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Found 26 results

  1. 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
  2. Patients with Cushing’s disease may develop post-traumatic stress symptoms, which are generally resolved once they undergo surgery to remove the tumor, but can persist in some cases, a study shows. The study, “Posttraumatic stress symptoms (PTSS) in patients with Cushing’s disease before and after surgery: A prospective study,” was published in the Journal of Clinical Neuroscience. Cushing’s disease is an endocrine disorder characterized by excess secretion of the adrenocorticotropic hormone (ACTH) by a pituitary adenoma (tumor of the pituitary gland). This leads to high levels of cortisol, a condition known as hypercortisolism. Chronic hypercortisolism is associated with symptoms such as central obesity, buffalo hump, body bruising, muscle weakness, high blood pressure, high blood sugar, and weak bones. Additionally, patients can develop psychiatric disorders including depression, anxiety, and cognitive dysfunction, all of which contribute considerably to a lower health-related quality of life. Depression and anxiety rates are particularly high in Cushing’s disease patients, with 54% of them experiencing major depression and 79% having anxiety. Due to the significant impact of psychological factors in these patients, they may be susceptible to post-traumatic stress symptoms (PTSS). But more information on this phenomenon in these patients is still needed. To address this lack of data, a group of Chinese researchers conducted a prospective study to investigate the occurrence, correlated factors, and prognosis of PTSS in patients with Cushing’s disease. A total of 49 patients newly diagnosed with Cushing’s disease who underwent transsphenoidal removal of the tumor as their first-line treatment were asked to participate in this study. Another group of 49 age- and sex-matched healthy individuals were included as controls. PTSS was measured using the Impact of Event Scale-Revised (IES-R), depression/anxiety were measured using the Hospital Anxiety and Depression scale (HADS), and quality of life was measured using the 36-item short-form (SF-36). These parameters were measured before surgery, and then at six and 12 months after the procedure. Before surgery, 15 patients (30.6%) had PTSS. These patients also had higher cortisol levels, worse levels of depression/anxiety, and worse quality of life scores than those without PTSS. While most of the patients recovered after the operation, there were five (33.3%) for whom PTSS persisted for more than a year. Additionally, one patient who had a recurrence of Cushing’s disease developed PTSS between six and 12 months after the first surgery. PTSS severity showed consistent improvement after surgery, which was correlated with better depression/anxiety scores and psychological aspects of the SF-36. However, Cushing’s disease patients in remission still performed worse than healthy individuals concerning their physical and mental health. Therefore, “patients with [Cushing’s disease] can develop PTSS, and they may persist for over a year even after successful surgery. Combined psychological intervention is advised for these patients,” the researchers concluded. From https://cushingsdiseasenews.com/2019/06/25/cushings-patients-often-have-post-traumatic-stress-symptoms
  3. 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
  4. 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/
  5. 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.
  6. TOKYO and LONDON, Feb. 20, 2019 /PRNewswire/ -- Sosei Group Corporation ("the Company"; TSE: 4565), announces that the first healthy subject has been dosed with a novel small molecule HTL0030310 in a Phase I clinical study, marking the start of a new in-house clinical program targeting endocrine disorders, including Cushing's disease. HTL0030310 is a potent and selective agonist of the SSTR5 (somatostatin 5) receptor and the sixth molecule designed by the Company using its GPCR Structure-Based Drug Design (SBDD) platform to enter clinical development. HTL0030310 has been designed to modulate the excess release of hormones from adenomas (benign tumors) of the pituitary gland. Highly elevated plasma levels of pituitary hormones result in a number of serious endocrine disorders, including Cushing's Disease. Cushing's disease is characterized by excessive cortisol release, crucial in regulating metabolism, maintaining cardiovascular function and helping the body respond to stress. A key design feature of HTL0030310 is its significant selectivity for SSTR5 over SSTR2. This selectivity is expected to improve the balance of efficacy vs. dose-limiting side effects and therefore, presents an opportunity to develop a best-in-class medicine for patients with Cushing's disease, in particular. The clinical trial with HTL0030310 is a double-blind, randomised, placebo-controlled first-in-human study in which single ascending subcutaneous doses of HTL0030310 will be administered to healthy male and female adult subjects. The study is being conducted in the UK and will assess the safety, tolerability, pharmacokinetics and pharmacodynamics of HTL0030310 in up to 64 subjects. Preliminary results are expected in the second half of 2019 and will provide a first insight into the effects of HTL0030310 on the control of glucose and other endocrine hormones and the potential to target Cushing's disease and other endocrine disorders. Dr. Malcolm Weir, Executive VP and Chief R&D Officer, said: "HTL0030310 is a novel and highly selective molecule, and is the sixth candidate originating from our SBDD platform to advance into human trials. We are not only pleased to begin this new study but also delighted with the productivity of our unique platform to generate attractive candidates targeting GPCRs involved in multiple diseases. These candidates present new prospects for our emerging proprietary pipeline, as well as unique opportunities for partnering, and provide a solid foundation to execute our strategy." About Cushing's disease Cushing's disease is a debilitating endocrine disorder caused by the overproduction of the hormone cortisol and is often triggered by a pituitary adenoma (benign tumour) secreting excess adrenocorticotropic hormone (ACTH). Cortisol has a crucial role regulating metabolism, maintaining cardiovascular function and helping the body respond to stress. Symptoms may include weight gain, central obesity, a round, red full face, severe fatigue and weakness, striae (purple stretch marks), high blood pressure, depression and anxiety. Cushing's disease affects 10-15 million people per year, most commonly adults between 20 to 50 years and women more often than men. The first line and most common treatment approach for Cushing's disease is surgical removal of the pituitary tumor followed by radiotherapy and drug therapy designed to reduce cortisol production. Ref: American Association of Neurological Surgeons (AANS) About Sosei Heptares We are an international biopharmaceutical group focused on the design and development of new medicines originating from its proprietary GPCR-targeted StaR® technology and structure-based drug design platform capabilities. The Company is advancing a broad and deep pipeline of partnered and wholly owned product candidates in multiple therapeutic areas, including CNS, immuno-oncology, gastroenterology, inflammation and other rare/specialty indications. Its leading clinical programs include partnered candidates aimed at the symptomatic treatment of Alzheimer's disease (with Allergan) and next generation immuno-oncology approaches to treat cancer (with AstraZeneca). Our additional partners and collaborators include Novartis, Pfizer, Daiichi-Sankyo, PeptiDream, Kymab and MorphoSys. The Company is headquartered in Tokyo, Japan with R&D facilities in Cambridge, UK and Zurich, Switzerland. "Sosei Heptares" is the corporate brand of Sosei Group Corporation, which is listed on the Tokyo Stock Exchange (ticker: 4565). For more information, please visit https://www.soseiheptares.com/ LinkedIn: @soseiheptaresco | Twitter: @soseiheptaresco | YouTube: @soseiheptaresco Forward-looking statements This press release contains forward-looking statements, including statements about the discovery, development and commercialization of products. Various risks may cause Sosei Group Corporation's actual results to differ materially from those expressed or implied by the forward-looking statements, including: adverse results in clinical development programs; failure to obtain patent protection for inventions; commercial limitations imposed by patents owned or controlled by third parties; dependence upon strategic alliance partners to develop and commercialize products and services; difficulties or delays in obtaining regulatory approvals to market products and services resulting from development efforts; the requirement for substantial funding to conduct research and development and to expand commercialization activities; and product initiatives by competitors. As a result of these factors, prospective investors are cautioned not to rely on any forward-looking statements. We disclaim any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. View original content:https://www.prnewswire.com/news-releases/sosei-heptares-starts-new-clinical-development-program-300798591.html SOURCE Sosei Heptares
