Exophthalmos and Cushing's Syndrome

A woman experienced red, irritated and bulging eyes. She saw an ophthalmologist who strongly suspected Graves’ ophthalmopathy. However, the patient did not have and never had hyperthyroidism.

Indeed, she had primary hypothyroidism optimally treated with levothyroxine. Her thyroid stimulating hormone level was 1.197 uIU/mL.

An MRI of the orbits showed normal extraocular muscles without thickening, but there was mild proptosis and somewhat increased intraorbital fat content. Both thyroid-stimulating immunoglobulins as well as thyrotropin receptor antibodies were negative.

The patient presented to her primary care physician a few months later. She had experienced a 40-lb weight gain over only a few months and also had difficult-to-control blood pressure.

After failing to respond to several antihypertensive medications, her primary care physician astutely decided to evaluate for secondary causes of hypertension. A renal ultrasound was ordered to evaluate for renal artery stenosis, and the imaging identified an incidental right-sided adrenal mass. A CT confirmed a 3.4-cm right-sided adrenal mass. Her morning cortisol was slightly high at 24.7 ug/dL (4.3 – 22.4) and her adrenocorticotropic hormone was slightly low at 5 pg/mL (10-60).

At this point I saw the patient in consultation. She definitely had many of the expected clinical exam findings of Cushing’s syndrome, including increased fat deposition to her abdomen, neck, and supraclavicular areas, as well as striae. Her 24-hour urine cortisol was markedly elevated at 358 mcg/24hrs (< 45) confirming our suspicions.

She asked me, “Do you think that my eye problem could be related to this?”

“I’ve not heard of it before,” I replied, “but that doesn’t mean there can’t be a connection. Wouldn’t it be wonderful if your eyes got better after surgery?”

The patient underwent surgery to remove what fortunately turned out to be a benign adrenal adenoma.

When we saw her in follow-up 2 weeks later, her blood pressures were normal off medication and her eye symptoms had improved. I had a medical student rotating with me, so I suggested that we do a PubMed literature search.

The first article to come up was a case report titled “Exophthalmos: A Forgotten Clinical Sign of Cushing’s Syndrome.” Indeed, not only did Harvey Cushing describe this clinical finding in his original case series in 1932, but others have reported that up to 45% of patients with active Cushing’s syndrome have exophthalmos.

The cause is uncertain but is theorized to be due to increased intraorbital fat deposition. Unlike exophthalmos due to thyroid disease, the orbital muscles are relatively normal — just as they were with our patient.

Some of you may have seen exophthalmos in your Cushing’s patients; however, this was the first time I had seen it. Just because one has not heard of something, does not mean it could never happen; no one knows everything. “When in doubt, look it up” is a good habit for both attending physicians and their students.

For more information:

Giugni AS, et al. Case Rep Endocrinol. 2013; 2013: 205208.

From http://www.healio.com/endocrinology/adrenal/news/blogs/%7B779bf3e5-e1da-459e-af27-955c9b4274a5%7D/thomas-b-repas-do-facp-face-cde/exophthalmos-and-cushings-syndrome

Day Three, Cushing's Awareness Challenge

On Becoming Empowered. Adapted from my blog post Participatory Medicine

This is kind of a "cheat" post since it's a compilation of other posts, web pages, message board posts and some original thoughts.  I wrote it to submit to Robin's Grand Rounds, hosted  on her blog.

 

For all of my early life, I was the good, compliant, patient.  I took whatever pills the doctor prescribed, did whatever tests h/she (most always a he) wrote for.  Believed that whatever he said was the absolute truth.  He had been to med school.  He knew what was wrong with me even though he didn't live in my body 24/7 and experience what I did.

I know a lot of people are still like this.  Their doctor is like a god to them.  He can do no wrong - even if they don't feel any better after treatment, even if they feel worse.  "But the doctor said..."

Anyway, I digress.

All this changed for me in 1983.

At first I noticed I'd stopped having my periods and, of course, I thought I was pregnant. I went to my Gynecologist who had no explanation. Lots of women lose their periods for a variety of reasons so no one thought that this was really significant.

Then I got really tired, overly tired. I would take my son to a half hour Choir rehearsal and could not stay awake for the whole time. I would lie down in the back of the van, set an alarm and sleep for the 30 minutes.

A whole raft of other symptoms started appearing - I grew a beard (Hirsuitism), gained weight even though I was on Weight Watchers and working out at the gym nearly every day, lost my period, everything hurt, got what is called a "moon face" and a "buffalo hump" on the back of my neck. I also got stretch marks. I was very depressed but it's hard to say if that was because of the hormone imbalance or because I felt so bad and no one would listen to me.

I came across a little article in the Ladies Home Journal magazine which said "If you have these symptoms...ask your doctor about Cushing's". After that, I started reading everything I could on Cushing's and asking my doctors. Due to all my reading at the library and medical books I bought, I was sure I had Cushing's but no one would believe me. Doctors would say that Cushing's Disease is too rare, that I was making this up and that I couldn't have it.

