What's New?

December 1, 2004
To read the archives of past newsletters, on the Internet, please click here.

In This Issue: Happenings Site News Meetings Chat Info

Young Sam has debuted on the Discovery Health show, "Mystery Diagnosis". There are several future airings...
DHEA Replacement May Be Beneficial for Hypoadrenal Women
Hormone Offsets Harmful Effects of Aging
Scientists Generate Human Islet Precursor Cells In Culture From Cadaveric Insulin-Producing Cells
A Study to Assess SOM230 in Patients with Pituitary Cushing’s Disease
Upcoming Meetings in California, Massachusetts and Florida; Local Meetings
Four new bios, one updated bio.
Read all about them below.


Next Online Newsletter will be Wednesday, December 8
read archived issues here »
News!
Discovery Health aired Sam's show, "Mystery Diagnosis", Monday, November 15, 10PM EST. Upcoming viewings will be 12/20, 12/23, 1/10/05, 1/13/05, 1/16/05. This show was be the first in a series called Diseases Doctors Miss. Every year, millions of Americans fall prey to ailments that go undiagnosed or misdiagnosed. Medical professionals struggle to understand their baffling conditions. More info here »

http://www.medscape.com/viewarticle/481406
DHEA Replacement May Be Beneficial for Hypoadrenal Women

Yael Waknine

Dehydroepiandrosterone (DHEA) replacement therapy improves general health perception, arousal, and learning efficiency in hypoadrenal women, according to the results of a randomized, double-blind, placebo-controlled, crossover study presented at the 86th annual meeting of The Endocrine Society in New Orleans, Louisiana.

The study investigated the possibility that 50 mg daily of DHEA may improve the quality of life in hypoadrenal women taking glucocorticoid and mineralocorticoid replacement.

"Rather than looking at people who’ve got low DHEA levels for replacement, we actually chose hypoadrenal women — women who have Addison’s disease or who have had their [adrenal] glands taken out — who do not produce DHEA," Ketan K. Dhatariya, MD, from the Mayo Clinic and Foundation in Rochester, Minnesota, and lead author of the study, told Medscape. "So results are...actually due to DHEA and not to any endogenous hormones [the women] may have."

The investigators enrolled 33 hypoadrenal women aged 21 to 80 years. The women were treated with 50 mg of DHEA or placebo daily for 12 weeks followed by a two-week washout period between phases.

General health perception was measured using the Memory Functioning, Changes in Sexual Functioning, and Health Status questionnaires, as well as the Beck Depression Inventory. Women receiving DHEA showed improvement in health perception compared with those receiving placebo (-0.19 ± 0.83 vs. 0.66 ± 0.92; P = .03), as well as significantly higher arousal scores (8.5 ± 1.98 vs. 7.67 ± 2.19; P = .02).

Likewise, Auditory Verbal Learning Test scores showed significant improvement after the DHEA phase (54.87 ± 10.23 vs. 51.42 ± 9.39; 95% confidence interval, 0.63 - 6.21; P = .03).

"In this study we measured a huge number of psychological variables, most of [the results] being...negative. However, there were three positives; [subjects] showed an increase in sexual arousal scores,...an increase in learning efficiency,...and an increase in general health perception when taking DHEA as compared with placebo," Dr. Dhatariya noted.

"Our conclusions were that while this was a broadly negative study, [DHEA] did improve scores in those three areas," Dr. Dhatariya said. "A trial of 50 mg DHEA daily would be warranted in those women who have got adequate glucocorticoid and mineralocorticoid replacement yet feel subjectively that they have a lower quality of life."

This study was supported by the National Institutes of Health.

ENDO 2004: Abstract P2-572. Presented June 17, 2004.

