Cushing’s Syndrome, Prostate Cancer and Adrenocortical Carcinoma

Posted on March 11, 2013 by MaryO

Orphagen has identified and characterized small molecule antagonists to steroidogenic factor-1 (SF-1). SF-1 binds to and regulates DNA promoter elements in the major transporters and enzymes required for adrenal steroid synthesis. It is also required for development of the adrenal gland. SF-1 antagonists inhibit cortisol secretion in adrenal cells and have potential application in two orphan indications, Cushing’s syndrome and adrenocortical carcinoma. In addition, SF-1 appears to have an important role in the progression of advanced prostate cancer.

 

cushings-adrenocortical-crop

 

Cushing’s syndrome:
An estimated 20,000 people in the US have Cushing’s, with more than 3,000 new cases diagnosed each year. The incidence is similar in Europe. Cushing’s syndrome disproportionately affects females, who make up about 75% of the diagnosed cases. Symptoms of Cushing’s syndrome can include obesity, diabetes, psychiatric disorders, osteoporosis and immune suppression. Cushing’s syndrome is caused by elevated secretion of cortisol from the adrenal gland, in association with pituitary, adrenal or other cancers.

Orphagen has identified small molecule antagonists to SF-1 that have the potential to suppress cortisol levels in all Cushing’s patients without serious side effects.

Adrenocortical carcinoma (ACC):
ACC is a rare malignancy with an extremely poor prognosis (5-year overall survival: 37-47%). Complete surgical resection offers hope for long-term survival but surgery is not an option in up to two-thirds of patients because metastasis has usually occurred by the time of diagnosis.

SF-1 is recognized as a potential mechanism-based therapeutic target for control of ACC and an SF-1 antagonist could be used in the treatment of ACC.

Pediatric ACC:
Pediatric ACC is a very rare but aggressive cancer with a long-term survival rate of about 50%. Approximately 60% of children with adrenocortical tumors are diagnosed before the age of four. The SF-1 gene is amplified and SF-1 protein is overexpressed in the vast majority of childhood adrenocortical tumors strongly implicating SF-1 in pediatric adrenocortical tumorigenesis.

Castration resistant prostate cancer (CRPC):
CRPC is the most common cancer in males. Surgery is not an option if the cancer has spread beyond the prostate gland, at which point patients typically receive hormonal therapy, essentially chemical castration. This course of therapy usually fails within two years, resulting in castration resistant prostate cancer (CRPC). Most patients eventually succumb to CRPC, which is the second leading cause of cancer deaths in men.
SF-1 antagonists may: (1) block the adrenal androgens that circumvent chemical castration, and are a primary cause of CRPC; and (2) inhibit synthesis of androgens within the prostate tumor itself, where SF-1 may control induction of enzymes for de novo androgen synthesis in treatment-resistant cancers.

From http://www.orphagen.com/research_cushings.html

Filed under: adrenal, Cushing's, Rare Diseases | Tagged: , , , , , , , , , , , , , , , , , , , | Leave a comment »

Predictors of Mortality, CVD Risk in Cushing’s Disease ID’d

Posted on February 28, 2013 by MaryO

(HealthDay News) – A number of factors, including the duration of glucocorticoid exposure, older age at diagnosis, and preoperative adrenocorticotropic hormone (ACTH) concentration, are associated with a higher risk of mortality in patients treated for Cushing’s disease (CD), according to research published online Feb. 7 in the Journal of Clinical Endocrinology & Metabolism.

In an effort to identify predictors of mortality, cardiovascular disease, and recurrence with long-term follow-up, Jessica K. Lambert, MD, of the Mount Sinai Medical Center in New York City, and colleagues performed a retrospective chart review of 346 patients with CD who underwent transsphenoidal adenectomy.

The researchers found that the average length of exposure to glucocorticoids was 40 months. The risk of death was higher for those patients who had a longer duration of glucocorticoid exposure, older age at diagnosis, and higher preoperative ACTH concentration. For patients who achieved remission, depressed patients had a higher risk of death. The risk of cardiovascular disease was highest for men, older people, and those with diabetes or depression.

“Our study has identified several predictors of mortality in patients with treated CD, including duration of exposure to excess glucocorticoids, preoperative ACTH concentration, and older age at diagnosis. Depression and male gender predicted mortality among patients who achieved remission,” the authors write. “These data illustrate the importance of early recognition and treatment of CD. Long-term follow-up, with management of persistent comorbidities by an experienced endocrinologist, is needed even after successful treatment of CD.”

