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  1. How stressed are you? Your earwax could hold the answer. A new method of collecting and analyzing earwax for levels of the stress hormone cortisol may be a simple and cheap way to track the mental health of people with depression and anxiety. Cortisol is a crucial hormone that spikes when a person is stressed and declines when they're relaxed. In the short-term, the hormone is responsible for the "fight or flight" response, so it's important for survival. But cortisol is often consistently elevated in people with depression and anxiety, and persistent high levels of cortisol can have negative effects on the immune system, blood pressure and other bodily functions. There are other disorders which involve abnormal cortisol, including Cushing's disease (caused by the overproduction of cortisol) and Addison's disease (caused by the underproduction of cortisol). People with Cushing's disease have abnormal fat deposits, weakened immune systems and brittle bones. People with Addison's disease have dangerously low blood pressure. There are a lot of ways to measure cortisol: in saliva, in blood, even in hair. But saliva and blood samples capture only a moment in time, and cortisol fluctuates significantly throughout the day. Even the experience of getting a needle stick to draw blood can increase stress, and thus cortisol levels. Hair samples can provide a snapshot of cortisol over several months instead of several minutes, but hair can be expensive to analyze — and some people don't have much of it. Andrés Herane-Vives, a lecturer at University College London's Institute of Cognitive Neuroscience and Institute of Psychiatry, and his colleagues instead turned to the ear. Earwax is stable and resistant to bacterial contamination, so it can be shipped to a laboratory easily for analysis. It also can hold a record of cortisol levels stretching over weeks. But previous methods of harvesting earwax involved sticking a syringe into the ear and flushing it out with water, which can be slightly painful and stressful. So Herane-Vives and his colleagues developed a swab that, when used, would be no more stressful than a Q-tip. The swab has a shield around the handle, so that people can't stick it too far into their ear and damage their eardrum, and a sponge at the end to collect the wax. In a small pilot study, researchers collected blood, hair and earwax from 37 participants at two different time points. At each collection point, they sampled earwax using a syringe from one ear, and using the new self-swab method from the other. The researchers then compared the reliability of the cortisol measurements from the self-swab earwax with that of the other methods. They found that cortisol was more concentrated in earwax than in hair, making for easier analysis. Analyzing the self-swabbed earwax was also faster and more efficient than analyzing the earwax from the syringe, which had to be dried out before using. Finally, the earwax showed more consistency in cortisol levels compared with the other methods, which were more sensitive to fluctuations caused by things like recent alcohol consumption. Participants also said that self-swabbing was more comfortable than the syringe method. The researchers reported their findings Nov. 2 in the journal Heliyon. Herane-Vives is also starting a company called Trears to market the new method. In the future, he hopes that earwax could also be used to monitor other hormones. The researchers also need to follow up with studies of Asian individuals, who were left out of this pilot study because a significant number only produce dry, flaky earwax as opposed to wet, waxy earwax. "After this successful pilot study, if our device holds up to further scrutiny in larger trials, we hope to transform diagnostics and care for millions of people with depression or cortisol-related conditions such as Addison's disease and Cushing syndrome, and potentially numerous other conditions," he said in a statement. Originally published in Live Science.
    3 points
  2. Christina Tatsi, Maria E. Bompou, Chelsi Flippo, Meg Keil, Prashant Chittiboina, Constantine A. Stratakis First published: 25 August 2021 https://doi.org/10.1111/cen.14560 Abstract Objective Diagnostic workup of Cushing disease (CD) involves imaging evaluation of the pituitary gland, but in many patients no tumour is visualised. The aim of this study is to describe the association of magnetic resonance imaging (MRI) findings with the postoperative course of paediatric and adolescent patients with CD. Patients Patients with a diagnosis of CD at less than 21 years of age with MRI evaluation of the pituitary before first transsphenoidal surgery were included. Measurements Clinical, imaging and biochemical data were analysed. Results One hundred and eighty-six patients with paediatric or adolescent-onset CD were included in the study. Of all patients, 127 (68.3%) had MRI findings consistent with pituitary adenoma, while the remaining had negative or inconclusive MRI. Patients with negative MRI were younger in age and had lower morning cortisol and adrenocorticotropin levels. Of 181 patients with data on postoperative course, patients with negative MRI had higher odds of not achieving remission after the first surgery (odds ratio = 2.6, 95% confidence intervals [CIs] = 1.1–6.0) compared to those with positive MRI. In patients with remission after first transsphenoidal surgery, long-term recurrence risk was not associated with the detection of a pituitary adenoma in the preoperative MRI (hazard risk = 2.1, 95% CI = 0.7–5.8). Conclusions Up to one-third of paediatric and adolescent patients with CD do not have a pituitary tumour visualised in MRI. A negative MRI is associated with higher odds of nonremission after surgery; however, if remission is achieved, long-term risk for recurrence is not associated with the preoperative MRI findings. Full text at https://onlinelibrary.wiley.com/doi/full/10.1111/cen.14560
    2 points
  3. SAN DIEGO, CA, USA I August 10, 2021 I Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX), a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for rare endocrine diseases and endocrine-related tumors, today announced positive preliminary findings from the single ascending dose (SAD) portion of a first-in-human Phase 1 clinical study with CRN04894 demonstrating pharmacologic proof-of-concept for this first-in-class, investigational, oral, nonpeptide adrenocorticotropic hormone (ACTH) antagonist that is being developed for the treatment of conditions of ACTH excess, including Cushing’s disease and congenital adrenal hyperplasia. “ACTH is the central hormone of the endocrine stress response. Even though we’ve known about its clinical significance for more than 100 years, there has never been an ACTH antagonist available to intervene in diseases of excess stress hormones. This is an important milestone for the field of endocrinology and for our company,” said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. “I am extremely proud of our team that conceived, discovered and developed CRN04894 this far. This is the second molecule to emerge from our in-house discovery efforts and demonstrate pharmacologic proof of concept. I am very excited to see what it can do in upcoming clinical studies.” The 39 healthy volunteers who enrolled in the SAD cohorts were administered oral doses of CRN04894 (10 mg to 80 mg, or placebo) two hours prior to a challenge with synthetic ACTH. Analyses of basal cortisol levels (before ACTH challenge) showed that CRN04894 produced a rapid and dose-dependent reduction of cortisol by 25-56%. After challenge with a supra-pathophysiologic dose of ACTH (250 mcg), CRN04894 suppressed cortisol (as measured by AUC) up to 41%. After challenge with a disease-relevant dose of ACTH (1 mcg), CRN04894 showed a clinically meaningful reduction in cortisol AUC of 48%. These reductions in cortisol suggest that CRN04894 is bound with high affinity to its target receptor on the adrenal gland and blocking the activity of ACTH. CRN04894 was well tolerated in the healthy volunteers who enrolled in these SAD cohorts and all adverse events were considered mild. “We are very encouraged by these single ascending dose data which clearly demonstrate proof of ACTH antagonism with CRN04894 exposure in healthy volunteers,” stated Alan Krasner, M.D., chief medical officer of Crinetics. “We look forward to completing this study and assessing results from the multiple ascending dose cohorts. As a clinical endocrinologist, I recognize the pioneering nature of this work and eagerly look forward to further understanding the potential of CRN04894 for the treatment of diseases of ACTH excess.” Data Review Conference Call Crinetics will hold a conference call and live audio webcast today, August 10, 2021 at 4:30 p.m. Eastern Time to discuss the results of the CRN04894 SAD cohorts. To participate, please dial 800-772-3714 (domestic) or 212-271-4615 (international) and refer to conference ID 21996541. To access the webcast, please visit the Events page on the Crinetics website. The archived webcast will be available for 90 days. About the CRN04894-01 Phase 1 Study Crinetics is enrolling healthy volunteers in this double-blind, randomized, placebo-controlled Phase 1 study of CRN04894. Participants will be divided into multiple cohorts in the single ascending dose (SAD) and multiple ascending dose (MAD) phases of the study. In the SAD phase, safety and pharmacokinetics are assessed. In addition, pharmacodynamic responses are evaluated before and after challenges with injected synthetic ACTH to assess pharmacologic effects resulting from exposure to CRN04894. In the MAD phase, participants will be administered placebo or ascending doses of study drug daily for 10 days. Assessments of safety, pharmacokinetics and pharmacodynamics will also be performed after repeat dosing. About CRN04894 Adrenocorticotropic hormone (ACTH) is synthesized and secreted by the pituitary gland and binds to melanocortin type 2 receptor (MC2R), which is selectively expressed in the adrenal gland. This interaction of ACTH with MCR2 stimulates the adrenal production of cortisol, a stress hormone that is involved in the regulation of many systems. Cortisol is involved for example in the regulation of blood sugar levels, metabolism, inflammation, blood pressure, and memory formulation, and excess adrenal androgen production can result in hirsutism, menstrual dysfunction, infertility in men and women, acne, cardiometabolic comorbidities and insulin resistance. Diseases associated with excess of ACTH, therefore, can have significant impact on physical and mental health. Crinetics’ ACTH antagonist, CRN04894, has exhibited strong binding affinity for MC2R in preclinical models and demonstrated suppression of adrenally derived glucocorticoids and androgens that are under the control of ACTH, while maintaining mineralocorticoid production. About Cushing’s Disease and Congenital Adrenal Hyperplasia Cushing’s disease is a rare disease with a prevalence of approximately 10,000 patients in the United States. It is more common in women, between 30 and 50 years of age. Cushing’s disease often takes many years to diagnose and may well be under-diagnosed in the general population as many of its symptoms such as lethargy, depression, obesity, hypertension, hirsutism, and menstrual irregularity can be incorrectly attributed to other more common disorders. Congenital adrenal hyperplasia (CAH) encompasses a set of disorders that are caused by genetic mutations that result in impaired cortisol synthesis with a prevalence of approximately 27,000 patients in the United States. This lack of cortisol leads to a loss of feedback mechanisms and results in persistently high levels of ACTH, which in turn causes overstimulation of the adrenal cortex. The resulting adrenal hyperplasia and over-secretion of other steroids (particularly androgens) and steroid precursors can lead to a variety of effects from improper gonadal development to life-threatening adrenal crisis. About Crinetics Pharmaceuticals Crinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for rare endocrine diseases and endocrine-related tumors. The company’s lead product candidate, paltusotine, is an investigational, oral, selective nonpeptide somatostatin receptor type 2 agonist for the treatment of acromegaly, an orphan disease affecting more than 26,000 people in the United States. A Phase 3 program to evaluate safety and efficacy of paltusotine for the treatment of acromegaly is underway. Crinetics also plans to advance paltusotine into a Phase 2 trial for the treatment of carcinoid syndrome associated with neuroendocrine tumors. The company is also developing CRN04777, an investigational, oral, nonpeptide somatostatin receptor type 5 (SST5) agonist for congenital hyperinsulinism, as well as CRN04894, an investigational, oral, nonpeptide ACTH antagonist for the treatment of Cushing’s disease, congenital adrenal hyperplasia, and other diseases of excess ACTH. All of the company’s drug candidates are new chemical entities resulting from in-house drug discovery efforts and are wholly owned by the company. SOURCE: Crinetics Pharmaceuticals From https://pipelinereview.com/index.php/2021081178950/Small-Molecules/Crinetics-Pharmaceuticals-Oral-ACTH-Antagonist-CRN04894-Demonstrates-Pharmacologic-Proof-of-Concept-with-Dose-Dependent-Cortisol-Suppression-in-Single-Ascending-Dose-Port.html