  7. 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
  8. 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/
  9. Pituitary Tumors Affect Patients’ Ability to Work, Reduce Quality of Life Pituitary tumor conditions, such as Cushing’s disease, have a substantial effect on patients’ work capabilities and health-related quality of life, researchers from The Netherlands reported. The study, “Work disability and its determinants in patients with pituitary tumor-related disease,” was published in the journal Pituitary. Pituitary tumors, like those that cause Cushing’s disease, have significant effects on a patient’s physical, mental, and social health, all of which influence their work status and health-related quality of life. However, the effects of the disease on work status is relatively under-investigated, investigators report. Here, researchers evaluated the work disability among patients who were treated for pituitary tumors in an attempt to understand the impact of disease diagnosis and treatment on their social participation and ability to maintain a paying job. In their study, researchers examined 241 patients (61% women) with a median age of 53 years. The majority (27%) had non-functioning pituitary tumors, which do not produce excess hormones, but patients with acromegaly, Cushing’s disease, prolactinomas, and Rathke’s cleft cyst also were included. Participants were asked to complete questionnaires to evaluate their health-related quality of life and disease-specific impact on their work capabilities. Each participant completed a set of five questionnaires. Participants also reported their hormonal status and demographic data, including gender, age, education, and marital status. Specific information, such as disease diagnosis, treatment, and tumor type was obtained from their medical records. Work status and productivity were assessed using two surveys, the Short-Form-Health and Labour Questionnaire (SF-HLQ) and the work role functioning questionnaire 2.0 (WRFQ). SF-HLQ was used to obtain information on the participants’ employment and their work attendance. Employment was either paid or unpaid. (Participation in household chores was considered not having a paid job.) WRFQ is a 27-question survey that determines work disability regarding being able to meet the productivity, physical, emotional, social, and flexible demands. A higher score indicates low self-perceived work disability. Disease-specific mood problems, social and sexual functioning issues, negative perceptions due to illness, physical and cognitive difficulties, were assessed using a 26-item survey called Leiden Bother and Needs for Support Questionnaire for pituitary patients(LBNQ-Pituitary). Overall, 28% of patients did not have a paid job, but the rates increased to 47% among those with Cushing’s disease. Low education, hormonal deficits, and being single were identified as the most common determinants of not having a paid job among this population. Further analysis revealed that more patients with Cushing’s disease and acromegaly had undergone radiotherapy. They also had more hormonal deficits than others with different tumor types. Overall, patients with a paid job reported working a median of 36 hours in one week and 41% of those patients missed work an average of 27 days during the previous year. Health-related problems during work also were reported by 39% with a paid job. Finally, health-related quality of life was determined using two questionnaires: SF-36 and EQ-5D. The physical, mental, and emotional well being was measured with SF-36, while ED-5D measured the health outcome based on the impact of pain, mobility, self-care, usual activities, discomfort, and anxiety or depression. In both SF-36 and EQ-5D, a higher score indicates a better health status. Statistical analysis revealed that the quality of life was significantly higher in patients with a job. Overall, patients with a paid job reported better health status and higher quality of life than those without a paid job. Although 40% of the patients reported being bothered by health-related problems in the past year, only 12% sought the help of an occupational physician, the researchers reported. “Work disability among patients with a pituitary tumor is substantial,” investigators said. “The determinants and difficulties at work found in this study could potentially be used for further research, and we advise healthcare professionals to take these results into consideration in the clinical guidance of patients,” they concluded. From https://cushingsdiseasenews.com/
  10. Cushing’s disease patients whose pituitary tumors carry a USP8 mutation are more likely to achieve remission after surgery than those without such mutations, a retrospective Italian study found. The study, “Clinical characteristics and surgical outcome in USP8-mutated human adrenocorticotropic hormone-secreting pituitary adenomas,” was published in the journal Endocrine. Cushing’s disease is a condition where a tumor on the pituitary gland produces too much of the adrenocorticotropin hormone (ACTH), which will act on the adrenal gland to make cortisol in excess. While rare, the condition can be life-threatening, as excess cortisol is linked to an increased risk of infections and cardiovascular complications, along with an increased likelihood of obesity and diabetes. The reasons some patients develop these pituitary adenomas are far from understood, but researchers recently found that some of these patients show mutations in the USP8 gene. These appear to increase EGFR signaling which, in turn, has a stimulatory role for the synthesis of ACTH. But more than influencing the development of Cushing’s disease, researchers believe the USP8 mutations may also determine response to treatment. Thus, a team in Italy examined whether patients with USP8 mutations presented different clinical features and responded differently to the standard surgical procedure, called transsphenoidal pituitary surgery. The study included 92 patients with ACTH-secreting pituitary tumors who received surgery at the neurosurgical department of the Istituto Scientifico San Raffaele in Milan between 1996 and 2016. “All surgical procedures were performed by the same experienced neurosurgeon, which is one of the most important factors affecting early and late surgical outcome of pituitary adenomas,” researchers explained. Among study participants, 22 (23.9%) had mutations in the USP8 gene, but these mutations were significantly more common in women than in men — 28.7% vs. 5.3%. Researchers think estrogens — a female sex hormone — may have a role in the development of mutated pituitary tumors. Overall, the two groups had similar tumor size and aggressiveness and similar ACTH and cortisol levels before surgery. But among those with microadenomas — tumors smaller then 10 mm in diameter — USP8-mutated patients had significantly larger tumor diameters. After receiving surgery, 81.5% of patients achieved surgical remission — deemed as low cortisol levels requiring glucocorticoid replacement therapy, normal cortisol levels in urine, and normal response to a dexamethasone-suppression test. But remission rates were significantly higher among those with USP8 mutations — 100% vs. 75.7%. Also, USP8 mutation carriers required steroid replacement therapy for shorter periods, despite ACTH and cortisol levels being similar among the two groups after surgery. Among patients who entered remission, 12 (16%) saw their disease return. While more patients with USP8 mutations experienced a recurrence — 22.7% vs. 13.2% — this difference was not significant. After five years, 73.8% of UPS8-mutated patients remained alive and recurrence-free, which researchers consider comparable to the 88.5% seen in patients without the mutation. Researchers also tested sex, age at surgery, and post-surgical ACTH and cortisol levels as possible predictors of disease recurrence, but none of these factors was associated with this outcome. “ACTH-secreting pituitary adenomas carrying somatic USP8 mutations are associated with a greater likelihood of surgical remission in patients operated on by a single neurosurgeon. Recurrence rates are not related with USP8-variant status,” researchers concluded. From https://cushingsdiseasenews.com/2018/10/23/cushings-disease-patients-usp8-mutations-more-likely-achieve-remission-after-surgery/
