Pituitary ACTH Hypersecretion (Cushing’s Disease) – Pipeline Review, H2 2013

Posted on November 6, 2013 by MaryO

DUBLIN — Research and Markets  (http://www.researchandmarkets.com/research/h78zrm/pituitary_acth) has announced the addition of the “Pituitary ACTH Hypersecretion (Cushing’s Disease) – Pipeline Review, H2 2013” report to their offering.

‘Pituitary ACTH Hypersecretion (Cushing’s Disease) – Pipeline Review, H2 2013’ provides an overview of the indication’s therapeutic pipeline. This report provides information on the therapeutic development for Pituitary ACTH Hypersecretion (Cushing’s Disease), complete with latest updates, and special features on late-stage and discontinued projects. It also reviews key players involved in the therapeutic development for Pituitary ACTH Hypersecretion (Cushing’s Disease).

Scope

– A snapshot of the global therapeutic scenario for Pituitary ACTH Hypersecretion (Cushing’s Disease).

– A review of the Pituitary ACTH Hypersecretion (Cushing’s Disease) products under development by companies and universities/research institutes based on information derived from company and industry-specific sources.

– Coverage of products based on various stages of development ranging from discovery till registration stages.

– A feature on pipeline projects on the basis of monotherapy and combined therapeutics.

– Coverage of the Pituitary ACTH Hypersecretion (Cushing’s Disease) pipeline on the basis of route of administration and molecule type.

– Key discontinued pipeline projects.

– Latest news and deals relating to the products.

Reasons to buy

– Identify and understand important and diverse types of therapeutics under development for Pituitary ACTH Hypersecretion (Cushing’s Disease).

– Identify emerging players with potentially strong product portfolio and design effective counter-strategies to gain competitive advantage.

– Plan mergers and acquisitions effectively by identifying players of the most promising pipeline.

– Devise corrective measures for pipeline projects by understanding Pituitary ACTH Hypersecretion (Cushing’s Disease) pipeline depth and focus of Indication therapeutics.

– Develop and design in-licensing and out-licensing strategies by identifying prospective partners with the most attractive projects to enhance and expand business potential and scope.

– Modify the therapeutic portfolio by identifying discontinued projects and understanding the factors that drove them from pipeline.

Companies Mentioned

Isis Pharmaceuticals, Inc.

Ipsen S.A.

Novartis AG

Corcept Therapeutics Incorporated

HRA Pharma, SA

Cortendo Invest AB

Orphagen Pharmaceuticals, Inc.

For more information visit http://www.researchandmarkets.com/research/h78zrm/pituitary_acth

About Research and Markets

Research and Markets is the world’s leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

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Remaining calm = Reducing illness

Posted on October 9, 2013 by MaryO

Have you ever noticed that when you are “stressed” you can feel either emotionally/physically depleted or energized?  When our body is under stress the brain responds by producing epheniphrine or adrenaline, sending signals to our adrenal glands, increasing the rate at which our heart beats while releasing oxygen to our muscles.  The long term response to this process produces cortisol (aka the stress hormone) facilitating the release of energy throughout our body.  However, when our body isn’t properly balanced these hormones can wreak havoc on our wellness possibly resulting in one of three conditions:  Cushing’s syndrome, Cushing’s disease or Addison’s disease.

adrenal-glandsThe actual Adrenal glands sit physically atop both kidneys, taking on a triangular shape and a roundish rectangular type shape.  These glands are responsible for our sex hormones and cortisol, helping us respond to stress amongst other functions.  When our body is under stress, physically and/or nutritionally, it responds one of two ways:  Produces too much or too little of the cortisol hormone.  Our Adrenal glands also contribute to regulating our blood sugar, blood pressure, salt and water.

Adrenal disorders can cause our body to make too much or not enough of these hormones, bringing about adrenal gland related syndromes and disease.  Cushing’s syndrome results from our body making too much versus Addison’s disease produces too little.

Cushing’s syndrome vs. Cushing’s disease

Glucocorticoids (naturally produced in our body or received through medicine) are groups of corticosteroids (cortisol or dexamethasone) involved in metabolizing our carbohydrate and protein.  When taken synthetically (i.e. treatment of allergies, skin problems, and respiratory problems) or over-produced naturally, the side effects can result in “Cushing’s syndrome”.

