Women and Anger
A Common & Difficult Problem
Help For Women Whose Hormones Are Raging
And Whose Lives Are Negatively Impacted By AngerMarch 31, 2005
9 PM (ET), 6 PM (PT)
Women & Anger Specialist
Laura Petracek, Ph.D.
In Power Surge Live!
Laura Petracek, Ph.D.
Laura Petracek, Ph.D., is assistant professor of Clinical Psychology at National University in Sacramento, CA. She maintains a private practice in San Francisco. Dr. Petracek's new book,
The Anger Workbook for Women:
How to Keep Your Anger from Undermining Your Self-Esteem,
Your Emotional Balance, and Your Relationships.
This workbook addresses the unique concerns of women with anger problems.
Dr. Petracek says, "Rigid social patterning conditions many women to stifle or deny their anger, and this repression can cause a range of other psychological problems. Others experience violent, outwardly focused anger." Whichever pattern your anger follows, this book provides a powerful set of anger management tools. Cognitive behavioral and attitude adjustment exercises help you limit the power of anger-triggering situations. Worksheets and assessments guide you in an examination of family-of-origin issues that might contribute to your problems with anger. Sections of the workbook explore the connection between anger and substance abuse, mood disorders, and spirituality, as well as the issue of domestic violence.FREE copies of
The Anger Workbook For Women
will be given away at the chat.Join Dr. Laura Petracek, March 31th in
Power Surge Live!
this month's Endocrine Society News - Cushing's as Cover Story!
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TV Show, House, on FoxTV Last Night, deals with Cushing's
A 10-year old girl, Jessica, is at home and not feeling well as she's going off to school. That day while exercising she complains of chest pains and collapses. As House is forced to decide which of his staff members he will fire, Jessica's case is referred to him and he's intrigued. They begun to run tests as House drops the news to his staff, and Jessica's mother disputes that Jessica's weight is the issue. Meanwhile House meets with an overweight woman, Lucille, suffering from heartburn who refuses to believe she's pregnant despite House's claims.
Jessica begins to turn irrational during testing as she apparently becomes hypoglycemic and the doctors are forced to sedate her. The lab tests prove negative for hypoglycemia and they suspect she may be taking diet pills. Meanwhile Vogler starts playing a few games of his own with House's staff to find out what they're thinking. And it turns out Lucille has a benign 30 lb. tumor but she refuses surgery believing it will make her ugly to her husband. Forman investigates Jessica's background and finds she has no friends but was apparently taking diet pills. Jessica admits she was taking the pills and they conclude they're responsible, but then Jessica starts bleeding from necrosis on her chest.
House suspects she's reacting to a drug and all but accuses Cameron and Chase of giving Jessica the wrong drug. That sets off another round of in-fighting and Vogler shoots down House's idea to keep everyone and cut the staff's pay. Lucille's husband expresses his concern and wants House to lie to her that it's cancer so she'll undergo surgery. Jessica's necrosis is spreading and they recommend amputation of the breasts – a radical mastectomy. They plan to wait as long as possible but otherwise have no choice.
House confronts Lucille, and he's deduced she's sleeping with other men – thus her reluctance to undergo the surgery. Chase meets with Vogler who points out how precarious Chase's position is if he finds someone else to feed him info on House. As they prepare Jessica for surgery, House deduces that her obesity is a symptom – along with her height (shorter then her parents), he concludes it's Cushing's, which causes hyper-cortisone levels that account for her symptoms. They use a MRI to locate the hyper-cortisonism. They find a tumor on the pituitary gland that accounts for the symptoms. Using surgery, they successfully remove Jessica's tumor and she starts losing weight.
House goes to Vogler with his decision – he's firing Chase. However, Vogler refuses to let him fire Chase and tells him to pick someone else . . . or it'll be the whole department that is fired. We're left with Cameron writing up her resume and everyone pondering the situation.
Cushing's Awareness Day. We are currently petitioning to
have April 8 be declared as Cushing's Awareness day. This date was chosen
because it was Dr. Harvey Cushing's Birthday.
Print out a sample letter
to send to your congress person or senator or download it in
See what Jayne has done! She wrote to her
representative and she's now in the
Congressional Record. She has her first response and it's a fantastic one!
