Jump to content

Leaderboard


Popular Content

Showing content with the highest reputation since 08/13/2019 in all areas

  1. 2 points
    Presented by Georgios A. Zenonos, MD Assistant Professor of Neurological Surgery Associate Director, Center for Skull Base Surgery University of Pittsburgh Medical Center 200 Lothrop Street, Pittsburgh PA, 15217 Presbyterian Hospital, Suite B400 Register Now! After registering you will receive a confirmation email containing information about joining the Webinar. Date: Wednesday July 1, 2020 Time: 3:00 PM Pacific Daylight Time, 6:00 PM Eastern Daylight Time
  2. 2 points
    Unfortunately a 4:30 pm cortisol test can't be used to diagnose or exclude Cushing's. The only useful blood measurement for cortisol would be a midnight one. You really need to do a 24 hour urinary cortisol test.
  3. 2 points
    Welcome, Ellie. I can't image how hard it would be to get a diagnosis (or not!) during these COVID times. Unfortunately, results from blood tests aren't going to be the answer - just a part of an answer. You need to get UFCs (urine free cortisol) Do you need to get a referral to an endo? They are the best to diagnose Cushing's - if you get one who is familar with testing. That's the important part. Not all endos "believe in Cushing's" which is incredible to me. Unfortunately, there's no real way of speeding a Cushing's diagnosis along. And, I don't think you'd want to (although I did when I was in the diagnosis phase!) You want to be absolutely sure that this is what you have AND the source - pituitary, adrenal, ectopic, steroid-induced... Best of luck to you and please keep us posted.
  4. 2 points
    Dr. Friedman will discuss topics including: Who should get an adrenalectomy? How do you optimally replace adrenal hormones? What laboratory tests are needed to monitor replacement? When and how do you stress dose? What about subcut cortisol versus cortisol pumps? Patient Melissa will lead a Q and A Sunday • May 17 • 6 PM PST Click here on start your meeting or https://axisconciergemeetings.webex.com/axisconciergemeetings/j.php?MTID=mb896b9ec88bc4e1163cf4194c55b248f OR Join by phone: (855) 797-9485 Meeting Number (Access Code): 802 841 537 Your phone/computer will be muted on entry. Slides will be available on the day of the talk here There will be plenty of time for questions using the chat button. Meeting Password: addison
  5. 2 points
    Hello Mary!! Thank you for replying!! It was a surprise for me having a relapse... I never knew or even heard it could happen... but last year I began to feel sooooo bad... and as I’ve had so many difficulties with the doctors I consulted the first time (I visited 40 doctors in ten years ... and only 3 of them understood my symptoms)... I decided to go to the laboratory by myself and asked them to perform the tests I thought I might have needed. And so I saw the cortisol beginning to increase ... but this January I presented a tachyarrhytmia sincope and although cardiologists intended to get me through a lot of heart testing I KNEW it was high cortisol levels again which led to this condition. And that is how it was... my cortisol was twice the normal levels... and again I went to an endocrinologist and she told me ... you have Cushing again... you can imagine it’s been the worst déjà-vu in my life. The etiology of my Cushing’s Disease the first time was very uncommon, as I thankfully never had any ACTH or cortisol secreting tumor, but I presented very high levels of cortisol (over ten times normal levels) and of ACTH, beyond high levels of other pituitary hormones: prolactine , TSH, FSH, LH ( a condition known as PANHYPERPITUITARISM) besides insulin, estrogens and so on... except for somatotropin (growth hormone), almost all of my hormones were in very high levels... and I was almost dying. Ten years and forty doctors later my neurosurgeon discovered in my latest MRI that besides I had a pituitary lesion that didn’t light up in the scan, my pituitary stalk and my hypothalamus (as well as the pituitary gland -presenting empty sella) were completely compressed by a suprasellar arachnoides cyst (meninges cyst), so that the hypothalamus hormones that regulated the pituitary hormones to stop over producing were stuck and never reached the pituitary... so it (pituitary gland) was continually producing all kind of hormones (except GH) without stopping. Finally in 2009 I had a neurosurgery resecting the meninges cyst, hoping that reliefing the pituitary stalk could lead hypothalamus hormones to reach the pituitary and regulate it to a normal hormone release... and so it happened!!! A month after neurosurgery my pituitary hormones levels were totally normal as well as my cortisol... and little by little the rest of almost my other health issues released... it took me over five years to have my liver in optimal conditions (Normal oxaloacetic and pyruvic transaminases) and to leave my diabetes medication at all controlling it only with a strict diet. So the last five years I’ve just struggled with hypertension , hypoglucemia and hypotiroidism (Primary subclicinal)... until last year ... I couldn’t understand what was happening to me... I couldn’t move my muscles.. extreme fatigue and great muscle pain... so I had my doubts and was checking upon suspicious high cortisol levels. This time as well as the first time I suppress cortisol with the dexametasona test... which indicates I do not over produce cortisol because of a tumor... so the etiology is again different from what’s common. And now my latest doctor has told me that my over production of cortisol is due to my previous Cushing’s disease and panhyperpituitarism and not because any possible ACTH or cortisol tumor. I decided to investigate what could help me to stop over producing cortisol and so I found Dr. Burton’s work. After founding out his investigation was still in the dark... well I decided to help him making his work known through your Forum... but I also needed help and so I continued researching and I found Isturisa (osilodrostat - LCI-699) which had just been approved in the EU this January. And so I spoke to the Director of Recordati Rare Diseases in México City and he told me that with my diagnosis and prescription they could send me the medication. As the annual treatment is about 55K euros, they are now helping me through IMSS (Mexican Institute of Social Security) so that the Mexican Federal Government can provide me the medication at no cost for the time I need it... it’s an administrative process but we’re starting it and we expect to have good results. And by far this is how my story goes... I know it was a long reply... but I think it is important for all of us to know this uncommon etiology of the Disease... because it took me over ten years and plenty of pain and suffering to get to the point of what was causing my over production of ACTH, cortisol and almost the whole of hormones in my body... and as my neurosurgeon told me... this etiology of Cushing’s Disease doesn’t even appear in medicine books .... So I hope my medical case can help anybody that unfortunately could be in this position to find quick answers from their doctors... and maybe teach them something as I did. Thank you very much for reading this... my best wishes... stay safe ... blessings!! Regards from Querétaro México MAYELA
  6. 2 points
    Hello Mary & dear Cushies!! I’ve just discovered this article two months ago and I was very pleased to speak directly to Dr. Gerardo Burton. He and his team developed a drug (21OH-6OP) which is a SPECIFIC antagonist for cortisol receptors, unlikely mifepristone which inhibits cortisol AND progesterone with so many undesired adverse effects. Unfortunately the pharmaceutical company didn’t choose this drug to start the clinical trials and so it is resting in Dr. Burton’s lab.... since 2007. The great humanity in Dr. Burton drop tears into my eyes when he told me that he would like that his whole work could help at least somebody to improve their quality of life. As a Cushing’s disease survivor ten years ago ... and now with a relapse of Cushing’s syndrome I keep wondering how is it possible that Dr. Burton’s work remains unknown, wasted, buried and in oblivion. For any of us either with Cushing’s Disease or Syndrome this drug is like the light at the end of the tunnel... I wish I could explain all this as clearly as I intended... and the reason why I post this topic is because I promised Dr. Burton I would try to help him to make his work known specially for all of us... and if somebody can help with a FDA contact and make this story known to them... that would be of so much help!!! Thank to all of you for reading this, my best wishes for all... stay safe this pandemic Regards from Querétaro, México Mayela https://www.intramed.net/contenidover.asp?contenidoid=48298
  7. 2 points
    Thank you so much, Mayela - I'll definitely check this out. We need all the help we can get and I'm glad that Dr. Burton is trying to help Cushing's patients. 13 years is a long time to withhold a potentially helpful drug. I'm so sorry you're having a relapse Are you planning another pituitary surgery, BLA or something else?
  8. 2 points
    Cushing syndrome, a rare endocrine disorder caused by abnormally excessive amounts of the hormone cortisol, has a new pharmaceutical treatment to treat cortisol overproduction. Osilodrostat (Isturisa) is the first FDA approved drug who either can’t undergo pituitary gland surgery or have undergone the surgery but still have the disease. The oral tablet functions by blocking the enzyme responsible for cortisol synthesis, 11-beta-hydroxylase. “Until now, patients in need of medications…have had few approved options, either with limited efficacy or with too many adverse effects. With this demonstrated effective oral treatment, we have a therapeutic option that will help address patients' needs in this underserved patient population," said Maria Fleseriu, MD, FACE, professor of medicine and neurological surgery and director of the Pituitary Center at Oregon Health Sciences University. Cushing disease is caused by a pituitary tumor that releases too much of the hormone that stimulates cortisol production, adrenocorticotropin. This causes excessive levels of cortisol, a hormone responsible for helping to maintain blood sugar levels, regulate metabolism, help reduce inflammation, assist in memory formulation, and support fetus development during pregnancy. The condition is most common among adults aged 30-50 and affects women 3 times more than men. Cushing disease can lead to a number of medical issues including high blood pressure, obesity, type 2 diabetes, blood clots in the arms and legs, bone loss and fractures, a weakened immune system, and depression. Patients with Cushing disease may also have thin arms and legs, a round red full face, increased fat around the neck, easy bruising, striae (purple stretch marks), or weak muscles. Side effects of osilodrostat occurring in more than 20% of patients are adrenal insufficiency, headache, nausea, fatigue, and edema. Other side effects can include vomiting, hypocortisolism (low cortisol levels), QTc prolongation (heart rhythm condition), elevations in adrenal hormone precursors (inactive substance converted into hormone), and androgens (hormone that regulated male characteristics). Osilodrostat’s safety and effectiveness was evaluated in a study consisting of 137 patients, of which about 75% were women. After a 24-week period, about half of patients had achieved normal cortisol levels; 71 successful cases then entered an 8-week, double-blind, randomized withdrawal study where 86% of patients receiving osilodrostat maintained normal cortisol levels, compared with 30% who were taking a placebo. In January 2020, the European Commission also granted marketing authorization for osilodrostat. From https://www.ajmc.com/newsroom/patients-with-cushing-have-new-nonsurgical-treatment-option
  9. 2 points
    The U.S. Food and Drug Administration today approved Isturisa (osilodrostat) oral tablets for adults with Cushing's disease who either cannot undergo pituitary gland surgery or have undergone the surgery but still have the disease. Cushing's disease is a rare disease in which the adrenal glands make too much of the cortisol hormone. Isturisa is the first FDA-approved drug to directly address this cortisol overproduction by blocking the enzyme known as 11-beta-hydroxylase and preventing cortisol synthesis. "The FDA supports the development of safe and effective treatments for rare diseases, and this new therapy can help people with Cushing's disease, a rare condition where excessive cortisol production puts them at risk for other medical issues," said Mary Thanh Hai, M.D., acting director of the Office of Drug Evaluation II in the FDA's Center for Drug Evaluation and Research. "By helping patients achieve normal cortisol levels, this medication is an important treatment option for adults with Cushing's disease." Cushing's disease is caused by a pituitary tumor that releases too much of a hormone called adrenocorticotropin, which stimulates the adrenal gland to produce an excessive amount of cortisol. The disease is most common among adults between the ages of 30 to 50, and it affects women three times more often than men. Cushing's disease can cause significant health issues, such as high blood pressure, obesity, type 2 diabetes, blood clots in the legs and lungs, bone loss and fractures, a weakened immune system and depression. Patients may have thin arms and legs, a round red full face, increased fat around the neck, easy bruising, striae (purple stretch marks) and weak muscles. Isturisa's safety and effectiveness for treating Cushing's disease among adults was evaluated in a study of 137 adult patients (about three-quarters women) with a mean age of 41 years. The majority of patients either had undergone pituitary surgery that did not cure Cushing's disease or were not surgical candidates. In the 24-week, single-arm, open-label period, all patients received a starting dose of 2 milligrams (mg) of Isturisa twice a day that could be increased every two weeks up to 30 mg twice a day. At the end of this 24-week period, about half of patients had cortisol levels within normal limits. After this point, 71 patients who did not need further dose increases and tolerated the drug for the last 12 weeks entered an eight-week, double-blind, randomized withdrawal study where they either received Isturisa or a placebo (inactive treatment). At the end of this withdrawal period, 86% of patients receiving Isturisa maintained cortisol levels within normal limits compared to 30% of patients taking the placebo. The most common side effects reported in the clinical trial for Isturisa were adrenal insufficiency, headache, vomiting, nausea, fatigue and edema (swelling caused by fluid retention). Hypocortisolism (low cortisol levels), QTc prolongation (a heart rhythm condition) and elevations in adrenal hormone precursors (inactive substance converted into a hormone) and androgens (hormone that regulates male characteristics) may also occur in people taking Isturisa. Isturisa is taken by mouth twice a day, in the morning and evening as directed by a health care provider. After treatment has started, a provider may re-evaluate dosage, depending upon the patient's response. Isturisa received Orphan Drug Designation, which is a special status granted to a drug intended to treat a rare disease or condition. The FDA granted the approval of Isturisa to Novartis. Media Contact: Monique Richards, 240-402-3014 Consumer Inquiries: Email, 888-INFO-FDA The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation's food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products. SOURCE U.S. Food and Drug Administration Related Links http://www.fda.gov From https://www.prnewswire.com/news-releases/fda-approves-new-treatment-for-adults-with-cushings-disease-301019293.html
  10. 2 points
    MENLO PARK, Calif., Aug. 28, 2019 (GLOBE NEWSWIRE) -- Corcept Therapeutics Incorporated (NASDAQ: CORT) announced today that the United States Patent and Trademark Office has issued a Notice of Allowance for a patent covering the administration of Korlym® with food. The patent will expire in November 2032. “This patent covers an important finding of our research – that for optimal effect, Korlym must be taken with food,” said Joseph K. Belanoff, MD, Corcept’s Chief Executive Officer. “Korlym’s label instructs doctors that ‘Korlym must always be taken with a meal.’” Upon issuance, Corcept plans to list the patent, entitled “Optimizing Mifepristone Absorption” (U.S. Pat. App. 13/677,465), in the U.S. Food and Drug Administration’s Approved Drug Products with Therapeutic Equivalence Evaluations (the “Orange Book”). Korlym is currently protected by ten patents listed in the Orange Book. Hypercortisolism Hypercortisolism, often referred to as Cushing’s syndrome, is caused by excessive activity of the hormone cortisol. Endogenous Cushing’s syndrome is an orphan disease that most often affects adults aged 20-50. In the United States, an estimated 20,000 patients have Cushing’s syndrome, with about 3,000 new patients diagnosed each year. Symptoms vary, but most people with Cushing’s syndrome experience one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper-body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Hypercortisolism can affect every organ system in the body and can be lethal if not treated effectively. About Corcept Therapeutics Incorporated Corcept is a commercial-stage company engaged in the discovery and development of drugs that treat severe metabolic, oncologic and psychiatric disorders by modulating the effects of the stress hormone cortisol. Korlym® (mifepristone) was the first treatment approved by the U.S. Food and Drug Administration for patients with Cushing’s syndrome. Corcept has discovered a large portfolio of proprietary compounds, including relacorilant, exicorilant and miricorilant, that selectively modulate the effects of cortisol but not progesterone. Corcept owns extensive United States and foreign intellectual property covering the composition of its selective cortisol modulators and the use of cortisol modulators, including mifepristone, to treat a variety of serious disorders. Forward-Looking Statements Statements in this press release, other than statements of historical fact, are forward-looking statements, which are based on Corcept’s current plans and expectations and are subject to risks and uncertainties that might cause actual results to differ materially from those such statements express or imply. These risks and uncertainties include, but are not limited to, Corcept’s ability to generate sufficient revenue to fund its commercial operations and development programs; the availability of competing treatments, including generic versions of Korlym; Corcept’s ability to obtain acceptable prices or adequate insurance coverage and reimbursement for Korlym; and risks related to the development of Corcept’s product candidates, including regulatory approvals, mandates, oversight and other requirements. These and other risks are set forth in Corcept’s SEC filings, which are available at Corcept’s website and the SEC’s website. In this press release, forward-looking statements include those concerning Corcept’s plans to list the patent “Optimizing Mifepristone Absorption” in the Orange Book; Korlym’s current protection by ten patents listed in the Orange Book; and the scope and protective power of Corcept’s intellectual property. Corcept disclaims any intention or duty to update forward-looking statements made in this press release. CONTACT: Christopher S. James, MD Director, Investor Relations Corcept Therapeutics 650-684-8725 cjames@corcept.com www.corcept.com
