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MaryO

~Chief Cushie~
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  1. MaryO

    Advice/encouragment.

    I hope your phone appointment went well and- you got some answers! Please keep us posted!
  2. Hypercortisolism Quickly Reversed With Oral Tx Oral osilodrostat (Isturisa) normalized cortisol levels in Cushing's disease patients who were ineligible for or not cured with pituitary surgery, according to the phase III LINC 3 trial. After 24 weeks of open-label treatment with twice-daily osilodrostat, 53% of patients (72 of 137; 95% CI 43.9-61.1) were able to maintain a complete response -- marked by mean 24-hour urinary free cortisol concentration of the upper limit of normal or below -- without any uptitration in dosage after the initial 12-week buildup phase, reported Rosario Pivonello, MD, of the Università Federico II di Napoli in Italy, and colleagues. As they explained in their study online in The Lancet Diabetes & Endocrinology, following the 24-week open-label period these complete responders to treatment were then randomized 1:1 to either remain on osilodrostat or be switched to placebo. During this 10-week randomization phase, 86% of patients maintained their complete cortisol response if they remained on osilodrostat versus only 29% of those who were switched to placebo (odds ratio 13.7, 95% CI 3.7-53.4, P<0.0001) -- meeting the trial's primary endpoint. As for adverse events, more than half of patients experienced hypocortisolism, and the most common adverse events included nausea (42%), headache (34%), fatigue (28%), and adrenal insufficiency (28%). "Alongside careful dose adjustments and monitoring of known risks associated with osilodrostat, our findings indicate a positive benefit-risk consideration of treatment for most patients with Cushing's disease," the researchers concluded. This oral inhibitor of 11β-­hydroxylase -- the enzyme involved in the last step of cortisol synthesis -- was FDA approved in March 2020 based on these findings, and is currently available in 1 mg, 5 mg, and 10 mg film-coated tablets. The prospective trial, consisting of four periods, included individuals between the ages of 18 and 75 with confirmed persistent or recurrent Cushing's disease -- marked by a mean 24-h urinary free cortisol concentration over 1.5 times the upper limit of normal (50 μg/24 hours), along with morning plasma adrenocorticotropic hormone above the lower limit of normal (9 pg/mL). All individuals had either undergone prior pituitary surgery or irradiation, were not deemed to be candidates for surgery, or had refused to have surgery. During the first open-label study period, all participants took 2 mg of oral osilodrostat twice daily, spaced 12 hours apart. This dose was then titrated up if the average of three 24-h urinary free cortisol concentration samples exceeded the upper limit of normal. During the second study period, which spanned weeks 12 through 24, all participants remained on their osilodrostat therapeutic dose. By week 24, about 62% of the participants were taking a therapeutic dose of 5 mg or less twice daily; only about 6% of patients needed a dose higher than 10 mg twice daily. In the third study period, which spanned weeks 26 through 34, "complete responders" who achieved normal cortisol levels were then randomized to continue treatment or be switched to placebo, while those who did not fully respond to treatment continued on osilodrostat. For the fourth study period, from weeks 24 through 48, all participants were switched back to active treatment with osilodrostat. Overall, 96% of participants were able to achieve a complete response at some point while on osilodrostat treatment, with two-thirds of these responders maintaining this normalized cortisol level for at least 6 months. The median time to first complete response was 41 days. Metabolic profiles also improved along with this reduction in cortisol levels. These included improvements in body weight, body mass index, fasting plasma glucose, both systolic and diastolic blood pressures, and total cholesterol levels. "Given the known clinical burden of cardiovascular risk associated with Cushing's disease, the improvement in clinical features shown here indicates important benefits of osilodrostat," the researchers said. "By improving multiple cardiovascular risk factors, our findings are likely to be clinically relevant." Along with metabolic improvements, patients also had "clinically meaningful improvements" in quality of life, as well as reductions in depressive symptoms measured by the Beck Depression Inventory score, the investigators reported. One limitation to the trial, they noted, was an inability to control for concomitant medications, since nearly all participants were taking other medications, particularly antihypertensive and antidiabetic therapies. "Further examination of the effects of osilodrostat on the clinical signs of Cushing's disease, and the reasons for changes in concomitant medications and the association between such medications and clinical outcomes would be valuable," Pivonello's group said. From https://www.medpagetoday.com/endocrinology/generalendocrinology/87827