Cushing’s syndrome can occur one of two ways:  Endogenous or Exogenous.  Endogenous is caused by the body (usually through tumors).  Exogenous is caused by medication.  In both cases, the body produces too much cortisol.

Symptoms: Severe fatigue/muscle weakness, high blood sugar and high blood pressure, upper body obesity, thin arms/legs, bruising easily

Treatment:  The cure and treatment for Cushing’s disease can come through medicine, surgery, or by lowering the dosage of your current synthetic hormone treatment.  Cushing’s syndrome can be cured.

Cushing’s disease is the most common form of endogenous Cushing’s syndrome and is likely treatable.  Caused by a tumor in the pituitary gland secreting too much Adrenocorticotropic hormone (ACTH), this type of tumor does not spread and can be removed through surgery.

Nutrition:  See a nutritionist or dietician for your condition.  Mostly, avoid excess sodium.  High blood sugar (hyperglycemia) and high blood pressure can easily occur with this condition.  Bone loss density is common with this condition, so be extra aware of your calcium (800 – 1200 mg per day, based upon age) and Vitamin D intake (5mcg from age 0-50, increasing up to 10 mcg 50-71, and 15 mcg after 71).  Eating healthy, balanced and whole food (versus processed) is extremely important.

(Resource:  http://www.aboutcushings.com/understanding-cushings-disease/causes-and-differences.jsp)

Addison’s disease

Opposite from Cushing’s syndrome, Addison’s disease doesn’t make “enough” of the sex hormones and cortisol.  The result of this disease causes our immune system to attack our tissue, damaging our adrenal glands.

Symptoms:  Weight loss, muscle weakness, increasingly worse fatigue, low blood pressure and patchy or dark skin.

Treatment:  If left untreated, the condition can be fatal.  Lifetime hormone treatment is usually required. Addison disease patients should always carry medical/emergency ID on them, listing their medication, dosage and disease

Lab tests can confirm that you have Addison’s disease. If you don’t treat it, it can be fatal. You will need to take hormone pills for the rest of your life. If you have Addison’s disease, you should carry an emergency ID. It should say that you have the disease, list your medicines and say how much you need in an emergency.”

(Ref: http://www.nlm.nih.gov/medlineplus/cushingssyndrome.html, NIH: National Institute of Neurological Disorders and Stroke)                                                                                                                                                                                                                                        Learning how to balance our stress-filled lives is extremely important to our overall health.  Healthy nutrition always contributes benefits to our overall wellness.  We can overwhelm our endocrine system by simply not eating nutritionally.  Understanding that “Food is a drug” is vitally important to how we help our body naturally heal itself.  The above two conditions are the result of our body not handling the stress we are putting it through, causing our body to producing too much or too little of the sex hormones and cortisol.

Unless we first address what we can do naturally through nutrition, the medicine we consume will only do so much in helping our body heal completely.  You simply cannot continue doing the same thing over and over again, expecting the medicine to do all the work.  Some diseases are brought upon us through our environment (emotionally as well as physically) as well as our diet/nutrition.  Reviewing our entire wellness is always wisdom whenever we’re diagnosed with anything.

Certainly listen to your doctor and their advice.  But also ask your doctor to refer you to a nutritionist or clinical/registered dietician for a complete evaluation that includes a review of your nutritional diet/wellness.  Too often we reach for a pill or a procedure to “fix” our health problems, ignoring what we should be doing on our own to help our body heal.  Medical intervention is the result of providing our body with what it cannot produce on its own.  Nutrition should always be the “natural” medicine we take, as well as what we might need through prescribed medication.

Adapted from (Spelling errors corrected) http://hamptonroads.com/2013/10/remaining-calm-reducing-illness

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NIH: An Open-Label Study of The Safety, Pharmacokinetics and Pharmacodynamics of Mifepristone in Children With Refractory Cushing’s Disease

Posted on September 13, 2013 by MaryO

This study is currently recruiting participants.