Jayne presented a table full of Cushing's info at her local Health Fair In
Fredericksburg, VA. She plans to set up something similar at the NIH Health
and Wellness Fair May 15th.
More info here »
Double click on any photo to view full-sized.
A Message Board area has been added to discuss ideas for
making Cushing's Awareness Day a reality. Please do what you can to help
the cause! Thank you for helping to make this
Cushing's Awareness Day a reality!
welcome your articles, letters to the editor, bios and Cushing's
Submit a Story or Article to either the snailmail CUSH Newsletter or to
an upcoming email newsletter at
These articles are provided in furtherance of the mission of
Cushing's Help and Support to help people with Cushing's or other endocrine
problems, their friends and families through research, education, support,
and advocacy. These news items are intended to serve as background
concerning its subject for patient-physician discussions and discussions
Cushing's Help and Support Message Board Members.
These articles contain
information by authors and publishers that is subject to the Copyright Act
of 1976, and "fair use doctrine" therein, effective on January 1, 1978 (17
U.S.C. § 101 et seq.). Cushing's Help and Support makes no representation
that the information and any of the views or comments contained in these
articles are completely accurate or current. Cushing's Help and Support
takes no responsibility for any of the content.
Ask the Doctor
BY PAUL G. DONOHUE, M.D.
Mar 28, 2005
DEAR DR. DONOHUE: Recently I was told that my potassium level was slightly high and to stop taking vitamins. What causes this, and what is the result of too much potassium? Why no vitamins? -- E.L.
ANSWER: When the kidneys are working well, blood potassium levels stay on an even keel. Poorly functioning kidneys, therefore, are one reason why the blood potassium level rises. Adrenal-gland failure is another reason for a rise in blood potassium, because the adrenal glands make hormones that regulate potassium balance. Body cells are the place where the most body potassium is stored. Cell trauma -- even from a bump or fall -- can cause cellular release of potassium into the blood.
Very often a slight potassium rise comes from a hitch in the way that blood was collected. If a tourniquet was left on the arm too long when blood was drawn, blood potassium is spuriously raised.
A true rise in potassium can weaken muscles. It throws off the body's acid-base balance. It interferes with the normal heartbeat and can affect nerve transmission.
Vitamins have no effect on blood potassium. I don't know why the vitamin ban was given to you.
You need a repeat blood test.
The booklet on potassium and sodium gives the details of these minerals. Readers can obtain a copy by writing: Dr. Donohue -- No. 202, Box 536475, Orlando, FL 32853-6475. Enclose a check or money order (no cash) for $4.50 U.S./$6.50 Can. with the recipient's printed name and address. Please allow four weeks for delivery.
* * *
Dr. Donohue regrets that he is unable to answer individual letters, but he will incorporate them in his column whenever possible. Readers may write him or request an order form of available health newsletters at P.O. Box 536475, Orlando, FL 32853-6475.
(c) 2005 North America Syndicate Inc.
All Rights Reserved
Cortisol's role in weight gain still up for debate
Mar. 29, 2005 12:00 AM
QUESTION: There has been lots of information lately about elevated levels of the hormone cortisol in women and the possible tie to weight gain. Is it true that coffee can lead to elevated cortisol levels and, therefore, stimulate unwanted weight gain?
ANSWER: Cortisol is a hormone secreted by the adrenal glands in response to stress, and recent research does suggest that there may be a tie between cortisol levels in women and the accumulation of excess weight in the abdominal area.
A study at Yale University in 2000 compared stress reactions among women who had a high waist-to-hip ratio (because their fat tended to be in the belly) with those among women with a low waist-to-hip ratio (indicating more fat storage in the hips than the waist). advertisement
The researchers noted that diseases caused by high levels of cortisol (Cushing's syndrome is one) are characterized by excessive amounts of fat in the abdominal area, an unhealthy distribution that increases the risk of high blood pressure, heart disease and diabetes. In addition to the link to weight gain, elevated cortisol levels can have adverse effects on the immune system, memory and sugar metabolism.
In the Yale study, women were given tests (involving puzzles and speech designed to stimulate stress) to see how they responded. The researchers found that women with a high waist-to-hip ratio, whether they were overweight or slim, secreted more cortisol under stress and also reported more stress in their daily lives than women with low waist-to-hip ratios. Results of the study were published in the September-October 2000 issue of Psychosomatic Medicine.