  3. Dr. Theodore Friedman (The Wiz) will host a webinar on Growth Hormone Deficiency, PCOS or Cushing’s: How do You Tell Them Apart? Dr. Friedman will discuss topics including: Signs and Symptoms of Cushing’s Syndrome Testing for Cushing’s Signs and Symptoms of Growth Hormone Deficiency Testing for Growth Hormone Deficiency Signs and Symptoms of PCOS Testing for PCOS How do you tell them apart? Sunday • August 2 • 6 PM PDT Click here on start your meeting or https://axisconciergemeetings.webex.com/axisconciergemeetings/j.php?MTID=m4eda0c468071bd2daf33e6189aca3489 OR Join by phone: (855) 797-9485 Meeting Number (Access Code): 133 727 0164 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: pcos For more information, email us at mail@goodhormonehealth.com
  4. Dr. Theodore Friedman (The Wiz) will host a webinar on Growth Hormone Deficiency, PCOS or Cushing’s: How do You Tell Them Apart? Dr. Friedman will discuss topics including: Signs and Symptoms of Cushing’s Syndrome Testing for Cushing’s Signs and Symptoms of Growth Hormone Deficiency Testing for Growth Hormone Deficiency Signs and Symptoms of PCOS Testing for PCOS How do you tell them apart? Sunday • August 2 • 6 PM PDT Click here on start your meeting or https://axisconciergemeetings.webex.com/axisconciergemeetings/j.php?MTID=m4eda0c468071bd2daf33e6189aca3489 OR Join by phone: (855) 797-9485 Meeting Number (Access Code): 133 727 0164 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: pcos For more information, email us at mail@goodhormonehealth.com
  5. This event has been postponed to Dec. 5, 2020 You are Cordially Invited! The PNA is pleased to announce our participation in this event! Saturday, December 5, 2020 8:30am – 4:30pm Zuckerman Research Center 417 E. 68th St. New York, NY Memorial Sloan Kettering Cancer Center Target Audience This course is intended for endocrinologists, neurosurgeons, otolaryngologists, radiation oncologists, neurologists, ophthalmologists, neuro-oncologists, family medicine and internal medicine physicians, physicians in training and other allied health professionals who treat and manage patients with pituitary diseases. We also invite patients with pituitary disease and their caregivers to attend this educational activity and participate in our interactive afternoon breakout sessions. Overall this course aims to improve patient care and outcomes through evidence-based discussion of clinical practice guidelines and emerging therapies. Our goal is to assess and update current practices to promote earlier diagnosis and treatment of pituitary diseases. The multidisciplinary nature of the course will allow for the dissemination of knowledge across the variety of practitioners caring for pituitary patients, and for the patients themselves. Pituitary patients will be able to review treatment options, learn about ongoing clinical trials, and discuss their comprehensive care with providers and other patients. The educational objective of this patient session is to provide a forum for pituitary patients to discuss treatment options and new therapies with providers and other patients. Patients with pituitary disease and their caregivers are invited to attend this educational activity FREE of charge. If you are a patient or caregiver interested in attending, please email cme@mskcc.org to register (registration is required in order to attend). Medical Professionals who wish to attend must register online: mskcc.org/PituitaryCourse View Course Flyer
  6. The Barrow Pituitary Center is dedicated to educating patients, caregivers, and loved ones by providing information which is current and non-biased. Experts at this conference will address management of the emotional and physical elements of living with pituitary disorders. We hope attendees will leave empowered to make better-informed decisions about their healthcare and achieve their goals for a long and fruitful life. In Person and Online Registration Options This conference will be offered in person and through live online format with Zoom. We reserve the right to transition to a solely live online format as a result of health concerns as we move into the fall. Participants will be notified if this change develops. Register here
