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  1. 2 points
    MENLO PARK, Calif., Aug. 28, 2019 (GLOBE NEWSWIRE) -- Corcept Therapeutics Incorporated (NASDAQ: CORT) announced today that the United States Patent and Trademark Office has issued a Notice of Allowance for a patent covering the administration of Korlym® with food. The patent will expire in November 2032. “This patent covers an important finding of our research – that for optimal effect, Korlym must be taken with food,” said Joseph K. Belanoff, MD, Corcept’s Chief Executive Officer. “Korlym’s label instructs doctors that ‘Korlym must always be taken with a meal.’” Upon issuance, Corcept plans to list the patent, entitled “Optimizing Mifepristone Absorption” (U.S. Pat. App. 13/677,465), in the U.S. Food and Drug Administration’s Approved Drug Products with Therapeutic Equivalence Evaluations (the “Orange Book”). Korlym is currently protected by ten patents listed in the Orange Book. Hypercortisolism Hypercortisolism, often referred to as Cushing’s syndrome, is caused by excessive activity of the hormone cortisol. Endogenous Cushing’s syndrome is an orphan disease that most often affects adults aged 20-50. In the United States, an estimated 20,000 patients have Cushing’s syndrome, with about 3,000 new patients diagnosed each year. Symptoms vary, but most people with Cushing’s syndrome experience 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. Hypercortisolism can affect every organ system in the body and can be lethal if not treated effectively. About Corcept Therapeutics Incorporated Corcept is a commercial-stage company engaged in the discovery and development of drugs that treat severe metabolic, oncologic and psychiatric disorders by modulating the effects of the stress hormone cortisol. Korlym® (mifepristone) was the first treatment approved by the U.S. Food and Drug Administration for patients with Cushing’s syndrome. Corcept has discovered a large portfolio of proprietary compounds, including relacorilant, exicorilant and miricorilant, that selectively modulate the effects of cortisol but not progesterone. Corcept owns extensive United States and foreign intellectual property covering the composition of its selective cortisol modulators and the use of cortisol modulators, including mifepristone, to treat a variety of serious disorders. Forward-Looking Statements Statements in this press release, other than statements of historical fact, are forward-looking statements, which are based on Corcept’s current plans and expectations and are subject to risks and uncertainties that might cause actual results to differ materially from those such statements express or imply. These risks and uncertainties include, but are not limited to, Corcept’s ability to generate sufficient revenue to fund its commercial operations and development programs; the availability of competing treatments, including generic versions of Korlym; Corcept’s ability to obtain acceptable prices or adequate insurance coverage and reimbursement for Korlym; and risks related to the development of Corcept’s product candidates, including regulatory approvals, mandates, oversight and other requirements. These and other risks are set forth in Corcept’s SEC filings, which are available at Corcept’s website and the SEC’s website. In this press release, forward-looking statements include those concerning Corcept’s plans to list the patent “Optimizing Mifepristone Absorption” in the Orange Book; Korlym’s current protection by ten patents listed in the Orange Book; and the scope and protective power of Corcept’s intellectual property. Corcept disclaims any intention or duty to update forward-looking statements made in this press release. CONTACT: Christopher S. James, MD Director, Investor Relations Corcept Therapeutics 650-684-8725 cjames@corcept.com www.corcept.com
  2. 2 points
    It sure sounds like you're on the right track!
  3. 2 points
    I received my dictation from Doctor F.. I pray that I am on the road to a diagnosis. I don’t know how much more of this I can take.
  4. 2 points
    Metoclopramide, a gastrointestinal medicine, can increase cortisol levels after unilateral adrenalectomy — the surgical removal of one adrenal gland — and conceal adrenal insufficiency in bilateral macronodular adrenal hyperplasia (BMAH) patients, a case report suggests. The study, “Retention of aberrant cortisol secretion in a patient with bilateral macronodular adrenal hyperplasia after unilateral adrenalectomy,” was published in Therapeutics and Clinical Risk Management. BMAH is a subtype of adrenal Cushing’s syndrome, characterized by the formation of nodules and enlargement of both adrenal glands. In this condition, the production of cortisol does not depend on adrenocorticotropic hormone (ACTH) stimulation, as usually is the case. Instead, cortisol production is triggered by a variety of stimuli, such as maintaining an upright posture, eating mixed meals — those that contain fats, proteins, and carbohydrates — or exposure to certain substances. A possible treatment for this condition is unilateral adrenalectomy. However, after the procedure, some patients cannot produce adequate amounts of cortisol. That makes it important for clinicians to closely monitor the changes in cortisol levels after surgery. Metoclopramide, a medicine that alleviates gastrointestinal symptoms and is often used during the postoperative period, has been reported to increase the cortisol levels of BMAH patients. However, the effects of metoclopramide on BMAH patients who underwent unilateral adrenalectomy are not clear. Researchers in Japan described the case of a 61-year-old postmenopausal woman whose levels of cortisol remained high after surgery due to metoclopramide ingestion. The patient was first examined because she had experienced high blood pressure, abnormal lipid levels in the blood, and osteoporosis for ten years. She also was pre-obese. She was given medication to control blood pressure with no results. The lab tests showed high serum cortisol and undetectable levels of ACTH, suggesting adrenal Cushing’s syndrome. Patients who have increased cortisol levels, but low levels of ACTH, often have poor communication between the hypothalamus, the pituitary, and the adrenal glands. These three glands — together known as the HPA axis — control the levels of cortisol in healthy people. Imaging of the adrenal glands revealed they were both enlarged and presented nodules. The patient’s cortisol levels peaked after taking metoclopramide, and her serum cortisol varied significantly during the day while ACTH remained undetectable. These results led to the BMAH diagnosis. The doctors performed unilateral adrenalectomy to control cortisol levels. The surgery was successful, and the doctors reduced the dose of glucocorticoid replacement therapy on day 6. Eight days after the surgery, however, the patient showed decreased levels of fasting serum cortisol, which indicated adrenal insufficiency — when the adrenal glands are unable to produce enough cortisol. The doctors noticed that metoclopramide was causing an increase in serum cortisol levels, which made them appear normal and masked the adrenal insufficiency. They stopped metoclopramide treatment and started replacement therapy (hydrocortisone) to control the adrenal insufficiency. The patient was discharged 10 days after the surgery. The serum cortisol levels were monitored on days 72 and 109 after surgery, and they remained lower than average. Therefore she could not stop hydrocortisone treatment. The levels of ACTH remained undetectable, suggesting that the communication between the HPA axis had not been restored. “Habitual use of metoclopramide might suppress the hypothalamus and pituitary via negative feedback due to cortisol excess, and lead to a delayed recovery of the HPA axis,” the researchers said. Meanwhile, the patient’s weight decreased, and high blood pressure was controlled. “Detailed surveillance of aberrant cortisol secretion responses on a challenge with exogenous stimuli […] is clinically important in BMAH patients,” the study concluded. “Caution is thus required for assessing the actual status of the HPA axis.” From https://cushingsdiseasenews.com/2019/05/07/metoclopramide-conceals-adrenal-insufficiency-after-gland-removal-bmah-patients-case-report/
  5. 2 points
    This is such great news, Donna - the endo sounds fantastic. Can you please share his info with others so that they might have a faster diagnosis, too? Hopefully, surgery will be soon and on to remission!
  6. 1 point
    Written by Kathleen Doheny with Maria Fleseriu, MD, FACE, and Vivien Herman-Bonert, MD Cushing's disease, an uncommon but hard to treat endocrine disorder, occurs when a tumor on the pituitary gland, called an adenoma—that is almost always benign—leads to an overproduction of ACTH (adrenocorticotropic hormone), which is responsible for stimulating the release of cortisol, also known as the stress hormone. Until now, surgery to remove the non-cancerous but problematic tumor has been the only effective treatment. Still, many patients will require medication to help control their serum cortisol levels, and others cannot have surgery or would prefer to avoid it. Finally, a drug proves effective as added on or alternative to surgery in managing Cushing's disease. Photo; 123rf New Drug Offers Alternative to Surgery for Cushing's Disease Now, there is good news about long-term positive results achieved with pasireotide (Signifor)—the first medication to demonstrate effectiveness in both normalizing serum cortisol levels and either shrinking or slowing growth of tumors over the long term.1,2 These findings appear in the journal, Clinical Endocrinology, showing that patients followed for 36 months as part of an ongoing study had improved patient outcomes for Cushing’s disease.2 "What we knew before this extension study was—the drug will work in approximately half of the patients with mild Cushing's disease," says study author Maria Fleseriu, MD, FACE, director of the Northwest Pituitary Center and professor of neurological surgery and medicine in the division of endocrinology, diabetes and clinical nutrition at the Oregon Health and Sciences University School of Medicine. “Pasireotide also offers good clinical benefits," says Dr. Fleseriu who is also the president of the Pituitary Society, “which includes improvements in blood pressure, other signs and symptoms of Cushing’s symptom], and quality of life.”2 What Symptoms Are Helped by Drug for Cushing's Disease? Among the signs and symptoms of Cushing’s disease that are lessened with treatment are:3 Changes in physical appearance such as wide, purple stretch marks on the skin (eg, chest, armpits, abdomen, thighs) Rapid and unexplained weight gain A more full, rounder face Protruding abdomen from fat deposits Increased fat deposits around the neck area The accumulation of adipose tissue raises the risk of heart disease, which adds to the urgency of effective treatment. In addition, many individuals who have Cushing’s disease also complain of quality of life issues such as fatigue, depression, mood and behavioral problems, as well as poor memory.2 As good as the results appear following the longer term use of pasireotide,2 Dr. Fleseriu admits that in any extension study in which patients are asked to continue on, there are some built-in limitations, which may influence the findings. For example, patients who agree to stay on do so because they are good responders, meaning they feel better, so they’re happy to stick with the study. “Fortunately, for the patients who have responded to pasireotide initially, this is a drug that can be continued as there are no new safety signals with longer use," Dr. Fleseriu tells EndocrineWeb, "and when the response at the start is good, very few patients will lose control of their urinary free cortisol over time. That's a frequent marker used to monitor patient's status. For those patients with large tumors, almost half of them had a significant shrinkage, and all the others had a stable tumor size." What Are the Reasons to Consider Drug Treatment to Manage Cushing’s Symptoms The extension study ''was important because we didn't have any long-term data regarding patient response to this once-a-month treatment to manage Cushing's disease," she says. While selective surgical removal of the tumor is the preferred treatment choice, the success rate in patients varies, and Cushing's symptoms persist in up to 35% of patients after surgery. In addition, recurrent rates (ie, return of disease) range from 13% to 66% after individuals experience different durations remaining in remission.1 Therefore, the availability of an effective, long-lasting drug will change the course of therapy for many patients with Cushing’s disease going forward. Not only will pasireotide benefit patients who have persistent and recurrent disease after undergoing surgery, but also this medication will be beneficial for those who are not candidates for surgery or just wish to avoid having this procedure, he said. Examining the Safety and Tolerability of Pasireotide This long-acting therapy, pasireotide, which is given by injection, was approved in the US after reviewing results of a 12-month Phase 3 trial.1 In the initial study, participants had a confirmed pituitary cause of the Cushing's disease. After that, the researchers added the optional 12-month open-label, extension study, and now patients can continue on in a separate long-term safety study. Those eligible for the 12-month extension had to have mean urinary free cortisol not exceeding the upper limit of normal (166.5 nanomoles per 24 hour) and/or be considered by the investigator to be getting substantial clinical benefit from treatment with long-action pasireotide, and to demonstrate tolerability of pasireotide during the core study.1 Of the 150 in the initial trial, 81 participants, or 54% of the patients, entered the extension study. Of those, 39 completed the next phase, and most also enrolled in another long-term safety study—these results not yet available).2 During the core study, 1 participants were randomly assigned to 10 or 30 mg of the drug every 28 days, with doses based on effectiveness and tolerability. When they entered the extension, patients were given the same dose they received at month.1,2 Study Outcomes Offer Advantages in Cushing’s Disease Of those who received 36 months of treatment with pasireotide, nearly three in four (72.2%) had controlled levels of urinary free cortisol at this time point.2 Equally good news for this drug was that tumors either shrank or did not grow. Of those individuals who started the trial with a measurable tumor (adenoma) as well as those with an adenoma at the two year mark (35 people), 85.7% of them experienced a reduction of 20% or more or less than a 20% change in tumor volume. No macroadenomas present at the start