From http://jcem.endojournals.org/cgi/content/abstract/91/10/3746

Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-0997

The Journal of Clinical Endocrinology & Metabolism Vol. 91, No. 10 3746-3753
Copyright © 2006 by The Endocrine Society

CLINICAL REVIEW
Cushing’s Syndrome: Important Issues in Diagnosis and Management
James W. Findling and Hershel Raff

Endocrine-Diabetes Center (J.W.F.) and Endocrine Research Laboratory (H.R.), St. Luke’s Medical Center, Milwaukee, Wisconsin 53215; and Department of Medicine (J.W.F., H.R.), Medical College of Wisconsin, Milwaukee, Wisconsin 53226

Address all correspondence and requests for reprints to: Hershel Raff, Ph.D., Endocrinology, St. Luke’s Physician’s Office Building, 2801 West KK River Parkway, Suite 245, Milwaukee, Wisconsin 53215. E-mail: hraff@mcw.edu.

Context: The diagnosis, differential diagnosis, and treatment of Cushing’s syndrome are challenging problems in clinical endocrinology. We focus on critical questions addressing screening for Cushing’s syndrome, differentiation of Cushing’s subtypes, and treatment options.

Evidence Acquisition: Ovid’s MEDLINE (1996 through April 2006) was used to search the general literature. We also relied on previously published reviews and a recent monograph and cite a mix of primary articles and recent reviews.

Evidence Synthesis: Although this article represents our opinion, it draws heavily on a recent consensus statement from experts in the field and a recent monograph on Cushing’s syndrome.

Conclusions: We concluded that:

1) measurement of late-night or bedtime salivary cortisol is a useful approach to screen for Cushing’s syndrome;

2) measurement of suppressed plasma ACTH by immunometric assay is useful to differentiate ACTH-dependent and -independent Cushing’s syndrome;

3) inferior petrosal sinus sampling for ACTH should be performed in patients with ACTH-dependent hypercortisolism in whom a pituitary magnetic resonance imaging is normal or equivocal (in the absence of a pituitary ACTH gradient, prolactin levels should be measured to confirm the integrity of venous sampling);

4) computed tomography of the chest and abdomen and somatostatin receptor scintigraphy should be performed in patients with the occult ectopic ACTH syndrome; and

5) patients with Cushing’s disease should be referred to a neurosurgeon with extensive experience operating on corticotroph microadenomas. Bilateral laparoscopic adrenalectomy should be considered in patients with Cushing’s disease who fail therapies directed at the pituitary.

Pituitary:

http://www.newswire.ca/en/releases/archive/October2006/23/c3257.html

Hormone resistance of pituitary tumors and Cushing disease explained

MONTREAL, Oct. 23 /CNW Telbec/ - Montréal scientists led by Dr Jacques Drouin, researcher at the Institut de recherches cliniques de Montréal (IRCM), and collaborators from around the world (Canada, France, the Netherlands and United States) unravel mechanism of hormone resistance in pituitary tumors of Cushing disease patients.

Cushing disease is caused by pituitary tumors that produce excessive amounts of hormone because the tumor cells have become resistant to negative feedback control by a class of steroid hormones, glucocorticoids. In Cushing disease, this excessive hormone production can lead to hypertension, obesity, diabetes and osteoporosis. Through detailed molecular investigation of the mechanism of this negative feedback, a Montréal research group has identified two essential components (proteins) of this feedback mechanism. Extrapolating from these basic studies, they have shown that about half of the pituitary tumors from Cushing disease patients are deficient in expression of either of these proteins, thus providing a molecular explanation for the hormone resistance that is the hallmark, and likely first event, in the formation of these tumors. The novel insight provided by knowledge of the basic mechanism of hormone resistance will lead to the rational design of therapeutic approaches for the better management of Cushing disease patients. This insight will also help understand other forms of hormone resistant cancers.

This work is published in Genes and Development (Bilodeau et al, Genes Dev 2006, 20:2871- 2886) and it was supported by grants from the Canadian Cancer Society and from the Canadian Institutes of Health Research.

Dr. Jacques Drouin is the Director of the Molecular Genetics Research
Unit at IRCM. He holds the GlaxoSmithKline Chair in Molecular Genetics.