Abstract
Full Text (subscription or payment may be required)

Filed under: Cushing's | Tagged: , , , , , , , | Leave a comment »

Early Detection, Treatment Needed To Reduce Risk Of Death, Cardiovascular Disease In Cushing’s Disease Patients

Posted on February 20, 2013 by MaryO

Even after successful treatment, patients with Cushing’s disease who were older when diagnosed or had prolonged exposure to excess cortisol face a greater risk of dying or developing cardiovascular disease, according to a recent study accepted for publication in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM).

Cushing’s disease is a rare condition where the body is exposed to excess cortisol – a stress hormone produced in the adrenal gland – for long periods of time.

Researchers have long known that patients who have Cushing’s disease are at greater risk of developing and dying from cardiovascular disease than the average person. This study examined whether the risk could be eliminated or reduced when the disease is controlled. Researchers found that these risk factors remained long after patients were exposed to excess cortisol.

“The longer patients with Cushing’s disease are exposed to excess cortisol and the older they are when diagnosed, the more likely they are to experience these challenges,” said Eliza B. Geer, MD, of Mount Sinai Medical Center and lead author of the study. “The findings demonstrate just how critical it is for Cushing’s disease to be diagnosed and treated quickly. Patients also need long-term follow-up care to help them achieve good outcomes.”

The study found cured Cushing’s disease patients who had depression when they started to experience symptoms of the disease had an elevated risk of mortality and cardiovascular disease. Men were more at risk than women, a trend that may be explained by a lack of follow-up care, according to the study. In addition, patients who had both Cushing’s syndrome and diabetes were more likely to develop cardiovascular disease.

The study examined one of the largest cohorts of Cushing’s disease patients operated on by a single surgeon. The researchers retrospectively reviewed charts for 346 Cushing’s disease patients who were treated between 1980 and 2011. Researchers estimated the duration of exposure to excess cortisol by calculating how long symptoms lasted before the patient went into remission. The patients who were studied had an average exposure period of 40 months.

The findings may have implications for people who take steroid medications, Geer said. People treated with high doses of steroid medications such as prednisone, hydrocortisone or dexamethasone are exposed to high levels of cortisol and may experience similar conditions as Cushing’s disease patients.

“While steroid medications are useful for treating patients with a variety of conditions, the data suggests health care providers need to be aware that older patients or those who take steroid medications for long periods could be facing higher risk,” Geer said. “These patients should be monitored carefully while more study is done in this area.”

From http://www.medicalnewstoday.com/releases/256284.php

Filed under: Cushing's, Health Care, pituitary | Tagged: , , , , , , , , , | 2 Comments »

Cushing’s on the Dr. Oz Show!

Posted on December 19, 2012 by MaryO

More than 150 staff members will receive the BRAVO! Team Values in Action Award for their collaborative efforts when The Dr. Oz Show came to videotape an inspirational patient story at Ohio State’s Wexner Medical Center.

Lori Burkhoff (Cushings-Help board member cmondwn), a 34-year-old mother from Long Island, NY, who came to Ohio State seeking a cure for Cushing’s disease, will be featured on The Dr. Oz Show along with Neurosurgeon Daniel Prevedello, MD, and Otolaryngology (ENT) Surgeon Ricardo Carrau, MD.

With only four days notice, staff members at Ohio State’s Wexner Medical Center and James Cancer Hospital and Solove Research Institute collaborated to make this visit a success for all — the patient and The Dr. Oz Show video crew.

Along with Collaboration, the Ohio State team also demonstrated the values of Leadership and of Acting with Integrity and Personal Accountability, as they worked to ensure the patient’s safety while accommodating the video crew.

Staff directly involved with this project spanned a broad spectrum of departments, including Admissions, Ambulatory Surgical Unit, Anesthesiology, Housekeeping, Pre-Op, Operating  Room, PACU/Post-Op/ Recovery, In-patient recovery on 7 East James, Marketing and Strategic Communications, Nutrition Services, Patient Experience, Security, and Media Relations.

Each year, our Media Relations team routinely handles hundreds of media escorts and requests for interviews with our expert staff members. But there was nothing routine about this media request. For starters, TV celebrity Dr. Oz would be on site for the entire shoot, starting at 5:30 a.m. Sept. 17, chronicling Burkhoff’s efforts to be cured of a debilitating disease she has battled since she was a teenager. Media Relations staffers escorted the crew throughout the visit.