  11. 1 point
    Study Authors: Tsung-Chieh Yao, Ya-Wen Huang, et al.; Beth I. Wallace, Akbar K. Waljee Target Audience and Goal Statement: Primary care physicians, rheumatologists, pulmonologists, dermatologists, gastroenterologists, cardiologists The goal of this study was to examine the associations between oral corticosteroid bursts and severe adverse events among adults in Taiwan. Question Addressed: What were the associations between steroid bursts and severe adverse events, specifically gastrointestinal (GI) bleeding, sepsis, and heart failure? Study Synopsis and Perspective: It has long been known that long-term use of corticosteroids can be both effective and toxic. Long-term use is associated with adverse effects such as infections, GI bleeding/ulcers, cardiovascular disease (CVD), Cushing syndrome, diabetes and metabolic syndromes, cataracts, glaucoma, and osteoporosis. Most clinical practice guidelines caution against long-term steroid use unless medically necessary. Action Points In a retrospective cohort study and self-controlled case series, prescriptions for oral steroid bursts were found to be associated with increased risks for gastrointestinal bleeding, sepsis, and heart failure within the first month after initiation, despite a median exposure of just 3 days. Note that the risks were highest 5 to 30 days after exposure, and attenuated during the subsequent 31 to 90 days. Instead, clinical practice guidelines recommend steroid bursts for inflammatory ailments such as asthma, inflammatory bowel disease, and rheumatoid arthritis. Waljee and colleagues noted in 2017 that they are most commonly used for upper respiratory infections, suggesting that many people are receiving steroids in the real world. In a retrospective cohort study and self-controlled case series, prescriptions for oral steroid bursts -- defined as short courses of oral corticosteroids for 14 or fewer days -- were found to be associated with increased risks for GI bleeding, sepsis, and heart failure within the first month after initiation, despite a median exposure of just 3 days, according to Tsung-Chieh Yao, MD, PhD, of Chang Gung Memorial Hospital in Taoyuan, and colleagues. The risks were highest 5 to 30 days after exposure, and attenuated during the subsequent 31 to 90 days, they reported in Annals of Internal Medicine. The self-controlled case series was based on national medical claims records. Included were adults, ages 20-64, covered by Taiwan's National Health Insurance in 2013-2015. Out of a population of more than 15.8 million, study authors identified 2,623,327 people who received a steroid burst during the study period. These individuals were age 38 on average, and 55.3% were women. About 85% had no baseline comorbid conditions. The most common indications for the steroid burst were skin disorders and respiratory tract infections. The incidence rates among patients prescribed steroid bursts were 27.1 per 1,000 person-years for GI bleeding (incidence rate ratio [IRR] 1.80, 95% CI 1.75-1.84), 1.5 per 1,000 person-years for sepsis (IRR 1.99, 95% CI 1.70-2.32), and 1.3 per 1,000 person-years for heart failure (IRR 2.37, 95% CI 2.13-2.63). Absolute risk elevations were similar in patients with and without comorbid conditions, meaning that the potential for harm was not limited to those at high risk for these adverse events. The study authors acknowledged that they could not adjust for disease severity and major lifestyle factors such as alcohol use, smoking, and body mass index; because these factors were static, the effect could be eliminated using the self-controlled case series design. Their reliance on prescription data also meant they could not tell if patients actually complied with oral corticosteroid therapy. Furthermore, the exclusion of the elderly and younger populations also left room for underestimation of the risks of steroid bursts, they said. Source References: Annals of Internal Medicine 2020; DOI: 10.7326/M20-0432 Editorial: Annals of Internal Medicine 2020; DOI: 10.7326/M20-4234 Study Highlights and Explanation of Findings: Over the 3-year study period, steroid bursts were commonly prescribed to adults. Such prescriptions were written for common conditions, including skin disorders and upper respiratory tract infections. The highest risks for GI bleeding, sepsis, and heart failure occurred within the first month after receipt of the steroid burst, and this risk was attenuated during the subsequent 31 to 90 days. "Our findings are important for physicians and guideline developers because short-term use of oral corticosteroids is common and the real-world safety of this approach remains unclear," the researchers wrote. Notably, one corticosteroid that fits the bill is dexamethasone -- a medication that holds promise for the treatment of critically ill COVID-19 patients, although it is not generally prescribed orally for these patients. Based on preliminary results, the NIH's COVID-19 treatment guidelines panel recommended the use of "dexamethasone (at a dose of 6 mg per day for up to 10 days) in patients with COVID-19 who are mechanically ventilated and in patients with COVID-19 who require supplemental oxygen but who are not mechanically ventilated." In addition, they recommend "against using dexamethasone in patients with COVID-19 who do not require supplemental oxygen." "We are now learning that bursts as short as 3 days may increase risk for serious AEs [adverse events], even in young and healthy people. As providers, we must reflect on how and why we prescribe corticosteroids to develop strategies that prevent avoidable harms," wrote Beth Wallace, MD, and Akbar Waljee, MD, both of the VA Ann Arbor Healthcare System and Michigan Medicine. On the basis of the reported risk differences in the study, Wallace and Waljee calculated that one million patients exposed to corticosteroid bursts experienced 41,200 GI bleeding events, 400 cases of sepsis, and 4,000 cases of new heart failure per year that were directly attributed to this brief treatment. "Although many providers already avoid corticosteroids in elderly patients and those with comorbid conditions, prescribing short bursts to 'low-risk' patients has generally been viewed as innocuous, even in cases where the benefit is unclear. However, Yao and colleagues provide evidence that this practice may risk serious harm, making it difficult to justify in cases where corticosteroid use lacks evidence of meaningful benefit," they wrote in an accompanying editorial. "Medication-related risks for AEs can, of course, be outweighed by major treatment benefit. However, this study and prior work show that corticosteroid bursts are frequently prescribed for self-limited conditions, where evidence of benefit is lacking," Wallace and Waljee noted. "As we reflect on how to respond to these findings, it is useful to note the many parallels between use of corticosteroid bursts and that of other short-term medications, such as antibiotics and opiates. All of these treatments have well-defined indications but can cause net harm when used -- as they frequently are -- when evidence of benefit is low," they emphasized. Last Updated August 07, 2020 Reviewed by Dori F. Zaleznik, MD Associate Clinical Professor of Medicine (Retired), Harvard Medical School, Boston Primary Source Annals of Internal Medicine Source Reference: Yao TC, et al "Association between oral corticosteroid bursts and severe adverse events: a nationwide population-based cohort study" Ann Intern Med 2020; DOI: 10.7326/M20-0432. Secondary Source Annals of Internal Medicine Source Reference: Wallace BI, Waljee AK "Burst case scenario: why shorter may not be any better when it comes to corticosteroids" Ann Intern Med 2020; DOI: 10.7326/M20-4234. Additional Source MedPage Today Source Reference: Lou N "Sobering Data on Risks of Short-Term Oral Corticosteroids" 2020. From https://www.medpagetoday.org/primarycare/generalprimarycare/87959?xid=nl_mpt_DHE_2020-08-08&eun=g1406328d0r&utm_term=NL_Daily_DHE_dual-gmail-definition&vpass=1
  12. 1 point
    Wow 8.4 on the first try. These are textbook adrenal numbers. I hope your doctors come to their senses.
  13. 1 point
    This event has been postponed to Dec. 5, 2020 You are Cordially Invited! The PNA is pleased to announce our participation in this event! Saturday, December 5, 2020 8:30am – 4:30pm Zuckerman Research Center 417 E. 68th St. New York, NY Memorial Sloan Kettering Cancer Center Target Audience This course is intended for endocrinologists, neurosurgeons, otolaryngologists, radiation oncologists, neurologists, ophthalmologists, neuro-oncologists, family medicine and internal medicine physicians, physicians in training and other allied health professionals who treat and manage patients with pituitary diseases. We also invite patients with pituitary disease and their caregivers to attend this educational activity and participate in our interactive afternoon breakout sessions. Overall this course aims to improve patient care and outcomes through evidence-based discussion of clinical practice guidelines and emerging therapies. Our goal is to assess and update current practices to promote earlier diagnosis and treatment of pituitary diseases. The multidisciplinary nature of the course will allow for the dissemination of knowledge across the variety of practitioners caring for pituitary patients, and for the patients themselves. Pituitary patients will be able to review treatment options, learn about ongoing clinical trials, and discuss their comprehensive care with providers and other patients. The educational objective of this patient session is to provide a forum for pituitary patients to discuss treatment options and new therapies with providers and other patients. Patients with pituitary disease and their caregivers are invited to attend this educational activity FREE of charge. If you are a patient or caregiver interested in attending, please email cme@mskcc.org to register (registration is required in order to attend). Medical Professionals who wish to attend must register online: mskcc.org/PituitaryCourse View Course Flyer
  14. 1 point
    Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the viral strain that has caused the coronavirus disease 2019 (COVID-19) pandemic, has presented healthcare systems around the world with an unprecedented challenge. In locations with significant rates of viral transmission, social distancing measures and enforced ‘lockdowns’ are the new ‘norm’ as governments try to prevent healthcare services from being overwhelmed. However, with these measures have come important challenges for the delivery of existing services for other diseases and conditions. The clinical care of patients with pituitary disorders typically involves a multidisciplinary team, working in concert to deliver timely, often complex, disease investigation and management, including pituitary surgery. COVID-19 has brought about major disruption to such services, limiting access to care and opportunities for testing (both laboratory and radiological), and dramatically reducing the ability to safely undertake transsphenoidal surgery. In the absence of clinical trials to guide management of patients with pituitary disease during the COVID-19 pandemic, herein the Professional Education Committee of the Pituitary Society proposes guidance for continued safe management and care of this population. Introduction In many centers worldwide, the evaluation and treatment of pituitary disorders has already been substantially impacted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the viral strain that has caused the coronavirus disease 2019 (COVID-19) pandemic. With reduced access to routine clinical services, patients with suspected or confirmed pituitary disease face the prospect of delays in diagnosis and implementation of effective treatment plans. Furthermore, patients undergoing surgery may be at increased risk from COVID-19, whilst the risk of infection to healthcare providers during pituitary surgery is of particular concern. Herein, we discuss several clinical scenarios where clinical care can be adjusted temporarily without compromising patient outcomes. For this expert guidance, The Pituitary Society Professional Education Committee, which includes neuroendocrinologists and neurosurgeons from four continents, held an online video conference call with subsequent discussions conducted through email communications. The suggestions are not evidence-based due to the novelty and timing of the pandemic; furthermore, re-evaluation every few months in light of emerging data, is recommended. The approach will also likely vary from country to country depending on the risk of viral infection, local rules for “lockdown”, and the capabilities of individual health care systems. Pituitary surgery challenges during the COVID-19 pandemic The significant challenges to pituitary surgery presented by COVID-19 can be considered in terms of the phase of the pandemic, the patient, the surgeon, and the healthcare institution (Table 1). Table 1 Pituitary surgery challenges and recommendations during COVID-19 pandemic Full size table The World Health Organization (WHO) recognizes several phases of a pandemic wave [1]. When the pandemic is in progress (WHO pandemic phase descriptions; Phase 6) [2] there is a high prevalence of active cases. In the immediate post-peak period, the pandemic activity appears to wane, but active cases remain, and additional waves may follow. Previous pandemics have had many such waves, each separated by several months (www.cdc.gov). The corollary is that there will remain a significant possibility of patients and surgeons contracting COVID-19 until a vaccine is developed or herd immunity is achieved by other means. The patient requiring pituitary surgery may be especially vulnerable to COVID-19 due to age and/or comorbidities. This is particularly true of patients with functioning pituitary adenomas such as those with Cushing’s disease (CD), where cortisol excess results in immunosuppression, hypercoagulability, diabetes mellitus and hypertension, and acromegaly which is also frequently complicated by diabetes mellitus and hypertension. Moreover, the risk for patients undergoing surgery that develop COVID-19 in the perioperative period appears to be very high. In a retrospective analysis of 34 patients who underwent elective—non pituitary—surgeries during the incubation period of COVID-19, 15 (44.1%) patients required admission to the intensive care unit, and 7 (20.5%) died [3]. Although this study included cases of variable technical difficulty, complexity and risk—from excision of breast lump to total hip replacement—we would suggest that patients undergoing pituitary surgery that develop COVID-19 are likely to be at similar or greater risk. These risks must be balanced carefully against the natural history of pituitary disease and, in particular, whether undue delay may result in irreversible morbidity such as visual loss in patients with pituitary apoplexy. The surgeon remains in direct contact with the patient throughout their operation and is therefore at risk of contracting COVID-19 if the patient has an active infection. Iorio-Morin et al. [4] suggest that surgeons performing transsphenoidal pituitary surgery (TSS) may be at the greatest risk, because such surgery is performed under general anesthesia, requiring intubation and extubation, exposes the colonized nasal mucosa, and usually involves sphenoid drilling, which can result in aerosolization of contaminated tissues. The healthcare institution will invariably divert resources from elective services to support the care of patients with COVID-19, with a knock-on effect on the capacity to manage patients with pituitary disease (Table 1). Bernstein et al. [5] suggest that surgery is particularly affected in such reorganization, because of both the need for redeployment of anesthesiologists able to manage patient airways, and availability of protective physical resources such as masks, gowns, and gloves (personal protective equipment; PPE). Furthermore, in areas with high number of infections, several operating rooms (OR)s were converted into intensive care units (ICU) to treat patients with COVID-19, thus limiting patients’ access to elective surgery even more. Recommendations for pituitary surgery When the viral risk is decreasing in a specific geographic area, we would advocate a stepwise, but flexible normalization of activity, addressing each of the aforementioned factors. Burke et al. [6] proposed a staged volume limiting approach to scheduling surgical cases depending on the number of community cases and inpatients with COVID-19, and staffing shortages. In extreme cases, where significant assistance is required from outside institutions, only emergent cases can proceed. Until further data become available, all patients undergoing pituitary surgery should undergo screening for COVID-19, until a vaccine is developed or herd immunity is achieved by other means. At the least, we recommend screening patients for cough, fever, or other recognized symptoms of infection with SARS-CoV-2, and taking swab samples for testing if there is any clinical suspicion. Depending on the level of COVID-19 activity in the community, and available resources, a more exhaustive strategy may be appropriate, including isolation of patients for up to 2 weeks before surgery, paired swabs and/or serological tests for all patients irrespective of symptoms, and routine chest X-ray or chest computed tomography (CT), depending on local guidance. In patients with COVID-19 in whom surgery is indicated, in general we recommend delaying surgery if possible, ideally until patients no longer have symptoms and have a negative swab test result. The nature of the patient’s pituitary disease is an important consideration, and we propose stratifying cases as emergent, urgent, or elective. We recommend that patients continue to be operated on in an