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

The Cables1 Gene in Glucocorticoid Regulation of Pituitary Corticotrope Growth and Cushing Disease

Abstract :
Context: Cushing disease (CD) is due to pituitary corticotrope adenomas that produce unrestrained ACTH secretion and have lost the negative feedback exerted by glucocorticoids (GCs). GCs also restrain corticotrope proliferation, and the mechanisms of this inhibition are poorly understood.
Objective: The aim of the study was to identify cell cycle regulatory genes that are regulated by GCs and the glucocorticoid receptor and to assess regulatory genes that have a rate-limiting action on corticotrope proliferation and may be disregulated in CD.
Design: The mouse corticotrope tumor cells AtT-20 were used to identify GC-regulated genes that contribute to control of cell cycle progression. Surgery sections from patients with CD were used to assess expression of CABLES1 in corticotrope adenomas.
Methods: Gene expression profiling, small interfering RNA knockdowns, cell cycle analyses, and genetic manipulations were performed in AtT-20 cells. Sequencing of chromatin immunoprecipitation for pituitary-restricted transcription factors and RNA polymerase II were used to identify regulatory elements and genes that bind GR and are direct transcriptional targets. A panel of previously well-characterized corticotrope adenomas was used to correlate expression of CABLES1 with that of other markers. Results: GCs altered expression of 3 positive and 3 negative regulators of cell cycle progression. Two Myc genes (L-Myc and N-Myc) and E2F2 are repressed by GCs, whereas genes for the negative regulators of the cell cycle, Gadd45, Gadd45, and Cables1 are activated by GCs. Cables1 small interfering RNA knockdown strongly stimulates AtT-20 cell proliferation and antagonizes the growth inhibition produced by GCs. The Gadd45 and Cables1 genes have the hallmarks of direct GC targets. CABLES1 is expressed in normal human pituitary cells, but expression is lost in 55% of corticotrope adenomas, and this is strongly correlated with the loss of p27 Kip1 expression.
Conclusions: CABLES1 is a critical regulator of corticotrope proliferation that defines a pathway often inactivated in CD and links proliferation to GC resistance. (J Clin Endocrinol Metab

Document type :

Journal articles
Journal of Clinical Endocrinology and Metabolism, Endocrine Society, 2016, 101 (2), pp.513-522. <10.1210/jc.2015-3324>

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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Rare Disease Day 2017

Today is #RareDiseaseDay 2017! Today, with events taking place in over 90 countries all around the world, we hope to raise more awareness than ever for rare diseases!

With the theme of research, and the slogan, ‘With research, the possibilities are limitless’, #RareDiseaseDay 2017 is an opportunity to call on all researchers, universities, students, companies, policymakers and clinicians to do more research and to make them aware of the importance of research for the rare disease community.

This year’s Rare Disease Day video, which has been viewed over a hundred thousand times and translated into over 30 languages,  draws a parallel with a routine that many of us go through multiple times a day – searching for an answer on the internet. The video highlights how isolating it is when you search on the internet but receive the response ‘your search had no results’. It also highlights the hope and promise that comes with additional research into rare diseases, something that must be continuously strived for.

You are still able to participate in raising awareness of the day and be part of the change, by sharing the video, the poster, or any Rare Disease Day material on your Facebook, Twitter or other social media platforms.

This year, on the tenth edition of the day, Rare Disease Day events will be held for the first time in four African nations, Botswana, Nigeria, Senegal and Sudan. Events will also be held for the first time in Saint Pierre and Miquelon.

Learn more at http://www.rarediseaseday.org/page/news/today-is-rare-disease-day-2017

What I’m doing for Rare Disease Day

rare disease day

 

Each and every day since 1897,  I tell anyone who will listen about Cushing’s.  I pass out a LOT Cushing’s business cards.

Adding to websites, blogs and more that I have maintained continuously since 2000 – at mostly my own expense.

Posting on the Cushing’s Help message boards about Rare Disease Day.  I post there most every day.

Tweeting/retweeting info about Cushing’s and Rare Disease Day today.

Adding info to one of my blogs about Cushing’s and Rare Disease Day.

Adding new and Golden Oldies bios to another blog, again most every day.

Thinking about getting the next Cushing’s Awareness Blogging Challenge set up for April…and will anyone else participate?

And updating https://www.facebook.com/CushingsInfo with a bunch of info today (and every day!)

~~~

Today is Rare Disease Day.

I had Cushing’s Disease due to a pituitary tumor. I was told to diet, told to take antidepressants and told that it was all my fault that I was so fat. My pituitary surgery in 1987 was a “success” but I still deal with the aftereffects of Cushing’s and of the surgery itself.

I also had another Rare Disease – Kidney Cancer, rare in younger, non-smoking women.

And then, there’s the adrenal insufficiency…

If you’re interested, you can read my bio here https://cushingsbios.com/2013/04/29/maryo-pituitary-bio/

 

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