Reviewed by Gary D. Vogin, MD

http://www.ivanhoe.com/channels/p_channelstory.cfm?storyid=9900

Hormone Offsets Harmful Effects of Aging

(Ivanhoe Newswire) -- Researchers at Washington University School of Medicine in St. Louis have found the hormone dehydroepiandrosterone (DHEA) may be able to offset the increase in abdominal fat and accompanying increased risk for diabetes that often occur with advancing age.

The study authors explain levels of DHEA peak at about age 20 and then gradually decline. They say by the time we are 70, we have only about 20 percent of the peak amount circulating in the body, which has been associated with the harmful effects of aging.

Dennis T. Villareal, M.D., and John O. Holloszy, M.D., set out to examine whether complications of aging could be reversed if DHEA levels in elderly people were returned to the levels of their youth. The study included 56 people with an average age of 71. For six months, half of the group was randomly assigned to receive a placebo while the other half received 50 milligrams of DHEA daily.

Using MRI measurements, the researchers found that DHEA supplementation resulted in a decrease in abdominal fat of 10.2 percent in women and 7.4 percent in men. It also resulted in a 6-percent decrease in fat below the skin surface for men and women.

"Among the different fat stores, visceral [abdominal] fat is specifically considered potent and metabolically active because its blood drains directly to the liver," the authors say. "Fatty acids from visceral fat get deposited in the liver and other organs and then mediate the decrease in insulin action that leads to an increased risk for diabetes."

In addition, patients receiving DHEA showed an improvement in insulin action. This shows a protective effect of DHEA against insulin resistance caused by a high-fat diet and the natural decrease in insulin responsiveness that occurs with older age, the study authors say.

Dr. Villareal and Dr. Holloszy are now recruiting people for a larger study on the effects of one year of DHEA replacement.

SOURCE: The Journal of the American Medical Association, 2004;292:2243-2248



U.S. Department of Health and Human Services

NATIONAL INSTITUTES OF HEALTH

NIH News

National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK)
http://www.niddk.nih.gov/

EMBARGOED FOR RELEASE
Thursday, November 25, 2004
2:00 p.m. ET

CONTACT:
Marcia Vital
301-496-3583

SCIENTISTS GENERATE HUMAN ISLET PRECURSOR CELLS IN CULTURE FROM CADAVERIC INSULIN-PRODUCING CELLS

Scientists at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), one of the National Institutes of Health (NIH), have induced human insulin-producing cells of the pancreas to revert to islet precursor cells. These precursor cells are capable of expansion and appear to naturally and efficiently differentiate into clusters of islet-like cells. This work may help to clarify the natural lifecycle of the beta cell and may eventually have applications for diabetes treatment. The study appears on-line today in "Science" Express, the rapid publication web site of the journal "Science".

Insulin-producing beta cells exist in spherical clusters, called islets, in the pancreas. Research shows that beta cells are born, die, and are replaced by other beta cells throughout a person's lifetime, but little is known about the process. When the body cannot produce or replace beta cells, insulin levels fall causing blood glucose levels to rise and diabetes results. This study's findings may eventually have implications for islet transplantation, an experimental treatment for type 1 diabetes.

"This is a step forward in the field, but we're still a long way from using this knowledge to develop a therapy for diabetes," says lead author, Marvin C. Gershengorn, M.D., Scientific Director of NIDDK's Division of Intramural Research and Chief of the institute's Clinical Endocrinology Branch. "For one thing these differentiated cells do not function as well as the original cells. They don't produce as much insulin and they are not as adaptable to changes in the environment. For another thing, we grew these cells in a culture that is not optimal for use in humans, so we are not ready to transplant these cells into people. Still, I am encouraged."

The researchers removed islets from human cadaver pancreata, as is done before islet transplantation, and exposed these islets to a medium containing fetal bovine serum. Over 17 days the cells in the clusters migrated out until the original islets were depleted. These migrating islet cells, identified as insulin-expressing cells, then transformed into more primitive precursor cells that do not produce insulin.

