Friday, June 6, 2008

Rigors of Testing







Testing for Cushing's is the most drawn out and convuluted experience I've every seen in the medical world.


STEP ONE: GET YOUR CORTISOL LEVELS TESTED

First, a patient must convince a doctor to test for Cushing's. As I stated before, doctors are reluctant to order tests. They often are completely dismissive and resort to pithy lectures about diet, exercise, nutrition, and portion control. Some, in fact many, patients are ridiculed by the doctor's completely inappropriate, unprofessional comments. On the message boards, we read heart-breaking yet infuriating exchanges like this nearly daily:

Doc: Just step away from the chocolate cake.

Patient: I don't eat chocolate cake.

Doc: Well, obviously, you do.


Second, women are five times more likely to be affected by this disease than men. We Cushing's patients feel that male doctors are dismissive of us female patients because most women are conscious of their weight. We know we sometimes eat stuff we aren't supposed to. However, we know that the rapid weight gain we experience can not be explained by one meal splurge, but the doctors won't listen. Many doctors push a patient off and tell them to diet and exercise and come back again in six months. I soon realized that the doctors are looking for a solution they can write down in their little charts to make it seem like they are helping us. They are not.

I do understand that the doctors are treating the most obvious symptoms. With weight, our society knows of no other ways of gaining weight other than eating more and losing less. So, I know that doctors are under that mindset, too.

However, as medical professionals, I was disappointed that doctors do not listen to the patients, do not spend any time analyzing the long list of symptoms that we Cushies bring to our appointments, do not proceed with medical curiosity to find what ails the patient. They are too quick to say, "High blood sugar... you're a diabetic. Aches and pains... must be fibromyalgia. Missed periods... you have PCOS."

So,


I have been extremely disappointed with the medical community and their approach to this rare disease.


STEP TWO: MAKE SURE THEY TEST YOUGET YOUR CORTISOL LEVELS TESTED
STEP FOUR: GET HIGH TEST RESULTS
Q: I just got some very high test results at Camp Cushie. I had high ACTHs at 4 am, high cortisol serums at midnight and during the day. What happens from here? Even though I'm still waiting for a few more test results , I am not sure how many might be needed.
A. That is a very good question. The answer eludes me. I have been on the boards for over a year, and I have yet to figure out how many 'greens' mean go.
In all likelihood, they will ask you to continue to test, no matter how high your numbers are.
It is not just about how many high tests you get, but how high each of those tests are.
They will also want you to test again to make sure your body can replicate these high numbers. Lab results aren't definitive with this disease. They are the start of suspicion about Cushing's, but your testing will likely continue in order to prove it.
You have a better shot at a quicker path if all tests point to Cushing's in a BIG way: UFCS, salivas, midnight cortisol serums, ACTHS, even daytime cortisol serums.
It will also depend on whether there is a visible tumor. If not, they may want you to test, no matter how high your results are, while they try to wait for a tumor to show.
Only your doctors can make that determination when the time is right for you.

SUMMARY OF MY CUSHING'S TESTING RESULTS

1) random ACTH plasma
Suggestive of Cushings: 48+; normal range: 5-27
My results: 14, 14, 15, 16, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 28, 29, 41, 78, 105

2) midnight salivary cortisol
Suggestive of Cushings: 5+; normal range: less than 0.17
My results: 0.07, 0.07, 1.1, 1.3, 1.6, 1.7, 1.7, 1.7, 2.2, 2.5, 2.8, 3.7, 4.1, 5.4

3) urine free cortisol (UFCs)
Suggestive of Cushings: 50 +; normal range: 4-50
My results: 7.5, 12.4, 14.4, 17.7, 22, 23.6, 23.6, 24.3, 26.6, 30.6, 37

4) cortisol serum
Suggestive of Cushings: 28+; normal range: 7-25

My results:
12 am 4.1, 5.9, 6.7, 7.0, 7.5 [midnight results: Suggestive of Cushings: 5+; normal range: less than 1)]
4 am 10, 12.5
8 am 7.6, 12, 14.3, 14.5
10 am* 4.8, 10.8, 11.3
12 pm* 3.3
4 pm* 3.6, 4.4, 5.1, 6.3, 7.1, 23
8 pm 3.5

* Low values suggest lack of diurnal rhythm.

NOTE: Lab error minimized because midnight test results processed in different labs in different states.


5) dexamethasone suppression test - I suppressed, so I failed the test.