    2 points
  4. All of our country is very encouraged by the declining rates in both COVID-19 infections and death, due mostly to President Trump’s vaccine production and trial effort called Operation Warp Speed and President Biden’s vaccine distribution efforts. As of July 2021, The United States has administered 334,600,770 doses of COVID-19 vaccines, 184,132,768 people had received at least one dose while 159,266,536 people are fully vaccinated. The pandemic is by no means over, as people are still getting infected with COVID-19 with the emergence of the Delta Variant. In fact, recently cases, hospitalizations and deaths due to COVID-19 have gone up. In Los Angeles, the increased infection rate has led to indoor mask requirements. The main reason that COVID-19 has not been eliminated is because of vaccine hesitancy, which is often due to misinformation propagated on websites and social media. One of Dr. Friedman's patients gave him a link of an alternative doctor who gave multiple episodes of misinformation subtitled “Evidence suggests people who have received the COVID “vaccine” may have a reduced lifespan” about the COVID-19 vaccine that Dr. Friedman wants to address. Almost 30% of American say they will not get the vaccine, up from 20% a few months ago. Statistics are that people who are vaccinated have a 1:1,000,000 chance of dying from COVID, while people who are unvaccinated have a 1:500 chance of dying from COVID. I think most people would take the 1:1,000,000 risk. Dr. Friedman has always been a proponent of the COVID-19 vaccine because he is a scientist and bases his decisions on peer-reviewed literature and not social media posts. As we are getting to the stage where the COVID-19 pandemic could end if vaccination rates increase, he feels that it is even more important for people to get correct information about the COVID-19 vaccine. MYTH: People are dying at high rates from the COVID-19 vaccine and the rates of complications and deaths are underreported. FACT: The rates of complications and deaths from the vaccine are overreported. It is a fact that when 200 million people get a vaccine, some of them will get blood clots, some of them will have a heart attack, some of them will have strokes, some of them will have optic neuritis and some will have Guillain-Barré syndrome. These complications may not be due to the vaccine, but people remember that they got the vaccine recently. Anti-vaccine websites seem to play up on this and give false information that COVID-19 complications are underreported and fail to note that there is no control group, so we do not know how many people would have gotten blood clots, strokes, and heart attacks if they did not get the vaccine. For example, one anti-vaccine website highlighted a Tamil (Indian) actor Vivek, who died of a massive heart attack 5 days after getting the COVID-19 vaccine and tried to make a case that the vaccine caused that. Of course, the massive heart attack was due to years of buildup of cholesterol in his coronary arteries and had nothing to do with the COVID-19 vaccine. In fact, the complications attributed to the COVID-19 vaccine occur less frequently in those vaccinated than unvaccinated. The only complication that seems to possibly be more common in people who get vaccinated is blood clots, and the rate of that is still quite low. Overwhelmingly, the COVID-19 vaccine is effective and safe. MYTH: I had COVID-19 before. I don't need a vaccine. Natural immunity is better than a vaccine immunity. FACT: Most studies have shown that the COVID-19 vaccines are more effective, with longer-lasting immunity, than only having the COVID-19 infection. The immunity after natural infection varies and may be quite minimal in patients who had mild COVID-19 and likely declines within a couple of months of infection. In contrast, those who got the vaccine seem to have high levels of immunity even months after getting the vaccine. The vaccine also protects against the COVID-19 variants. If someone had one variant, it is unlikely that their natural immunity would protect them against other variants. MYTH: The COVID-19 vaccine leads to spike proteins circulating in your body for months after the vaccine. FACT: The mRNA from the vaccine, the spike protein that it generates, and all of the products of the COVID-19 vaccine are gone within hours, if not days, and do not hang around the body. MYTH: There is likely to be long-term effects, including infertility effects, of the COVID-19 vaccine. FACT: As the viral particles and proteins are gone within a couple hours to days and the vaccine only enters the cytoplasm and does not enter the DNA, it is very unlikely that there will be long-term effects. So far, the clinical trials of the COVID-19 vaccine have not resulted in any detrimental effects, and it has been a year since the trials started. Other vaccines have been used safely and do not give long-term side effects. There is no reason to think that this vaccine would give long-term side effects, and we have not seen any evidence of long-term side effects currently. Pregnant women who received COVID-19 vaccines have similar rates adverse pregnancy and neonatal outcomes (e.g., fetal loss, preterm birth, small size for gestational age, congenital anomalies, and neonatal death) as with pregnant women who did not receive vaccines. MYTH: People with autoimmune disease should not get the vaccine. FACT: Persons with autoimmune disease are likely more susceptible to COVID-19, and they should especially get the vaccine. People with preexisting conditions, including autoimmune diseases, have been shown to be give generally excellent immune responses to the vaccine, and it should especially be given to patients with Addison’s disease or Cushing's disease who may have higher rates of getting more severe COVID-19. In fact, the CDC as well Dr. Friedman recommends EVERYONE getting the vaccine, except 1) those under 12, 2) those who had an anaphylactic reaction to their first COVID-19 vaccine. Patients with AIDS, and those on immunosuppressive therapy for cancers, organ transplants and rheumatological conditions, may not be fully protected from vaccines and should be cautious (including wearing masks and social distancing), but still should get vaccinated. MYTH: Patients with autoimmune diseases, and other conditions do not mount an adequate immune response to the vaccine and may even should get a booster shot. FACT: The only patients that have been found not to have a good immune response to the vaccine is those with AIDS or on immunosuppressive drugs that are used in people with rheumatological diseases or transplants. With these exception, patients appear to mount a good immune response to the vaccine regardless of their preexisting condition and do not need a booster shot. MYTH: Why should I bother with the vaccine if it is going to require a booster shot? FACT: It is unclear whether booster shots will be required or not. Currently, the CDC and FDA do not recommend a booster shot, but Pfizer has petitioned the FDA to consider it and is starting more studies on whether a booster shot is effective. It is currently believed that the vaccine retains effectiveness for months to years after it is given. MYTH: We are almost at herd immunity now. Why bother getting a vaccine? FACT: We are not at herd immunity as people are still getting sick and dying from COVID-19. Dr. Friedman recently lost to COVID-19 his 43-year old patient with obesity and diabetes at MLK Outpatient Center. There are pockets in the United States with low vaccine rates, especially in the South. The vaccine is spreading among unvaccinated people, while the rate of spread among vaccinated people is quite low. Approximately 98% of those hospitalized with COVID-19 are unvaccinated. It is important from a public health viewpoint for all Americans to get vaccinated. MYTH: There is nothing to be concerned with about the variants. FACT: Especially the delta variant appears to be more contagious and aggressive than the other variants currently. The vaccines do appear to be effective against the delta variant but possibly a little less so. Variants multiply and can generate new variants only if they are infected into patients who are unvaccinated. To end the emergence of new variants, it is important for all Americans to get vaccinated. MYTH: I could just be careful, and I will not get the COVID-19 vaccine. FACT: Thousands of people who were careful and got COVID-19 and either died from it or became extremely sick. The best prevention against getting COVID-19 is to get vaccinated. MYTH: I am young. I do not have to worry about getting COVID. FACT: Many young people have gotten sick and died of COVID-19 and also, they are contagious and can spread COVID-19 if they are not vaccinated. Everyone, regardless of their age, as long as they are over 12, should get vaccinated. MYTH: If children under 12 are not vaccinated, the virus will still spread. FACT: The FDA and CDC do not recommend the vaccine for those under 12. They are very unlikely to get COVID-19 and are very unlikely to transmit it to others. They are the one group that does not need to get vaccinated. MYTH: COVID-19 vaccines are an experimental vaccine. FACT: While it is true that the FDA approved COVID-19 vaccines were granted emergency use authorization in December 2020 (Pfizer and Moderna) and Johnson and Johnson in February 2021. Both Pfizer and Moderna have petitioned the FDA for full approval, but by no means are these vaccines experimental. As mentioned, over 180 million Americans and many more worldwide have received the vaccine. This is more than any other FDA approved medication. Clinical trials are still ongoing and have enrolled thousands of people and Israel has monitored the effect of COVID-19 vaccines in 7 million Israelis. MYTH: The COVID-19 vaccine is a government plot to kill or injure people or a war against G-d. FACT: Yeah right If you want the pandemic to end, please get vaccinated and encourage your friends and colleagues to get vaccinated. For more information or to schedule an appointment with Dr. Friedman, go to goodhormonehealth.com
    2 points
  5. Rachel Acree, Caitlin M Miller, Brent S Abel, Nicola M Neary, Karen Campbell, Lynnette K Nieman Journal of the Endocrine Society, Volume 5, Issue 8, August 2021, bvab109, https://doi.org/10.1210/jendso/bvab109 Abstract Context Cushing syndrome (CS) is associated with impaired health-related quality of life (HRQOL) even after surgical cure. Objective To characterize patient and provider perspectives on recovery from CS, drivers of decreased HRQOL during recovery, and ways to improve HRQOL. Design Cross-sectional observational survey. Participants Patients (n = 341) had undergone surgery for CS and were members of the Cushing’s Support and Research Foundation. Physicians (n = 54) were Pituitary Society physician members and academicians who treated patients with CS. Results Compared with patients, physicians underestimated the time to complete recovery after surgery (12 months vs 18 months, P = 0.0104). Time to recovery did not differ by CS etiology, but patients with adrenal etiologies of CS reported a longer duration of cortisol replacement medication compared with patients with Cushing disease (12 months vs 6 months, P = 0.0025). Physicians overestimated the benefits of work (26.9% vs 65.3%, P < 0.0001), exercise (40.9% vs 77.6%, P = 0.0001), and activities (44.8% vs 75.5%, P = 0.0016) as useful coping mechanisms in the postsurgical period. Most patients considered family/friends (83.4%) and rest (74.7%) to be helpful. All physicians endorsed educating patients on recovery, but 32.4% (95% CI, 27.3-38.0) of patients denied receiving sufficient information. Some patients did not feel prepared for the postsurgical experience (32.9%; 95% CI, 27.6-38.6) and considered physicians not familiar enough with CS (16.1%; 95% CI, 12.2-20.8). Conclusion Poor communication between physicians and CS patients may contribute to dissatisfaction with the postsurgical experience. Increased information on recovery, including helpful coping mechanisms, and improved provider-physician communication may improve HRQOL during recovery. Read the entire article in the enclosed PDF. bvab109.pdf
    2 points
  6. Mayela, I'm so sorry you went through COVID but glad you're on the other side of it now. And a relapse doesn't sound like any fun Thanks for the update on The GRACE trial, though. Please keep us updated on your recovery from COVID and your relapse.