  11. A plasma adrenocorticotropic hormone suppression test performed shortly after surgical adenomectomy may accurately predict both short- and long-term remission of Cushing’s disease, according to research published in Pituitary. “Cushing’s disease is caused by hypersecretion of adrenocorticotropic hormone (ACTH) by a pituitary adenoma, resulting in hypercortisolism,” Erik Uvelius, MD, of the department of clinical sciences, Skåne University Hospital, Lund University, Sweden, and colleagues wrote in the study background. “Surgical adenomectomy is the first line of treatment. Postoperative remission is reported in 43% to 95% of cases depending on factors such as adenoma size, finding of pituitary adenoma on preoperative MRI and surgeons’ experience. However, there is no consensus on what laboratory assays and biochemical thresholds should be used in determining or predicting remission over time.” In the study, the researchers retrospectively gathered data from medical records of 28 patients who presented with Cushing’s disease to Skåne University Hospital between November 1998 and December 2011, undergoing 45 transsphenoidal adenomectomies. On postoperative days 2 and 3, oral betamethasone was administered (1 mg at 8 a.m., 0.5 mg at 2 p.m., and 0.5 mg at 8 p.m.). Researchers assessed plasma cortisol and plasma ACTH before betamethasone administration and again at 24 and 48 hours, and measured 24-urinary free cortisol on postoperative day 3. At 3 months postoperatively and then annually, plasma concentrations of morning cortisol and ACTH along with urinary-free cortisol and/or a low-dose dexamethasone suppression test were evaluated at the endocrinologists’ discretion. The researchers defined remission as lessening of clinical signs and symptoms of hypercortisolism, as well as laboratory confirmation through the various tests. The researchers used Youden’s index to establish the cutoff with the highest sensitivity and specificity in predicting remission over the short term (3 months) and long term (5 years or more). Clinical accuracy of the different tests was illustrated through the area under curve. The study population consisted of mainly women (71%), with a median age of 49.5 years. No significant disparities were seen in age, sex or surgical technique between patients who underwent a primary procedure and those who underwent reoperation. Two of the patients were diagnosed with pituitary carcinoma and 11 had a macroadenoma. ACTH positivity was identified in all adenomas and pathologists confirmed two cases of ACTH-producing carcinomas. Of the 28 patients, 12 (43%) demonstrated long-term remission at last follow-up. Three patients were not deemed in remission after primary surgery but were not considered eligible for additional surgical intervention, whereas 13 patients underwent 17 reoperations to address remaining disease or recurrence. Four patients demonstrated long-term remission after a second or third procedure, equaling 16 patients (57%) achieving long-term remission, according to the researchers. The researchers found that both short- and long-term remission were most effectively predicted through plasma cortisol after 24 and 48 hours with betamethasone. A short-term remission cutoff of 107 nmol/L was predicted with a sensitivity of 0.85, specificity of 0.94 and a positive predictive value of 0.96 and AUC of 0.92 (95% CI, 0.85-1). A long-term remission cutoff of 49 nmol/L was predicted with a sensitivity of 0.94, specificity of 0.93, positive predictive value of 0.88 and AUC of 0.98 (95% CI, 0.95-1). This cutoff was close to the suppression cutoff for the diagnosis of Cushing’s disease, 50 nmol/L. The cutoff of 25 nmol/L showed that the use of such a strict suppression cutoff would cause a low level of true positives and a higher occurrence of false negatives, according to the researchers. “A 48 h 2 mg/day betamethasone suppression test day 2 and 3 after transsphenoidal surgery of Cushing’s disease could safely predict short- and long-term remission with high accuracy,” the researchers wrote. “Plasma cortisol after 24 hours of suppression showed the best accuracy in predicting 5 years’ remission. Until consensus on remission criteria, it is still the endocrinologists’ combined assessment that defines remission.” – by Jennifer Byrne Disclosures: The authors report no relevant financial disclosures. From https://www.healio.com/endocrinology/neuroendocrinology/news/in-the-journals/%7B0fdfb7b0-e418-4b53-b59d-1ffa3f7b8cd3%7D/acth-test-after-adenomectomy-may-accurately-predict-cushings-disease-remission
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    Presented by Eliza Geer, MD Medical director, Multidisciplinary Pituitary & Skull Base Tumor Center Associate Attending, Endocrine Service Memorial Sloan 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: Wednesday, July 18, 2018 Time: 10:00 AM - 11:00 AM Pacific Daylight Time 1:00 PM - 2:00 PM Eastern Daylight Time Webinar Description: Learning Objectives: Review Cushing’s disease treatment guidelines Evaluate currently available medical therapies for Cushing’s disease Discuss new therapies in clinical trials Presenter Bio: Dr. Geer is an endocrinologist who specializes in caring for people with pituitary and neuroendocrine diseases. She is the Medical Director of Memorial Sloan Kettering’s Multidisciplinary Pituitary & Skull Base Tumor Center, located at Memorial Hospital in Manhattan. Their multidisciplinary pituitary team provides personalized surgical and medical treatment for people with pituitary and skull base tumors, including prolactinomas, growth-hormone secreting adenomas (acromegaly), and Cushing’s disease. Their overall goal is to improve and advance the care of people with these conditions. Dr. Geer’s research interests focus on achieving a better understanding of how and why pituitary tumors develop, and characterizing long-term outcomes in patients with Cushing’s disease. She has conducted a number of studies investigating body composition, adipose tissue regulation, and appetite in patients with Cushing’s disease, and she is involved in clinical trials investigating new medical therapies for patients with Cushing’s and acromegaly. Dr. Geer completed her internship and residency at the NewYork-Presbyterian Hospital/Columbia Medical Center. She was a fellow in endocrinology and metabolism at the Icahn School of Medicine/Mount Sinai Medical Center, after which she was a member of the faculty for ten years. She is currently an associate professor of medicine and an active member of the Endocrine Society, the Pituitary Society, the Pituitary Network Association and the American Association of Clinical Endocrinologists.
  13. Presented by Eliza Geer, MD Medical director, Multidisciplinary Pituitary & Skull Base Tumor Center Associate Attending, Endocrine Service Memorial Sloan 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: Wednesday, July 18, 2018 Time: 10:00 AM - 11:00 AM Pacific Daylight Time 1:00 PM - 2:00 PM Eastern Daylight Time Webinar Description: Learning Objectives: Review Cushing’s disease treatment guidelines Evaluate currently available medical therapies for Cushing’s disease Discuss new therapies in clinical trials Presenter Bio: Dr. Geer is an endocrinologist who specializes in caring for people with pituitary and neuroendocrine diseases. She is the Medical Director of Memorial Sloan Kettering’s Multidisciplinary Pituitary & Skull Base Tumor Center, located at Memorial Hospital in Manhattan. Their multidisciplinary pituitary team provides personalized surgical and medical treatment for people with pituitary and skull base tumors, including prolactinomas, growth-hormone secreting adenomas (acromegaly), and Cushing’s disease. Their overall goal is to improve and advance the care of people with these conditions. Dr. Geer’s research interests focus on achieving a better understanding of how and why pituitary tumors develop, and characterizing long-term outcomes in patients with Cushing’s disease. She has conducted a number of studies investigating body composition, adipose tissue regulation, and appetite in patients with Cushing’s disease, and she is involved in clinical trials investigating new medical therapies for patients with Cushing’s and acromegaly. Dr. Geer completed her internship and residency at the NewYork-Presbyterian Hospital/Columbia Medical Center. She was a fellow in endocrinology and metabolism at the Icahn School of Medicine/Mount Sinai Medical Center, after which she was a member of the faculty for ten years. She is currently an associate professor of medicine and an active member of the Endocrine Society, the Pituitary Society, the Pituitary Network Association and the American Association of Clinical Endocrinologists.
