Corcept Therapeutics Announces Presentations on Mifepristone for the Treatment of Patients with Hypercortisolism

MENLO PARK, CA — (Marketwired) — 05/04/17 — Corcept Therapeutics Incorporated (NASDAQ: CORT), a pharmaceutical company engaged in the discovery, development and commercialization of drugs that treat severe metabolic, oncologic and psychiatric disorders by modulating the effects of cortisol, today announced that presentations about hypercortisolism and mifepristone’s role in treating that disorder will be presented at the 26th Annual Congress of the American Association of Clinical Endocrinologists (AACE) being held at the Austin Convention Center in Austin, Texas.

“There is growing awareness that even less severe degrees of hypercortisolism are harmful,” said Joseph K. Belanoff, M.D., Corcept’s Chief Executive Officer. “As a result, physicians are increasingly screening patients whose metabolic and cardiovascular symptoms have not responded to conventional therapy and finding cases of previously undetected Cushing’s syndrome.”

In addition to viewing the posters described below, AACE attendees may attend “Evolving Paradigms of Hypercortisolism,” a product theater talk by Ty Carroll, M.D. Corcept is a sponsor of the talk.

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                            Thursday, May 4, 2017
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             Poster #124
 Screening of Diabetic Patients Using
                U500
Insulin Uncovers a High Percentage of     Joseph W. Mathews, M.D., FACE
     Undiagnosed Hypercortisolism              James J. Smith, PhD
             Consistent
        with Cushing Syndrome
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                    Friday, May 5, 2017, 12:45 - 1:30pm
                              Product Theater B
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        Evolving Paradigms of
           Hypercortisolism                      Ty Carroll, M.D.
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                             Friday, May 5, 2017
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             Poster #131
      Medical Management of Mild
     Hypercortisolism and Primary
   Aldosteronism in a Patient with            Sandi-Jo Galati, M.D.
    ACTH-Independent Macronodular         Michele Lamerson, RN, MS, CPNP
             Hyperplasia
      Presenting with Resistant
            Hypertension
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                                     Adriana G. Ioachimescu, M.D., PhD, FACE
             Poster #608                  Jonathan G. Ownby, M.D., FACE
   Improving Glycemic Control with       Nicole G. Greyshock, M.D., FACE
            Mifepristone                   Thomas C. Jones, M.D., FACE
in Cushing Syndrome Patients May Lead     Gary S. Wand, M.D., PhD, FACE
     to Significant Weight-loss                James J. Smith, PhD
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             Poster #725
  Successful Medical Management with           Saima Farghani, M.D.
Mifepristone in a Patient with Occult     Michele Lamerson, RN, MS, CPNP
      Ectopic Cushing Syndrome
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             Poster #836
  Mifepristone Therapy Significantly
              Improved
Insulin Resistance, Glycemic Control,     Jonathan G. Ownby, M.D., FACE
  and Weight Loss in a Patient with            James J. Smith, PhD
           Cushing Disease
 Previously Treated with Pasireotide
----------------------------------------------------------------------------
             Poster #839
  Mifepristone Reduced U500 Insulin
   Usage in a Patient with Cushing       Kimberley A. Bourne, M.D., FACE
  Disease and Normalized Concomitant           James J. Smith, PhD
 Fatty Liver Disease and Retinopathy
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About Corcept Therapeutics Incorporated
Corcept is a pharmaceutical company engaged in the discovery, development and commercialization of drugs that treat severe metabolic, oncologic and psychiatric disorders by modulating the effects of cortisol. Korlym®, a first-generation cortisol modulator, is the company’s first FDA-approved medication. The company has a portfolio of proprietary compounds that modulate the effects of cortisol but not progesterone. Corcept owns extensive intellectual property covering the use of cortisol modulators, including mifepristone, in the treatment of a wide variety of serious disorders, including Cushing’s syndrome. It also holds composition of matter patents covering its selective cortisol modulators.

From http://news.sys-con.com/node/4073068

Reasons You Have Flab Around Your Abdomen

Some diseases and conditions could be responsible for your abdominal fat.
Mita Majumdar | Updated: April 24, 2017 6:15 pm

Visceral fat or unhealthy belly fat that surrounds the liver and other organs in the abdomen puts you at risk for serious health problems, such as, metabolic syndrome, heart disease, and type 2 diabetes. But, what causes your pot belly or beer fat in the first place? The most obvious answers you will get is – ‘You are not exercising enough’, or, ‘you are eating too much of fatty foods or sugary foods’, or ‘you are not eating the right foods’, or ultimately, ‘It’s genetics! You got it from your parents’. All of these reasons are true, of course. However, some diseases/ disorders and conditions, too, could be responsible for your abdominal fat and these have nothing to do with not exercising or not eating right. Following are some of these disorders.