I asked doctors for three years - PCP, gynecologist, neurologist, podiatrist - all said the now-famous refrain.  It's too rare.  You couldn't have Cushing's.  I kept persisting in my reading, making copies of library texts even when I didn't understand them, keeping notes.  I just knew that someone, somewhere would "discover" that I had Cushing's.

My husband was on the doctors' sides.  He was sure it was all in my mind (as opposed to all in my head!) and he told me to just think "happy thoughts" and it would all go away.

A Neurologist gave me Xanax. Since he couldn't see my tumor with his Magnetic Resonance Imaging (MRI) machine there was "no possibility" that it existed. Boy was he wrong!

Later in 1986 I started bruising incredibly easily. I could touch my skin and get a bruise. On New Year's Day of 1987 I started bleeding under the skin. My husband made circles around the outside perimeter each hour with a marker, like the rings of a tree. When I went to my Internist the next day he was shocked at the size. He now thought I had a blood disorder so he sent me to a Hematologist/Oncologist.

Fortunately, the Hematologist/Oncologist ran a twenty-four hour urine test and really looked at me. Both he and his partner recognized that I had Cushing's. Of course, he was sure that he did the diagnosis.  No matter that I had been pursuing this with other doctors for 3 years.

It was not yet determined if it was Cushing's Disease (Pituitary) or Syndrome (Adrenal). However, he couldn't help me any further so the Hematologist referred me to an Endocrinologist.

The Endocrinologist, of course, didn't trust the other tests I had had done so I was back to square one. He ran his own multitude of tests. He had to draw blood at certain times like 9 AM. and 5 PM. There was a dexamethasone suppression test where I took a pill at 10 p.m. and gave blood at 9 am the next day. I collected gallons of urine in BIG boxes (Fun in the fridge!). Those were from 6 a.m. to 6 a.m. to be delivered to his office by 9 a.m. same day. I was always worried that I'd be stopped in rush hour and the police would ask about what was in that big container. I think I did those for a week. He also did standard neurological tests and asked lots of questions.

When the endo confirmed that I had Cushing's in 1987 he sent me to a local hospital where they repeated all those same tests for another week and decided that it was not my adrenal gland (Cushing's Syndrome) creating the problem. The doctors and nurses had no idea what to do with me, so they put me on the brain cancer ward.

When I left this hospital after a week, we didn't know any more than we had before.

As luck would have it, NIH (National Institutes of Health, Bethesda, Maryland) was doing a clinical trial of Cushing's. I live in the same area as NIH so it was not too inconvenient but very scary at first to think of being tested there. At that time I only had a choice of NIH, Mayo Clinic and a place in Quebec to do this then-rare pituitary surgery called a Transsphenoidal Resection. I chose NIH - closest and free. After I was interviewed by the Doctors there, I got a letter that I had been accepted into the clinical trial. The first time I was there was for 6 weeks as an inpatient. More of the same tests.

There were about 12 of us there and it was nice not to be alone with this mystery disease. Many of these Cushies (mostly women) were getting bald, couldn't walk, having strokes, had diabetes. One was blind, one had a heart attack while I was there. Towards the end of my testing period, I was looking forward to the surgery just to get this whole mess over with. While I was at NIH, I was gaining about a pound a day!

The MRI still showed nothing, so they did a Petrosal Sinus Sampling Test. That scared me more than the prospect of surgery. (This test carries the risk of stroke and uncontrollable bleeding from the incision points.) Catheters were fed from my groin area to my pituitary gland and dye was injected. I could watch the whole procedure on monitors. I could not move during this test or for several hours afterwards to prevent uncontrolable bleeding from a major artery. The test did show where the tumor probably was located. Also done were more sophisticated dexamethasone suppression tests where drugs were administered by IV and blood was drawn every hour (they put a heplock in my arm so they don't have to keep sticking me). I got to go home for a weekend and then went back for the surgery - the Transsphenoidal Resection. I fully expected to die during surgery (and didn't care if I did) so I signed my will and wrote last letters to those I wanted to say goodbye to. During the time I was home just before surgery, a college classmate of mine (I didn't know her) did die at NIH of a Cushing's-related problem. I'm so glad I didn't find out until a couple months later!

November 3, 1987, the surgeon, Dr. Ed Oldfield, cut the gum above my front teeth under my upper lip so there is no scar. He used tiny tools and microscopes. My tumor was removed successfully. In some cases (not mine) the surgeon uses a plug of fat from the abdomen to help seal the cut. Afterwards, I was in intensive care overnight and went to a neurology ward for a few days until I could walk without being dizzy. I had some major headaches for a day or two but they gave me drugs (morphine) for those. Also, I had cotton plugs in my nostrils. It was a big day when they came out. I had diabetes insipidus (DI) for a little while, but that went away by itself - thank goodness!

I had to use a foam product called "Toothies" to brush my teeth without hitting the incision. Before they let me go home, I had to learn to give myself an injection in my thigh. They sent me home with a supply of injectible cortisone in case my level ever fell too low (it didn't). I was weaned gradually off cortisone pills (scary). I now take no medications. I had to get a Medic Alert bracelet. I will always need to tell medical staff when I have any kind of procedure - the effects of my excess cortisone will remain forever.

