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MaryO

Pituitary tumor size not definitive for Cushing's

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By: SHERRY BOSCHERT, Family Practice News Digital Network
 
SAN FRANCISCO – The size of a pituitary tumor on magnetic resonance imaging in a patient with ACTH-dependent Cushing’s syndrome can’t differentiate between etiologies, but combining that information with biochemical test results could help avoid costly and difficult inferior petrosal sinus sampling in some patients, a study of 131 cases suggests.
 
If MRI shows a pituitary tumor larger than 6 mm in size, the finding is 40% sensitive and 96% specific for a diagnosis of Cushing’s disease as the cause of adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome, and additional information from biochemical testing may help further differentiate this from ectopic ACTH secretion, Dr. Divya Yogi-Morren and her associates reported at the Endocrine Society’s Annual Meeting.
 
Pituitary tumors were seen on MRI in 6 of 26 patients with ectopic ACTH secretion (23%) and 73 of 105 patients with Cushing’s disease (69%), with mean measurements of 4.5 mm in the ectopic ACTH secretion group and 8 mm in the Cushing’s disease group. All but one tumor in the ectopic ACTH secretion group were 6 mm or smaller in diameter, but one was 14 mm.
 
Because pituitary "incidentalomas" as large as 14 mm can be seen in patients with ectopic ACTH secretion, the presence of a pituitary tumor can’t definitively discriminate between ectopic ACTH secretion and Cushing’s disease, said Dr. Yogi-Morren, a fellow at the Cleveland Clinic.
 
That finding contradicts part of a 2003 consensus statement that said the presence of a focal pituitary lesion larger than 6 mm on MRI could provide a definitive diagnosis of Cushing’s disease, with no further evaluation needed in patients who have a classic clinical presentation and dynamic biochemical testing results that are compatible with a pituitary etiology (J. Clin. Endocrinol. Metab. 2003;88:5593-602). The 6-mm cutoff, said Dr. Yogi-Morren, came from an earlier study reporting that 10% of 100 normal, healthy adults had focal pituitary abnormalities on MRI ranging from 3 to 6 mm in diameter that were consistent with a diagnosis of asymptomatic pituitary adenomas (Ann. Intern. Med. 1994;120:817-20).
 
A traditional workup of a patient with ACTH-dependent Cushing’s syndrome might include a clinical history, biochemical testing, neuroimaging, and an inferior petrosal sinus sampling (IPSS). Biochemical testing typically includes tests for hypokalemia, measurement of cortisol and ACTH levels, a high-dose dexamethasone suppression test, and a corticotropin-releasing hormone (CRH) stimulation test. Although IPSS is the gold standard for differentiating between the two etiologies, it is expensive and technically difficult, especially in institutions that don’t regularly do the procedure, so it would be desirable to avoid IPSS if it’s not needed in a subset of patients, Dr. Yogi-Morren said.
 
The investigators reviewed charts from two centers (the Cleveland Clinic and the M.D. Anderson Cancer Center, Houston) for patients with ACTH-dependent Cushing’s syndrome seen during 2000-2012.
 
ACTH levels were significantly different between groups, averaging 162 pg/mL (range, 58-671 pg/mL) in patients with ectopic ACTH secretion, compared with a mean 71 pg/mL in patients with Cushing’s disease (range, 16-209 pg/mL), she reported. Although there was some overlap between groups in the range of ACTH levels, all patients with an ACTH level higher than 210 pg/mL had ectopic ACTH secretion.
 
Median serum potassium levels at baseline were 2.9 mmol/L in the ectopic ACTH secretion group and 3.8 mmol/L in the Cushing’s disease group, a significant difference. Again, there was some overlap between groups in the range of potassium levels, but all patients with a baseline potassium level lower than 2.7 mmol/L had ectopic ACTH secretion, she said.
 
Among patients who underwent a high-dose dexamethasone suppression test, cortisol levels decreased by less than 50% in 88% of patients with ectopic ACTH secretion and in 26% of patients with Cushing’s disease.
 