    2 points
  7. Osilodrostat therapy was found to be effective in improving blood pressure parameters, health-related quality of life, depression, and other signs and symptoms in patients with Cushing disease, regardless of the degree of cortisol control, according to study results presented at the 30th Annual Scientific and Clinical Congress of the American Association of Clinical Endocrinologists (ENVISION 2021). Investigators of the LINC 3 study (ClinicalTrials.gov Identifier: NCT02180217), a phase 3, multicenter study with a double-blind, randomized withdrawal period, sought to assess the effects of twice-daily osilodrostat (2-30 mg) on signs, symptoms, and health-related quality of life in 137 patients with Cushing disease. Study endpoints included change in various parameters from baseline to week 48, including mean urinary free cortisol (mUFC) status, cardiovascular-related measures, physical features, Cushing Quality-of-Life score, and Beck Depression Inventory score. Participants were assessed every 2, 4, or 12 weeks depending on the study period, and eligible participants were randomly assigned 1:1 to withdrawal at week 24. The median age of participants was 40.0 years, and women made up 77.4% of the cohort. Of 137 participants, 132 (96%) achieved controlled mUFC at least once during the core study period. At week 24, patients with controlled or partially controlled mUFC showed improvements in blood pressure that were not seen in patients with uncontrolled mUFC; at week 48, improvement in blood pressure occurred regardless of mUFC status. Cushing Quality-of-Life and Beck Depression Inventory scores, along with other metabolic and cardiovascular risk factors, improved from baseline to week 24 and week 48 regardless of degree of mUFC control. Additionally, most participants reported improvements in physical features of hypercortisolism, including hirsutism, at week 24 and week 48. The researchers indicated that the high response rate with osilodrostat treatment was sustained during the 48 weeks of treatment, with 96% of patients achieving controlled mUFC levels; improvements in clinical signs, physical features, quality of life, and depression were reported even among patients without complete mUFC normalization. Disclosure: This study was sponsored by Novartis Pharma AG; however, as of July 12, 2019, osilodrostat is an asset of Recordati AG. Please see the original reference for a full list of authors’ disclosures. Visit Endocrinology Advisor‘s conference section for complete coverage from the AACE Annual Meeting 2021: ENVISION. Reference Pivonello R, Fleseriu M, Newell-Price J, et al. Effect of osilodrostat on clinical signs, physical features and health-related quality of life (HRQoL) by degree of mUFC control in patients with Cushing’s disease (CD): results from the LINC 3 study. Presented at: 2021 AACE Virtual Annual Meeting, May 26-29, 2021. From https://www.endocrinologyadvisor.com/home/conference-highlights/aace-2021/osilodrostat-improves-blood-pressure-hrqol-and-depression-in-patients-with-cushing-disease/
    2 points
  8. HRA Pharma Rare Diseases, an affiliate of privately-held French healthcare company HRA Pharma, has revealed data from the six-month extension of PROMPT, the first ever prospective study designed to evaluate metyrapone long-term efficacy and tolerability in endogenous Cushing’s syndrome. After confirming good efficacy and safety of metyrapone in the first phase of the study that ran for 12 weeks, the results of the six-month extension showed that metyrapone successfully maintains low urinary free cortisol (UFC) levels with good tolerability. The data will be presented at the European Congress of Endocrinology 2021 next week. Metyrapone is approved in Europe for the treatment of endogenous Cushing’s syndrome. It works by inhibiting the 11-beta-hydroxylase enzyme, the final step in cortisol synthesis. From https://www.thepharmaletter.com/in-brief/brief-metyrapone-effective-and-safe-in-endogenous-cushing-s-syndrome-in-long-term-says-hra-pharma-rare-diseases
    2 points
  9. WASHINGTON--Endogenous Cushing's syndrome, a rare hormonal disorder, is associated with a threefold increase in death, primarily due to cardiovascular disease and infection, according to a study whose results will be presented at ENDO 2021, the Endocrine Society's annual meeting. The research, according to the study authors, is the largest systematic review and meta-analysis to date of studies of endogenous (meaning "inside your body") Cushing's syndrome. Whereas Cushing's syndrome most often results from external factors--taking cortisol-like medications such as prednisone--the endogenous type occurs when the body overproduces the hormone cortisol, affecting multiple bodily systems. Accurate data on the mortality and specific causes of death in people with endogenous Cushing's syndrome are lacking, said the study's lead author, Padiporn Limumpornpetch, M.D., an endocrinologist from Prince of Songkla University, Thailand and Ph.D. student at the University of Leeds in Leeds, U.K. The study analyzed death data from more than 19,000 patients in 92 studies published through January 2021. "Our results found that death rates have fallen since 2000 but are still unacceptably high," Limumpornpetch said. Cushing's syndrome affects many parts of the body because cortisol responds to stress, maintains blood pressure and cardiovascular function, regulates blood sugar and keeps the immune system in check. The most common cause of endogenous Cushing's syndrome is a tumor of the pituitary gland called Cushing's disease, but another cause is a usually benign tumor of the adrenal glands called adrenal Cushing's syndrome. All patients in this study had noncancerous tumors, according to Limumpornpetch. Overall, the proportion of death from all study cohorts was 5 percent, the researchers reported. The standardized mortality ratio--the ratio of observed deaths in the study group to expected deaths in the general population matched by age and sex--was 3:1, indicating a threefold increase in deaths, she stated. This mortality ratio was reportedly higher in patients with adrenal Cushing's syndrome versus Cushing's disease and in patients who had active disease versus those in remission. The standardized mortality ratio also was worse in patients with Cushing's disease with larger tumors versus very small tumors (macroadenomas versus microadenomas). On the positive side, mortality rates were lower after 2000 versus before then, which Limumpornpetch attributed to advances in diagnosis, operative techniques and medico-surgical care. More than half of observed deaths were due to heart disease (24.7 percent), infections (14.4 percent), cerebrovascular diseases such as stroke or aneurysm (9.4 percent) or blood clots in a vein, known as thromboembolism (4.2 percent). "The causes of death highlight the need for aggressive management of cardiovascular risk, prevention of thromboembolism and good infection control and emphasize the need to achieve disease remission, normalizing cortisol levels," she said. Surgery is the mainstay of initial treatment of Cushing's syndrome. If an operation to remove the tumor fails to put the disease in remission, other treatments are available, such as medications. Study co-author Victoria Nyaga, Ph.D., of the Belgian Cancer Centre in Brussels, Belgium, developed the Metapreg statistical analysis program used in this study. ### Endocrinologists are at the core of solving the most pressing health problems of our time, from diabetes and obesity to infertility, bone health, and hormone-related cancers. The Endocrine Society is the world's oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions. The Society has more than 18,000 members, including scientists, physicians, educators, nurses and students in 122 countries. To learn more about the Society and the field of endocrinology, visit our site at http://www.endocrine.org. Follow us on Twitter at @TheEndoSociety and @EndoMedia. Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system. From https://www.eurekalert.org/pub_releases/2021-03/tes-lao031621.php
    2 points
  10. Context Late-night salivary cortisol (LNSC) measured by enzyme immunoassay (EIA-F) is a first-line screening test for Cushing’s syndrome (CS) with a reported sensitivity and specificity of >90%. However, liquid chromatography-tandem mass spectrometry, validated to measure salivary cortisol (LCMS-F) and cortisone (LCMS-E), has been proposed to be superior diagnostically. Objective, Setting, and Main Outcome Measures Prospectively evaluate the diagnostic performance of EIA-F, LCMS-F, and LCMS-E in 1453 consecutive late-night saliva samples from 705 patients with suspected CS. Design Patients grouped by the presence or absence of at least one elevated salivary steroid result and then subdivided by diagnosis. Results We identified 283 patients with at least one elevated salivary result; 45 had an established diagnosis of neoplastic hypercortisolism (CS) for which EIA-F had a very high sensitivity (97.5%). LCMS-F and LCMS-E had lower sensitivity but higher specificity than EIA-F. EIA-F had poor sensitivity (31.3%) for ACTH-independent CS (5 patients with at least one and 11 without any elevated salivary result). In patients with Cushing’s disease (CD), most non-elevated LCMS-F results were in patients with persistent/recurrent CD; their EIA-F levels were lower than in patients with newly diagnosed CD. Conclusions Since the majority of patients with ≥1 elevated late-night salivary cortisol or cortisone result did not have CS, a single elevated level has poor specificity and positive predictive value. LNSC measured by EIA is a sensitive test for ACTH-dependent Cushing’s syndrome but not for ACTH-independent CS. We suggest that neither LCMS-F nor LCMS-E improves the sensitivity of late-night EIA-F for CS. Cushing’s disease, ectopic ACTH, adrenal Cushing’s syndrome, diagnosis, assay performance Issue Section: Clinical Research Article From https://academic.oup.com/jes/advance-article/doi/10.1210/jendso/bvaa107/5876040
    2 points
  11. 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
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  12. 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.
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  13. 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.
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  14. 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
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  15. 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
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  16. 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
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  17. 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?
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  18. 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
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  19. 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
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  20. 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
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  21. It sure sounds like you're on the right track!
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  22. I received my dictation from Doctor F.. I pray that I am on the road to a diagnosis. I don’t know how much more of this I can take.
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  23. 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/
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  24. This is such great news, Donna - the endo sounds fantastic. Can you please share his info with others so that they might have a faster diagnosis, too? Hopefully, surgery will be soon and on to remission!
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  25. I never had a hump but still had Cushing's. Unfortunately your symptoms (and most Cushing's symptoms) can also be caused by other medical conditions so it's important to test everything and if you're concerned about Cushing's I would do some cortisol testing if you haven't already. Have you done any 24 hour urinary free cortisol tests? or had your ACTH checked?
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  26. 1) Visit RareVoiceAwards.org 2) Review the 2021 RareVoice categories 3) Nominate an advocate who gave rare disease patients a voice on Capitol Hill and in state government in 2020 and 2021. 4) Submit! The RareVoice Awards recipients are chosen by a committee from nominations received from the rare disease community. Nominations close August 27th, 2021 Federal Advocacy – Congressional Staff Honors congressional staffers who have worked to create and enact policies for the rare disease community Federal Advocacy – Patient/Organization Honors advocates or organizations that have worked to create and pass federal legislation State Advocacy – State Legislator Honors state legislators who have worked to create and enact policies for the rare disease community State Advocacy – Patient/Organization Honors advocates or organizations that have worked to create and pass state legislation Federal or State Advocacy by a Teenager Honors teen advocates that have advocated for state or federal legislation Diversity Empowerment - Patient/Organization Honors advocates or organizations that empowered diverse voices in advocacy Artist-to-Advocate Honors individuals who have utilized their artwork to advocate for federal or state legislation For information about sponsorship, please contact Elissa Taylor, etaylor@everylifefoundation.org EveryLife Foundation For Rare Diseases 1012 14th Street, NW, Suite 500 | Washington, District of Columbia 20005 202-697-7273 | info@everylifefoundation.org
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  27. Ahmed Saeed Mubarak Mohamed1, Ahmed Iqbal2, Suveera Prasad3, Nigel Hoggard4, Daniel Blackburn1 Correspondence to Dr Daniel Blackburn, Sheffield Teaching Hospitals NHS Foundation Trust Department of Clinical Neurology, Sheffield S10 2JF, UK; d.blackburn@sheffield.ac.uk Abstract Cushing’s disease is a rare endocrine condition in which a pituitary corticotroph adenoma drives excess adrenal cortisol production, and is one cause of endogenous Cushing’s syndrome. We present a young woman with 3 weeks of headaches and cognitive disturbance who subsequently developed florid psychosis requiring multiple admissions under neurology and psychiatry. Her clinical stigmata of hypercortisolism and biochemical abnormalities prompted an MR scan of the pituitary, which confirmed a pituitary microadenoma. Treatment with metyrapone and subsequent surgery led to complete recovery within 2 months. Cushing’s disease commonly causes neuropsychiatric symptoms and can present with psychosis. Diagnosing Cushing’s disease can be challenging, but with early diagnosis and treatment it has an excellent prognosis. http://dx.doi.org/10.1136/practneurol-2021-002974 Get the full text
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  28. Posted because it's interesting for a few reasons, especially the fact that this apparent adrenal Cushing's (bilateral micronodular hyperplasia) did not present with suppressed ACTH. Those values ranged from 8.9 to 38 pg/mL throughout the day, and yet this was not a mild case biochemically. The investigators--who I should point out are the leading experts on this particular subtype of Cushing's--seemed baffled by the discordant results for locating the source. Furthermore, this novel mutation has a different proposed mechanism of action than previously-identified mutations. Finally, the rather young pediatric patient has been successfully treated with low-dose ketoconazole for five years.