I went back to the NIH for several follow-up visits of a week each where they did all the blood and urine testing again. After a few years NIH set me free. Now I go to my "outside" endocrinologist every year for the dexamethasone suppression test, 24-hour urine and regular blood testing.

As I get further away from my surgery, I have less and less chance that my tumor will grow back. I have never lost all the weight I gained and I still have the hair on my chin but most of my other symptoms are gone. I am still and always tired and need a nap most days. I do not, however, still need to take whole days off just to sleep.

I consider myself very lucky that I was treated before I got as bad as some of the others on my floor at NIH but think it is crazy that these symptoms are not taken seriously by doctors.

My story goes on and if you're interested some is on this blog and some is here:

Forbes Magazine | MaryO's bio | Cushing's and Cancer Blog | Guest Speakers | Interview Archive  1/3/08 | Cushing's Awareness Day Testimonial Archive |

Because of this experience in getting a Cushing's diagnosis - and later, a prescription for growth hormone - I was concerned that there were probably other people not being diagnosed with Cushing's. When I searched online for Cushing's, all the sites that came up were for dogs and horses with Cushing's.  Not what I was looking for!

In July of 2000, I was talking with my dear friend Alice, who runs a wonderful menopause site, Power Surge, wondering why there weren't many support groups online (OR off!) for Cushing's.  This thought percolated through my mind for a few hours and I realized that maybe this was my calling.  Maybe I should be the one to start a network of support for other "Cushies" to help them empower themselves.

I wanted to educate others about the awful disease that took doctors years of my life to diagnose and treat - even after I gave them the information to diagnose me.  I didn't want anyone else to suffer for years like I did.  I wanted doctors to pay more attention to Cushing's disease.

The first website (http://www.cushings-help.com) went "live" July 21, 2000.  It was just a single page of information. The message boards began September 30, 2000 with a simple message board which then led to a larger one, and a larger.  Today, in 2010, we have over 7 thousand members.  Some "rare disease"!

The message boards are now very active and we have weekly online text chats, weekly live interviews, local meetings, conferences, email newsletters, a clothing exchange, a Cushing's Awareness Day Forum, podcasts, phone support and much more. Because I wanted to spread the word to others not on "the boards" we have extended out to social networking sites - twitter groups, facebook groups, twines, friendfeeds, newsletters, websites, chat groups, multiply.com, and much, much more.

People are becoming more empowered and participating in their own diagnoses, testing and treatment.  This have changed a lot since 1983!

When I had my Cushing's over 20 years ago, I never thought that I would meet another Cushing's patient in real life or online. Back then, I'd never even been aware that there was anything like an "online". I'm so glad that people struggling with Cushing's today don't have to suffer anymore thinking that they're the only one who deals with this.

Because of my work on the websites - and, believe me it is a ton of work! - I have had the honor of meeting over a hundred other Cushies personally at local meetings, conferences, at NIH (the National Institutes of Health in Bethesda, MD where I had my final diagnosis and surgery). It occurred to me once that this is probably more than most endocrinologists will ever see in their entire career. I've also talked to countless others on the phone. Amazing for a "rare" disease!

I don't know what pushed me in 1983, how I got the confidence and self-empowerment to challenge these doctors and their non-diagnoses over the years.  I'm glad that I didn't suffer any longer than I did and I'm glad that I have a role in helping others to find the medical help that they need.

What do *YOU* think?  How are you becoming empowered?

 

Day Two, Cushing's Awareness Challenge

I would be remiss if I didn't use today's Challenge post to remind readers that there is a wonderful opportunity to ask Dr. Theodore Friedman questions about thyroid or other issues.  Dr. Friedman (or Dr. F, as he is called on the boards) has been a help to so many Cushies.  He specializes in cyclical Cushing's and seems to be able to diagnose what other, lesser, doctors cannot.

Dr. Theodore Friedman

According to his website, goodhormonehealth.com:

So many of us believe that fatigue, weight gain, loss of libido and other problems are just symptoms we must learn to live with. What if these symptoms are not the result of stress, diet, or aging, but are actually caused by a hormonal disorder? Symptoms of hormone deficiency or excess may be subtle and difficult to diagnose. Many hormonal problems are misdiagnosed as depression, especially in women.

You know your own body better than anyone else, and you know when something is wrong. Dr. Friedman is a compassionate, caring physician who will listen carefully to your concerns and work with you to establish a treatment plan. As an experienced, board-certified endocrinologist and researcher, he has the capabilities to diagnose and treat even the most difficult hormonal problems.