emergent fashion if they present with pituitary apoplexy, acute severe visual loss, or other significant mass effect, or if there is concern regarding malignant pathology. Selected patients with slowly progressive visual loss, functioning tumors with aggressive clinical features, and those with an unclear diagnosis, may also benefit from urgent (but not emergent) surgery, with decisions made on a case-by-case basis. Patients with incidental and asymptomatic tumors, known nonfunctioning adenomas [7] or functioning tumors, which are well controlled with medical therapy, can be scheduled as elective cases. In most cases, TSS remains the safest, most effective, and most efficient approach to pituitary tumors. In a series of 9 consecutive patients without COVID-19 undergoing pituitary and skull base surgery during the pandemic, Kolias et al. [8] reported that none of the patients or staff contracted COVID-19 following adoption of a standardized risk-mitigation strategy. In the rare instances where a patient with COVID-19 requires emergent surgery that cannot be deferred, alternative transcranial approaches may be considered (avoiding nasal mucosa). To replace high-speed drilling, the use of non-powered tools such as rongeurs and chisels has been recommended. If this is not possible large suction tubes can be used to aspirate as much particulate matter as possible [9]. In such cases, the availability and use of PPE, and in particular filtering facepiece (FFP3) respirators, is mandated. Depending on the level of COVID-19 activity in the community, and the availability and effectiveness of testing, PPE may be appropriate in all cases. At an institutional level, there must remain flexibility in anticipation of further waves of COVID-19. This necessitates a reduction in capacity, particularly in available ICU beds, that must be recognized when scheduling challenging surgical cases. In the long term, resumption of full elective workloads depends on wider national and international factors, including widespread testing, and widespread immunity through vaccination or other means. Pituitary diseases diagnosis and management Acromegaly Acromegaly, a condition that arises from growth hormone (GH) excess, generally occurs as a result of autonomous GH secretion from a somatotroph pituitary adenoma [10, 11], is associated with substantial morbidity and excess mortality, which can be mitigated by prompt and adequate treatment [12]. Diagnosis is often delayed because of the low prevalence of the disease, the frequently non-specific nature of presenting symptoms, and the typically subtle progression of clinical features [10, 11]. During the COVID-19 pandemic many outpatient clinics have closed or limited work hours. Patients are often reluctant to seek care out of fear of possible exposure to the coronavirus. Therefore, even longer diagnostic delays are anticipated. In addition, patients who present with vision loss and larger tumors encroaching upon the optic apparatus are at risk for experiencing persistent visual compromise unless the optic chiasm and nerves are promptly decompressed. To improve patient access to care and minimize potentially deleterious delays in diagnosis and treatment, clinicians may conduct virtual visits (VV) using secure, internet-based electronic medical record platforms. A detailed history can be obtained and a limited physical examination is possible, including inspection of the face, skin and extremities. Diagnosis Establishing the diagnosis of acromegaly requires testing of serum insulin-like growth factor-I (IGF-I) levels [11] (Box 1). Access to accurate IGF-I assays is critical in light of the substantial analytical and post-analytical problems that have plagued several IGF-I immunoassays. While the oral glucose tolerance test (OGTT) is considered the diagnostic “gold standard”, this test is not essential in many patients, including those with a clear-cut clinical picture and an unequivocally elevated serum IGF-I level. Deferring the lengthy (2-h) OGTT may minimize the risk of potential exposure to infectious agents. Given the over-representation of macroadenomas in patients with acromegaly, pituitary imaging is indicated, preferably by a pituitary-specific magnetic resonance imaging (MRI) protocol, although CT may be performed to rule out a large tumor if MRI is not feasible. Obtaining imaging at satellite sites detached from major hospitals may also decrease the risk of infection exposure. Management Transsphenoidal pituitary surgery remains the treatment of choice for most patients with acromegaly [10, 11], and patients with visual compromise as a result of a pituitary adenoma compressing the optic apparatus should still undergo pituitary surgery promptly. Other patients could be treated medically until the pandemic subsides. Medical treatment options are somatostatin receptor ligands (SRLs), octreotide long-acting release (LAR), lanreotide depot and pasireotide LAR, pegvisomant and cabergoline (used off-label) [13]. Medical therapies can be effective in providing symptomatic relief, control GH excess or action, and potentially reduce tumor size (except pegvisomant, which does not have direct antiproliferative effects). Preoperative medical therapy has been reported to improve surgical outcomes in some, but not all studies. Pasireotide, which potentially can induce QTc prolongation, should be used with caution in patients who are taking, either as prophylaxis or treatment, medications for COVID-19 (azithromycin, hydroxychloroquine), which can also have an effect on QTc interval. Furthermore, as hyperglycemia is very frequent in patients treated with pasireotide and needs close monitoring at start of the treatment, this treatment should be reserved for truly resistant cases, with large tumors and who cannot have surgery yet. Notably, lanreotide depot, cabergoline or pegvisomant can be administered by the patient or a family member and therefore an in-person visit to a clinic is not required. If SRLs that require health care professional administration are required, raising the dose may allow the interval between injections to be extended beyond 4 weeks while maintaining disease control. Virtual visits can be implemented to monitor the patient’s course and response to medical therapy during the pandemic. Careful management of comorbidities associated with acromegaly remains an essential part of patient care [14, 15]. Prolactinomas Hyperprolactinemia may be physiological in origin or arise because of an underlying pathophysiologic cause, medication use or laboratory artifact. Therefore, an initial evaluation for hyperprolactinemia should include a comprehensive medication history, a thorough evaluation for secondary causes, including primary hypothyroidism, and a careful assessment for clinical features of hyperprolactinemia, including hypogonadism and galactorrhea. Unless a secondary cause of hyperprolactinemia can be established definitively, further investigation is indicated to evaluate the etiology of hyperprolactinemia. Diagnosis The diagnosis of a lactotroph adenoma can be inferred in most patients based on the presence of a pituitary adenoma and an elevated prolactin level, which is typically proportionate in magnitude to adenoma size. Pituitary imaging (MRI or CT) is therefore a key step in the investigation of hyperprolactinemia. Evaluation for hypopituitarism is also necessary. Management Although observation and routine follow-up with serial prolactin levels and imaging is acceptable for patients who are asymptomatic and who have a microadenoma, most patients diagnosed with a prolactinoma will require treatment. Dopamine-agonists (DA) can normalize prolactin levels and lead to reduction in size of the lactotroph adenoma [16]. In patients who have a microadenoma and who are not seeking fertility, hormone-replacement therapy may also be appropriate if serum prolactin is routinely followed and imaging performed as necessary. Medical therapy can be managed effectively and efficiently via VVs coupled with laboratory/imaging studies as needed. However, in all patients in whom a DA will be initiated, it is critical that a comprehensive psychiatric history is obtained prior to commencing treatment. Patients may not readily volunteer their psychiatric history and may not appreciate the relevance of such information. For example, until specifically questioned about their psychiatric history, the patient described in the illustrative case (Box 2) did not report a history of severe depression, suicide attempt and prolonged psychiatric hospitalization 8 months prior to presentation with hyperprolactinemia. At the time of the visit, he was not taking any psychiatric medications and was not under the care of a mental health team. Given this patient’s significant psychiatric history, lack of ongoing psychiatric care, and the well-recognized adverse effects of DA therapy, including increased impulsivity, depression and psychosis [17], a DA was not initiated. Counseling on potential DA side-effects is crucial, as they may also present in individuals with no prior psychiatric history [17]. Furthermore, during the COVID-19 pandemic when there is reduced access to routine medical and mental health care, patients who develop symptoms of severe depression may not have ready access to mental health services, or may not seek care. Therefore, it is particularly important to make patients aware of these potential side effects and the critical importance of reporting them. In the small number of patients for whom medical therapy is not possible and where surveillance is not appropriate (e.g., macroprolactinoma with visual loss) the risks and benefits of surgical intervention will need to be carefully weighed. Cushing’s disease Left untreated, CD has significant morbidity and mortality, and delays in diagnosis (from a few months to even years) are common. Clinical presentation is also very variable with some patients having subtle symptoms while others present with more striking/classical features. Severe hypercortisolemia induces immunosuppression, which may place patients with untreated CD at particular risk from COVID-19. New patients referred for endocrinology evaluation with clinical suspicion of Cushing’s Diagnosis Screening for, and confirmation of Cushing’s syndrome (CS) and, furthermore, localization for CD is laborious and requires serial visits and testing procedures [18, 19]. If initial laboratory abnormalities are consistent with hypercortisolemia, a VV should allow for an estimate of the severity of clinical presentation and facilitate planning for further testing and treatment. Careful questioning for potential causes of exogenous CS (including, but not limited to, history of high-dose oral corticosteroids, intraarticular injections or topical preparations) is an important first step. Subsequently, establishing the likelihood and pretest probability of CS is more important than ever now, when testing may be delayed. While presentation varies significantly between patients, some features, although not all highly sensitive, are more specific, e.g. easy bruising, facial plethora, large wide > 1 cm violaceous striae, proximal weakness and hypokalemia. Diagnosis of CS is often challenging even under normal circumstances, however, a diagnosis by VV is more nuanced and difficult. Conversely, if a patient has a high likelihood of CS, we recommend limited laboratory evaluation (urinary free cortisol (UFC), adrenocorticotropic hormone (ACTH), liver panel, basic metabolic panel), preferably at a smaller local laboratory rather than a Pituitary Center, to reduce viral risk exposure. Salivary cortisol samples could represent a hazard for laboratory staff and they are prohibited in some countries [18, 19]. In the US, laboratories have continued to process salivary cortisol samples and salivary cortisol has higher sensitivity compared with UFC and has the convenience of mailing multiple specimens at a time, without travel [18, 19]. Though usually we strongly recommend sequential laboratory testing under normal circumstances, limiting trips to a laboratory is preferred during COVID-19. If preliminary assessment confirms ACTH-dependent CS [18, 19] and no visual symptoms are reported, imaging may be delayed. However, in the presence of any visual symptoms, and recognizing the challenges of undertaking a formal visual field assessment, proceeding directly with MRI or CT (shorter exam time and easier machine access) imaging, will allow confirmation or exclusion of a large pituitary adenoma compressing the optic chiasm. If the latter is confirmed, the patient will need to be evaluated by a neurosurgeon. In contrast, a small pituitary adenoma may not be visible on CT, but in such cases MRI may be deferred for a few months until COVID-19 restrictions limiting access to care are lifted. Another VV will help to decide, in conjunction with patient’s preference, the best next step, which in cases of more severe clinical Cushing’s, and in the absence of a large pituitary adenoma, would be medical therapy. The magnitude of 24 h-UFC elevation could also represent a criterion for primary therapy, since higher values have been associated with increased risk of infection. In parallel, it is also important to address comorbidities including diabetes mellitus, hypertension and hyperlipidemia. In light of the increased risk of venous thromboembolism, in discussion with primary care providers, plans for regular mobilization/exercise as permitted (including at home when orders to stay in are in place) and/or prophylactic low weight molecular heparin should be considered. Management First line medical therapy options vary, depending on country availability, regulatory approval and patient comorbidities. Ideally, an oral medication, which is easier to administer is preferred; options include ketoconazole, osilodrostat or metyrapone [20, 21]. Cabergoline therapy, which has lesser efficacy [20, 21] compared with adrenal steroidogenesis inhibitors, can be also attempted in very mild cases. The initial laboratory profile should be reviewed to exclude significant abnormalities of renal and/or liver function prior to commencing treatment. Starting doses of all medications should be the lowest possible to avoid adrenal insufficiency (AI) and up titration should be slow, with VVs weekly if possible. All patients with CS on any type of medical therapy should have prescribed glucocorticoids (GC) both in oral and injectable forms available at home and information regarding AI should be provided during a VV when starting therapy for CS. Down titration of other medications for diabetes and hypertension may also be needed over time. Pasireotide (both subcutaneous and LAR preparations) would be a second line option, reflecting higher risk of significant hyperglycemia that would require treatment [22]. If the clinical features of CS are mild and longstanding, with no acute deterioration, another possibility is to aggressively treat the associated comorbidities for a few months; depending on local circumstances, this may actually be less risky for the patient by avoiding the risk of AI/crisis and the need for an emergency department (ED) visit and/or admission. For patients with Cushing’s disease with endocrinology chronic care Patients in remission after surgery with adrenal insufficiency on glucocorticoid replacement These patients are likely to remain at slightly higher risk of COVID-19 infection due to immunosuppression from previous hypercortisolemia. Furthermore, GC doses should be adjusted to prevent adrenal crisis and visits to an ED. Lower GC daily doses (10–15 mg hydrocortisone/day) are now frequently used for replacement and virtual and/or phone visits are encouraged to evaluate an appropriate regimen and sufficient supplies of medication and injectable GC (at home) should be prescribed. Patients with potential symptoms of under replacement may require an increase in daily dose, while balancing any risk of GC over replacement and possible consequent immunosuppression. Patients in non-remission treated with medical therapy (dependent on country availability) Doses may need to be adjusted to reduce the risk of AI/crisis and reduce the need for serial laboratory work. Monthly or bimonthly VVs are appropriate for clinical evaluation and up titration should be slower than usual. Patients with CD on medical therapy need to have at home prescriptions for oral and injectable GC and instruction on AI surveillance. Patients should also be advised, that if they develop a fever, to stop Cushing’s medication for few days; if they develop AI symptoms, GC administration will be required. In some countries, block and replace regimens are also employed to avoid risk of AI. Of note, for mifepristone, a glucocorticoid receptor (GR) antagonist, patients will require much higher doses of GC to reverse the blockade (1 mg of dexamethasone approximately per 400 mg of mifepristone) and for several days, as drug metabolites also have GR antagonist effects. Furthermore, for all patients who have made dose changes or discontinued medications for Cushing’s, it is essential to follow very closely and consider adjustments in the doses of concomitant medications, especially insulin, other antidiabetic and antihypertensive medications, and potassium supplements. If patients have history of radiotherapy and are still on medications for CD, a VV every few months should be performed to determine if anti-Cushing’s treatment can be slowly down-titrated (to avoid AI). A morning serum cortisol would be ideal to rule out AI off medications, however, if laboratory testing cannot be undertaken safely, clinical evaluation by serial VVs can be helpful. While head-to-head data will never be available, in COVID-19 hotspots, given the higher risk of infection with laboratory testing or face to face visits, mild hypercortisolemia might be “better” than adrenal crisis, especially in the short term! Patients with CD have increased rates of depression, anxiety and can have decreased quality of life (QoL) even when in long-term remission, thus in the challenging circumstances of the current pandemic it is it even more important to focus on psychological evaluation during virtual endocrinology visits, with referral to virtual counseling as needed. From https://link.springer.com/article/10.1007/s11102-020-01059-7?utm_source=newsletter_370
  15. 1 point
    Hi Amanda, Based on what you posted, this is a slam dunk. If they don't diagnose you quickly you should go elsewhere. The lit recommends removing anything over 4 cm. You actually have convincing biochemical evidence with a rather high UFC and concurrent low ACTH (<10 pg/mL). I'm assuming you're using Quest for the UFC since he said it's not 2x high. Most people don't get to 2x on LC/MS-MS with mild/adrenal Cushing's. Let us know the dex results. The cutoff is 1.8 ug/dL.
