What's New?

The current issue of "The Pituitary Connection" - the Australian Pituitary Foundation's newsletter (Issue 30 - December 2004) focuses on Latest Acromegaly Treatments, and includes information about how patients can find out more about their medications.

The newsletter is now available: Word version (132KB): http://www.pituitary.asn.au/newsletter/NL30Nov04Acro.doc
Adobe PDF version (386KB, Booklet Spread - 12 printed in 6 pages):

http://www.pituitary.asn.au/newsletter/NL30Nov04AcroBooklet.pdf

If you are unable to open the files from the APF websites above, then you can request that the newsletter files be sent to you as attachments.

To open PDF files, you need to download Adobe Acrobat Reader software to your computer, or get an up-to-date version of it. If you do not already have this, you can go to the following address to download their free software; http://www.adobe.com/products/acrobat/readstep2.html
Kind Regards

Kathryn
____________________
Kathryn Skelsey BAppSc

Information Research / Newsletter Editor
Australian Pituitary Foundation Ltd
PO Box 327
ALLAWAH NSW 2218
Australia
Ph: 61-2-9580-6050
Fx: 61-2-9585-2642
Mb: 0408-912-248

www.pituitary.asn.au

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http://story.news.yahoo.com/news?tmpl=story&cid=594&e=7&u=/nm/20041129/hl_nm/diabetes_testosterone_dc

Low Testosterone Seen Common in Diabetic Men

Mon Nov 29, 4:27 PM ET Health - Reuters

NEW YORK (Reuters Health) - About one third of men with type 2 diabetes show low levels of testosterone, and this is seems to be related to abnormal function of the pituitary gland -- the master regulator of hormone production -- according to a new study.

Although lower total testosterone levels have been reported in type 2 diabetics, the underlying cause has not been known, Dr. Paresh Dandona of the State University of New York at Buffalo and colleagues note in the Journal of Clinical Endocrinology and Metabolism.

Specifically, it has been clear whether the testes were somehow defective and unable to produce sufficient testosterone, or whether the underlying problem was a low level of the pituitary hormones that trigger testosterone secretion.

To investigate, the researchers studied 103 diabetic men who ranged in age from 28 to 80 years, and who had had type 2 diabetes for an average of 7.7 years.

A total of 33 percent of patients were found to have low testosterone. The team found that levels of two pituitary hormones -- luteinizing hormone and follicle stimulating hormone -- were also significantly lower in these men than in subjects with normal free testosterone levels.

In addition, Dandona and colleagues report that the higher the men's body weight, the lower was their testosterone.

Given these findings, the researchers conclude that low testosterone is "a common defect in type 2 diabetes that requires further assessment."

SOURCE: Journal of Clinical Endocrinology and Metabolism, November 2004.

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Meri found this article on Why Hormone Replacement is So IMPORTANT...
Wasted Muscles, Low Blood Pressure, Inattentive Eyes

By LISA SANDERS, M.D.


Published: December 5, 2004

1. Symptoms

"He wasn't always like this, you know," the woman said. She turned her tanned, earnest face away from her son, still strapped in his wheelchair, and stood to face the doctor. "He was a pretty normal kid." The physician, Dr. Joel Ehrenkranz, focused his dark, intent eyes on the wheelchair and its motionless passenger. His long, thin legs were tucked tightly against the chair; his chin rested on his chest as if his neck were too weak to hold it upright. Raised pink scars slashed across his scalp -- evidence of some long-ago surgery. His face was thin and drawn; his eyes were dull and inattentive. A pale fringe of light hair barely covered his ears.

At 13, he found out he had a brain tumor. He survived an operation and an infection. Then he got better. With physical therapy, he learned to walk again, and he eventually went back to school, back to his friends, back to his life. Then he had more operations, followed by radiation, and his health began to unravel. "That was 25 years ago," his mother said. "Now he's just a ghost of who he used to be." At 43, the patient hadn't walked in more than five years. He had hardly spoken in a decade. "We initially thought he'd recover completely, but somehow he's only gotten worse." Over the years, he had seen many doctors -- surgeons, neurologists, endocrinologists. One started him on steroids, and that helped for a while. Thyroid hormone helped, too. But nothing had stopped this progressive decline, or even really explained it.

Then, just over a year ago, his mother took him to the community hospital for an operation on his legs. Years of immobility had shortened and contracted his muscles and tendons. The operation was supposed to fix that and make him more comfortable and flexible. "But after the surgery, he really lost it," his mother reported. A couple of days later, he started vomiting everything he was fed. Every touch seemed painful. "He didn't know what day it was or even where he was. I don't know if he even knew who I was. You could put a ringing phone in his lap and he wouldn't respond at all." She wondered if the end had finally come.

2. Investigation

Two months after that surgery, she took her son back to their family doctor, David Sherwood, she told Ehrenkranz. As one of just three physicians attending to the residents of their Colorado town, he had known and cared for the young man and his mother for the past couple of years. He was shocked by the change after the operation. "I'd seen him quite a few times," Sherwood recounted to me. "He'd always been about the same -- debilitated and weak, but alert. You felt that even if he couldn't express himself, he could understand. He had a tough history with the brain surgery and all, and I figured that he was who he was because of that. Seeing him after this fairly minor procedure, it was like all the life was gone from him. I got this gut feeling I was really missing something here." The patient had already been to the local specialists, so Sherwood was reluctant to send him back. Instead, he suggested that they drive across the state to see Dr. Ehrenkranz, an endocrinologist who had recently come to his attention.