of the study showed a change of more than 20% at either month 24 or 36.2 Improvements in blood pressure, body mass index (BMI) and waist circumference continued throughout the extension study.1 Those factors influence CVD risk, the leading cause of death in those with Cushing's.4 As for adverse events, most of the study participants, 91.4%, did report one or more complaint during the extension study—most commonly, it was high blood sugar, which was reported by nearly 40% of participants.2. This is not surprising when you consider that most (81.5%) of the individuals participating in the extension trial entered with a diagnosis of diabetes or use of antidiabetic medication, and even more of them (88.9%) had diabetes at the last evaluation.1 This complication indicates the need for people with Cushing’s disease to check their blood glucose, as appropriate. Do You Have Cushing’s Disese? Here's What You Need to Know Women typically develop Cushing’s disease more often than men. What else should you be aware of if you and your doctor decide this medication will help you? Monitoring is crucial, says Dr. Fleseriu, as you will need to have your cortisol levels checked, and you should be on alert for any diabetes signals, which will require close monitoring and regular follow-up for disease management. Another understanding gained from the results of this drug study: "This medication works on the tumor level," she says. "If the patient has a macroadenoma (large tumor), this would be the preferred treatment." However, it should be used with caution in those with diabetes given the increased risk of experiencing high blood sugar. The researchers conclude that "the long-term safety profile of pasireotide was very favorable and consistent with that reported during the first 12 months of treatment. These data support the use of long-acting pasireotide as an effective long-term treatment option for some patients with Cushing's Disease."1 Understanding Benefits of New Drug to Treat Cushing's Diseease Vivien S. Herman-Bonert, MD, an endocrinologist and clinical director of the Pituitary Center at Cedars-Sinai Medical Center in Los Angeles, agreed to discuss the study findings, after agreeing to review the research for EndocrineWeb. As to who might benefit most from monthly pasireotide injections? Dr. Herman-Bonert says, "any patient with Cushing's disease that requires long-term medical therapy, which includes patients with persistent or recurrent disease after surgery." Certainly, anyone who has had poor response to any other medical therapies for Cushing's disease either because they didn't work well enough or because the side effects were too much, will likely benefit a well, she adds. Among the pluses that came out of the study, she says, is that nearly half of the patients had controlled average urinary free cortisol levels after two full years, and 72% of the participants who continued on with the drug for 36 months were able to remain in good urinary cortisol control .1 As the authors stated, tumor shrinkage was another clear benefit of taking long-term pasireotide. That makes the drug a potentially good choice for those even with large tumors or with progressive tumor growth, she says. It’s always good for anyone with Cushing’s disease to have an alterative to surgery, or a back-up option when surgery isn’t quite enough, says Dr. Herman-Bonert. The best news for patients is that quality of life scores improved,1 she adds. Dr Herman-Bonert did add a note of caution: Although the treatment in this study is described as ''long-term, patients will need to be on this for far longer than 2 to 3 years," she says. So, the data reported in this study may or may not persist, and we don’t yet know what the impact will be 10 or 25 years out. Also, the issue of hyperglycemia-related adverse events raises a concern, given the vast majority (81%) of patients who have both Cushing’s disease and diabetes. Most of those taking this drug had a dual diagnosis—having diabetes, a history of diabetes, or taking antidiabetic medicine. If you are under care for diabetes and you require treatment for Cushing’s disease, you must be ver mindful that taking pasireotide will likely lead to high blood sugar spikes, so you should plan to address this with your healthcare provider. Dr. Fleseriu reports research support paid to Oregon Health & Science University from Novartis and other 0companies and consultancy fees from Novartis and Strongbridge Biopharma. Dr. Herman-Bonert has no relevant disclosures. The study was underwritten by Novartis Pharma AG, the drug maker. From https://www.endocrineweb.com/news/pituitary-disorders/62449-cushings-disease-monthly-injection-good-alternative-surgery
  7. 1 point
    In patients with Cushing’s disease, removing the pituitary tumor via an endoscopic transsphenoidal surgery (TSS) leads to better remission rates than microscopic TSS, according to new research. But regardless of surgical approach, plasma cortisol levels one day after surgery are predictive of remission, researchers found. The study, “Management of Cushing’s disease: Changing trend from microscopic to endoscopic surgery,” was published in the journal World Neurosurgery. Because it improves visualization and accessibility, endoscopic TSS has been gaining popularity over microscopic TSS to remove pituitary tumors in Cushing’s disease patients. Yet, although this surgery has been associated with high remission rates, whether it outperforms microscopic surgery and determining the factors affecting long-term outcomes may further ease disease recurrence after TSS. A team with the All India Institute of Medical Sciences addressed this topic in 104 patients who underwent surgery from January 2009 to June 2017. Among these patients, 47 underwent microscopic surgery and 55 endoscopic surgery. At presentation, their ages ranged from 9 to 55 (mean age of 28). Also, patients had been experiencing Cushing’s symptoms over a mean duration of 24 months. Eighty-seven patients showed weight gain. Hypertension (high blood pressure) and diabetes mellitus were among the most common co-morbidities, found in 76 and 33 patients, respectively. Nineteen patients had osteoporosis and 12 osteopenia, which refers to lower-than-normal bone mineral density. As assessed with magnetic resonance imaging, 68 patients had a microadenoma (a tumor diameter smaller than one centimeter) and 27 had a macroadenoma (a tumor one centimeter or larger). Only two patients had an invasive pituitary adenoma. Two patients with larger tumors were operated on transcranially (through the skull). The surgery resulted in total tumor removal in 90 cases (86.5%). A blood loss greater than 100 milliliter was more common with endoscopic than with microscopic TSS. Ten patients developed transient diabetes inspidus, two experienced seizures after surgery, and six of nine patients with macroadenoma and visual deterioration experienced vision improvements after TSS. The incidence of intraoperative leak of cerebrospinal fluid — the liquid surrounding the brain and spinal cord — was 23.2%, while that of post-operative leak was 7.7% and was more common in microadenoma than macroadenoma surgery (9.8% vs. 5.0%). Seventeen patients were lost to follow-up and two died due to metabolic complications and infections. The average follow-up was shorter for endoscopic than with microscopic surgery (18 months vs. 35 months). Among the remaining 85 cases, 65 (76.5%) experienced remission, as defined by a morning cortisol level under 5.0 μg/dL, restored circadian rhythm (the body’s internal clock, typically impaired in Cushing’s patients), and suppression of serum cortisol to below 2 μg/dl after overnight dexamethasone suppression test. The remission rate was 54.5% in pediatric patients and was higher with endoscopic than with microscopic TSS (88.2% vs. 56.6%). Also, patients with microadenoma showed a trend toward more frequent remission than those with macroadenoma (73.2% vs. 64.3%). Ten of the remaining 20 patients experienced disease recurrence up to 28 months after surgery. Sixteen cases revealed signs of hypopituitarism, or pituitary insufficiency, which were managed with replacement therapy. A subsequent analysis found that morning cortisol level on day one after surgery was the only significant predictor of remission. Specifically, a one-unit increase in cortisol lowered the likelihood of remission by 7%. A cortisol level lower than 10.7 μgm/dl was calculated as predicting remission. Overall, the study showed that “postoperative plasma cortisol level is a strong independent predictor of remission,” the researchers wrote, and that “remission provided by endoscopy is significantly better than microscopic approach.” From https://cushingsdiseasenews.com/2019/09/24/cortisol-levels-predict-remission-cushings-patients-undergoing-transsphenoidal-surgery/
  8. 1 point
    So do we need to get our bones checked too? https://www.sciencealert.com/our-bones-provide-our-bodies-with-a-secret-weapon-that-saves-us-in-times-of-danger Bizarre Discovery Shows Your Bones Could Be Triggering The 'Fight-or-Flight' Response MIKE MCRAE 13 SEP 2019 When faced with a threat, hormones flood our bodies in preparation either for battle or a quick escape - what's commonly known as the 'fight-or-flight' response. For decades, we've generally thought this response was driven by hormones such as adrenaline. But it now seems that one of the most important of these messengers could come from a rather unexpected place – our skeleton. We usually think of chemicals like cortisol and adrenaline as the things that get the heart racing and muscles pumping. But the real star player could actually be osteocalcin, a calcium-binding protein produced by our bones. As a response to acute stress, steroids of the glucocorticoid variety are released by the body's endocrine system, where they manage the production of a cascade of other 'get ready to rumble' chemicals throughout various tissues. Researchers from the US, the UK, and India argue there's one tiny problem with this explanation of the fight-or-flight reaction. It isn't exactly fast. While nobody is disputing that our bodies produce cortisol when stressed, the fact their main action is to trigger cells into transcribing specific genes – a process that takes time – makes it an unlikely candidate for a rapid physiological response. "Although this certainly does not rule out that glucocorticoid hormones may be implicated in some capacity in the acute stress response, it suggests the possibility that other hormones, possibly peptide ones, could be involved," says geneticist Gerard Karsenty of Columbia University. So Karsenty and colleagues went on the hunt for something a little more expedient, focussing on proteins released by bone cells that would potentially have a more immediate effect on animal metabolism. Looking to the skeleton as a source might not be as weird as it first seems. After all, our bones evolved as a way to protect our squishy bits from being squashed, either by predator or accident. "If you think of bone as something that evolved to protect the organism from danger – the skull protects the brain from trauma, the skeleton allows vertebrates to escape predators, and even the bones in the ear alert us to approaching danger – the hormonal functions of osteocalcin begin to make sense," says Karsenty. Osteocalcin isn't in any way new to science, either. We've understood its function in bone development for nearly half a century, and in recent years begun to suspect it also has a hand in regulating our energy levels by affecting glucose metabolism. It also seems to give an ageing memory a boost, at least in lab rodents. All useful things in moments of danger. But it's still a surprising discovery that osteocalcin might also help to kickstart our acute stress response. "It completely changes how we think about how acute stress responses occur," says Karsenty. To test their suspicions, the researchers put lab mice under duress by restraining them for a 45 minute period. During that time, osteocalcin levels in the peripheral blood rose by half, while other skeletal hormones barely budged. In another test, just 15 minutes after a few harmless (but uncomfortable) shocks to the feet, osteocalcin levels in the stressed mice jumped by a whole 150 percent. Giving the test subjects a whiff of a chemical found in fox urine also elevated their peripheral osteocalcin levels. Importantly, these went up before their corticosterone levels began to climb, starting a few minutes after exposure and remaining high for another three hours. Just to make sure it wasn't only a mouse thing, the team also checked the hormone in humans who volunteered to do a public speech and undergo a pulse-raising cross-examination. Sure enough, up the osteocalcin went. In yet another series of tests, the team used rodents that were genetically engineered to lack the usual corticosteroid and other stress hormones, and found these animals continued to present a stress response. In addition, a shot of osteocalcin in otherwise unstressed mice was all they needed to get twitchy, raising their heart rate, temperature, and levels of circulating glucose. "Osteocalcin could explain past observations of an intact flight-or-flight response in humans and other animals lacking glucocorticoids and additional molecules produced by the adrenal glands," says Karsenty. With the evidence building for the bone protein as such a strong motivator for dealing with stress, it stands to ask why we need hormones like cortisol at all. The researchers plan to unravel this mystery in future investigations. This research was published in Cell Metabolism.
  9. 1 point
    Presented by Andrew Lin, MD Neuro-Oncologist & Neurologist Memorial Sloak Kettering Cancer Center After registering you will receive a confirmation email with details about joining the webinar. Contact us at webinar@pituitary.org with any questions or suggestions. Date: September 18, 2019 Time: 10:00 AM - 11:00 AM. Pacific Daylight Time, 1:00 PM - 2:00 PM Eastern Daylight Time Learning Objectives: During the conversation I will be: 1) Defining aggressive pituitary tumors. 2) Reviewing the current treatment options for aggressive pituitary tumors. 3) Discussing experimental treatment options including a phase II trial investigating the activity of the immunotherapies nivolumab and ipilimumab. Presenter Biography: I am a neuro-oncologist at Memorial Sloan Kettering Cancer Center (MSK) and a member of the Multidisciplinary Pituitary & Skull Base Tumor Center. In collaboration with my colleagues in endocrine, neurosurgery, and radiation oncology, I treat patients with aggressive pituitary tumors, who are resistant to conventional treatments (i.e. surgery and radiation), with chemotherapy. With my colleagues at MSK, I have published several research articles on pituitary tumors and opened several clinical trials.
