Thanks to Those Who Have Bought Bravelets!

Posted on October 13, 2014 by MaryO

I was very surprised this week to get a check from Bravelets – I only wish I knew who to thank for supporting Cushing’s Help in this way.

They’re running a sale today.  Only a few hours left to get 10% OFF with our Columbus Day Sale!  Support Cushing’s Help and discover savings with coupon code COLUMBUS14.

All items come in yellow, dark or light blue although only yellow are shown in the image below.

Thanks for your support!

bravelets

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Mutation of ARMC5 gene characterized as the cause of meningeal tumour growth

Posted on October 13, 2014 by MaryO

Scientists at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have published their findings that mutations in a gene known as “ARMC5” promote the growth of benign tumours in the adrenal glands and on the meninges: ARMC5 appears to belong to the group of so-called tumour suppressor genes. It is the first time in years that scientists have characterized such a gene.

The ARMC5 gene was discovered by independent workgroups studying – so-called adrenal adenomas – in connection with Cushing’s syndrome. In this disease, the body produces too much of the . Now, for the first time, a mutation of ARMC5 has been characterized as the cause behind the growth of meningeal tumours. The results on this tumour syndrome, obtained by the group of Dr. Patrick May and PD. Dr. Jochen Schneider together with colleagues from Charité Berlin (Dr. Ulf Elbelt) and the Universities of Würzburg (Prof. Dr. Bruno Allolio) and Cologne (Dr. Michael Kloth), have been published recently in the Journal of Clinical Endocrinology Metabolism.

Cortisol is an important hormone. It influences many metabolic pathways in the body and has a suppressing effect on the immune system. Accordingly, it is commonly employed as an anti-inflammatory medication. Prolonged, elevated levels of cortisol in the body can lead to obesity, muscular dystrophy, depression and other symptoms. To maintain the correct concentration in the blood, the body has a refined regulation system: Certain areas of the brain produce the hormone corticotropin as a stimulator of cortisol release; the actual formation of cortisol takes place in the . As the concentration of cortisol in the blood rises, the brain reduces the production of corticotropin.

In search of the causes of Cushing’s syndrome, scientists recently encountered certain genetic causes of benign tumours of the adrenal cortex. Growth of these adrenal cortex adenomas is based on a combination of hereditary and spontaneous mutations: It affects people in whom one of two “alternative copies” – one of the so-called alleles – of the ARMC5 gene is mutated from birth. If the second allele of ARMC5 later also undergoes a spontaneous mutation in the adrenal cortex, then the gene no longer functions. “What is interesting is that the failure of ARMC5 has no direct influence on cortisol production. However, because the tumour cells multiply faster than other body cells, and the number of cells in the tumour increases, the blood cortisol level rises in the course of the disease”, says Dr Schneider. Then, the level in the body rises and ultimately results in the onset of Cushing’s syndrome.

When other scientific workgroups discovered that further benign tumours – in this case meningeal tumours – occur more often in ARMC5-Cushing families, the group of Patrick May and Jochen Schneider sequenced the ARMC5 gene and studied it using bioinformatic techniques. “We demonstrated for the first time, in a patient with an adrenal cortex tumour and simultaneously a meningeal tumour, that somatic, that is non-hereditary, ARMC5 mutations are present in both tumours. This observation suggests that ARMC5 is a true tumour-suppressor gene.”

It must now be explored, Schneider continues, to what extent patients with adrenal cortex tumours ought to be screened for simultaneous presence of meningioma, and in which other types of tumour ARMC5 mutations are responsible for tumour growth: “Building upon that, we can learn whether the gene and the metabolic pathways it influences offer new approaches for treating the tumour syndrome.”

Explore further: Are you carrying adrenal Cushing’s syndrome without knowing it?