  16. 1 point
    Hi everybody! I am Andy Goacher (John Goacher's eldest son) The article itself is particularly badly written if I'm honest, so I would like to share my own account.. Dad was a kind, gentle man, incredibly gifted, logical, technical. A senior reliability engineer working rocket and missile systems... "Basically our father is a rocket scientist" me and my brother would joke.. He had been gaining weight and suffering health problems for some time before he got really ill. He ballooned a bit in his final years, but facially and in the abdomen as well as a fatty hump between the shoulders on his back. His legs and arms were always fairly normal looking.. He had a growing increasingly cantankerous in his later years, but nothing that seemed a major psychiatric cause for concern. One day he left for work, as normal, got to work, and collapsed that day while there. He couldn't be woken up by the paramedics, and was hospitalised. When he eventually woke up, it was as if he had suffered some kind of mental breakdown. He was saying strange things, and appeared to be suffering bouts of amnesia as well as paranoia. He escaped his ward I think several times, and at one point failed to recognise my mum. I was away finishing uni at the time, so most of this is how I remember hearing it.. He came home after a short stay in hospital and appeared to make good progress with doctors still thinking it was a mental breakdown or psychotic episode.. Then the truly terrifying bit... As if a very slow second wave hit, he began to show signs that something was wrong. His driving became increasingly scary (yes he was deemed safe to drive) his focus was off, his logic started to go, he began to buy things impulsively, and randomly, then buy the same thing again. He was slowly going baserk. Even when I visited, I knew something was seriously wrong and I was scared of him! We were all scared of him and what he might do next! It was like living with maniac, and he was completely oblivious! He could 100% not see anything wrong with himself, he couldn't even wire a plug properly (and he was a trained electronics engineer for goodness sake! As his wierd behaviour got slowly worse, it became apparent that certain triggers (such as my mum getting cross and saying something he didn't want to hear) would send him into a trance like state. I can only described this as altered consciousness. He would slump or fall, eyes closed, body limp. You could pinch him and get no response, lift his eyelids, slap him on the cheeks, but with no response. This would go on for minutes not seconds until you went to walk away saying something abrupt like 'OKAY WE ARE LEAVING NOW!' Just like that he would snap out of it. He would claim he was never out of it at all, and heard every word (even recounting what you had said during the episode) Of course every time the doctors visited this wouldn't happen at first, but eventually it did, and they were absolutely gobsmacked! He was then sectioned again and taken into psychiatric care where his behaviour continued to get more and more bizarre. He would escape from the Premesis and somehow manage to wander to the shops. We once had to drive up to help search for him.. we found him, with bags full of cracked eggs and other strange items. He grew a beard, began smoking, and continued to have frequent bouts of strange altered consciousness. The doctors were dumbfounded, which is why WE began frantically searching the internet for something, anything like it. We put all his previous symptoms in, and cushings/pituitary disorders kept coming up. The breakthrough was when my mother found a illustrations of a human with Cushing's disease along with a side and front profile of a woman with a severe case. Our mouths fell open... The diagrams were as if someone had sketched my father, and the woman looked like his identical twin! We took this to show the doctors, and that lead to his tests, scans and eventual diagnosis. In the end, with the right medication, we got dad back for a few months before the operation, albeit by now in poor physical health. By the time he went for his op, he could barely walk and I had to push him around in a wheelchair when I visited. He was just too weak to survive the op, and deteriorated afterwards. He died of massive nasal bleed from a major artery rupture. Tragically, the post op test results showed signs of his pituitary hormone levels returning to normal, but it just wasn't meant to be. My dad's demise was just so incredibly strange (even by Cushing's disease standards) with so many questions left unanswered, and perhaps there was something else at play other than just the Cushing's?? We'll never know, and we just try as family to go on remembering him as the brilliant and gifted man he was when he was well. I have typed my personal account up on Father's Day week in the hopes that it may help someone else out there one day.
  17. 1 point
    https://doi.org/10.1016/S2213-8587(20)30215-1 Over the past few months, COVID-19, the pandemic disease caused by severe acute respiratory syndrome coronavirus 2, has been associated with a high rate of infection and lethality, especially in patients with comorbidities such as obesity, hypertension, diabetes, and immunodeficiency syndromes.1 These cardiometabolic and immune impairments are common comorbidities of Cushing's syndrome, a condition characterised by excessive exposure to endogenous glucocorticoids. In patients with Cushing's syndrome, the increased cardiovascular risk factors, amplified by the increased thromboembolic risk, and the increased susceptibility to severe infections, are the two leading causes of death.2 In healthy individuals in the early phase of infection, at the physiological level, glucocorticoids exert immunoenhancing effects, priming danger sensor and cytokine receptor expression, thereby sensitising the immune system to external agents.3 However, over time and with sustained high concentrations, the principal effects of glucocorticoids are to produce profound immunosuppression, with depression of innate and adaptive immune responses. Therefore, chronic excessive glucocorticoids might hamper the initial response to external agents and the consequent activation of adaptive responses. Subsequently, a decrease in the number of B-lymphocytes and T-lymphocytes, as well as a reduction in T-helper cell activation might favour opportunistic and intracellular infection. As a result, an increased risk of infection is seen, with an estimated prevalence of 21–51% in patients with Cushing's syndrome.4 Therefore, despite the absence of data on the effects of COVID-19 in patients with Cushing's syndrome, one can make observations related to the compromised immune state in patients with Cushing's syndrome and provide expert advice for patients with a current or past history of Cushing's syndrome. Fever is one of the hallmarks of severe infections and is present in up to around 90% of patients with COVID-19, in addition to cough and dyspnoea.1 However, in active Cushing's syndrome, the low-grade chronic inflammation and the poor immune response might limit febrile response in the early phase of infection.2 Conversely, different symptoms might be enhanced in patients with Cushing's syndrome; for instance, dyspnoea might occur because of a combination of cardiac insufficiency or weakness of respiratory muscles.2 Therefore, during active Cushing's syndrome, physicians should seek different signs and symptoms when suspecting COVID-19, such as cough, together with dysgeusia, anosmia, and diarrhoea, and should be suspicious of any change in health status of their patients with Cushing's syndrome, rather than relying on fever and dyspnoea as typical features. The clinical course of COVID-19 might also be difficult to predict in patients with active Cushing's syndrome. Generally, patients with COVID-19 and a history of obesity, hypertension, or diabetes have a more severe course, leading to increased morbidity and mortality.1 Because these conditions are observed in most patients with active Cushing's syndrome,2 these patients might be at an increased risk of severe course, with progression to acute respiratory distress syndrome (ARDS), when developing COVID-19. However, a key element in the development of ARDS during COVID-19 is the exaggerated cellular response induced by the cytokine increase, leading to massive alveolar–capillary wall damage and a decline in gas exchange.5 Because patients with Cushing's syndrome might not mount a normal cytokine response,4 these patients might parodoxically be less prone to develop severe ARDS with COVID-19. Moreover, Cushing's syndrome and severe COVID-19 are associated with hypercoagulability, such that patients with active Cushing's syndrome might present an increased risk of thromboembolism with COVID-19. Consequently, because low molecular weight heparin seems to be associated with lower mortality and disease severity in patients with COVID-19,6 and because anticoagulation is also recommended in specific conditions in patients with active Cushing's syndrome,7 this treatment is strongly advised in hospitalised patients with Cushing's syndrome who have COVID-19. Furthermore, patients with active Cushing's syndrome are at increased risk of prolonged duration of viral infections, as well as opportunistic infections, particularly atypical bacterial and invasive fungal infections, leading to sepsis and an increased mortality risk,2 and COVID-19 patients are also at increased risk of secondary bacterial or fungal infections during hospitalisation.1 Therefore, in cases of COVID-19 during active Cushing's syndrome, prolonged antiviral treatment and empirical prophylaxis with broad-spectrum antibiotics1, 4 should be considered, especially for hospitalised patients (panel). Panel Risk factors and clinical suggestions for patients with Cushing's syndrome who have COVID-19 Reduction of febrile response and enhancement of dyspnoea Rely on different symptoms and signs suggestive of COVID-19, such as cough, dysgeusia, anosmia, and diarrhoea. Prolonged duration of viral infections and susceptibility to superimposed bacterial and fungal infections Consider prolonged antiviral and broad-spectrum antibiotic treatment. Impairment of glucose metabolism (negative prognostic factor) Optimise glycaemic control and select cortisol-lowering drugs that improve glucose metabolism. Hypertension (negative prognostic factor) Optimise blood pressure control and select cortisol-lowering drugs that improve blood pressure. Thrombosis diathesis (negative prognostic factor) Start antithrombotic prophylaxis, preferably with low-molecular-weight heparin treatment. Surgery represents the first-line treatment for all causes of Cushing's syndrome,8, 9 but during the pandemic a delay might be appropriate to reduce the hospital-associated risk of COVID-19, any post-surgical immunodepression, and thromboembolic risks.10 Because immunosuppression and thromboembolic diathesis are common Cushing's syndrome features,2, 4 during the COVID-19 pandemic, cortisol-lowering medical therapy, including the oral drugs ketoconazole, metyrapone, and the novel osilodrostat, which are usually effective within hours or days, or the parenteral drug etomidate when immediate cortisol control is required, should be temporarily used.9 Nevertheless, an expeditious definitive diagnosis and proper surgical resolution of hypercortisolism should be ensured in patients with malignant forms of Cushing's syndrome, not only to avoid disease progression risk but also for rapidly ameliorating hypercoagulability and immunospuppression;9 however, if diagnostic procedures cannot be easily secured or surgery cannot be done for limitations of hospital resources due to the pandemic, medical therapy should be preferred. Concomitantly, the optimisation of medical treatment for pre-existing comorbidities as well as the choice of cortisol-lowering drugs with potentially positive effects on obesity, hypertension, or diabates are crucial to improve the eventual clinical course of COVID-19. Once patients with Cushing's syndrome are in remission, the risk of infection is substantially decreased, but the comorbidities related to excess glucocorticoids might persist, including obesity, hypertension, and diabetes, together with thromboembolic diathesis.2 Because these are features associated with an increased death risk in patients with COVID-19,1 patients with Cushing's syndrome in remission should be considered a high-risk population and consequently adopt adequate self-protection strategies to minimise contagion risk. In conclusion, COVID-19 might have specific clinical presentation, clinical course, and clinical complications in patients who also have Cushing's syndrome during the active hypercortisolaemic phase, and therefore careful monitoring and specific consideration should be given to this special, susceptible population. Moreover, the use of medical therapy as a bridge treatment while waiting for the pandemic to abate should be considered. RP reports grants and personal fees from Novartis, Strongbridge, HRA Pharma, Ipsen, Shire, and Pfizer; grants from Corcept Therapeutics and IBSA Farmaceutici; and personal fees from Ferring and Italfarmaco. AMI reports non-financial support from Takeda and Ipsen; grants and non-financial support from Shire, Pfizer, and Corcept Therapeutics. BMKB reports grants from Novartis, Strongbridge, and Millendo; and personal fees from Novartis and Strongbridge. AC reports grants and personal fees from Novartis, Ipsen, Shire, and Pfizer; personal fees from Italfarmaco; and grants from Lilly, Merck, and Novo Nordisk. All other authors declare no competing interests. References 1 P Kakodkar, N Kaka, MN Baig A comprehensive literature review on the clinical presentation, and management of the pandemic coronavirus disease 2019 (COVID-19) Cureus, 12 (2020), Article e7560 View Record in ScopusGoogle Scholar 2 R Pivonello, AM Isidori, MC De Martino, J Newell-Price, BMK Biller, A Colao Complications of Cushing's syndrome: state of the art Lancet Diabetes Endocrinol, 4 (2016), pp. 611-629 ArticleDownload PDFView Record in ScopusGoogle Scholar 3 DW Cain, JA Cidlowski Immune regulation by glucocorticoids Nat Rev Immunol, 17 (2017), pp. 233-247 CrossRefView Record in ScopusGoogle Scholar 4 V Hasenmajer, E Sbardella, F Sciarra, M Minnetti, AM Isidori, MA Venneri The immune system in Cushing's syndrome Trends Endocrinol Metab (2020) published online May 6, 2020. DOI:10.1016/j.tem.2020.04.004 Google Scholar 5 Q Ye, B Wang, J Mao The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19 J Infect, 80 (2020), pp. 607-613 ArticleDownload PDFView Record in ScopusGoogle Scholar 6 N Tang, H Bai, X Chen, J Gong, D Li, Z Sun Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy J Thromb Haemost, 18 (2020), pp. 1094-1099 CrossRefView Record in ScopusGoogle Scholar 7 AM Isidori, M Minnetti, E Sbardella, C Graziadio, AB Grossman Mechanisms in endocrinology: the spectrum of haemostatic abnormalities in glucocorticoid excess and defect Eur J Endocrinol, 173 (2015), pp. R101-R113 View Record in ScopusGoogle Scholar 8 LK Nieman, BM Biller, JW Findling, et al.Treatment of Cushing's syndrome: an endocrine society clinical practice guideline J Clin Endocrinol Metab, 100 (2015), pp. 2807-2831 CrossRefView Record in ScopusGoogle Scholar 9 R Pivonello, M De Leo, A Cozzolino, A Colao The treatment of Cushing's disease Endocr Rev, 36 (2015), pp. 385-486 CrossRefView Record in ScopusGoogle Scholar 10 J Newell-Price, L Nieman, M Reincke, A Tabarin Endocrinology in the time of COVID-19: management of Cushing's syndrome Eur J Endocrinol (2020) published online April 1. DOI:10.1530/EJE-20-0352 Google Scholar View Abstract From https://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30215-1/fulltext
  18. 1 point
    J Clin Endocrinol Metab . 2003 Apr;88(4):1554-8. doi: 10.1210/jc.2002-021518. Francesca Pecori Giraldi 1, Mirella Moro, Francesco Cavagnini, Study Group on the Hypothalamo-Pituitary-Adrenal Axis of the Italian Society of Endocrinology Affiliations PMID: 12679438 DOI: 10.1210/jc.2002-021518 Abstract Cushing's disease (CD) presents a marked female preponderance, but whether this skewed gender distribution has any relevance to the presentation and outcome of CD is not known. The aim of the present study was the comparison of clinical features, biochemical indices of hypercortisolism, and surgical outcome among male and female patients with CD. The study population comprised 280 patients with CD (233 females, 47 males) collected by the Italian multicentre study. Epidemiological data, frequency of clinical signs and symptoms, urinary free cortisol (UFC), plasma ACTH and cortisol levels, responses to dynamic testing, and surgical outcome were compared in female and male patients. Male patients with CD presented at a younger age, compared with females (30.5 +/- 1.93 vs. 37.1 +/- 0.86 yr, P < 0.01), with higher UFC and ACTH levels (434.1 +/- 51.96 vs. 342.1 +/- 21.01% upper limit of the normal range for UFC, P < 0.05; 163.9 +/- 22.92 vs. 117.7 +/- 9.59% upper limit of the normal range for ACTH, P < 0.05). No difference in ACTH and cortisol responses to CRH, gradient at inferior petrosal sinus sampling, and cortisol inhibition after low-dose dexamethasone was recorded between sexes. In contrast, the sensitivity of the high-dose dexamethasone test was significantly lower in male than in female patients. Of particular interest, symptoms indicative of hypercatabolic state were more frequent in male patients; indeed, males presented a higher prevalence of osteoporosis, muscle wasting, striae, and nephrolitiasis. Conversely, no symptom was more frequent in female patients with CD. Patients with myopathy, hypokalemia, and purple striae presented significantly higher UFC levels, compared with patients without these symptoms. Lastly, in male patients, pituitary imaging was more frequently negative and immediate and late surgical outcome less favorable. In conclusion, CD appeared at a younger age and with a more severe clinical presentation in males, compared with females, together with more pronounced elevation of cortisol and ACTH levels. Furthermore, high-dose dexamethasone suppression test and pituitary imaging were less reliable in detecting the adenoma in male patients, further burdening the differential diagnosis with ectopic ACTH secretion. Lastly, the postsurgical course of the disease carried a worse prognosis in males. Altogether, these findings depict a different pattern for CD in males and females. From https://pubmed.ncbi.nlm.nih.gov/12679438/
  19. 1 point
    Braun LT, Fazel J, Zopp S Journal of Bone and Mineral Research | May 22, 2020 This study was attempted to assess bone mineral density and fracture rates in 89 patients with confirmed Cushing's syndrome at the time of diagnosis and 2 years after successful tumor resection. Researchers ascertained five bone turnover markers at the time of diagnosis, 1 and 2 years postoperatively. Via chemiluminescent immunoassays, they assessed bone turnover markers osteocalcin, intact procollagen‐IN‐propeptide, alkaline bone phosphatase, CrossLaps, and TrAcP 5b in plasma or serum. For comparison, they studied 71 gender‐, age‐, and BMI‐matched patients in whom Cushing's syndrome had been excluded. The outcomes of this research exhibit that the phase immediately after surgical remission from endogenous CS is defined by a high rate of bone turnover resulting in a striking net increase in bone mineral density in the majority of patients. Read the full article on Journal of Bone and Mineral Research.