As far as caffeine is concerned, a study published in the July-August 1998 issue of Psychosomatic Medicine showed that caffeine can elevate levels of cortisol and another stress hormone, ACTH (adrenocorticotropic hormone), in men prone to high blood pressure as well as in men at low risk for this disease. That's all we know. I doubt that caffeine has much impact on weight gain as a result of any effect on cortisol levels.
Although these findings are interesting, it would be a mistake to blame all weight gain on cortisol. Heredity plays a role, too, as well as such lifestyle factors as smoking, alcohol consumption and lack of exercise. If you want to decrease the impact of stress in your life, which may result in lower cortisol levels, be sure to get regular exercise and sufficient sleep. Incorporate meditation and relaxation techniques into your daily routine. Breathing exercises also will help you be calm.
Andrew Weil, M.D., is a pioneer in the field of integrative medicine and is a professor of medicine and the founder and director of the Program in Integrative Medicine at the University of Arizona in Tucson. Weil is also a bestselling author, monthly columnist for Prevention magazine, and editor of Self Healing Newsletter. Go to www.DrWeil.com for more information.
Reported March 29, 2005
Problems and Benefits From Growth Hormone Deficiency
(Ivanhoe Newswire) -- A new study shows a deficiency of growth hormone and IGF-1 (insulin-like growth factor 1) may reduce cancer and kidney disease late in life, but they may also create problems. Researchers from Wake Forest University Baptist Medical Center in Winston-Salem, N.C., and four other centers found these deficiencies may lead to cartilage degeneration as well as impaired memory and learning ability.
Researchers developed a strain of dwarf rats that were naturally deficient in growth hormone and IGF-1. To mimic the rise in these compounds that occurs in adolescence in normal rats, researchers gave the rats growth hormone during their adolescence. Then the hormone treatment was stopped.
Sixty-three percent of rats with a lifelong deficiency of growth hormone had tumors, while 88 percent of "normal" male rats had tumors at death. The same pattern was true for kidney disease. No growth-hormone deficient rats developed it, while 74 percent of normal male animals had kidney disease when they died. Growth-hormone deficient animals also had a longer average lifespan.
However, growth-hormone deficient rats had impaired learning and memory abilities compared to normal rats. They also had accelerated cartilage degeneration.
Researchers conclude cancer risk may be reduced by inducing a modest growth hormone deficiency early in life. However, a tradeoff exists because of how that deficiency impairs learning and memory and accelerates degenerative diseases.
This article was reported by Ivanhoe.com, who offers Medical Alerts by e-mail every day of the week. To subscribe, go to: http://www.ivanhoe.com/newsalert/.
SOURCE: Endocrinology, published online March 24, 2005
Deficiency of growth hormone and IGF-1 reduces cancer and kidney disease, but creates other problems
25 Mar 2005
Deficiencies of growth hormone and similar compounds may reduce cancer and kidney disease late in life, but also may lead to cartilage degeneration and impaired memory and learning ability, according to research at Wake Forest University Baptist Medical Center and four other institutions.
The researchers used a rat model to explore the effects of growth hormone and another compound, IGF-1 (insulin-like growth factor 1) on adult rats and found paradoxical effects, according to William E. Sonntag, Ph.D., professor of physiology and pharmacology at Wake Forest University Baptist Medical Center and the lead investigator.
"Things that happen when you are an adolescent may have an impact on how long you live and what you die of," he said.
"The presence of growth hormone and IGF-1 is necessary for maintenance of cognitive function and prevention of cartilage degeneration," Sonntag and his colleagues reported in an article in Endocrinology, published on-line today. But the hormones also increase cancer and other diseases that limit lifespan.
The researchers developed a strain of dwarf rats that were naturally deficient in both growth hormone and in IGF-1. To mimic the rise in growth hormone and IGF-1 during adolescence in normal rats, some of these deficient rats were given growth hormone while they were between 4 and 14 weeks of age - rat adolescence. Then hormone treatment was stopped and the animals had lower growth hormone and IGF-1 levels the rest of their lives.