PITUITARY TUMORS PRESENT







  • a 5 mm lesion on right mid pituitary, 1.5 machine



  • a 3 mm lesion on left pituitary, 3T machine

    We might take that to suggest that there is actually a tumor of the type occasionally seen, in which a "wrap-around" effect is seen as the tumor embraces the gland from both sides with a connecting portion in the middle--thus giving the appearance of 2 tumors when really only one is there. This kind of thing can only be determined at the time of a pituitary surgery. ~ email from Dr. McCutcheon






























Tim in Chicago (my Wonder Twin and fellow sassologist) says:




Melissa, some of your post are pretty tough to get through because they are so technical. I make my way through them b/c I care about you, but some days, it’s pretty challenging.




MRT says:




I pity the fool who can't get through the medical jargon. No really, I know. Imagine how I feel?! My life depends on knowing what this stuff means. Just picture another 10+ articles on this one procedure COUPLED WITH the mounds of medical articles on every other aspect of this disease. It is rough, but it is necessary. Believe it or not, I try really hard to simplify these technical posts. Sometimes I succeed, sometimes I don’t.




The Cushing’s mind is known to have difficulty with concentration, focus, memory, and word recall. One of my greatest heartbreaks of this disease is forgetting words when I sing songs. I have always prided myself on my singing bee abilities. Not anymore. But I try.




I try to give you the technical side as much as the emotional side in these posts, so that you can understand what all this means for me: the testing protocol, the diagnostic benchmarks, what kind of results we are hoping to see, and what I am going through. Just wait until I have to explain the surgery part to you!




I am including the description of the IPSS article that I found to be the MOST helpful and MOST simplified. Then I tried to summarize that. Now reading it, I think THEY did a better job than me. Besides, I know I have extremely smart friends and family. I bet you can make your way through it. ~MRT







"The role of inferior petrosal sinus sampling in the diagnosticlocalization of Cushing’s disease." Neurosurg Focus 23 (3):E2, 2007.

SHIVANAND P. LAD, M.D., PH.D., CHIRAG G. PATIL, M.D., EDWARD R. LAWS JR., M.D., AND LAURENCE KATZNELSON, M.D. Department of Neurosurgery, Stanford University School of Medicine, Stanford, California




Inferior Petrosal Sinus Sampling
The most sensitive method for differentiating between pituitary and ectopic ACTH secretion, IPSS is considered the gold standard for confirming the origin of ACTH secretion in patients with Cushing's Disease (CD). Originally described by Corrigan and colleagues in 1977, unilateral catheterization for selective venous sampling was introduced to differentiate ectopic ACTH secretion from pituitary Cushing’s syndrome. Inferior petrosal sinus sampling is recommended in cases of Cushing’s syndrome in which clinical, biochemical, or imaging studies have not clearly identified either a pituitary or an ectopic origin of the ACTH production. The high diagnostic sensitivity, specificity, and accuracy of IPSS have made it a standard tool in the investigation of ACTH-dependent Cushing’s syndrome. Technical Considerations Bilateral IPSS was initially introduced at the National Institutes of Health by Oldfield and Doppman in the early 1980s. In the early 1990s, Oldfield et al. described the use of bilateral petrosal sinus sampling with and without administration of CRH for the differential diagnosis of Cushing’s syndrome. (sorry, had to break it here)




