The Retrospective: Part IV (a guest post)

What Could Have Been Better

[This is the fourth post of a multi-post series. Part I, Part II, and Part III were posted earlier this week. ~Robin]

by Vivant Malgré*

This is unfortunately going to sound like a rant. Because it is. Because we learn from the criticism and it is more often than not unpleasant. That is part of how we learn to do better.

The local endocrinologists:

Local endocrinologists are a mixed bag – some are great, some not so much. I feel for them. I have two requests. First, if I schedule an appointment and say that I have Cushing’s Disease, I expect the endocrinologist to have familiarized him or herself with what the tests are, and their limitations, at the level of say, the endocrine society's clinical practice guidelines, and if not willing to do so, to let me know in advance that this is not within his or her expertise. If you are willing to take on this kind of project, thank you!

If you are going to consult with the big “university guru” about a patient, ask the permission of the patient first and have some idea as the consultant’s actual success rate in accurately diagnosing Cushing’s, or you may be made a fool of by a pathology report. For example, a friend of mine was diagnosed with Cushing’s Disease by an endocrinologist with a specialized Cushing’s practice. She scheduled surgery locally. The hospital endocrinologist (who was not even the patient’s treating physician) decided to question the diagnosis, wanted to prevent the surgery and called in the “big guns” from the NIH. The NIH reportedly recommended that the surgery be scrapped. It wasn’t. Her pathology showed Cushing’s Disease. Egg. On. Face.

I had problems with the NIH – they couldn’t even understand what my test results were and I spent hours, literally hours, trying to explain to the fellow assigned to me what the tests for Cushing’s Disease are. Months into the exercise, the fellow admitted he did not know what the reference ranges were for the tests, much less what was diagnostic. When I complained, the more senior doctor still couldn’t figure it out—an author of the guidelines, no less. I’m not the only one. See this blog http://www.shouldhaveseenit.com/ and this blog http://missdiagnosis-rene.blogspot.com/ for others with pathology proven Cushing’s who were turned away at the NIH. Just because someone has a big name doesn’t mean that they can diagnose their way out of a paper bag. By my count, NIH is 0 for 5. Not a great average. But also not much different than the other major “big name” teaching hospitals with a “pituitary” practice. Do some due diligence before asking someone’s opinion or referring a patient.

The Research/University Endocrinologists:

For this group, I frankly have nothing kind to say.

One, it is not fair to either me or their trainees to assign me to their untrained fellows. For some reason, the research university endocrinologists think it’s a great idea to delegate the patient history and physical exam of a Cushing’s patient to some green fellow. The proper diagnosis of Cushing’s requires a careful history, a careful physical exam, and careful analysis of lab results by someone who knows more than a thirty second scan of the wiki on Cushing’s. With one notable exception, every single fellow I have seen has been completely incompetent – and it is not their fault. It takes a substantial amount of work to be familiar with the body of knowledge necessary to understand Cushing’s – I know because I have done the work myself.


Second, the Cushing’s Disease diagnosis process resembles 1960’s, pay-$1000-for-a-toilet-seat weapon development.

I consult on government acquisitions. In government acquisition, developers try to balance four things: schedule, money and risk (which includes quality) to get the best solution. You want no risk/perfect quality, its going to either take you a long time or cost you a lot of money. Or both. And if you take long enough on schedule so that you can have a theoretically “perfect” solution, you may end up with obsolete technology or dead soldiers who really could have used a less prefect version of what you were working on. You are looking for a balance. As someone who worked on development programs that ran into the billions, you also learn fast that certainty and data cost money. Tests cost money. The number of tests needed to prove 98% certainty can costs exponentially less, and can have substantially less “cycle time” than testing and manufacturing to a 99.999999 percent level of certainty.

In other words, you can spend a ton of money for something that is “perfect” and you perfectly know that it is perfect – and take so long doing so that its purpose is long gone and that it is unaffordable to build. Or spend something you can afford and be 98% sure. We always were very mindful of the level of “perfect” being required – too low and you have things exploding where they shouldn’t; too high and you will waste money studying something you can’t afford to use.

The research endocrinologists want years of testing, with perfect test results, before putting a diagnostic toe out. Early in the process, I looked at my test results, the good and the bad, the studies that had validated the tests in question and made some rough and ready calculations as to the odds that I had Cushing’s or not. It came out to something like a half billion to one in favor of diagnoses. I played with the assumptions. The odds were still eye-popping. Yet the big-wig endo at UVA saw fit to cancel my surgery, over the objection of the surgeon, in favor of “gathering more data.” To me, it’s like refusing to diagnose breast cancer until you are “sure” it is cancer by waiting until it metastasizes. Because after all, benign tumors don’t metastasize. Who cares if the certainty of the diagnosis comes at the cost of killing the patient?

Why did this doctor want more data? The cynical part of me thinks she just wanted the data so that I would be an appropriately validated patient for her latest study. Maybe she was just not very competent. Maybe she had a bad day (I certainly did). Some might say that is it fear of liability. But as a licensed attorney, my observation is that it would be a heck of a lot easier to sue successfully a doctor who does not diagnose Cushing’s when the patient has Cushing’s and ends up with a positive pathology report than to succeed in suing a doctor who has treated a person who ends up without a positive pathology report. One can always argue that the pathological tissue got caught in the sucker.

But I continue to see University endos demanding what is frankly, an insane amount of confirming tests over an unjustifiably long period of time. The testing done by any other doctor is never accepted and is instead nitpicked into oblivion. The cost of my testing and retesting could have paid for vaccinations for hundreds of children. It could have provided a year’s worth of medical supplies for an inner city clinic. And yet I had doctors who thought I should spend years more of these costs to “prove” what was obvious (and proven by pathology). I had Cushing’s.

