Dr. Karen Thames has been sharing these on her Facebook Page, Battleground Diagnosis: The War to Survive Cushing’s Disease.
She has graciously given me permission to share them here and in the CushieWiki and on the Cushing’s Help message boards.
Find these pages here, under the Myths and Facts category.
Thanks, Karen!
Filed under: Cushing's, Myths and Facts | Tagged: Cushing's, Myths and Facts | Leave a comment »
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
Filed under: Cushing, Cushing's, Treatments | Tagged: Blood, cortisol, Cushing Syndrome, Cushing's, depression, diabetes, high blood pressure, hypercortisolism, ketoconazole, liver, radiotherapy, surgery, tumor | Leave a comment »
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.
Filed under: Cushing's | Tagged: Adrenal cortex, adrenocorticotropic hormone–dependent Cushing’s syndrome, Amidate, Cushing's, Etomidate, hypercortisolism, ICE/ENDO 2014, sedative, serum cortisol | Leave a comment »
Who’d have believed it? Today, July 21, 2014 is our 14th birthday!
It’s unbelievable but the idea for Cushing’s Help and Support arrived 14 years ago last night. I was talking with my dear friend Alice, who ran a wonderful menopause site called Power Surge, wondering why there weren’t many support groups online (OR off!) for Cushing’s and I wondered if I could start one myself and we decided that I could.
The first website (http://www.cushings-help.com) first went “live” July 21, 2000 and the message boards September 30, 2000. Hopefully, with these sites, I’m going to make some helpful differences in someone else’s life!
The message boards are very active and we have weekly online text chats, weekly live interviews, local meetings, email newsletters, a clothing exchange, a Cushing’s Awareness Day Forum, podcasts, phone support and much more.
Whenever one of the members of the boards gets into NIH, I try to go to visit them there. Other board members participate in the “Cushie Helper” program where they support others with one-on-one support, doctor/hospital visits, transportation issues and more.
Filed under: Cushing's, Thankfulness | Tagged: Alice, Alice Stamm (Dearest), anniversary, birthday, Cushing's, Cushing's Help, message boards, Power Surge | 2 Comments »
AT ICE/ENDO 2014
CHICAGO – Late-night salivary cortisol exceeded normal limits in 10 women with recurrent Cushing’s disease a mean of 3.5 years after transsphenoidal surgery, but their urinary free cortisol remained in normal limits, according to a retrospective review from the Medical College of Wisconsin, Milwaukee.
That adds strength to the notion that late-night salivary cortisol (LNSC) catches recurrent Cushing’s that’s missed by urinary free cortisol, even though UFC remains a standard screening approach in some places.
The study is tiny and retrospective, but at the joint meeting of the International Congress of Endocrinology and the Endocrine Society, lead investigator Dr. Ty Carroll explained why the findings still matter, and also why two LNSC measurements are better than one.
Filed under: Clinical trials, Cushing's, Meetings and Conferences, pituitary, Rare Diseases | Tagged: Cushing's, Cushing's Disease, Cyclical Cushing's, Dr. Ty Carroll, ICE/ENDO 2014, late-night, late-night salivary cortisol, LNSC, Medical College of Wisconsin, salivary cortisol, study, transsphenoidal, UFC, urinary free cortisol, video | Leave a comment »
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