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    In Memory ~ Sarah Fraik

    Sarah had recently had surgery to remove a tumor from her pituitary gland in the hopes of treating her Cushing’s Disease. She died on June 13, 2011 after a brief illness at the age of 28. Read more at https://cushingsbios.com/2013/09/14/sarah-fraik/
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    Presented By: Russell Lonser, MD, FAANS Professor and Chair Department of Neurological Surgery Ohio State University Wexner Medical 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: April 10, 2018 Time: 10:00 AM-11:00 AM Pacific Daylight Time, 1:00 PM - 2:00 PM Eastern Daylight Time Learning Objectives: To define clinical features of Cushing’s disease. To describe management paradigms for Cushing’s disease. To understand the evaluation of Cushing’s disease patients. Presenter Bio: Russell R. Lonser graduated with a B.A. in economics from Andrews University in 1990 and received his M.D. from Loma Linda University in 1994. He completed his neurosurgical training at the University of Utah in 2001. During his residency, he performed a 2-year research fellowship under the mentorship of Edward H. Oldfield, M.D., in the Surgical Neurology Branch at the National Institutes of Health (NIH). Upon completion of his residency, he joined the staff of the Surgical Neurology Branch at the NIH. He was Chief of the Surgical Neurology Branch at NIH before becoming Professor and Chair of the Department of Neurological Surgery at Ohio State University in 2012. He holds the Dardinger Family Chair in Neurosurgical Oncology. Dr. Lonser’s research interests include development of drug delivery paradigms for the central nervous system pathology, as well as investigation of tumor pathogenesis and biology. Specifically, his scientific efforts are directed toward studying convective delivery and neoplasia pathogenesis/propagation in familial tumor suppressor syndromes, including von Hippel-Lindau disease. His clinical and surgical interests are centered on the treatment of brain, temporal bone and spinal cord tumors. He is an author on over 300 scientific and clinical publications. He received the Tumor Young Investigator Award from the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Tumors in 2001 and Mahaley Clinical Research Award from the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Tumors in 2013. He was the 2017 American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Tumors Bittner Lecturer. He is a co-inventor on a patent for methods for convection-enhanced delivery of therapeutic agents. His contributions to organized neurosurgery include membership on the Executive Committee of the Congress of Neurological Surgeons. He was the Treasurer of the Congress of Neurological Surgeons and is President of the Congress of Neurological Surgeons. He also served on the Executive Committee for the American Association of Neurological Surgeons/Congress of Neurological Surgeons Section on Tumors. He has served on a number national committees for organizations involved in neurosurgical research. He is head of the Research Subcommittee in Head, Neck and Spine Injury Committee for the National Football League. He has been actively involved in the mentoring and training of over 40 neurosurgical fellows. He is on the Editorial Boards for NEUROSURGERY, World Neurosurgery and Journal of Neurosurgery. He is an Academic Editor for PLoS One and Science Reports. He is Consulting Editor for Neurosurgery Clinics of North America. Dr. Lonser is married to Carolyn. They have 3 daughters, Hannah (born 2001), Sarah (2004) and Alicia (2007).
  16. The ratio between adrenocorticotropic hormone levels and cortisol levels in the blood is higher among Cushing’s disease patients than in healthy people, a new study has found, suggesting that measurement could be used to help diagnose the disease. Also, higher values at diagnosis could predict if the disease will recur and indicate larger and more invasive tumors. The research, “The Utility of Preoperative ACTH/Cortisol Ratio for the Diagnosis and Prognosis of Cushing’s Disease,” was published in the Journal of Neurosciences in Rural Practice. Cushing’s syndrome (CS) is characterized by excess levels of cortisol. In patients with suspected CS, clinicians recommend testing late-night salivary or plasma (blood) cortisol, 24-hour urine-free cortisol (UC), as well as morning cortisol levels after low-dose suppression with dexamethasone, a corticosteroid. CS may be ACTH-dependent or ACTH-independent, meaning that the high cortisol levels are caused by excess ACTH production. Patients with CD have elevated levels of ACTH. A tumor, usually an adenoma, causes the pituitary gland to produce excess levels of ACTH, which stimulate the release of cortisol from the adrenal glands. Cortisol usually inhibits ACTH production. However, in CD patients, this feedback mechanism is absent. Despite extensive research and clinical data, the variable and usually nonspecific signs and symptoms of CD still represent relevant challenges for diagnosis. Clinical manifestations must be associated with biochemical tests, which often have led to conflicting results. Studies showed that although ACTH levels correlate with the size of the pituitary adenoma, the levels of cortisol do not increase as much. In fact, lower cortisol/ACTH ratios have been reported in patients with macroadenoma – which is greater than 10 millimeters in size – than in those with microadenoma, which is smaller than 10 millimeters. Conversely, the research team hypothesized that besides their utility for determining the cause of CS, the inverse ratio – ACTH/cortisol – also may be useful for diagnosis. The team evaluated the pretreatment plasma ACTH/cortisol levels in CS patients with excess cortisol production due to abnormal pituitary or adrenal function. Data from patients were compared with that of individuals without CS. The study included 145 CS patients diagnosed from 2007 to 2016, 119 patients with CD, 26 with ACTH-independent CS (AICS), and 114 controls with no CS. Patients’ clinical, laboratory, imaging, postsurgical and follow-up data were analyzed. Results showed that patients with CD had a significantly higher basal ACTH/cortisol ratio than controls or those with AICS. “These results showed ACTH/cortisol ratio might be a simple and useful test for the diagnosis of ACTH-dependent CS,” the researchers wrote. Importantly, the scientists observed that a ACTH/cortisol ratio above 2.5 indicated identified 82 percent of positive CS cases and 63 percent of controls. Overall, “an ACTH/cortisol ratio [greater than] 2.5 would be beneficial to diagnose CD together with other diagnostic tests,” they concluded. Patients with recurrent CD showed higher pretreatment ACTH levels and ACTH/cortisol ratio than those who achieved sustained remission. CD patients also exhibited more invasive, atypical and larger tumors, as well as lower postoperative remission and higher recurrence rates. “Higher ACTH/cortisol ratio might predict poorer prognosis,” the investigators said. From https://cushingsdiseasenews.com/2018/03/16/acth-cortisol-ratio-reliable-test-diagnose-cushings-disease/
  17. Erica was a fellow Cushing’s Disease survivor. She had been through pituitary surgery, radiation, and a BLA in an effort to receive her cure. Read more at https://cushingsbios.com/2015/03/11/in-memory-erica-michelle-gaga-meno/