Dr. Friedman has found that some of his patients suffer from undiagnosed pituitary or adrenal problems. These include many people suffering from Cushing's disease, which can present a baffling array of symptoms and is frequently misdiagnosed. Other patients may have pituitary or adrenal insufficiency, which has numerous symptoms and is equally hard to diagnose. Dr. Friedman is a world expert in these difficult-to-diagnose diseases and he welcomes inquiries from patients and their physicians.

~~~

Dr. Friedman is not a stranger to Cushings Help.

Have questions about thyroid issues?

Ask Dr. Theodore Friedman.

Theodore C. Friedman, M.D., Ph.D. has opened a private practice, specializing in treating patients with adrenal, pituitary, thyroid and fatigue disorders. Dr. Friedman has privileges at Cedars-Sinai Medical Center and Martin Luther King Medical Center. His practice includes detecting and treating hormone imbalances, including hormone replacement therapy. Dr. Friedman is also an expert in diagnosing and treating pituitary disorders, including Cushings disease and syndrome.

Dr. Friedman's career reflects his ongoing quest to better understand and treat endocrine problems. With both medical and research doctoral degrees, he has conducted studies and cared for patients at some of the country's most prestigious institutions, including the University of Michigan, the National Institutes of Health, Cedars-Sinai Medical Center, and UCLA's Charles Drew University of Medicine and Science.

Read Dr. Friedman's First Guest Chat, November 11, 2003.
Read Dr. Friedman's Second Guest Chat, March 2, 2004.

Listen to Dr. Friedman First Live Voice Interview, January 29, 2009.
Listen to Dr. Friedman Second Live Voice Interview, March 12, 2009.
Listen to Dr. Friedman Third Live Voice Interview, February 13, 2011.
Listen to Dr. Friedman Fourth Live Voice Interview, March 12, 2012.

Dr. Friedman will return tonight, April 2, 2012.  The call in number with questions or comments is (646) 200-0162.

Listen live at http://www.blogtalkradio.com/cushingshelp

This interview will be archived afterwards at the same link and on iTunes Cushie Podcasts

 

 

 

Healthy New Year Video Challenge

$5,000 in prizes!

 

Let’s get the new year off to a healthy start! The Office of the National Coordinator for Health Information Technology (ONC) Healthy New Year Video Challenge (#HealthIT4U2012) invites you to create a short, compelling video (up to 2 minutes in length) sharing one New Year’s resolution for improving your health or the health of a loved one, and how you will use technology to achieve your resolution. 

 
We encourage you to create videos that are creative, inspiring and instructive — share a resolution that others can relate to, and demonstrate how technology will make it easier to achieve. Your resolution can be anything health related, such as quitting smoking or drinking, eating healthier, losing weight, reducing stress, or managing a chronic condition. Videos must show how you will use information technology to achieve your resolution and how you plan to maintain it. Entries could include the following kinds of resolutions (these are just examples — be creative and craft your own resolution!):

• I will set up an online personal health record for myself (or another family member) so I can have all of my health information conveniently stored in one place.
• I will ask my doctor for a copy of my own health records — electronically if available — and help him or her to identify any important information that may be missing or need to be corrected.
• I will find an online community that helps me figure out the best ways to manage my health condition (depression, cancer, diabetes, etc.)
• I will use an electronic pedometer to help me track my physical activity and will try to take 10,000 steps per day.
• I will find an app on my smartphone to help me track my food intake so I can lose 10 pounds by my high school reunion.
• I will sign up for a text reminder program on my cell phone to help me stop smoking or remind me to take my medications on time.

The goal of the challenge is to make 2012 a healthier year by motivating and inspiring others to use health information technology to be more engaged in improving health and increasing adoption of consumer health technology.

Note: To participate, you must be a citizen or permanent resident of the United States. Team members must be at least 18, but your video can include minors under 18 as long as a parent or legal guardian signs their consent forms. For details on eligibility, review the Official Rules.

More at http://healthynewyea...v/details/about

(Adrenal Cushing's) Tumour behind 7-yr-old's weight gain, moustache

By: Priyanka Vora   Date: 2012-01-03   Place: Mumbai

 

Tanzania resident Mohammad Abdulrazaq Jussa recuperating after city doctors removed 7-cm tumour from his adrenaline [sic] gland, which was responsible for his 12-kg weight gain, growth of facial hair

Painful and embarrassing stories about one's childhood years, when inexplicable physical changes take place, are not uncommon. But for Mohammad Abdulrazaq Jussa, a resident of Tanzania, it wasn't just ordinarily painful. The seven-year-old was harbouring a tumour in his adrenaline [sic] gland, causing him to suddenly gain 12 kg in a year, and develop a pencil moustache, much to the amusement of his classmates.

Growing pains: Mohammad at age six weighed 25 kg but suddenly his 
weight shot up to 37 kg without any explanation. Doctors are now hoping 
that after the removal of the tumour, the physical changes will regress.

 

The tumour was discovered last year when the boy suddenly started becoming fatter and started growing facial hair. "We had to start buying bigger clothes for him. Initially, my son was thin and active but suddenly, he began growing at a considerable pace.

"He would keep complaining to me about stomach pains but I thought it was just an excuse to miss school and the taunts he received from his friends. Now I regret not paying heed to his cries for help," said Bilkis, Mohammad's mother.

When the weight gain did not stop and he had put on about 12 kg, Mohammad's family sensed something was amiss and took him to doctors in Tanzania.