These new cells, called human islet-derived precursor cells (hIPCs), reproduce easily. The researchers observed that the hIPCs showed substantial proliferative potential, doubling in number about every 60 hours, and by 90 days had expanded by almost a billion fold. Not stem cells, these precursor cells are transitional cells since they originated from insulin-producing islets. The authors note, however, that this finding does not preclude the possible existence of islet stem cells, as yet undiscovered.

"We knew that islets regenerate," says Gershengorn. "When old islets die out, the pancreas produces new ones to take their place. So, we thought, there must be cells within the pancreas that can reproduce and efficiently differentiate into hormone-producing cells or even intact islets. The challenge was to identify them and make them work."

After isolating significant numbers of hIPCs and showing that they are highly proliferative, the researchers wanted to see if they could reverse the process and induce the new cells to become insulin-producing again. In the second stage of their study, the researchers exposed cultures of hIPCs to a serum-free medium. They saw a highly efficient, gradual transition from precursor hIPCs to epithelial islet-like cell aggregates over a period of several weeks. The cell aggregates produced insulin and other hormones, but at much lower levels than that of human islets - about 0.02 percent of the level of insulin produced by healthy islets. Still, the islet-like cells did show many of the characteristics of the original beta cells. "It appears, therefore, that hIPCs are pre-determined to transition back into hormone-producing cells under minimal conditions in culture," added Gershengorn.

One of NIDDK's goals for long-term diabetes research is to better understand the beta cell and how it regenerates. These findings may eventually have implications for diabetes treatments, including islet transplantation. Islet transplantation involves the infusion of islets derived from donor pancreata into a person with complicated type 1 diabetes. The hope is that some of the transplanted cells will survive in the pancreas and continue producing insulin. A major obstacle to the wider use of islet transplantation as a treatment for type 1 diabetes is the small number of donor pancreata that become available for use each year and the large number of islets needed for transplantation. The NIDDK is focusing its research on understanding the beta cell and its regeneration and on efforts to develop alternative sources of beta cells.

The researchers hope that future studies will corroborate their findings and address some of the unanswered questions. For example, the researchers plan to conduct studies to try to define the optimal environmental conditions to grow precursor cells and to stimulate them to differentiate into hormone-producing cells. Their goal is to design a cellular environment as close as possible to the natural environment of a healthy human pancreas. Another challenge is to develop a culture medium that does not rely on animal serum, so cells grown in the lab can be transplanted back into people with a minimum risk of side effects.

More information on islet transplantation can be found on the NIDDK web site:
http://diabetes.niddk.nih.gov/dm/pubs/pancreaticislet/

Accredited media can access the journal article on the "Eurekalert!" web site:
http://www.eurekalert.org/


This NIH News Release is available online at:
http://www.nih.gov/news/pr/nov2004/niddk-25.htm



A Study to Assess SOM230 in Patients with Pituitary Cushing’s Disease

This study is currently recruiting patients.

Sponsored by: Novartis Pharmaceuticals
Information provided by: Novartis Pharmaceuticals

Purpose

The study treatment period is 15 days in length and includes patients with pituitary Cushing’s disease who are candidates for surgical intervention as well as and patients who have recurrent Cushing’s post operatively.
Condition Treatment or Intervention Phase
Cushing's Syndrome
 
 Drug: SOM230 s.c.
 
Phase II
 

MedlinePlus related topics:  Adrenal Gland Disorders
 

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study

Official Title: A Multicenter, Open Label Study to Assess the Safety and Efficacy of 600 µg SOM230, Administered Subcutaneously, b.i.d. in patients with Cushing’s disease

Further Study Details: 

Expected Total Enrollment:  26

Study start: April 2004
 

Eligibility

Ages Eligible for Study:  18 Years   -   80 Years,  Genders Eligible for Study:  Both
Criteria
Inclusion Criteria:
  • Patients with pituitary Cushing’s disease within the two months prior to study entry
  • Patients for whom written informed consent to participate in the study has been obtained
  • Female patients of child bearing potential who have not undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation must agree to use barrier contraception throughout the course of the study, and for one month after the study has ended