Summary

Number 13-CH-0170
Sponsoring Institute National Institute of Child Health and Human Development (NICHD)
Recruitment Detail Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 6
Max Age: 17
Referral Letter Required No
Population Exclusion(s) None
Special Instructions Currently Not Provided
Keywords Child;
Cushing Syndrome;
Metabolism;
Mifepristone;
Pharmacokinetic-Pharmacodynamic
Recruitment Keyword(s) None
Condition(s) Cushing’s Syndrome;
Cushing Syndrome
Investigational Drug(s) Mifepristone
Investigational Device(s) None
Intervention(s) Drug: mifepristone
Supporting Site National Institute of Child Health and Human Development

Background:

– There are currently no approved therapies for children with Cushing’s disease who are not cured by surgery alone. A drug called mifepristone has been approved to treat adults with Cushing’s syndrome and elevated blood glucose caused by Cushing’s. The drug is marketed under the name Korlym(Registered Trademark). The study drug may have a different effect on a child’s body than an adult’s, so researchers want to know how much of the drug to give children and what effect it will have. They want to learn if mifepristone improves Cushing’s disease in children as it does in adults. They also want to know about the drug’s side effects in children.

Objectives:

– To study the effect of a medication called mifepristone in children with Cushing’s disease that has not been helped by pituitary surgery.

Eligibility:

– Children ages 6 to 17 with active Cushing’s disease following pituitary surgery and who have a body weight higher than expected for their height and age.

Design:

– Participants will be screened for up to 8 weeks with a physical exam, medical history, and medical tests including blood tests and X-rays.

– Participants will take tablets of the study drug each day for 12 weeks.

– Participants will stay at the clinic for 4 nights at the beginning of the study. They will have three 1-day visits during the study. They will stay at the clinic the last 3 days of the study.

– At these visits, participants will be given several tests. In one test, a small wire is inserted under the skin of the belly and a small monitor is attached taped to the belly. In another, the participant drinks a liquid and blood samples are taken.

– Follow-up visits will occur 4 weeks and 12 weeks after the study ends.

–Back to Top–

Eligibility

INCLUSION CRITERIAPatients who are eligible for enrollment must meet the following eligibility criteria:

– Males and females 6-17 years at informed consent

– Active Cushing’s disease as demonstrated by the following:

–24 hour Urinary Free Cortisol greater than the upper limit of normal for age on two urine collections during screening and

— midnight serum cortisol > 4.4 mcg/dL (mean of two determinations on a single day at 2330 and 2400 during screening)

– Previous trans-sphenoidal surgery (TSS) for ACTH secreting pituitary tumor at least 3 months prior to screening

– Increased body weight defined by BMI Z-score of 1.5 or above

– Able to provide consent/assent

– Able to swallow study drug tablets (not crushed or split)

– Willing to use non-hormonal method of contraception in patients of reproductive potential

– Primary health care provider in home location

EXCLUSION CRITERIA:

– Hypercortisolism not due to Cushing’s disease.

– Type 1 diabetes mellitus

– HbA1c geater than or equal to 9.5% at Screening

– Body weight < 25 kg

– Use of certain medications that are CYP3A substrates with narrow therapeutic ranges, such as simvastatin, lovastatin, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus during the 4 weeks prior to starting study drug. Use of these medications is also prohibited until 2 weeks after end of dosing.

– Use of certain medications that are strong CYP3A inhibitors such as itraconazole, nefazodone, ritonavir, nelfinavir, indinavir, atazanavir, amprenavir, fosamprenavir, boceprevir, clarithromycin, conivaptan, lopinavir, mibefradil, posaconazole, saquinavir, telaprevir, telithromycin, and voriconazole during the 2 weeks prior to starting study drug.

Use of these medications is also prohibited until 2 weeks after end of dosing. Grapefruit and grapefruit juice are prohibited during this time frame.

– Use of certain medications that are strong inducers on CYP3A such as rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine, St. John’s wort during the 2 weeks prior to starting study drug. Use of these medications is also prohibited until 2 weeks after end of dosing.

– Use of medications used to treat hypercortisolism from the duration indicated below prior to Day 1. Use of the medications is also prohibited until after the end of study 4 week follow up visit.