As she finished her story, the patient's mother looked expectantly at the doctor she had traveled so far to see. Ehrenkranz said nothing throughout her long and complicated tale. Occasionally he glanced through the voluminous records she had brought from the years of their ordeal. Mostly he looked at her son.

At last, Ehrenkranz reached into an old-fashioned black medical bag and took out his stethoscope. He gently wrapped the blood pressure cuff around the patient's wasted arm. His pressure was remarkably low, 90 over 70. A normal blood pressure for a man in his 40's was maybe 120 over 80. "That was a clue," Ehrenkranz recalled. "His tumor, all the surgeries on his brain, that wouldn't affect his blood pressure." He had almost no hair on his face or body. The incisions in his groin from his recent surgery were well healed, without any redness or swelling.

Ehrenkranz focused on the most striking physical finding: the low blood pressure. Infection was the most common cause of such a symptom. The patient didn't appear acutely ill, the way he would if he had a raging infection. But could he have an infection at the surgical site? An abscess -- a walled-off infection -- was capable of this type of insidious process. Still, the patient had not shown any evidence of pain when the doctor touched his surgical scars. Ehrenkranz had felt no lumps or bumps suggestive of a well-contained pocket of pus. Low blood pressure could also be caused by a heart that's not pumping properly. Yet the physical exam suggested that his heart was a normal size, and there were no extra heart sounds that would suggest a faulty valve.

Either an infection or heart disease was possible, and yet neither quite fit. Ehrenkranz continued to look at the patient. "It's like figuring out a math problem," he told me. "You just keep looking and looking, and it's like a light goes on." What if the patient were in a physiologic crisis after this operation because he lacked an essential hormone: cortisol? He was on a low dose of a steroid hormone, and while it might have been enough to keep him alive, it wasn't enough to deal with the stress of surgery. The nausea, vomiting and loss of alertness could be symptoms of insufficient stress hormone. But would this have caused his slow deterioration too? What if he were missing more than just stress hormone? He had also been put on thyroid hormone. Both are controlled through the tiny gland at the base of the brain called the pituitary. Referred to historically as the "master gland," this complex structure regulates the production of thyroid hormone and cortisol, the stress hormone. It also regulates growth hormone and sex hormones, including testosterone. The doctor theorized that this master gland had been destroyed by the radiation the patient had received decades earlier and that his subsequent decline was driven not by the brain destroyed by the tumor and its surgical cure but by the loss of the pituitary.

3. Resolution

At once, Ehrenkranz knew he was right. He sent the patient to the lab to have blood drawn to confirm his suspicion but was confident enough to start treatment. He wrote a prescription for large doses of steroid hormones to replace those the patient could no longer produce himself. He also wrote prescriptions for growth hormone, thyroid hormone and testosterone. Two days later, the patient got his first "stress dose" of steroids. The next morning, the mother went to see her son. He looked up at her, said, "Hello, Mom" and smiled a tiny smile. They were his first spontaneous words since the groin surgery. Ehrenkranz got the test results confirming the diagnosis the next week, but the patient's mother already knew. "I didn't need any tests to tell me the doctor was right," she said. "Two days after starting on these hormones, my son was able to stand up just using handrails. He hasn't been able to do that since the surgery."

That was 10 months ago. Now he is talking, eating and working out. He has gained about 40 pounds and grown a beard. He's listening to music, drawing, telling jokes. He has even been out riding horses -- a childhood passion. Ehrenkranz calls him Rip Van Winkle, just waking from a long, long sleep. He still uses a wheelchair -- his legs and body remain weak from the decades of debilitation. I spoke with him just before Thanksgiving. He said he had a lot to be grateful for. And he's certain he will walk one day. "Someday soon," he told me.

http://www.nytimes.com/2004/12/05/magazine/05DIAGNOSIS.html?oref=login

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http://www.registercitizen.com/site/news.cfm?newsid=13503339&BRD=1652&PAG=461&dept_id=12530&rfi=6

Druggist: Reluctant help to estranged wife
TRACY KENNEDY, Register Citizen Staff
12/07/2004

WATERBURY - In a court affidavit released Monday, the family and doctors of Suzanne Jolly describe a woman whose lifestyle, health and reliance on prescription drugs spiraled downward over the past two years.

And her husband, charged with manslaughter for forging prescriptions on her behalf, told police that he had been estranged from her for the same amount of time, living on a separate floor in their Waterbury home and reluctantly agreeing to forge prescriptions for the drugs her doctors and police say led to her death.

David Smudin, 38, manager of the Torrington Stop & Shop pharmacy, has posted a $200,000 bond and is free awaiting an appearance in Waterbury Superior Court Dec. 15.

According to court documents, Smudin admitted to police that he provided more than 1,000 steroid tablets for his wife, who died June 26 at age 34.

Dr. Wayne Carver, the chief medical examiner for the state of Connecticut, reported that Jolly, a medical transcriptionist, died from taking too much of the steroid drug Prednisone.

In an interview with Waterbury police in October that was detailed in an arrest affidavit released at Waterbury Superior Court on Tuesday, Smudin admitted he began filling out fake prescriptions for Prednisone for Jolly earlier this year, but according to pharmacy records reviewed by police, the abuse began the year before.

According to evidence collected by police, Smudin allegedly falsified his wife’s prescriptions 31 times between June 2003 and June 2004 by making out forms at the pharmacy at the Stop and Shop in Torrington, where he worked as manager of the pharmacy. When police confronted him with a partial list of prescriptions he admitted there were more filled in the name of some of Jolly’s 17 cats.