Cushing’s disease is caused by the pituitary gland releasing too much adrenocorticotropic hormone (ACTH).  People with Cushing’s disease accumulate an excessive amount of ACTH, and this stimulates the production and release of cortisol, which is a stress hormone. If left untreated, Cushing’s disease can cause severe illness and even death.

In Burkhoff’s case, despite three previous surgeries to remove benign tumors on or near her pituitary gland, the disease had returned with a vengeance, causing her to gain weight and putting her at risk for diabetes, stroke, high blood pressure and heart disease, among other complications.

In an effort to raise awareness about the often-misdiagnosed Cushing’s disease, Burkhoff had contacted The Dr. Oz Show.

In the meantime, she learned about the innovative surgical procedure performed at Ohio State. Burkhoff met with Prevedello, the Ohio State neurosurgeon who works in tandem with ENT surgeon Ricardo Carrau, to perform endoscopic endonasal surgery. This is a minimally invasive neurosurgical technique that gives surgeons access to the base of the skull, intracranial cavity and top of the spine by operating via the nose and paranasal sinuses.

Prevedello is one of only a few neurosurgeons worldwide trained in this approach that leaves no facial incisions or scarring, causes less trauma to the brain and nerves, has fewer side effects and results in quicker recovery times.

Burkhoff and the surgeons agreed to be videotaped “documentary style” — meaning that Dr. Oz wanted to capture everything that happened to Burkhoff leading up to and including her surgery. Cameras were rolling at 6 a.m. when Dr. Oz warmly greeted Burkhoff as she walked through the main lobby doors of Rhodes Hall.

Dr. Oz and his video crew remained with Burkhoff as she was admitted to the hospital and during a pre-op discussion with her surgeons in the Ambulatory Surgical Unit. They were with her during the 2.5-hour surgery in University Hospital OR 16, and they followed her into the Post Anesthesia Care Unit recovery area after surgery. By noon, Dr. Oz had departed and the video crew had called it a “wrap.”

During the surgery, Prevedello removed two benign tumors near the pituitary gland. However, Burkhoff did not respond as well as doctors had hoped.

Within a few days, Prevedello and Carrau decided to schedule an unprecedented fifth surgery on Sept. 22.

Even though Dr. Oz couldn’t make it back for the fifth and final surgery, his video crew arrived at 6 a.m. on a football home-game Saturday. The crew interviewed Burkhoff and the surgeons before the four-hour surgery, and the surgeons again after the operation. This surgery proved successful, and Burkhoff continues to improve.

Prevedello and Carrau, members of Ohio State’s Cranial Base Center, will join Burkhoff on the set of The Dr. Oz Show in New York City to share her inspirational story with an international audience during an episode slated to air on Thursday, December 20, 2012.

 

More information at http://oncampus.osu.edu/pdf/Insight10-18-12.pdf

Filed under: Cushing's, pituitary | Tagged: , , , , , , | 1 Comment »

Magic Foundation Cushing’s Conference, 2013

Posted on November 30, 2012 by MaryO

Dates:
Friday, April 19, 2013 – Registration and exhibits-4 PM to 9 PM

Saturday, April 20, 2013 – Educational segments

Sunday, April 21, 2013 – Educational Segments

Monday, April 22, 2013 – Departure or visiting sites of Las Vegas

Registration: $155 for members $190 for non-members (includes 1 yr membership)

Registration fee includes: Thursday exhibits and refreshments, Friday continental breakfast, and lunch and Saturday continental breakfast and lunch. An optional dinner will be held on Friday night for $25.00 per person.

For additional attendees in your family there will be no registration fee but a $75 charge for inclusion of the segments and meals. (optional dinner on Friday night not included in the $75 fee)

Accommodations:
Tuscany Suites & Casino (Just off the Las Vegas Strip)

255 East Flamingo Rd

Las Vegas, NV

Guest room costs:

Friday and Saturday $105 per guestroom, single or double occupancy ($117.60 w/tax)

Sunday thru Thursday $65 per guestroom, single or double occupancy ($72.80 w/tax)

Reservations made after March 20, 2013 at noon will be charged the prevailing room rate if accommodations are available. To book your room you must call Tuscany Room Reservations, 877-887-2261 and ask for MAGIC Foundation group rates. You will be required to provide a major credit card for the first night’s room and tax deposit, which will be charged in order to guarantee accommodations.

Filed under: Cushing's, pituitary | Tagged: , , , , | Leave a comment »

« Previous Page — Next Page »