–steroidogenesis inhibitors such as ketoconazole, metyrapone: 4 weeks

–cabergoline, bromocriptine, somatostatin analogs such as octreotide, lanreotide, pasireotide long acting formulations: 8 weeks (immediate release formulations: 2 weeks)

–mitotane: 8 weeks

– Use of systemic glucocorticoid medications beginning 1 month prior to screening or anticipated use of these medications except for the treatment of adrenal insufficiency. Use of glucocorticoid medications is prohibited during the study until after the end of study 4 week study visit.

– Inflammatory, rheumatological, proliferative or other disorder(s) that would be anticipated to worsen with glucocorticoid blockade (e.g. inflammatory bowel disease, rheumatoid arthritis, psoriasis, etc.).

– Uncontrolled hypo- or hyperthyroidism.

– Uncorrected hypokalemia (< 3.5 mEq/L). The screening period may be used to correct hypokalemia prior to starting study drug. Use of potassium and/or mineralocorticoid antagonists is permitted during the study.

– QTc geater than or equal to 450 msec on Screening electrocardiogram

– Unexplained vaginal bleeding in females and/or any history of endometrial pathology.

– Positive pregnancy test in females.

From http://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2013-CH-0170.html

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Differences Between Cushing’s Syndrome and Cushing’s Disease

Posted on August 28, 2013 by MaryO

What’s the difference between Cushing’s Disease and Cushing’s Syndrome?

disease-syndrome

Cushing’s syndrome is a hormonal disorder

Cortisol is a normal hormone produced in the outer portion of the adrenal glands. When functioning normally, cortisol helps the body respond to stress and change. It mobilizes nutrients, modifies the body’s response to inflammation, stimulates the liver to raise blood sugar, and helps control the amount of water in the body. Cortisol production is regulated by the adrenocorticotrophic hormone (ACTH), produced in the pituitary gland. Spontaneous overproduction of cortisol in the adrenals is divided into two groups – those attributed to an excess of ACTH and those that are independent of ACTH.

Cushing’s syndrome is the term used to describe a group of symptoms that occur when a persons’ cortisol levels are too high (known as hypercortisolism) for too long. The majority of people have Cushing’s syndrome because they are regularly taking certain medicine(s) that continually add too much cortisol to the body. Doctors call this an “exogenous” (outside the body) cause of Cushing’s syndrome. Other people have Cushing’s syndrome because something is causing the adrenal gland(s) to overproduce cortisol. Doctors call this an “endogenous” (inside the body) cause of Cushing’s syndrome.

Cushings-causes.png

Cushing’s disease is a form of Cushing’s syndrome

Cushing’s disease is the most common form of endogenous Cushing’s syndrome. It is caused by a tumor in the pituitary gland that secretes excessive amounts of a hormone called Adrenocorticotropic hormone, or ACTH. Fortunately, this type of tumor is typically benign. Unlike a cancerous (malignant) tumor, a benign tumor stays in its original location and will not spread. After you are diagnosed with Cushing’s syndrome, it is important that your doctor continues the diagnostic process to determine the cause of hypercortisolism.

From the message boards It is not only a tumor that causes Cushings Disease—many of us have the rarer form of this rare disease which is Pituitary Hyperplasia. It also causes CD and may be nodular (shown on MRI s a tumor) or dispersed (meaning spread throughout the gland).

How a pituitary tumor causes Cushing’s disease

Pituitary.jpg

ACTH is a hormone produced in your pituitary gland. ACTH travels to your adrenal glands and signals them to produce cortisol.

Pituitary adenomas are benign tumors of the pituitary gland which secrete increased amounts of ACTH, causing excessive cortisol production. Most patients have a single adenoma. First described in 1912 by neurosurgeon Harvey Cushing in his book The Pituitary Body and its Disorders, Cushing’s disease is the most common cause of spontaneous Cushing’s syndrome, accounting for 60 to 70 percent of cases.

If a person has Cushing’s disease, it means that a group of abnormal cells has built up in the pituitary gland to form an ACTH-producing pituitary tumor. These abnormal cells produce ACTH, just as normal pituitary gland cells do—only far too much. The excess ACTH travels to adrenal glands. The adrenal glands are then bombarded with signals to produce more and more cortisol. As a result, the adrenal glands continuously secrete too much cortisol.