  18. The chemotherapy temozolomide partially improved a case of an aggressive pituitary tumor that caused symptoms of Cushing’s disease (CD), according to a new study in Poland. However, after tumor mass and cortisol levels were stabilized for a few months, the patient experienced rapid progression, suggesting that new methods for extending the effects of temozolomide are needed. The study, “Temozolomide therapy for aggressive pituitary Crooke’s cells corticotropinoma causing Cushing’s Disease: A case report with literature review,” appeared in the journal Endokrynologia Polska. Aggressive pituitary tumors are usually invasive macroadenomas, or benign tumors larger than 10 mm. A very rare subset of pituitary adenoma — particularly corticotropinoma, or tumors with excessive secretion of corticotropin (ACTH) — exhibit Crooke’s cells. These tumors are highly invasive, have a high recurrence rate, and are often resistant to treatment. Information is not widely available about the effectiveness of treating aggressive pituitary tumors, particularly those that cause Cushing’s disease. The management of these tumors usually requires neurosurgery, followed by radiotherapy, and pharmacotherapy. However, the chemotherapy medication temozolomide has been increasingly used as a first-line treatment after initial evidence of its effectiveness in treating glioblastoma, the most common form of brain cancer. In this study, researchers at the Jagiellonian University, in Poland, discussed the case of a 61-year-old man with ACTH-dependent Cushing’s syndrome caused by Crooke’s cell corticotropinoma. The patient first presented with symptoms of severe hypercorticoidism — the excessive secretion of steroid hormones from the adrenal cortex — in December 2011. He also showed advanced heart failure, severe headaches, and impaired vision, which had started two or three years before diagnosis. Examinations revealed osteoporosis and a fracture in the Th5 vertebra. His morning ACTH levels were high. The same was observed for mean cortisol levels even after dexamethasone treatment, which was suggestive of a pituitary tumor secreting ACTH. MRIs showed the existence of a tumor mass, later identified as a macroadenoma with high cell polymorphism, the presence of Crooke’s cells, and ACTH secretion. The patient was referred for transsphenoidal nonradical neurosurgery, performed through the nose and the sphenoid sinus, and bilateral adrenalectomy, or the surgical removal of the adrenal glands, in 2012-2013. However, he developed fast, postoperative recurrence of hypercorticoidism and tumor regrowth. This led to three additional transsphenoidal neurosurgeries and radiotherapy. The patient’s clinical status worsened as he developed severe cardiac insufficiency. Doctors began temozolomide treatment in April 2015, which did not result in adverse effects throughout treatment. The initial standard dose (150–200 mg/m2) was given once daily in the morning for five consecutive days, in a 28-day cycle. The patient also received 600 mg of ketoconazole, an antifungal medication. Ondansetron was administered to prevent nausea and vomiting. Subsequent examinations revealed clinical and biochemical improvements, including a reduction in ACTH and cortisol levels. In addition, the patient also showed reduced cardiac insufficiency, less frequent and less severe headaches, visual field improvements, and better physical fitness and mood. However, clinical symptoms worsened after the eighth temozolomide cycle. The tumor size also suddenly increased after the ninth cycle, reaching the inner ear. Temozolomide was then discontinued and ACTH levels increased by 28 percent one month later. The patient also demonstrated deteriorated vision, hearing loss, and strong headaches. Clinicians then decided to start treatment with the Cushing’s disease therapy Signifor (pasireotide), but a worsening of diabetes was observed, and the patient died in February 2016. “The most probable reason for death was compression of the brainstem, which had been observed in the last MRI of the pituitary,” the researchers wrote, adding that “due to the very short duration of treatment, any conclusions on the treatment with Signifor cannot be drawn.” Overall, “the results of the presented case suggest that [temozolomide] treatment monotherapy could have only partial response in aggressive corticotroph adenoma causing Cushing’s disease, followed by sudden progression,” the investigators wrote. This contrasts with mostly responsive cases reported in research literature, they noted. “Therefore, further research on the factors of responsiveness and on novel methods to extend the duration of the effect of [temozolomide] should be carried out,” they wrote. From https://cushieblog.com/2018/02/10/temozolomide-may-partially-improve-aggressive-pituitary-tumors-causing-cushings-disease/
  19. Abstract Objective Cushing's disease (CD) is a rare endocrine disorder characterized by excess secretion of ACTH due to a pituitary adenoma. Current treatment options are limited and may pose additional risks. A literature review was conducted to assess the holistic burden of CD. Design Studies published in English were evaluated to address questions regarding the epidemiology of CD, time to diagnosis, health-related quality of life (HRQoL), treatment outcomes, mortality, prevalence of comorbidities at diagnosis, and reversibility of comorbidities following the treatment. Methods A two-stage literature search was performed in Medline, EMBASE, and Science Citation Index, using keywords related to the epidemiology, treatment, and outcomes of CD: i) articles published from 2000 to 2012 were identified and ii) an additional hand search (all years) was conducted on the basis of bibliography of identified articles. Results At the time of diagnosis, 58–85% of patients have hypertension, 32–41% are obese, 20–47% have diabetes mellitus, 50–81% have major depression, 31–50% have osteoporosis, and 38–71% have dyslipidemia. Remission rates following transsphenoidal surgery (TSS) are high when performed by expert pituitary surgeons (rates of 65–90%), but the potential for relapse remains (rates of 5–36%). Although some complications can be partially reversed, time to reversal can take years. The HRQoL of patients with CD also remains severely compromised after remission. Conclusions These findings highlight the significant burden associated with CD. As current treatment options may not fully reverse the burden of chronic hypercortisolism, there is a need for both improved diagnostic tools to reduce the time to diagnosis and effective therapy, particularly a targeted medical therapy. Introduction Cushing's disease (CD) is a rare condition caused by a pituitary adenoma that secretes excess ACTH (1), which promotes excess cortisol production from the adrenal glands. Excess cortisol induces a clinical phenotype that harbors all components of the metabolic syndrome, such as central obesity, diabetes mellitus, dyslipidemia, and hypertension, as well as muscle weakness, hirsutism, increased bruisability, psychological dysfunction, and osteoporosis (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11). Patients with CD experience a significant clinical burden due to comorbidities, increased mortality, and impaired health-related quality of life (HRQoL) due to prolonged exposure to elevated cortisol levels (3, 5, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20). In particular, patients with CD often experience severe fatigue and weakness, physical changes, emotional instability, depression, and cognitive impairments, which have a profound impact on daily life (13, 21). Although there have been several consensus statements published recently on the definition of remission, diagnosis, and the management of CD, the severity and diversity of the clinical scenario and associated morbidities continue to present a management challenge (1, 22, 23). Additionally, there is recent evidence of persistent deleterious effects after remission, most notably persistent elevated cardiovascular risk (3, 22). The main objective of the current literature review is to describe the current burden of the disease and to summarize data on specific aspects of this burden, which underscores the need for improved diagnostic and therapeutic approaches. Materials and methods Available literature were evaluated to address questions regarding the epidemiology of CD, time to diagnosis, mortality, prevalence of comorbidities at diagnosis, reversibility of comorbidities after treatment (in particular, after disease remission), outcomes and complications of current treatment options, and HRQoL associated with CD and interventions. The literature search was performed in Medline, EMBASE, and Science Citation Index, using keywords related to the epidemiology, treatment, and outcomes of CD. It was conducted in two stages: i) articles published between 2000 and 2012 were identified through a PubMed search using the following keywords: CD, incidence, prevalence, mortality, treatment, remission, cure, excess cortisol, outcomes, cost, QoL, morbidities, transsphenoidal surgery (TSS), adrenalectomy, radiotherapy, steroidogenesis inhibitors, ketoconazole, mitotane, aminoglutethimide, etomidate, metyrapone, pasireotide, and cortisol receptor antagonists; and ii) an additional hand search was conducted on the