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  29. With the goal of reducing false positives for adrenal insufficiency (AI), scientists are recommending a new, more precise diagnostic cutoff of 14-15 μg/dL of serum cortisol, rather than the current 18 μg/dL. The new data were published in the Journal of the Endocrine Society. Among the 110 patients evaluated in the retrospective analysis, new cortisol cutoffs after adrenocorticotropic hormone (ACTH) stimulation were identified when using several of the newer, more widely used diagnostic assays currently available, including Elecsys II (14.6 μg/dL), Access (14.8 μg/dL), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) (14.5 μg/dL). Bradley Javorsky, MD, an endocrinologist and researcher at the Medical College of Wisconsin, served as the study's first author. He recently discussed the findings with MedPage Today. The exchange has been edited for length and clarity. What was the key knowledge gap your study was designed to address? Javorsky: It is safe to say that most clinicians, including many endocrinologists -- not to mention practice guidelines and clinical information resources -- still regard 18 μg/dL as the cutoff for making the biochemical diagnosis of AI after ACTH stimulation testing. However, this cutoff was derived from older polyclonal immunoassays that are no longer being used in many institutions. Newer, more specific monoclonal immunoassays and LC-MS/MS are being used instead. With these more specific assays, one might expect the cutoffs to be lower. What was your finding? Javorsky: After ACTH stimulation, the cutoff values for the newer, more specific cortisol assays were indeed lower at 14-15 μg/dL. Although there was excellent correlation between the new and older assays, the results from the new assays were 22-39% lower than those found by the older and less-specific Elecsys I assay, hence the lowered threshold. Did anything surprise you about the study results? Javorsky: Baseline cortisol had to be very low (approximately <2 μg/dL) in order to be predictive of subnormal cortisol values. This underscores the observation that ACTH stimulation testing is not perfectly sensitive. What are the clinical takeaways from these results? Javorsky: To avoid false-positive ACTH stimulation testing results -- and by extension avoid over-treating patients with glucocorticoids -- clinicians should be aware of the cortisol assay used in their institution and the new cortisol cutoff when evaluating patients for adrenal insufficiency. It should also be reinforced that careful interpretation in the context of clinical history is still essential to making the correct diagnosis. Discordant results among different assays underscore the importance of clinical judgment from an experienced physician when diagnosing AI. What are the takeaways? Javorsky: I think it is important that laboratories make the type of cortisol assay used in their institution easily accessible to clinicians and strongly consider posting the new cortisol cutoff after ACTH stimulation testing when reporting results. Read the study here and expert commentary on the clinical implications here. Disclosures Javorsky reported being a consultant for Clarus Therapeutics and a research investigator for Novartis Pharmaceuticals. Primary Source Journal of the Endocrine Society Source Reference: Javorsky BR, et al "New cutoffs for the biochemical diagnosis of adrenal insufficiency after ACTH stimulation using specific cortisol assays" J Endocrine Soc 2021; 5(4): bvab022. From https://www.medpagetoday.com/endocrine-society/adrenal-disorders/93188
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  30. https://doi.org/10.1002/jbmr.4033 ABSTRACT Endogenous Cushing's syndrome (CS) is a rare cause of secondary osteoporosis. The long‐term consequences for bone metabolism after successful surgical treatment remain largely unknown. We assessed 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. We determined five bone turnover markers at the time of diagnosis, 1 and 2 years postoperatively. The bone turnover markers osteocalcin, intact procollagen‐IN‐propeptide (PINP), alkaline bone phosphatase, CTX‐I, and TrAcP 5b were measured in plasma or serum by chemiluminescent immunoassays. For comparison, 71 sex‐, age‐, and body mass index (BMI)‐matched patients in whom Cushing's syndrome had been excluded were studied. None of the patients received specific osteoanabolic treatment. At time of diagnosis, 69% of the patients had low bone mass (mean T‐score = −1.4 ± 1.1). Two years after successful surgery, the T‐score had improved in 78% of patients (mean T‐score 2 years postoperatively −1.0 ± 0.9). The bone formation markers osteocalcin and intact PINP were significantly decreased at time of diagnosis (p ≤ 0.001 and p = 0.03, respectively), and the bone resorption marker CTX‐I and TrAcP 5b increased. Postoperatively, the bone formation markers showed a three‐ to fourfold increase 1 year postoperatively, with a moderate decline thereafter. The bone resorption markers showed a similar but less pronounced course. This study shows that the phase immediately after surgical remission from endogenous CS is characterized by a high rate of bone turnover resulting in a striking net increase in bone mineral density in the majority of patients. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research. Introduction Cushing's syndrome (CS) is a rare disease with approximately 0.7 to 2.4 new cases per 1 million per year.1 Osteoporosis and osteopenia are typical comorbidities of patients with endogenous and exogenous CS. Depending on the study, 60% to 80% of patients have evidence for a reduced bone mineral density2 characteristically affecting the entire skeleton.3 About 5% of all cases of secondary osteoporosis are caused by hypercortisolism.4 However, data from prospective, well‐powered studies are rare, and few risk factors that would predict bone health have been identified so far. Guidelines for the management of osteoporosis due to endogenous CS are still missing.5 In terms of risk assessment, the subtype of CS does not seem to influence osteoporosis risk,6 whereas the morning cortisol levels are negatively correlated with lumbar bone mineral density.6 The duration of endogenous Cushing's syndrome (or the duration of exogenous replacement therapy after successful surgery) obviously affects bone mineral density.7 Whether the T‐score is the best predictor for fracture risk is not quite clear.2 Another area of uncertainty is the natural course of osteoporosis and bone turnover markers once the diagnosis of Cushing's syndrome has been established. A number of studies have addressed this topic, but the interpretation of the results is hampered because of limited patient numbers, concomitant osteoanabolic treatment, or both.8-10 In‐depth insight on bone remodeling in CS might come from bone turnover marker studies. For example, the bone formation marker osteocalcin is suppressed in untreated CS,3 a consistent observation making it useful as a diagnostic marker for CS.2 Based on the paucity of data, the lack of evidence for treatment guidelines, and the pressing open questions regarding risk assessment and management of osteoporosis, we performed a sufficiently powered study to analyze the natural course of bone turnover and bone mineral density in a monocentric cohort of patients with endogenous Cushing's syndrome. To the best of our knowledge, this is the first such study, and the data obtained will be instrumental for clinicians who care for patients with Cushing's syndrome. Materials and Methods Patients This study was performed as part of the prospective German Cushing registry, which has included 450 consecutive patients referred to our department for suspected CS since 2012. Structure and general characteristics of the registry have been described in detail previously.11-14 All patients included in the registry underwent a standardized biochemical screening and clinical examination at time of diagnosis and a yearly follow‐up after treatment to treat comorbidities and diagnose recurrence of the disease early. In all patients, standard screening for CS with a 1 mg low‐dose overnight dexamethasone suppression test (LDDST), collection of 24‐hour urine (UFC), and sampling of midnight salivary cortisol were performed. When the diagnosis of CS was confirmed, further subtyping was based on plasma adrenocorticotropic hormone (ACTH), corticotropin‐releasing hormone (CRH) test, high‐dose dexamethasone suppression test, imaging, and inferior petrosal sinus sampling (in case of ACTH dependence). Final diagnosis was CS in 156 patients and exclusion of CS in the remaining 294 patients. Patients with excluded CS were a quite heterogenic group with lead symptoms such as obesity (73%), arterial hypertension (50%), or hirsutism (33%). Final diagnoses in these subjects were metabolic syndrome, polycystic ovary syndrome (PCOS), obesity, depression, or primary hyperaldosteronism. Patient selection is shown in Fig. 1. Figure 1 Open in figure viewerPowerPoint Patient selection. *Very young age; patient conducted densitometry in a different clinic/outpatient clinic; patient refused densitometry. CS = Cushing's syndrome; BMD = bone mineral density; BMI = body mass index. Bold text indicates actual cohort of the study. In our analysis, we excluded patients for whom no densitometry data were available (n = 63) and patients receiving pharmacologic treatment for osteoporosis following diagnosis (n = 4). Densitometry data were not available for multiple reasons (very young age, external densitometry in a different clinic, missing consent to perform densitometry). We matched the remaining 89 patients with 71 controls subjects selected from those subjects in whom CS was excluded. Matching was done according to sex, age, and body mass index (BMI). None of the patients and controls received specific osteoanabolic or antiresorptive treatment, but 47% of patients with CS received vitamin D supplementation after remission. At time of diagnosis, 11% of controls and 17% of patients with CS received vitamin D supplementation. Methods In patients with confirmed CS, a bone mineral densitometry was conducted. Bone mineral density (BMD) was determined at the lumbar spine and the femur (neck and total femur). If a reduced bone mineral density was diagnosed, a follow‐up densitometry was performed 2 years after surgery. If bone mineral density was normal initially or during follow‐up, only one further densitometry was performed 2 or 3 years after initial diagnosis. An improvement or decrease of bone mineral density was defined according to the least significant change (LSC = 2.8 × 1.8%).15 Accordingly, an alteration of more than 5.04% of BMD was rated as significant. A detailed fracture history was taken and X‐ray of the spine was performed when clinical suspicion for fractures was high. In all patients, blood samples (serum and plasma) were taken at time of diagnosis and also 1 and 2 years after successful transsphenoidal surgery or adrenalectomy. Blood was taken in the fasting state between 8:00 and 10:00 a.m. Samples were centrifuged within 20 minutes at 4°C and stored at −80° until assayed. Three bone formation markers and two bone resorption markers were measured: osteocalcin, intact procollagen I‐N‐propeptide (PINP), and bone alkaline phosphatase (BAP) as bone formation markers, and CrossLaps (CTX‐I) and tartrate‐resistant acid phosphatase (5b TrAcP5b) as bone resorption marker, on basis of published data demonstrating their usefulness in CS and primary osteoporosis.2, 16 Samples were measured at the Endocrine Laboratory of the Department of Internal Medicine IV on the iSYS automated analyzer (IDS‐iSYS, Boldon, UK) by well‐validated assays.17, 18 Published, method‐specific reference intervals are available from a large healthy population.19, 20 For the determination of osteocalcin, an N‐MID assay was used, as pre‐analytics are less critical in this assay.21 TrAcp 5b is a new marker, which, in contrast to CTX‐1, can also reliably be measured in the non‐fasting state.22 Statistical analysis In a priori power analysis, we calculated that a total sample size of 102 would be sufficient to identify significant differences between groups, assuming a medium effect size (0.5), a power of 1 – β = 0.80 and a type I error of α = 0.05, with 51 subjects having Cushing's syndrome and 51 subjects being control subjects after excluding Cushing's syndrome. For statistical analysis, SPSS 25 (IBM Corp., Armonk, NY, USA) was used. Clinical characteristics are shown as mean and standard deviation when data is normal distributed; otherwise as median and ranges. Because of the lack of normal distribution of bone turnover markers, nonparametric tests were used to test differences between groups. Differences between bone turnover markers at different times were tested by Friedman test. Multiple regression analysis was used to investigate differences between CS and the control group regarding bone turnover markers adjusted for sex, age, and BMI. Any p values < 0.05 were