Postoperative ACTH, cortisol levels may predict Cushing’s disease remission rate

Early and midterm nonremission after transsphenoidal surgery in people with Cushing’s disease may be predicted by normalized early postoperative values for adrenocorticotropic hormone and cortisol, study data show.

Prashant Chittiboina, MD, MPH, assistant clinical investigator in the neurosurgery unit for pituitary and inheritable diseases at the National Institute of Neurological Diseases and Stroke at the NIH, and colleagues evaluated 250 patients with Cushing’s disease who received 291 transsphenoidal surgery procedures during the study period to determine remission after the procedure. Patients were treated between December 2003 and July 2016. Early remission was assessed at 10 days and medium-term remission was assessed at 11 months.

Early nonremission was predicted by normalized early postoperative values for cortisol (P = .016) and by normalized early postoperative values for adrenocorticotropic hormone (ACTH; P = .048). Early nonremission was further predicted with 100% sensitivity, 39% specificity, 100% negative predictive value and 18% positive predictive value for a cutoff of –12 µg/mL in normalized early postoperative values for cortisol and with 88% sensitivity, 41% specificity, 96% negative predictive value and 16% positive predictive value for a cutoff of –40 pg/mL in normalized early postoperative values for ACTH.

Medium-term nonremission was also predicted by normalized early postoperative values for cortisol (P = .023) and ACTH (P = .025).

“We evaluated the utility of early postoperative cortisol and ACTH levels for predicting nonremission after transsphenoidal adenomectomy for Cushing’s disease,” the researchers wrote. “Postoperative operative day 1 values at 6 a.m. performed best at predicting early nonremission, albeit with a lower [area under the receiver operating characteristic curve]. Normalizing early cortisol and ACTH values to post-[corticotropin-releasing hormone] values improved their prognostic value. Further prospective studies will explore the utility of normalized very early postoperative day 0 cortisol and ACTH levels in identifying patients at risk for nonremission following [transsphenoidal surgery] in patients with [Cushing’s disease].” – by Amber Cox

Disclosure: The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7B7de200ed-c667-4b48-ab19-256d90a7bbc5%7D/postoperative-acth-cortisol-levels-may-predict-cushings-disease-remission-rate

Scalp Hair Cortisol Accurate in Cushing’s Syndrome Diagnosis

Scalp hair cortisol measurement is an accurate first-line diagnostic test for Cushing’s syndrome in adults and offers several advantages over other first-line diagnostic procedures, according to findings published in the European Journal of Endocrinology.

“[Hair cortisol content] has practical advantages over currently used diagnostic tests, since sample collection can easily be performed in an outpatient setting and is not dependent on patient adherence to sampling instructions,” Elisabeth F. C. van Rossum, MD, PhD, professor at Erasmus MC, University Medical Center Rotterdam in the Netherlands, and colleagues wrote. “Furthermore, [hair cortisol content] measurement offers retrospective information about cortisol levels over months of time in a single measurement, thereby potentially circumventing the limitations posed by the variability in cortisol secretion in endogenous [Cushing’s syndrome].”

Van Rossum and colleagues analyzed data from 43 patients with confirmed endogenous Cushing’s syndrome and 35 patients with suspected Cushing’s syndrome in whom diagnosis was excluded after testing (patient controls), all evaluated between 2009 and 2016 at an endocrinology outpatient clinic at Erasmus MC. Adults from a previously published validation study served as healthy controls (n = 174). Researchers measured scalp hair samples, 24-hour urinary free cortisol, serum cortisol and salivary cortisol, and used Pearson’s correlation to determine associations between hair cortisol content and first-line screening tests for Cushing’s syndrome.

Hair cortisol content was highest in patients with Cushing’s syndrome (geometric mean, 106.9 pg/mg; 95% CI, 77.1-147.9) and higher compared with both healthy controls (mean, 8.4 pg/mg; 95% CI, 7-10) and patient controls (mean, 12.7 pg/mg; 95% CI, 8.6-18.6). Using healthy controls as the reference population, researchers found that the optimal cutoff for diagnosis of Cushing’s syndrome via hair cortisol content was 31.1 pg/mg; sensitivity and specificity were 93% and 90%, respectively (area under the curve = 0.958). Results were similar when using patient controls as the reference population, according to the researchers.