I think that part of the cause is an irrational view of what is medically acceptable risk. Laparoscopic bilateral adrenalectomy is a well-studied treatment for Cushing’s Disease with a mortality rate of 0.2% -- less than gallbladder surgery. The mortality rate for transphenoidal pituitary surgery is less than 1%. By comparison, the 90 day mortality rate for a revision hip replacement is reported as over 2.5% and the one year reported mortality for gastric bypass at the Mayo Clinic is 0.5%. No reasonable doctor would, under any normal circumstance, require a patient undergo years of testing at six month intervals before a referral for hip replacement revision or gastric bypass, both of which are routine surgeries in this country and both of which typically treat maladies less serious than Cushing’s. [Robin’s note: The mortality for not treating Cushing’s Disease is huge. The mortality risk from surgery is directly proportional to the time it takes to diagnose and treat a Cushing’s patient. See recommended reading at the end of the article. ]

After my first surgery, it was clear that it was not successful – by the published criteria. I went to the NIH because they had an experienced adrenal surgeon and my preference was an adrenalectomy. As noted, for more than half a year, I battled with a completely hapless fellow who could not manage to keep my test results straight and frankly admitted that he neither knew of the tests nor of the correct reference ranges. I elevated my concerns. What I was told was:

“We think that CS is only clinically important when there are significant increases in cortisol over enough time to cause clinical problems.”

At that point, I had had clinically elevated cortisol for over four years. My blood pressure was jumping to levels that my neurologist said were “dangerous.” My fatigue prevented me from working. Labs showed that I was losing kidney function. I had had two rounds of septic infections. I had clear signs of bone loss and had a fracture from a very minor trauma. I had a hump and brightly red checks. I was 100 lbs overweight, even though I had previously been a regular swimmer. I had lost substantial amounts of muscle and could not walk normally. It’s still not clear if the “scientist” in question had repudiated her previously published work as to the criteria for evaluating Cushing’s or did not think I had “clinical problems.” I could not get a straight answer. My labs were diagnostic, per her own published criteria. If these aren’t enough symptoms, I hate to think of how sick one would need to be for this doctor to think it “clinically” relevant.

I was further told:

“I would not recommend any treatment, particularly ketoconazole or adrenalectomy, both of which can cause significant problems, including death. The benefit doesn’t exceed the risk…” (emphasis added)

As I said at the beginning of this series, I am a little over a month past my bilateral adrenalectomy. I am beginning to lose weight. Six months of declining kidney function tests appear to be reversing. The fatigue, while there as I weaning from cortisol, is improving. I am feeling more optimistic about life. The grey seems to be lifting. I have not had a single episode of malignant hypertension since my BLA. I can breathe. I think that the benefit well exceeded the risk.

The sad thing is that other doctors still consult with this “expert,” undoubtedly to the detriment of many.

I don’t know why Cushing’s is so stigmatized by the medical profession. Maybe it’s prejudice against fat people. Maybe it’s that doctors just don’t think that the lives of women count for much. Or maybe they wring all of the compassion out of endocrinologists before they are board certified. The reality is that there are more doctors who perform late term abortions than will promptly diagnose and treat Cushing’s Disease. I would not have had to travel as far to have had a 26 week pregnancy terminated than I had to go to have a life-threatening tumor removed.

So much for my right to choose.

[Robin's note:  The female-to-male incidence ratio is approximately 5:1 for Cushing's in some studies. Other studies say 15:1.]

*pseudonym

To read more:
Mortality in Patients Treated for Cushing’s Disease Is Increased, Compared with Patients Treated for Nonfunctioning Pituitary Macroadenoma
"Conclusions: Mortality in patients previously treated for Cushing’s disease is increased, compared with patients treated for NFMAs. This implies that previous, transient overexposure to cortisol is associated with increased mortality."

Mortality in Patients with Pituitary Disease
Control of cortisol secretion and GH hypersecretion (and cardiovascular risk factor reduction) is key in the reduction of mortality in patients with Cushing’s disease and acromegaly, retrospectively...Although standardized mortality ratios in pituitary disease are falling due to improved treatment, mortality for many conditions are still elevated above that of the general population, and therefore further measures are needed.

Blood coagulation and fibrinolysis in patients with Cushing's syndrome: increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels.In conclusion, we found some important differences in the hemostatic parameters between the patients with CS and healthy controls. Increased platelet count, fibrinogen, PAI-1, and decreased TFPI levels in these patients represent a potential hypercoagulable and hypofibrinolytic state, which might augment the risk for atherosclerotic and atherothrombotic complications. This condition may contribute to the excess of mortality due to cardiovascular disease seen in patients with CS.
 
Cortisol excess linked with increased mortality rate 
According to the researchers, these findings imply that overexposure to cortisol is associated with increased mortality, and the mortality seems to be correlated with the duration of overexposure. “The effects of transient cortisol overproduction may not be reversible with respect to certain biological properties that influence mortality,” the researchers wrote.

Bilateral adrenalectomy: low mortality and morbidity in Cushing's disease 
Bilateral adrenalectomy, in experienced hands, is a relatively safe and useful management option in patients with hypercortisolism. Growth of a pituitary adenoma post-operatively is now the most worrying complication.


Cyclical Cushing's syndrome: an update 
Cyclical Cushing's ... 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.

Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis of mild Cushing’s syndrome
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.

Bariatric surgery: Not the answer for obesity and "hidden" Cushing's Syndrome
This article outlines possible contra-indications of bariatric surgery for obese patients, especially those with possible Cushing's. Those, along with the delay in diagnosis may cause "irreversible sequelae in patients with undiagnosed Cushing syndrome"

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