The IRCM (www.ircm.qc.ca) is recognized as one of the country's top-performing research centres. It has a mandate to establish links between research and patients, promote the prevention of illness, and train a new generation of high-level scientists. The IRCM has 37 research units and a staff of more than 450. The IRCM is also affiliated to Université de Montréal.



For further information: Lucette Thériault, Communications Director,
Institut de recherches cliniques de Montréal, (514) 987-5535, lucette.theriault@ircm.qc.ca

From http://www.radioiowa.com/gestalt/go.cfm?objectid=8244194E-8CAA-4EB5-99F57AC68092354C&dbtranslator=local.cfm

Surgeon uses new technique to operate on the brain

Doctor Jeremy Greenlee

by Matt Kelley

An Iowa City brain surgeon is among the first in the Midwest to use a new surgical technique that sounds unorthodox but which he says streamlines the entire process. Doctor Jeremy Greenlee, a professor of neurosurgery at the University of Iowa, says the innovative technique is called endoscopic trans-nasal brain surgery.

Dr. Greenlee says "It's a newer technique where we insert endoscopes and instruments through the nose itself to remove usually pituitary tumors right at the base of the brain. It's a less invasive way to get to the tumors that normally require a larger, more open type exposure in the past." The endoscope is a thin fiber optic tube that lets the surgeon see well without making a large incision. He says the procedure uses the approach of going through the nose to access tumors in hard-to-reach areas of the brain and even the spine.

Greenlee says "The benefit is the patients tend to have less post-operative pain and faster recoveries and shorter hospital stays." He learned the technique through special training in Australia, working with a world-reknown Sydney surgeon who has perfected the procedure. Greenlee says in the past year, he's done 25 or 30 surgeries in Iowa City using the technique.

He says he's almost certainly the first in Iowa to use the technique and one of very few in the Midwest to offer it, though he says more and more surgeons are seeing the advantages of this practice and will start using it. Patients who are subjected to the new technique may only have a three-day hospital stay where those opting for the traditional method may be there at least five days.

---

Obese from Secret Disease
From http://abclocal.go.com/kfsn/story?section=health&id=4663369

October 18, 2006 - Imagine exercising everyday, eating very little and still gaining weight. That's what happens to hundreds of people with a rare metabolic disorder that often goes undiagnosed for years. But there is hope and help.

As a young teen, 22-year-old Jaimie Augustine weighed 130 pounds. She started gaining weight at 15. At 22 she weighed 220. "I was at the gym every day for an hour and a half; I was consuming 1,000 calories or less a day," she says.

Augustine also had insomnia, excess hair growth, severe acne, depression and stopped menstruating. But it took five years before she found a doctor who recognized the symptoms of this mystery disease.

"I felt validation because I had friends and family that didn't believe me," Augustine says. "They're just thinking, 'Oh, you're sneaking Oreos at

"Virtually all the symptoms and physical features of Cushing's can be associated with other diseases -- and diseases that are more common than Cushing's," William Ludlam, M.D., Ph.D., an endocrinologist at Oregon Health and Science University in Portland, tells Ivanhoe.

Cushing is caused by a tumor in the pituitary gland that imbalances your hormones. Glands on the kidneys then release too much of the hormone cortisol. "So despite what you do, your metabolism has been hijacked by too much of a hormone that you actually need to live," Dr. Ludlam says.

No one knows exactly how many people have Cushing's disease because it often goes undiagnosed. But about 1,000 people are told they have it each year in the United States. The first step in diagnosing it is to find an experienced endocrinologist -- the diagnosis can then be confirmed through blood and urine tests.

Some centers treat it through drugs and radiation, and surgery can remove the tumor, with the greatest chance for a cure in the hands of an experienced neurosurgeon.

Augustine's first surgery didn't work, so last fall she had a second procedure. It worked, and she's already lost 40 pounds.

If you would like more information, please contact:
http://www.cushings-help.com

---

Misdiagnosed
It took 15 years before Joyce Dixon finally learned what was really wrong with her.
Cushing's article in Reader's Digest (on the Reader's Digest site)

---

Cortisol:

WOMEN’S HEALTH | Stress hormone linked to miscarriages Kansas City Star - MO, USA

Researchers found that women with high levels of the stress hormone cortisol were nearly three times as likely to miscarry as women with normal levels...

http://www.kansascity.com/mld/kansascity/living/
15773422.htm?template=contentModules/printstory.jsp

Posted on Tue, Oct. 17, 2006

WOMEN’S HEALTH | Stress hormone linked to miscarriages
Stress hormone linked to miscarriages

Women have long worried that stress could increase their risk of miscarriage. Now, the first study to look at stress and early pregnancy loss shows a connection.