Cushing’s Syndrome

Cushing’s syndrome, also called hypercortisolism, is an endocrine disorder that occurs when your body is exposed to high cortisol levels over a long period of time. It is a treatable disorder, however, if it is chronic, the symptoms can last lifelong.

Symptoms: Symptoms vary according to the severity of the disorder. The characteristic symptoms include –

  • Fatty tissue deposits in the midsection
  • Fatty deposits in the upper back, especially between the shoulders, so that it resembles a hump
  • Puffy face
  • Violaceous stretch marks (pink or purple) on the arms, breast, stomach, and thighs that are more than 1 cm wide. [1]
  • Easy bruising
  • Fatigue
  • Hirsutism and irregularity in menstruation in women
  • Loss of libido and erectile dysfunction in men
  • Cognitive dysfunction, depression, unpredictable emotional outbursts, irritability is present in 70-85 percent of people with Cushing’s syndrome.[1]

Causes:

  • Overuse of corticosteroids
  • Overproduction of cortisol by the adrenal glands

Management:

  • Surgery is the first line of treatment for Cushing’s syndrome.
  • Medication include: [2]

a.Pituitary gland directed therapy

b.Adrenal-blocking drugs

c.Glucocorticoid receptor-antagonizing drugs

  • Pituitary radiotherapy

Addison’s disease

Addison’s disease, also called adrenal insufficiency, is a disorder where your adrenal glands produce insufficient hormones, especially, glucocorticoids including cortisol and aldosterone. It is a life-threatening disease that can affect anyone irrespective of their gender or age.

How do glucocorticoids influence abdominal fats? Glucocorticoids including cortisol convert the fats into energy in the liver. They also help your body respond to stress. When sufficient amount of glucocorticoids are not produced by the adrenal glands, the fats accumulate in the abdominal area, and you see it as flab around your middle.

Symptoms:

  • Hyperpigmentation
  • Extreme fatigue
  • Low blood sugar and low blood pressure
  • Salt craving as one of the functions of adrenal glands is to maintain the sodium-potassium balance in the body
  • Nausea, vomiting, abdominal pain
  • Weight loss but gain in abdominal fat

Causes:

  • Insufficient production of adrenal cortex hormones
  • Stopping of prescribed corticosteroids
  • Tuberculosis and other infections of adrenal glands
  • Spread of cancer to the adrenal glands

Management:

  • Oral corticosteroids or corticosteroid injections
  • Intravenous injections of hydrocortisone, saline solution, and dextrose in case of Addisonian crisis

Stress

Chronic stress is a very big cause of belly fat. When you are exposed to stress, a chain reaction starts in the body because of the dysregulation of HPA axis of the neuroendocrine system. HPA axis is a complex interaction between the hypothalamus, pituitary gland, and adrenal glands. The hypothalamus produces a corticotropin releasing hormone (CRH) and vasopressin. These together stimulate the secretion of adrenocorticotropic hormone (ACTH). ACTH is transported by the blood to the adrenal glands, which then produces corticosteroids, mainly, cortisol from cholesterol. One of the functions of cortisol is to signal the body to store fat, and specifically, the fat storage occurs in the abdominal area, where the cortisol receptors are greater. Researchers have found that stress causes hyperactivation of HPA axis, leading to accumulation of fat tissue, especially in the abdomen region.

So, the more and longer you are stressed (or if you are chronically stressed), chances are that you will be carrying more belly fat!

Ascites

Ascites is the buildup of fluid in the abdominal space. Ascites usually occurs in people with cancer, and it is then called malignant ascites. Onset of ascites is generally the terminal phase in cancer. Ascites also occurs in patients with liver cirrhosis, kidney failure, or heart disease.

Symptoms:

The first sign of ascites is an increase in abdominal girth accompanied by weight gain. [4] Although it looks like it is belly fat, it is actually the fluid that causes the bulging.

Other symptoms include:

  • Shortness of breath
  • Nausea and vomiting
  • Swelling in the feet and ankle
  • Decreased appetite, sense of fullness, bloating
  • Fatigue
  • Haemorrhoids

Management:

If the ascites is not causing any discomfort, it may not require any treatment. Treatment of ascites can have many side effects. Talk to your doctor before you go in for management/ treatment.

Abdominal hernia

Abdominal hernia is a swelling or a bulge in the abdominal area where an organ or fatty tissue pushes through a weak spot in the abdominal wall. The abdominal wall is made up of tough connective tissue and tendons that stretch from the ribs to the groin. Depending on the position of the weakness in your abdominal wall, the hernia can be inguinal (groin), femoral (upper thigh), umbilical (belly button), hiatal (upper stomach), or even incisional. Incisional hernia can occur when the intestine pushes through a weak spot at the site of abdominal surgery.