Exclusion Criteria:

  • Female patients who are pregnant or lactating
  • Patients who have been previously treated with certain medications may be required to be without certain medications prior to entering the study
  • Poorly controlled diabetes mellitus as indicated by the presence of ketoacidosis or HgbA1C > 10
  • Patients who have congestive heart failure, unstable angina, cardiac arrhythmia or history of acute MI less than one year prior to the study entry or clinically significant impairment in cardiovascular function (e.g. blood pressure of 190/100mmHg or greater)
  • Patients with chronic liver disease
  • Patients with clotting disorders or abnormal blood counts
  • History of immuno-compromise, including a positive HIV test result
  • Patients with active gall bladder disease
  • Patients who have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
  • Patients with active malignant disease (with the exception of basal cell carcinoma or carcinoma in situ of the cervix)

Location and Contact Information

Jesse Lee      862-778-2793    jesse.lee@pharma.novartis.com

California
      Cedars-Sinai Pituitary Center, Los Angeles,  California,  90048,  United States; Not yet recruiting
Shlomo Melmed, MD  310-423-4691 
Shlomo Melmed, MD,  Principal Investigator


Massachusetts
      Massachusetts General Hospital NE Unit, Boston,  Massachusetts,  02114,  United States; Not yet recruiting

Beverly Biller, MD  617-726-3870 
Beverly Biller, MD,  Principal Investigator


Pennsylvania
      University of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States; Not yet recruiting

Peter Snyder, MD  215-898-0208 
Peter Snyder, MD,  Principal Investigator


France
      Service des Maladies, Paris,  75014,  France; Recruiting

Jerome Bertherat, MD  33 (0) 1 58411895 
Jerome Bertherat, MD, PhD,  Principal Investigator


Italy
      Clinical di Endocrinologia, Ancona,  Italy; Recruiting

Marco Boscaro, MD  39 071 5964740 
Marco Boscaro, MD,  Principal Investigator


United Kingdom
      Sir George E.Clark Metabolic Unit-Royal Victoria Hospital, Belfast,  United Kingdom; Recruiting

Brew Atkinson, MD   Ab.atkinson@royalhospitals.n-i.nhs.uk 
Brew Atkinson, MD,  Principal Investigator

More Information

Study ID Numbers:  CSOM230B2208
Record last reviewed:  July 2004
Record first received:  July 30, 2004
ClinicalTrials.gov Identifier:  NCT00088608
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-11-17

Trial Information

Summary: Cushing's Disease Study 2208

Novartis is conducting a study to assess the effectiveness and tolerability of multiple doses of a study drug in patients with Cushing’s disease.

Patients with a confirmed diagnosis of Cushing’s disease may be eligible for this study. Patients will self-administer the study drug via injections twice daily for 15 days. If after 15 days the investigator finds the treatment is providing benefit to the patients, they will be allowed to continue therapy. Patients may chose to stop therapy at any time.

Patients must meet all of the following criteria:

  • Male or female patients 18 years or older
  • Patients with Cushing’s disease which has been confirmed by a Doctor’s diagnosis and lab test results
  • Ability to complete at least 15 days of study drug treatment
  • Female patients must not be pregnant and must agree to use acceptable forms of birth control throughout the course of the study, and for one month after the study has ended

Patients will be excluded from the study for any of the following reasons:

  • Have Cushing’s syndrome due to ectopic ACTH secretion
  • Patients with hypercortisolism secondary to adrenal tumors or Nodular ( primary) bilateral adrenal hyperplasia
  • Patients who have a known inherited syndrome as the cause for hormone over secretion (i.e. Carney Complex, McCune-Albright syndrome, MEN-1)
  • Patient with a diagnosis of glucocorticoid-remedial aldosteronism (GRA)
  • Patients who have thyroid malfunction
  • Patients with the presence of active or suspected, acute or chronic, uncontrolled infection
  • Patients who have undergone major surgery one month before starting the study
  • Poorly controlled diabetes
  • Patients who have cardiovascular problems (i.e. congestive heart failure, unstable angina, etc.),
  • Patients with liver disease
  • History of immuno-compromise, including a positive HIV test result.
  • Patients with active gall bladder disease
  • Patients with active malignant disease (with the exception of basal cell carcinoma)

For additional information about this trial click here.