  20. 1 point
    Those are all definitely symptoms of Cushing's...and excess cortisol. I think I had every one of them while I was being diagnosed. Have you taken steroids, especially often? They can cause these symptoms. Definitely mention these symptoms to your doctor. Please keep us posted.
  21. 1 point
    Presented by Jamie J. Van Gompel, M.D., B.S., Professor in Neurosurgery and Otolaryngology specializing in endoscopic/open skull base focusing on Pituitary tumors as well as Epilepsy at the Mayo Clinic in Rochester, Minnesota, USA and Garret W. Choby, M.D., a fellowship-trained rhinologist and endoscopic skull base surgeon practicing at the Mayo Clinic. Objectives: - Understand the additional considerations that are key to performing endonasal surgery during the COVID pandemic - Identify the practice changes that are allowing pituitary surgery to proceed safely - Characterize the nasal cavity and nasopharynx as a reservoir for the coronavirus - Identify the risk of undergoing pituitary surgery during the Covid -19 pandemic Register Now! After registering you will receive a confirmation email containing information about joining the Webinar. Date: Monday, May 11, 2020 Time: 4:00 PM Pacific Daylight Time - 5:15 PM Pacific Daylight Time
  22. 1 point
    Presented by Nelson M. Oyesiku, MD, PhD, FACS Professor of Neurosurgery and Medicine Vice-Chairman, Neurosurgery Residency Program Director Emory University School of Medicine Register Now! After registering you will receive a confirmation email containing information about joining the Webinar. Date: Sunday, May 10, 2020 Time: 11:00 AM Pacific Daylight Time to 12:15 PM Pacific Daylight Time/ 2:00 PM - 3:15 PM Eastern Daylight Time
  23. 1 point
    Dr. Friedman will discuss topics including: Who should get an adrenalectomy? How do you optimally replace adrenal hormones? What laboratory tests are needed to monitor replacement? When and how do you stress dose? What about subcut cortisol versus cortisol pumps? Patient Melissa will lead a Q and A Sunday • May 17 • 6 PM PST Click here on start your meeting or https://axisconciergemeetings.webex.com/axisconciergemeetings/j.php?MTID=mb896b9ec88bc4e1163cf4194c55b248f OR Join by phone: (855) 797-9485 Meeting Number (Access Code): 802 841 537 Your phone/computer will be muted on entry. Slides will be available on the day of the talk here There will be plenty of time for questions using the chat button. Meeting Password: addison For more information, email us at mail@goodhormonehealth.com
  24. 1 point
    Dr. Friedman will discuss topics including: Who should get an adrenalectomy? How do you optimally replace adrenal hormones? What laboratory tests are needed to monitor replacement? When and how do you stress dose? What about subcut cortisol versus cortisol pumps? Patient Melissa will lead a Q and A Sunday • May 17 • 6 PM PST Click here on start your meeting or https://axisconciergemeetings.webex.com/axisconciergemeetings/j.php?MTID=mb896b9ec88bc4e1163cf4194c55b248f OR Join by phone: (855) 797-9485 Meeting Number (Access Code): 802 841 537 Your phone/computer will be muted on entry. Slides will be available on the day of the talk here There will be plenty of time for questions using the chat button. Meeting Password: addison For more information, email us at mail@goodhormonehealth.com
  25. 1 point
    Has anyone suggested Cyclic Cushing's to you? That's where tests cycle normal/abnormal but no one knows how long a person's cycle could be. That's even harder to diagnose due to the constant fluctuations and some endos don't believe in it, although I don't understand how a doctor can't believe in a disease. Here are the bios of some Cushies with Cyclic Cushing's: https://cushingsbios.com/category/cyclic/
  26. 1 point
    I had a lot of unexplained bruising. Around New Year's Day, I started bleeding by my ankle. My doctor wasn't available so my husband used a magic marker to draw a circle around the area of the bleed, then made more circles as it spread out. The size of the area with the rings are what alerted my GP to send me to the hematologist for more testing. Previously, I had told him, my gynecologist, a (new during Cushing's) foot doctor, a neurologist that I was sure I had Cushing's - all said it was too rare. I couldn't have it.
  27. 1 point
    Endocrinologists have underlined the importance that physicians consider "a stress dose" of glucocorticoids in the event of severe COVID-19 infection in endocrine, and other, patients on long-term steroids. People taking corticosteroids on a routine basis for a variety of underlying inflammatory conditions, such as asthma, allergies, and arthritis, are at elevated risk of being infected with, and adversely affected by, COVID-19. This also applies to a rarer group of patients with adrenal insufficiency and uncontrolled Cushing syndrome, as well as secondary adrenal insufficiency occurring in hypopituitarism, who also rely on glucocorticoids for day-to-day living. In the event of COVID-19, all of these individuals may be unable to mount a normal stress response, and "in the case of adrenal suppression...such patients may run into severe difficulties, particularly if on intensive care units," warns Paul Stewart, MD, University of Leeds, UK, and editor-in-chief of the Journal of Clinical Endocrinology & Metabolism (JCEM). As such, it is vitally important to recognize that "Injectable supplemental glucocorticoid therapy in this setting can reverse the risk of potentially fatal adrenal failure and should be considered in every case," Stewart and colleagues emphasize in a newly published editorial in JCEM. They note this advice must be considered alongside World Health Organization (WHO) guidance against prescribing therapeutic glucocorticoids to treat complications of COVID-19, based on prior experience in patients with acute respiratory distress syndrome, as well as those affected by severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The key difference here is not to use pharmacologic doses of glucocorticoids as treatment for COVID-19 (where they have no effect), but rather to prevent death from adrenal failure by using "stress" doses of replacement glucocorticoid, Stewart explained to Medscape Medical News. "No patient with a history of prior exposure to chronic glucocorticoid therapy (> 3 months)...should die without consideration" for a stress dose of replacement glucocorticoid therapy. "The intent here is to ensure that no patient with a history of prior exposure to chronic glucocorticoid therapy (> 3 months) by whatever route should die without consideration for parenteral glucocorticoid therapy," the editorialists write. He advises using physiological stress doses of hydrocortisone (50-100 mg intravenously tid). Specific Advice for Adrenal Insufficiency: Follow Sick Day Rules A separate statement by the American Association of Clinical Endocrinologists (AACE) also emphasizes that it is particularly important for patients with adrenal insufficiency to follow advice from the Centers for Disease Control and Prevention (CDC) or similar guidance on preventing COVID-19 infection, including social distancing and frequent hand washing. Such patients should continue to take medications as prescribed and ensure they have appropriate supplies of oral and injectable steroids, ideally for 90 days, AACE advises. And if there is a shortage of hydrocortisone, the statement advises patients ask a pharmacist or physician about replacement hydrocortisone with different doses that might be available. Stewart agrees that patients with adrenal insufficiency need to be hypervigilant, but says that "if they do become ill, for the most part they are well counseled to respond appropriately to intercurrent infections." Nevertheless, it is "invaluable to reiterate 'sick day rules'" for suspected COVID-19 infection. "Any patient who develops a dry continuous cough and fever should immediately double their daily oral glucocorticoid dose and continue on this regimen until the fever has subsided." If a patient still deteriorates on this regimen, develops diarrhea or vomiting, or is unable to take oral glucocorticoids for other reasons, they should contact their physicians or seek urgent medical care to receive parenteral treatment with a glucocorticoid. J Clin Endocrinol Metab. Published online March 31, 2020. Position statement For more diabetes and endocrinology news, follow us on Twitter and Facebook. From https://www.medscape.com/viewarticle/928072?nlid=134869_3901&src=wnl_newsalrt_200404_MSCPEDIT&uac=295048SY&impID=2335560&faf=1&fbclid=IwAR1zZe6fqDS3tKuHUYoFpbvBMkQYJ4JN59RzC93xdzVcGGkJIz5bnmmE4LY
  28. 1 point
    Along with all of you, NADF is monitoring this outbreak by paying close attention to CDC and FDA updates. We have also asked our Medical Advisor to help answer your important questions as they come up. We asked Medical Director Paul Margulies, MD, FACE, FACP to help us with this question: Question: Does Adrenal Insufficiency cause us to have a weakened immune system and therefore make us more susceptible? Response: Individuals with adrenal insufficiency on replacement doses of glucocorticoids do not have a suppressed immune system. The autoimmune mechanism that causes Addison’s disease does not cause an immune deficiency that would make one more likely to get an infection. The problem is with the individual’s ability to deal with the stress of an infection once it develops. Those with adrenal insufficiency fall into that category. When sick with a viral infection, they can have a more serious illness, and certainly require stress dose steroids to help to respond to the illness. If someone with adrenal insufficiency contracts the coronavirus, it is more likely to lead to the need for supportive care, including hospitalization. This information from the CDC Website provides important information regarding Prevention & Treatment. You can find this information here: https://www.cdc.gov/coronavirus/2019-ncov/about/prevention-treatment.html From https://www.nadf.us/
  29. 1 point
    The Barrow Pituitary Center is dedicated to educating patients, caregivers, and loved ones by providing information which is current and non-biased. Experts at this conference will address management of the emotional and physical elements of living with pituitary disorders. We hope attendees will leave empowered to make better informed decisions about their healthcare and achieve their goals for a long and fruitful life. Saturday, March 14, 2020 8:00 a.m. to 4:00 p.m. $30 per person To register call 1 (877) 728-5414 or visit us at https://www.barrowneuro.org/outreach/pituitary-center-patient-education-day/ For additional information contact Maggie Bobrowitz, RN, MBA at (602) 406.7585 or margaret.bobrowitz@ dignityhealth.org Agenda 7:00 am Registration & Refreshments 8:00 am Welcome Maggie Bobrowitz, RN, MBA 8:05 am 3D Anatomy of The Pituitary Gland Andrew Little, MD 8:15 am New Medicines on The Horizon Kevin Yuen, MD 9:00 am Nutrition Impact on Managing Pituitary Disorders Lee Renda, RD 9:30 am Break 9:45 am Emotional and Mental Health for Pituitary Patients and Their Families Linda Rio, MA, MFT 10:45 am Fertility in The Pituitary Patient Ketan Patel, MD 11:15 am Q & A Panel Morning Speakers 11:45 am Lunch 12:45 pm Intimacy and Other Forgotten Fun Dawn Herring, LMFT 1:30 pm Creating Your Image of Healing Debbie Harbinson, MHI, RN 2:30 pm Break 2:40 pm Breakout sessions: LMFT Men’s Group – Telepresence Room Dawn Herring, LMFT Women’s Group – Sonntag Pavilion Linda Rio, M.A, MFT Caregiver’s Group – Goldman Auditorium Debbie Harbinson, MHI, RN 3:40 pm Raffle Drawing – Exhibitor Table Bingo Game Maggie Bobrowitz, RN, MBA 3:45 pm Adjourn
  30. 1 point
    Presented by Varun Kshettry, MD Director, Advanced Endoscopic & Microscopic Neurosurgery Cleveland Clinic Lerner College of Medicine Register Now After registering you will receive a confirmation email with details about joining the webinar. Date: Tuesday, February 18, 2020 Time: 10:00 AM - 11:00 AM Pacific Standard Time, 1:00 PM - 2:00 PM Eastern Standard Time Learning Objectives: Discuss patient expectations for pituitary surgery and recovery Discuss best practices to minimize risk of complications What questions to ask your medical providers Presenter Bio Dr. Varun R. Kshettry, a neurosurgeon specializing in skull base and pituitary disorders at the Cleveland Clinic. He is also the director of the Advanced Endoscopic & Microscopic Neurosurgery Laboratory. He is an assistant professor of neurosurgery at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. Dr. Kshettry received his BA in philosophy at the University of Pennsylvania. He earned his medical degree from Northwestern University. He completed his residency training at the Cleveland Clinic, during which he performed a research fellowship in skull base & microsurgical anatomy at Ohio State University. He then performed a clinical fellowship in minimally invasive cranial base & pituitary surgery at Thomas Jefferson University under Dr. James Evans. Dr. Kshettry has authored more than 100 peer-reviewed publications and book chapters and is an editor for a book entitled Endoscopic and Keyhole Cranial Base Surgery. He serves as an editor or reviewer for multiple neurosurgical journals. He serves on the Value-Based Healthcare Committee for the North American Skull Base Society. He serves as faculty director for the Cleveland Clinic Pituitary Tumor Board and is an investigator in several multi-center pituitary clinical trials. Dr. Kshettry collaborates closely with pituitary endocrinologists, neuro-ophthalmologists, otolaryngologists, pituitary pathologists, and radiation oncologists for multi-disciplinary care for patients with pituitary diseases.