"The doctors we consulted at first told us that we should restrict his diet but when we told them that there was no change in his diet, doctors started investigating further. We even went to Jerusalem where physicians finally diagnosed that he had a tumour in his adrenaline gland. Seeking treatment for our son, we finally reached Mumbai," added Bilkis.

What doctors found

After the family finally reached city shores a week back, doctors at Saifee Hospital started treatment.

According to Mohammad's doctors, a tumour had grown inside his left adrenaline gland, causing the excess release of hormones resulting in weight gain. Doctors say that Mohammad is suffering from Cushing's syndrome

Under the knife

On Thursday, Mohammad underwent a laparoscopic surgery to remove the tumour, which was seven-cm long and weighed approximately 450 g.

"Mohammad's case was a challenging surgery as he is just seven and at the same time the tumour was as big as his kidney. As we did the surgery laparoscopically, there was no blood loss, giving us excellent post-operative results," said Dr Anup Ramani, uro-oncological surgeon at Saifee Hospital.

'Hoping for normalcy'

Now recuperating at the hospital, Mohammad and his family hope the boy starts looking his age again. Commenting on the changes, Bilkis said, "He was really active before but once he started putting on weight, he started becoming introverted and his studies were also affected. I now pray that everything returns to normal."

When asked about the pace of growth, Dr Ramani said most physical changes would regress in a year's time. "We have put him on a dose of steroids to compensate for the growth spurts he has experienced and hope that all the changes regress."

Cushing's syndrome

Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumours that produce cortisol. Cushing's disease refers to one specific cause of the syndrome: a tumour in the pituitary gland that elevates cortisol.

From http://www.mid-day.com/news/2012/jan/030112-Tumour-behind-7-yr-olds-weight-gain-moustache.htm

 

Corlux: Corcept Therapeutics Announces Third Quarter Results and Corporate and Development Update

MENLO PARK, CA, Nov 07, 2011 (MARKETWIRE via COMTEX) -- Corcept Therapeutics IncorporatedCORT -1.58% , a pharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of severe metabolic and psychiatric disorders, today reported financial results for the quarter ended September 30, 2011, and updated its corporate progress.

"Following the acceptance by the U.S. Food and Drug Administration (FDA) of our New Drug Application (NDA) for the use of our lead product candidate, Korlym(TM), in Cushing's Syndrome," said Joseph Belanoff, M.D., Chief Executive Officer of Corcept, "we continue to focus our efforts on building our commercial capabilities to support the launch of Korlym, if Korlym is approved by the FDA, in order to allow us to provide an important treatment option to patients suffering from Cushing's Syndrome."

Corporate and Development Highlights

--  Received notification in October 2011 that the FDA had accepted our proposed brand name, Korlym (formerly referred to as CORLUX(R)), for our lead product candidate in the treatment of endogenous Cushing's Syndrome.   --  Advanced our commercial launch preparations related to Korlym for the treatment of Cushing's Syndrome, including developing our internal infrastructure and engaging third-party vendors to provide market analytics and to support distribution and other logistical needs in the event Korlym is approved by the FDA.   --  Received notification in October 2011 that the European Commission had granted Korlym Orphan Designation for the treatment of endogenous Cushing's Syndrome (hypercortisolism) in the European Union (EU). Benefits of Orphan Drug Designation in the EU are similar to those in the U.S., but include ten years of marketing exclusivity in all 27 member states, free scientific advice during drug development, access to a centralized review process and a reduction or complete waiver of fees levied by the European Medicines Agency.   --  Enrolled additional patients in our double-blind placebo controlled Phase 3 trial of Korlym for the treatment of the psychotic features of psychotic depression.   --  Continued the clinical portion of our Phase 1b/2a multi-dose safety and proof of concept studies of CORT 108297, one of our selective GR-II antagonists.   --  Identified additional compounds from among our proprietary series of selective GR-II antagonists to advance toward an Investigational New Drug submission.

Third Quarter Financial Results

For the third quarter of 2011, Corcept reported a net loss of $6.4 million, or $0.08 per share, compared to a net loss of $7.1 million, or $0.10 per share, for the third quarter of 2010.

In the third quarter of 2011, research and development expenses decreased to $3.2 million from $5.2 million in the third quarter of 2010. This decrease in research and development expenses was due primarily to decreases in clinical trial costs related to drug-drug interaction and other NDA-supportive studies with Korlym, which were substantially completed in late 2010, and decreases in the clinical trial costs related to the Phase 1b/2a studies with CORT 108297. These decreases were partially offset by increased costs associated with the prosecution of our NDA for Korlym for the treatment of Cushing's Syndrome. General and administrative expenses increased to $3.2 million for the third quarter of 2011 from $1.9 million for the same period in 2010 due primarily to additional expenditures on commercialization activities for the potential launch of Korlym for Cushing's Syndrome.

Our cash balance as of September 30, 2011 was $45.9 million, up from $24.6 million at December 31, 2010. "We anticipate that our current cash balance is sufficient to fund the company through the end of 2012," said Charles Robb, the company's Chief Financial Officer.

Anticipated Activities for the Remainder of 2011

We continue to concentrate our efforts on advancing Korlym toward approval and commercialization for the treatment of Cushing's Syndrome. We also continue our efforts to be prepared to respond in a timely fashion to any questions posed by the FDA during the course of their review of our NDA.