In this technique, sheaths are inserted bilaterally via the femoral veins and advanced into the internal jugular veins and then into the inferior petrosal sinuses, where blood samples are obtained from each sinus. The plasma ACTH levels in these samples are compared with the levels in samples from a peripheral vein. Samples are taken simultaneously from both central catheters and the peripheral vein. Serial samples for central and peripheral plasma ACTH concentrations are drawn before and after CRH administration (1 mg/kg body weight). In Cushing’s Disease, a central-to-peripheral (central/peripheral) ACTH gradient results from high ACTH levels in venous drainage from the pituitary, and contrasts with the absence of a gradient in ectopic ACTH secretion. Without CRH administration, a basal ratio of central/peripheral ACTH values of 2.0 or greater is strongly indicative of Cushing’s Disease (mine was 14 to 1). Because ACTH secretion is episodic and sampling can miss the burst of ACTH secretion, however, CRH is used as a stimulating agent to increase the sensitivity of the test. Plasma ACTH samples are obtained from both inferior petrosal sinuses and peripherally at intervals following CRH administration. Without CRH administration, a basal ratio of central/peripheral ACTH values of 2.0 or greater is strongly indicative of Cushing’s Disease (mine was 14 to 1). A central/peripheral ACTH ratio of 3.0 or greater is strongly indicative of Cushing’s disease. (mine was 93 to 1) Most patients with Ectopic ACTH Syndrome have a central/peripheral ACTH ratio of less than 2.0 before and after CRH administration. Newell-Price et al. in a systematic analysis that included 21 studies and 569 patients, found that IPSS with CRH stimulation achieved 96% sensitivity and 100% specificity in discriminating Cushing’s disease from Ectopic ACTH Syndrome. With the increased adoption of IPSS worldwide and combining various reports of 726 patients who had Cushing’s Disease and 112 who had Ectopic ACTH Syndrome, there were 41 false negatives and seven false positives, providing a diagnostic sensitivity and specificity for IPSS of 94%. In a recent study by Swearingen et al. lower sensitivity and specificity for predicting a pituitary or an ectopic source were found. In that study, more than 50% of patients in whom the results of IPSS suggested an ectopic source were found to have an ectopic pituitary tumor. Therefore, lack of central localization by IPSS should lead to a search for an ectopic source, although the presence of a pituitary source should be considered further in such patients. In addition, in approximately 15% of patients in whom the results of IPSS are positive for central localization, histological confirmation of an ACTH-secreting pituitary tumor is absent. These unusual and contradictory findings need to be noted in the interpretation of this test. The validity of IPSS relies on successful cannulation of the inferior petrosal sinuses. Digital subtraction angiography must be performed to ensure correct catheter placement and to evaluate venous anatomy properly. A hypoplastic or anomalous inferior petrosal sinus was believed to underlie the false-negative IPSS results that were obtained in 0.8% of the patients in a large case series (501 patients). These patients were subsequently found to have surgically proven Cushing’s Disease. Other causes of ambiguous results include IPSS performed during a period of normal cortisol levels in patients with intermittent ectopic ACTH secretion and false-positive test results caused by CRH-secreting tumors. Efforts to improve the diagnostic accuracy include additional sampling during IPSS for other anterior pituitary hormones, including prolactin for normalization of ACTH ratios. When performed by a radiologist experienced in the technique, IPSS is successful in the great majority of procedures, and serious complications like stroke can be minimized.
















Pituitary Lateralization
Inferior petrosal sinus sampling has limited utility in localization of ACTH-secreting pituitary adenomas within the gland. A literature review, in which the authors analyzed data from 313 cases in which lateralization studies had been performed and used pituitary surgery as the criterion, revealed a range of diagnostic accuracy for localization of IPSS between 50 and 100%. A gradient of 1.4 or greater across both sides of the pituitary correctly predicted tumor location in 78% of cases. Booth et al. compared the efficacy of IPSS and the results of imaging studies for localization of pituitary tumors and demonstrated 70% likelihood of accurate localization using IPSS compared with 49% using imaging.








Lucy in Lousiana writes:




Q: Why did the doctor start in your groin and then go all the way up to your sinuses? Wouldn’t it be easier if they started in your neck and went up from there?




A: Alternative Sampling Methods: Jugular Venous Sampling
It has been suggested that stopping cannulation [inserting a cannula into a bodily cavity, duct, or vessel, as for the drainage of fluid or the administration of medication] at the level of the jugular vein and using jugular venous sampling may be a simpler alternative for localizing ACTH-secreting tumors, given the slightly higher technical demand of cannulating the petrosal sinus (that is, IPSS) recently compared the results of jugular vein sampling and IPSS in 74 patients who had surgically confirmed Cushing’s Disease and 11 patients with ectopic ACTH secretion. The specificity was 100% for both techniques, but the sensitivity of IPSS was 94% compared with 83% for jugular vein sampling. As might be expected, ACTH values and central/peripheral ratios from jugular samples are usually lower than IPSS ratios due to dilution within the jugular vein and are therefore not as reliable.










These results confirmed that the pituitary is the source of ACTH excess in my body. This means that my two pituitary tumors are releasing too much ACTH which triggers the overproduction of cortisol, which causes Cushing's disease. These test results are undeniable. Diagnostic ratios from the petrosal sinuses to the peripheral are 3 to 1. Mine were 93 to 1 and 78 to 1.