That had an effect on cancer: 88 percent of "normal" male rats have tumors at death. The male rats that had a lifelong deficiency of growth hormone had substantially fewer tumors - 63 percent - and the percent of tumors that were fatal was reduced from 57 percent to 31 percent.
The same pattern occurred for kidney disease, which was found in 74 percent of the normal male animals at the time of their deaths. None of the growth-hormone deficient animals developed kidney disease.
They found that animals with a deficiency in growth hormone initiated after adolescence had up to a 14.6 percent increase in lifespan. All animals in the study lived until they died of natural causes.
The researchers used several tests to measure memory and learning. They found that growth-hormone-deficient rats had impaired learning ability compared to normal animals of the same age. A similar pattern occurred in memory tests.
"The presence of growth hormone and IGF-1 are required for optimal performance on tests of learning and memory throughout life," they said. "Growth hormone/IGF-1 replacement in older animals reverses the age-related decline in cognitive function."
The group also found that "cartilage degeneration that normally accompanies aging is accelerated by the absence of growth hormone."
The researchers concluded that cancer risk as well as other age-related pathologies could be substantially decreased in these animals by inducing a modest deficiency of growth hormone and IGF-1 early in life. However, there is a tradeoff and deficiency of growth hormone and IGF-1 may impair learning and memory and accelerate some degenerative diseases.
Media Contacts: Robert Conn, email@example.com, Shannon Koontz, firstname.lastname@example.org, or Karen Richardson, email@example.com, at 336-716-4587.
TV Editor/Producer Note: Wake Forest Baptist can arrange live interviews from an on-campus studio via a fiber-to-satellite uplink. Please call (336) 716-4434 with questions or to set up an interview with one of our experts.
About Wake Forest University Baptist Medical Center:
Wake Forest Baptist is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university's School of Medicine. The system comprises 1,298 acute care, psychiatric, rehabilitation and long-term care beds and is consistently ranked as one of "America's Best Hospitals" by U.S. News & World Report.
Contact: Robert Conn
Wake Forest University Baptist Medical Center
Plasma leptin and ghrelin in the neonatal rat: Interaction of dexamethasone and hypoxia
Eric D Bruder1, Lauren Jacobson2 and Hershel Raff1,3
1 Endocrine Research Laboratory, St Luke's Medical Center, Milwaukee, WI 53215
2 Center for Neuropharmacology and Neurosciences, Albany Medical College, Albany NY 12208
3 Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226
(Requests for offprints should be addressed to H Raff, Endocrinology, St Luke's Physician's Office Building, 2801 W. KK River Pky, Suite 245, Milwaukee, WI 53215 USA)
Ghrelin, leptin, and endogenous glucocorticoids play a role in appetite regulation, energy balance, and growth. The present study assessed the effects of dexamethasone (DEX) on these hormones, and on ACTH and pituitary POMC and CRHR1 mRNA expression, during a common metabolic stress – neonatal hypoxia. Newborn rats were raised in room air (21% O2) or under normobaric hypoxia (12% O2) from birth to postnatal day (PD) 7. DEX was administered on PD3 ( 0.5 mg/kg), PD4 (0.25 mg/kg), PD5 (0.125 mg/kg), and PD6 (0.05 mg/kg). Pups were studied on PD7 (24 h after last dose of DEX). DEX significantly increased plasma leptin and ghrelin in normoxic pups, but only increased ghrelin in hypoxic pups. Hypoxia alone resulted in a small increase in plasma leptin. Plasma corticosterone and pituitary POMC mRNA expression were decreased 24 h following the last dose of DEX, whereas plasma ACTH and pituitary CRHR1 mRNA expression had already increased (normoxia and hypoxia). Hypoxia alone increased corticosterone, but had no effect on ACTH or pituitary POMC and CRHR1 mRNA expression. Neonatal DEX treatment, hypoxia, and the combination of both affect hormones involved in energy homeostasis. Pituitary function in the neonate was quickly restored following dexamethasone-induced suppression of the HPA axis. The changes in ghrelin, leptin, and corticosterone may be beneficial to the hypoxic neonate through the maintenance of appetite and shifts in intermediary metabolism.
Journal of Endocrinology
Download the ACCEPTED PREPRINT (i.e. full text) of this article in Acrobat PDF format.