"I fraudulently filled about 10 or more of these prescriptions in a quantity of 100 5-mg pills. This is the truth," Smudin told police during an interview in October.

Waterbury police arrested Smudin Friday night at the pharmacy and charged him with first-degree manslaughter, second-degree forgery and illegally obtaining or dispensing drugs.

On June 25, Jolly, reported feeling weak and suffering from diabetic shock. She was transported by Campion ambulance to Waterbury Hospital for treatment but died the next day.

When physicians asked Jolly’s siblings, Lisa, Debra and Christopher Jolly, if they knew their sister was taking steroids, they said they had no idea. The physicians told them to check for drugs at her home that ended in the letters "sone."

"We found all kinds of medications everywhere in the house, under the mattress, under the bed, in the bathroom, in her coat pockets, just about everywhere." Lisa Jolly, the victim’s sister, told police. They didn’t find any ending with "sone" in the house, but her brother Christopher checked the trash, and inside a cereal box they discovered several bottles labeled Prednisone.

Jolly and Smudin were married in 1998 after dating for two years. Other than when she attended rehabilitation in 1999 and 2000 for addiction to pain pills, she was in good health, he told police. But the relationship became rocky in 2002, Smudin told police, and he moved to the second floor of their Southmayd Road home in Waterbury, while she lived a separate life on the first floor.

Months before his wife’s death, Smudin said he warned his wife to call her doctor for her own prescriptions. "She always looked run down, haggard," he told police, according to the arrest affidavit. He told police that his wife admitted to him she was using a Floven inhaler and an Albuterol inhaler, with a Nasonex steroid, and he knew that she was not using them properly. "She would call me at work asking me for refills," he told police. "I told her that I would do it once but to call her doctor for a prescription."

But Smudin allegedly kept refilling the Prednisone, he told police. "I filled out a pre-printed form that we use for phone-in prescriptions from physicians." During his interview with police Smudin also admitted to refilling Exfexxor and antidepressant, Compro suppositories, Albuterol and Flovent that may have been initially ordered by a physician, with no refills.

While there may be some discrepancy in the dates, the victim’s sister, Lisa Jolly, told police she noticed Jolly’s declining health two years ago.

"Sometime in 2000, Suzanne started acting strange, very bizarre. We didn’t know it then, but it was the drugs," she told police, according to the affidavit.

Last year, after Jolly underwent surgery to remove half of her thyroid at Yale-New Haven Hospital, her sister noticed at that time Jolly was gaining weight, had circular scratches on her arms that were not healing and she was losing her hair, Lisa Jolly said. "She told me that the doctors she saw did not know what was happening or were crazy or thought she was crazy," Lisa Jolly said to police, as indicated in the arrest affidavit. "I could see she was getting sicker and sicker."

Lisa Jolly said she saw many doctors and gained about 70 pounds and her skin lesions were worse, getting bigger and deeper. Her sister was isolating herself from people and her condition continued to deteriorate. Her family members urged her to see physicians, but she made up excuses for not going, or if she did go she didn’t return if she didn’t get pain medication she wanted, she reportedly told police.

"The last time she saw Dr. (Sandy) Hamill, which was on June 23, 2004, he refilled her (pain) prescriptions. Her sugar levels were out of control, very high. He prescribed insulin and syringes. Dr. Hamill wanted to wait until Monday to see if he would admit her into the hospital. Suzanne did not live until Monday," Lisa Jolly told police.

Dr. Hamill told police that Jolly was a "non-compliant patient" and "active participant in taking medicines." He believed she may have suffered from Munchausen’s Syndrome, in which she made up her illnesses to get attention or medication, Cushing’s Syndrome, which results from an excess of the cortisol hormone, and that steroids simulate cortisol, a naturally occurring, anti-inflammatory hormone produced by the adrenal glands.

He warned Jolly before her death, he told police during an interview on July 6, about the dangers of taking the steroids, and she denied taking the medicines. He attempted to admit her to the hospital, he told police. One time she did not go, and the second time she was admitted but left against medical advice, he said. When she initially came to him, she had skin lesions to her left breast and left arm doctors felt may have been self-inflicted. Dr. Hamill and her other physicians, and veterinarian denied prescribing Jolly any medications for steroids.

Just before her death, her doctor said the initial treatment for her symptoms was to administer high doses of steroids ,which may have hid the laboratory levels of the drugs already in her system.

In his opinion, he said, Jolly died of necrotic pneumonia-asperguillus attributed to taking large amounts of Prednisone, a steroid that has a debilitating effect on the immune system.

An autopsy report indicates Jolly was diagnosed with septicemia with septic shock, necrotizing pneumonia with multiple abscesses secondary to Aspergillus, Cushingoid habitus cerebral swelling with anoxic changes, multiple skin lesions on upper extremities and chest. No specific cause or manner of death was listed, police said.

A state licensing commission is expected to review whether Smudin should be allowed to continue to fill prescriptions.

Department of Consumer Protection Commissioner Edwin R. Rodriguez said in a press release Monday that the Drug Control Division of his office completed a lengthy criminal investigation and he expects the case to be reviewed by the department’s Commission of Pharmacy before a decision about Smudin’s license is finalized.

Tracy Kennedy can be reached by e-mail at courts@registercitizen.com.

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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11383480

Double pituitary lesions in three patients with Cushing's disease.

Meij BP, Lopes MB, Vance ML, Thorner MO, Laws ER Jr.