"We are focused intently on developing the commercial and logistical capabilities we will need to make Korlym available to patients suffering from Cushing's Syndrome, should the FDA approve our drug for this indication," added Dr. Belanoff. "Korlym is the first step in unlocking the value of our scientific platform. The regulation of cortisol is a critical biological function; its dysregulation is equally critical in many important disease states. Our own research and research from increasing numbers of academic investigators point to the potential importance of cortisol antagonism in a wide variety of diseases. We believe our expanding library of selective cortisol antagonists may help address these unmet medical needs."

About Cushing's Syndrome

Endogenous Cushing's Syndrome is caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol and is generated by tumors that produce cortisol or ACTH. Cushing's Syndrome is an orphan indication which most commonly affects adults aged 20 to 50. An estimated 10 to 15 of every one million people are newly diagnosed with this syndrome each year, resulting in over 3,000 new patients in the United States. An estimated 20,000 patients in the United States have Cushing's Syndrome. Symptoms vary, but most people have one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Cushing's Syndrome can affect every organ system in the body and can be lethal if not treated effectively.

About Psychotic Depression

Psychotic depression is a serious psychiatric disorder that affects approximately three million people annually in the United States. It is more prevalent than either schizophrenia or bipolar I disorder. The disorder is characterized by severe depression accompanied by delusions, hallucinations or both. People with psychotic depression are approximately 70 times more likely to commit suicide than the general population and often require lengthy and expensive hospital stays. There is no FDA-approved treatment for psychotic depression.

About Weight Gain Caused by Antipsychotic Medications

The group of medications known as second-generation antipsychotics, including olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel) and clozapine (Clozaril), are widely used to treat schizophrenia and bipolar disorder. All medications in this group are associated with treatment emergent weight gain of varying degrees and also carry warning labels relating to treatment emergent hyperglycemia and diabetes mellitus. There is no FDA-approved treatment for the weight gain associated with the use of antipsychotic medications.

About Korlym

Corcept's first-generation compound, Korlym, also known as mifepristone, directly blocks the cortisol (GR-II) receptor and the progesterone (PR) receptor. Intellectual property protection is in place to protect important methods of use for Korlym. Corcept retains worldwide rights to its intellectual property related to Korlym.

About CORT 108297

CORT 108297 is a potent, selective antagonist of the cortisol (GR-II) receptor that we have discovered and for which Corcept owns worldwide intellectual property rights. In in vitro binding affinity and functional assays this compound has no affinity for the progesterone (PR), estrogen (ER), androgen (AR) or mineralocorticoid (GR-I) receptors.

About Corcept Therapeutics Incorporated

Corcept is a pharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of severe metabolic and psychiatric disorders. The company has completed its Phase 3 study of Korlym for the treatment of Cushing's Syndrome, and has an ongoing Phase 3 study of Korlym for the treatment of the psychotic features of psychotic depression. Corcept also has a Phase 2 program for CORT 108297, a selective GR-II antagonist that blocks the effects of cortisol but not progesterone. Corcept has developed an extensive intellectual property portfolio that covers the use of GR-II antagonists in the treatment of a wide variety of psychiatric and metabolic disorders, including the prevention of weight gain caused by the use of antipsychotic medication, as well as composition of matter patents for our selective GR-II antagonists.

Statements made in this news release, other than statements of historical fact, are forward-looking statements, including, for example, statements relating to the potential benefit of Korlym for patients diagnosed with Cushing's Syndrome, Corcept's clinical development and research programs, the outcome of the FDA's review of our NDA filing, our estimates for our capital requirements and needs for additional financing, the introduction of Korlym and future product candidates, including CORT 108297, the ability to create value from Korlym or other future product candidates or our scientific platform and our commercialization plans. Forward-looking statements are subject to a number of known and unknown risks and uncertainties that might cause actual results to differ materially from those expressed or implied by such statements. For example, there can be no assurances with respect to the cost, rate of spending, completion or success of clinical trials; financial projections may not be accurate; there can be no assurances that Corcept will pursue further activities with respect to the development of Korlym, CORT 108297, or any of its other selective GR-II antagonists. These and other risk factors are set forth in the Company's SEC filings, all of which are available from our website ( www.corcept.com ) or from the SEC's website ( www.sec.gov ). We disclaim any intention or duty to update any forward-looking statement made in this news release.

