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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Medical Therapies in Cushing’s Syndrome

Chapter

The Hypothalamic-Pituitary-Adrenal Axis in Health and Disease

pp 165-179

Date: 03 December 2016

Medical Therapies in Cushing’s Syndrome

Abstract

Medical therapy has an important, albeit secondary, role in patients with Cushing’s syndrome. While medications are not currently used as definitive therapy of this condition, they can be very effective in controlling hypercortisolism in patients who fail surgery, those who are not surgical candidates, or those whose tumor location is unknown. Medical therapies can be particularly helpful to control hypercortisolism in patients with Cushing’s disease who underwent radiation therapy and are awaiting its salutary effects.

Currently available treatment options include several steroidogenesis inhibitors (ketoconazole, metyrapone, mitotane, etomidate), which block one or several steps in cortisol synthesis in the adrenal glands, centrally acting agents (cabergoline, pasireotide), which decrease ACTH secretion, and glucocorticoid receptor antagonists, which are represented by a single agent (mifepristone). With the exception of pasireotide and mifepristone, available agents are used “off-label” to manage hypercortisolism. Several other medications are at various stages of development and may offer additional options for the management of this serious condition.

As more potential molecular targets become known and our understanding of the pathogenesis of Cushing’s syndrome improves, it is anticipated that novel, rationally designed medical therapies may emerge. Clinical trials are needed to further investigate the relative risks and benefits of currently available and novel medical therapies and examine the potential role of combination therapy in the management of Cushing’s syndrome.

Keywords

Cabergoline, Etomidate, Ketoconazole, Levoketoconazole, Metyrapone, Mifepristone, Mitotane, Osilodrostat, Pasireotide, Pituitary adenoma

Etomidate drip quickly curbs severe hypercortisolism


AT ICE/ENDO 2014


VITALS  Key clinical point: The anesthetic induction agent etomidate is a potent suppressor of cortisol synthesis in the adrenal cortex at subhypnotic doses, making it a safe and effective agent for management of severe hypercortisolism in Cushing’s syndrome.

Major finding: Continuous infusion of etomidate using a standardized protocol resulted in a reduction in serum cortisol from a mean of 138 mcg/dL to a goal range of 10-20 mcg/dL in an average of 64 hours.

Data source: This was a retrospective case series involving six patients with severe hypercortisolism caused by adrenocorticotropic hormone–dependent Cushing’s syndrome.

Disclosures: The study was carried out with institutional funds. The presenter reported having no financial conflicts.

Continuous intravenous infusion of etomidate safely and swiftly gains control of severe hypercortisolism in patients with adrenocorticotropic hormone–dependent Cushing’s syndrome when conventional presurgical oral treatment is problematic.

“From our cumulative experience, we have now developed a standardized titrated etomidate infusion protocol, which should provide clinicians with a simple, safe, and effective means to lower serum cortisol in patients with severe clinical, metabolic, and neuropsychiatric consequences of prodigious hypercortisolism as a bridge to definitive medical or surgical therapy,” explained Dr. Katarzyna G. Zarnecki at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.

Etomidate (Amidate) is a sedative hypnotic agent with an excellent cardiovascular safety profile. It is widely used in emergency settings, such as reduction of dislocated joints and cardioversion. It suppresses adrenal steroidogenesis by potently inhibiting 11-beta hydroxylase. Fortunately for endocrinologic purposes, etomidate suppresses cortisol synthesis even at subhypnotic doses. In using it off label for management of severe hypercortisolism, it’s essential to keep the drug at subhypnotic doses, meaning not more than 0.3 mg/kg per hour, emphasized Dr. Zarnecki of the University of Wisconsin, Milwaukee.

Dr. Zarnecki and her coworkers utilize as their standard etomidate infusion protocol an initial 5-mg bolus followed by an infusion at 0.02 mg/kg per hour, with dose titration in increments of 0.01-0.02 mg/kg per hour every 4-6 hours based on changes in serum cortisol level. The goal is to bring the cortisol down to a target range of 10-20 mcg/dL.

She presented an illustrative six-patient series in which she and her colleagues turned to continuous infusion of etomidate because conventional oral therapy would have taken too long to rein in the severe hypercortisolism or because medication side effects were intolerable.