Department of Neurosurgery, Health Sciences Center, University of Virginia, Charlottesville, Virginia 22908-0214, USA.

Double pituitary adenomas are rare in surgical specimens and the most common clinical feature in reported patients has been acromegaly. We report 3 cases of double pituitary lesions in patients who presented with Cushing's disease. In a 22-year-old man (case 1) with delayed puberty and low testosterone levels, mild hyperprolactinemia was diagnosed and treated with dopamine agonist therapy that reduced the prolactin (PRL) levels to normal. Over a 1-year period Cushing's disease developed gradually and was confirmed with classical endocrine testing.

In a 27-year-old woman (case 2) who initially presented with severe depression and morbid obesity there was a gradual onset of Cushing's disease; initially she had minimally elevated serum PRL. In a 33-year-old woman (case 3) there was a 2-year history of Cushing's disease characterized by hirsutism, hypertension and weight gain; serum PRL was normal. Magnetic resonance imaging in all 3 patients revealed a microadenoma that was successfully removed by transsphenoidal pituitary surgery. Histology and immunocytochemistry in case 1 and case 3 revealed a corticotroph cell adenoma and a PRL cell adenoma in separate areas of the pituitary. In case 3 the PRL cell adenoma was "silent" but in case 1 the PRL cell adenoma may have been the cause of the mild hyperprolactinemia. In case 2 nodular corticotroph hyperplasia was the cause of Cushing's disease and a "silent" PRL cell adenoma was also identified. We conclude from these cases and a literature review that double pituitary lesions may occur in patients with Cushing's disease. The corticotroph part of the double lesion may consist of a corticotroph cell adenoma or, as reported in this study, of corticotroph nodular hyperplasia. The counterpart of the double lesion may consist either of a "silent" PRL cell adenoma or a functional PRL cell adenoma causing hyperprolactinemia.

Publication Types:

• Case Reports


• Review


• Review of Reported Cases

PMID: 11383480 [PubMed - indexed for MEDLINE]

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U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH
NIH News
NIH Office of the Director (OD)
http://www.nih.gov/icd/od/

FOR IMMEDIATE RELEASE
Friday, December 17, 2004

CONTACT:
John Burklow,
Don Ralbovsky,
Office of Communications and Public Liaison
301-496-5787

NIH HALTS USE OF COX-2 INHIBITOR IN LARGE CANCER PREVENTION TRIAL

The National Institutes of Health (NIH) announced today that it has suspended the use of COX-2 inhibitor celecoxib (Celebrex TM Pfizer, Inc.) for all participants in a large colorectal cancer prevention clinical trial conducted by the National Cancer Institute (NCI). The study, called the Adenoma Prevention with Celecoxib (APC) trial, was stopped because analysis by an independent Data Safety and Monitoring Board (DSMB) showed a 2.5-fold increased risk of major fatal and non-fatal cardiovascular events for participants taking the drug compared to those on a placebo.

Additional cardiovascular expertise was added to the safety monitoring committees at the request of the Steering Committees for this trial after a September 2004 report that the COX-2 inhibitor rofecoxib (Vioxx TM) caused a two-fold increased risk of cardiovascular toxicities in a trial to prevent adenomas. The APC is a study of more than 2,000 people who have had a precancerous growth (adenomatous polyp) removed. They were randomized to take either 200 mg of celecoxib twice a day, 400 mg of celecoxib twice a day, or a placebo for three years. The trial began in early 2000 and is scheduled to have been completed by Spring 2005.

Investigators at the 100 sites in the APC trial located primarily in the United States, with a few additional sites in the United Kingdom, Australia, and Canada, have been instructed to immediately suspend study drug use for all participants on the trial, although the participants will remain under observation for the planned remainder of the study.

"Data from the report on rofecoxib (Vioxx TM) informed us of the need to focus on specific cardiovascular issues, and our Institutes brought in the experts to do so," said Elias A. Zerhouni, M.D., NIH Director. "Our overwhelming commitment is to advance the health and to protect the safety of participants in clinical trials. We are examining the use of these agents in all NIH-sponsored clinical studies. In addition, we are working closely with our colleagues at FDA to ensure that the public has the information they need to make informed decisions about the use of this class of drug."

"The rigor of our clinical trials system has allowed us to find this problem," said NCI Director Andrew C. von Eschenbach, M.D. "We have a strong system that provides us with the opportunity to both find ways to effectively treat and prevent disease and to do so in a way that protects the lives and safety of the participants."

NIH sponsors over 40 studies using celecoxib for the prevention and treatment of cancer, dementia and other diseases. In light of these new findings, NIH Director Zerhouni requested:
--a full review of all NIH-supported studies involving this class of drug.

-- NIH Institutes to inform the principal investigators for all of these studies and will ask them to communicate directly with their study participants and explain the risks and benefits
-- NIH to ask each investigator to inform us of their plan to analyze their data in light of the information
-- the Institutional Review Boards (IRBs) for all related trials to assess the new information and to conduct a safety review as well

The NIH comprises the Office of the Director and 27 Institutes and Centers. The Office of the Director is the central office at NIH, and is responsible for setting policy for NIH and for planning, managing, and coordinating the programs and activities of all the NIH components. The NIH, the Nation's medical research agency, is a component of the U.S. Department of Health and Human Services.