  31. 1 point
    Lacroix A, et al. Pituitary. 2019;doi:10.1007/s11102-019-01021-2. January 7, 2020 Andre Lacroix Most adults with persistent or recurrent Cushing’s disease treated with the somatostatin analogue pasireotide experienced a measurable decrease in MRI-detectable pituitary tumor volume at 12 months, according to findings from a post hoc analysis of a randomized controlled trial. “Pasireotide injected twice daily during up to 12 months to control cortisol excess in patients with residual or persistent Cushing's disease was found to reduce the size of pituitary tumors in a high proportion of the 53 patients in which residual tumor was still visible at initiation of this medical therapy,” Andre Lacroix, MD, FCAHS, professor of medicine at the University of Montreal Teaching Hospital in Montreal, Canada, told Healio. “Pituitary tumors causing Cushing's syndrome which cannot be removed completely by surgery have the capacity to grow in time, and a medical therapy that can reduce tumor growth in addition to control excess cortisol production should be advantageous for the patients.” Lacroix and colleagues analyzed data from 53 adults with persistent or recurrent Cushing’s disease, or those with newly diagnosed Cushing’s disease who were not surgical candidates, who had measurable tumor volume data (78% women). Researchers randomly assigned participants to 600 g or 900 g subcutaneous pasireotide (Signifor LAR, Novartis) twice daily. Tumor volume was assessed independently at 6 and 12 months by two masked radiologists and compared with baseline value and urinary free cortisol response. Most adults with persistent or recurrent Cushing’s disease treated with the somatostatin analogue pasireotide experienced a measurable decrease in MRI-detectable pituitary tumor volume at 12 months. Source: Shutterstock Researchers found that reductions in tumor volume were both dose and time dependent. Tumor volume reduction was more frequently observed at month 6 in the 900 g group (75%) than in the 600 g group (44%). Similarly, at month 12 (n = 32), tumor volume reduction was observed more frequently in the 900 g group (89%) than in the 600 g group (50%). Results were independent of urinary free cortisol levels. The researchers did not observe a relationship between baseline tumor size and change in tumor size. “Taken together, the results of the current analysis demonstrate that treatment with pasireotide, a pituitary-directed medical therapy that targets somatostatin receptors, can frequently lead to radiologically measurable reductions in pituitary tumor volume in patients with Cushing’s disease,” the researchers wrote. “Tumor volume reduction is especially relevant in patients with larger microadenomas, suggesting that pasireotide is an attractive option for these patients, especially in cases in which patients cannot undergo transsphenoidal surgery or do not respond to surgical management of disease.” – by Regina Schaffer For more information: Andre Lacroix, MD, FCAHS, can be reached at the University of Montreal Teaching Hospital, Endocrine Division, 3840 Saint-Urbain, Montreal, H2W 1T8, Canada; email: andre.lacroix@umontrael.ca. Disclosures: Novartis supported this study and provided writing support. Lacroix reports he has received funding from Novartis Pharmaceuticals to conduct clinical studies with pasireotide and osilodrostat in Cushing’s disease and served as a consultant, advisory board member or speaker for EMD Serono, Ipsen and Novartis. Please see the study for all other authors’ relevant financial disclosures. From https://www.healio.com/endocrinology/neuroendocrinology/news/online/%7B8e4d31fb-d61a-4cf8-b4c4-7d0bdf012fbd%7D/pasireotide-reduces-pituitary-tumor-volume-in-cushings-disease
  32. 1 point
    Sethi A, et al. Clin Endocrinol. 2019;doi:10.1111/CEN.14146. January 5, 2020 Obesity is common at diagnosis of pituitary adenoma in childhood and may persist despite successful treatment, according to findings published in Clinical Endocrinology. “The importance of childhood and adolescent obesity on noncommunicable disease in adult life is well recognized, and in this new cohort of patients, we report that obesity is common at presentation of pituitary adenoma in childhood and that successful treatment is not necessarily associated with weight loss,” Aashish Sethi, MD, MBBS, a pediatric endocrinologist in the department of endocrinology at Alder Hey Children’s Hospital in Liverpool, United Kingdom, and colleagues wrote. “We have reported obesity, and obesity-related morbidity in a mixed cohort of children and young adults previously, but [to] our knowledge, this is the first time this observation has been reported in a purely pediatric cohort.” In a retrospective study, Sethi and colleagues analyzed clinical and radiological data from 24 white children from Alder Hey Children’s Hospital followed for a median of 3.3 years between 2000 and 2019 (17 girls; mean age at diagnosis, 15 years). Researchers assessed treatment modality (medical, surgical or radiation therapy), pituitary hormone deficiencies and BMI, as well as results of any genetic testing. Within the cohort, 13 girls had prolactinomas (mean age, 15 years), including 10 macroadenomas between 11 mm and 35 mm in size. Children presented with menstrual disorders (91%), headache (46%), galactorrhea (46%) and obesity (38%). Nine children were treated with cabergoline alone, three also required surgery, and two were treated with the dopamine agonist cabergoline, surgery and radiotherapy. Five children had Cushing’s disease (mean age, 14 years; two girls), including one macroadenoma. Those with Cushing’s disease presented with obesity (100%), short stature (60%) and headache (40%). Transsphenoidal resection resulted in biochemical cure; however, two patients experienced relapse 3 and 6 years after surgery, respectively, requiring radiotherapy. One patient also required bilateral adrenalectomy. Six children had a nonfunctioning pituitary adenoma (mean age, 16 years; two girls), including two macroadenomas. These children presented with obesity (67%), visual field defects (50%) and headache (50%). Four required surgical resections, with two experiencing disease recurrence after surgery and requiring radiotherapy. During the most recent follow-up exam, 13 children (54.1%) had obesity, including 11 who had obesity at diagnosis. “The persistence of obesity following successful treatment, in patients with normal pituitary function, suggests that mechanisms other than pituitary hormone excess or deficiency may be important,” the researchers wrote. “It further signifies that obesity should be a part of active management in cases of pituitary adenoma from diagnosis.” – by Regina Schaffer Disclosures: The authors report no relevant financial disclosures. From https://www.healio.com/endocrinology/adrenal/news/online/%7Bde3fd83b-e8e0-4bea-a6c2-99eb896356ab%7D/long-term-obesity-persists-despite-pituitary-adenoma-treatment-in-childhood
  33. 1 point
    A diagnostic technique called bilateral inferior petrosal sinus sampling (BIPSS), which measures the levels of the adrenocorticotropic hormone (ACTH) produced by the pituitary gland, should only be used to diagnose cyclic Cushing’s syndrome patients during periods of cortisol excess, a case report shows. When it is used during a spontaneous remission period of cycling Cushing’s syndrome, this kind of sampling can lead to false results, the researchers found. The study, “A pitfall of bilateral inferior petrosal sinus sampling in cyclic Cushing’s syndrome,” was published in BMC Endocrine Disorders. Cushing’s syndrome is caused by abnormally high levels of the hormone cortisol. This is most often the result of a tumor on the pituitary gland that produces too much ACTH, which tells the adrenal glands to increase cortisol secretion. However, the disease may also occur due to adrenal tumors or tumors elsewhere in the body that also produce excess ACTH — referred to as ectopic Cushing’s syndrome. Because treatment strategies differ, doctors need to determine the root cause of the condition before deciding which treatment to choose. BIPSS can be useful in this regard. It is considered a gold standard diagnostic tool to determine whether ACTH is being produced and released by the pituitary gland or by an ectopic tumor. However, in people with cycling Cushing’s syndrome, this technique might not be foolproof. Researchers reported the case of a 43-year-old woman who had rapidly cycling Cushing’s syndrome, meaning she had periods of excess cortisol with Cushing’s syndrome symptoms — low potassium, high blood pressure, and weight gain — followed by normal cortisol levels where symptoms resolved spontaneously. In general, the length of each period can vary anywhere from a few hours to several months; in the case of this woman, they alternated relatively rapidly — over the course of weeks. After conducting a series of blood tests and physical exams, researchers suspected of Cushing’s syndrome caused by an ACTH-producing tumor. The patient eventually was diagnosed with ectopic Cushing’s disease, but a BIPSS sampling performed during a spontaneous remission period led to an initial false diagnosis of pituitary Cushing’s. As a result, the woman underwent an unnecessary exploratory pituitary surgery that revealed no tumor on the pituitary. Additional imaging studies then identified a few metastatic lesions, some of which were removed surgically, as the likely source of ACTH. However, the primary tumor still hasn’t been definitively identified. At the time of publication, the patient was still being treated for Cushing’s-related symptoms and receiving chemotherapy. There is still a question of why the initial BIPSS result was a false positive. The researchers think that the likely explanation is that BIPSS was performed during an “off phase,” when cortisol levels were comparatively low. In fact, a later BIPSS performed during a period of high cortisol levels showed no evidence of ACTH excess in the pituitary. This case “demonstrates the importance of performing diagnostic tests only during the phases of active cortisol secretion, as soon as first symptoms appear,” the researchers concluded. From https://cushingsdiseasenews.com/2020/01/02/cushings-syndrome-case-study-shows-drawback-in-bipss-method/
  34. 1 point
    until
    Wed, Jan 8, 2020, from 4:00 PM - 5:00 PM EST Presented by Paul Gardner, MD Associate Professor of Neurological Surgery Neurosurgical Director, Center for Cranial Base Surgery Executive Vice Chairman for Surgical Services University Pittsburgh Medical Center (UPMC) Learning Objectives: Upon completion of this webinar, participants should be able to: Recognize the role for surgery in treating recurrent adenomas Understand the risk and role of radiosurgery for treatment of recurrent Identify treatment indications for recurrent adenomas. Presenter Bio Paul A. Gardner, MD, is an Associate Professor in the Department of Neurological Surgery at the University of Pittsburgh School of Medicine and Neurosurgical Director of the Center for Cranial Base Surgery as well as Executive Vice Chairman for Surgical Services for the Department of Neurological Surgery at the University of Pittsburgh Medical Center (UPMC). Dr. Gardner joined the faculty of the Department of Neurological Surgery at the University of Pittsburgh School of Medicine in 2008 after completing his residency and fellowship training at the University of Pittsburgh. He completed his undergraduate studies at Florida State University, majoring in biochemistry, and received his Medical Degree from the University of Pittsburgh School of Medicine. Dr. Gardner completed a two-year fellowship in endoscopic endonasal pituitary and endoscopic and open skull base surgery at the University of Pittsburgh Medical Center. His research has focused on evaluating patient outcomes following these surgeries and more recently on molecular phenotyping of rare tumors. He is recognized internationally as a leader in the field of endoscopic endonasal surgery, a minimally invasive surgical approach to the skull base. His other surgical interests include pituitary tumors, open cranial base surgery, and vascular surgery. Register here
  35. 1 point
    Wed, Jan 8, 2020, from 4:00 PM - 5:00 PM EST Presented by Paul Gardner, MD Associate Professor of Neurological Surgery Neurosurgical Director, Center for Cranial Base Surgery Executive Vice Chairman for Surgical Services University Pittsburgh Medical Center (UPMC) Learning Objectives: Upon completion of this webinar, participants should be able to: Recognize the role for surgery in treating recurrent adenomas Understand the risk and role of radiosurgery for treatment of recurrent Identify treatment indications for recurrent adenomas. Presenter Bio Paul A. Gardner, MD, is an Associate Professor in the Department of Neurological Surgery at the University of Pittsburgh School of Medicine and Neurosurgical Director of the Center for Cranial Base Surgery as well as Executive Vice Chairman for Surgical Services for the Department of Neurological Surgery at the University of Pittsburgh Medical Center (UPMC). Dr. Gardner joined the faculty of the Department of Neurological Surgery at the University of Pittsburgh School of Medicine in 2008 after completing his residency and fellowship training at the University of Pittsburgh. He completed his undergraduate studies at Florida State University, majoring in biochemistry, and received his Medical Degree from the University of Pittsburgh School of Medicine. Dr. Gardner completed a two-year fellowship in endoscopic endonasal pituitary and endoscopic and open skull base surgery at the University of Pittsburgh Medical Center. His research has focused on evaluating patient outcomes following these surgeries and more recently on molecular phenotyping of rare tumors. He is recognized internationally as a leader in the field of endoscopic endonasal surgery, a minimally invasive surgical approach to the skull base. His other surgical interests include pituitary tumors, open cranial base surgery, and vascular surgery. Register here
  36. 1 point
    Written by Kathleen Doheny with Maria Fleseriu, MD, FACE, and Vivien Herman-Bonert, MD Cushing's disease, an uncommon but hard to treat endocrine disorder, occurs when a tumor on the pituitary gland, called an adenoma—that is almost always benign—leads to an overproduction of ACTH (adrenocorticotropic hormone), which is responsible for stimulating the release of cortisol, also known as the stress hormone. Until now, surgery to remove the non-cancerous but problematic tumor has been the only effective treatment. Still, many patients will require medication to help control their serum cortisol levels, and others cannot have surgery or would prefer to avoid it. Finally, a drug proves effective as added on or alternative to surgery in managing Cushing's disease. Photo; 123rf New Drug Offers Alternative to Surgery for Cushing's Disease Now, there is good news about long-term positive results achieved with pasireotide (Signifor)—the first medication to demonstrate effectiveness in both normalizing serum cortisol levels and either shrinking or slowing growth of tumors over the long term.1,2 These findings appear in the journal, Clinical Endocrinology, showing that patients followed for 36 months as part of an ongoing study had improved patient outcomes for Cushing’s disease.2 "What we knew before this extension study was—the drug will work in approximately half of the patients with mild Cushing's disease," says study author Maria Fleseriu, MD, FACE, director of the Northwest Pituitary Center and professor of neurological surgery and medicine in the division of endocrinology, diabetes and clinical nutrition at the Oregon Health and Sciences University School of Medicine. “Pasireotide also offers good clinical benefits," says Dr. Fleseriu who is also the president of the Pituitary Society, “which includes improvements in blood pressure, other signs and symptoms of Cushing’s symptom], and quality of life.”2 What Symptoms Are Helped by Drug for Cushing's Disease? Among the signs and symptoms of Cushing’s disease that are lessened with treatment are:3 Changes in physical appearance such as wide, purple stretch marks on the skin (eg, chest, armpits, abdomen, thighs) Rapid and unexplained weight gain A more full, rounder face Protruding abdomen from fat deposits Increased fat deposits around the neck area The accumulation of adipose tissue raises the risk of heart disease, which adds to the urgency of effective treatment. In addition, many individuals who have Cushing’s disease also complain of quality of life issues such as fatigue, depression, mood and behavioral problems, as well as poor memory.2 As good as the results appear following the longer term use of pasireotide,2 Dr. Fleseriu admits that in any extension study in which patients are asked to continue on, there are some built-in limitations, which may influence the findings. For example, patients who agree to stay on do so because they are good responders, meaning