Symptoms:

  • Visible bulge that may or may not cause discomfort
  • Feeling of heaviness in the abdomen
  • Sharp pain when you strain or lift objects

Causes:

  • Constipation and diarrhoea
  • Persistent coughing and sneezing
  • Straining or suddenly lifting a heavy object

Management:

  • Umbilical hernia, common in young children, mostly resolves by itself as the abdominal muscles get stronger.
  • Other abdominal hernia normally do not resolve by themselves. Doctors suggest waiting and watching.
  • If treatment is required, surgery is the only option. Surgery involves pushing the hernia back into the abdomen and repairing the abdominal wall.

Menopause

Menopause is certainly not a disease or a disorder. It is the time in a woman’s life when she stops menstruating and cannot become pregnant because her ovaries stop producing the required amounts of hormones oestrogen and progesterone. A woman reaches menopause when she has not had her periods for 12 months.

Symptoms:

  • Hot flashes and/ or night sweats
  • Vaginal dryness
  • Mood swings
  • Sleep disturbances

It is very common to gain belly fat during menopause. This is because of the low oestrogen levels. Oestrogen seems to influence the distribution of fat in the body, in a way that the fat is redistributed from the hips, buttocks, and thighs to the belly. However, a study published in the journal Metabolism reported that though women did significantly gain belly fat, especially deep inside the belly, relative fat distribution is not significantly different after menopause. [5] But the fact remains that women do gain flab in the abdomen after menopause.

Belly fat can be seriously harmful. If your belly fat is not because of the above-mentioned conditions, you can lose it by adopting a healthy lifestyle that includes sleeping enough, exercising regularly, eating right, and reducing stress.

Reference

  1. Sharma ST, Nieman LK, Feelders RA. Cushing’s syndrome: epidemiology and developments in disease management. Clinical Epidemiology. 2015;7:281-293. doi:10.2147/CLEP.S44336.
  1. Feelders RA, Hofland LJ. Medical treatment of Cushing’s disease. J Clin Endocrinol Metab. 2013;98:425–438.
  1. Kyrou I, Chrousos GP, Tsigos C. Stress, visceral obesity, and metabolic complications. Ann N Y Acad Sci. 2006 Nov;1083:77-110.
  1. Sinicrope FA. Ascites. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003.
  2. Franklin RM, Ploutz-Snyder L, Kanaley JA. Longitudinal changes in abdominal fat distribution with menopause. Metabolism. 2009 Mar;58(3):311-5. doi: 10.1016/j.metabol.2008.09.030.

Adapted from http://www.thehealthsite.com/diseases-conditions/reasons-you-have-flab-around-your-abdomen-f0417/

 

Lower health-related quality of life observed in patients with Addison’s disease, Cushing’s syndrome

Patients with hypothalamic-pituitary-adrenal axis dysregulations report health-related quality of life that is far lower than that of the general population, according to findings of a prospective study.

“In most centers, both patients with adrenal deficiency and patients with Cushing’s syndrome are managed by the same team,” Charlotte DeBucy, of the Center for Rare Adrenal Diseases at Cochin Hospital in Paris, and colleagues wrote. “Despite the usual perception that both types of diseases alter quality of life, few studies have similarly investigated the impact of cortisol dysregulations on [health-related quality of life]. Such studies are important, however, to identify meaningful differences that would be important to consider to improve management and outcome.”

De Bucy and colleagues analyzed data from 343 patients with Addison’s disease or Cushing’s syndrome followed in routine practice at a single center in France between September 2007 and April 2014 (78% women; mean age, 48 years; mean length of time since diagnosis, 7.8 years; 61% married). All participants completed the short-form health survey (SF-36), a survey of health-related quality-of-life measures and the 12-item general health questionnaire (GHQ-12), a measure of psychological well-being or distress. Questionnaires were completed at baseline and at 6, 12, 24 and 36 months. Patients with Cushing’s syndrome were also assessed for cortisol status at baseline and at follow-up evaluations.

Within the cohort, 206 had Cushing’s syndrome of pituitary origin, 91 had Cushing’s syndrome of adrenal origin and 46 patients had Addison’s disease; 16% were included in the study before any treatment was initiated.

Researchers found that mean standard deviation scores for psychological and physical dimensions of the SF-36 were “well below” those of the general population, but diagnosis, cortisol status and time since treatment initiation all influenced individual scores. Cushing’s syndrome of pituitary origin was associated with worse health-related quality of life, especially for physical functioning, social functioning and mental health. In Cushing’s syndrome, health-related quality of life was generally worse during periods of hypercortisolism, but scores for these patients were lower than those of patients with Addison’s disease even during periods of hypocortisolism or eucortisolism, according to the researchers.

“The differences were particularly large for physical functioning and role-physical subscales,” the researchers wrote.