  7. Abstract Despite various approaches to immunoassay and chromatography for monitoring cortisol concentrations, conventional methods require bulky external equipment, which limits their use as mobile health care systems. Here, we describe a human pilot trial of a soft, smart contact lens for real-time detection of the cortisol concentration in tears using a smartphone. A cortisol sensor formed using a graphene field-effect transistor can measure cortisol concentration with a detection limit of 10 pg/ml, which is low enough to detect the cortisol concentration in human tears. In addition, this soft contact lens only requires the integration of this cortisol sensor with transparent antennas and wireless communication circuits to make a smartphone the only device needed to operate the lens remotely without obstructing the wearer’s view. Furthermore, in vivo tests using live rabbits and the human pilot experiment confirmed the good biocompatibility and reliability of this lens as a noninvasive, mobile health care solution. INTRODUCTION The steroid hormone, cortisol, which is known as a stress hormone, is secreted by the adrenal gland when people are stressed psychologically or physically (1). This secretion occurs when the adrenal gland is stimulated by adrenocorticotropic hormone, which is secreted by the pituitary gland when it is stimulated by the corticotropin-releasing hormone secreted by the hypothalamus. This serial cortisol secretion system is referred to as a hypothalamus–pituitary gland–adrenal gland axis, which is affected by chronic stress, resulting in abnormal secretion of cortisol (2, 3). The accumulation of cortisol caused by the abnormal secretion of cortisol increases the concentrations of fat and amino acid, which can result in diverse severe diseases (e.g., Cushing’s disease, autoimmune disease, cardiovascular complications, and type 2 diabetes) and neurological disorders (such as depression and anxiety disorders) (2–7). In contrast, abnormally low cortisol levels can lead to Addison’s disease, which results in hypercholesterolemia, weight loss, and chronic fatigue (8). In addition, it was recently reported that plasma cortisol can be correlated to the prognosis of traumatic brain injury (9). Furthermore, the extent of cortisol secretion varies from person to person, and it changes continuously (10, 11). Thus, developing health care systems for real-time monitoring of the cortisol level has been explored extensively over the past decade as the key to the quantitative analysis of stress levels. Although various efforts have led to the development of cortisol sensors that can measure the concentration of cortisol in blood, saliva, sweat, hair, urine, and interstitial fluid (12–17), the accurate measurement of cortisol concentrations has been limited because of the difficulties associated with the transportation and storage of cortisol as well as the instability of the biologically active cortisol in these body fluids at room temperature. In addition, these conventional sensing methods require bulky equipment for the extraction and analysis of these body fluids, which is not suitable for mobile health care systems (12, 18). Therefore, the development of noninvasive and wearable sensors that can monitor cortisol concentration accurately is highly desirable for a smart health care solution. For example, the immunoassay method, which uses an antigen-antibody binding reaction, has been used extensively for electrochemical cortisol immunosensors using saliva and interstitial fluid, except tears (12, 14, 19). However, these immunosensors still require the use of bulky impedance analyzers for the analysis of the Nyquist plot from electrochemical impedance spectroscopy. Although the cyclic voltammetry (CV) technique can be used as an alternative approach for sensing cortisol, additional bulky electrochemical instruments still are necessary for analyzing the CV curves (13, 14, 19). Recently, wearable forms of cortisol sensors that use sweat were developed (15), but they still required bulky measurement equipment (15, 16). Therefore, portable and smart sensors that can monitor the accurate concentration of cortisol in real time are highly desirable for use in mobile health care. Among the various body fluids, tears, in particular, contain important biomarkers, including cortisol (20, 21). Thus, the integration of biosensors with contact lenses is a potentially attractive candidate for the noninvasive and real-time monitoring of these biomarkers from tears (22–25). However, an approach for fabricating a smart contact lens for sensing the cortisol in tears has not been demonstrated previously. Thus, here, we present an extraordinary approach for the formation of a smart, soft contact lens that enables remote, real-time monitoring of the cortisol level in the wearer’s tears using mobile phones. This smart, soft contact lens is composed of a cortisol sensor, a wireless antenna, capacitors, resistors, and integrated circuit chips that use stretchable interconnects without obstructing the wearer’s view. The components of this device (except the antenna) were protected from mechanical