Hair cortisol content was correlated with urinary free cortisol (P < .001), serum cortisol (P < .001) and late-night salivary cortisol (P < .001). In addition, in two patients with ectopic Cushing’s syndrome, researchers observed a gradual rise in hair cortisol content in the 3 to 6 months before disease diagnosis.

“Together with a straightforward sample collection procedure, this method may prove to be a convenient noninvasive screening test for [Cushing’s syndrome],” the researchers wrote. “Additionally, our results indicate that hair cortisol measurements provide clinicians a tool to retrospectively assess cortisol secretion in patients with [Cushing’s syndrome], months to years back in time. This also offers the opportunity to estimate the onset of hypercortisolism and thus the duration of the disease before diagnosis.” – by Regina Schaffer

Disclosure: The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7B72da0183-e1a8-48cb-a1fd-332c7999beb5%7D/scalp-hair-cortisol-accurate-in-cushings-syndrome-diagnosis

Cushing’s Disease Treatment Market to Witness an Outstanding Growth by 2017 – 2025

Cushing disease is caused by tumour in the pituitary gland which leads to excessive secretion of a hormone called adrenocorticotrophic (ACTH), which in turn leads to increasing levels of cortisol in the body. Cortisol is a steroid hormone released by the adrenal glands and helps the body to deal with injury or infection. Increasing levels of cortisol increases the blood sugar and can even cause diabetes mellitus. However the disease is also caused due to excess production of hypothalamus corticotropin releasing hormone (CRH) which stimulates the synthesis of cortisol by the adrenal glands.

The condition is named after Harvey Cushing, the doctor who first identified the disease in 1912. Cushing disease results in Cushing syndrome. Cushing syndrome is a group of signs and symptoms developed due to prolonged exposure to cortisol.

Signs and symptoms of Cushing syndrome includes hypertension, abdominal obesity, muscle weakness, headache, fragile skin, acne, thin arms and legs, red stretch marks on stomach, fluid retention or swelling, excess body and facial hair, weight gain, acne, buffalo hump, tiredness, fatigue, brittle bones, low back pain, moon shaped face etc.

Symptoms vary from individual to individual depending upon the disease duration, age and gender of the patient.  Disease diagnosis is done by measuring levels of cortisol in patient’s urine, saliva or blood. For confirming the diagnosis, a blood test for ACTH is performed. The first-line treatment of the disease is through surgical resection of ACTH-secreting pituitary adenoma, however disease management is also done through medications, Cushing disease treatment market comprises of the drugs designed for lowering the level of cortisol in the body. Thus patients suffering from Cushing disease are prescribed medications such as ketoconazole, mitotane, aminoglutethimide metyrapone, mifepristone, etomidate and pasireotide.

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Cushing’s disease treatment market revenue is growing with a stable growth rate, this is attributed to increasing number of pipeline drugs. Also increasing interest of pharmaceutical companies to develop Cushing disease drugs is a major factor contributing to the revenue growth of Cushing disease treatment market over the forecast period. Current and emerging players’ focuses on physician education and awareness regarding availability of different drugs for curing Cushing disease, thus increasing the referral speeds, time to diagnosis and volume of diagnosed Cushing disease individuals. Growing healthcare expenditure and increasing awareness regarding Cushing syndrome aids in the revenue growth of Cushing’s disease treatment market. Increasing number of new product launches also drives the market for Cushing’s disease Treatment devices. However availability of alternative therapies for curing Cushing syndrome is expected to hamper the growth of the Cushing’s disease treatment market over the forecast period.

The Cushing’s disease Treatment market is segment based on the product type, technology type and end user

Cushing’s disease Treatment market is segmented into following types:

By Drug Type

  • Ketoconazole
  • Mitotane
  • Aminoglutethimide
  • Metyrapone
  • Mifepristone
  • Etomidate
  • Pasireotide

By End User

  • Hospital Pharmacies
  • Retail Pharmacies
  • Drug Stores
  • Clinics
  • e-Commerce/Online Pharmacies

Cushing’s disease treatment market revenue is expected to grow at a good growth rate, over the forecast period. The market is anticipated to perform well in the near future due to increasing awareness regarding the condition. Also the market is anticipated to grow with a fastest CAGR over the forecast period, attributed to increasing investment in R&D and increasing number of new product launches which is estimated to drive the revenue growth of Cushing’s disease treatment market over the forecast period.

