Basal Cortisol Elevated in Patients with ACTH-Staining Pituitary Macroadenoma

Preoperative identification of patients with silent adrenocorticotrophic hormone-secreting tumors could potentially change the approach to management. A new study aimed to determine whether a preoperative adrenocorticotrophic hormone stimulation test for evaluation of nonfunctional pituitary macroadenoma could aid in identifying adrenocorticotrophic hormone-staining pathology yielded large variability and did not allow clinical utility.

Thus, researchers concluded that larger, multicenter research is needed to determine whether this test can be useful.

“As ACTH stimulation tests are performed routinely when evaluating macroadenoma when there is no suspicion for a state of endogenous hypercortisolism, we sought to determine if the test could reliably identify these pathologies during the preoperative evaluation. We hypothesized that patients with subclinical Cushing’s disease or silent ACTH-secreting tumors would have a higher delta cortisol on the ACTH stimulation tests vs. other types of macroadenoma pathologies,” Kevin Pantalone, DO, ECNU, FACE, staff endocrinologist and director of clinical research in the department of endocrinology at Cleveland Clinic, told Endocrine Today.

Pantalone and colleagues performed a retrospective chart review of 148 patients with pituitary macroadenoma who underwent preoperative ACTH stimulation tests, with the goal of determining whether the test can aid in the identification of ACTH-staining pathology.

Overall, 9.5% of patients showed diffuse staining, 50.6% showed other-staining (diffuse staining for anterior pituitary hormones other than ACTH) and 39.9% showed no staining (no staining for any anterior pituitary hormones).

The researchers calculated delta total cortisol at 30 and 60 minutes from baseline and reviewed preoperative ACTH stimulation tests. Additionally, Pantalone and colleagues compared the basal and maximal delta cortisol between the ACTH-staining pituitary macroadenoma and the non-ACTH staining (n = 134), other staining (n = 75) and non-staining (n = 59) tumors.

According to data reported at the American Association of Clinical Endocrinologists Annual Scientific and Clinical Congress, the ACTH-staining group had higher mean basal cortisol levels compared with the non-ACTH-staining (P = .012), other staining (P = .018) and the non-staining (P = .012) tumors. The researchers found no significant differences in maximal delta cortisol between the groups.

“While we found basal cortisol levels were higher in patients with ACTH-staining pituitary microadenoma vs. non-ACTH-staining macroadenoma, the large variability in cortisol values did not allow for clinical utility,” Pantalone told Endocrine Today.

“Unfortunately, in the end, our study was limited by the number of cases with ACTH-staining pathology. Thus, we were unable to determine if the ACTH stimulation test could reliably assist clinicians in potentially identifying ACTH-staining pathology in the preoperative setting,” he said. “A multicenter study, affording a large number of ACTH-staining tumors, is needed. This may allow for us to determine if the ACTH-stimulation test can really be clinically useful in preoperatively identifying ACTH-staining pathology.” – by Amber Cox

8 Things You Should Know About Addison’s Disease

adrenal-insufficiency

 

Cortisol gets a bad rap these days. (Guilty!) Yes, this hormone surges when you’re stressed. And yes, chronic stress is bad news for your health. But while too much cortisol can lead to all sorts of stress-related side effects, too little cortisol is equally debilitating.

Just ask someone with Addison’s disease. If you suffer from this condition, your adrenal glands fail to make adequate amounts of cortisol, says Betul Hatipoglu, MD, an endocrinologist at Cleveland Clinic.

Cortisol plays a role in regulating your blood pressure, heart function, digestion, and a lot else, Hatipoglu explains. So if your adrenal glands poop out and your cortisol levels plummet, a lot can go wrong. (In as little as 30 days, you can be a whole lot slimmer, way more energetic, and so much healthier just by following the simple, groundbreaking plan in The Thyroid Cure!)

Here’s what you need to know about this condition—starting with its craziest symptom.

It can make your teeth appear whiter.

Hatipoglu once met with a patient who was suffering from fatigue, belly pain, and mild weight loss. “Her doctors thought she was depressed,” Hatipoglu recalls. Toward the end of their appointment, Hatipoglu noticed the woman’s teeth looked very white. She realized they looked white because the woman’s skin was tan. “I asked her if she’d been on vacation, and she said she hadn’t been in the sun, and that’s when I knew,” Hatipoglu says. Some Addison’s-related hormone shifts can make the skin appear darker, almost like a tan. “Addison’s is the only disease I know of that can cause darkening of the skin,” she says.

Its (other) symptoms are popular ones.

 Along with darker skin, other symptoms of Addison’s include nausea, mild-to-severe abdominal or bone pain, weight loss, a lack of energy, forgetfulness, and low blood pressure, Hatipoglu says. Of course, those same symptoms are linked to many other health issues, from thyroid disease to cancer. “It’s very easy to confuse with other disorders, so many people see a lot of doctors before finally receiving a proper diagnosis,” she says. (One exception: For young women who develop Addison’s disease, loss of body hair is a warning sign, Hatipoglu adds.)
It’s rare.
Doctors also miss or misinterpret the symptoms of Addison’s disease because it’s very uncommon. “I’m not sure if it’s quite one in a million, but it’s very rare,” Hatipoglu says. “It makes sense that many doctors don’t think of it when examining a patient with these symptoms.”
It’s often confused with adrenal insufficiency.