They also found that mental health scores for patients with Cushing’s syndrome decreased during periods of hypocortisolism, whereas other adrenal conditions were associated with higher mental health scores.

More than half of patients, regardless of diagnosis and cortisol status, had psychological distress requiring attention, according to the GHQ-12 survey.

“Our findings are important for clinical practice,” the researchers wrote. “The consequences of cortisol dysregulation on [health-related quality of life] should be considered in the management of adrenal insufficiency and even more (in) Cushing’s syndrome patients, and these consequences can be long term, affecting apparently cured patients. Early information on these consequences might be helpful for patients who often perceive a poor quality of life as the result of inadequate disease control or treatment. Even if this possibility exists, knowing that adrenal diseases have long-lasting effects on [health-related quality of life] may be helpful for patients to cope with them.” – by Regina Schaffer

Disclosure: L’association Surrénales supported this study. The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7B842655ce-e710-4476-a3c2-2909b06434ed%7D/lower-health-related-quality-of-life-observed-in-patients-with-addisons-disease-cushings-syndrome

A Faster Way to Diagnose Cushing’s Syndrome

Diagnosing Cushing’s syndrome can take 24 hours of complicated and repeated analysis of blood and urine, brain imaging, and tissue samples from sinuses. But that may soon be in the past: National Institutes of Health (NIH) researchers have found that measuring cortisol levels in hair samples can do the same job faster.

Patients with Cushing’s syndrome have a high level of cortisol, perhaps from a tumor of the pituitary or adrenal glands, or as a side effect from medications. In the study, 36 participants—30 with Cushing’s syndrome, six without—provided hair samples divided into three equal segments. The researchers found that the segments closest to the scalp had the most cortisol (96.6 ± 267.7 pg/mg for Cushing’s syndrome patients versus 14.1 ± 9.2 pg/mg in control patients). Those segments’ cortisol content correlated most closely with the majority of the initial biochemical tests, including in blood taken at night (when cortisol levels normally drop).

The study was small; Cushing’s syndrome is rare, and it’s hard to recruit large numbers of patients. Still, the researchers believe it is the largest of its kind to compare hair cortisol levels to diagnostic tests in Cushing’s patients. “Our results are encouraging,” said Mihail Zilbermint, MD, the study’s senior author and an endocrinologist at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. “We are hopeful that hair analysis may ultimately prove useful as a less-invasive screening test for Cushing’s syndrome or in helping to confirm the diagnosis.” The authors suggest the test is also a convenient alternative with the “unique ability” for retrospective evaluation of hypercortisolemia over months.

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From https://www.ptcommunity.com/journal/article/full/2017/4/271/research-briefs-april-2017

Postoperative ACTH, cortisol levels may predict Cushing’s disease remission rate

Early and midterm nonremission after transsphenoidal surgery in people with Cushing’s disease may be predicted by normalized early postoperative values for adrenocorticotropic hormone and cortisol, study data show.

Prashant Chittiboina, MD, MPH, assistant clinical investigator in the neurosurgery unit for pituitary and inheritable diseases at the National Institute of Neurological Diseases and Stroke at the NIH, and colleagues evaluated 250 patients with Cushing’s disease who received 291 transsphenoidal surgery procedures during the study period to determine remission after the procedure. Patients were treated between December 2003 and July 2016. Early remission was assessed at 10 days and medium-term remission was assessed at 11 months.

Early nonremission was predicted by normalized early postoperative values for cortisol (P = .016) and by normalized early postoperative values for adrenocorticotropic hormone (ACTH; P = .048). Early nonremission was further predicted with 100% sensitivity, 39% specificity, 100% negative predictive value and 18% positive predictive value for a cutoff of –12 µg/mL in normalized early postoperative values for cortisol and with 88% sensitivity, 41% specificity, 96% negative predictive value and 16% positive predictive value for a cutoff of –40 pg/mL in normalized early postoperative values for ACTH.

Medium-term nonremission was also predicted by normalized early postoperative values for cortisol (P = .023) and ACTH (P = .025).

“We evaluated the utility of early postoperative cortisol and ACTH levels for predicting nonremission after transsphenoidal adenomectomy for Cushing’s disease,” the researchers wrote. “Postoperative operative day 1 values at 6 a.m. performed best at predicting early nonremission, albeit with a lower [area under the receiver operating characteristic curve]. Normalizing early cortisol and ACTH values to post-[corticotropin-releasing hormone] values improved their prognostic value. Further prospective studies will explore the utility of normalized very early postoperative day 0 cortisol and ACTH levels in identifying patients at risk for nonremission following [transsphenoidal surgery] in patients with [Cushing’s disease].” – by Amber Cox

Disclosure: The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7B7de200ed-c667-4b48-ab19-256d90a7bbc5%7D/postoperative-acth-cortisol-levels-may-predict-cushings-disease-remission-rate

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