basis of the bibliographies of identified articles. All studies that provided data (regardless of publication year) related to these research questions were retained. Definitions Different criteria for defining the remission of hypercortisolism have been proposed, ranging from the occurrence of definitive or transient postoperative hypocortisolemia to the adequate suppression of cortisol after dexamethasone administration. According to a recent consensus statement (23), persistent postoperative morning serum cortisol levels of <2 μg/dl (∼50 nmol/l) are associated with remission and a low recurrence rate of ∼10% at 10 years. Persistent serum cortisol levels above 5 μg/dl (∼140 nmol/l) for up to 6 weeks following surgery require further evaluation. When serum cortisol levels are between 2 and 5 μg/dl, the patient can be considered in remission and can be observed without additional treatment for CD. A subset of patients can even develop complete adrenal insufficiency (serum cortisol levels below 2 μg/dl (∼50 nmol/l)) up to 12 weeks postsurgery (24, 25). Therefore, repeated evaluation in the early postoperative period is recommended. However, long-term follow-up is necessary for all patients because no single cortisol cutoff value excludes those who later experience disease recurrence, and up to 25% of patients develop a recurrent adenoma within 10 years after surgery (26, 27, 28). Results Incidence and prevalence of CD Although epidemiologic data on CD are limited, several population-based studies indicate an incidence of 1.2–2.4 per million (14, 19) and the prevalence of diagnosed cases to be ∼39 per million population (14). Lindholm et al. (19) used the case definition as either the presence of a corticotroph adenoma or remission after neurosurgery, which yielded an estimated incidence rate of 1.2–1.7 per million per year. Etxabe & Vazquez (14) reported an incidence of 2.4 per million in Vizcaya, Spain. A large-scale retrospective survey carried out in New Zealand by Bolland et al. (29) found the approximate prevalence of all forms of Cushing's syndrome (CS) (the majority of these cases were of pituitary origin) to be 79 per million and the incidence to be 1.8 per million per year. Differences in epidemiologic estimates may be attributable to varying case definitions (for instance, the study by Lindholm excluded cases in which the adenoma could not be localized or those that could not achieve remission from surgery), geographical differences, and temporal effects. The prevalence of CD may be underestimated due to unrecognized patients with mild symptoms and patients with a cyclic form of CD (30). Time to diagnosis Data on the time from onset of symptoms to diagnosis are also limited. In a prospective study by Flitsch et al. (31) of 48 patients with pituitary adenomas, including 19 who had ACTH-secreting adenomas causing CD, the reported time from onset of symptoms to diagnosis was 4.3 years. A study by Martinez Ruiz et al. (32), which was based on only four pediatric CD patients, reported the time between onset of symptoms and diagnosis as ranging from 2.5 to 5 years. Etxabe & Vazquez (14) estimated that the average time from onset of clinical symptoms to diagnosis in 49 CD patients was 45.8±2.7 months (6–144 months), thus 3.8 years. This is corroborated by the findings from a Belgian cross-sectional study on pituitary adenomas including CD, which estimated that patients experienced symptoms for an average of 45 months before diagnosis (33). However, the reliability and generalizability of these data are limited by small sample sizes and the retrospective nature of the studies. Indeed, the New Zealand data from Bolland et al. (29) report that on presentation, patients experienced symptoms for a median of 2.0 years (but ranging up to 20 years) before diagnosis. On the basis of data from the prospective European Registry on Cushing's syndrome (ERCUSYN) (total number of patients=481, of whom 66% of patients had CD), median delay in diagnosis was 2 years (34). Mortality in patients with CD Mortality in patients with CD has been analyzed in several small studies, with overall rates reported as standardized mortality ratio (SMR) ranging from 1.7 to 4.8 (Table 1) (14, 15, 17, 19). In studies in which mortality was assessed among those in remission and those with persistent disease separately, patients with persistent hypercortisolemia consistently had the highest mortality risk (15, 19, 35, 36). In addition, TSS as a first-line treatment has been an important advance as high remission rates after initial surgery have been accompanied by mortality rates that mirror those observed in the general population (17, 35, 37). In a case series from the UK, it was found that the majority of deaths occurred before 1985, which was before TSS was employed as the routine first-line treatment at the center (36). In a recent retrospective study, 80 patients undergoing TSS for CD between 1988 and 2009 were evaluated, and long-term cure (defined as ongoing absence of hypercortisolism at last follow-up) was reported in 72% of patients. However, overall elevated mortality persisted in patients (SMR 3.17 (95% CI: 1.70–5.43)), including those who achieved ‘cure’ (SMR 2.47 (95% CI: 0.80–5.77)), although even higher mortality was seen in those with postoperative recurrence/persistent disease (SMR 4.12 (95% CI: 1.12–10.54) (38). Additionally, a nationwide, retrospective study in New Zealand reported significant persistently increased mortality both in macro- and microadenomas (SMR 3.5 (1.3–7.8) and 3.2 (2.0–4.8) respectively), despite long-term biochemical remission rates of 93 and 91% of patients, respectively (29). Read more at http://m.eje-online.org/content/167/3/311.full
  20. Nearly half of adults with Cushing’s disease that persists or recurs after surgical treatment require second and sometimes third therapeutic interventions, including pituitary surgical reintervention, radiotherapy, pharmacotherapy or bilateral adrenalectomy, study data from Mexico show. Moisés Mercado, MD, FRCPC, of the ABC Hospital Neurological and Cancer Centers in Mexico City, and colleagues evaluated 84 adults (median age, 34 years; 77 women) with Cushing’s disease to determine the long-term efficacy of secondary interventions for persistent and recurrent Cushing’s disease. Median follow-up was 6.3 years. Overall, 81 participants were primarily treated with transsphenoidal surgery. More than half experienced long-lasting remission (61.7%); disease remained active in 16%, who were diagnosed with persistent Cushing’s disease; and 22% experienced relapse after remission and were diagnosed with recurrent Cushing’s disease. After the initial procedure, 18 participants required pituitary surgical reintervention, including 10 with recurrent and eight with persistent disease. Radiation therapy was administered to 14 participants, including two as primary therapy and 12 after failed pituitary surgery. Pharmacologic treatment with ketoconazole was prescribed for 15 participants at one point during the course of disease. Bilateral adrenalectomy was performed in 12 participants. Pituitary surgical reintervention was the most commonly used secondary treatment (22.2%), followed by pharmacologic therapy with ketoconazole (16%), radiotherapy (14.8%) and bilateral adrenalectomy (14.8%). More than half of participants experienced early remissions after a second operation (66.6%) and radiotherapy (58.3%), whereas long-lasting remission was reached in only 33.3% of participants who underwent a second surgery and 41.6% of participants who underwent radiotherapy. Half of participants who underwent bilateral adrenalectomy were diagnosed with Nelson’s syndrome. Overall, 88% of participants achieved remission, and disease was biochemically controlled with pharmacologic treatment in 9.5% of participants after their initial, secondary and third-line treatments. “The efficacy of treatment alternatives for recurrent or persistent [Cushing’s disease] vary among patients, and often, more than one of these interventions is required in order to achieve a long-lasting remission,” the researchers wrote. – by Amber Cox Disclosure: The researchers report no relevant financial disclosures. From http://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7B5519b312-5912-4c65-b2ed-2ece3f68e83f%7D/postsurgical-treatment-often-necessary-in-persistent-recurrent-cushings-disease