A lot of online resources mention Addison’s disease and adrenal insufficiency as though they were two names for the same condition. They’re not the same, Hatipoglu says. While a thyroid issue or some other hormone-related imbalance could mess with your adrenal function, Addison’s disease refers to an autoimmune disorder in which your body attacks and destroys your adrenal glands.

That destruction can happen quickly.

While it takes months or even years for some Addison’s sufferers to lose all hormone production in their adrenal glands, for others the disease can knock out those organs very rapidly—in a matter of days, Hatipoglu says. “That’s very uncommon,” she adds. But compared to other less-severe adrenal issues, the symptoms of Addison’s tend to present more dramatically, she explains. That means a sufferer is likely to experience several of the symptoms mentioned above, and those symptoms will continue to grow worse as time passes.

Anybody can get it.

Addison’s is not picky. It can strike at any age, regardless of your sex or ethnicity, Hatipoglu says. While there’s some evidence that genetics may play a role—if other people in your family have the disease or some other endocrine disorder, that may increase your risk—there’s really no way to predict who will develop the disease, she adds.

Screening for Addison’s is pretty simple.

If your doctor suspects Addison’s, he or she will conduct a blood test to check for your levels of cortisol and another hormone called ACTH. “Usually the results of that screening are very clear,” Hatipoglu says. If they’re not, some follow-up tests can determine for sure if you have the condition.

There are effective treatments.

Those treatments involve taking oral hormone supplements.  In extreme cases, if the patient’s body does not properly absorb those supplements, injections may be necessary, Hatipoglu explains. “But patients live a normal life,” she adds. “It’s a treatable disease, and the treatments are effective.”

From http://www.prevention.com/health/addisons-disease-symptoms

Interview May 13 with Michelle B (MichelleB), Cyclic Cushing’s Patient

Hello all, I’m Michelle mother of 3 beautiful children, I work part-time, 33yrs young, non-smoker, non-drinker, overall health is good for the most part…..Where do I even begin.

I just recently received the diagnosis of cyclic Cushing’s. I’m not really sure how long I have actually had Cushing’s because I have had a diagnosis of PCOS since I was 17 yrs. old ( I’m now the ripe young age of 33). However looking back through labs with my endocrinologist who I see every 6 months, my ACTH levels have been elevated for a bit over 1 yr. It was not until recently January of 2015- things were going terribly wrong.

Starting in January I started to feel genuinely unwell, on a regular basis. I cant really explain all my symptoms there were so many different sensations and feelings that were seemingly different daily. However the red flag was I was having blood pressure spikes from really high, to very low back to back. I never had any blood pressure issues so this was a concern that led me to see a cardiologist. Upon tons of testing the cardio MD felt that something was telling my otherwise very healthy heart to do this and I should see a endocrinologist. (thank goodness for him) I contacted my endo and let him know…. the testing began.

I did every test: the midnightcortisol saliva test, dex suppression, 24 hr urine test, CRH stimulation testing. And I did them more than once. Each time it was a different response either, inconclusive, normal high, or high. I was then referred to the head of the Cleveland clinics pituitary department Dr. Kennedy. He said he is having a hard time believing when he looks at me that its Cushing’s. However all my labs say it is. I will say I do fit the mold of PCOS to a tee- which symptoms of that do coincide with Cushing’s but he still said we have to be sure its Cushing’s. To add to the mix I did have a normal MRI as well.

Dr. Kennedy started me on a 2 week midnight cortisol saliva test- Upon completion we noted levels of cortisol all over the place, some Normal, normal on high range, high, and really high. He confirmed with all the other tests this is Cushing’s. Now we are trying to figure out what is next…. and where is this damn little tumor at. he feels that it is most likely in the pituitary from my test results, but we still are not ruling out else where. He is thinking that the next step would be exploratory neurosurgery or the IPSS. I’m not sure what to think of all this, except I want to hope for the best like everyone- and just be cured!!

On a side note during all of this I also had episodes of severe pain in my chest and nausea. I went to see a GI who did an upper endo scope. They found I had eosinpphilic esophagitis. I also have never had any GI problems until now; and they came on suddenly. Im also having pain in my pancreas area- not sure if any of the two are related at all to Cushing’s. But once again I was fine until recently with all these issues at once it seems.

wish me luck on further testing, treatment, and ultimately a CURE!!

interview

Michelle was our guest in an interview on BlogTalk Radio  Wednesday, May 13, 2015.

The archived interview is available now through iTunes Podcasts (Cushie Chats) or BlogTalkRadio. There are currently 83 other past interviews for your listening pleasure!

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Pituitary tumor size not definitive for Cushing’s

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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