Contact:
Helen Peachey, Study Coordinator
U Penn
778 Clinical Research Building
415 Curie Boulevard
Philadelphia, PA 19104-6149

Telephone: 215-898-5664
Fax: 215-614-0418
Email: peacheyh@mail.med.upenn.edu

 

If you would like to learn more about participating in this study, please send an e-mail message using the form below.

 

Name:
Address:
City:
State:
Zip:
Phone:
Email address:
Message:


 

Please note: A number of commercial online services display an error message after you click on Send. Please be assured that your message has been received.

This site is run by CenterWatch, a publishing company that focuses on the clinical trials industry. The information provided in this service is designed to help patients find clinical trials that may be of interest to them, and to help patients contact the centers conducting the research. CenterWatch is neither promoting this research nor involved in conducting any of these trials.



We welcome your articles, letters to the editor, bios and Cushing's information. Submit a Story or Article to either the snailmail CUSH Newsletter or to an upcoming email newsletter at
http://www.cushings-help.com/newsletter_story.htm

Newest Bios:
To add or edit your bio, please click here.
Bonnietta Bonnietta has been diagnosed and is now awaiting treatment Surrey, England
Janice E Janice (pronounced JaNeece) is not yet diagnosed Broadway, N.C.
Kim V Kim had pituitary surgery at NIH and is now considering a BLA Hot Springs, Arkansas
Samara Samara will be having pit surgery on December 7th, 2004  
Sandie R Sandie has updated her bio and added pictures Devon, England


If you've been diagnosed with Cushing's, please participate in the Cushing's Register »

The information you provide will be used to create a register and will be shared with the medical world. It would not be used for other purposes without your expressed permission. Note: This information will not be sold or shared with other companies.

Lynne Clemens, Secretary of CUSH Org is be the person responsible for the creation of this register. If you have any questions you may contact her at lynnecush@comcast.net. You do not have to be a member of CUSH to fill out this questionnaire, as long as you are a Cushing’s patient. We do not believe that the world has an accurate accounting of Cushing’s patients. The only way to authenticate accuracy is with actual numbers. Your help will be appreciated. Thank you."

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Upcoming Conventions, Meetings and Seminars:
December 4, 2004, UCLA Pituitary and Neuroendocrine Program and Harbor-UCLA Pituitary Center present a Second California Pituitary Conference in Beverly Hills, CA. More info and registration here » December 4, 2004 (possibly to be rescheduled for December 18), Massachusetts, local meeting. Malden (near Boston), MA, a get-together to view the Discovery Health Channel show on Sam. More info and registration here »

January 28, 2005, Pituitary Update Conference For Patients And Physicians. More info here.

June 4-7, 2005, ENDO 2005, San Diego. Mainly for physicians, but patients may attend. More info here.

More upcoming local meetings are listed here »

Sign up for notification of local meetings. You need not be a CUSH member to participate.

Online Chats:
Please join us in the Chat Room TONIGHT at 9 PM Eastern.

The new chatroom is available through http://www.cushings-help.com/chatroom.htm. Since this is our own room, you won't need to go into another area after first logging in. You'll be right there!

The very first time you go in, you will have to register for this chat. Although you may use your user name and password from the message boards, you will still need to register those before being allowed into the room.

This room is always open, and has convenient links so that you can get needed information while you're chatting.

I hope to see you tonight!


~~~~~~~~~~~

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