  21. I find it amazing that it's newsworthy in this day and age for anyone receiving support after a diagnosis. Of course, a diagnosed person should be getting support as a matter of course. If she had cancer, everyone would be all over this. For Kara Murrow, the most rewarding moments as a teacher come when students learn about animals in the classroom. So it’s difficult for the Bonham Elementary fifth-grade science and social studies teacher to be away from school while she prepares for surgery. “I enjoy it, and I know my kids enjoy the class and enjoy science because of it,” Murrow said. “With the science club I do after school once a week, the kids get upset when it gets canceled because of meetings. Not having it now is upsetting, too.” Murrow was diagnosed this month with Cushing’s disease, a condition that develops when a tumor on the pituitary gland causes it to secrete too much adrenocorticotropic hormone. Murrow, who moved to West Texas from Arizona three years ago, said she has received support from Midland ISD employees and others in the local community. Murrow’s mother, Louise Gonzalez, also appreciates Midlanders’ concerns for her daughter. “People in Midland have been wonderful, considering how new we are to the area,” Gonzalez said. “The school district sent out the GoFundMe page and there’s been an outpouring of support for that. People at my church always ask me.” Murrow’s family is collecting donations from the website GoFundMe to cover the costs of medical and travel expenses. Murrow and her husband, Kai, recently spent money on hospital stays connected to their 4-year-old son’s food sensitivities. “They’ve been paying off those bills and doing OK until this came,” Gonzalez said. “Plus, she’s been going to the doctor about this. Because Cushing’s is so rare, doctors don’t recognize it.” Murrow was diagnosed with the disease after medical professionals discovered a tumor on her pituitary gland. For six years, she experienced symptoms — including weight gain, dizziness and headaches — but said doctors couldn’t determine the cause. Murrow was thankful when she received an answer. “It was a huge relief to finally have a diagnosis and know that I wasn’t crazy or making things up,” Murrow said. “It’s weird to be excited about a brain tumor. It’s a relief to know what was happening and that I have a solution.” Murrow traveled this week to Barrow Neurological Institute in Phoenix, where she’s scheduled to undergo surgery to remove the tumor. Though Murrow said recovery lasts several months, she hopes to return to the classroom next school year. Jaime White, fourth-grade language arts and social studies teacher at Bonham, said both staff and students miss her presence. She said Murrow expresses concern for her students during her time away. “She’s worried about how kids will do on the STAAR [state of Texas Assessments of Academic Readiness],” White said. “She doesn’t want them to think she abandoned them. The disease has to take center stage.” At school, White said she noticed her colleague’s dedication toward helping her students understand science. “She’s hands-on,” White said. “When it comes to science, she’s always making sure the kids are doing some sort of experiment. She wants to make sure the kids grasp it.” Murrow teaches students about animals through dissections and presentations. Before she became a teacher nine years ago, she coordinated outreach programs at an Arizona zoo. When she came to MISD, Murrow saw an opportunity to generate enthusiasm about science. She launched an invite-only science club for fifth-graders who show interest in the subject. “I started it because there wasn’t really anything,” Murrow said. “They have tutorials for reading and math. There’s not a lot kids can do with science after school. They get science in the younger grades, but the focus is on reading and math. Science is something kids really enjoy.” Though Murrow is disappointed about not being able to facilitate the club, she recognizes the importance of her upcoming surgery. She’s happy her mother, husband and two children will be in Phoenix for support. “I hope that it will bring about a sense of relief to all the symptoms I’ve been dealing with and provide a chance for myself and my family to continue along with a full life,” Murrow said. From http://www.mrt.com/news/local/article/Science-teacher-receives-support-after-11026581.php
  22. Early and midterm nonremission after transsphenoidal surgery in people with Cushing’s disease may be predicted by normalized early postoperative values for adrenocorticotropic hormone and cortisol, study data show. Prashant Chittiboina, MD, MPH, assistant clinical investigator in the neurosurgery unit for pituitary and inheritable diseases at the National Institute of Neurological Diseases and Stroke at the NIH, and colleagues evaluated 250 patients with Cushing’s disease who received 291 transsphenoidal surgery procedures during the study period to determine remission after the procedure. Patients were treated between December 2003 and July 2016. Early remission was assessed at 10 days and medium-term remission was assessed at 11 months. Early nonremission was predicted by normalized early postoperative values for cortisol (P = .016) and by normalized early postoperative values for adrenocorticotropic hormone (ACTH; P = .048). Early nonremission was further predicted with 100% sensitivity, 39% specificity, 100% negative predictive value and 18% positive predictive value for a cutoff of –12 µg/mL in normalized early postoperative values for cortisol and with 88% sensitivity, 41% specificity, 96% negative predictive value and 16% positive predictive value for a cutoff of –40 pg/mL in normalized early postoperative values for ACTH. Medium-term nonremission was also predicted by normalized early postoperative values for cortisol (P = .023) and ACTH (P = .025). “We evaluated the utility of early postoperative cortisol and ACTH levels for predicting nonremission after transsphenoidal adenomectomy for Cushing’s disease,” the researchers wrote. “Postoperative operative day 1 values at 6 a.m. performed best at predicting early nonremission, albeit with a lower [area under the receiver operating characteristic curve]. Normalizing early cortisol and ACTH values to post-[corticotropin-releasing hormone] values improved their prognostic value. Further prospective studies will explore the utility of normalized very early postoperative day 0 cortisol and ACTH levels in identifying patients at risk for nonremission following [transsphenoidal surgery] in patients with [Cushing’s disease].” – by Amber Cox Disclosure: The researchers report no relevant financial disclosures. From http://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7B7de200ed-c667-4b48-ab19-256d90a7bbc5%7D/postoperative-acth-cortisol-levels-may-predict-cushings-disease-remission-rate
  23. Cushing disease is caused by tumour in the pituitary gland which leads to excessive secretion of a hormone called adrenocorticotrophic (ACTH), which in turn leads to increasing levels of cortisol in the body. Cortisol is a steroid hormone released by the adrenal glands and helps the body to deal with injury or infection. Increasing levels of cortisol increases the blood sugar and can even cause diabetes mellitus. However the disease is also caused due to excess production of hypothalamus corticotropin releasing hormone (CRH) which stimulates the synthesis of cortisol by the adrenal glands. The condition is named after Harvey Cushing, the doctor who first identified the disease in 1912. Cushing disease results in Cushing syndrome. Cushing syndrome is a group of signs and symptoms developed due to prolonged exposure to cortisol. Signs and symptoms of Cushing syndrome includes hypertension, abdominal obesity, muscle weakness, headache, fragile skin, acne, thin arms and legs, red stretch marks on stomach, fluid retention or swelling, excess body and facial hair, weight gain, acne, buffalo hump, tiredness, fatigue, brittle bones, low back pain, moon shaped face etc. Symptoms vary from individual to individual depending upon the disease duration, age and gender of the patient. Disease diagnosis is done by measuring levels of cortisol in patient’s urine, saliva or blood. For confirming the diagnosis, a blood test for ACTH is performed. The first-line treatment of the disease is through surgical resection of