MY RESULTS FROM INFERIOR PETROSAL SINUS SAMPLING, NOVEMBER 2007

TIME-------PERIPHERAL-----RIGHT INFERIOR -----LEFT INFERIOR
--------------------------------------PETROSAL VEIN------PETROSAL VEIN

baseline---------9-----------------------124-----------------------11




3 min-----------26---------------------2020----------------------198




5 min-----------37---------------------3440----------------------199




10 min--------- 59---------------------1500-----------------------75




15 min----------62---------------------2040-----------------------99




baseline differential: peripheral to right ratio: 1 : 14 (1:2 is diagnostic)
3 min differential: peripheral to right ratio: 1 : 78 (1:3 is diagnostic)
5 min differential: peripheral to right ratio: 1 : 93 (1:3 is diagnostic)
10 min differential: peripheral to right ratio: 1 : 25 (1:3 is diagnostic)
15 min differential: peripheral to right ratio: 1 : 33 (1:3 is diagnostic

baseline differential: peripheral to left ratio: 1 : 1 (1:2 is diagnostic)
3 min differential: peripheral to right ratio: 1 : 8 (1:3 is diagnostic)
5 min differential: peripheral to right ratio: 1 : 5 (1:3 is diagnostic)
10 min differential: peripheral to right ratio: 1 : 1 (1:3 is diagnostic)
15 min differential: peripheral to right ratio: 1 : 2 (1:3 is diagnostic)

Pituitary Gland & Surgery FAQs

Where is the pituitary gland located?
The pituitary is a small, pea-sized gland located at the base of the brain that functions as "the Master Gland."




Why is the pituitary gland so important?
From its lofty position above the rest of the body it sends signals to the thyroid gland, adrenal glands, ovaries and testes, directing them to produce thyroid hormone, cortisol, estrogen, testosterone, and many more. These hormones have dramatic effects on metabolism, blood pressure, sexuality, reproduction, and other vital body functions. In addition, the pituitary gland produces growth hormone for normal development of height and prolactin for milk production.

The pituitary is the control center for the endocrine system, which controls all of the hormones produced in the body.






Is pituitary surgery the only cure for Cushing's?
YES. Researchers are currently doing clinical trials with medications, but the use of that medicine to cure Cushing's could be years and years away.


When and where will you have surgery?
I plan to have pituitary surgery in the Spring of 2009. March or April.

Lucky for me, a very skilled neurosurgeon works right here in Houston at MD Anderson Cancer Center. My husband and I consulted with him in November 2007, and he has agreed to take me on as a patient and do my surgery. People come from all over the US and Canada to have him do surgery.

Did you have a second opinion?
Yes, of course. I spoke to a San Antonio neurosurgeon as well. He is willing to do surgery, too. Due to the proximity of my friends and family, as well as the skill of the Houston surgeon, I have decided to have surgery here at home.


What's your tumor like?
This is from an email from my neurosurgeon:

"It is true that the two MRI brain scans have somewhat different readings, and they really do look different. The earlier 1.5 scan from Seattle does suggest that, as you mentioned, a 5 mm tumor is present on the right. It also suggests a separate focus on the left, but this is more subtle and you can argue over whether it is really there or not, as this spot abuts the wall of the cavernous sinus and thus is difficult to pinpoint with certainty. However, that may explain why the later scan, at higher magnet strength of 3T, showed a left lesion or tumor better. It also suggests that there is something on the right, but more subtly. Thus, both scans really do suggest both lesions but one is better at showing the left, and the other is better at showing the right. Why this is so, I cannot give a good explanation for. We might take that to suggest that there is actually a tumor of the type occasionally seen, in which a "wrap-around" effect is seen as the tumor embraces the gland from both sides with a connecting portion in the middle--thus giving the appearance of 2 tumors when really only one is there. This kind of thing can only be determined at the time of pituitary surgery. The right way to do such an operation is to go first to the point on the scan that looks suspicious for tumor, but then look at all the rest of the gland too, so as not to miss something subtle hiding somewhere else in its substance. Two separate tumors are possible, but that is pretty rare and I think most such cases actually are one tumor with a bilobed shape that looks like two on scans, but really isn't."

So, how's that for specific?

What does the pituitary look like with a tumor in it?





What is involved in pituitary surgery ?




Neurosurgeons access the pituitary gland through the nose or under the lip.
The team at Thomas Jefferson University Hospital in Philadelphia, PA use endoscopic endonasal transsphenoidal surgery. If you would like to watch the video, click here, then select Web Broadcast on the right tool bar. I did watch this video after I got my first batch of high cortisol results. I cried for the first 20 minutes out of fear. Soon, I became so intrigued by the medical advances that make such a surgery possible that I forgot about myself and focused instead on the intricacies of the surgery and skill of the surgeons.