they feel better, so they’re happy to stick with the study. “Fortunately, for the patients who have responded to pasireotide initially, this is a drug that can be continued as there are no new safety signals with longer use," Dr. Fleseriu tells EndocrineWeb, "and when the response at the start is good, very few patients will lose control of their urinary free cortisol over time. That's a frequent marker used to monitor patient's status. For those patients with large tumors, almost half of them had a significant shrinkage, and all the others had a stable tumor size." What Are the Reasons to Consider Drug Treatment to Manage Cushing’s Symptoms The extension study ''was important because we didn't have any long-term data regarding patient response to this once-a-month treatment to manage Cushing's disease," she says. While selective surgical removal of the tumor is the preferred treatment choice, the success rate in patients varies, and Cushing's symptoms persist in up to 35% of patients after surgery. In addition, recurrent rates (ie, return of disease) range from 13% to 66% after individuals experience different durations remaining in remission.1 Therefore, the availability of an effective, long-lasting drug will change the course of therapy for many patients with Cushing’s disease going forward. Not only will pasireotide benefit patients who have persistent and recurrent disease after undergoing surgery, but also this medication will be beneficial for those who are not candidates for surgery or just wish to avoid having this procedure, he said. Examining the Safety and Tolerability of Pasireotide This long-acting therapy, pasireotide, which is given by injection, was approved in the US after reviewing results of a 12-month Phase 3 trial.1 In the initial study, participants had a confirmed pituitary cause of the Cushing's disease. After that, the researchers added the optional 12-month open-label, extension study, and now patients can continue on in a separate long-term safety study. Those eligible for the 12-month extension had to have mean urinary free cortisol not exceeding the upper limit of normal (166.5 nanomoles per 24 hour) and/or be considered by the investigator to be getting substantial clinical benefit from treatment with long-action pasireotide, and to demonstrate tolerability of pasireotide during the core study.1 Of the 150 in the initial trial, 81 participants, or 54% of the patients, entered the extension study. Of those, 39 completed the next phase, and most also enrolled in another long-term safety study—these results not yet available).2 During the core study, 1 participants were randomly assigned to 10 or 30 mg of the drug every 28 days, with doses based on effectiveness and tolerability. When they entered the extension, patients were given the same dose they received at month.1,2 Study Outcomes Offer Advantages in Cushing’s Disease Of those who received 36 months of treatment with pasireotide, nearly three in four (72.2%) had controlled levels of urinary free cortisol at this time point.2 Equally good news for this drug was that tumors either shrank or did not grow. Of those individuals who started the trial with a measurable tumor (adenoma) as well as those with an adenoma at the two year mark (35 people), 85.7% of them experienced a reduction of 20% or more or less than a 20% change in tumor volume. No macroadenomas present at the start of the study showed a change of more than 20% at either month 24 or 36.2 Improvements in blood pressure, body mass index (BMI) and waist circumference continued throughout the extension study.1 Those factors influence CVD risk, the leading cause of death in those with Cushing's.4 As for adverse events, most of the study participants, 91.4%, did report one or more complaint during the extension study—most commonly, it was high blood sugar, which was reported by nearly 40% of participants.2. This is not surprising when you consider that most (81.5%) of the individuals participating in the extension trial entered with a diagnosis of diabetes or use of antidiabetic medication, and even more of them (88.9%) had diabetes at the last evaluation.1 This complication indicates the need for people with Cushing’s disease to check their blood glucose, as appropriate. Do You Have Cushing’s Disese? Here's What You Need to Know Women typically develop Cushing’s disease more often than men. What else should you be aware of if you and your doctor decide this medication will help you? Monitoring is crucial, says Dr. Fleseriu, as you will need to have your cortisol levels checked, and you should be on alert for any diabetes signals, which will require close monitoring and regular follow-up for disease management. Another understanding gained from the results of this drug study: "This medication works on the tumor level," she says. "If the patient has a macroadenoma (large tumor), this would be the preferred treatment." However, it should be used with caution in those with diabetes given the increased risk of experiencing high blood sugar. The researchers conclude that "the long-term safety profile of pasireotide was very favorable and consistent with that reported during the first 12 months of treatment. These data support the use of long-acting pasireotide as an effective long-term treatment option for some patients with Cushing's Disease."1 Understanding Benefits of New Drug to Treat Cushing's Diseease Vivien S. Herman-Bonert, MD, an endocrinologist and clinical director of the Pituitary Center at Cedars-Sinai Medical Center in Los Angeles, agreed to discuss the study findings, after agreeing to review the research for EndocrineWeb. As to who might benefit most from monthly pasireotide injections? Dr. Herman-Bonert says, "any patient with Cushing's disease that requires long-term medical therapy, which includes patients with persistent or recurrent disease after surgery." Certainly, anyone who has had poor response to any other medical therapies for Cushing's disease either because they didn't work well enough or because the side effects were too much, will likely benefit a well, she adds. Among the pluses that came out of the study, she says, is that nearly half of the patients had controlled average urinary free cortisol levels after two full years, and 72% of the participants who continued on with the drug for 36 months were able to remain in good urinary cortisol control .1 As the authors stated, tumor shrinkage was another clear benefit of taking long-term pasireotide. That makes the drug a potentially good choice for those even with large tumors or with progressive tumor growth, she says. It’s always good for anyone with Cushing’s disease to have an alterative to surgery, or a back-up option when surgery isn’t quite enough, says Dr. Herman-Bonert. The best news for patients is that quality of life scores improved,1 she adds. Dr Herman-Bonert did add a note of caution: Although the treatment in this study is described as ''long-term, patients will need to be on this for far longer than 2 to 3 years," she says. So, the data reported in this study may or may not persist, and we don’t yet know what the impact will be 10 or 25 years out. Also, the issue of hyperglycemia-related adverse events raises a concern, given the vast majority (81%) of patients who have both Cushing’s disease and diabetes. Most of those taking this drug had a dual diagnosis—having diabetes, a history of diabetes, or taking antidiabetic medicine. If you are under care for diabetes and you require treatment for Cushing’s disease, you must be ver mindful that taking pasireotide will likely lead to high blood sugar spikes, so you should plan to address this with your healthcare provider. Dr. Fleseriu reports research support paid to Oregon Health & Science University from Novartis and other 0companies and consultancy fees from Novartis and Strongbridge Biopharma. Dr. Herman-Bonert has no relevant disclosures. The study was underwritten by Novartis Pharma AG, the drug maker. From https://www.endocrineweb.com/news/pituitary-disorders/62449-cushings-disease-monthly-injection-good-alternative-surgery
  37. 1 point
    In patients with Cushing’s disease, removing the pituitary tumor via an endoscopic transsphenoidal surgery (TSS) leads to better remission rates than microscopic TSS, according to new research. But regardless of surgical approach, plasma cortisol levels one day after surgery are predictive of remission, researchers found. The study, “Management of Cushing’s disease: Changing trend from microscopic to endoscopic surgery,” was published in the journal World Neurosurgery. Because it improves visualization and accessibility, endoscopic TSS has been gaining popularity over microscopic TSS to remove pituitary tumors in Cushing’s disease patients. Yet, although this surgery has been associated with high remission rates, whether it outperforms microscopic surgery and determining the factors affecting long-term outcomes may further ease disease recurrence after TSS. A team with the All India Institute of Medical Sciences addressed this topic in 104 patients who underwent surgery from January 2009 to June 2017. Among these patients, 47 underwent microscopic surgery and 55 endoscopic surgery. At presentation, their ages ranged from 9 to 55 (mean age of 28). Also, patients had been experiencing Cushing’s symptoms over a mean duration of 24 months. Eighty-seven patients showed weight gain. Hypertension (high blood pressure) and diabetes mellitus were among the most common co-morbidities, found in 76 and 33 patients, respectively. Nineteen patients had osteoporosis and 12 osteopenia, which refers to lower-than-normal bone mineral density. As assessed with magnetic resonance imaging, 68 patients had a microadenoma (a tumor diameter smaller than one centimeter) and 27 had a macroadenoma (a tumor one centimeter or larger). Only two patients had an invasive pituitary adenoma. Two patients with larger tumors were operated on transcranially (through the skull). The surgery resulted in total tumor removal in 90 cases (86.5%). A blood loss greater than 100 milliliter was more common with endoscopic than with microscopic TSS. Ten patients developed transient diabetes inspidus, two experienced seizures after surgery, and six of nine patients with macroadenoma and visual deterioration experienced vision improvements after TSS. The incidence of intraoperative leak of cerebrospinal fluid — the liquid surrounding the brain and spinal cord — was 23.2%, while that of post-operative leak was 7.7% and was more common in microadenoma than macroadenoma surgery (9.8% vs. 5.0%). Seventeen patients were lost to follow-up and two died due to metabolic complications and infections. The average follow-up was shorter for endoscopic than with microscopic surgery (18 months vs. 35 months). Among the remaining 85 cases, 65 (76.5%) experienced remission, as defined by a morning cortisol level under 5.0 μg/dL, restored circadian rhythm (the body’s internal clock, typically impaired in Cushing’s patients), and suppression of serum cortisol to below 2 μg/dl after overnight dexamethasone suppression test. The remission rate was 54.5% in pediatric patients and was higher with endoscopic than with microscopic TSS (88.2% vs. 56.6%). Also, patients with microadenoma showed a trend toward more frequent remission than those with macroadenoma (73.2% vs. 64.3%). Ten of the remaining 20 patients experienced disease recurrence up to 28 months after surgery. Sixteen cases revealed signs of hypopituitarism, or pituitary insufficiency, which were managed with replacement therapy. A subsequent analysis found that morning cortisol level on day one after surgery was the only significant predictor of remission. Specifically, a one-unit increase in cortisol lowered the likelihood of remission by 7%. A cortisol level lower than 10.7 μgm/dl was calculated as predicting remission. Overall, the study showed that “postoperative plasma cortisol level is a strong independent predictor of remission,” the researchers wrote, and that “remission provided by endoscopy is significantly better than microscopic approach.” From https://cushingsdiseasenews.com/2019/09/24/cortisol-levels-predict-remission-cushings-patients-undergoing-transsphenoidal-surgery/
  38. 1 point
    So do we need to get our bones checked too? https://www.sciencealert.com/our-bones-provide-our-bodies-with-a-secret-weapon-that-saves-us-in-times-of-danger Bizarre Discovery Shows Your Bones Could Be Triggering The 'Fight-or-Flight' Response MIKE MCRAE 13 SEP 2019 When faced with a threat, hormones flood our bodies in preparation either for battle or a quick escape - what's commonly known as the 'fight-or-flight' response. For decades, we've generally thought this response was driven by hormones such as adrenaline. But it now seems that one of the most important of these messengers could come from a rather unexpected place – our skeleton. We usually think of chemicals like cortisol and adrenaline as the things that get the heart racing and muscles pumping. But the real star player could actually be osteocalcin, a calcium-binding protein produced by our bones. As a response to acute stress, steroids of the glucocorticoid variety are released by the body's endocrine system, where they manage the production of a cascade of other 'get ready to rumble' chemicals throughout various tissues. Researchers from the US, the UK, and India argue there's one tiny problem with this explanation of the fight-or-flight reaction. It isn't exactly fast. While nobody is disputing that our bodies produce cortisol when stressed, the fact their main action is to trigger cells into transcribing specific genes – a process that takes time – makes it an unlikely candidate for a rapid physiological response. "Although this certainly does not rule out that glucocorticoid hormones may be implicated in some capacity in the acute stress response, it suggests the possibility that other hormones, possibly peptide ones, could be involved," says geneticist Gerard Karsenty of Columbia University. So Karsenty and colleagues went on the hunt for something a little more expedient, focussing on proteins released by bone cells that would potentially have a more immediate effect on animal metabolism. Looking to the skeleton as a source might not be as weird as it first seems. After all, our bones evolved as a way to protect our squishy bits from being squashed, either by predator or accident. "If you think of bone as something that evolved to protect the organism from danger – the skull protects the brain from trauma, the skeleton allows vertebrates to escape predators, and even the bones in the ear alert us to approaching danger – the hormonal functions of osteocalcin begin to make sense," says Karsenty. Osteocalcin isn't in any way new to science, either. We've understood its function in bone development for nearly half a century, and in recent years begun to suspect it also has a hand in regulating our energy levels by affecting glucose metabolism. It also seems to give an ageing memory a boost, at least in lab rodents. All useful things in moments of danger. But it's still a surprising discovery that osteocalcin might also help to kickstart our acute stress response. "It completely changes how we think about how acute stress responses occur," says Karsenty. To test their suspicions, the researchers put lab mice under duress by restraining them for a 45 minute period. During that time, osteocalcin levels in the peripheral blood rose by half, while other skeletal hormones barely budged. In another test, just 15 minutes after a few harmless (but uncomfortable) shocks to the feet, osteocalcin levels in the stressed mice jumped by a whole 150 percent. Giving the test subjects a whiff of a chemical found in fox urine also elevated their peripheral osteocalcin levels. Importantly, these went up before their corticosterone levels began to climb, starting a few minutes after exposure and remaining high for another three hours. Just to make sure it wasn't only a mouse thing, the team also checked the hormone in humans who volunteered to do a public speech and undergo a pulse-raising cross-examination. Sure enough, up the osteocalcin went. In yet another series of tests, the team used rodents that were genetically engineered to lack the usual corticosteroid and other stress hormones, and found these animals continued to present a stress response. In addition, a shot of osteocalcin in otherwise unstressed mice was all they needed to get twitchy, raising their heart rate, temperature, and levels of circulating glucose. "Osteocalcin could explain past observations of an intact flight-or-flight response in humans and other animals lacking glucocorticoids and additional molecules produced by the adrenal glands," says Karsenty. With the evidence building for the bone protein as such a strong motivator for dealing with stress, it stands to ask why we need hormones like cortisol at all. The researchers plan to unravel this mystery in future investigations. This research was published in Cell Metabolism.
