Day 7, Cushing’s Awareness Challenge

Posted on April 7, 2026 by MaryO

On Becoming Empowered. Adapted from my blog post Participatory Medicine

The Society for Participatory Medicine - MemberThis 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 ran 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 2016, we have over 12 thousand members and many others on Facebook.  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, interviews, websites, chat groups, LinkedIn, Tumblr, Pinterest 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 nearly 30 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?

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Day 6, Cushing’s Awareness Challenge

Posted on April 6, 2026 by MaryO

In March of 1987, after the endo finally  confirmed that I had Cushing’s, I was sent 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.

My husband asked my endo if it were his wife, if he would recommend this surgery.  The endo responded that he was divorcing his wife – he didn’t care what happened to her.  Oh, my!

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 night before I was admitted, I signed my will.  I was sure I was going to die there.  If not during testing, as a result of surgery.

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. Several were from Greece.

My first roommate was a nurse.  She spent the entire first night screaming in pain.  I was very glad when they moved me to a new room!

Towards the end of my testing period, I was looking forward to the surgery just to get this whole mess over with – either a cure or dying. While I was at NIH, I was gaining about a pound a day!

During the time I was home the weekend  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 reading the alumnae magazine a couple months later!  She was the same class, same major, same home-town, same disease…

We have a Scottish doctor named James Lind to thank for the clinical trial.  He  conducted the first ever clinical trial in 1747 and developed the theory that citrus fruits cured scurvy.  Lind  compared the effects of various different acidic substances, ranging from vinegar to cider, on groups of afflicted sailors, and found that the group who were given oranges and lemons had largely recovered from scurvy after 6 days.

I’d like to think that I advanced the knowledge of Cushing’s at least a little bit by being a guinea  pig in 1987-1989.

From the NIH: http://endocrine.niddk.nih.gov/pubs/cushings/cushings.aspx

Hope through Research

Several components of the National Institutes of Health (NIH) conduct and support research on Cushing’s syndrome and other disorders of the endocrine system, including the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Child Health and Human Development (NICHD), the National Institute of Neurological Disorders and Stroke, the National Cancer Institute, and the National Center for Research Resources.

NIH-supported scientists are conducting intensive research into the normal and abnormal function of the major endocrine glands and the many hormones of the endocrine system. Researchers continue to study the effects of excess cortisol, including its effect on brain structure and function. To refine the diagnostic process, studies are under way to assess the accuracy of existing screening tests and the effectiveness of new imaging techniques to evaluate patients with ectopic ACTH syndrome. Researchers are also investigating jugular vein sampling as a less invasive alternative to petrosal sinus sampling. Research into treatment options includes study of a new drug to treat the symptoms of Cushing’s syndrome caused by ectopic ACTH secretion.

Studies are under way to understand the causes of benign endocrine tumor formation, such as those that cause most cases of Cushing’s syndrome. In a few pituitary adenomas, specific gene defects have been identified and may provide important clues to understanding tumor formation. Endocrine factors may also play a role. Increasing evidence suggests that tumor formation is a multistep process. Understanding the basis of Cushing’s syndrome will yield new approaches to therapy.

The NIH supports research related to Cushing’s syndrome at medical centers throughout the United States. Scientists are also treating patients with Cushing’s syndrome at the NIH Clinical Center in Bethesda, MD. Physicians who are interested in referring an adult patient may contact Lynnette Nieman, M.D., at NICHD, 10 Center Drive, Room 1-3140, Bethesda, MD 20892-1109, or by phone at 301-496-8935. Physicians interested in referring a child or adolescent may contact Constantine Stratakis, M.D., D.Sc., at NICHD, 10 Center Drive, Room 1-3330, Bethesda, MD 20892-1103, or by phone at 301-402-1998.

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Clinical Trial: Multicenter Study of Seliciclib (R-roscovitine) for Cushing Disease

Posted on January 18, 2026 by MaryO
Sponsor:
Information provided by (Responsible Party):
Shlomo Melmed, MD, Cedars-Sinai Medical Center
Brief Summary:

This phase 2 multicenter, open-label clinical trial will evaluate safety and efficacy of 4 weeks of oral seliciclib in patients with newly diagnosed, persistent, or recurrent Cushing disease.