From their Pituitary team at Thomas Jefferson University Hospital:

At Jefferson’s Center for Minimally Invasive Cranial Base Surgery and Endoscopic Neurosurgery, surgeons are now applying an advanced, “pure” endoscopic endonasal transsphenoidal surgery, which is a new approach for the removal of pituitary tumors.

This leading-edge, minimally invasive procedure uses the nose and nasal sinuses to gain access to the cranial base and brain, providing surgeons improved exposure to pituitary, sino-nasal, skull base and other intracranial tumors. Benefits of this innovative procedure include enhanced exposure leading to improved resection rates, lower incidence of neurological impairment and reduced hospital stay. In addition, the shortened recovery time often allows certain patients requiring adjuvant therapy, such as radiation and chemotherapy, to begin these treatments sooner. As a result, we are able to achieve a better patient outcome and satisfaction.

Minimally Invasive Pituitary Surgery
Using an endoscope with a camera attached, surgeons enter a patient’s nose and sinuses, allowing them to approach the tumor without any external incisions. Guided by the endoscope and enhanced computer navigation, surgeons open small holes in the base of the skull and membrane covering the brain to remove the tumor. Better visualization and access to these lesions have enabled improved resection of the tumor without causing damage to the brain and lower risk of complications and follow up surgery. This results in surgery with a shorter hospital stay, a faster recovery and improved outcomes.



The video/procedure lasts 1 hour.
http://www.or-live.com/jeffersonhospital/1346/event/webcast.cfm?

How long does it take to recovery from surgery?

Recovery from pituitary surgery is a long battle.

  • It varies from patient to patient.

  • Recovery is directly related to the length of time you've had Cushing's because of the damage that high cortisol does to the body's systems.

  • This process can take 12 to 18 months before the patient returns to ‘normal.’ This is only if further pituitary surgeries are not needed.

Once the tumor is removed from the pituitary, the body switches from producing too much cortisol to not producing enough. Cortisol supplements are taken to replace the off-kilter cortisol production. This must be taken not only on a daily and timed basis but also in certain situations: sickness and stress (good or bad). Cortisol supplements are taken after surgery to replicate the patient’s normal hormonal production. Each week, the patient reduces the amount of cortisol replacements. If the patient experiences terrible symptoms associated with adrenal insufficiency, then the patient must temporarily increase the amount of cortisol replacement hormones he/she takes and often go to the emergency room. This process varies from person to person, and it makes recovery very difficult for the patient.


Once you have surgery, are you cured?
Not necessarily, and isn’t that so unfortunate.

The pituitary is so small (less than 2 cms), and the tumors are so small, that the neurosurgeon does his best to remove all of the cells that are producing too much ACTH. In 60% of the cases, the surgeon succeeds. In 40% of the cases, he doesn’t. For some patients, several surgeries are needed to try to remove all the cells. A patient may choose to have a bilateral adrenalectomy, the removal of both adrenal glands. This surgery is performed after two pituitary surgeries fail to remove all of the tumor(s) present. The pituitary tumors secrete ACTH which stimulates the adrenals to produce cortisol. Since a surgeon does not want to remove all of the pituitary gland--as it controls many other vital hormones that the body needs--many opt for the final road to end Cushing's, which is to remove both adrenal glands aka bilateral adrenalectomy. These glands are responsible for the production of cortisol, and removing these glands is the only permanent way to end cortisol production once and for all. However, due to the important life-saving functions of cortisol, the patient must take cortisol medicine in pill form for the rest of his/her life.

However, it is not as simple as popping a pill every day. Let’s compare a Cushing’s patients post BLA with a Type I diabetic. Stress management for Cushing's patients is just as critically important as blood sugar management is for diabetics.

A diabetic must look at a plate of food, estimate the amount of carbohydrates contained therein, and take insulin for that amount of carbohydrates (which calculations are often aided by the nutritional facts on the packaging).

A Cushing's patient post BLA must take cortisol replacement medicine in response to the amount of 'sickness' or 'stress.' These events are unquantifiable and lack data on packaging. In addition, there is not a day goes by without stress or challenges of some sort. These episodes can prove challenging for a Cushing’s patient in determining how much medicine to take to offset these challenges. This makes it difficult for the Cushing’s patient to fully return to his/her lifestyle before Cushing’s.

What does a person need to watch for after pituitary surgery?

I have not had surgery yet, but I saw this summary online and thought it contained some things I have seen other Cushing's patients say after surgery.

To read Vanderbilt Medical Center Pituitary Clinic's discharge instructions for pituitary surgery patients, click here.