  39. 1 point
    until
    Presented by Andrew Lin, MD Neuro-Oncologist & Neurologist Memorial Sloak Kettering Cancer Center After registering you will receive a confirmation email with details about joining the webinar. Contact us at webinar@pituitary.org with any questions or suggestions. Date: September 18, 2019 Time: 10:00 AM - 11:00 AM. Pacific Daylight Time, 1:00 PM - 2:00 PM Eastern Daylight Time Learning Objectives: During the conversation I will be: 1) Defining aggressive pituitary tumors. 2) Reviewing the current treatment options for aggressive pituitary tumors. 3) Discussing experimental treatment options including a phase II trial investigating the activity of the immunotherapies nivolumab and ipilimumab. Presenter Biography: I am a neuro-oncologist at Memorial Sloan Kettering Cancer Center (MSK) and a member of the Multidisciplinary Pituitary & Skull Base Tumor Center. In collaboration with my colleagues in endocrine, neurosurgery, and radiation oncology, I treat patients with aggressive pituitary tumors, who are resistant to conventional treatments (i.e. surgery and radiation), with chemotherapy. With my colleagues at MSK, I have published several research articles on pituitary tumors and opened several clinical trials.
  40. 1 point
    For patients with persistent or recurring Cushing’s disease, monthly pasireotide therapy was safe and effective, leading to normal urinary free cortisol levels in 47% of patients after 2 years, according to findings published in Clinical Endocrinology. Maria Fleseriu “The management of Cushing’s syndrome, and particularly Cushing’s disease, remains challenging,” Maria Fleseriu, MD, FACE, professor of neurological surgery and professor of medicine in the division of endocrinology, diabetes and clinical nutrition in the School of Medicine at Oregon Health & Science University and director of the OHSU Northwest Pituitary Center, told Endocrine Today. “Long-acting pasireotide provided sustained biochemical improvements and clinical benefit in a significant proportion of patients with Cushing’s disease who elected to continue in this extension study. There were many adverse events reported overall, but no new safety signals emerging over long-term treatment.” In the last decade, medical treatment for Cushing’s disease has progressed from a few steroidogenesis inhibitors to three novel drug groups: new inhibitors for steroidogenic enzymes with possibly fewer adverse effects, pituitary-directed drugs that aim to inhibit the pathophysiological pathways of Cushing’s disease, and glucocorticoid receptor antagonists that block cortisol’s action, Fleseriu, who is also an Endocrine Today Editorial Board member, said. In an open-label extension study, Fleseriu and colleagues analyzed data from 81 adults with confirmed Cushing’s disease with mean urinary free cortisol not exceeding the upper limit of normal, who transitioned from a 12-month, randomized controlled trial where they were assigned 10 mg or 30 mg once-monthly intramuscular pasireotide (Signifor LAR, Novartis). During the main study, researchers recruited participants with mean urinary free cortisol level concentration 1.5 to five times the upper limit of normal, normal or greater than normal plasma and confirmed pituitary source of Cushing’s disease. Participants who elected to continue in the extension were considered biochemical responders or benefited from the study drug per the clinical investigator, Fleseriu said. “As in all extension studies, the bias is inherent that patients deemed responders tend to continue, but for any type of treatment for pituitary tumors, and particularly Cushing’s disease, long-term, robust data on efficacy and safety parameters is essential,” Fleseriu said. Median overall exposure to pasireotide at the end of the extension study was 23.9 months, with nearly half of patients receiving at least 1 year of treatment during the extension phase. Researchers found that improvements in clinical signs of hypercortisolism were sustained throughout the study and median urinary free cortisol remained within normal range. Overall, 38 participants (47%) had controlled urinary free cortisol at month 24 (after 12 months of treatment during the extension phase), with researchers noting that the proportion of participants with controlled or partially controlled urinary free cortisol was stable throughout the extension phase. “Interestingly, the median salivary cortisol level decreased but remained above normal (1.3 times upper limit of normal) at 3 years,” Fleseriu said. As seen in other pasireotide studies, and expected based on the mechanism of action, researchers observed hyperglycemia-related adverse events in 39.5% of participants, with diabetes medications initiated or escalated in some patients, Fleseriu said. However, mean fasting glucose and HbA1c were stable during the extension phase, after increasing in the main study. Within the cohort, 81.5% had type 2 diabetes at baseline (entering extension phase) and 88.9% patients had type 2 diabetes at last assessment. “Pasireotide acts at the tumor level, and tumor shrinkage is seen in many patients,” Fleseriu said. “In this study, 42% and 32.1% had a measurable microadenoma or macroadenoma, respectively, on MRI at the start of pasireotide treatment; an adenoma was not visible in almost a quarter of patients at 2 years.” Among patients with a measurable adenoma at baseline and at month 24 (n = 35), 85.7% experienced a reduction of at least 20% or a 20% change in tumor volume between the two time points. Improvements in median systolic and diastolic blood pressure, BMI and waist circumference were sustained during the extension, Fleseriu said. “The long-term safety profile of pasireotide was favorable and consistent with that reported during the first 12 months of treatment,” the researchers wrote. “These data support the use of long-acting pasireotide as an effective long-term treatment option for some patients with [Cushing’s disease].” Fleseriu said individualized treatment selecting patients who will derive benefit from therapy will be crucial, balancing both efficacy and the potential risks and costs. – by Regina Schaffer Disclosures: Fleseriu reports she has received consultant fees and her institution has received research support from Novo Nordisk and Pfizer. Please see the study for all other authors’ relevant financial disclosures. From https://www.healio.com/endocrinology/neuroendocrinology/news/online/%7B5da4611f-34b2-4306-80b8-46babd2aad4a%7D/long-acting-pasireotide-provides-sustained-biochemical-improvements-in-cushings-disease?page=2
  41. 1 point
    Abstract OBJECTIVE: To report our management of bilateral adrenalectomy with autologous adrenal gland transplantation for persistent Cushing's disease, and to discuss the feasibility of autologous adrenal transplantation for the treatment of refractory Cushing's disease. MATERIAL AND METHODS: A retrospective analysis was performed in 4 patients (3 females, aged 14-36 years) who underwent autologous adrenal transplantation for persistent Cushing's disease after endonasal transsphenoidal resection of a pituitary tumor. The procedure was performed by implanting a vascularized adrenal graft into the left iliac fossa with direct and indirect anastomoses. Postoperative follow-up was performed in 1, 1.5, 8, and 10 years, and an over 8-year long-term follow-up was reached in 2 out of the 4 cases. Hormone replacement dosage was guided by clinical symptoms and endocrine results including serum cortisol (F), 24 h urine-free cortisol, and adrenocorticotrophic hormone levels. RESULTS: All 4 patients with symptomatic Cushing's disease experienced resolution of symptoms after autotransplantation without Nelson Syndrome. Functional autografts were confirmed through clinical evaluation and endocrine results. One year after transplantation, adrenal function and hormone replacement dosage remained stable without adrenal hyperplasia. After long-term follow-up, dosages of hormone replacement were reduced in all patients. CONCLUSIONS: In this series of 4 patients, we demonstrate the long-term efficacy of bilateral adrenalectomy with autologous adrenal transplantation and propose this procedure as a viable treatment option for refractory Cushing's disease. © 2019 S. Karger AG, Basel. KEYWORDS: Cortisol; Adrenalectomy; Autologous adrenal gland transplantation ; Cushing’s disease; Nelson syndrome PubMed http://www.ncbi.nlm.nih.gov/pubmed/31434089 TAGS: cortisol, adrenalectomy, Autologous adrenal gland transplantation , Cushing's disease, Nelson syndrome
  42. 1 point
    I would be very interested to learn the current status of any Disability Claim for Agent Orange with Cushing. My 47 year old daughter had surgery in 2008 for unilateral adrenal Cushings in Orlando, FL. Frank
  43. 1 point
    Presented by Nathan T Zwagerman MD Director of Pituitary and Skull base surgery Department of Neurosurgery Medical College of Wisconsin After registering you will receive a confirmation email with details about joining the webinar. Date: Wednesday, August 21, 2019 Time: 10:00 AM - 11:00 AM Pacific Daylight Time 1:00 PM - 2:00 PM Eastern Daylight Time Webinar Description: Learning Objectives: Describe the signs and symptoms of Cushing's Disease Describe the work up for patients with Cushing's Disease Understand the goals, risks, and expected outcomes for treatment Describe alternative treatments when surgery is not curative. Presenter Bio: Dr. Zwagerman is a Professor of Neurosurgery at the Medical College of Wisconsin. He did his undergraduate work in psychology at Calvin College in Grand Rapids, Michigan. He earned his medical degree at Wayne State University in Detroit. He did his fellowship in endoscopic and open cranial base surgery, and then his residency in neurological surgery at the University of Pittsburgh Medical Center.
  44. 1 point
    Metoclopramide, a gastrointestinal medicine, can increase cortisol levels after unilateral adrenalectomy — the surgical removal of one adrenal gland — and conceal adrenal insufficiency in bilateral macronodular adrenal hyperplasia (BMAH) patients, a case report suggests. The study, “Retention of aberrant cortisol secretion in a patient with bilateral macronodular adrenal hyperplasia after unilateral adrenalectomy,” was published in Therapeutics and Clinical Risk Management. BMAH is a subtype of adrenal Cushing’s syndrome, characterized by the formation of nodules and enlargement of both adrenal glands. In this condition, the production of cortisol does not depend on adrenocorticotropic hormone (ACTH) stimulation, as usually is the case. Instead, cortisol production is triggered by a variety of stimuli, such as maintaining an upright posture, eating mixed meals — those that contain fats, proteins, and carbohydrates — or exposure to certain substances. A possible treatment for this condition is unilateral adrenalectomy. However, after the procedure, some patients cannot produce adequate amounts of cortisol. That makes it important for clinicians to closely monitor the changes in cortisol levels after surgery. Metoclopramide, a medicine that alleviates gastrointestinal symptoms and is often used during the postoperative period, has been reported to increase the cortisol levels of BMAH patients. However, the effects of metoclopramide on BMAH patients who underwent unilateral adrenalectomy are not clear. Researchers in Japan described the case of a 61-year-old postmenopausal woman whose levels of cortisol remained high after surgery due to metoclopramide ingestion. The patient was first examined because she had experienced high blood pressure, abnormal lipid levels in the blood, and osteoporosis for ten years. She also was pre-obese. She was given medication to control blood pressure with no results. The lab tests showed high serum cortisol and undetectable levels of ACTH, suggesting adrenal Cushing’s syndrome. Patients who have increased cortisol levels, but low levels of ACTH, often have poor communication between the hypothalamus, the pituitary, and the adrenal glands. These three glands — together known as the HPA axis — control the levels of cortisol in healthy people. Imaging of the adrenal glands revealed they were both enlarged and presented nodules. The patient’s cortisol levels peaked after taking metoclopramide, and her serum cortisol varied significantly during the day while ACTH remained undetectable. These results led to the BMAH diagnosis. The doctors performed unilateral adrenalectomy to control cortisol levels. The surgery was successful, and the doctors reduced the dose of glucocorticoid replacement therapy on day 6. Eight days after the surgery, however, the patient showed decreased levels of fasting serum cortisol, which indicated adrenal insufficiency — when the adrenal glands are unable to produce enough cortisol. The doctors noticed that metoclopramide was causing an increase in serum cortisol levels, which made them appear normal and masked the adrenal insufficiency. They stopped metoclopramide treatment and started replacement therapy (hydrocortisone) to control the adrenal insufficiency. The patient was discharged 10 days after the surgery. The serum cortisol levels were monitored on days 72 and 109 after surgery, and they remained lower than average. Therefore she could not stop hydrocortisone treatment. The levels of ACTH remained undetectable, suggesting that the communication between the HPA axis had not been restored. “Habitual use of metoclopramide might suppress the hypothalamus and pituitary via negative feedback due to cortisol excess, and lead to a delayed recovery of the HPA axis,” the researchers said. Meanwhile, the patient’s weight decreased, and high blood pressure was controlled. “Detailed surveillance of aberrant cortisol secretion responses on a challenge with exogenous stimuli […] is clinically important in BMAH patients,” the study concluded. “Caution is thus required for assessing the actual status of the HPA axis.” From https://cushingsdiseasenews.com/2019/05/07/metoclopramide-conceals-adrenal-insufficiency-after-gland-removal-bmah-patients-case-report/
  45. 1 point
    How sad. He never got to know life after Cushings, either.
  46. 1 point
    Thanks for posting this Robin. The poor unfortunate man and his family - it is dreadful. And so very descriptive - makes you wish you could have been there for him to help.
  47. 1 point
    Thanks for sharing this story Robin. Kinda tugs on the ol' strings doesn't it.
  48. 1 point
    MK---I think things are much the same way here---the doctor's look for the obvious---and just treat the symptoms---which doesn't always save any of us money...sadly, some pay with their lives---as you've indicated. Healthy people are productive people---that should be what we're aiming for...not trying to save a nickel...
  49. 1 point
    Wow, What a heart wrenching story. I think we all must have a double dose of empathy when we read about the trials of another cushings patient. I agree that publishing the story will really help raise awareness. It also makes me even more resolved to fight and encourage others to fight diligently to get a diagnosis and treatment plan as soon as possible!!!! Time is not our friend with this disease! Gina
  50. 1 point
    This must be so devastating for his family, but I'm glad they are bringing this disease to public view. It makes me more thankful that I saw a GP who was able to put all my symptoms together & immediately referred me. This is not always the case over here. Most GP's treat symptoms, they do not look for an underlying cause, that's the way it is over here, they are constantly under pressure to reduce the costs to the NHS, so any referral to a specialist has to be for a DAMNED GOOD REASON! For diagnosis they look for the lowest common denominator, this goes for all diseases, the simplest illness is the one they DX. My father was DX'd with asthma at 62, he went on to have a stroke, then passed away suddenly with a heart-attack at 69. It turned out, when he was opened-up, he didn't have asthma at all, his lungs were fine, his arteries were clogged which caused his breathing difficulties, and he could have had an operation to resolve this. My father-in-law died from pneumonia, because when he had a chest x-ray, they said he had a massive cancerous lung tumour which was inoperable, so didn't offer any kind of treatment. When he was opened up, there was no tumour, he also died needlessly. That's just the way it is over here, it varies from region to region though, we call it the Postcode Lottery, it's difficult to see how it will ever change. Melanie XXX
×
×
  • Create New...