Depending on geographic region, the Cushing’s disease treatment market is segmented into five key regions: North America, Latin America, Europe, Asia Pacific (APAC) and Middle East & Africa (MEA).

North America is occupying the largest regional market share in the global Cushing’s disease treatment market owing to the presence of more number of market players, high awareness levels regarding Cushing syndrome. Healthcare expenditure and relatively larger number of R&D exercises pertaining to drug manufacturing and marketing activities in the region. Also Europe is expected to perform well in the near future due to increasing prevalence of the condition in the region.

Asia Pacific is expected to grow at the fastest CAGR because of increase in the number of people showing the symptoms of Cushing syndrome, thus boosting the market growth of Cushing’s disease treatment market throughout the forecast period.

Some players of Cushing’s disease Treatment market includes CORCEPT THERAPEUTICS, HRA Pharma, Strongbridge Biopharma plc, Novartis AG, etc. However there are numerous companies producing branded generics for Cushing disease. The companies in Cushing’s disease treatment market are increasingly engaged in strategic partnerships, collaborations and promotional activities to capture a greater pie of market share.

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Hair Test for Cushing Syndrome?

Cortisol levels in hair correlated strongly with standard tests

by Jeff Minerd
Contributing Writer, MedPage Today

Analyzing the levels of cortisol in hair may aid in the diagnosis of Cushing syndrome, perhaps one day replacing invasive blood tests, scientists said.

Cortisol levels in the proximal ends of hair samples taken from patients with the syndrome correlated strongly with blood tests (R=0.4; P=0.03) and urine tests (R=0.5; P=0.005) for cortisol, reported Mihail Zilbermint, MD, of the National Institute of Child Health and Human Development in Bethesda, Md., and colleagues.

“The diagnosis of Cushing syndrome is often challenging and inconclusive, despite numerous tests used for the detection of hypercortisolemia and its origin, and is associated with high morbidity and high risk for mortality, if undiagnosed and untreated,” Zilbermint and colleagues wrote online in Endocrine: International Journal of Basic and Clinical Endocrinology.

“As a potential solution to the limitations of these tests, hair cortisol has been increasingly studied as an additional means to diagnose patients with Cushing Syndrome. Much like hemoglobin A1C is a longitudinal marker of blood glucose levels, hair cortisol can be a measure of the body’s glucocorticoid levels over the previous several weeks to months.”

“Our results are encouraging,” Zilbermint said in a statement. “We are hopeful that hair analysis may ultimately prove useful as a less-invasive screening test for Cushing syndrome or in helping to confirm the diagnosis.”

The study included 30 patients with Cushing syndrome and six control individuals without the disease. The participants’ average age was 26, and 75% were female and 75% were Caucasian.

The investigators took 3 cm-long hair samples from all patients, analyzed the proximal, medial, and distal segments of the samples for cortisol, and compared the results with results of standard blood and urine tests. Cortisol levels were highest in the proximal segments and correlated best with the standard tests, the investigators reported.

“We found that proximal hair cortisol directly correlates with late night serum cortisol and UFC [urinary free cortisol] in patients with and without Cushing syndrome. The most proximal 1 cm of hair was the best section of hair for stratifying the two groups of patients in our cohort.

“These findings support further research on the use of this modality in the workup for Cushing syndrome.”

Regarding the study’s limitations, the team pointed to the small control group of only six patients. Another limitation is that more than half of the participants (58%) were younger than age 18, and pubertal status on cortisol metabolism may be a factor in hair cortisol measurement.

“However, our study’s strengths are that it is the largest sample so far to analyze segmental hair cortisol in Cushing syndrome, and that it is the largest study to compare hair cortisol to any biochemical test for hypercortisolemia in patients with Cushing syndrome,” Zilbermint and colleagues said. “Our study also included a large cohort of Cushing Disease patients, which has been under-represented in prior studies on hair cortisol.”

The study was funded by the National Institutes of Health. Zilbermint and colleagues reported having no relevant financial relationships with industry.

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

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