Where can I find out more about the pituitary gland? I'm intrigued!

One in five people have pituitary tumors.

The Pituitary Network Association has a great information about the pituitary. Check it out!


NOTES FROM THE NEUROSURGEON

Click here to read New Approaches to Managing Tumors of the Pituitary Gland Offer Patients Hope.

Click here to read The Problem of the Aggressive Pituitary Tumor.



Pituitary Tumors: A Neurosurgeon’s Approach


Great features from the Cushing's Support & Research Foundation

The Cushing's Support & Research Foundation has some very good tools to help people understand Cushing's.

In particular, I like the Faces of Cushing's powerpoint and the Do I Have Cushing's section.

Meet the Faces of Cushing's - Diagnosis, Treatment and Recovery slideshow (powerpoint slideshow)

What to Do if You Think You Have Cushing's

How long do you think you've had Cushing's?

Many people ask this question. It is a very interesting one, but one that is really difficult to answer.

I didn’t have the full slate of symptoms—to my knowledge—until 2006. However, I feel like I can trace a few milestone periods in my life and it adds a bit of insight with what I now know.

It will be at least 11 years from when I first started showing symptoms to when I got diagnosed with Cushing's disease.

The only commonality I can see when reviewing the timeline below is when I experienced great amounts of stressed. Since my body was already producing excessive amounts of cortisol, any drop of additional stress caused my cups to runneth over. Weight gain was my most obvious symptom.


Here are the timeline tidbits I can piece together:

1996 to 1999 – gained weight unexpectedly in grad school and during first big jobs. 5-10 pounds per year.

2000 – reached highest weight to date. Stress at job, moving back home to Houston, career change/stress.

2001 – completed a marathon in Rome, Italy. Success in losing 20 pounds before high school reunion.

2001 to 2002 – gained weight despite efforts.

June 2002 to May 2003 – period of weight loss. Atlkins diet worked well for me, as I embraced the carb-is-my-enemy mantra.

August 2003 – bridesmaid in friend Nancy’s wedding. I was measured for dress in March and by June/July, the dress was too tight and had to be let out. Gained 15 pounds from May to August despite earnest efforts to lose.

2004 – First paid political campaign job. Very stressful. Worked two full time jobs and ran a local political campaign’s volunteer activities. Gained weight.

Summer 2004 – buffalo hump pain begins. Neck and back pain cause me to call into work because I can’t move or get up. This pain continues to this day.

June 2005 – dating husband-to-be Jonathan. When I discuss weight gain, he notes that I have very good eating habits, so he can’t figure it out either. I go to internist who runs tests and prescribes Thyrolar for subclinical hypothyroidism. Symptoms subsist but soon return.

December 2005 – started new political job. Very stressful. Started missing my menstrual periods for 5 cycles until May 2006.

Summer/Fall 2006 – unexpected weight gain. Many public appearances. My suit jackets no longer closed, and I worried about my clothes prior to every event I attended. Cried frequently behind closed doors, at least bimonthly. Depression and anxiety were high.

November 2006 – Political campaigns end. Quit job, bought first home, and move with husband-to-be to San Antonio for his job. Unpack, settle in, start planning April 2007 wedding. Prepare for holiday season. Anxiety remains high despite decompressing environment. More crying, more depression, inability to focus, concentrate. Muscle aches become more pronounced in new two-story home. Started missing my menstrual periods again (November 2006 to April 2007).

December 2006 – Postpone wedding until October 2007, thinking that more time will relieve stress. Symptoms continue.

March 2007 – Visit to new PCP in San Antonio; I explain symptoms; He runs tests for thyroid.

March 28, 2007 – Doctor’s office calls with normal thyroid tests. I cried. I knew something was wrong. I took to the internet and within one hour of searching, I first read about Cushing's. I diagnosed myself that day.
05/09/07---first endo appt about Cushing's (he was totally dismissive, but I squeezed him for lab orders)

June 28, 2007 – saw specialist out-of-state; first high test results diagnostic of cushing's (MN cortisol serums 6.7, 7.0, 7.5; ACTH 78, 105; MN salivary 4.1, 5.4)

November 2, 2007 – IPSS, showed diagnostic results at baseline of 14 to 1 (diagnostic: 2 to 1); timed intervals were diagnostic: 93 to 1, 78 to 1 (stimmed to 3,440!)

December 20, 2007 – diagnosed with Cushing's disease. Declined pituitary surgery for 12/27/07 to try for 1st baby.

December 31, 2007 – eloped