CORCEPT THERAPEUTICS INCORPORATED CONDENSED BALANCE SHEETS (in thousands)  September 30,  December 31, 2011           2010 -------------- -------------- (Unaudited)      (Note) ASSETS: Current assets: Cash and cash equivalents                    $       45,909 $       24,578 Other current assets                                    427            418 -------------- -------------- Total current assets                               46,336         24,996  Other assets                                               43            108 -------------- -------------- Total assets                               $       46,379 $       25,104 ============== ==============  LIABILITIES AND STOCKHOLDERS' EQUITY: Current liabilities: Accounts payable                             $        1,066 $          817 Other current liabilities                             1,647          3,043 -------------- -------------- Total current liabilities                           2,713          3,860  Total stockholders' equity                             43,666         21,244 -------------- --------------  Total liabilities and stockholders' equity $       46,379 $       25,104 ============== ==============  Note: Derived from audited financial statements at that date.  CORCEPT THERAPEUTICS INCORPORATED CONDENSED STATEMENTS OF OPERATIONS (in thousands, except per share amounts)  (Unaudited)  For the Three Months Ended   For the Nine Months Ended September 30,               September 30, --------------------------  -------------------------- 2011          2010          2011          2010 ------------  ------------  ------------  ------------  Operating expenses: Research and development*      $      3,228  $      5,224  $     14,355  $     14,286 General and administrative*          3,209         1,881         8,049         5,327 ------------  ------------  ------------  ------------ Total operating expenses               6,437         7,105        22,404        19,613 ------------  ------------  ------------  ------------  Loss from operations       (6,437)       (7,105)      (22,404)      (19,613)  Interest and other income, net                    3             4             3           758 Other expense                  (1)           (3)          (17)          (18) ------------  ------------  ------------  ------------ Net loss         $     (6,435) $     (7,104) $    (22,418) $    (18,873) ============  ============  ============  ============   Basic and diluted net loss per share  $      (0.08) $      (0.10) $      (0.27) $      (0.28) ============  ============  ============  ============ Shares used in computing basic and diluted net loss per share                 84,188        72,045        83,000        66,982 ============  ============  ============  ============  *Includes non-cash stock-based compensation of the following: Research and development     $        110  $         45  $        432  $        170 General and administrative           844           500         1,971         1,361 ------------  ------------  ------------  ------------ Total non-cash stock-based compensation  $        954  $        545  $      2,403  $      1,531 ============  ============  ============  ============

CONTACT: Charles Robb Chief Financial Officer Corcept Therapeutics 650-688-8783 Email Contact  www.corcept.com

SOURCE: Corcept Therapeutics

http://www2.marketwire.com/mw/emailprcntct?id=150008C85C40D638      http://www.corcept.com/

Archived Interviews with MaryO, Cushing's Help Founder

From August 10, 2011

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From January 3, 2008

Interview with Mary O'Connor (MaryO), founder of Cushings-Help.com and 20-year pituitary Cushing's Survivor. Robin (staticnrg) hosts.

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Read MaryO's bio

Check-Up: Cushing's Syndrome

MARION KERR

I’ve been diagnosed with Cushing’s syndrome which my doctor says is the result of many years of steroid use for rheumatoid arthritis. 

Cushing’s syndrome is a disorder that occurs when your body is exposed to high levels of the hormone cortisol. As in your case it can be caused by taking too much corticosteroid medications. These drugs are used to treat chronic conditions such as rheumatoid arthritis and asthma. Other people develop Cushing’s syndrome because their bodies produce too much cortisol, a hormone normally made in the adrenal gland.

Causes of too much cortisol produced by the body include Cushing’s disease (in which the pituitary gland makes too much of a hormone called ACTH, which in turn promotes the production of increased levels of cortisol). Tumours of the pituitary gland, adrenal gland or elsewhere in the body may also cause high levels of cortisol.

I’ve put on an awful lot of weight, especially around my tummy and face. 

Most people with Cushing’s syndrome will develop upper body obesity while their arms and legs remain thin. Typically, the face becomes round and full. Skin changes are common with purple marks (striae) on the skin developing on the abdomen, thighs and breasts. The skin may thin and bruise easily. Muscle and bone changes may occur which can result in backache, bone pain and tenderness. There may also be a marked collection of fat between the shoulders. Women with Cushing’s syndrome may experience excess hair growth and menstrual cycles may become irregular or stop altogether. Men may experience a decrease in fertility, libido problems and impotence. Both sexes may suffer from depression, anxiety, fatigue, headache and high blood pressure.

Will I need a lot of tests to confirm the diagnosis? 

Tests to confirm the diagnosis may include blood and urine tests in addition to abdominal and bone scans. Treatment will depend on the cause. Cushing’s syndrome caused by corticosteroid use will involve slowly decreasing the drug dose (if possible) under medical supervision. If the medication cannot be discontinued, blood sugar, cholesterol levels and bone health will be closely monitored.

Cushing’s syndrome caused by a pituitary or other tumour that releases ACTH will be surgically removed. In some cases, radiation therapy may be required.

Following surgery, long-term cortisol replacement therapy may be required. Cushing’s syndrome due to an adrenal or other tumour will also be removed by surgery.

If the tumour cannot be removed, medications to help block the release of cortisol are prescribed.

From http://www.irishtimes.com/newspaper/health/2011/0621/1224299297903.html

Cushing's and Cancer - the Reality of it all

This post is by Judy, a long-time message board member who is in the middle of Cushing's patients.  Both children and her ex-husband have dealt with Cushing's.  Judy is a Cushie-Blogger.

She posted this on her blog at http://judcol.blogspot.com/2011/06/okay-im-probably-ready-to-get.html

Okay, I'm probably ready to get politically incorrect here. Oh well.
It seems that at least once a day, sometimes many times a day,I see a post on Facebook that in its short version says a cancer patient has just one wish, that is to live. Repost.......