ACTH-secreting pituitary adenoma, however disease management is also done through medications, Cushing disease treatment market comprises of the drugs designed for lowering the level of cortisol in the body. Thus patients suffering from Cushing disease are prescribed medications such as ketoconazole, mitotane, aminoglutethimide metyrapone, mifepristone, etomidate and pasireotide. Request to View Tables of Content @ http://www.persistencemarketresearch.com/toc/14155 Cushing’s disease treatment market revenue is growing with a stable growth rate, this is attributed to increasing number of pipeline drugs. Also increasing interest of pharmaceutical companies to develop Cushing disease drugs is a major factor contributing to the revenue growth of Cushing disease treatment market over the forecast period. Current and emerging players’ focuses on physician education and awareness regarding availability of different drugs for curing Cushing disease, thus increasing the referral speeds, time to diagnosis and volume of diagnosed Cushing disease individuals. Growing healthcare expenditure and increasing awareness regarding Cushing syndrome aids in the revenue growth of Cushing’s disease treatment market. Increasing number of new product launches also drives the market for Cushing’s disease Treatment devices. However availability of alternative therapies for curing Cushing syndrome is expected to hamper the growth of the Cushing’s disease treatment market over the forecast period. The Cushing’s disease Treatment market is segment based on the product type, technology type and end user Cushing’s disease Treatment market is segmented into following types: By Drug Type Ketoconazole Mitotane Aminoglutethimide Metyrapone Mifepristone Etomidate Pasireotide By End User Hospital Pharmacies Retail Pharmacies Drug Stores Clinics e-Commerce/Online Pharmacies Cushing’s disease treatment market revenue is expected to grow at a good growth rate, over the forecast period. The market is anticipated to perform well in the near future due to increasing awareness regarding the condition. Also the market is anticipated to grow with a fastest CAGR over the forecast period, attributed to increasing investment in R&D and increasing number of new product launches which is estimated to drive the revenue growth of Cushing’s disease treatment market over the forecast period. Depending on geographic region, the Cushing’s disease treatment market is segmented into five key regions: North America, Latin America, Europe, Asia Pacific (APAC) and Middle East & Africa (MEA). North America is occupying the largest regional market share in the global Cushing’s disease treatment market owing to the presence of more number of market players, high awareness levels regarding Cushing syndrome. Healthcare expenditure and relatively larger number of R&D exercises pertaining to drug manufacturing and marketing activities in the region. Also Europe is expected to perform well in the near future due to increasing prevalence of the condition in the region. Asia Pacific is expected to grow at the fastest CAGR because of increase in the number of people showing the symptoms of Cushing syndrome, thus boosting the market growth of Cushing’s disease treatment market throughout the forecast period. Some players of Cushing’s disease Treatment market includes CORCEPT THERAPEUTICS, HRA Pharma, Strongbridge Biopharma plc, Novartis AG, etc. However there are numerous companies producing branded generics for Cushing disease. The companies in Cushing’s disease treatment market are increasingly engaged in strategic partnerships, collaborations and promotional activities to capture a greater pie of market share. 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  24. Even after successful treatment, patients with Cushing’s disease who were older when diagnosed or had prolonged exposure to excess cortisol face a greater risk of dying or developing cardiovascular disease, according to a recent study accepted for publication in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM). Cushing’s disease is a rare condition where the body is exposed to excess cortisol – a stress hormone produced in the adrenal gland – for long periods of time. Researchers have long known that patients who have Cushing’s disease are at greater risk of developing and dying from cardiovascular disease than the average person. This study examined whether the risk could be eliminated or reduced when the disease is controlled. Researchers found that these risk factors remained long after patients were exposed to excess cortisol. “The longer patients with Cushing’s disease are exposed to excess cortisol and the older they are when diagnosed, the more likely they are to experience these challenges,” said Eliza B. Geer, MD, of Mount Sinai Medical Center and lead author of the study. “The findings demonstrate just how critical it is for Cushing’s disease to be diagnosed and treated quickly. Patients also need long-term follow-up care to help them achieve good outcomes.” The study found cured Cushing’s disease patients who had depression when they started to experience symptoms of the disease had an elevated risk of mortality and cardiovascular disease. Men were more at risk than women, a trend that may be explained by a lack of follow-up care, according to the study. In addition, patients who had both Cushing’s syndrome and diabetes were more likely to develop cardiovascular disease. The study examined one of the largest cohorts of Cushing’s disease patients operated on by a single surgeon. The researchers retrospectively reviewed charts for 346 Cushing’s disease patients who were treated between 1980 and 2011. Researchers estimated the duration of exposure to excess cortisol by calculating how long symptoms lasted before the patient went into remission. The patients who were studied had an average exposure period of 40 months. The findings may have implications for people who take steroid medications, Geer said. People treated with high doses of steroid medications such as prednisone, hydrocortisone or dexamethasone are exposed to high levels of cortisol and may experience similar conditions as Cushing’s disease patients. “While steroid medications are useful for treating patients with a variety of conditions, the data suggests health care providers need to be aware that older patients or those who take steroid medications for long periods could be facing higher risk,” Geer said. “These patients should be monitored carefully while more study is done in this area.” From http://www.medicalnewstoday.com/releases/256284.php
  25. (HealthDay News) – A number of factors, including the duration of glucocorticoid exposure, older age at diagnosis, and preoperative adrenocorticotropic hormone (ACTH) concentration, are associated with a higher risk of mortality in patients treated for Cushing's disease (CD), according to research published online Feb. 7 in the Journal of Clinical Endocrinology & Metabolism. In an effort to identify predictors of mortality, cardiovascular disease, and recurrence with long-term follow-up, Jessica K. Lambert, MD, of the Mount Sinai Medical Center in New York City, and colleagues performed a retrospective chart review of 346 patients with CD who underwent transsphenoidal adenectomy. The researchers found that the average length of exposure to glucocorticoids was 40 months. The risk of death was higher for those patients who had a longer duration of glucocorticoid exposure, older age at diagnosis, and higher preoperative ACTH concentration. For patients who achieved remission, depressed patients had a higher risk of death. The risk of cardiovascular disease was highest for men, older people, and those with diabetes or depression. "Our study has identified several predictors of mortality in patients with treated CD, including duration of exposure to excess glucocorticoids, preoperative ACTH concentration, and older age at diagnosis. Depression and male gender predicted mortality among patients who achieved remission," the authors write. "These data illustrate the importance of early recognition and treatment of CD. Long-term follow-up, with management of persistent comorbidities by an experienced endocrinologist, is needed even after successful treatment of CD." Abstract Full Text (subscription or payment may be required)
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