considered to indicate statistical significance. Results Patient characteristics The clinical and biochemical characteristics of the patient sample are summarized in Table 1. Sixty‐five percent of patients had pituitary CS, 28% adrenal, and 7% suffered from ectopic CS. Patients and controls were well‐matched regarding sex, age, and vitamin D levels and supplementation, but differed in terms of diabetes prevalence. Table 1. Clinical and Biochemical Baseline Characteristics of Patients with Cushing's Syndrome (CS) and Control Subjects in Whom CS Has Been Excluded CS at time of diagnosis (n = 89) CS excluded (n = 71) p Value Sex 66 women (74%), 23 men (26%) 53 women (75%), 18 men (25%) 0.94 Age (years) 44 ± 13 43 ± 14 0.56 BMI 30 ± 7 31 ± 6 0.11 Vitamin D (ng/mL) 24 ± 10 24 ± 12 0.59 Vitamin D supplementation 17% 11% 0.37 Diabetes mellitus 30% (26) 11% (7) 0.007 Morning serum cortisol (μg/dL) 18 (11.7–24.9) 8.4 (5.9–11.6) ≤0.001 LDDST (μg/dL) 14.7 (7.7–23.7) 1.0 (0.8–1.2) ≤0.001 UFC (μg/24 h) 587 (331–843) 140 (78–216) ≤0.001 ACTH (pg/mL) 47 (9–76) 13 (9–18) ≤0.001 Late‐night salivary cortisol (ng/mL) 7.9 (3.3–11.8) 1.2 (0.6–1.8) ≤0.001 Bone turnover markers Osteocalcin (ng/mL) 8 (5–13) 13 (10–17) <0.001 PINP (ng/mL) 35 (29–62) 52 (35–73) 0.025 BAP (μg/L) 23 (16–31) 17 (14–24) 0.006 CTX‐I (ng/mL) 0.28 (0.17–0.42) 0.23 (0.12–0.32) 0.033 TrAcP (U/L) 2.3 (1.7–3.4) 1.9 (1.3–2.4) 0.009 Date are shown as mean ± standard deviation or median and ranges. BMI = body mass index; LDDST = low‐dose dexamethasone suppression test; UFC = urinary free cortisol; ACTH = adrenocorticotropic hormone; PINP = intact procollagen I‐N‐propeptide; BAP = bone alkaline phosphatase; CTX‐I = CrossLaps; TrAcP = tartrate‐resistant acid phosphatase. Bold numbers indicate statistical significance. Baseline evaluation At time of diagnosis, the mean levels of bone formation markers osteocalcin and intact PINP were significantly decreased compared with the controls, and the bone formation marker bone alkaline phosphatase was increased (Table 1; Fig. 2). Both bone degradation markers CTX and TrAcP were increased (Table 1). Taken together, this demonstrates increased bone resorption and decreased bone formation in florid CS. Results of multiple linear regression analysis comparing Cushing's syndrome patients and controls are shown in Table 2. Bone markers were similar in patients with a reduced bone mass versus those with a normal bone mass (data not shown). Figure 2 Open in figure viewerPowerPoint Bone turnover markers and bone mineral density at baseline and 1 and 2 years after remission. Boxplot = median and ranges of bone turnover marker in patients with Cushing's syndrome.Gray box = median and ranges of bone turnover markers in the control group.PINP = procollagen I‐N‐propeptide; BAP = bone alkaline phosphatase; TrAcP = tartrate‐resistant acid phosphatase; CTX‐I = CrossLaps. Table 2. Results of Multiple Linear Regression Analysis Comparing Cushing's Syndrome Patients Versus Controls Dependent variable Standardized regression coefficient and p value for group variable Unadjusted Adjusted for age, sex, and BMI Osteocalcin (ng/mL) −0.392, 0.006 −0.375, 0.010 PINP (ng/mL) −0.215, 0.204 −0.256, 0.145 BAP (μg/L) 0.404, 0.001 0.470, <0.001 CTX‐I (ng/mL) 0.111, 0.366 0.065, 0.616 TrAcP (U/L) 0.227, 0.014 0.186, 0.069 PINP = procollagen I‐N‐propeptide; BAP = bone alkaline phosphatase; CTX‐I = CrossLaps; TrAcP = tartrate‐resistant acid phosphatase. Bold numbers indicate statistical significance. Overall, bone mineral density was decreased with an average lowest T‐score of −1.4 (±1.1). BMD was significantly lower (p = 0.001) at the femoral neck (T‐score = −0.9 ± 1.0) and the spine (T‐score = −1.0 ± 1.5) compared with the total femur (T‐score = −0.5 ± 1.2). Twenty‐eight patients (32%) had a normal bone mineral density, 46 (52%) osteopenia, and the other 15 patients (17%) osteoporosis with a T‐score lower than −2.5. Seventeen of the patients (19%) had a history of low‐trauma osteoporotic fractures (9 vertebral fractures, 8 nonvertebral fractures). The fractures took place shortly before diagnosis (58%) or more than 2 years before diagnosis of the CS (42%). Patients with osteoporotic fractures had a significantly lower T‐score than patients without fractures (T‐score = −1.9 ± 0.8 versus −1.3 ± 1.1, p = 0.03) but did not differ in the values of the bone turnover markers or standard biochemical screening. Subtype, age, or BMI also did not differ between groups. However, men were significantly at higher risk of having fractures than women (35% of men had fractures versus 14% of women, p = 0.03). Both severity of hypercortisolism and duration of CS did not contribute to fractures rates (data not shown), but UFC was significantly higher in patients with a T‐score lower than −1.5 (Table 3). Table 3. Biochemical Markers in Patients With Cushing's Syndrome With a T‐Score Lower Than −1.5 and Above −1.5 Shown in Median and Ranges Variable T‐score < −1.5 (n = 39) T‐score ≥ −1.5 (n = 42) p Values LDDST (μg/dL) 16.6. (10.3–28.3) 11.9 (6.1–21.9) 0.12 UFC (μg/24 h) 706 (410–906) 398 (285–787) 0.03 Late‐night salivary cortisol (ng/mL) 8.3 (3.5–13.6) 5.7 (2.9–11.7) 0.39 ACTH (pg/mL) 53 (16–73) 42 (6–82) 0.88 LDDST = low‐dose dexamethasone suppression test; UFC = urinary free cortisol; ACTH = adrenocorticotropic hormone. Bold numbers indicate statistical significance. One‐ and 2‐year follow‐up Surgical tumor resection leading to biochemical remission of CS resulted in a strong increase of bone formation markers tested at 1‐year follow‐up (Table 4; Fig. 2A, B). After 2 years, the markers had decreased slightly but remained elevated. Bone resorption markers were mildly increased at time of diagnosis, increased further at 1 year post‐surgery, and returned almost to normal levels at 2 years (Table 4; Fig. 2D, E). A follow‐up bone densitometry conducted in 40 patients showed a parallel increase of the T‐score of 0.6 ± 0.8 (Fig. 2F). In particular, BMD of the spine improved (Table 5). Table 4. Bone Turnover Markers and Bone Mass in Patients With Cushing's Syndrome at Time of Diagnosis and During 2 Years of Follow‐Up Time of diagnosis (n = 50) 1 year in remission (n = 45) 2 years in remission (n = 38) p (0 versus 1) p (0 versus 2) p (1 versus 2) T‐score −1.5 (−2.0 to −0.8) – −1.1 (−1.5 to −0.4) – <0.001 – Osteocalcin (ng/mL) 8 (5–13) 30 (14–60) 21 (13–31) <0.001 0.008 0.3 PINP (ng/mL) 35 (29–62) 117 (52–221) 69 (46–113) <0.001 0.1 0.1 BAP (μg/L) 23 (16–31) 26 (19–38) 22 (15–31) 0.2 0.4 0.1 CTX‐I (ng/mL) 0.28 (0.17–0.42) 0.51 (0.22–0.91) 0.25 (0.18–0.73) 0.01 0.1 0.04 TrAcP (U/L) 2.3 (1.7–3.4) 2.8 (1.8–4.0) 2.3 (2–3.2) 0.1 0.6 0.002 PINP = procollagen I‐N‐propeptide; BAP = bone alkaline phosphatase; CTX‐I = CrossLaps; TrAcP = tartrate‐resistant acid phosphatase. Bold numbers indicate statistical significance. Table 5. Overview: T‐Scores, Z‐Scores, and BMD Values With Percent Changes (Mean and Standard Deviation) Variable CS at time of diagnosis CS 2 years in remission p Values, percent changes (↑) Femoral neck T‐score femoral neck −0.81 ± 0.97 −0.59 ± 0.86 0.06 Z‐score femoral neck −0.59 ± 0.98 −0.28 ± 0.79 0.02 BMD (g/cm2) femoral neck 0.91 ± 0.12 0.95 ± 0.12 0.16; 4% ↑ Femur T‐score femur −0.49 ± 1.11 −0.42 ± 1.04 0.67 Z‐score femur −0.40 ± 1.04 −0.37 ± 0.85 0.31 BMD (g/cm2) femur 0.95 ± 0.15 0.97 ± 0.14 0.77, 2% ↑ Spine T‐score spine −0.96 ± 1.56 −0.55 ± 1.25 <0.001 Z‐score spine −0.85 ± 1.53 −0.58 ± 1.14 <0.001 BMD (g/cm2) spine 1.08 ± 0.22 1.13 ± 0.15 0.001, 0.6% ↑ BMD = bone mineral density; CS = Cushing's syndrome. Bold numbers indicate statistical significance. In 78% of patients, bone mineral density improved after 2 years; in 45% of patients, T‐score improved more than 0.5. No clinical fractures occurred after successful treatment of the CS. There was no significant correlation between improvement of bone mineral density and any of the bone turnover markers. Discussion This study investigated for the first time to our knowledge a panel of bone formation and resorption markers in a large cohort of patients with CS over the long term. The unique and comprehensive data show that initially bone metabolism is characterized by decreased bone formation and increased bone resorption, in line with the classical action of glucocorticoids. Successful treatment of endogenous Cushing's syndrome leads to a strong activation of bone turnover, characterized by increased bone formation and bone resorption, a process that is continuous beyond year 2 after remission of CS, although at a reduced activity level. In parallel, bone mineral density increases in the majority of patients. Although 19% had low‐trauma fractures at baseline, none of the subjects experienced clinical fractures during follow‐up. In summary, these data give new insight into bone healing after remission of CS. They strongly suggest that an observational approach to the bone phenotype is justified as long as remission from CS is secured. Reversibility of osteoporosis and bone turnover markers Although established in osteoporosis research, bone turnover markers are not measured on a routine basis in patients with CS. However, it is a consistent result from different studies that osteocalcin is depressed in patients with CS. In fact, this finding is so reliable that it was even suggested to use osteocalcin in the diagnosis of CS.2 P1NP and procollagen carboxy‐terminal propeptide (P1CP) have also been studied in several studies, with contradictory results.23 In a retrospective study with 21 patients with CS, it was shown that osteocalcin is depressed; this applies also for PINP, whereas CTX is increased.24 Some studies already have focused on the reversibility of osteoporosis after treatment of CS. In the majority of patients, bone mineral density increased within 2 years after successful treatment8-10, 25 Hermus and colleagues showed in a study with 20 patients that bone mineral density did not change 3 or 6 months after surgery but increased thereafter in almost all patients.8 In a study with 68 patients, the patients were followed up for 4 years. Bone mineral density increased over lumbar spine and femur but decreased at the forearm.25 The authors concluded that bone minerals were redistributed from the peripheral to the axial skeleton. In our study, bone mineral density also improved in the majority of patients but remained reduced in some. We did not find any difference in bone turnover markers between patients with improvement and without improvement. Current treatment guidelines and treatment suggestions As observed in our study, bone formation markers increase significantly after surgical cure, whereas bone degradation markers are mildly elevated at baseline and increase slightly at 1 year, returning within the normal range at 2 years. So far, there is no international guideline on the treatment of osteoporosis induced by endogenous CS and very few controlled interventional studies. In an opinion paper, Scillitani and colleagues recommended to treat all patients with vitamin D and calcium but not with bisphosphonates.5 In a randomized open‐label study by Di Somma and colleagues,26 39 patients (18 patients with active CS and 21 patients with CS in remission) received alendronate or no medication. Patients with active CS also received ketoconazole to control hypercortisolism. Bone mineral density improved and serum levels of osteocalcin increased in patients who received alendronate to a greater extent than those receiving no alendronate. In a small study by the same research group,27 15 patients with CS (9 adolescent patients and 6 adults) were observed for 2 years after successful treatment, showing that osteocalcin levels and bone mineral density increased significantly. Strengths and limitations Although this study has several strengths, including the large prospective design and measuring a panel of bone formation and resorption markers, there are a few limitations. Some asymptomatic fractures may have been overlooked because an X‐ray was not taken systematically in each patient. Furthermore, a follow‐up bone densitometry was not available for all patients. Additionally, patients in the control group suffered from diabetes, overweight, arterial hypertension, or other diseases. Novel aspects and outlook This study analyzes for the first time in a comprehensive way bone turnover markers during the course of CS. The data show that cure from CS leads to increases in bone remodeling and bone mineral density, in line with spontaneous “bone healing.” Our data support a wait‐and‐watch strategy despite a high endogenous risk for additional fractures, based on the baseline assessment. This observation will influence future therapeutic strategies in patients with CS. Our data suggest that the phase immediately after remission from CS is characterized by a high rate of bone turnover, resulting in a spontaneous net increase in bone mineral density in the majority of patients. Both bone attachment and bone degradation markers increase significantly, leading to an increase in bone mass and to a reduced risk of osteoporotic fractures. This unconstrained increase in bone formation markers after remission should be considered before specific therapy is initiated. Our data do not favor specific pharmacologic interventions with bisphosphonates or denosumab during this phase of remodeling because they may disrupt the osteoblast‐mediated bone mass increase. Disclosures All authors state that they have no conflicts of interest. Acknowledgments This work is part of the German Cushing's Registry CUSTODES and has been supported by a grant from the Else Kröner‐Fresenius Stiftung to MR (2012_A103 and 2015_A228). Additionally, AR, FB, and MR received funding by the Deutsche Forschungsgemeinschaft (CRC/TRR 205/1 “The Adrenal Gland”). Furthermore, funds for this project were provided by the Verein zur Förderung von Wissenschaft und Forschung an der Medizinischen Fakultät der Ludwig‐Maximilians‐Universität München eV to LB. The data are stored on the following repository: https://figshare.com/ and will be made accessible after publication of the article. Authors’ roles: LB served as the principal investigator in this work and was responsible for the study conception and design, the analysis and interpretation of the data, and the drafting of the manuscript. JF, SZ, AO, AR, GR and SB contributed to the collection and analysis of the data. MS, FB, MD, MB substantially contributed to the interpretation of the data and the drafting of the manuscript. RS contributed to the conceptual design of the study, the interpretation of data and the revision of the paper. MR contributed to the conceptual design of the study, the collection, analysis and interpretation of data, and the drafting and revision of the paper. All authors contributed to the critical revision of the manuscript and approved the final version for publication. From https://asbmr.onlinelibrary.wiley.com/doi/full/10.1002/jbmr.4033