More information: “Molecular and Clinical Evidence for an ARMC5 Tumor Syndrome: Concurrent Inactivating Germline and Somatic Mutations are Associated with both Primary Macronodular Adrenal Hyperplasia and Meningioma.” Journal of Clinical Endocrinology Metabolism, October 2014. DOI: 10.1210/jc.2014-2648

Journal reference: Journal of Clinical Endocrinology & Metabolism search and more info website

Provided by University of Luxembourg search and more info

From http://medicalxpress.com/news/2014-10-mutation-armc5-gene-characterized-meningeal.html

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Brains in jars at the Cushing Center in the Yale Medical Library

Posted on October 7, 2014 by MaryO

harvey-cushing-memorial

Sitting quietly in jars in a custom-built room at Yale’s medical library are 550 human brains. The collection once belonged to pioneering neurosurgeon Harvey Cushing, who preserved the brains from 1903 to 1932 as part of his tumor registry. When Cushing died in 1939, his undergraduate alma mater Yale inherited the brains.

Cushing was among a handful of doctors operating on the brain during the early 20th century. At the time, about a third of patients who underwent brain tumor surgery did not survive the operation. Cushing introduced practices that dramatically lowered the mortality rate, such as monitoring blood pressure during surgery and operating with a local anesthesic instead of ether. He was also the first to use x-rays to diagnose brain tumors.

 

Read the entire article here: Brains in jars at the Cushing Center in the Yale Medical Library.

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EU Looks to Okay Ketoconazole for Use in Cushing’s Syndrome

Posted on September 27, 2014 by MaryO

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended granting a marketing authorization for ketoconazole (Ketoconazole HRA; Laboratoire HRA Pharma) for the treatment of Cushing’s syndrome, a rare hormonal disorder sometimes called hypercortisolism.

Cushing’s syndrome is characterized by an excess of the hormone cortisol in the blood, which may be caused by a tumor. Treatment options currently available in the European Union include surgery to remove the tumor responsible for the high cortisol levels and radiotherapy, as well as several medicines that reduce the production of cortisol.

But pharmacological options remain very limited, and there is an unmet medical need for additional treatments, especially when surgery fails or for patients who cannot undergo surgery or take other medications. For this reason, the EMA’s CHMP evaluated the medicine under expedited review.

The opinion adopted by the CHMP at its September 2014 meeting is an intermediary step on Ketoconazole HRA’s path to patient access.

The CHMP opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorization. Once a marketing authorization has been granted, decisions about price and reimbursement will then take place at the level of each member state considering the potential role/use of this medicine in the context of the national health system of that country.

The recommendation is that Ketoconazole HRA is to be prescribed only by physicians specialized in treating Cushing’s syndrome, as the dosing needs to be individualized for each patient.

This is because oral ketoconazole was previously suspended in the European Union for the indication it was first approved for, fungal infections, due to risk for liver injury. The US Food and Drug Administration (FDA) also decreed, at the same time, that doctors should no longer prescribe ketoconazole tablets as a first-line therapy for any fungal infection, for the same reason.

Information will be sent to healthcare professionals to allow them to advise patients and prescribe the medicine safely and effectively.

A Medicine Used Off-Label for More than 30 Years

Doctors have used ketoconazole to treat Cushing’s syndrome for more than 30 years, although it has never been authorized for this indication in the European Union. The drug is also frequently used off-label in the United States and elsewhere for this purpose.

The CHMP’s recommendation builds on information from published literature and documented off-label use in clinical practice.

At the time of the suspension of ketoconazole for fungal infections, healthcare professionals and patients were concerned that ketoconazole would no longer be available for patients with Cushing’s syndrome.

The CHMP therefore reviewed Ketoconazole HRA through accelerated assessment to facilitate patients’ access to a fully authorized medicine as soon as possible with evidence-based information for patients and doctors.

When assessing Ketoconazole HRA for the treatment of Cushing’s syndrome, the CHMP considered that “in this rare and potentially life-threatening condition, the medicine’s benefits are greater than its risks, which can be manageable in clinical practice by specific measures mitigating the risk of liver toxicity, including close monitoring of the patients’ liver function.”

In 2012, it was estimated that the disease affected approximately 46,000 people in the European Union. Cushing’s syndrome is a long-lasting condition that can be life-threatening because of its complications, including diabetes, high blood pressure, and depression.

From http://www.medscape.com/viewarticle/832399?src=rss

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Etomidate drip quickly curbs severe hypercortisolism

Posted on August 1, 2014 by MaryO

By: BRUCE JANCIN, Clinical Endocrinology News Digital Network

JULY 31, 2014

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

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