Researchers found that women with high levels of the stress hormone cortisol were nearly three times as likely to miscarry as women with normal levels.

Pablo A. Nepomnaschy, a postdoctoral fellow at the National Institutes of Health, measured cortisol in 61 Guatemalan women three times a week for up to a year. Of the 22 pregnancies that occurred, 13 ended in miscarriage. In pregnancies where the mother’s cortisol was higher than normal, 90 percent ended in miscarriage. But only 33 percent of pregnancies were lost when levels were normal.

The likely reason, he says, is that too much cortisol suppresses production of progesterone, a hormone that helps sustain pregnancy.

Although some stress is unavoidable, Nepomnaschy suggests doing whatever you can to eliminate pressure points from your life when you’re trying to become pregnant. Then forget it: There’s no use stressing over stress.

| Rodale Press

---

Growth Hormone:

From http://jcem.endojournals.org/cgi/content/abstract/91/10/3935
Twenty-Four Hour Growth Hormone and Leptin Secretion in Active Postpubertal Adolescent Girls:
Impact of Fitness, Fatness, and Age at Menarche

Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-2841

The Journal of Clinical Endocrinology & Metabolism Vol. 91, No. 10 3935-3940
Copyright © 2006 by The Endocrine Society
Twenty-Four Hour Growth Hormone and Leptin Secretion in Active Postpubertal Adolescent Girls: Impact of Fitness, Fatness, and Age at Menarche
J. Z. Kasa-Vubu, W. Ye, K. T. Borer, A. Rosenthal and T. Meckmongkol

Departments of Pediatrics (J.Z.K.-V., A.R., T.M.), Biostatistics (W.Y.), and Movement Science (K.T.B.), University of Michigan, Ann Arbor, Michigan 48109

Address all correspondence and requests for reprints to: Josephine Z. Kasa-Vubu, M.D., M.S., Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan 48019-0718.

Context: GH is strongly related to body composition, physical activity, and pubertal progression. Adolescent girls decrease physical activity during puberty, whereas their weight increases. Because leptin is a good index of energy balance in active young women, we hypothesized that leptin is related to GH secretion in this population while taking into account fitness, fatness, and age at menarche.

Methods: We measured body composition and maximal oxygen consumption (VO2max) in 37 postpubertal adolescent girls aged 16–21 yr. GH was sampled every 10 min and leptin hourly for 24 h. We first analyzed 6-h time blocks by repeated measures for GH and leptin, with body mass index (BMI), percent body fat, and VO2max as covariates for the entire group and a lean subgroup. The deconvolution method was used to characterize GH pulsatility from individual time points.

Results: GH varied through the day (P < 0.0001), with the highest concentrations overnight. BMI, percent body fat, and VO2max were related to GH concentrations in the entire group, whereas leptin predicted GH in the entire group as well as the lean subgroup of girls. Higher leptin was related to lower GH concentrations (P = 0.011), regardless of time. A log leptin level increase by 1 unit decreased GH by 27%. Pulsatility characteristics showed a 1-yr increase of age at menarche increasing total GH input by 20% (P = 0.0035) independently from BMI.

Conclusion: In postpubertal adolescent girls, leptin is related to GH concentration across the lean to overweight BMI spectrum. GH pulsatile secretion was greater in girls with later age at menarche.

---

New Feature! Add your Helpful Hints for Dealing with Cushing's to the website and the email Newsletters.