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH
NIH News
NIH Office of the Director (OD)
http://www.nih.gov/icd/od/
National Cancer Institute (NCI)
http://www.nci.nih.gov/

FOR IMMEDIATE RELEASE
Friday, December 17, 2004

CONTACTS:
NIH Press Office
(301) 496-5787

NCI Press Office
(301) 496-6641

QUESTIONS AND ANSWERS
NIH HALTS USE OF COX-2 INHIBITOR IN LARGE CANCER PREVENTION TRIAL

The National Institutes of Health (NIH) announced today that it has suspended the use of COX-2 inhibitor celecoxib (Celebrex TM Pfizer, Inc.) for all participants in a large colorectal cancer prevention clinical trial conducted by the National Cancer Institute (NCI). The study, called the Adenoma Prevention with Celecoxib (APC) trial, was stopped because analysis by an independent Data Safety and Monitoring Board (DSMB) showed a 2.5-fold increased risk of major fatal and non-fatal cardiovascular events for participants taking the drug compared to those on a placebo. (Press release: http://www.nih.gov/news/pr/dec2004/od-17.htm )

Q: WHAT IS NIH DOING IN RESPONSE TO THESE FINDINGS?

NIH has halted the use of COX-2 inhibitor celecoxib (Celebrex TM Pfizer, Inc.) for all participants in a large colorectal cancer prevention clinical trial. Additionally, Elias A. Zerhouni, M.D., Director, NIH, has called for an immediate review of the entire grant portfolio for studies using COX-2 inhibitor drugs. NIH is also notifying all principal investigators of the NCI study findings and will ask investigators to inform the agency of their plan to analyze their data in light of this information. In addition, NIH is asking the Institutional Review Boards (IRBs) for all related trials to assess the new information and to conduct a safety review.

Q: ARE OTHER NIH STUDIES USING COX-2 INHIBITORS?

NIH sponsors more than 40 studies using celecoxib for the prevention and treatment of cancer, rheumatoid and osteoarthritis, dementia and other diseases. NIH's commitment is to advance the health and to protect the safety of participants in clinical trials. The agency is examining the use of these agents in all NIH-sponsored clinical studies. In addition, NIH is working closely with colleagues at FDA to ensure that the public has the information they need to make informed decisions about the use of this class of drug.

Q: WHY HAS NCI BEEN USING COX-2 INHIBITORS IN CLINICAL TRIALS?

Numerous compounds are examined by the National Cancer Institute (NCI) for their potential to prevent or treat cancer. One class of compounds, cyclooxygenase (COX) inhibitors, is currently being tested in both prevention and treatment clinical trials. Epidemiologic studies have shown that people who regularly take non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen to treat conditions like arthritis, have lower rates of colorectal polyps, colorectal cancer, and death due to colorectal cancer. NSAIDs block cyclooxygenase enzymes, which are produced by the body when there is inflammation and are also produced by precancerous tissues. Inhibition of COX-2 may help treat and prevent cancer, while inhibition of COX-1 may induce certain medical problems, like stomach bleeding, that occur when NSAIDS are taken regularly for long periods of time.

Q: WHAT IS CELEBREX AND WHY HAS NCI USED THIS DRUG IN THEIR TRIALS?

Pharmaceutical companies have created NSAIDs that block only COX-2; one of them, celecoxib (Celebrex(tm)), manufactured by Pfizer, Inc., New York, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of both osteoarthritis and adult rheumatoid arthritis (diseases in which the joints are inflamed) in December 1998. Because over a decade of scientific work has suggested the potential of COX-2 inhibitors to prevent and treat cancer, the National Cancer Institute (NCI) has clinical trials under way to look at the efficacy and safety of these drugs.

Q: WHAT SPECIFIC TRIALS HAS NCI BEEN CONDUCTING WITH CELEBREX?

NCI's Division of Cancer Prevention (DCP) began its studies with celecoxib with a trial in people with Familial Adenomatous Polyposis (FAP). Patients with FAP develop hundreds to thousands of precancerous polyps (adenomas) throughout the colon and rectum. Left untreated, nearly all FAP patients develop colorectal cancer by their 40s and 50s. The primary treatment for FAP is surgical removal of most or all of the colon and rectum with subsequent surveillance of any remaining colorectal segment. In an NCI-sponsored trial, celecoxib helped reduce the number of colon polyps in patients with FAP. The results of this study were published in the New England Journal of Medicine on June 29, 2000, and led to FDA-approval of celecoxib as an adjunctive drug (an accessory or auxiliary agent) that could be added to the standard of care in people with FAP.

As of October 2004, DCP sponsored 23 trials of varying sizes to test the potential of celecoxib to prevent cancer in a number of organ sites. These trials range in size from under 10 participants to more than 2,000 and aim to prevent bladder, breast, cervical, colorectal, esophageal, head and neck, skin, lung, oral, and prostate cancers, as well as multiple myeloma. The majority of these trials are in collaboration with Pfizer, Inc.

Additionally, to examine potential benefits of COX-2 inhibitors for the treatment of patients with cancer, NCI's Division of Cancer Treatment and Diagnosis (DCTD) is sponsoring approximately 20 trials of varying sizes with celecoxib. The majority of these studies are small phase I or II clinical trials in cancers such as pancreatic, breast, ovarian, non-small cell lung, and solid tumors. DCTD also is sponsoring two ongoing randomized phase III clinical trials: the first trial compares two chemotherapy agents, exemestane vs anastrozole, in postmenopausal women with estrogen receptor-positive primary breast cancer; the second trial compares several chemotherapy agents in node-negative breast cancer patients. Both phase III trials randomized women to either those taking celecoxib or not taking celecoxib, in addition to the agents mentioned above.

