no one will help me."

"Who is your doctor? I can't find one here who can help me."

"I think I have symptoms of Cushing's. I had no clue until I googled my symptoms and found your blog. Can you help me?"

That happens to all of us who blog about Cushing's. Countless folks have been helped and found treatment for their symptoms through our network of bloggers. We are active in support boards, Facebook groups, Twitter, and more. We care.

Why do we care? Cushing's Disease/Syndrome kills. Period. The quality of life of someone who suffers is tremendously reduced. Mortality and morbidity rise. Many suffer from panhypopituitarism, too. And so much more.

So join me and all the others this week in spreading the news about Cushing's. You will save lives.

Coming soon all over the blogosphere!

survivethejourney@gmail.com (RobinS) — Mon, 26 Mar 2012 14:51:35 PDT

My BLAnniversary

survivethejourney@gmail.com (RobinS) — Sat, 18 Jun 2011 11:17:14 PDT

....or my "ReBirthday" as my friend, Nancy, says, was a few days ago on June 16th. It has been a year since I had both of my adrenal glands removed to control my Cushing's Disease.

How am I? Perhaps I'll give you a clue by saying I've been too busy to write this post. In fact, I'm having trouble finding time to blog at all! So, I am good. No, I am great!! I will always have to deal with some of the ravages of Cushing's Disease, but in comparison to what life was like prior to my BLA (bilateral adrenalectomy), I'm SUPERTASTIC!!

Some of the good things which have happened:

I now go up steps most of the time without even thinking about it. (Going down is still a problem due to a former broken ankle and a bad knee on the same side.)
I've lost almost 80 pounds without even trying.
Instead of parking in handicapped parking and using a scooter in stores, I can now park in Timbuktoo and walk all over a store. Wait...I can even tag along with my daughters and walk through multiple parking lots and multiple stores.
I have great hopes now of living to be a decent mother and grandmother. Shoot, maybe even awesome sometimes! (My first grandchild is due in July!)
I don't mind traveling/driving all by myself and do it often. I've made more trips to see my girls (and hubby/boyfriend) in the past few months than I have in the previous 8 years.
My mental state is beyond awesome.
I find myself smiling and singing all the time.
I'm umpteen sizes smaller. (The bad part is all the sagging skin and eyelids. Maybe that can be fixed in the future.) I still have quite a bit of weight to lose.
I don't dread things anymore. I used to dread getting up, walking, and so much more.
I can see my ears when I look into the mirror.
I have skinny ankles. Pretty shoes fit again.
I sleep all night, every night. I go to bed at a normal hour and get up at a normal hour.

I'm sure there are a zillion other things I can write, and I'll think of them later. There is so much improvement and I notice something every day!

Are there any "cons"? No, not in my book. I wouldn't trade my BLA for anything! Sure, I have to take medication every day to live, but I get to control how much "cortisol" my body gets instead of it controlling me. I have been fortunate and haven't had a crisis at all. I haven't had one visit to the emergency department anywhere. Sure, infections throw me into insufficiency pretty quickly, but the high side of that is I know I have an infection way before most folks would.

They say a picture is worth a thousand words. I'm going to let these pictures say the rest for me about the cyclic nature of my Cushing's Disease and how long I had it:

Don't I look like a grandma in that last one??? ;) I don't know what I was thinking with some of those hair styles.

Read more about episodic/cyclic Cushing's:
High Prevalence of Normal Tests Assessing Hypercortisolism in Subjects with Mild and Episodic Cushing ’ s Syndrome Suggests that the Paradigm for Diagnosis and Exclusion of Cushing ’ s Syndrome Requires Multiple Testing

Postlude:

Thank you, Dr. M. for finally realizing in 2005 that what I had was endocrine and for sticking with me. Thank you, Dr. Friedman, for believing me and listening to me, for making me a partner in my health, and for testing me. You saved my life. Thank you, Dr. Chiang, for trusting Dr. Friedman and for being the most caring doctor/surgeon I've ever met. And most of all, thank you Mary O'Connor, for all you do to spread awareness of Cushing's Disease/Syndrome. You helped me find my life again. I love you. I hope all of you see this so you can see what a wonderous work you do.

This would not be complete without thanking my family. My daughters have been my lifeline. They took two weeks out of their lives and lost vacation time just to take me to surgery and stay with me. Prior to that, they were here with me when I needed them, helped me do so many things, went with me on trips to see Dr. F, and so much more. I love you dearly, my daughters, and love the women you are.

My parents took care of me after surgery, finding any treat they could, cooking anything they could to help me find something I could eat. They took me for labwork, helped me find DHEA, went to the store at odd hours to get me some gatorade, and so much more. I love you, Mother and Dad. And I thank you.

Thanks to all my Cushie folks who support each other. I'm sorry you have Cushing's, too, but I'm proud to have met you, shared the triumphs and the pain with you, laughed and cried with you. Hugs.

In memory of Sarah

survivethejourney@gmail.com (RobinS) — Tue, 14 Jun 2011 17:46:51 PDT

Sarah recently had surgery to remove a tumor from her pituitary gland. This was to treat Cushing's Disease. She died today. I hate this disease.

Sarah was only 28.

You will be remembered, Sarah.