deformations by locating each of the components on discrete, rigid islands and by embedding these islands inside an elastic layer. A graphene field-effect transistor (FET; with the binding of monoclonal antibody) was used as this cortisol immunosensor, which exhibited a sufficiently low detection limit, i.e., 10 pg/ml, for its sensing of cortisol in human tears in which the cortisol concentration ranges from 1 to 40 ng/ml (26). This sensor was integrated with a near-field communication (NFC) chip and antenna inside the soft contact lens for the real-time wireless transmission of the data to the user’s mobile device (e.g., a smart phone or a smart watch). The antenna occupies a relatively large area of this soft lens, so it requires its high stretchability, good transparency, and low resistance for operating a standard NFC chip at 13.56 MHz. In our approach, the hybrid random networks of ultralong silver nanofibers (AgNFs) and fine silver nanowires (AgNWs) enabled high transparency and good stretchability of this antenna and its low sheet resistance for reliable standard NFCs (at 13.56 MHz) inside this smart contact lens. Thus, the fully integrated system of this smart contact lens provided wireless and battery-free operation for the simultaneous detection and transmission of the cortisol concentration from tears to a mobile phone using standard NFC. In addition, a human pilot trial and in vivo tests conducted using live rabbits demonstrated the biocompatibility of this lens, and its safety against inflammation and thermal/electromagnetic field radiation suggests its substantial usability as a noninvasive, mobile health care solution. RESULTS Cortisol immunosensor A graphene FET sensor was fabricated by binding the cortisol monoclonal antibody (C-Mab) to the surface of graphene for the immunosensing of cortisol. Here, graphene acts as a transducer that converts the interaction between cortisol and C-Mab into electrical signals. Figure 1A shows the immobilization process of C-Mab to graphene. Immobilization proceeds through amide bonding of the C-Mab onto the carboxyl group of the graphene surface via the EDC [1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride]/NHS (N-hydroxysulfosuccinimide) coupling reaction. A chemical vapor deposition–synthesized graphene layer was transferred onto a desired substrate and exposed to ultraviolet ozone (UVO) to activate the surface of the graphene with the carboxylate group. Figure S1 shows the contact angle between this surface of the graphene and a droplet of deionized (DI) water. Longer exposure time to UVO can decrease the hydrophobicity of graphene with decreasing the contact angle. Table S1 shows the increase in the electrical resistance of graphene that resulted from this UVO treatment. In our experiment, 2 min of exposure time to UVO decreased the contact angle from 70° to 38° without increasing the resistance of the graphene notably. UVO exposure times longer than this threshold time degraded the resistance of the graphene excessively, so the time of exposure of our samples to UVO was limited to 2 min. Figure S2A illustrates the process of immobilizing C-Mab through the EDC/NHS coupling reaction. This two-step coupling reaction of EDC and NHS can mediate the amide bonding between the carboxylate group of the UVO-exposed graphene and the amine group of the protein (12, 17, 27, 28). Here, EDC forms reactive O-acylisourea ester, thereby making the surface unstable. This O-acylisourea ester reacts with the NHS to form amine-reactive NHS ester with the surface still remaining semistable. Then, C-Mab with the amine group reacts with the amine-reactive NHS ester, thereby forming stable amide bonding that can immobilize C-Mab to the NHS on the surface of the graphene. Figure S2B shows the Fourier transform infrared (FTIR) spectroscopy spectra of the DI water after the cortisol sensor had been immersed for 24 hours. The spectra of the DI water in which the sensor was immersed were not significantly different from those of the pristine DI water. However, the C-Mab solution that had a concentration of 1 μg/ml had a significant peak intensity in the range of 3000 to 2800 cm−1, representing the N-H bonding in the C-Mab. These results indicated that C-Mab formed stable bonding on the carboxylated graphene and was negligibly detached by exposure to water. From https://advances.sciencemag.org/content/6/28/eabb2891