Q: WHAT IS THE STATUS OF THE APC (ADENOMA PREVENTION WITH CELECOXIB) TRIAL?

The National Cancer Institute suspended the use of COX-2 inhibitor celecoxib (Celebrex(tm); Pfizer) on December 17, 2004, for all participants in a large colorectal cancer prevention clinical trial, the Adenoma Prevention with Celecoxib (APC) trial, because analysis by an independent Data Safety Monitoring Board (DSMB) showed a 2.5-fold increased risk of major fatal and non-fatal cardiovascular events for participants taking the drug compared to those on a placebo. Safety monitoring of a similar study that was sponsored by Pfizer, called the PreSAP cancer trial, did not find an increased risk of cardiovascular events.

Additional cardiovascular expertise was added to the safety monitoring committees at the request of the steering committees for these trials after a September 2004 report that the COX-2 inhibitor rofecoxib (Vioxx(tm)) caused a two-fold increased risk of cardiovascular toxicities in a trial to prevent adenomas. The APC trial is a study of more than 2,000 people who have had a precancerous growth (adenomatous polyp) removed. They were randomized to take either 200 mg of celecoxib twice a day, 400 mg of celecoxib twice a day, or a placebo for three years. The trial began in early 2000 and is scheduled to be completed by spring 2005.

Investigators at the 100 sites in the APC trial, located primarily in the United States, with a few additional sites in the United Kingdom, Australia, and Canada, have been instructed to immediately suspend study drug use for all participants on the trial, although the participants will remain under observation for the planned remainder of the study.

Q: WHAT ACTIONS IS NCI PLANNING TO TAKE TO NOTIFY PATIENTS ON OTHER COX-2 INHIBITOR CLINICAL TRIALS?

NCI will notify all of the principal investigators of its sponsored trials involving COX-2 inhibitors. They will be instructed to notify their institutional review boards, data safety monitoring boards, and participants about this new information. NCI will also require that the informed consent for these trials be revised to reflect this new information and that individuals in the trials be re-consented (asked to sign new consent forms with updated information about risks and benefits of the trials).

For more information about cancer, please visit the NCI Web site at http://www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

For more information about regulation of COX-2 inhibitors by the FDA, please visit the FDA Web site at http://www.fda.gov/cder/drug/default.htm .

This NIH News Release is available online at:
http://www.nih.gov/news/pr/dec2004/od-17.htm

The Questions and Answers regarding this release are available online at:
http://www.nih.gov/news/pr/dec2004/od-17Q&A.htm

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Trial Using Pain Relieve Aleve Suspended

By PAUL RECER
.c The Associated Press

WASHINGTON (AP) - An Alzheimer's disease prevention trial was suspended after researchers said there were more heart attacks and strokes among patients taking naproxen, an over-the-counter pain reliever in use for 28 years and commonly known under the brand name Aleve.

The study, involving some 2,500 patients, was to test whether naproxen or Celebrex, both pain relievers, could reduce the risk of Alzheimer's disease among healthy elderly patients who were at an increased risk of the disease.

Officials at the National Institutes of Health said the study was suspended after three years when it was found that patients taking naproxen had a 50 percent greater incidence of cardiovascular events - heart attack or stroke - than patients taking placebo.

Another factor, officials said, was the announcement last week that advertising for Celebrex was being halted after a study found that high doses of the drug were associated with an increase in heart attack risk. Preliminary data from the Alzheimer's study, however, did not indicate an increased risk for heart attack or stroke for Celebrex, officials said.

Lester Crawford, acting commissioner of the Food and Drug Administration, acknowledged Tuesday that the conflicting studies are confusing and call for continued evaluation. For now, he recommended following the dosage recommendations for the drugs.

"Any drug taken long enough and at high enough dosage can cause some difficulty," Crawford said on NBC's "Today."

"It would be premature to say what we we're going to do with either one of these drugs, Celebrex or Aleve," he said. "However, we will keep all regulator options open and make some determinations as quickly as possible based on the data."

Celebrex, a prescription drug, and naproxen are both commonly used to treat the joint pain of arthritis. Naproxen has been approved for sale, first as a prescription and then as an over-the-counter drug, since 1976. Celebrex is in the same class - COX2 enzyme inhibitors - as Vioxx, an arthritis drug recently taken off the market by its manufacturer after it was linked to an increase in heart attack and stroke.

Officials acknowledged that the implications for the continued use of naproxen are not clear and will require further study.

Dr. Sandra Kweder of the FDA said the NIH study is the first to show that naproxen might increase the risk of heart attack or stroke and that the findings are "confusing." No immediate action, however, is expected toward naproxen, she said.

"We are not contemplating any specific regulatory action over the next few days," Kweder said. "We will be working with the NIH to try to understand the data better and determine what will be appropriate from there."

Patients who routinely take naproxen should follow the drug package instructions carefully, Kweder said, including the directions to not take it for more than 10 days, and to consult a doctor if pain persists.

Efforts to obtain reaction Monday night produced no answers at phone numbers for Bayer Healthcare, the maker of Aleve.

In the earlier studies of the COX2 drugs, an increase in cardiovascular events was noted only after a long-term use of the medications.

The Alzheimer's disease study was being conducted by the National Institute on Aging, an arm of the NIH. It called for 2,500 patients aged 70 or older and who had a family history of Alzheimer's, to take either Celebrex, naproxen or a placebo.