Adrenal Suppression From Topical Corticosteroids Surprisingly High
By Alicia Ault
MedPage Today Staff Writer
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
Source News Article: Yahoo
MedPage Today Action Points
- Understand hypothalamic-pituitary-adrenal axis suppression and its potential effects on your patients.
- Explain to patients that prescription corticosteroids for topical use are usually stronger and for different indications than those currently sold over-the-counter, and require careful monitoring for side effects and appropriate use.
- Check in with your patients on whether they use over-the-counter hydrocortisone appropriately.
- Understand that the FDA panel's recommendations were aimed at manufacturers and the FDA, who will likely work together on applying them to future new drug applications.
GAITHERSBURG, Md.-Prescription topical corticosteroids may have more potential to cause adrenal suppression than many physicians realize, according to data presented yesterday at an FDA advisory committee hearing.
The data reviewed at a joint meeting of the Nonprescription Drugs and Dermatologic and Ophthalmic Drugs advisory committees surprised many panelists, who said they were not aware the drugs had such a high incidence of hypothalamic-pituitary-adrenal (HPA) axis suppression.
The suppression can lead to debilitating and potentially fatal conditions such as Cushing's syndrome.
The committees were meeting to give advice on what data manufacturers would need to submit to convince the FDA that their products were safe to be sold over-the-counter. The panel did not discuss any specific application, though GlaxoSmithKline representatives presented data from studies of consumer use of hydrocortisone creams.
Denise Cook, M.D., a medical officer in FDA's Division of Dermatology and Dental Drug Products, presented data from studies in adults and children for 10 currently marketed topical corticosteroids.
The biggest problems seemed to be with betamethasone propionate, which was approved in 2001, and comes as a cream, ointment or lotion.
In one study of Diprolene AF Cream (0.05%) in 60 patients with atopic dermatitis, ages 1 to 12, 58% had adrenal suppression. For Diprosone Ointment (0.05%), the rate was 53%.
For Clobex lotion (clobetasol propionate), which was approved in 2003, 56% of adults in a small study of atopic dermatitis using the drug for two weeks had suppression. In another Clobex study, 8 of 10 adults treated for four weeks twice daily had adrenal suppression.
Though the effects seemed to be reversible after discontinuation, the high incidence gave panelists pause.
Michael Wilkerson, M.D., a panel member and dermatologist at Utica Park Clinic in Tulsa, Okla., said he was surprised, and that physicians should be more concerned about prescription use. "I think this is the biggest safety signal to come out of this entire meeting," he said.
He and other panelists said it would be difficult to approve these drugs for over-the-counter use. They sought better data on how to avoid adrenal suppression and who it disproportionately affects.
Currently, all the drugs in the class carry warnings that systemic absorption can cause HPA axis suppression, leading to Cushing's syndrome, hyperglycemia and glucosuria. Children are at greater risk, and are more vulnerable to growth retardation, delayed weight gain, and intracranial hypertension.
Since 1969, the FDA has received reports of severe adrenal suppression in 65 adults and 29 children, said Dr. Cook. Two adults died, and two children died. Most of the serious problems followed prolonged or excessive use of the drugs, use of a super-potent steroid, using multiple topical steroids, or using them at the same time as oral or inhaled steroids.
Manufacturers first applied to sell topical steroids over-the-counter in the mid-1950s. The FDA rejected the move in 1957. But in 1973, the FDA said that topicals of 0.25% to 0.5% were generally recognized as safe, opening the door to over-the-counter sales in those strengths. In 1990, the agency agreed that strengths up to 1% were safe for drugstore sales.
Topical corticosteroids that came on the market after 1975 are regulated under a different scheme. To be moved over the counter, manufacturers have to submit a new drug application. The expert panelists gave their input on what would be needed to convince them over the counter use was safe.
Most panelists agreed that the adrenal suppression and growth retardation were significant side effects that should block over-counter sales, although some said consumers should be given the benefit of the doubt.
The American Academy of Dermatology Association disagreed. A spokesman said the AADA was opposed to OTC sales. "Used improperly, these medications can cause great harm," said Sandra Read, M.D., a dermatologist in private practice in Washington, DC.
"If you remove the physician from this equation you'd be effectively removing a very important safeguard," she said.