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  31. A retrospective cohort study was performed to compare mortality risk and causes of death in adrenal insufficiency with an individually-matched reference population. Researchers examined 6,821 patients with adrenal insufficiency (primary, 2052; secondary, 3948) and 6,7564 individually-matched controls (primary, 20366; secondary, 39134). It was shown that in adrenal insufficiency, mortality was elevated, particularly primary, even with individual matching, and was found early in the disease course. The data demonstrated that cardiovascular disease was the major cause but mortality from infection was also high. The adrenal crisis was a common contributor. The outcomes suggested that early education for prompt treatment of infections and avoidance of adrenal crisis hold the potential to decrease mortality. The Journal of Clinical Endocrinology & Metabolism, dgab096, https://doi.org/10.1210/clinem/dgab096 Abstract Context Mortality data in patients with adrenal insufficiency are inconsistent, possibly due to temporal and geographical differences between patients and their reference populations. Objective To compare mortality risk and causes of death in adrenal insufficiency with an individually-matched reference population. Design Retrospective cohort study. Setting UK general practitioner database (CPRD). Participants 6821 patients with adrenal insufficiency (primary, 2052; secondary, 3948) and 67564 individually-matched controls (primary, 20366; secondary, 39134). Main outcome measures All-cause and cause-specific mortality; hospital admission from adrenal crisis. Results With follow-up of 40799 and 406899 person-years for patients and controls respectively, the hazard ratio (HR; [95%CI]) for all-cause mortality was 1.68 [1.58 - 1.77]. HRs were greater in primary (1.83 [1.66 - 2.02]) than in secondary (1.52 [1.40 - 1.64]) disease; (HR; primary versus secondary disease, 1.16 [1.03 - 1.30]). The leading cause of death was cardiovascular disease (HR 1.54 [1.32-1.80]), along with malignant neoplasms and respiratory disease. Deaths from infection were also relatively high (HR 4.00 [2.15 - 7.46]). Adrenal crisis contributed to 10% of all deaths. In the first two years following diagnosis, the patients’ mortality rate and hospitalisation from adrenal crisis were higher than in later years. Conclusion Mortality was increased in adrenal insufficiency, especially primary, even with individual matching and was observed early in the disease course. Cardiovascular disease was the major cause but mortality from infection was also high. Adrenal crisis was a common contributor. Early education for prompt treatment of infections and avoidance of adrenal crisis hold potential to reduce mortality. PDF available at https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgab096/6141434?redirectedFrom=fulltext
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  32. Do you mean dexamethasone suppression test?
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  33. 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
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  34. Levels of adrenocorticotropic hormone (ACTH) in circulation after pituitary surgery may help predict which Cushing’s disease patients will achieve early remission and which will eventually see the disease return, a study shows. Also, the earlier that patients reached their lowest peak of ACTH levels, the better their long-term outcomes. The study, “Prognostic usefulness of ACTH in the postoperative period of Cushing’s disease,” was published in the journal Endocrine Connections. Removing the pituitary tumor through a minimally invasive surgery called transsphenoidal surgery is still the treatment of choice for Cushing’s disease patients. But not all patients enter remission, and even among those who do, a small proportion will experience disease recurrence. While cortisol levels have been suggested as a main predictor of remission and recurrence, there is no consensus as to which cutoff point should be used after surgery, or the best time for measuring this hormone. Because Cushing’s disease is caused by an ACTH-producing tumor in the pituitary gland, and ACTH has a short half-life (approximately 10 minutes), it is expected that ACTH levels drop markedly within a few hours after surgery. Thus, a group of researchers in Spain aimed to determine whether blood levels of ACTH could be useful for predicting remission of Cushing’s disease both immediately after surgery (defined as less than 72 hours) and in the long term. Researchers analyzed 65 patients with Cushing’s disease who had undergone transsphenoidal surgery (seven required a second intervention) between 2005 and 2016. Remission within three months was seen in 56 of 65 cases; late disease recurrence was seen in 18 of 58 cases. Investigators measured the ACTH nadir concentration (defined as the lowest concentration) and the time taken to reach nadir levels after surgery, as well as the plasma ACTH concentration before hospital discharge. While ACTH levels had no predictive value, the team found that people who went into remission had significantly lower ACTH nadir levels and ACTH levels at discharge. On the other hand, levels of ACHT nadir and at discharge were significantly higher for people who experienced a relapse, compared to those who remained in remission. Using artificial intelligence algorithms, the researchers further found that ACTH nadir, ACTH at discharge, and cortisol nadir values were all of great relevance to predict remission within three months. Analysis indicated that using a cutoff point of 3.3 pmol/L of ACTH after surgery and before discharge gave the best sensitivity and specificity for predicting a patient’s prognosis. Researchers further found that the time patients took to reach their ACTH nadir, regardless of nadir levels, also influenced their outcomes. In fact, patients reaching this nadir in less than than 46 hours more likely achieved early remission. And taking longer than 39 hours to reach the ACTH nadir was significantly more frequent in patients who experienced recurrence. This indicates that the time to ACTH nadir is an important measure for prognosis. “In the immediate postoperative period of patients with [Cushing’s disease], the ACTH concentration is of prognostic utility in relation to late disease remission,” the researchers said. Overall, “we propose an ACTH value <3.3 pmol/L as a good long-term prognostic marker in the postoperative period of CD. Reaching the ACTH nadir in less time is associated to a lesser recurrence rate,” the study concluded. PATRICIA INACIO, PHD EDITOR Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York. From https://cushingsdiseasenews.com/2019/08/29/acth-levels-after-surgery-help-predict-remission-recurrence-in-cushings-study-suggests/
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  35. Wannachalee T, et al. Clin Endocrinol. 2019;doi:10.1111/cen.14008. May 20, 2019 A radioactive diagnostic agent for PET imaging effectively localized primary tumors or metastases in most adults with ectopic Cushing’s syndrome, leading to changes in clinical management for 64% of patients, according to findings from a retrospective study published in Clinical Endocrinology. As Endocrine Today previously reported, the FDA approved the first kit for the preparation of gallium Ga-68 dotatate injection (Netspot, Advanced Accelerator Applications USA Inc.), a radioactive diagnostic agent for PET scan imaging, in June 2016. The radioactive probe is designed to help locate tumors in adult and pediatric patients with somatostatin receptor-positive neuroendocrine tumors. Ga-68 dotatate, a positron-emitting analogue of somatostatin, works by binding to the hormone. In a retrospective review, Richard Auchus, MD, PhD, professor of pharmacology and internal medicine in the division of metabolism, endocrinology and diabetes at the University of Michigan, and colleagues analyzed data from 28 patients with ectopic Cushing’s syndrome who underwent imaging with gallium Ga-68 dotatate for identification of the primary tumor or follow-up between November 2016 and October 2018 (mean age, 50 years; 22 women). All imaging was completed at tertiary referral centers at Mayo Clinic, University of Michigan and The University of Texas MD Anderson Cancer Center. Researchers assessed patient demographics, imaging modalities, histopathological results and treatment data. Diagnosis of Cushing’s syndrome was confirmed by clinical and hormonal evaluation. The clinical impact of gallium Ga-68 dotatate was defined as the detection of primary ectopic Cushing’s syndrome or new metastatic foci, along with changes in clinical management. Within the cohort, 17 patients underwent imaging with gallium Ga-68 dotatate for identification of the primary tumor and 11 underwent the imaging for follow-up. Researchers found that gallium Ga-68 dotatate identified suspected primary ectopic Cushing’s syndrome in 11 of 17 patients (65%), of which seven tumors were solitary and four were metastatic. Diagnosis was confirmed by pathology in eight of the 11 patients: Five patients had a bronchial neuroendocrine tumor, one patient had a thymic tumor, one had a pancreatic neuroendocrine tumor, and one metastatic neuroendocrine tumor was of unknown primary origin. One patient had a false positive scan, according to researchers. Among the 11 patients with ectopic Cushing’s syndrome who underwent gallium Ga-68 dotatate imaging to assess disease burden or recurrence, the imaging led to changes in clinical management in seven cases (64%), according to researchers. “Our study demonstrates the high sensitivity of [gallium Ga-68 dotatate] in the localization of [ectopic Cushing’s syndrome], for both occult primary tumors and metastatic lesions,” the researchers wrote. “Importantly, the use of [gallium Ga-68 dotatate] impacted clinical management in 64% of patients with [ectopic Cushing’s syndrome] overall.” The researchers noted that the high cost and limited availability of PET/CT imaging might preclude the widespread use of gallium Ga-68 dotatate for imaging in patients with suspected ectopic Cushing’s syndrome, and that experience with the scans remains limited vs. other imaging studies. “Nevertheless, combing the experience of three large referral centers, our study gathers the largest number of [patients with ectopic Cushing’s syndrome] imaged with [gallium Ga-68 dotatate] to date and provides a benchmark for the utility of this diagnostic modality for this rare but highly morbid condition,” the researchers wrote. – by Regina Schaffer Disclosures: The authors report no relevant financial disclosures. From https://www.healio.com/endocrinology/adrenal/news/online/%7B69e458a8-e9a0-4567-a786-00868118b435%7D/imaging-agent-effectively-detects-localizes-tumors-in-cushings-syndrome
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  36. Hi, Deb - I looked in the bios but couldn't find anyone who mentioned Alpha 1 antitrypsin deficiency There are several people who mentioned liver issues -https://cushingsbios.com/?s=liver and some who mentioned lung problems - https://cushingsbios.com/?s=lung Best of luck to you.