The group was divided and each division, or arm, was assigned to receive one of the drugs or placebo. The drugs were blinded, which means the patients did not know which medication they were taking, or if they were taking a placebo.

The goal was to determine if the pain-relieving drugs lowered the risk of developing Alzheimer's disease. The study started three years ago and was to continue for a few more years. Officials said the patients in the study will be monitored for developing Alzheimer's or cognitive decline, but will not be given the test drugs.

Dr. Elias A. Zerhouni, the director of the National Institutes of Health, said the study linking heart attack to Celebrex last week was a major factor in deciding to suspend the Alzheimer's study.

He said there was a question whether patients in the study would continue to take their medicine since they knew they might be taking Celebrex.

Suspending the study, Zerhouni said, "is the prudent thing to do."

John Breitner of the Veterans Affairs medical facility in Seattle and the University of Washington, an investigator in the trial, said only preliminary data is available. But he said it suggests that among the 2,500 patients in the study, about 70 suffered stroke or heart attack. There were 23 deaths. There were 50 percent more of the cardiovascular events among patients taking naproxen than among those taking placebo, he said.

On the Net:

National Institutes of Health: http://www.nih.gov


12/21/04 09:57 EST

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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/

FOR IMMEDIATE RELEASE
Friday, December 17, 2004

CONTACTS:
Mary Harris, NIH
301-435-8114

Tim Parsons, JHSPH
410-955-6878

FEW AMERICANS ARE AWARE THEY HAVE CHRONIC KIDNEY DISEASE

Ten to 20 million people in the United States have kidney disease but most don't know it, according to researchers at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health, the Johns Hopkins Bloomberg School of Public Health, and the National Center for Health Statistics (NCHS) at the Centers for Disease Control and Prevention. The findings are in the "Journal of the American Society of Nephrology."

Over the past decade the number of people with kidney failure doubled and the number starting dialysis or having a first kidney transplant increased by 50 percent, so that more than 400,000 Americans are now being treated for kidney failure at a cost of $25 billion annually. In contrast to these dramatic increases, the study also found that the number of people with earlier stages of kidney disease remained stable. About 7.4 million people have less than half the kidney function of a healthy young adult. Another 11.3 million have at least half of what's considered normal function, but they also have persistent protein in their urine, a sign of kidney disease. The researchers can't explain the paradox between stable prevalence of kidney disease and rising incidence of kidney failure, but they suggest that fewer patients may be dying and more may be progressing faster to dialysis.

"Given the high prevalence of chronic kidney disease, we need to increase awareness, diagnosis and treatment if we are going to reduce the rate of progression and complications. Most critical are control of diabetes and hypertension," said Josef Coresh, M.D., Ph.D., lead author of the study and professor of epidemiology, medicine and biostatistics at the Bloomberg School of Public Health in Baltimore.

Coresh and his colleagues estimated awareness of chronic kidney disease among 4,101 people in the United States from 1999 to 2000 and compared disease prevalence in those years with that from 1988 to 1994, when 15,488 people were surveyed. Data were from two National Health and Nutrition Examination Surveys by NCHS of nationally representative, non-institutionalized adults.

In the most recent survey, participants were asked: "Have you ever been told by a doctor or other health professional that you had weak or failing kidneys (excluding kidney stones, bladder infections, or incontinence)?" Less than 10 percent of adults with moderately decreased kidney function (one half to one quarter the filtering capacity of a young healthy adult) reported being told they had weakened or failing kidneys. Awareness was low in all but the most severe stages of kidney disease. Women with moderately decreased kidney function were significantly less aware of their illness compared to similarly affected men. The researchers determined actual kidney function from blood and urine tests and estimated glomerular filtration rate (GFR), a measure of how well the kidneys are filtering waste from the blood.

Lack of awareness may be due in part to doctors' sole reliance on the blood level of a substance known as creatinine. Because muscle mass and other person- to-person variables can alter creatinine levels, a "normal" reading can provide a false sense of security. Instead, creatinine should be considered along with a patient's age, gender, and race to estimate GFR.

"Kidney disease can be well advanced before it's found with creatinine alone. GFR is a more accurate gauge of how well the kidneys work, and our free calculator makes finding the rate a snap," said Thomas H. Hostetter, M.D., senior author of the study and director of NIDDK's National Kidney Disease Education Program (NKDEP). "The earlier we identify kidney disease the sooner we can treat it," said Hostetter.

NKDEP is asking labs to streamline the process for identifying kidney disease. "The GFR calculator is a great tool, but it's still one more step for busy doctors' offices. We are really pleased that several major labs have agreed to automatically report estimated GFR whenever creatinine is measured, removing a potential barrier to finding kidney disease early," said Hostetter. "We are still working quite hard to standardize tests for kidney disease by all labs."

People with chronic kidney disease are at high risk for premature death, heart attacks and strokes as well as hypertension, anemia, bone disease and malnutrition. NKDEP strives to increase awareness about kidney disease and offers the GFR calculator and other free tools at http://www.nkdep.nih.gov .

"Chronic Kidney Disease Awareness, Prevalence and Trends among U.S. Adults, 1999 to 2000" was written by Josef Coresh, Danita Byrd-Holt, Brad C. Astor, Josephine P. Briggs, Paul W. Eggers, David A. Lacher and Thomas H. Hostetter. The paper was published online on November 24, 2004, and will appear in print January 2004 in the "Journal of the American Society of Nephrology."

Funding for the study was provided by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Center for Research Resources at the National Institutes of Health and by the American Heart Association Established Investigators Award.