Mean baseline pretreatment serum cortisol was 138 mcg/dL, with an adrenocorticotropic hormone level of 419 pg/mL. Five of the six patients reached the goal of 10-20 mcg/dL in an average time of 64 hours. The mean rate of serum cortisol reduction was 1.93 mcg/dL per hour. The average etomidate infusion rate at the time the target level was reached was 0.07 mg/kg per hour, with a maximum rate of 0.1 mg/kg per hour. Monitoring via the Richmond Agitation Sedation Scale confirmed that none of the patients experienced sedative effects.

In the sole patient who didn’t reach goal, etomidate therapy was suspended because the patient entered palliative care because of extensive tumor progression.

Dr. Zarnecki reported having no financial conflicts of interest.

From Clinical Endocrinology News

Cushing’s Disease – Rare Disease Quick Facts

cushings-diagnosis

 

 

Cushing’s disease is a rare condition due to excess cortisol levels that result from a pituitary tumor secreting adrenocorticotropic hormone (ACTH), which stimulates cortisol secretion.  Cushing’s disease should not be confused with Cushing’s syndrome which is increased cortisol levels but that increase can be due to any number of factors. However, Cushing’s disease is the most common form of Cushing’s syndrome.

Symptoms

The symptoms related to Cushing’s disease and Cushing’s syndrome are the same, since both are related to an excess of cortisol. Also, symptoms vary extensively among patients and that, with the inherent fluctuation in hormone levels make it difficult to diagnosis both conditions.

Changes in physical characteristics of the body

  • Fullness and rounding of the face
  • Added fat on back of neck (so-called “buffalo hump”)
  • Easy bruising
  • Purplish stretch marks on the abdomen (abdominal striae)
  • Excessive weight gain, especially in abdominal region
  • Red cheeks
  • Excess hair growth on the face, neck, chest, abdomen and thighs

Changes in physiology/psychology

  • Generalized weakness and fatigue
  • Menstrual disorder
  • Decreased fertility and/or sex drive
  • High blood pressure that is often difficult to treat
  • Diabetes mellitus
  • Mood and behavior disorders

Diagnosis

The early stages of Cushing’s disease may be difficult to recognize. However, if it is suspected, diagnosis is generally a 2 stage process. First to determine if cortisol levels are high, and if so, why they are high.

Tests to confirm high cortisol levels:

  • 24-hour urine cortisol
  • Dexamethasone suppression test (low dose)

Tests to determine cause:

  • Blood ACTH level
  • Brain MRI
  • Corticotropin-releasing hormone test
  • Dexamethasone suppression test (high dose)
  • Petrosal sinus sampling

Treatment

Surgery

  • Most patients with Cushing’s disease undergo surgery to remove the pituitary adenoma offers.
  • If the tumor is isolated to the pituitary, cure rates of 80-85% are common.
  • If the tumor has spread to nearby organs, cure rates of 50-55% are common.

Medicine (approved orphan drugs)

Signifor (pasireotide)

  • Approved for patients with Cushing’s disease for whom pituitary is not an option or surgery has been ineffective.
  • Signifor is a somatostatin receptor agonist that leads to inhibition of ACTY secretion (and subsequently decreased cortisol levels).

Korlym (mifepristone)

  • Approved for patients with Cushing’s syndrome who have type 2 diabetes or glucose intolerance and have failed surgery (or not candidates for surgery).
  • Korlym is a glucocorticoid receptor antagonist which in turn blocks the effects of the high levels of cortisol in the body. Korlym is used to treat high glucose levels due to elevated cortisol.

Medicines used but not indicated for Cushing’s disease include

Mitoden

ketoconazole

Metyrapone

Etomidate

Radiation

  • Radiation therapy may be used in some patients and can be very effective in controlling the growth of these tumors.

Prognosis

In most cases, treatment can cure Cushing’s disease. If not treated properly, the chronic hypercortisolism can lead to excess morbidity and mortality due to increased cardiovascular and other risk factors.

For more information

National Library of Medicine, National Institute of Health

Cushing’s Disease Information (provided by Novartis Pharmaceuticals)

 

Images courtesy of the open access journal Orhanet Journal for Rare Diseases.  Castinetti et al. Orphanet J Rare Dis. 2012 7:41   doi:10.1186/1750-1172-7-41

– See more at: http://www.raredr.com/front-page-medicine/articles/cushings-disease-rare-disease-quick-facts-0

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