  10. 1 point
    For patients with persistent or recurring Cushing’s disease, monthly pasireotide therapy was safe and effective, leading to normal urinary free cortisol levels in 47% of patients after 2 years, according to findings published in Clinical Endocrinology. Maria Fleseriu “The management of Cushing’s syndrome, and particularly Cushing’s disease, remains challenging,” Maria Fleseriu, MD, FACE, professor of neurological surgery and professor of medicine in the division of endocrinology, diabetes and clinical nutrition in the School of Medicine at Oregon Health & Science University and director of the OHSU Northwest Pituitary Center, told Endocrine Today. “Long-acting pasireotide provided sustained biochemical improvements and clinical benefit in a significant proportion of patients with Cushing’s disease who elected to continue in this extension study. There were many adverse events reported overall, but no new safety signals emerging over long-term treatment.” In the last decade, medical treatment for Cushing’s disease has progressed from a few steroidogenesis inhibitors to three novel drug groups: new inhibitors for steroidogenic enzymes with possibly fewer adverse effects, pituitary-directed drugs that aim to inhibit the pathophysiological pathways of Cushing’s disease, and glucocorticoid receptor antagonists that block cortisol’s action, Fleseriu, who is also an Endocrine Today Editorial Board member, said. In an open-label extension study, Fleseriu and colleagues analyzed data from 81 adults with confirmed Cushing’s disease with mean urinary free cortisol not exceeding the upper limit of normal, who transitioned from a 12-month, randomized controlled trial where they were assigned 10 mg or 30 mg once-monthly intramuscular pasireotide (Signifor LAR, Novartis). During the main study, researchers recruited participants with mean urinary free cortisol level concentration 1.5 to five times the upper limit of normal, normal or greater than normal plasma and confirmed pituitary source of Cushing’s disease. Participants who elected to continue in the extension were considered biochemical responders or benefited from the study drug per the clinical investigator, Fleseriu said. “As in all extension studies, the bias is inherent that patients deemed responders tend to continue, but for any type of treatment for pituitary tumors, and particularly Cushing’s disease, long-term, robust data on efficacy and safety parameters is essential,” Fleseriu said. Median overall exposure to pasireotide at the end of the extension study was 23.9 months, with nearly half of patients receiving at least 1 year of treatment during the extension phase. Researchers found that improvements in clinical signs of hypercortisolism were sustained throughout the study and median urinary free cortisol remained within normal range. Overall, 38 participants (47%) had controlled urinary free cortisol at month 24 (after 12 months of treatment during the extension phase), with researchers noting that the proportion of participants with controlled or partially controlled urinary free cortisol was stable throughout the extension phase. “Interestingly, the median salivary cortisol level decreased but remained above normal (1.3 times upper limit of normal) at 3 years,” Fleseriu said. As seen in other pasireotide studies, and expected based on the mechanism of action, researchers observed hyperglycemia-related adverse events in 39.5% of participants, with diabetes medications initiated or escalated in some patients, Fleseriu said. However, mean fasting glucose and HbA1c were stable during the extension phase, after increasing in the main study. Within the cohort, 81.5% had type 2 diabetes at baseline (entering extension phase) and 88.9% patients had type 2 diabetes at last assessment. “Pasireotide acts at the tumor level, and tumor shrinkage is seen in many patients,” Fleseriu said. “In this study, 42% and 32.1% had a measurable microadenoma or macroadenoma, respectively, on MRI at the start of pasireotide treatment; an adenoma was not visible in almost a quarter of patients at 2 years.” Among patients with a measurable adenoma at baseline and at month 24 (n = 35), 85.7% experienced a reduction of at least 20% or a 20% change in tumor volume between the two time points. Improvements in median systolic and diastolic blood pressure, BMI and waist circumference were sustained during the extension, Fleseriu said. “The long-term safety profile of pasireotide was favorable and consistent with that reported during the first 12 months of treatment,” the researchers wrote. “These data support the use of long-acting pasireotide as an effective long-term treatment option for some patients with [Cushing’s disease].” Fleseriu said individualized treatment selecting patients who will derive benefit from therapy will be crucial, balancing both efficacy and the potential risks and costs. – by Regina Schaffer Disclosures: Fleseriu reports she has received consultant fees and her institution has received research support from Novo Nordisk and Pfizer. Please see the study for all other authors’ relevant financial disclosures. From https://www.healio.com/endocrinology/neuroendocrinology/news/online/%7B5da4611f-34b2-4306-80b8-46babd2aad4a%7D/long-acting-pasireotide-provides-sustained-biochemical-improvements-in-cushings-disease?page=2
  11. 1 point
    Abstract OBJECTIVE: To report our management of bilateral adrenalectomy with autologous adrenal gland transplantation for persistent Cushing's disease, and to discuss the feasibility of autologous adrenal transplantation for the treatment of refractory Cushing's disease. MATERIAL AND METHODS: A retrospective analysis was performed in 4 patients (3 females, aged 14-36 years) who underwent autologous adrenal transplantation for persistent Cushing's disease after endonasal transsphenoidal resection of a pituitary tumor. The procedure was performed by implanting a vascularized adrenal graft into the left iliac fossa with direct and indirect anastomoses. Postoperative follow-up was performed in 1, 1.5, 8, and 10 years, and an over 8-year long-term follow-up was reached in 2 out of the 4 cases. Hormone replacement dosage was guided by clinical symptoms and endocrine results including serum cortisol (F), 24 h urine-free cortisol, and adrenocorticotrophic hormone levels. RESULTS: All 4 patients with symptomatic Cushing's disease experienced resolution of symptoms after autotransplantation without Nelson Syndrome. Functional autografts were confirmed through clinical evaluation and endocrine results. One year after transplantation, adrenal function and hormone replacement dosage remained stable without adrenal hyperplasia. After long-term follow-up, dosages of hormone replacement were reduced in all patients. CONCLUSIONS: In this series of 4 patients, we demonstrate the long-term efficacy of bilateral adrenalectomy with autologous adrenal transplantation and propose this procedure as a viable treatment option for refractory Cushing's disease. © 2019 S. Karger AG, Basel. KEYWORDS: Cortisol; Adrenalectomy; Autologous adrenal gland transplantation ; Cushing’s disease; Nelson syndrome PubMed http://www.ncbi.nlm.nih.gov/pubmed/31434089 TAGS: cortisol, adrenalectomy, Autologous adrenal gland transplantation , Cushing's disease, Nelson syndrome
  12. 1 point
    Authors Ježková J, Ďurovcová V, Wenchich L, Hansíková H, Zeman J, Hána V, Marek J, Lacinová Z, Haluzík M, Kršek M Received 18 March 2019 Accepted for publication 13 June 2019 Published 19 August 2019 Volume 2019:12 Pages 1459—1471 DOI https://doi.org/10.2147/DMSO.S209095 Checked for plagiarism Yes Review by Single-blind Peer reviewers approved by Dr Melinda Thomas Peer reviewer comments 3 Editor who approved publication: Dr Antonio Brunetti Jana Ježková,1 Viktória Ďurovcová,1 Laszlo Wenchich,2,3 Hana Hansíková,3 Jiří Zeman,3Václav Hána,1 Josef Marek,1 Zdeňka Lacinová,4,5 Martin Haluzík,4,5 Michal Kršek1 1Third Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 2Institute of Rheumatology, Prague, Czech Republic; 3Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 4Institute of Medical Biochemistry and Laboratory Diagnostic, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic; 5Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic Correspondence: Jana Ježková Third Department of Medicine, First Faculty of Medicine, Charles University and General University Hospital, U Nemocnice 1128 02 Praha 2, Prague, Czech Republic Tel +420 60 641 2613 Fax +420 22 491 9780 Email fjjezek@cmail.cz Purpose: Cushing’s syndrome is characterized by metabolic disturbances including insulin resistance. Mitochondrial dysfunction is one pathogenic factor in the development of insulin resistance in patients with obesity. We explored whether mitochondrial dysfunction correlates with insulin resistance and other metabolic complications. Patients and methods: We investigated the changes of mRNA expression of genes encoding selected subunits of oxidative phosphorylation system (OXPHOS), pyruvate dehydrogenase (PDH) and citrate synthase (CS) in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM) and mitochondrial enzyme activity in platelets of 24 patients with active Cushing’s syndrome and in 9 of them after successful treatment and 22 healthy control subjects. Results: Patients with active Cushing’s syndrome had significantly increased body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR) and serum lipids relative to the control group. The expression of all investigated genes for selected mitochondrial proteins was decreased in SCAT in patients with active Cushing’s syndrome and remained decreased after successful treatment. The expression of most tested genes in SCAT correlated inversely with BMI and HOMA-IR. The expression of genes encoding selected OXPHOS subunits and CS was increased in PM in patients with active Cushing’s syndrome with a tendency to decrease toward normal levels after cure. Patients with active Cushing’s syndrome showed increased enzyme activity of complex I (NQR) in platelets. Conclusion: Mitochondrial function in SCAT in patients with Cushing’s syndrome is impaired and only slightly affected by its treatment which may reflect ongoing metabolic disturbances even after successful treatment of Cushing’s syndrome. Keywords: Cushing’s syndrome, insulin resistance, mitochondrial enzyme activity, gene expression This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms. Download Article [PDF] View Full Text [Machine readable]
  13. 1 point
    I would be very interested to learn the current status of any Disability Claim for Agent Orange with Cushing. My 47 year old daughter had surgery in 2008 for unilateral adrenal Cushings in Orlando, FL. Frank
  14. 1 point
    Recovery of the hypothalamus-pituitary-adrenal (HPA) axis can occur as late as 12 months after transsphenoidal adenomectomy (TSA), according to study results published in The Journal of Clinical Endocrinology & Metabolism. These findings emphasize the need to periodically assess these patients to avoid unnecessary hydrocortisone replacement. The primary treatment for most pituitary lesions is TSA. After pituitary surgery, the recovery of pituitary hormone deficits may be delayed; limited data are available regarding the postsurgical recovery of hormonal axes or predictors of recovery. The goal of this study was to assess HPA axis dysfunction and predictive markers of recovery following TSA, as well as time to recovery, to identify subgroups of patients who may be more likely to recover. This single-center observational retrospective study enrolled 109 patients in the United Kingdom (71 men; mean age, 56 years; range, 17 to 82 years) who underwent TSA between February 2015 and September 2018 and had ≥1 reevaluation of the HPA axis with the short Synacthen (cosyntropin) test. The primary outcome was recovery of HPA axis function 6 weeks, 3 months, 6 months, and 9 to 12 months after TSA. In 23 patients (21.1%), there was no evidence of pituitary hormone deficit before TSA. In 44 patients (40.4%), there was 1 hormone deficiency and in 25 patients (22.9%), preoperative evaluation showed >1 hormone deficiency. Of the 23 patients with abnormal HPA function before surgery, 8 patients (34.8%) had recovered 6 weeks after the surgery. Patients who recovered were younger (mean age, 50±14 vs 70±9 years; P =.008) compared with patients who did not respond. Of the 15 remaining patients, 2 (13.3%) recovered at 3 months and 3 (20%) recovered at 9 to 12 months. With regard to HPA function in the entire cohort 6 weeks after surgery, 32 patients (29.4%) did not pass the short Synacthen test. Of this group, 5 patients (15.6%) recovered at 3 months, 4 (12.5%) at 6 months, and 2 (6.2%) recovered 9 to 12 months after the surgery. Predictors of future adrenal recovery at 6 weeks included having preoperative 30-minute cortisol >430 nmol/L (P <.001) and a day 8 postoperative cortisol >160 nmol/L (P =.001). With these cutoffs, 80% of patients with preoperative 30-minute cortisol >430 nmol/L (odds ratio [OR], 7.556; 95% CI, 2.847-20.055) and 80% of patients with day 8 postoperative cortisol >160 nmol/L (OR, 9.00; 95% CI, 2.455-32.989) passed the short Synacthen test at 6 weeks postsurgery. In addition, a 6-week baseline short Synacthen test cortisol level above or below 180 nmol/L (P <.001) predicted adrenal recovery at that time point. None of the patients with all 3 variables below the aforementioned cutoffs recovered HPA axis within 1 year. On the other hand, 91.8% of patients with all 3 variables above those cutoffs had normal adrenal function at 6 weeks (OR, 12.200; 95% CI, 5.268-28.255). In addition to the retrospective design, the study had other limitations, including the potential for selection bias, a heterogeneous patient cohort, and no data beyond 12 months after the surgery. “[T]hese data offer the opportunity for patients who may have been given life-long replacement, to safely come off therapy and therefore avoid unnecessary glucocorticoid exposure,” wrote the researchers. Reference Pofi R, Gunatilake S, Macgregor V, et al. Recovery of the hypothalamo-pituitary-adrenal axis following transsphenoidal adenomectomy for non-ACTH secreting macroadenomas [published online June 21, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2019-00406 From https://www.endocrinologyadvisor.com/home/topics/adrenal/recovery-of-hpa-axis-can-occur-late-after-transsphenoidal-adenomectomy/
  15. 1 point
    Dr. Theodore Friedman hosts Gautam Mehta, MD for a fascinating webinar on Approaches for Pituitary Surgery Dr. Mehta is a neurosurgeon specializing in pituitary surgery at the House Clinic in Los Angeles. He was trained by Ian McCutcheon, MD and Ed Oldfield, MD Topics to be discussed include: • How does Dr. Friedman diagnose Cushing’s Disease • How does Dr. Friedman determine who goes to surgery? • What type of patients need surgery besides those with Cushing’s Disease? • How do the neurosurgeon and the Endocrinologist work together? • How does the neurosurgeon read pituitary MRIs? • What types of surgical approaches are used for pituitary surgery? • How long does surgery take and how long will a patient be in the hospital? • What are the risks of pituitary surgery and how can they be minimized? Sunday • August 4 • 6 PM PDT Click here to start your meeting. or https://axisconciergemeetings.webex.com/axisconciergemeetings/j.php?MTID=ma1d8d5ef99605e305980e2f7cdfdb7bd OR Join by phone: (855) 797-9485 Meeting Number (Access Code): 807 028 597 Your phone/computer will be muted on entry. Slides will be available on the day of the talk at slides There will be plenty of time for questions using the chat button. Meeting Password: hormones For more information, email us at mail@goodhormonehealth.com
  16. 1 point
    Cases of adrenocorticotropic hormone (ACTH)-independent Cushing’s syndrome are often caused by unilateral tumors in the adrenal glands, but Indian researchers have now reported a rare case where the condition was caused by tumors in both adrenal glands. Fewer than 40 cases of bilateral tumors have been reported so far, but an accurate diagnosis is critical for adequate and prompt treatment. Sampling the veins draining the adrenal glands may be a good way to diagnose the condition, researchers said. The study, “Bilateral adrenocortical adenomas causing adrenocorticotropic hormone-independent Cushing’s syndrome: A case report and review of the literature,” was published in the World Journal of Clinical Cases. Cushing’s syndrome, a condition characterized by excess cortisol in circulation, can be divided into two main forms, depending on ACTH status. Some patients have tumors that increase the amount of ACTH in the body, and this hormone will act on the adrenal glands to produce cortisol in excess. Others have tumors in the adrenal glands, which produce excess cortisol by themselves, without requiring ACTH activation. This is known as ACTH-independent Cushing’s syndrome. Among the latter, the disease is mostly caused by unilateral tumors — in one adrenal gland only — with cases of bilateral tumors being extremely rare in this population. Now, researchers reported the case of a 31-year-old Indian woman who developed ACTH-independent Cushing’s syndrome because of tumors in both adrenal glands. The patient complained of weight gain, red face, moon face, bruising, and menstrual irregularity for the past two years. She recently had been diagnosed with high blood pressure and had started treatment the month prior to the presentation. A physical examination confirmed obesity in her torso, moon face, buffalo hump, thin skin, excessive hair growth, acne, swollen legs and feet, and skin striae on her abdomen, arms, and legs. Laboratory examinations showed that the woman had an impaired tolerance to glucose, excess insulin, and elevated cortisol in both the blood and urine. Consistent with features of Cushing’s syndrome, cortisol levels had no circadian rhythm and were non-responsive to a dexamethasone test, which in normal circumstances lowers cortisol production. Because ACTH levels were within normal levels, researchers suspected an adrenal tumor, which led them to conduct imaging scans. An abdominal computed tomography (CT) scan showed adrenal adenomas in both adrenal glands (right: 3.1 cm × 2.0 cm × 1.9 cm; left: 2.2 cm × 1.9 cm × 2.1 cm). A magnetic resonance imaging (MRI) scan showed that the pituitary gland (which normally produces ACTH) was normal. To determine whether both adrenal tumors were producing cortisol, researchers sampled the adrenal veins and compared their cortisol levels to those of peripheral veins. They found that the left adrenal gland was producing higher amounts of cortisol, thought the right adrenal gland was also producing cortisol in excess. “Our case indicates that adrenal vein [blood] sampling might be useful for obtaining differential diagnoses” in cases of Cushing’s syndrome, researchers stated. Also, they may help design a surgical plan that makes much more sense.” The tumors were surgically removed — first the left, and three months later the right — which alleviated many of her symptoms. She also started prednisolone treatment, which helped resolve many disease symptoms. “Bilateral cortisol-secreting tumors are a rare cause of Cushing’s syndrome,” researchers said. So when patients present bilateral adrenal lesions, “it is crucial to make a definitive diagnosis before operation since various treatments are prescribed for different causes,” they said. The team recommends that in such cases the two tumors should not be removed at the same time, as this approach may cause adrenal insufficiency and the need for glucocorticoid replacement therapy. From https://cushingsdiseasenews.com/2019/06/27/rare-case-of-cs-due-to-bilateral-tumors-in-the-adrenal-glands/