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  37. this is terrifying to read. is this accurate and current?
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  38. Laparoscopic adrenalectomy — a minimally invasive procedure that removes the adrenal glands through a tiny hole in the abdomen — can be safely performed in obese patients with Cushing’s syndrome, a retrospective study reports. The surgery resolved symptoms in 95% of cases, reducing cortisol levels, lowering blood pressure, and leading to a significant loss of weight in morbidly obese patients. The study, “Minimally invasive approach to the adrenal gland in obese patients with Cushing’s syndrome,” was published in the journal Minimally Invasive Therapy & Allied Technologies. Cushing’s syndrome results from the prolonged secretion of excess cortisol, the major glucocorticoid hormone. While most cases are caused by tumors in the pituitary gland, up to 27% result from tumors in the adrenal glands. In these cases, the standard therapeutic strategy is to remove one or both adrenal glands, a surgical procedure called adrenalectomy. However, because glucocorticoids are key hormones regulating fat metabolism, Cushing’s syndrome patients are known to be prone to obesity, a feature that is often associated with post-operative complications. In this study, researchers aimed to compare the outcomes of morbidly obese patients versus the mildly obese and non-obese who underwent a minimally invasive procedure to remove their adrenal glands. The approach, called laparoscopic adrenalectomy, inserts tiny surgical tools through a small hole in the abdomen, along with a camera that helps guide the surgeon. The study included 228 patients (mean age 53.4 years). Of them, 62 were non-obese, 87 were moderately obese, and 79 were considered morbidly obese. There were 121 patients with tumors in the right adrenal gland, 96 in the left gland, and 11 in both glands. High blood pressure was the most common symptom, affecting 66.7% of the participants. Surgery lasted 101 minutes on average, and patients remained in the hospital for a median 4.3 days afterward. Six patients had to be converted into an open surgery because of uncontrollable loss of blood or difficulties in the procedure. Post-surgery complications, most of which were minor, were seen in seven patients. One patient had blood in the peritoneal cavity and had to have surgery again; another patient had inflammation of the pancreas that required a longer admission. The analysis showed no statistical differences among the three groups regarding the length of surgery, length of stay in the hospital, or the rate of conversion into open surgery. However, in obese women, surgeons chose a different surgical incision when removing the left adrenal gland, “suggesting that the distribution of visceral fat in these patients could constitute a drawback for the [standard] approach,” researchers said. After the surgery, 95% of patients saw their symptoms resolve, including cortisol levels, high blood pressure, and glucose metabolism, and none had a worsening of symptoms in the 6.3 years of follow-up. Obese patients also showed a significant reduction in their weight — 2 kg by 18 months, and 5 kg by the end of follow-up. Overall, “laparoscopic adrenalectomy is safe and feasible in obese patients affected with Cushing’s disease and it can lead to the resolution of the related symptoms,” researchers said. The benefits of the surgery in patients with Cushing’s syndrome “could be extended to the improvements and in some cases to the resolution of hypercortisolism related symptoms (i.e. hypertension or even morbid obesity),” the study concluded. Adapted from https://cushingsdiseasenews.com/2019/02/07/laparoscopic-removal-of-adrenal-glands-safe-for-obese-cushings-patients/
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  39. Patna: Improper functioning of the Pituitary gland usually results in excess or under production of hormones that leads to a formation of mass called tumor, which can be benign or malignant. Such tumors in this gland can create numerous serious medical conditions by interfering with the normal functioning of the endocrine system and pituitary gland. “Though the occurrence of tumor is more likely after the age of 30 years, it still can impact at an early age. The survival rates of tumor due to its complicated location also depend on other factors like the patient’s age, type and size of tumor. Mostly, pituitary gland tumors are non cancerous but the exact causes are unknown. Some of them are hereditary and some are caused by a rare genetic disorder called as multiple endocrine neoplasia type 1. This disorder can also lead to over-activity or enlargement of 3 different endocrine-related glands, which also includes the pituitary gland. “Dr Aditya Gupta, Director, Neurosurgery, Agrim institute for neuro sciences, Artemis Hospital Diagnosis at an early stage can help the treatment procedure to be totally non-invasive with the use of advances technology called as Cyberknife. Cyberknife which is the most advanced radiation therapy is completely non-invasive therapy available for the treatment of benign as well as malignant tumors. This therapy works the best for some pituitary tumors that are upto 2 cm in size and is a very powerful and effective technique for treating patients suffering from early stage primary and medically inoperable tumors. The treatment is safe to administer and also offers a new option in patients with recurrent disease or a single disease in the body. “Highlights of the therapy being ease of access to any complex location without the need to use the surgical knife, precision of the beam with high dose radiation to the tumor location, and the safety. It is a day care procedure without pain and risk, and the patient can get back to daily chores as soon as the session gets over which depends on the tumor typically (30 minutes) and hence eliminates the requirement of any hospital stay.” Added Dr Gupta Depending upon the hormonal variations in the body, there can be a variety of symptoms. The most common symptoms include Headaches, vision problem, tiredness, mood changes, irritability, changes in menstrual cycle in women, impotence, infertility, Inappropriate breast growth or production of breast milk, Cushing’s syndrome which is a combination of weight gain, high blood pressure, diabetes, and easy bruising, the enlargement of the extremities or limbs, thickening of the skull and jaw caused by too much growth hormone. Pituitary gland, which is also known as the master gland has the most important function of producing hormones that regulates the critical organs of the body including thyroid, adrenal glands, ovaries and testes. It is a small pea-size gland located behind the eyes and below the front of the brain. Some tumors produce hormones known as functional tumors, and others can cause the glands to secrete too few or too many hormones. Also if the tumor pressed on the nearby structure, for instance the optic nerve, can also limit a person’s vision. Moreover the procedure makes use of the most sophisticated image guidance technique to focus high doses of radiation directly to the tumor spot which eliminates the chances to damage the healthy cells as in any other methods of treatment. “Each session of treatment usually lasts for about 30 -50 min and is cost effective with a success rate of 98% in such complicated tumors. Patients with pituitary adenomas receive stereotactic radio surgery with CyberKnife and are followed up for more than 12 months. After 2-3 weeks of therapy patients are monitored for positive responses and ensure there is no recurrence of any mass. Stereotactic radio surgery with the CyberKnife is effective and safe against pituitary adenomas.” Said Dr Gupta From https://www.apnnews.com/hormonal-imbalance-indication-of-pituitary-gland-tumors-2/
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  40. Cushing’s syndrome patients with tumors on both adrenal glands — which sit on top of the kidneys — could undergo adrenal venous sampling, a procedure where blood samples are taken from both adrenal glands to determine which tumors to remove, researchers suggest. Their study, “Outcomes of Adrenal Venous Sampling in Patients with Bilateral Adrenal Masses and ACTH-Independent Cushing’s Syndrome,” was published in the World Journal of Surgery. The work was a collaboration between SUNY Upstate Medical University in Syracuse and the University of Pittsburgh. Cushing’s syndrome, a condition characterized by excess cortisol, can be divided into two main subtypes. In some patients, the disease is dependent on tumors secreting the adrenocorticotropic hormone (ACTH), which stimulates the release of cortisol from the adrenal glands. In others, adrenal tumors are solely responsible for excess cortisol and do not require ACTH for functioning. ACTH-independent Cushing’s syndrome (AICS), the latter subtype, constitutes about 10% to 15% of endogenous — an overproduction of cortisol within the body — Cushing’s syndrome cases, with cortisol-secreting adenomas in just one gland (unilateral) being the most common cause. Compared to unilateral adenomas, adrenal tumors in both glands (bilateral) in patients with AICS are difficult to diagnose. Disease management in these rare cases depends on the challenging determination of the lesion’s exact location and of the functional status of the benign tumors (if they are actively secreting cortisol). Surgical removal of both adrenal glands, also known as bilateral adrenalectomy, “ensures cure of AICS, but leads to permanent corticosteroid dependence and a lifelong risk of adrenal crisis,” investigators explained. Therefore, screening for the presence of unilateral or bilateral adenomas is essential to avoid unnecessary surgery. “Adrenal venous sampling (AVS) has been reported in a single institutional series … to aid in successful localization of cortisol-secreting adrenal adenomas in patients with bilateral adrenal masses and AICS,” researchers wrote. Researchers retrospectively assessed the usefulness of AVS in guiding management of patients with bilateral adrenal masses plus AICS. Nine women (age 51-73) with bilateral adrenal masses and AICS were included in the study. All subjects had undergone AVS at the University of Pittsburgh Medical Center from 2008 to 2016. None of the patients had apparent symptoms of Cushing’s syndrome. “Samples were obtained for testing of epinephrine [also called adrenaline] and cortisol from both [adrenal veins] and the external iliac vein. Multiple samples were obtained to ensure adequate sampling,” they wrote. Adrenal glands produce cortisol and epinephrine, among other hormones, which are critical for maintaining good health. In AICS, there’s an overproduction of both hormones that’s independent on the release of ACTH, which is produced by the brain’s pituitary gland. Successful adrenal venous sampling was achieved in eight women. “One patient with unsuccessful catheterization had [other additional diseases] and passed away from unrelated reasons,” researchers reported. AVS results indicated that all patients had bilateral cortisol-secreting adenomas. “Surgical management was strongly influenced by adrenal mass size. However, AVS may have influenced surgical decision-making in some cases, particularly when minimal difference in size was noted in adrenal mass sizes,” they reported. Six women underwent adrenalectomy: three had the gland with larger size mass removed (unilateral type of surgery); two had both glands removed; and one had the right gland removed followed by the left one, five months later, due to continuous hormonal overproduction without experiencing symptoms of Cushing’s syndrome. Evidence suggests that removal of the larger adrenal mass in patients with bilateral cortisol-secreting adenomas improves Cushing’s syndrome presentation. In theory, unilateral adrenalectomy reduces cortisol production through the removal of the oversecreting mass. Because of this, unilateral adrenalectomy of the larger adrenal mass was chosen in half of this study’s surgical cases, instead of bilateral adrenalectomy. Tissue analysis revealed multiple-lump masses, also known as macronodular adrenal hyperplasia (MAH), in all six surgical cases. In addition, computed tomography (CT) scan findings were predictive of bilateral MAH, with scans showing evidence of one or multiple nodules on one or both adrenal glands. “To the best of our knowledge, this is the second study to evaluate the utility of AVS in guiding management of patients with bilateral adrenal masses and AICS,” investigators said. The first study was by Young and included 10 patients with a more severe presentation of Cushing’s syndrome and other individual characteristics, which contributed to the differences in results, compared to the current study. In Young’s study, half the subjects had unilateral adrenal masses. Patients with bilateral cortisol-secreting masses frequently have a milder form of Cushing’s syndrome, which corroborates researchers’ findings. Despite suggesting that adrenal venous sampling is useful in excluding a unilateral adenoma as the cause of AICS, this study’s sample size is small. “More data are needed before AVS can be advocated as essential for management of patients with bilateral adrenal masses and AICS,” researchers concluded. From https://cushingsdiseasenews.com/2018/10/02/adrenal-venous-sampling-helps-surgical-decisions-type-cushings-syndrome/?utm_source=Cushing%27s+Disease+News&utm_campaign=a990429aad-RSS_WEEKLY_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_ad0d802c5b-a990429aad-72451321
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  41. Responses from Facebook: Shauna : Heard all that for 4 years before my doc sent me to endocrinologist who took great pleasure in calling my doc to advise and ask what surgeon she should sent me too. Robyn: I did all the research and my dr did the testing to shut me up. I was right, unfortunately, and do have Cushings. You have to advocate for yourself. Diana :You will need a variety of tests, if she says just one test, move on. She's wrong. Find a doctor who is willing to test and not tell you what you couldn't possiblly have. Maxine: I heard that same bs. Get a 2nd opinion. It might save your life Sheryl: Get them to check your cortisol level.
