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."
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
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
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.
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.
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
10 min--------- 59---------------------1500-----------------------75
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)