Newest Bios:
To add or edit your bio, http://cushings-info.com/tinc?key=ryQTnONX&formname=Bio
Adrenal Patients
Jennifer	Jennifer has had symptoms since middle school.  She was finally diagnosed while in the Army after being sent by MediVac from Iraq. She found this site when she saw Jayne's article in the (Fredericksburg, VA) Free Lance-Star	Fredericksburg, VA
Patricia Ann (Ann)	Patti first started having Cushing's symptoms in 1966. She went to OHSU where she was used as a research patient. She had a pituitary tumor and a bilateral adrenalectomy (BLA) March 21, 1971.	Oregon
Not Yet Diagnosed Patients
Barbara T	Barbara T has been told by many doctors throughout the years that she may have Cushing's syndrome but tests are always inconclusive.	Northern Michigan
Betty Lou (Betty Lou)	Betty Lou takes medications for a great many of her Cushing's-like symptoms but she has not been diagnosed with Cushing's. She has been diagnosed with Systemic Lupus and secondary fibromyalgia. She has taken prednisone for them and is wondering if Relacore could help her.	Condon, OR
Larissa (Rissa)	Larissa has not yet been diagnosed with Cushing's but she has a great many symptoms.  Larissa is a pharmacist.	Martinsburg, WV
Michelle	Michelle has not yet been diagnosed with Cushing's but has many symptoms. A nurse friend showed her the Cushing's article in Reader's Digest and she found this site. Michelle invites people to email her.	Maryland
Molly (MollyKate)	Molly was most recently diagnosed with PCOS.  She has many Cushing's symptoms and will start testing on October 24th.	Oklahoma City, Ok
Sheila F	Sheila F is not yet diagnosed but has many symptoms of Cushing's. Her endo suggested Cushing's.	Georgia
Shiela	Shiela not yet diagnosed with Cushing's but has an appointment October 27, 2006 to see if her doctor will confirm her self-diagnosis of Cushing's.	Thunder Bay, Ontario, Canada
Pituitary Patients
Art Russell	Art is the author of a free (PDF) book in which he shares his experiences with pituitary Cushing's, a BLA and his faith. He includes before and after pictures.	Tulsa, OK Hilo, HI
Gail (Gail G.)	Gail had surgery May 2003.  She has since had other tumors and Gamma Knife	Greenville, NC
LeAnne	LeAnne had pituitary surgery March 23, 2004	Provo UT
Melissa D (honeybee30)	Melissa had pituitary surgery September 15, 2006.  She's feeling much better.	Manteca CA
Patricia Ann (Ann)	Patti first started having Cushing's symptoms in 1966. She went to OHSU where she was used as a research patient. She had a pituitary tumor and a bilateral adrenalectomy (BLA) March 21, 1971.	Oregon
Stephanie (steph)	Stephanie had a pituitary tumor removed Sept 1, 2006. Sept 6 they went in and got part of tumor they missed.	Virginia
To add or edit your bio, http://cushings-info.com/tinc?key=ryQTnONX&formname=Bio
Newest Helpful Doctors:
To add your helpful doctor, http://cushings-info.com/tinc?key=ryQTnONX&formname=Doctors

---

• 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, President of CUSH Org is be the person responsible for the creation of this register.  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.

---

Fundraising:

The Cushing's Store

for all kinds of Cushing's Labeled clothing, US Postage Stamps, coffee mugs, totebags and much more. Great for your endo or Secret Someone. Order Cushing's Awareness Wrist Bands here.

---

Remember iGive.com...

... all year round. iGive.com allows online stores to donate a percentage of their profit to running these Cushing's Support sites: the message boards at http://cushings.invisionzone.com/index.php, http://www.cushings-help.com, http://www.CUSH.org, http://www.cushings-support.com and http://www.cushingsonline.com. See the list of participating merchants ===>  FREE $5 DONATIONS!  <===     Each new member who joins iGive and shops will earn an additional $5 for the Cushing's Support sites! That's on top of the standard donations from shopping (up to 26% of each purchase benefits Cushing's Help and Support!). Only one hitch: supporters must shop within 45 days of joining to get the bonus. With over 600 stores now at iGive.com, we have something for everyone! Thank you so much for your support.

Upcoming Conventions, Meetings and Seminars:

December 7-10, 2006, "December in the Desert 2006" Conference, Rancho Mirage, California.
More info here 

June 2-5, 2007, ENDO 2007, Toronto, Canada, Metro Toronto Center. More info as it becomes available.

More upcoming local meetings are listed here

---

Online Chats:

Please join us in the Chat Room TONIGHT at 9 PM Eastern. Click to access through the message boards

If you are not yet a member of the message boards, please use this page: http://cushings.invisionzone.com/chatroom.htm

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!