  17. 1 point
    Are adrenal incidentalomas, which are found by chance on imaging, really harmless? In this paper, the authors looked at 32 studies, including 4121 patients with benign non-functioning adrenal tumours (NFATs) or adenomas that cause mild autonomous cortisol excess (MACE). Only 2.5% of the tumours grew to a clinically significant extent over a mean follow-up period of 50 months, and no one developed adrenal cancer. Of those patients with NFAT or MACE, 99.9% didn’t develop clinically significant hormone (cortisol) excess. This was a group (especially those with MACE) with a high prevalence of hypertension, diabetes, and obesity. This could be because adrenal adenomas promote cardiometabolic problems, or vice versa, or maybe this group with multimorbidities is more likely be investigated. Adrenal incidentalomas are already found in around 1 in 20 abdominal CT scans, and this rate is likely to increase as imaging improves. So it’s good news that this study supports existing recommendations, which say that follow-up imaging in the 90% of incidentalomas that are smaller than 4 cm diameter is unnecessary. From https://blogs.bmj.com/bmj/2019/07/03/ann-robinsons-journal-review-3-july-2019/
  18. 1 point
    Removal of pituitary adenomas by inserting surgical instruments through the nose (transsphenoidal resection) remains the best treatment option for pediatric patients, despite its inherent technical difficulties, a new study shows. The study, “Transsphenoidal surgery for pituitary adenomas in pediatric patients: a multicentric retrospective study,” was published in the journal Child’s Nervous System. Pituitary adenomas are rare, benign tumors that slowly grow in the pituitary gland. The incidence of such tumors in the pediatric population is reported to be between 1% and 10% of all childhood brain tumors and between 3% and 6% of all surgically treated adenomas. Characteristics of patients that develop these pituitary adenomas vary significantly in different studies with regards to their age, gender, size of adenoma, hormonal activity, and recurrence rates. As the pituitary gland is responsible for hormonal balance, alterations in hormone function due to a pituitary adenoma can significantly affect the quality of life of a child. In most cases, pituitary adenomas can be removed surgically. A common removal method is with a transsphenoidal resection, the goal of which is to completely remove the growing mass and cause the least harm to the surrounding structures. In this study, the researchers report the surgical treatment of pediatric pituitary adenomas at three institutions. They collected data from 27 children who were operated for pituitary adenoma using one of two types of transsphenoidal surgeries — endoscopic endonasal transsphenoidal surgery (EETS) and transsphenoidal microsurgery (TMS) — at the University Cerrahpasa Medical Faculty in Istanbul, Turkey, at San Matteo Hospital in Pavia, and at the University of Insubria-Varese in Varese, Italy. The study included 11 males (40.7%) and 16 females (59.3%), with a mean age of 15.3 (ranging between 4 and 18). Medical records indicated that 32 surgical procedures were performed in the 27 patients, as six children required a second operation. Among the patients, 13 had Cushing’s disease, while the rest had growth-hormone-secreting adenomas, prolactinomas, or non-functional adenomas. The researchers found that most patients underwent remission following their surgery. Among the 27 patients, 22 patients (81.4%) underwent remission while five patients (18.5%) did not. Four patients underwent remission after a second operation. Based on these findings, the team believes that the transsphenoidal surgical approach adequately removes pituitary tumors and restores normal hormonal balance in the majority of pediatric patients with pituitary adenomas. “Satisfactory results are reported with both EETS and TMS in the literature,” they wrote. “Despite the technical difficulties in pediatric age, transsphenoidal resection of adenoma is still the mainstay treatment that provides cure in pediatric patients.” From https://cushingsdiseasenews.com/2019/05/30/transsphenoidal-surgery-effective-remove-pituitaty-adenomas-children-study/
  19. 1 point
    Scientists have discovered a potential biological reason why women are more likely to develop adrenal disorders, including cancer. According to the researchers, the answer could lie in the increased turnover of hormone-producing cells found in the adrenal glands of females. The adrenal gland is a hormone producing organ that sits on top of the kidneys. The outer part, or cortex, is responsible for the production of several hormones, including the stress-related hormone cortisol and the blood pressure controlling aldosterone. Adrenal cancer is relatively rare but occurs approximately three times more in women than in men. The cellular basis for this difference has not been investigated in detail but uncovering it might lead to sex-specific treatments and has huge implications for many areas of research. Dr Andreas Schedl, from INSERM, France, who led the study said: To our surprise we found that adrenal cells in female mice show a much more rapid turnover compared to males, which we could trace back to a different behaviour of adrenal stem cells between the two sexes. Furthermore, we could show that the observed differences are due to hormones that are produced by testes that suppress cell division, thus slowing down renewal in the male adrenal." The scientists studied the adrenal cortex of male and female adult mice and found that female mice replace their entire set of hormone-producing cells within 3 months, while it takes male mice an entire 9 months. Using different techniques to label cells within the adrenal cortex, they established that females not only have a higher proliferation rate of cells, but also recruit stem cells from a different part of the adrenal gland. The research has wide reaching implications, as it demonstrates the basic mechanism underlying the increased turnover of cells within the adrenal gland, providing a possible explanation for the increased incidence of adrenal disorders in women. Dr Schedl explained: "It is early days and many more experiments will need to be performed before our research can directly benefit patients. However, we believe that our study teaches a number of important lessons that are of immediate relevance to scientists, pharmacologists and clinicians." This research might lead to sex-specific treatment options for diseases like adrenal cancer and, according to Dr Schedl, could have implications on a far wider field of disorders: "Importantly, while our study concentrated on the adrenals, we are convinced that similar differences may also be found in other organ systems." Dr Helen Rippon, Chief Executive of the charity Worldwide Cancer Research, whose supporters helped fund the study, said: "Sex differences are not necessarily the first thing that comes to mind when thinking about cancer research or treatments. But this study has shown that it is crucial to consider potential differences between male and female when trying to understand the basis of cancer biology. Most importantly, these findings could have implications for treatment options further down the line and highlight the importance of early-stage, discovery research. We are delighted to fund this kind of research, as we believe that these innovative approaches are ultimately going to lead to a world where no life is cut short by cancer." Worldwide Cancer Research, La Ligue Contre le Cancer and the ANR supported this research. The research was published in Cell Stem Cell. Source: Worldwide Cancer Research Journal reference: Grabek, A. et al. (2019) The Adult Adrenal Cortex Undergoes Rapid Tissue Renewal in a Sex-Specific Manner. Cell Stem Cell. doi.org/10.1016/j.stem.2019.04.012. From https://www.news-medical.net/news/20190522/Scientists-discover-biological-reason-why-women-are-more-likely-to-develop-adrenal-disorders.aspx
  20. 1 point
    In patients with a diagnosis of Cushing disease in whom magnetic resonance imaging (MRI) shows either no abnormalities or nonspecific abnormalities, surgery is preferable to medical treatment, according to study results published in The Journal of Clinical Endocrinology & Metabolism. There is a consensus that the first line of treatment for Cushing disease is transsphenoidal surgery to remove the pituitary adenoma causing the disease, with an 80% remission rate following the intervention. However, in the absence of clear evidence of a pituitary adenoma on imaging, there is some controversy regarding the best treatment. The goal of this retrospective single-center study was to assess the outcomes of surgery in patients with Cushing disease with clear evidence of a pituitary adenoma on MRI compared with outcomes in patients with inconclusive or normal MRI. The cohort included 195 patients treated with transsphenoidal surgery between 1992 and 2018 (156 women; mean age at surgery, 41 years) classified into 4 MRI groups: 89 patients were found to have microadenoma, 18 had macroadenoma, 44 had nonspecific/inconclusive abnormalities on MRI results, and 44 had normal imaging results. The researchers reported that MRI performance in their neuroradiology department improved with time; the proportion of inconclusive or normal MRI results decreased from 60% in 1992 to 1996 to 27% in 2012 to 2018 (P =.037). In analyzing the influence of MRI findings on remission rates, the researchers found no significant difference among the 4 groups: remission rate was 85% for microadenomas, 94% for macroadenomas, 73% for inconclusive MRI, and 75% for negative MRI (P =.11). This finding indicates the overall percentage of patients in remission after transsphenoidal surgery is only slightly lower in those with normal or inconclusive MRI results compared with patients with clear evidence of microadenoma or macroadenoma. There was no difference in remission rate after a microscopic vs endoscopic surgical approach (P =.16). The researchers found that endoscopic-assisted surgery allowed a higher visualization rate than microscopic-assisted surgery. Although the neurosurgeon had a better visualization rate than MRI (100% vs 72%, respectively), there were some false-positive findings; thus, positive predictive value was similar (84% vs 78%, respectively). The study had several limitations including the retrospective design. In addition, in light of the long study duration, the researchers noted that changes in MRI technology and surgical procedures occurred over time. The researchers proposed that after exclusion of nonneoplastic hypercortisolism, patients with Cushing disease, an inconclusive or normal MRI, and a pituitary adrenocorticotropic hormone gradient at bilateral inferior petrosal sampling be directed to an expert neurosurgeon for transsphenoidal surgery rather than treated medically. Reference Cristante J, Lefournier V, Sturm N, et al. Why we should still treat by neurosurgery patients with Cushing’s disease and a normal or inconclusive pituitary MRI [published online May 14, 2019]. J Clin Endocrinol Metab. doi:10.1210/jc.2019-00333 From https://www.endocrinologyadvisor.com/home/topics/adrenal/transsphenoidal-surgery-recommended-for-cushing-disease-with-inconclusive-or-normal-mri/
  21. 1 point
    Presented by Irina Bancos, MD Assistant Professor of Medicine Endocrinology Department Mayo Clinic, Rochester, MN Space is limited. Reserve your webinar seat. After registering you will receive a confirmation email containing information about joining the webinar. Contact us at webinar@pituitary.org if you have any questions. Date: Tuesday, May 28, 2019 Time: 10:00 AM - 11:00 AM Pacific Daylight Time, 1:00 PM - 2:00 PM Eastern Daylight Time Webinar Description Learning Objectives: To distinguish between primary and secondary adrenal insufficiency To understand the pitfalls of current diagnostic tests to diagnose adrenal insufficiency. To describe physiological replacement therapy for adrenal insufficiency To distinguish between adrenal insufficiency and glucocorticoid withdrawal syndrome. Presenter Bio Dr. Irina Bancos is the Assistant Professor of Medicine and works in the Pituitary-Adrenal-Gonadal subdivision of Endocrinology division at Mayo Clinic, Rochester. She also serves as Director of the Endocrine testing center. Dr. Bancos received her M.D. from the Iuliu Hatieganu Medical University in Cluj-Napoca, Romania. She has completed her Internal Medicine Residency at Danbury Hospital in CT and Endocrinology Fellowship at Mayo Clinic, Rochester. In addition, Dr. Bancos completed a two year research fellowship (Mayo Foundation Scholarship) at the University of Birmingham, United Kingdom where she received training in steroid profiling and adrenal disorders. In 2015 she returned to Mayo Clinic, where her clinical and research interests include adrenal and pituitary tumors, adrenal insufficiency, congenital adrenal hyperplasia, Cushing syndrome, and mechanisms of steroid regulation of metabolism. Between 2015 and 2018, Dr. Bancos was the principal investigator and leader of the Transform the Adrenal Practice team at Mayo Clinic. Dr. Bancos has published 77 scientific articles. In addition to clinical practice in the pituitary-adrenal-gonadal clinic, Dr. Bancos enjoys teaching fellows, residents and medical students. She is the principal investigator of several ongoing prospective studies in Cushing syndrome, adrenal insufficiency, prolactinoma, and adrenal tumors. Dr. Bancos currently holds several grants in the field of steroid regulation of aging, metabolism and body composition.
  22. 1 point
  23. 1 point
    Wannachalee T, et al. Clin Endocrinol. 2019;doi:10.1111/cen.14008. May 20, 2019 A radioactive diagnostic agent for PET imaging effectively localized primary tumors or metastases in most adults with ectopic Cushing’s syndrome, leading to changes in clinical management for 64% of patients, according to findings from a retrospective study published in Clinical Endocrinology. As Endocrine Today previously reported, the FDA approved the first kit for the preparation of gallium Ga-68 dotatate injection (Netspot, Advanced Accelerator Applications USA Inc.), a radioactive diagnostic agent for PET scan imaging, in June 2016. The radioactive probe is designed to help locate tumors in adult and pediatric patients with somatostatin receptor-positive neuroendocrine tumors. Ga-68 dotatate, a positron-emitting analogue of somatostatin, works by binding to the hormone. In a retrospective review, Richard Auchus, MD, PhD, professor of pharmacology and internal medicine in the division of metabolism, endocrinology and diabetes at the University of Michigan, and colleagues analyzed data from 28 patients with ectopic Cushing’s syndrome who underwent imaging with gallium Ga-68 dotatate for identification of the primary tumor or follow-up between November 2016 and October 2018 (mean age, 50 years; 22 women). All imaging was completed at tertiary referral centers at Mayo Clinic, University of Michigan and The University of Texas MD Anderson Cancer Center. Researchers assessed patient demographics, imaging modalities, histopathological results and treatment data. Diagnosis of Cushing’s syndrome was confirmed by clinical and hormonal evaluation. The clinical impact of gallium Ga-68 dotatate was defined as the detection of primary ectopic Cushing’s syndrome or new metastatic foci, along with changes in clinical management. Within the cohort, 17 patients underwent imaging with gallium Ga-68 dotatate for identification of the primary tumor and 11 underwent the imaging for follow-up. Researchers found that gallium Ga-68 dotatate identified suspected primary ectopic Cushing’s syndrome in 11 of 17 patients (65%), of which seven tumors were solitary and four were metastatic. Diagnosis was confirmed by pathology in eight of the 11 patients: Five patients had a bronchial neuroendocrine tumor, one patient had a thymic tumor, one had a pancreatic neuroendocrine tumor, and one metastatic neuroendocrine tumor was of unknown primary origin. One patient had a false positive scan, according to researchers. Among the 11 patients with ectopic Cushing’s syndrome who underwent gallium Ga-68 dotatate imaging to assess disease burden or recurrence, the imaging led to changes in clinical management in seven cases (64%), according to researchers. “Our study demonstrates the high sensitivity of [gallium Ga-68 dotatate] in the localization of [ectopic Cushing’s syndrome], for both occult primary tumors and metastatic lesions,” the researchers wrote. “Importantly, the use of [gallium Ga-68 dotatate] impacted clinical management in 64% of patients with [ectopic Cushing’s syndrome] overall.” The researchers noted that the high cost and limited availability of PET/CT imaging might preclude the widespread use of gallium Ga-68 dotatate for imaging in patients with suspected ectopic Cushing’s syndrome, and that experience with the scans remains limited vs. other imaging studies. “Nevertheless, combing the experience of three large referral centers, our study gathers the largest number of [patients with ectopic Cushing’s syndrome] imaged with [gallium Ga-68 dotatate] to date and provides a benchmark for the utility of this diagnostic modality for this rare but highly morbid condition,” the researchers wrote. – by Regina Schaffer Disclosures: The authors report no relevant financial disclosures. From https://www.healio.com/endocrinology/adrenal/news/online/%7B69e458a8-e9a0-4567-a786-00868118b435%7D/imaging-agent-effectively-detects-localizes-tumors-in-cushings-syndrome
  24. 1 point
    Thank you Mary. Much appreciated. I am doing a massive research in this area. Will share anything i find.:)
  25. 1 point
    I am currently looking into what seems to be a limited study. Can i ask if any Cushies have been tested for Alpha 1 antitrypsin deficiency and then where diagnosed with Cushing's. Or Were treated for Cushing's, now in remission but experiencing lung issues or found to have liver issues..... have since been tested for A1AD and found to be deficient? I am looking for any studies, papers, personal stories in this area. Any info would be gratefully accepted.
