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

Suspecting Pituitary Disorders: “What’s Next?”

In this “3 in 3” video, Ji Hyun (CJ) Chun, PA-C, BC-ADM, covers 3 types of pituitary disorders and describes useful workups for use by primary care clinicians.

Clinician Reviews’ “3 in 3” video series delivers 3 take-home points in 3 minutes—or less.

View the video here

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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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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