Funding Source – FDA Office of Orphan Products Development (OOPD)

Condition or disease  Intervention/treatment  Phase 
Cushing Disease Drug: Seliciclib Phase 2
Detailed Description:
This phase 2 multicenter, open-label clinical trial will evaluate safety and efficacy of two of three potential doses/schedules of oral seliciclib in patients with newly diagnosed, persistent, or recurrent Cushing disease. Up to 29 subjects will be treated with up to 800 mg/day oral seliciclib for 4 days each week for 4 weeks and enrolled in sequential cohorts based on efficacy outcomes. The study will also evaluate effects of seliciclib on quality of life and clinical signs and symptoms of Cushing disease.
Ages Eligible for Study: 18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
Criteria

Inclusion criteria:

  • Male and female patients at least 18 years old
  • Patients with confirmed pituitary origin of excess adrenocorticotropic hormone (ACTH) production:
    • Persistent hypercortisolemia established by two consecutive 24 h UFC levels at least 1.5x the upper limit of normal
    • Normal or elevated ACTH levels
    • Pituitary macroadenoma (>1 cm) on MRI or inferior petrosal sinus sampling (IPSS) central to peripheral ACTH gradient >2 at baseline and >3 after corticotropin-releasing hormone (CRH) stimulation
    • Recurrent or persistent Cushing disease defined as pathologically confirmed resected pituitary ACTH-secreting tumor or IPSS central to peripheral ACTH gradient >2 at baseline and >3 after CRH stimulation, and 24 hour UFC above the upper limit of normal reference range beyond post-surgical week 6
    • Patients on medical treatment for Cushing disease. The following washout periods must be completed before screening assessments are performed:
      • Inhibitors of steroidogenesis (metyrapone, ketoconazole): 2 weeks
      • Somatostatin receptor ligand pasireotide: short-acting, 2 weeks; long-acting, 4 weeks
      • Progesterone receptor antagonist (mifepristone): 2 weeks
      • Dopamine agonists (cabergoline): 4 weeks
      • CYP3A4 strong inducers or inhibitors: varies between drugs; minimum 5-6 times the half-life of drug

Exclusion criteria:

  • Patients with compromised visual fields, and not stable for at least 6 months
  • Patients with abutment or compression of the optic chiasm on MRI and normal visual fields
  • Patients with Cushing’s syndrome due to non-pituitary ACTH secretion
  • Patients with hypercortisolism secondary to adrenal tumors or nodular (primary) bilateral adrenal hyperplasia
  • Patients who have a known inherited syndrome as the cause for hormone over secretion (i.e., Carney Complex, McCune-Albright syndrome, Multiple endocrine neoplasia (MEN) 1
  • Patients with a diagnosis of glucocorticoid-remedial aldosteronism (GRA)
  • Patients with cyclic Cushing’s syndrome defined by any measurement of UFC over the previous 1 months within normal range
  • Patients with pseudo-Cushing’s syndrome, i.e., non-autonomous hypercortisolism due to overactivation of the hypothalamic-pituitary-adrenal (HPA) axis in uncontrolled depression, anxiety, obsessive compulsive disorder, morbid obesity, alcoholism, and uncontrolled diabetes mellitus
  • Patients who have undergone major surgery within 1 month prior to screening
  • Patients with serum K+< 3.5 while on replacement treatment
  • Diabetic patients whose blood glucose is poorly controlled as evidenced by HbA1C >8%
  • Patients who have clinically significant impairment in cardiovascular function or are at risk thereof, as evidenced by congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, high grade atrioventricular (AV) block, history of acute MI less than one year prior to study entry
  • Patients with liver disease or history of liver disease such as cirrhosis, chronic active hepatitis B and C, or chronic persistent hepatitis, or patients with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 1.5 x ULN, serum total bilirubin more than ULN, serum albumin less than 0.67 x lower limit of normal (LLN) at screening
  • Serum creatinine > 2 x ULN
  • Patients not biochemically euthyroid
  • Patients who have any current or prior medical condition that can interfere with the conduct of the study or the evaluation of its results, such as
    • History of immunocompromise, including a positive HIV test result (ELISA and Western blot). An HIV test will not be required, however, previous medical history will be reviewed
    • Presence of active or suspected acute or chronic uncontrolled infection
    • History of, or current alcohol misuse/abuse in the 12 month period prior to screening
  • Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control. If a woman is participating in the trial then one form of contraception is sufficient (pill or diaphragm) and the partner should use a condom. If oral contraception is used in addition to condoms, the patient must have been practicing this method for at least two months prior to screening and must agree to continue the oral contraceptive throughout the course of the study and for 3 months after the study has ended. Male patients who are sexually active are required to use condoms during the study and for three month afterwards as a precautionary measure (available data do not suggest any increased reproductive risk with the study drugs)
  • Patients who have participated in any clinical investigation with an investigational drug within 1 month prior to screening or patients who have previously been treated with seliciclib
  • Patients with any ongoing or likely to require additional concomitant medical treatment to seliciclib for the tumor
  • Patients with concomitant treatment of strong CYP3A4 inducers or inhibitors.
  • Patients who were receiving mitotane and/or long-acting somatostatin receptor ligands octreotide long-acting release (LAR) or lanreotide
  • Patients who have received pituitary irradiation within the last 5 years prior to the baseline visit
  • Patients who have been treated with radionuclide at any time prior to study entry
  • Patients with known hypersensitivity to seliciclib
  • Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will be unable to complete the entire study
  • Patients with presence of Hepatitis B surface antigen (HbsAg)
  • Patients with presence of Hepatitis C antibody test (anti-HCV)

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Study Examines Therapy Options for Post-adrenalectomy Low Glucocorticoid Levels

Posted on January 12, 2026 by MaryO

Hydrocortisone and prednisone have comparable safety and effectiveness when used as glucocorticoid replacement therapy in patients with adrenal adenoma or Cushing’s disease who underwent adrenalectomy, a new study shows.

The study, “Comparison of hydrocortisone and prednisone in the glucocorticoid replacement therapy post-adrenalectomy of Cushing’s Syndrome,” was published in the journal Oncotarget.

The symptoms of Cushing’s syndrome are related to excessive levels of glucocorticoids in our body. Glucocorticoids are a type of steroid hormones produced by the adrenal gland. Consequently, a procedure called adrenalectomy – removal of the adrenal glands – is usually conducted in patients with Cushing’s syndrome.

Unfortunately, adrenalectomy leads to a sharp drop in hormones that are necessary for our bodies. So, post-adrenalectomy glucocorticoid replacement therapy is required for patients.

Hydrocortisone and prednisone are synthetic glucocorticoids that most often are used for glucocorticoid replacement therapy.

Treatment with either hydrocortisone or prednisone has proven effective in patients with Cushing’s syndrome. However, few studies have compared the two treatments directly to determine if there are significant advantages of one therapy over another.

Chinese researchers set out to compare the effectiveness and safety of hydrocortisone and prednisone treatments in patients with Cushing’s syndrome, up to six months after undergoing adrenalectomy.

Patients were treated with either hydrocortisone or prednisone starting at day two post-adrenalectomy. The withdrawal schedule varied by individual patients.

At baseline, both groups had similar responses to the adrenalectomy, including the correction of hypertension (high blood pressure), hyperglycemia (high blood glucose levels), and hypokalemia (low potassium levels). Furthermore, most patients in both groups lost weight and showed significant improvement, as judged by a subjective evaluation questionnaire.

Hydrocortisone did show a significant advantage over prednisone in the improvement of liver function, but its use also was associated with significant swelling of the lower extremities, as compared to prednisone.