  26. 1 point
    Hi, Deb - I looked in the bios but couldn't find anyone who mentioned Alpha 1 antitrypsin deficiency There are several people who mentioned liver issues -https://cushingsbios.com/?s=liver and some who mentioned lung problems - https://cushingsbios.com/?s=lung Best of luck to you.
  27. 1 point
    Dr. Theodore Friedman hosts Jay Khorsandi, DDS and Barbara Burggraaff, MD from Snore Experts for an important webinar on insomnia Topics to be discussed include: • What are the causes of insomnia? • How do hormone imbalances lead to insomnia? • What lifestyle changes can you do to help with insomnia? • What supplements are helpful for insomnia? • What medicines are helpful for insomnia? Sunday • June 2nd • 6 PM PST Click here on start your meeting.or https://axisconciergemeetings.webex.com/axisconciergemeetings/j.php?MTID=m2f7d9547a80ec47e43869517ef006f34 OR Join by phone: (855) 797-9485 Meeting Number (Access Code): 807 924 444 Meeting Password: hormones Your phone/computer will be muted on entry. There will be plenty of time for questions using the chat button. For more information, email us at mail@goodhormonehealth.com
  28. 1 point
    I'm so sorry to read this, Donna I'll never understand how a doctor can't "believe in" a disease. Boggles my mind. I sure hope Dr. F can help you - he's helped so many others over the years. Please keep us posted.
  29. 1 point
    Oh no, Donna - does this mean Dr. Zwart didn't work out after all? I've heard very good things about Dr. F, though. Got my fingers crossed that he's the answer for you.
  30. 1 point
    by Kristen Monaco, Staff Writer, MedPage Today LOS ANGELES -- An investigational therapy improved quality of life and reduced disease symptoms for patients with endogenous Cushing's syndrome, according to new findings from the phase III SONICS study. Patients taking oral levoketoconazole twice daily had significant reductions in mean scores for acne (-1.8), peripheral edema (-0.4), and hirsutism (-2.6), all secondary endpoints of the pivotal trial (P<0.03 for all), reported Maria Fleseriu, MD, of Oregon Health and Science University in Portland. "We're looking forward to see the results of further studies and to add this therapy to the landscape of Cushing's," Fleseriu said here during a presentation of the findings at AACE 2019, the annual meeting of the American Association of Clinical Endocrinologists. "We have a newer medication and still we cannot make a dent in the outcomes of Cushing's, especially for patient-reported outcomes." Free testosterone levels significantly decreased in women taking levoketoconazole (a ketoconazole stereoisomer and potent steroidogenesis inhibitor), from an average of 0.32 ng/dL down to 0.12 ng/dL (0.011 to 0.004 nmol/L, P<0.0001). Men had a non-significant increase: 5.1 ng/dL up to 5.8 ng/dL (0.177 to 0.202 nmol/L). There were no significant changes from baseline to the end of maintenance for other secondary endpoints in the analysis: moon facies, facial plethora, striae, bruising, supraclavicular fat, irregular menstruation, and dysmenorrhea. However, significant improvements after 6 months of therapy were seen in patient-reported quality of life compared with baseline (mean 10.6 change on the Cushing QOL questionnaire) as well as a significant reduction in depressive symptoms (mean -4.3 change on the Beck Depression Inventory II). The open-label, multicenter SONICS (Study of Levoketoconazole in Cushing's Syndrome) trial included 94 adult men and women with a confirmed diagnosis of Cushing's syndrome and elevated 24-hour mean urinary free cortisol (mUFC) levels at least 1.5 times the upper limit of normal. In the dose-titration phase of the study (weeks 2 to 21), patients were titrated up to a max dose of 600 mg levoketoconazole twice daily until mUFC normalization. A 6-month maintenance phase followed with no dose increases, but decreases were allowed if adverse events emerged. An additional 6-month extended evaluation phase followed thereafter. The study met it's previously reported primary endpoint, with 30% of patients achieving normalized mUFC levels after 6 months of maintenance therapy without a dose increase (95% CI 21%-40%, P=0.0154). Levoketoconazole was well tolerated, with only 12.8% of patients discontinuing treatment due to adverse events. The most commonly reported adverse events were nausea (31.9%), headache (27.7%), peripheral edema (19.1%), hypertension (17%), and fatigue (16%), some of which were expected due to steroid withdrawal, Fleseriu said. Serious adverse events were reported in 14 patients, including prolonged QTc interval in two patients, elevated liver function in one patient, and adrenal insufficiency in another, events similar to those seen with ketoconazole (Nizoral) therapy. Fleseriu explained that drug-drug interaction is a problem in Cushing's, as all of the available medications prolong QT interval. She noted that in SONICS, QT prolongation with levoketoconazole was observed in few patients. It's still a "concern," said Fleseriu, especially for patients on other drugs that prolong QT. Although not yet approved, levoketoconazole has received orphan drug designation from the FDA and the European Medicines Agency for endogenous Cushing's syndrome. The tentative brand name is Recorlev. The study was supported by Strongbridge Biopharma. Fleseriu reported relationships with Strongbridge, Millendo Therapeutics, and Novartis. Co-authors also disclosed relevant relationships with industry. Primary Source American Association of Clinical Endocrinologists Source Reference: Fleseriu M, et al "Levoketoconazole in the treatment of endogenous Cushing's syndrome: Improvements in clinical signs and symptoms, patient-reported outcomes, and associated biochemical markers in the phase 3 SONICS study" AACE 2019; Poster 369. From https://www.medpagetoday.com/meetingcoverage/aace/79465
  31. 1 point
    Corcept Therapeutics is recruiting participants for its Phase 3 clinical trial evaluating relacorilant as a potential treatment for Cushing’s syndrome-related side effects such as high blood pressure and impaired glucose tolerance. Also, findings from the study “A Randomized-Withdrawal, Placebo-Controlled, Phase 3 Study to Assess the Efficacy and Safety of Selective Glucocorticoid Receptor Antagonist, Relacorilant, in Patients with Cushing Syndrome (GRACE Study),” were presented at the 2019 Annual Meeting of the Endocrine Society (ENDO), in New Orleans, Louisiana. In endogenous Cushing’s syndrome there is an “internal” culprit — usually a benign tumor — that makes the body produce too much of the hormone cortisol. The excessive amount of circulating cortisol can lead to serious problems, such as type 2 diabetes and high blood pressure. Relacorilant is designed to prevent the effects of excess cortisol by blocking one of its receptors, the glucocorticoid receptor. Results from a Phase 2 trial (NCT02804750) suggest that relacorilant may manage the effects of prolonged cortisol excess in Cushing’s patients faster and without the known side effects of approved medications like Korlym (mifepristone). Also, the treatment improved glucose tolerance and improved blood pressure in patients, suggesting it could be used to treat those with endogenous Cushing’s syndrome and concurrent type 2 diabetes mellitus, impaired glucose tolerance, and/or uncontrolled high blood pressure (hypertension). Corcept has now designed the GRACE Phase 3 trial (NCT03697109), a multicenter, double-blind, placebo-controlled, randomized-withdrawal study, to evaluate relacorilant’s safety and effectiveness in these patients. GRACE will be conducted in two stages. First, all patients will be given oral relacorilant each day for 22 weeks, at doses rising from 100 mg to a maximum of 400 mg. Those who complete that stage and show improvements in pre-specified parameters of glucose tolerance or hypertension will move into the second, randomized phase of the trial. Here, they will be randomly assigned to placebo or relacorilant at the same dose they received at the end of the first stage. This new round of treatment will last 12 weeks. Treatment-related adverse events (side effects) also will be assessed for up to 48 weeks (about 11 months) as a main outcome. Additional primary goals include changes in glucose tolerance and blood pressure between the end of the first and second stages of the study. Secondary objectives include identifying the proportion of patients achieving a response in glucose tolerance and high blood pressure criteria and the proportion of those who worsened at the end of the first stage, and the changes in quality of life throughout the study. Researchers plan to enroll 130 people in these U.S. cities: Indianapolis, Indiana; Metairie, Louisiana; Jackson, Mississippi; Albany, New York; Jamaica, New York; Wilmington, North Carolina; Miami, Florida; Summerville, South Carolina; El Paso, Texas; Oklahoma City, Oklahoma, and; Aurora, Colorado. More detailed information is available here. “We look forward to presenting new findings concerning cortisol modulation in patients with hypercortisolism,” Joseph K. Belanoff, MD, Corcept’s CEO, said in a press release.
  32. 1 point
    The use of an insulin pump to deliver continuous pulsatile cortisol may be a viable treatment option in patients with severe adrenal insufficiency who are unresponsive to oral corticosteroids, according to study results presented at the 28th Annual Congress of the American Association of Clinical Endocrinologists, held April 24 to 28, 2019, in Los Angeles, California. According to the investigators, increasing oral steroid doses may be required to prevent adrenal crisis in patients with adrenal insufficiency. However, in light of the associated side effects of long-term use of steroids, an alternative treatment method is needed. Insulin pumps, typically used to treat patients with diabetes, can be used to deliver steroids and may provide symptom control, prevent adrenal crisis, and lower required corticosteroid dose. The current study enrolled patients with adrenal insufficiency who could not absorb oral corticosteroid treatment or were not responding to treatment. Of 118 patients with adrenal insufficiency, 6 patients were switched to pump treatment. The results indicated that the use of cortisol pumps was associated with a 78.5% risk reduction for adrenal crisis compared with oral corticosteroids. As hydrocortisone dose was gradually tapered using the cortisol pump, there was a mean dose reduction of 62.77 mg compared with oral corticosteroid therapy. The researchers noted that in addition to reducing the number of adrenal crises, use of a cortisol pump was found to be associated with better symptom control and quality of life. “Continuous pulsatile cortisol replacement via pump is an option for management of severe adrenal insufficiency in patients unresponsive to oral therapy,” concluded the researchers. Reference Khalil A, Ahmed F, Alzohaili O. Insulin pump for adrenal insufficiency, a novel approach to the use of insulin pumps to deliver corticosteroids in patients with poor cortisol absorption. Presented at: American Association of Clinical Endocrinologists 28th Annual Scientific & Clinical Congress; April 24-28, 2019; Los Angeles, CA. From https://www.endocrinologyadvisor.com/home/conference-highlights/aace-2019/cortisol-pumps-may-be-viable-option-to-reduce-adrenal-crisis-in-severe-adrenal-insufficiency/
  33. 1 point
    In: Pituitary, ISSN 1386-341X, E-ISSN 1573-7403, Vol. 22, no 2, p. 179-186Article in journal (Refereed) Published Abstract [en] Background: Studies on the incidence of Cushing's disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden. Methods: Patients registered with a diagnostic code for Cushing's syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data. Results: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4-1.8) cases per million. 1987-1995, 1996-2004, and 2005-2013, the mean annual incidence was 1.5 (1.1-1.8), 1.4 (1.0-1.7) and 2.0 (1.7-2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P<0.05). Conclusion: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987-2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research. Place, publisher, year, edition, pages SPRINGER , 2019. Vol. 22, no 2, p. 179-186 Keywords [en] Cushing's syndrome, Epidemiology, Incidence, Validation National Category Endocrinology and Diabetes Identifiers URN: urn:nbn:se:uu:diva-380429DOI: 10.1007/s11102-019-00951-1ISI: 000461291200010PubMedID: 30799512OAI: oai:DiVA.org:uu-380429DiVA, id: diva2:1300822 From http://uu.diva-portal.org/smash/record.jsf?aq2=%5B%5B%5D%5D&c=1&af=%5B%5D&searchType=LIST_LATEST&sortOrder2=title_sort_asc&query=&language=en&pid=diva2%3A1300822&aq=%5B%5B%5D%5D&sf=all&aqe=%5B%5D&sortOrder=author_sort_asc&onlyFullText=false&noOfRows=50&dswid=-3880
  34. 1 point
    NEW ORLEANS — The investigational drug osilodrostat (Novartis) continues to show promise for treating Cushing's disease, now with new phase 3 trial data. The data from the phase 3, multicenter, double-blind randomized withdrawal study (LINC-3) of osilodrostat in 137 patients with Cushing's disease were presented here at ENDO 2019: The Endocrine Society Annual Meeting by Beverly M.K. Biller, MD, of the Neuroendocrine & Pituitary Tumor Center at Massachusetts General Hospital, Boston. "Osilodrostat was effective and shows promise for the treatment of patients with Cushing's disease," Biller said. Osilodrostat is an oral 11β-hydroxylase inhibitor, the enzyme that catalyzes the last step of cortisol biosynthesis in the adrenal cortex. Its mechanism of action is similar to that of the older Cushing's drug metyrapone, but osilodrostat has a longer plasma half-life and is more potent against 11β-hydroxylase. Significantly more patients randomized to osilodrostat maintained a mean urinary free cortisol (mUFC) response versus placebo at 34 weeks following a 24-week open-label period plus 8-week randomized phase, with rapid and sustained mUFC reduction in most patients. Patients also experienced improvements in clinical signs of hypercortisolism and quality of life. The drug was generally well-tolerated and had no unexpected side effects. Asked to comment, session comoderator Julia Kharlip, MD, associate medical director of the Pituitary Center at the University of Pennsylvania, Philadelphia, told Medscape Medical News, "This drug is incredibly exciting because over 80% of people were controlled fairly rapidly. People could get symptom relief but also a reliable response. You don't have to wonder when you're treating a severely affected patient if it's going to work. It's likely going to work." However, Kharlip cautioned that it remains to be seen whether osilodrostat continues to work long-term, given that the older drug metyrapone — which must be given four times a day versus twice daily for osilodrostat — is known to become ineffective over time because the pituitary tumor eventually overrides the enzyme blockade. "Based on how osilodrostat is so much more effective at smaller doses, there's more hope that it will be effective long term...If the effectiveness