American Academy of Dermatology Issues Statement Urging FDA Advisory Committees to Maintain Dermatologic Corticosteroids as Prescription Medications
Wednesday March 23, 11:44 am ET
SCHAUMBURG, Ill., March 23 /PRNewswire/ -- The American Academy of Dermatology (Academy) today issued a statement in response to a proposed change being considered by the U.S. Food and Drug Administration's (FDA) Dermatologic and Ophthalmic Drugs Advisory Committee and the Nonprescription Drugs Advisory Committee in which topical corticosteroids would be available to patients over-the-counter instead of by prescription.
"The American Academy of Dermatology is deeply concerned that if the FDA allows topical corticosteroids to be marketed over-the-counter instead of by prescription, patients could self-medicate without being monitored by their physician for serious side effects associated with long-term or improper steroid use," said dermatologist Clay J. Cockerell, M.D., president of the American Academy of Dermatology and the American Academy of Dermatology Association. "While weaker topical corticosteroids are available over-the- counter, we have seen some complications with their use. For the safety of patients, we urge the FDA to keep these stronger topical corticosteroids where they belong -- behind the pharmacy counter as prescription medications."
Topical corticosteroids -- which include prescription-strength cortisone creams - currently are prescribed by dermatologists and other physicians to safely treat a range of mild to severe skin conditions. Topical corticosteroids are relatively small molecules that penetrate the skin when applied topically, especially at higher concentrations, and can be absorbed in the bloodstream. The side effects that can occur from topical corticosteroid use include:
- Hypothalamic Pituitary Adrenal (HPA) axis suppression - Studies
demonstrate that if sufficient topical corticosteroids are absorbed
into the bloodstream, they can reduce the normal function of the
adrenal glands that are responsible for producing the body's natural
steroid hormones. In some rare cases, this acute adrenal insufficiency
can be life-threatening or lead to Cushing's syndrome -- a serious
disease causing upper body obesity, weakened bones, and thinning of the
skin which makes it fragile and susceptible to infection.
- Growth suppression -- Long-term systemic exposure to topical
corticosteroids may result in slowed body growth and development, a
special concern in children who have an increased risk of systemic
exposure because of their higher ratio of skin to body volume.
- Adverse effects in the skin and eyes -- Inappropriate or overuse of
topical corticosteroids can lead to obvious visible changes. The most
common side effects of topical corticosteroid overuse include thinning
of the skin, permanent stretch marks in body fold sites such as the arm
pits and behind the knees, swelling of tiny blood vessels beneath the
skin surface especially on the face, hypopigmentation and slowed wound
healing. Cataracts and glaucoma also could develop.
The purpose of the hearing is for the FDA advisory committees to address these potential side effects and how they can be monitored through a sufficient safety database in evaluating the prescription to over-the-counter switch of topical corticosteroids.
Tomorrow, dermatologist Sandra Read, M.D., of Washington, D.C., will speak on behalf of the American Academy of Dermatology Association at the FDA's joint advisory committee meeting. She will stress the importance of keeping topical corticosteroids as prescription medications.
"As well informed as patients can be, I do not believe that they should be self-diagnosing and self-treating symptoms with medications that have the potential for such serious side effects," said Dr. Read. "By removing the physician from the equation, you would be effectively eliminating a very important safeguard and protection for patients."
The American Academy of Dermatology (Academy), founded in 1938, is the largest, most influential, and most representative of all dermatologic associations. A sister organization to the Academy, the American Academy of Dermatology Association is the resource for government affairs, health policy and practice information for dermatologists, and plays a major role in formulating socioeconomic policies that can enhance the quality of dermatologic care. With a membership of more than 14,000 physicians worldwide, the Academy is committed to: advancing the diagnosis and medical, surgical, and cosmetic treatment of the skin, hair and nails; advocating high standards in clinical practice, education, and research in dermatology; and supporting and enhancing patient care for a lifetime of healthier skin. For more information, contact the Academy at 1-888-462-DERM (3376) or http://www.aad.org.
• If you've been diagnosed with Cushing's, please
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The information you provide will be used to create a register
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Lynne Clemens, Secretary of
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person responsible for the creation of this register. If you
have any questions you may contact her at
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."