Patients in both groups went on to develop adrenal insufficiency (AI) during glucocorticoid withdrawal. However, there were no significant differences in the AI incidence rate – 35 percent in the hydrocortisone group versus 45 percent in the prednisone group. The severity of A also was not significantly different between the groups.

Furthermore, most of the AI symptoms were relieved by going back to the initial doses of the glucocorticoid replacement.

As there were no significant differences between the two treatments, the findings support “the use of both hydrocortisone and prednisone in the glucocorticoid replacement therapy post-adrenalectomy for patients of adrenal adenoma or Cushing’s disease,” researchers concluded.

From https://cushingsdiseasenews.com/2018/01/11/post-adrenalectomy-glucocorticoid-replacement-therapy/

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FDA Declines to Approve Relacorilant for Hypertension Linked to Hypercortisolism

Posted on January 6, 2026 by MaryO

Key takeaways:

  • The FDA issued a complete response letter for relacorilant to treat hypertension tied to hypercortisolism.
  • The investigational drug induced BP reductions for adults with hypertension in the phase 3 GRACE trial.

The FDA has issued a complete response letter for an oral selective glucocorticoid receptor antagonist under investigation for the treatment of hypertension secondary to hypercortisolism, according to an industry press release.

Corcept Therapeutics announced the FDA issued a complete response letter for relacorilant (Corcept Therapeutics). The drug is under investigation for the treatment of endogenous hypercortisolism, ovarian cancer and other disorders, according to the company.

As Healio previously reported, the phase 3 GRACE trial enrolled 152 adults with Cushing’s syndrome plus hypertension, hyperglycemia or both conditions. Participants received relacorilant for 22 weeks during an open-label phase. At 22 weeks, adults who met criteria for hypertension or hyperglycemia control entered a withdrawal phase where they were randomly assigned, 1:1, to continue relacorilant or switch to placebo for 12 weeks.

In the GRACE trial, adults with hypertension had a 7.9 mm Hg decrease in systolic blood pressure and a 5.1 mm Hg decline in diastolic BP at 22 weeks. During the randomized withdrawal phase, adults who remained on relacorilant had no change in systolic and diastolic BP, whereas those receiving placebo had a BP increase from the start of the phase to week 12.

In a press release from Corcept Therapeutics from 2024, the company announced results from the phase 3 GRADIENT trial, a randomized, double-blind, placebo-controlled trial where adults with Cushing’s syndrome caused by an adrenal adenoma or adrenal hyperplasia were randomly assigned, 1:1, to relacorilant or placebo for 22 weeks. According to the press release, the relacorilant group had a 6.6 mm Hg decline in mean systolic BP compared with baseline at 22 weeks. However, there was no significant difference in mean systolic BP change between the relacorilant and placebo groups.

As Healio previously reported, relacorilant was also assessed in a long-term extension study that enrolled adults who completed the GRACE and GRADIENT trials as well as a phase 2 hypercortisolism study. In that trial, relacorilant conferred a 10 mm Hg drop in 24-hour ambulatory systolic BP and a 7.3 mm Hg reduction in 24-hour ambulatory diastolic BP at 24 months.

In the company’s press release announcing receipt of the complete response letter, Corcept Therapeutics said the FDA acknowledged that the GRACE trial met its primary endpoint and that the GRADIENT trial provided “confirmatory evidence.” However, the FDA said it did not view relacorilant offered “a favorable benefit-risk assessment” without more data of its effectiveness, according to the press release.

“We are surprised and disappointed by this outcome,” Joseph K. Belanoff, MD, CEO of Corcept Therapeutics, said in a press release. “Our commitment to patients suffering from the effects of hypercortisolism is unwavering. I am confident we will find a way to get relacorilant to the patients it could help. We will meet with the FDA as soon as possible to discuss the best path forward.”

https://www.healio.com/news/endocrinology/20251231/fda-declines-to-approve-relacorilant-for-hypertension-linked-to-hypercortisolism?utm_source=selligent&utm_medium=email&utm_campaign=20251231ENDO&utm_content=20251231ENDO

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