and safety profile that we're observing now continues to show the same performance years in a row, then we've got our drug." Osilodrostat Potentially Addresses an Unmet Medical Need Cushing's disease is a rare disorder of chronic hypercortisolism with significant burden, increased mortality, and decreased quality of life. Pituitary surgery is the recommended first-line treatment for most patients, but not all patients remit with surgery and some require additional treatment. Pasireotide (Signifor, Novartis), an orphan drug approved in the United States and Europe for the treatment of Cushing's disease in patients who fail or are ineligible for surgical therapy, is also only effective in a minority of patients. "There hasn't been a medicine effective for long-term treatment, so a lot of patients end up getting bilateral adrenalectomy, thereby exchanging one chronic medical disease for another," Kharlip explained. Biller commented during the question-and-answer period, "I think because not all patients are placed in remission with surgery initially and because other patients subsequently recur — a problem that is more common than we used to believe — we do need medical therapies." She continued, "I think it's important to have a large choice of medical therapies that work in different places in the hypothalamic-pituitary-adrenal axis. "Even though surgery is the right initial therapy for everyone, I think in terms of subsequent medical therapy we have to tailor that to the individual circumstances of the patient in terms of the goals of treatment, and perhaps what other medicines they're on, the degree of cortisol excess [and other factors]." Highly Significant Normalization in Mean UFC Versus Placebo In a prior 22-week phase 2 study (LINC-2), osilodrostat normalized mUFC in most patients. Results of the extension phase were reported by Medscape Medical News 2 years ago. The current phase 3 study, LINC-3, was conducted on the basis of that proof-of-concept study, Biller said. The trial was conducted in 19 countries across four continents in patients with persistent or recurrent Cushing's disease screened for mUFC > 1.5 times the upper limit of normal and other entry criteria. In total, 137 patients were enrolled and randomized. Participants were a median age of 40 years, 77% were female, and 88% had undergone prior pituitary surgery. Nearly all (96%) had received at least one previous treatment for Cushing's. At baseline, patients' mean mUFC (364 µg/24 hours) was 7.3 times the upper limit of normal, which is "quite significant hypercortisolemia," Biller noted. All patients initially received osilodrostat, with a rapid dose uptitration every 2 weeks from 2 to 30 mg orally twice daily until they achieved a normal UFC. They continued on open-label medication until week 24, when urine samples were collected. Patients who had an mUFC less than the upper limit of normal and had not had a dose increase in the prior 12 weeks were eligible for the double-blind phase. Those who were ineligible continued taking open-label drug. The 70 eligible patients were randomized to continue taking osilodrostat (n = 36) or were switched to placebo (n = 34) for another 8 weeks. After that, the patients taking placebo were switched back to osilodrostat until week 48. A total of 113 patients completed the 48 weeks. The primary efficacy endpoint was mUFC at 34 weeks (the end of the 8-week randomized phase). For those randomized to continue on the drug, mUFC remained in the normal range in 86.1% of patients versus just 29.4% of those who had been switched to placebo for the 8 weeks. The difference was highly significant (odds ratio, 13.7; P < .001), Biller reported. A key secondary endpoint, proportion of patients with an mUFC at or below the ULN at 24 weeks without up-titration after week 12, was achieved in 53%. The mean dose at 48 weeks was 11.0 mg/day, "a fairly low dose," she noted. Clinical features were also improved at week 48, including systolic and diastolic blood pressure (percentage change –6.8 and –6.6, respectively), weight (–4.6), waist circumference (–4.2), fasting plasma glucose (–7.1), and HbA1c (–5.4). Scores on the Cushing Quality of Life scale improved by 52.4 points, and Beck Depression Inventory scores dropped by 31.8 points. Most Adverse Events Temporary, Manageable The most commonly reported adverse events were nausea (41.6%), headache (33.6%), fatigue (28.5%), and adrenal insufficiency (27.7%), and 10.9% of patients overall discontinued because of an adverse event. Adverse events related to hypocortisolism occurred in 51.1% of patients overall, with 10.2% being grade 3 or 4. However, most of these were single episodes of mild-to-moderate intensity and mainly occurred during the initial 12-week titration period. Most patients responded to dose reduction or glucocorticoid supplementation. Adverse events related to accumulation of adrenal hormone precursors occurred in 42.3% of patients overall, with the most common being hypokalemia (13.1%) and hypertension (12.4%). No male patients had signs or symptoms related to increased androgens or estrogens. However, 12 female patients experienced hirsutism, most of those patients also had acne, and one had hypertrichosis. None discontinued because of those symptoms. Kharlip commented, "What's really inspiring was that even though half of the patients had symptoms related to adrenal insufficiency, it sounded as if they were quickly resolved with treatment and none discontinued because of it." "And it may have been related to study design where the medication was titrated very rapidly. There is probably a way to do this more gently and get the good results without the side effects." Kharlip also praised the international consortium that devised the protocol and collaborated in the research effort. "It's incredibly exciting and gratifying to see the world come together to get these data. It's such a rare disease. To be able to have something like that in the field is a dream, to have a working consortium. The protocol was effective in demonstrating efficacy. It's just a win on so many levels for a disease that currently doesn't have a good therapy...I struggle with these patients all the time so I'm thrilled that there is hope." An ongoing confirmatory phase 3 study, LINC-4, is evaluating patients up to 48 weeks. Biller is a consultant for and has received grants from Novartis and Strongbridge. Kharlip has reported no relevant financial relationships. For more diabetes and endocrinology news, follow us on Twitter and on Facebook. From https://www.medscape.com/viewarticle/910864#vp_1
  35. 1 point
    I plan to do the Cushing's Awareness Challenge again. Last year's info is here: https://cushieblogger.com/2018/03/11/time-to-sign-up-for-the-cushings-awareness-challenge-2018/ The original page is getting very slow loading, so I've moved my own posts to this newer blog. As always, anyone who wants to join me can share their blog URL with me and I'll add it to the links on the right side, so whenever a new post comes up, it will show up automatically. If the blogs are on WordPress, I try to reblog them all to get even more exposure on the blog, on Twitter and on Facebook at Cushings Help Organization, Inc. If you have photos, and you give me permission, I'll add them to the Pinterest page for Cushing's Help. The Cushing’s Awareness Challenge is almost upon us again! Do you blog? Want to get started? Since April 8 is Cushing’s Awareness Day, several people got their heads together to create the Eighth Annual Cushing’s Awareness Blogging Challenge. All you have to do is blog about something Cushing’s related for the 30 days of April. There will also be a logo for your blog to show you’ve participated. Please let me know the URL to your blog in the comments area of this post, on the Facebook page, in one of the Cushing's Help Facebook Groups, on the message boards or an email and I will list it on CushieBloggers ( http://cushie-blogger.blogspot.com/ ) The more people who participate, the more the word will get out about Cushing’s. Suggested topics – or add your own! In what ways have Cushing’s made you a better person? What have you learned about the medical community since you have become sick? If you had one chance to speak to an endocrinologist association meeting, what would you tell them about Cushing’s patients? What would you tell the friends and family of another Cushing’s patient in order to garner more emotional support for your friend? challenge with Cushing’s? How have you overcome challenges? Stuff like that. I have Cushing’s Disease….(personal synopsis) How I found out I have Cushing’s What is Cushing’s Disease/Syndrome? (Personal variation, i.e. adrenal or pituitary or ectopic, etc.) My challenges with Cushing’s Overcoming challenges with Cushing’s (could include any challenges) If I could speak to an endocrinologist organization, I would tell them…. What would I tell others trying to be diagnosed? What would I tell families of those who are sick with Cushing’s? Treatments I’ve gone through to try to be cured/treatments I may have to go through to be cured. What will happen if I’m not cured? I write about my health because… 10 Things I Couldn’t Live Without. My Dream Day. What I learned the hard way Miracle Cure. (Write a news-style article on a miracle cure. What’s the cure? How do you get the cure? Be sure to include a disclaimer) Give yourself, your condition, or your health focus a mascot. Is it a real person? Fictional? Mythical being? Describe them. Bonus points if you provide a visual! 5 Challenges & 5 Small Victories. The First Time I… Make a word cloud or tree with a list of words that come to mind when you think about your blog, health, or interests. Use a thesaurus to make it branch more. How much money have you spent on Cushing’s, or, How did Cushing’s impact your life financially? Why do you think Cushing’s may not be as rare as doctors believe? What is your theory about what causes Cushing’s? How has Cushing’s altered the trajectory of your life? What would you have done? Who would you have been What three things has Cushing’s stolen from you? What do you miss the most? What can you do in your Cushing’s life to still achieve any of those goals? What new goals did Cushing’s bring to you? How do you cope? What do you do to improve your quality of life as you fight Cushing’s? How Cushing’s affects children and their families Your thoughts…?
  36. 1 point
    Written by Kathleen Doheny With Oskar Ragnarsson, MD, PHD, and Tamara Wexler, MD, PhD Adults with Cushing's syndrome, also called hypercortisolism, have a three-fold higher risk of dying from heart disease compared to the general population,1 according to findings reported by a Swiss research team. Although the researchers found that the risk drops when patients are under care, receiving treatment, and are in remission, the risks don't disappear completely. For some perspective, heart disease is common in the United States, affecting, one in four adults, regardless of health status.2 "Patients with Cushing's disease have excess mortality [risk]," says Oskar Ragnarsson, MD, PhD, associate professor and a senior consultant in internal medicine and endocrinology at Sahlgrenska University Hospital in Gothenburg, Sweden. He is the author of the study, which appears in the Journal of Clinical Endocrinology & Metabolism. Having Cushing's Requires Vigilance Beyond Disease Symptoms Still, the news is not all bleak, he says. Simple awareness of the increased risks can help individuals reduce their risk, just as following your doctor’s treatment plan so remain in remission, Dr. Ragnarsson tells EndocrineWeb. In addition, patients who received growth hormone replacement appear to have better overall outcomes.1 Cushing’s syndrome occurs when your body is exposed to high levels of the hormone cortisol over a long period of time. This can be caused either by taking corticosteroid medicine orally, or if your body just makes too much cortisol. Common symptoms of this condition include: having a fatty hump between the shoulders, a rounded face, and stretch marks with pink or purple coloring on the skin. Complications, if Cushing’s disease goes untreated, may include bone loss (leading to increased risk of fractures and osteoporosis), high blood pressure, type 2 diabetes, and other problems. Usual treatment includes medication and surgery that are aimed to normalize cortisol levels.3 Increased Risks Are Cause for Concern in Cushing’s Disease The researchers analyzed data from 502 men and women, all of whom were diagnosed with Cushing's disease between 1987 and 2013 as indicated in a Swedish health database.1 The average age of these patients at diagnosis was 43 years, and, 83% of these individuals were in remission. During a median follow up of 13 years—half followed for longer, half followed for less time—the researchers noted 133 deaths, more than the 54 that had been anticipated in this patient population. From this data,1 Dr. Ragnarsson and his team calculated that people with Cushing's disease were about 2.5 times more likely to die than the general population. The most common reason, with more than a 3-fold increased risk, was attributed to events associated with cardiovascular disease, encompassing both heart disease and stroke. This group also appeared to have a higher risk of death from infectious and respiratory diseases, and conditions related to gastrointestinal problems. Fortunately, just being in disease remission helps to reduce the risk of all-cause mortality,1 the researchers' report, with both men and women whose Cushing’s disease is well-managed having a two-fold lower risk of death during the follow-up period.1 Those in remission who were receiving growth hormone had an even lower risk of death than those on other forms of treatment. In addition, the researchers looked at the 55 patients with Cushing’s disease who were in remission and also had diabetes, finding that their risks remained the same. In other words, despite a strong relationship between diabetes and increased heart disease, the risks of death were not increased in this group of patients.1 In considering the impact that treatments may have, the researchers found: 3 in 4 of these patients (75%) had undergone pituitary surgery 28% had undergone radiotherapy 1 in 4 (24%) had had both adrenal glands removed Those who had their adrenal glands removal experienced a 2.7-fold higher risk of death, while those who were treated with radiotherapy or had pituitary surgery did not have an increased risk associated with cardiovascular events. When glucocorticoid therapy was added, it did not affect results, according to Dr. Ragnarsson and his research team. Bottom line? "Even though patients in remission have a better prognosis than patients not in remission, they still have more than a 2-fold increased mortality [risk]," he says. The study, he says, is the first to uncover a high rate of death from suicide in Cushing's patients. It has been reported before, but the numbers found in this study were higher than in others. The findings, he