This NIH News Release is available online at:
http://www.nih.gov/news/pr/dec2004/niddk-17.htm

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Centerwatch Trial Notification Service

1) Do you suffer from Fibromyalgia?. This study is being conducted in:

    - Rochester, NY (http://www.centerwatch.com/patient/studies/stu66243.html)

2) Cholesterol Research Study. This study is being conducted in:

    - Mogadore, OH (http://www.centerwatch.com/patient/studies/stu66570.html)

3) Fibromyalgia Research Study. This study is being conducted in:

    - Mogadore, OH (http://www.centerwatch.com/patient/studies/stu66569.html)

4) Clinical Research Opportunities for Cholesterol. This study is being
conducted in:

    - Tacoma, WA (http://www.centerwatch.com/patient/studies/stu66580.html)

5) Double-Blind treatment of outpatients with Dysthymic Disorder with Wellbutrin
XL.. This study is being conducted in:

    - New York, NY (http://www.centerwatch.com/patient/studies/stu66216.html)

6) Hot Flashes Research Study. This study is being conducted in:

    - Tacoma, WA (http://www.centerwatch.com/patient/studies/stu66581.html)

7) Struggling With Your Weight?  Want to do Something About It?. This study is
being conducted in:

    - Boston, MA (http://www.centerwatch.com/patient/studies/stu66338.html)

8) Cerebral Metabolic Correlates of Treatment Response in Social Anxiety
Disorder. This study is being conducted in:

    - Boston, MA (http://www.centerwatch.com/patient/studies/stu66368.html)

9) Obesity, Nutrition and Prevention of Diabetes and Heart Disease. This study
is being conducted in:

    - Boston, MA (http://www.centerwatch.com/patient/studies/stu66067.html)

10) Are you struggling with your weight?. This study is being conducted in:

    - Boston, MA (http://www.centerwatch.com/patient/studies/stu66828.html)

11) Have you been feeling down, had loss of energy, and/or changes in your sleep
or appetite?. This study is being conducted in:

    - Belmont, MA (http://www.centerwatch.com/patient/studies/stu66256.html)

12) Planning to stop use of your antidepressant?. This study is being conducted
in:

    - Belmont, MA (http://www.centerwatch.com/patient/studies/stu66257.html)

13) We are looking for subjects to participate in a research study for Knee Pain
Due To Arthritis.. This study is being conducted in:

    - Ann Arbor, MI (http://www.centerwatch.com/patient/studies/stu66060.html)

14) Menopause:  Are your symptoms out of control?. This study is being conducted
in:

    - Philadelphia, PA (http://www.centerwatch.com/patient/studies/stu66149.html)

15) Depressed and Sexually Active?. This study is being conducted in:

    - Charlottesville, VA (http://www.centerwatch.com/patient/studies/stu65862.html)

16) Cholesterol Research Study. This study is being conducted in:

    - Santa Rosa, CA (http://www.centerwatch.com/patient/studies/stu66577.html)

17) Are you concerned about Osteoporosis?. This study is being conducted in:

    - Anaheim, CA (http://www.centerwatch.com/patient/studies/stu66058.html)

18) Are you suffering from Osteoporosis?. This study is being conducted in:

    - Charlottesville, VA (http://www.centerwatch.com/patient/studies/stu66565.html)

19) Are your waistline and blood pressure on the rise?. This study is being conducted in:

    - Eugene, OR (http://www.centerwatch.com/patient/studies/stu66922.html)

20) We are looking for women to participate in a research study for the treatment of hot flashes due to menopause. The investigational medication is a hormone gel applied to the arm once daily.. This study is being conducted in:

    - Ann Arbor, MI (http://www.centerwatch.com/patient/studies/stu66848.html)

21) Omega 3 Fatty-Acid/ Depression Study. This study is being conducted in:

    - Boston, MA (http://www.centerwatch.com/patient/studies/stu66846.html)

22) Do your hot flashes cause you to sweat?. This study is being conducted in:

    - Philadelphia, PA (http://www.centerwatch.com/patient/studies/stu66990.html)

23) Cholesterol Research Study. This study is being conducted in:

    - Cincinnati, OH (http://www.centerwatch.com/patient/studies/stu66863.html)

Additional educational resources that may be of interest to you:
Informed Consent: A Guide to the Risks and Benefits of Volunteering for Clinical Trials. http://www.centerwatch.com/bookstore/pubs_cons_infconsent.html

Volunteering for a Clinical Trial, a brief educational pamphlet. If you would
like to order this pamphlet click here: http://www.centerwatch.com/bookstore/pubs_cons_brochureform.html

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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

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Newest Bios:
To add or edit your bio, please click here »
Anne	Anne is not yet diagnosed.	North Carolina
Cindy A	Cindy is not yet diagnosed.	Swedesboro, NJ
Elaine	Elaine has been diagnosed with Empty Sella (pituitary) so far	Florida
Jaime H	Jaime H has had two surgeries on pituitary tumors and had Gamma Knife Radiation in Virginia in Sept 2004	Springville, Alabama
JoAnn	JoAnn is scheduled for pituitary surgery January 3, 2005	Bakersfield, California
Kathie B	Kathie B is not yet diagnosed.	Franklin, Massachusetts
Khuyen	Khuyen will have an adrenalectomy in January 2005.	Fort Worth, Texas
Merlenna	Updated.  Merlenna had an adrenalectomy December 20., 2004	Dixon, California

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• 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."

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.

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!

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