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  42. We have a new form to add your own bio! Try it out here: https://cushingsbios.com/2018/08/28/we-have-a-new-bio-form/ Thank you for submitting your bio - sometimes it takes a day or so to get them formatted for the website and listed on the pages where new bios are listed. If you are planning to check the button that reads "Would you like to be considered for an interview? (Yes or No)" please be sure to read the Interview Page for information on how these interviews work. Please do not ask people to email you answers to your questions. Your question is probably of interest to other Cushing's patients and has already been asked and answered on the Message Boards. Occasionally, people may comment on your bio. To read your bio and any comments, please look here for the date you submitted yours and click on the link. Please post any questions for which you need answers on the message boards. HOME | Sitemap | Adrenal Crisis! | Abbreviations | Glossary | Forums | Donate | Bios | Add Your Bio | Add Your Doctor | MemberMap | CushieWiki
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  43. I asked some of the other Cushies I know. One said: "I was dx with dex suppression test. Normal levels in AM, normal 24 hr urine."
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  44. Only 8 days until the Cushing’s Awareness Challenge 2018 begins. At night, when I’m supposed to be sleeping, ideas for posts keep swarming through my head. Sometimes, they form into fully-written posts. Then, when I wake up, the posts are gone. I plan to follow the suggestions to some extent and have a few ideas of my own. Over the years, I’ve posted lots on several blogs but I don’t know if I can get 30 days of Cushing’s stuff together...again! This is the eighth year of the Cushing's Awareness Challenge. The list of bloggers is on the right side and is constantly updated as new URLs come in. If you want to join us, it's not too late. Directions and suggestions for posts can be found here: https://cushieblogger.com/2018/03/11/time-to-sign-up-for-the-cushings-awareness-challenge-2018/ If you have ideas for what you’d like to read about (Cushing’s related, of course), please feel free to put it in the comments area.
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  45. The chemotherapy temozolomide partially improved a case of an aggressive pituitary tumor that caused symptoms of Cushing’s disease (CD), according to a new study in Poland. However, after tumor mass and cortisol levels were stabilized for a few months, the patient experienced rapid progression, suggesting that new methods for extending the effects of temozolomide are needed. The study, “Temozolomide therapy for aggressive pituitary Crooke’s cells corticotropinoma causing Cushing’s Disease: A case report with literature review,” appeared in the journal Endokrynologia Polska. Aggressive pituitary tumors are usually invasive macroadenomas, or benign tumors larger than 10 mm. A very rare subset of pituitary adenoma — particularly corticotropinoma, or tumors with excessive secretion of corticotropin (ACTH) — exhibit Crooke’s cells. These tumors are highly invasive, have a high recurrence rate, and are often resistant to treatment. Information is not widely available about the effectiveness of treating aggressive pituitary tumors, particularly those that cause Cushing’s disease. The management of these tumors usually requires neurosurgery, followed by radiotherapy, and pharmacotherapy. However, the chemotherapy medication temozolomide has been increasingly used as a first-line treatment after initial evidence of its effectiveness in treating glioblastoma, the most common form of brain cancer. In this study, researchers at the Jagiellonian University, in Poland, discussed the case of a 61-year-old man with ACTH-dependent Cushing’s syndrome caused by Crooke’s cell corticotropinoma. The patient first presented with symptoms of severe hypercorticoidism — the excessive secretion of steroid hormones from the adrenal cortex — in December 2011. He also showed advanced heart failure, severe headaches, and impaired vision, which had started two or three years before diagnosis. Examinations revealed osteoporosis and a fracture in the Th5 vertebra. His morning ACTH levels were high. The same was observed for mean cortisol levels even after dexamethasone treatment, which was suggestive of a pituitary tumor secreting ACTH. MRIs showed the existence of a tumor mass, later identified as a macroadenoma with high cell polymorphism, the presence of Crooke’s cells, and ACTH secretion. The patient was referred for transsphenoidal nonradical neurosurgery, performed through the nose and the sphenoid sinus, and bilateral adrenalectomy, or the surgical removal of the adrenal glands, in 2012-2013. However, he developed fast, postoperative recurrence of hypercorticoidism and tumor regrowth. This led to three additional transsphenoidal neurosurgeries and radiotherapy. The patient’s clinical status worsened as he developed severe cardiac insufficiency. Doctors began temozolomide treatment in April 2015, which did not result in adverse effects throughout treatment. The initial standard dose (150–200 mg/m2) was given once daily in the morning for five consecutive days, in a 28-day cycle. The patient also received 600 mg of ketoconazole, an antifungal medication. Ondansetron was administered to prevent nausea and vomiting. Subsequent examinations revealed clinical and biochemical improvements, including a reduction in ACTH and cortisol levels. In addition, the patient also showed reduced cardiac insufficiency, less frequent and less severe headaches, visual field improvements, and better physical fitness and mood. However, clinical symptoms worsened after the eighth temozolomide cycle. The tumor size also suddenly increased after the ninth cycle, reaching the inner ear. Temozolomide was then discontinued and ACTH levels increased by 28 percent one month later. The patient also demonstrated deteriorated vision, hearing loss, and strong headaches. Clinicians then decided to start treatment with the Cushing’s disease therapy Signifor (pasireotide), but a worsening of diabetes was observed, and the patient died in February 2016. “The most probable reason for death was compression of the brainstem, which had been observed in the last MRI of the pituitary,” the researchers wrote, adding that “due to the very short duration of treatment, any conclusions on the treatment with Signifor cannot be drawn.” Overall, “the results of the presented case suggest that [temozolomide] treatment monotherapy could have only partial response in aggressive corticotroph adenoma causing Cushing’s disease, followed by sudden progression,” the investigators wrote. This contrasts with mostly responsive cases reported in research literature, they noted. “Therefore, further research on the factors of responsiveness and on novel methods to extend the duration of the effect of [temozolomide] should be carried out,” they wrote. From https://cushieblog.com/2018/02/10/temozolomide-may-partially-improve-aggressive-pituitary-tumors-causing-cushings-disease/
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  46. Laura, Shaw is absolutely correct. Usually, to diagnose Cushing's, you need many tests, some at specific times of the day and some ALL day. If you can, get to an endocrinologist who is very familiar with Cushing's and Cushing's testing. Best of luck to you and please keep us posted.
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  47. Shaw is correct. Most of the info on this board is available to members only to protect their privacy. We hope you join us so you can read everything and share with us. In the meantime, there's information about IPSS on our Wiki at http://www.cushings-info.com/index.php?title=Diagnostic_Testing#Petrosal_Sinus_Sampling Best of luck to you!
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  48. Kathy, I would put your story on face book and tell all your friends to pass it along to their friends, and their friends, etc. Be sure to mention Kaiser. I'm sure someone will pick up on your dilemma. I went through a similar battle getting my condition diagnosed. Thank God my Endocrinologist was one of the best and insisted on an IPSS test after my MRI was negative. This led to pituitary surgery by a Neurosurgeon from the Cleveland Clinic. Best in the nation and true lifesavers in my book. You cannot give up. You (or your son) must take control of his health and insist, insist, insist, on getting specific responses from his physicians. Develop a team of physicians starting with a Primary Care Physician, Endocrinologist and Neurosurgeon. Good luck. Again, don't settle or accept something that doesn't sound right. The squeaky wheel gets the grease. I bugged the heck out of my team and had pituitary surgery within two months of being diagnosed with Cushings.
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  49. I have several symptoms of Cushings: weight gain around middle, puffy face, extreme fatigue/no energy, feel weak going upstairs, buffalo hump, insomnia, numbness in feet, headache... Do not have: Striae, skin that bruises easily, slow healing cuts, acne, more body hair, absent menstrual periods Other Symptoms: Lymph glands in neck burning/throbbing from time to time, still reoccurring knee pain (Lymes?) Recently diagnosed/treated for Lymes disease Creatinine 1833 (Range 700-1800) Positive Thyroid Antibody test (not extremely high though 76 (Range 0-34) TSH 2.5 in April now 1.650 (Range 0.340-4.820) Free T4 0.74 (range 0.59-1.40) Low Vit D. Treated white cell count normal I took the 24 hour Free urine Cortisol test and it was only 2.5 points above the normal range 52.5 (range 4.0-50.0). I have another appt. with Endo but should I just cancel it as she said unless my Thyroid levels were out of range she would not treat me? I feel so horrible...mainly from the extreme weight gain and fatigue. I don't know what I should do next? Could this be Cushings? Hashimotos (but not affecting my thyroid levels yet), still Lymes disease? Appreciate your insight and Medical Expertise
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