says, emphasize the importance of treating Cushing's with a goal of remission. Ongoing surveillance and management are crucial, he says. "Also, evaluation and active treatment of cardiovascular risk factors and mental health is of utmost importance," Dr. Ragnarsson tells EndocrineWeb. Remission Reduces But Doesn't Eliminate Serious Risks The study findings underscore the message that ''the priority for patients is to achieve biochemical remission," says Tamara L. Wexler, MD, PhD, director of the NYU Langone Medical Center Pituitary Center, in reviewing the findings for EndocrineWeb. "One question raised by the study findings is whether patients listed as being in remission were truly in (consistent) remission," Dr. Wexler says. "One or more of several testing methods may have been used, and the data were based on medical record reviews so we can’t be certain about the status of these patients’ remission. In addition, we don’t know how much excess cortisol patients were exposed over time, which may change their risks.'' I have another concern about the findings, she says. While the method of analysis used in the study suggests that the length of time from diagnosis to remission is not associated with increased death risk, ''it may be that the total exposure to excess cortisol—the amplitude as well as duration—is related to morbidity [illness] and mortality [death] risk.'' And, she adds, any negative effects experienced by patients with Cushing’s disease may be reduced further as remission status continues. In addition, Dr. Wexler considers the authors' comments that sustained high cortisol levels may impact the cardiovascular system in a way that is chronic and irreversible ''may be overly strong." She believes that the total cortisol exposure and the duration of remission may both play important roles in patients' ongoing health. She does agree, however, with the researchers' recommendation of the need to treat heart disease risk factors more aggressively in patients with a history of Cushing's disease. Equally important, is for patients to be warned that there is an increased concern about suicide, she says, urging anyone with Cushing’s disease to raise all of these concerns with your health practitioner. Overall, the study findings certainly suggest that it is important for you to know that if you have Cushing’s syndrome, you are at increased risk for not just heart disease but also mental health disorders and other ailments than the general population, she says, and that the best course of action is to work closely with your doctor to achieve remission and stick to your overall treatment plan. Steps to Take to Reduce Your Risks for Heart Disease and Depression Dr. Ragnarsson suggests those with Cushing's disease make adjustments as needed to achieve the following risk-reducing strategies: Be sure your food choices meet the parameters of a heart-healthy diet You are getting some kind of physical activity most every day You see your doctor at least once a year to have annual checks of your blood pressure, blood sugar, and other heart disease risk factors. For those of you receiving cortisone replacement therapy, you should be mindful of the need to have a boost in your medication dose with your doctors' supervision when you're are sick or experiencing increased health stresses. From https://www.endocrineweb.com/news/adrenal-disorders/61675-cushings-disease-stresses-your-heart-your-mental-health
  37. 1 point
    Cushing’s disease patients in Sweden have a higher risk of death than the general Swedish population, particularly of cardiovascular complications, and that increased risk persists even in patients in remission, a large nationwide study shows. The study, “Overall and disease-specific mortality in patients with Cushing’s disease: a Swedish nationwide study,” was published in the Journal of Clinical Endocrinology and Metabolism. The outcomes of Cushing’s disease patients have improved with the introduction of several therapeutic approaches, such as minimally invasive surgery and cortisol-lowering therapies. However, mortality is still high, especially among those who do not achieve remission. While currently patients in remission are thought to have a better prognosis, it is still unclear whether these patients still have a higher mortality than the general population. Understanding whether these patients are more likely to die and what risk factors are associated with increased mortality is critical to reduce death rates among Cushing’s patients. A team of Swedish researchers thus performed a retrospective study that included patients diagnosed with Cushing’s disease who were part of the Swedish National Patient Registry between 1987 and 2013. A total of 502 patients with Cushing’s disease were included in the study, 419 of whom were confirmed to be in remission. Most patients (77%) were women; the mean age at diagnosis was 43 years, and the median follow-up time was 13 years. During the follow-up, 133 Cushing’s patients died, compared to 54 expected deaths in the general population — a mortality rate 2.5 times higher, researchers said. The most common causes of death among Cushing’s patients were cardiovascular diseases, particularly ischemic heart disease and cerebral infarctions. However, infectious and respiratory diseases (including pneumonia), as well as diseases of the digestive system, also contributed to the increased mortality among Cushing’s patients. Of those in remission, 21% died, compared to 55% among those not in remission. While these patients had a lower risk of death, their mortality rate was still 90% higher than that of the general population. For patients who did not achieve remission, the mortality rate was 6.9 times higher. The mortality associated with cardiovascular diseases was increased for both patients in remission and not in remission. Also, older age at the start of the study and time in remission were associated with mortality risk. “A more aggressive treatment of hypertension, dyslipidemia [abnormal amount of fat in the blood], and other cardiovascular risk factors might be warranted in patients with CS in remission,” researchers said. Of the 419 patients in remission, 315 had undergone pituitary surgery, 102 had had their adrenal glands removed, and 116 had received radiation therapy. Surgical removal of the adrenal glands and chronic glucocorticoid replacement therapy were associated with a worse prognosis. In fact, glucocorticoid replacement therapy more than twice increased the mortality risk. Growth hormone replacement was linked with better outcomes. In remission patients, a diagnosis of diabetes mellitus or high blood pressure had no impact on mortality risk. Overall, “this large nationwide study shows that patients with [Cushing’s disease] continue to have excess mortality even after remission,” researchers stated. The highest mortality rates, however, were seen in “patients with persistent disease, those who were treated with bilateral adrenalectomy and those who required glucocorticoid replacement.” “Further studies need to focus on identifying best approaches to obtaining remission, active surveillance, adequate hormone replacement and long-term management of cardiovascular and mental health in these patients,” the study concluded. From https://cushingsdiseasenews.com/2019/02/28/even-in-remission-cushings-patients-have-excess-mortality-swedish-study-says/
  38. 1 point
    Irina Bancos, M.D., an endocrinologist at Mayo Clinic in Rochester, Minnesota, and Jamie J. Van Gompel, M.D., a neurosurgeon at Mayo Clinic's campus in Minnesota, discuss Mayo's multidisciplinary approach to adrenocorticotropic hormone (ACTH)-secreting pituitary tumors. Pituitary tumors are common and often don't cause problems. But some pituitary tumors produce the hormone ACTH, which stimulates the production of another hormone (cortisol). Overproduction of cortisol can result in Cushing syndrome, with signs and symptoms such as weight gain, skin changes and fatigue. Cushing syndrome is rare but can cause significant long-term health problems. Treatment for Cushing syndrome caused by a pituitary tumor generally involves surgery to remove the tumor. Radiation therapy and occasionally adrenal surgery may be needed to treat Cushing syndrome caused by ACTH-secreting pituitary tumors. Mayo Clinic has experience with this rare condition.
  39. 1 point
    Laparoscopic adrenalectomy — a minimally invasive procedure that removes the adrenal glands through a tiny hole in the abdomen — can be safely performed in obese patients with Cushing’s syndrome, a retrospective study reports. The surgery resolved symptoms in 95% of cases, reducing cortisol levels, lowering blood pressure, and leading to a significant loss of weight in morbidly obese patients. The study, “Minimally invasive approach to the adrenal gland in obese patients with Cushing’s syndrome,” was published in the journal Minimally Invasive Therapy & Allied Technologies. Cushing’s syndrome results from the prolonged secretion of excess cortisol, the major glucocorticoid hormone. While most cases are caused by tumors in the pituitary gland, up to 27% result from tumors in the adrenal glands. In these cases, the standard therapeutic strategy is to remove one or both adrenal glands, a surgical procedure called adrenalectomy. However, because glucocorticoids are key hormones regulating fat metabolism, Cushing’s syndrome patients are known to be prone to obesity, a feature that is often associated with post-operative complications. In this study, researchers aimed to compare the outcomes of morbidly obese patients versus the mildly obese and non-obese who underwent a minimally invasive procedure to remove their adrenal glands. The approach, called laparoscopic adrenalectomy, inserts tiny surgical tools through a small hole in the abdomen, along with a camera that helps guide the surgeon. The study included 228 patients (mean age 53.4 years). Of them, 62 were non-obese, 87 were moderately obese, and 79 were considered morbidly obese. There were 121 patients with tumors in the right adrenal gland, 96 in the left gland, and 11 in both glands. High blood pressure was the most common symptom, affecting 66.7% of the participants. Surgery lasted 101 minutes on average, and patients remained in the hospital for a median 4.3 days afterward. Six patients had to be converted into an open surgery because of uncontrollable loss of blood or difficulties in the procedure. Post-surgery complications, most of which were minor, were seen in seven patients. One patient had blood in the peritoneal cavity and had to have surgery again; another patient had inflammation of the pancreas that required a longer admission. The analysis showed no statistical differences among the three groups regarding the length of surgery, length of stay in the hospital, or the rate of conversion into open surgery. However, in obese women, surgeons chose a different surgical incision when removing the left adrenal gland, “suggesting that the distribution of visceral fat in these patients could constitute a drawback for the [standard] approach,” researchers said. After the surgery, 95% of patients saw their symptoms resolve, including cortisol levels, high blood pressure, and glucose metabolism, and none had a worsening of symptoms in the 6.3 years of follow-up. Obese patients also showed a significant reduction in their weight — 2 kg by 18 months, and 5 kg by the end of follow-up. Overall, “laparoscopic adrenalectomy is safe and feasible in obese patients affected with Cushing’s disease and it can lead to the resolution of the related symptoms,” researchers said. The benefits of the surgery in patients with Cushing’s syndrome “could be extended to the improvements and in some cases to the resolution of hypercortisolism related symptoms (i.e. hypertension or even morbid obesity),” the study concluded. Adapted from https://cushingsdiseasenews.com/2019/02/07/laparoscopic-removal-of-adrenal-glands-safe-for-obese-cushings-patients/
  40. 1 point
    Huang X, et al. Pituitary. 2019;doi:10.1007/s11102-018-0927-x. March 3, 2019 The use of 3D-printed models could lead to less operation time and blood loss and fewer postoperative complications in adults who undergo endoscopic endonasal transsphenoidal surgery for pituitary adenomas and other conditions, according to findings published in Pituitary. “Several factors influence the outcome of endoscopic endonasal surgery, including the tumor volume, patient age, lesion location and sphenoid pneumatolysis,” Xiaobing Jiang, of the department of neurosurgery at Union Hospital of Tongji Medical College of Huazhong University of Science and Technology in Wuhan, Hubei, China, and colleagues wrote. “An accurate model of the target tumor structure is a major prerequisite for a successful [pituitary adenoma] resection, especially for macroadenomas, as this may avoid disastrous complications due to suboptimal treatment.” Jiang and colleagues conducted a retrospective analysis of 20 adults who underwent endoscopic endonasal transsphenoidal surgery at Union Hospital in Wuhan. Participants were included based on similar tumor sizes, the presence of no other diseases and nonintuitive tumor identification. All surgeries in the cohort occurred between January and August 2017, with 10 participants (mean age, 44.4 years; 50% women) receiving CT and MRI before surgery; the remaining 10 also received an operation with 3D printing (mean age, 41.2 years; 50% women). To create the 3D models, images from CT and MRIs were combined. The 3D printer then used this information to create the model, which took between 2 hours, 10 minutes, and 4 hours, 32 minutes, to design and 10 hours, 12 minutes, and 22 hours, 34 minutes, to print. After surgery, the researchers found that mean operation time was lower in participants who had 3D models compared with participants who did not (127 minutes vs. 143.4 minutes; P = .007). In addition, there was less blood loss in participants with 3D printing compared with participants without (159.9 mL vs. 170 mL; P = .009). The researchers noted that there were postoperative complications in 20% of the 3D-printing group and 40% of the CT and MRI alone group. “As it is highly precise and allows personalization, 3D-printing technology has started to be applied in medicine in recent years. In neurosurgery, 3D-printing technology can provide models for the patients’ disease characteristics, such as skull defects, brain tumors, intracranial aneurysms and intracranial vascular malformations,” the researchers wrote. “We believe that with its continuous development, 3D-printing technology will be applied in clinical practice in the near future.” – by Phil Neuffer Disclosures: The authors report no relevant financial disclosures. From https://www.healio.com/endocrinology/neuroendocrinology/news/online/%7B582c6512-708a-4900-ad20-f0adb5a79390%7D/3d-printing-technology-improves-outcomes-in-pituitary-adenoma-surgery
  41. 1 point
    Is anyone having any issues or problems with the site upgrade? I was surprised how smoothly it went...and the skin still works!