Most patients did not undergo a standardized, formal CRH stimulation test, so investigators extracted the ACTH response to CRH in peripheral plasma during the IPSS test. As expected, they found a significantly higher percent increase in ACTH in response to CRH during IPSS in the Cushing’s disease group, ranging up to more than a 1,000% increase. In the ectopic ACTH secretion group, 40% of patients did have an ACTH increase greater than 50%, ranging as high as a 200%-300% increase in ACTH in a couple of patients.
 
"Although there was some overlap in the biochemical testing, it is possible that it provides some additional proof to differentiate between ectopic ACTH secretion and Cushing’s disease," Dr. Yogi-Morren said.
 
In the ectopic ACTH secretion group, the source of the secretion remained occult in seven patients. The most common identifiable cause was a bronchial carcinoid tumor, in six patients. Three patients each had small cell lung cancer, a thymic carcinoid tumor, or a pancreatic neuroendocrine tumor. One patient each had a bladder neuroendocrine tumor, ovarian endometrioid cancer, medullary thyroid cancer, or a metastatic neuroendocrine tumor from an unknown primary cancer.
 
The ectopic ACTH secretion group had a median age of 41 years and was 63% female. The Cushing’s disease group had a median age of 46 years and was 76% female.
 
Dr. Yogi-Morren reported having no financial disclosures.
 
sboschert@frontlinemedcom.com
 
On Twitter @sherryboschert
 
From Famiiy Practice News

 

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Not a surprise, but puts institutions in a hard spot as it basically implies that most Cushing's patients where adrenal has been ruled out need an IPSS, yet few institutions have experience performing them.

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In simple terms is this like picking the full grown bloom as opposed to "nipping it in the bud" ?

 

Dave

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I think sometimes they never get huge they just spread. See dr. F's article called "cushings not necessarily a progressive fatal disease". I've had symptoms for a loooooong time and my pit had tiny globs that got sucked up. Tiny.

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Well, they don't necessarily spread. The tumors that cause Cushing's disease are generally very tiny. Microscopic, in fact. Sometimes people that have cyclical Cushing's have tumors that look like goopy blobs (for lack of a better description). My tumor was not visible even when my surgeon did my surgery. But my pathology report showed that I had a tumor. Or possibly a few. Sometimes there are several microscopic areas of disease on the gland.

I hope that helped.

:)Kathy

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Well, they don't necessarily spread. The tumors that cause Cushing's disease are generally very tiny. Microscopic, in fact. Sometimes people that have cyclical Cushing's have tumors that look like goopy blobs (for lack of a better description). My tumor was not visible even when my surgeon did my surgery. But my pathology report showed that I had a tumor. Or possibly a few. Sometimes there are several microscopic areas of disease on the gland.

I hope that helped.

:)Kathy

Goopy blob huh......that description fits a lot of kids in my neighbourhood. 

Seriously the more I read about pituitary tumours and how small they can be the more I tend to compare them to "brain wiring malfunctions" and the more I believe that pituitary Cushing's is pretty well incurable . I've had 6 pit MRIs over a similar number of years and despite some radiologists concerns about "hypointense areas post gadolineum contrast" nobody has ever said  ' we think you may have Cushing's ' or  ' we should do an IPSS  to evaluate this '

Adrenal problem is a very different kettle of fish as we all know. Maybe that pituitary based disease is still an imprecise area for surgery and therefore why there are so many recurrences and indeed why so many folk don't get to surgery or even diagnosis...after all , as was remarked recently in another post .... all surgeons know how to operate but some know when to operate and when to leave it alone .

just my view.

 

Dave

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Many surgeons are now doing exploratory pit surgery where the make thin slices to look for the tiniest tumors/blobs - even with no MRI evidence. Obviously pituitary Cushings is more difficult to cure when your body decides to make microscopic trouble makers! Your areas of hypointensity would have gotten you filleted by the top neurosurgeons here;).

Even with us ambiguous blob makers in the mix, they still keep saying 80% cure. Ill call it remission so I don't freak out later if it comes back, but right this second the above procedure worked for me!

 

Mags

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