Ectopic ACTH Syndrome

Some benign or malignant (cancerous) tumors that arise outside the pituitary can produce ACTH. This condition is known as ectopic ACTH syndrome. Lung tumors cause more than 50 percent of these cases. Other less common types of tumors that can produce ACTH are thymomas, pancreatic islet cell tumors, and medullary carcinomas of the thyroid.

Adrenal Tumors

Adrenal glands.jpg

An abnormality of the adrenal glands such as an adrenal tumor may cause Cushing’s syndrome. Most of these cases involve non-cancerous tumors called adrenal adenomas, which release excess cortisol into the blood.

Adrenocortical carcinomas, or adrenal cancers, are the least common cause of Cushing’s syndrome. Cancer cells secrete excess levels of several adrenal cortical hormones, including cortisol and adrenal androgens. Adrenocortical carcinomas often cause very high hormone levels and rapid onset of symptoms.

Familial Cushing’s syndrome

Most cases of Cushing’s syndrome are not genetic. However, some individuals may develop Cushing’s syndrome due to an inherited tendency to develop tumors of one or more endocrine glands. In Primary Pigmented Micronodular Adrenal Disease, children or young adults develop small cortisol-producing tumors of the adrenal glands. In Multiple Endocrine Neoplasia Type I (MEN I), hormone secreting tumors of the parathyroid glands, pancreas and pituitary occur. Cushing’s syndrome in MEN I may be due to pituitary, ectopic or adrenal tumors.

Risk factors

Obesity, type 2 diabetes, poorly controlled blood glucose (blood sugar levels), and high blood pressure may increase the risk of developing this disorder.

Adapted from http://www.cushiewiki.com/index.php?title=Cushing%27s_Disease_or_Syndrome

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Mortality in Cushing’s syndrome: data from 386 patients from a single tertiary referral center

Posted on August 16, 2013 by MaryO

Source

M Yaneva, Endocrinology, Medical University, Sofia, 1341, Bulgaria.

European Journal of Endocrinology, 08/16/2013  Review Article

Yaneva MK et al. – Data on the incidence, mortality and causes of death in patients with Cushing’s syndrome (CS) are scarce, due to the rarity of CS. The aim of the study was to analyze mortality rates in CS in a large cohort of patients of all etiologies and to determine the cause of death. Patients with CS have increased mortality due to vascular events and infections.

Abstract

OBJECTIVE:

Data on the incidence, mortality and causes of death in patients with Cushing’s syndrome (CS) are scarce, due to the rarity of CS. The aim of the study was to analyze mortality rates in CS in a large cohort of patients of all etiologies and to determine the cause of death.

DESIGN:

This was a retrospective study of patients with CS, treated over a period of 45 years in the main tertiary referral center in Bulgaria.

METHODS:

386 patients with CS of all etiologies were included. The main outcome measures were the standardized mortality ratio (SMR) and the cause of death.

RESULTS:

Mean (± SD) age at diagnosis was 38±13 years; 84% of patients were women; mean follow up was 85 months (range: 0-494 months). The SMR in the CS cohort was 4.05 (95% confidence interval (CI) 2.50-5.80) (p<0.0001). The following subgroups did not have a significantly increased SMR: patients with Cushing’s disease SMR – 1.88 (95%CI 0.69-4.08), adrenal adenomas 1.67 (95%CI 0.20-6.02) and ACTH-independent bilateral adrenal hyperplasia 1.14 (95 %CI 0.21-6.34). Patients with adrenal carcinomas, ectopic CS and those with CS of undetermined etiology had significantly increased SMR: 48.00 (95%CI 30.75-71.42), 13.33 (95%CI 0.00-24.59) and 4.00 (95%CI 0.48-14.45), respectively (p<0.0001). The significant predictors for mortality were active disease at death, age, male sex, etiology of the disease, the overall duration of active disease. The major causes of death were vascular events (40%) -cardiovascular 29% and cerebrovascular 11%, followed by infections (12%).

CONCLUSIONS:

Patients with CS have increased mortality due to vascular events and infections.

Read more at MDLinx

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