I have no doubt that is true. I have known several cancer patients & it is a real struggle and sometimes the outcome isn't good (understatement).

Now here is the *but* & my own little personal rant.

A Cushing's patient has many wishes.
1. Finding a doctor that believes they can actually be sick, not just fat & depressed (which happen to be symptoms).
2. Having friends & family that thought they were truly sick not just lazy.
3. Having enough energy to make it through the day and not being totally exhausted whether they did or didn't accomplish something that day.
4.Being able to find an understanding doctor that isn't halfway across (or clear across) the country. The same can be said of finding surgeons.
5. Wanting their mind to be clear enough that they can keep up with their job & their peers.
6. Wishing their body was physically able to do just some of the simple tasks set before it.
7. Wishing that they didn't feel like they could throw up most of the day.
8. Praying they can get a nights sleep so they can make it through work the next day. And that they didn't have so much muscle & bone pain.
9. Wanting their mood swings to go away so they can keep up with their emotions.
10. Praying (literally) that they live long enough to get a diagnosis.

This list could go on & on. The really sad part is that there were times I wished my family had cancer. Getting a dx would of (usually) been so much easier. Cancer doesn't usually affect every system in the body. If you get a cure from cancer you aren't usually left with permanent damage to random body systems.

Statistics say that Cushing's is rare. I know it's not. As the Cushie community says - it's just rarely diagnosed. Most people think they don't know anyone with Cushing's. Most people would be wrong. They just don't know a diagnosed Cushing's patient.

That overweight woman in front of you in the checkout line? The one that has terrible mood swings? She might have Cushing's. The coworker that suddenly can barely do her job because she is so exhausted and has terrible brain fog? She might also have Cushing's. You know that girl at school that now has arms so hairy it looks like fur? You know, the one that also smells funky sometimes? Yeah, she probably has Cushing's. You laugh at her but you know what? This disease doesn't discriminate. It might be you someday wondering why the weight keeps piling on when you barely have an appetite and work out every day.
As with the list of *wishes* I could go on & on because Cushing's truly is the disease that keeps on giving & giving & giving. Even after a cure (relative term) it still keeps on giving.

As a wonderful neurosurgeon has said "Cushing's kills." It just does it at a very slow, painful pace.

MaryO'Note:

This is fantastic, Judy. Thanks for saying it!

I've often seen that stupid FB post and haven't reposted it.

I am both a Cushing's and a cancer survivor. For me, the cancer was easier to deal with.

I have been dealing with Cushing's and the after-effects since the early 1980's.

All I'm left with after my cancer is a scar and some bad memories.

I think Sarah's death got lots of us thinking. We've seen so many unnecessary Cushing's deaths and it just breaks my heart.

Judy, may I use this as a guest post on my Cushing's and Cancer blog? It's perfect!

Cushing's Disease Treatment

A 19-year-old woman was referred to Dr. Adriana Ioachimescu for evaluation following an abnormal 1-mg dexamethasone suppression test. She started to experience weight gain, hirsutism and oligomenorrhea at age 16. At that time, she was diagnosed with type 2 diabetes, which was not controlled, despite oral medications and 200 units of insulin daily. A few months before her initial visit to the Emory Pituitary Center, the patient experienced a hip fracture and required surgery. On examination, it was discovered that she had typical Cushing’s stigmata, severe proximal myopathy and depression. She was unable to walk without assistance.

Laboratory testing results were remarkable for hypokalemia, elevated serum cortisol and adrenocorticotropic hormone (ACTH) levels, and elevated bedtime salivary cortisol (15 times above normal). A high-dose dexamethasone suppression test was equivocal. Magnetic resonance imaging (MRI) of the pituitary gland showed no abnormalities. The patient was scheduled for a corticotropin-releasing hormone (CRH) test; however, she was unable to keep the appointment due to MRSA sepsis/perineal cellulitis.

Dr. Ioachimescu started the patient on ketoconazole, which she took for three months, along with multiple courses of antibiotics, during which her diabetes and hypokalemia improved. Once the MRSA infection cleared, she underwent inferior petrosal sinus sampling at Emory University Hospital, which showed a 5:1 central-to-periphery gradient on the right side. A computed tomography (CT) scan of the neck, chest, abdomen and pelvis and an octreoscan did not identify a tumor.

Dr. Oyesiku performed 3-D transsphenoidal endoscopic surgery to remove the tumor causing Cushing’s disease, and her postoperative cortisol on postoperative day three was low at 1.4 mcg/dL. The patient did not experience postoperative endocrine or neurosurgical complications. She required hydrocortisone postoperatively and lost 19 kg in the first three months following the procedure. Her appearance, mood and muscle strength improved significantly.

This case illustrates challenges related to diagnosis of Cushing’s disease in the setting of multiple complications. An accurate diagnosis was made only after inferior petrosal sinus sampling. Treatment with transsphenoidal surgery was successful, despite a lack of tumor identification by preoperative imaging. At the Emory Pituitary Center, Cushing’s disease has a 92% rate of remission at three months following surgery. These statistics are based on the electronic database review of almost 70 patients with Cushing’s disease operated on by Dr. Oyesiku over a period of 15 years. Based on Dr. Ioachimescu’s research, cortisol levels lower than 5 mcg/dL in the first two postoperative days are predictive of surgical success, but do not correlate with recurrence rate.

From http://emoryheartfailure.com/neurosciences/case-studies/cushings-treatment.html