  42. 1 point
    Cushing’s syndrome patients who undergo adrenal surgery are more likely to have venous thromboembolism — blood clots that originate in the veins — than patients who have the same procedure for other conditions, a study suggests. Physicians should consider preventive treatment for this complication in Cushing’s syndrome patients who are having adrenal surgery and maintain it for four weeks after surgery due to late VTE onset. The study, “Is VTE Prophylaxis Necessary on Discharge for Patients Undergoing Adrenalectomy for Cushing Syndrome?” was published in the Journal of Endocrine Society. Cushing’s syndrome is a condition characterized by too much cortisol in circulation. In many cases, it is caused by a tumor in the pituitary gland, which produces greater amounts of the cortisol-controlling adrenocorticotropic hormone (ACTH). In other cases, patients have tumors in the adrenal glands that directly increase cortisol production. When the source of the problem is the pituitary gland, the condition is known as Cushing’s disease. The imbalance in cortisol levels generates metabolic complications that include obesity, high blood pressure, diabetes, and cardiovascular complications. Among the latter, the formation of blood clots in the deep veins of the leg, groin or arm — a condition called venous thromboembolism (VTE) — is higher in both Cushing’s disease and Cushing’s syndrome patients. VTE is believed to be a result of excess coagulation factors that promote blood clot formation, and is thought to particularly affect Cushing’s disease patients who have pituitary gland surgery. Whether Cushing’s syndrome patients who have an adrenalectomy — surgical removal of one or both adrenal glands — are at a higher risk for VTE is largely unknown. This is important for post-operative management, to decide whether they should have preventive treatment for blood clot formation. Researchers at the National Cancer Institute in Maryland did a retrospective analysis of a large group of patients in the American College of Surgeons National Quality Improvement Program database. A total of 8,082 patients underwent adrenal gland surgery between 2005 and 2016. Data on these patients included preoperative risk factors, as well as 30-day post-surgery mortality and morbidity outcomes. Patients with malignant disease and without specified adrenal pathology were excluded from the study. The final analysis included 4,217 patients, 61.8% of whom were females. In total, 310 patients had Cushing’s syndrome or Cushing’s disease that required an adrenalectomy. The remaining 3,907 had an adrenal disease other than Cushing’s and were used as controls. The incidence of VTE after surgery — defined as pulmonary embolism (a blockage of an artery in the lungs) or deep-vein thrombosis — was 1% in the overall population. However, more Cushing’s patients experienced this complication (2.6%) than controls (0.9%). Those diagnosed with Cushing’s syndrome were generally younger, had a higher body mass index, and were more likely to have diabetes than controls. Their surgery also lasted longer — 191.2 minutes versus 142 minutes — as did their hospital stay – 2.4 versus two days. Although without statistical significance, the researchers observed a tendency for longer surgery time for patients with Cushing’s syndrome than controls with VTE. They saw no difference in the time for blood coagulation between Cushing’s and non-Cushing’s patients, or postoperative events other than pulmonary embolism or deep-vein thrombosis. In addition, no differences were detected for VTE incidence between Cushing’s and non-Cushing’s patients according to the type of surgical approach — laparoscopic versus open surgery. These results suggest that individuals with Cushing syndrome are at a higher risk for developing VTE. “Because the incidence of VTE events in the CS group was almost threefold higher than that in the non-CS group and VTE events occurred up to 23 days after surgery in patients with CS undergoing adrenalectomy, our data support postdischarge thromboprophylaxis for 28 days in these patients,” the researchers concluded. From https://cushingsdiseasenews.com/2019/02/14/cushings-syndrome-patients-blood-clots-adrenal-surgery/
  43. 1 point
    Journal of Clinical Endocrinology and Metabolism — Lee IT, et al. | February 07, 2019 Using immunohistochemistry, researchers determined whether adipose tissue (AT) inflammation in humans is associated with chronic endogenous glucocorticoid (GC) exposure due to Cushing’s disease (CD). Abdominal subcutaneous AT samples were evaluated for macrophage infiltration and mRNA expression of pro-inflammatory cytokines in 10 patients with active CD and 10 age, gender and BMI- matched healthy subjects. The presence of AT macrophages, a hallmark of AT inflammation, increases chronic exposure to GCs due to CD. AT inflammation can, therefore, be the source of systemic inflammation in these patients, which in turn can contribute to obesity, insulin resistance and cardiovascular disease. In patients with CD, PCR showed no differences in mRNA expression of any analyzed markers. Read the full article on Journal of Clinical Endocrinology and Metabolism
  44. 1 point
    Dr. Theodore Friedman will be joined by Shira Miller, MD hosting a webinar on New and Traditional Treatments for Male Hypogonadism Spouses welcome Topics to be discussed include: How to Diagnose Male Hypogonadism? Testosterone Replacement HCG and Clomid Treatment Supplements for Male Hypogonadism Diets for Male Hypogonadism Sunday • February 10, 2019 • 6 PM PST Click here to join the meeting or https://axisconciergemeetings.webex.com/axisconciergemeetings/j.php?MTID=m4969cba4e8f0960a9053f2d03a5e56db OR Join by phone: (855) 797-9485 Slides will be available before the webinar at slides Meeting Number (Access Code): 800 925 805, Your phone/computer will be muted on entry. There will be plenty of time for questions using the chat button. Meeting Password: hormones For more information, email us at mail@goodhormonehealth.com
  45. 1 point
    Tumors located outside the pituitary gland that produce the adrenocorticotropic hormone (ACTH) may cause, on rare occasions, cyclic Cushing’s syndrome — when cortisol levels show substantial fluctuations over time. That finding, based on the case of a patient with ACTH-secreting lung cancer, is found in the study, “Cyclic Cushing’s syndrome caused by neuroendocrine tumor: a case report,” which was published in Endocrine Journal. Cushing’s syndrome is characterized by too much cortisol, either due to adrenal tumors that produce cortisol in excess, or because too much ACTH in circulation — resulting from ACTH-producing tumors — act on the adrenal glands to synthesize cortisol. Cyclic Cushing’s syndrome (CCS) is a rare type of Cushing’s in which cortisol production is not steadily increased. Instead, it cyclically fluctuates, from periods with excessive cortisol production interspersed with periods of normal levels. The fluctuations in cortisol levels over time pose difficulties for a definite diagnosis. Moreover, the precise mechanism underlying the periodic peaks of cortisol peaks are unknown. Investigators now reported the case of a 37-year-old man admitted to the hospital due to repeated attacks of dizziness, weakness, and high cortisol levels for two weeks. Repeated tests measuring the levels of cortisol in the blood and a 24-hour urine free cortisol (24 hUFC) assay confirmed a cyclic fluctuation of cortisol, with levels peaking three times and dropping twice (the standard rule for diagnosing CSC). Upon hospitalization, he further developed high blood pressure and weight gain. The patient underwent computed tomography (CT) scans, which revealed the presence of an ACTH-secreting tumor in the lungs, the likely cause of the patient’s Cushing’s symptoms. These type of tumors are called neuroendocrine tumors because they are able to release hormones into the blood in response to signals from the nervous system. Additional scans detected tumors in the adrenal and pituitary glands, but further analysis revealed they were non-functioning tumors, i.e., as their name indicates, they didn’t release excessive ACTH. The thyroid gland also was positive for a tumor. The patient underwent resection surgery to remove the tumor located in the lungs and nearby lymph nodes. After the surgery, the levels of cortisol in the blood and urine returned to normal, confirming the tumor as the source of the CSC. The patient also received surgery to remove his thyroid tumor. An analysis of the patient’s genomic DNA revealed a novel mutation in the PDE11A gene, which is linked to a rare form of ACTH-independent Cushing’s syndrome called primary pigmented nodular adrenocortical disease (PPNAD) type 2. Whether the patient developed PPNAD, however, and the contribution of a potential PPNAD diagnosis to the CCS, requires further investigation. “To explore pathogenicity of the genetic mutation, we will still plan for a follow-up visit to this patient,” researchers wrote. From https://cushingsdiseasenews.com/2019/01/24/patient-develops-cyclic-cushings-syndrome-due-to-lung-neuroendocrine-tumor/
  46. 1 point
    A simple test that measures free cortisol levels in saliva at midnight — called a midnight salivary cortisol test — showed good diagnostic performance for Cushing’s syndrome among a Chinese population, according to a recent study. The test was better than the standard urine free cortisol levels and may be an alternative for people with end-stage kidney disease, in whom measuring cortisol in urine is challenging. The study, “Midnight salivary cortisol for the diagnosis of Cushing’s syndrome in a Chinese population,” was published in Singapore Medical Journal. Cushing’s syndrome, defined by excess cortisol levels, is normally diagnosed by measuring the amount of cortisol in bodily fluids. Traditionally, urine free cortisol has been the test of choice, but this method is subject to complications ranging from improper collection to metabolic differences, and its use is limited in people with poor kidney function. Midnight salivary cortisol is a test that takes into account the normal fluctuation of cortisol levels in bodily fluids. Cortisol peaks in the morning and declines throughout the day, reaching its lowest levels at midnight. In Cushing’s patients, however, this variation ceases to exist and cortisol remains elevated throughout the day. Midnight salivary cortisol was first proposed in the 1980s as a noninvasive way to measure cortisol levels, but its efficacy and cutoff value for Cushing’s disease in the Chinese population remained unclear. Researchers examined midnight salivary cortisol, urine free cortisol, and midnight serum cortisol in Chinese patients suspected of having Cushing’s syndrome and in healthy volunteers. These measurements were then combined with imaging studies to make a diagnosis. Overall, the study included 29 patients with Cushing’s disease, and 19 patients with Cushing’s syndrome — 15 caused by an adrenal mass and four caused by an ACTH-producing tumor outside the pituitary. Also, 13 patients excluded from the suspected Cushing’s group were used as controls and 21 healthy volunteers were considered the “normal” group. The team found that the mean midnight salivary cortisol was significantly higher in the Cushing’s group compared to both control and normal subjects. Urine free cortisol and midnight serum cortisol were also significantly higher than those found in the control group, but not the normal group. The optimal cutoff value of midnight salivary cortisol for diagnosing Cushing’s was 1.7 ng/mL, which had a sensitivity of 98% — only 2% are false negatives — and a specificity of 100% — no false positives. While midnight salivary cortisol levels correlated with urine free cortisol and midnight serum cortisol — suggesting that all of them can be useful diagnostic markers for Cushing’s — the accuracy of midnight salivary cortisol was better than the other two measures. Notably, in one patient with a benign adrenal mass and impaired kidney function, urine free cortisol failed to reach the necessary threshold for a Cushing’s diagnosis, but midnight salivary and serum cortisol levels both confirmed the diagnosis, highlighting how midnight salivary cortisol could be a preferable diagnostic method over urine free cortisol. “MSC is a simple and non-invasive tool that does not require hospitalization. Our results confirmed the accuracy and reliability of [midnight salivary cortisol] as a diagnostic test for [Cushing’s syndrome] for the Chinese population,” the investigators said. The team also noted that its study is limited: the sample size was quite small, and Cushing’s patients tended to be older than controls, which may have skewed the results. Larger studies will be needed to validate these results in the future. From https://cushingsdiseasenews.com/2019/01/10/midnight-salivary-cortisol-test-helps-diagnose-cushings-chinese-study-shows/
  47. 1 point
    A man with Cushing’s disease — caused by an adrenocorticotrophic hormone (ACTH)-secreting pituitary adenoma — who later developed metastases in the central nervous system without Cushing’s recurrence, was successfully treated over eight years with radiation and chemotherapy, according to a case report. The report, “Long-term survival following transformation of an adrenocorticotropic hormone secreting pituitary macroadenoma to a silent corticotroph pituitary carcinoma: Case report,” was published in the journal World Neurosurgery. Pituitary carcinomas make up only 0.1-0.2% of all pituitary tumors and are characterized by a primary pituitary tumor that metastasizes into cranial, spinal, or systemic locations. Fewer than 200 cases have been reported in the literature. Most of these carcinomas secrete hormones, with ACTH being the most common. Though the majority of ACTH-secreting carcinomas present with Cushing’s disease, about one-third do not show symptoms of the condition and have normal serum cortisol and ACTH levels. These are called silent corticotroph adenomas and are considered more aggressive. A research team at the University of Alabama at Birmingham presented the case of a 51-year-old Caucasian man with ACTH-dependent Cushing’s disease. He had undergone an incomplete transsphenoidal (through the nose) resection of an ACTH-secreting pituitary macroadenoma – larger than 10 mm in size – and radiation therapy the year before. At referral in August 1997, the patient had persistent high cortisol levels and partial hypopituitarism, or pituitary insufficiency. He exhibited Cushing’s symptoms, including facial reddening, moon facies, weight gain above the collarbone, “buffalo hump,” and abdominal stretch marks. About two years later, the man was weaned off ketoconazole — a medication used to lower cortisol levels — and his cortisol levels had been effectively reduced. He also had no physical manifestations of Cushing’s apart from facial reddening. In May 2010, the patient reported two episodes of partial seizures, describing two spells of right arm tingling, followed by impaired peripheral vision. Imaging showed a 2.1-by-1-cm mass with an associated cyst within the brain’s right posterior temporal lobe, as well as a 1.8-by-1.2-cm mass at the cervicomedullary junction, which is the region where the brainstem continues as the spinal cord. His right temporal cystic mass was then removed by craniotomy. A histopathologic analysis was consistent with pituitary carcinoma. Cell morphology was generally similar to the primary pituitary tumor, but cell proliferation was higher. Physical exams showed no recurrence of Cushing’s disease and 24-hour free urinary cortisol was within the normal range. His cervicomedullary metastasis was treated with radiation therapy in July 2010. He took the oral chemotherapy temozolomide until August 2011, and Avastin (bevacizumab, by Genentech) was administered from September 2010 to November 2012. At present, the patient continues to undergo annual imaging and laboratory draws. He receives treatment with hydrocortisone, levothyroxine — synthetic thyroid hormone — and testosterone replacement with androgel. His most recent exam showed no progression over eight years of a small residual right temporal cyst, a residual mass along the pituitary stalk — the connection between the hypothalamus and the pituitary gland — and a small residual mass at the cervicomedullary junction. Lab results continue to show no Cushing’s recurrence. “Our case is the first to document a patient who initially presented with an endocrinologically active ACTH secreting pituitary adenoma and Cushing’s disease who later developed cranial and spinal metastases without recurrence of Cushing’s disease and transformation to a silent corticotroph pituitary carcinoma,” the scientists wrote. They added that the report is also the first documenting “8 years of progression-free survival in a patient with pituitary carcinoma treated with radiotherapy, [temozolomide] and bevacizumab.” Adapted from https://cushingsdiseasenews.com/2019/01/03/successful-treatment-pituitary-carcinoma-radiation-chemo-case-report/
  48. 1 point
    A 42-year-old woman who presented to hospital with acute vision loss in her right eye was diagnosed with a benign tumour in her adrenal gland. Writing in BMJ Case Reports, clinicians described how the patient presented with a visual acuity of 6/36 in her right eye and 6/6 in her left eye. Investigations revealed an exudative retinal detachment in her right eye as well as a pigment epithelial detachment. The patient had multifocal central serous retinopathy in both eyes. The woman, who had hypertension and diabetes, was diagnosed with Cushing syndrome and a right adrenal adenoma was also discovered. During a treatment period that spanned several years, the patient received an adrenalectomy followed by a maintenance dose of steroids. The patient subsequently developed central serous retinopathy again which the clinicians believe might be related to steroid use. The authors advised “careful deliberation” in prescribing a maintenance dose of steroids following removal of the adrenal glands because of the potential link to retinopathy. From https://www.aop.org.uk/ot/science-and-vision/research/2018/12/17/vision-loss-the-first-sign-of-adrenal-tumour-in-42-year-old-patient
  49. 1 point
    Is there any way for you to post this for all to see? The Doctor that I am seeing is Dr. Zwart. He is located in Tucson Arizona. Tucson Endocrine Associates. 5910 N La Cholla Blvd. Tucson Arizona, 85741. (520) 297-0404
  50. 1 point
    I Went to my Endo appt yesterday (prepared) I had a list of all of my symptoms and a few photos of me to show the dramatic changes that my body has gone through over a short period of time. Without my prompting, He is sure that I have Cushings. Now, to prove it. I Walked away with a long list of labs to do, including...blood, urine, and saliva. Although I already knew in my heart that this is what I had, it was still very hard to hear. I know this is not gonna be an easy road to travel and I would be lying if I said I wasn’t scared. (I’m terrified) I had a hysterectomy 4 years ago and ended up with sepsis, e-coli, c-diff, just to name a few. It nearly ended my life. I’ll keep you guys updated when I know more. Thanks to everyone that has helped me along the way and to those that will continue to do so.
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