  8. Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the viral strain that has caused the coronavirus disease 2019 (COVID-19) pandemic, has presented healthcare systems around the world with an unprecedented challenge. In locations with significant rates of viral transmission, social distancing measures and enforced ‘lockdowns’ are the new ‘norm’ as governments try to prevent healthcare services from being overwhelmed. However, with these measures have come important challenges for the delivery of existing services for other diseases and conditions. The clinical care of patients with pituitary disorders typically involves a multidisciplinary team, working in concert to deliver timely, often complex, disease investigation and management, including pituitary surgery. COVID-19 has brought about major disruption to such services, limiting access to care and opportunities for testing (both laboratory and radiological), and dramatically reducing the ability to safely undertake transsphenoidal surgery. In the absence of clinical trials to guide management of patients with pituitary disease during the COVID-19 pandemic, herein the Professional Education Committee of the Pituitary Society proposes guidance for continued safe management and care of this population. Introduction In many centers worldwide, the evaluation and treatment of pituitary disorders has already been substantially impacted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the viral strain that has caused the coronavirus disease 2019 (COVID-19) pandemic. With reduced access to routine clinical services, patients with suspected or confirmed pituitary disease face the prospect of delays in diagnosis and implementation of effective treatment plans. Furthermore, patients undergoing surgery may be at increased risk from COVID-19, whilst the risk of infection to healthcare providers during pituitary surgery is of particular concern. Herein, we discuss several clinical scenarios where clinical care can be adjusted temporarily without compromising patient outcomes. For this expert guidance, The Pituitary Society Professional Education Committee, which includes neuroendocrinologists and neurosurgeons from four continents, held an online video conference call with subsequent discussions conducted through email communications. The suggestions are not evidence-based due to the novelty and timing of the pandemic; furthermore, re-evaluation every few months in light of emerging data, is recommended. The approach will also likely vary from country to country depending on the risk of viral infection, local rules for “lockdown”, and the capabilities of individual health care systems. Pituitary surgery challenges during the COVID-19 pandemic The significant challenges to pituitary surgery presented by COVID-19 can be considered in terms of the phase of the pandemic, the patient, the surgeon, and the healthcare institution (Table 1). Table 1 Pituitary surgery challenges and recommendations during COVID-19 pandemic Full size table The World Health Organization (WHO) recognizes several phases of a pandemic wave [1]. When the pandemic is in progress (WHO pandemic phase descriptions; Phase 6) [2] there is a high prevalence of active cases. In the immediate post-peak period, the pandemic activity appears to wane, but active cases remain, and additional waves may follow. Previous pandemics have had many such waves, each separated by several months (www.cdc.gov). The corollary is that there will remain a significant possibility of patients and surgeons contracting COVID-19 until a vaccine is developed or herd immunity is achieved by other means. The patient requiring pituitary surgery may be especially vulnerable to COVID-19 due to age and/or comorbidities. This is particularly true of patients with functioning pituitary adenomas such as those with Cushing’s disease (CD), where cortisol excess results in immunosuppression, hypercoagulability, diabetes mellitus and hypertension, and acromegaly which is also frequently complicated by diabetes mellitus and hypertension. Moreover, the risk for patients undergoing surgery that develop COVID-19 in the perioperative period appears to be very high. In a retrospective analysis of 34 patients who underwent elective—non pituitary—surgeries during the incubation period of COVID-19, 15 (44.1%) patients required admission to the intensive care unit, and 7 (20.5%) died [3]. Although this study included cases of variable technical difficulty, complexity and risk—from excision of breast lump to total hip replacement—we would suggest that patients undergoing pituitary surgery that develop COVID-19 are likely to be at similar or greater risk. These risks must be balanced carefully against the natural history of pituitary disease and, in particular, whether undue delay may result in irreversible morbidity such as visual loss in patients with pituitary apoplexy. The surgeon remains in direct contact with the patient throughout their operation and is therefore at risk of contracting COVID-19 if the patient has an active infection. Iorio-Morin et al. [4] suggest that surgeons performing transsphenoidal pituitary surgery (TSS) may be at the greatest risk, because such surgery is performed under general anesthesia, requiring intubation and extubation, exposes the colonized nasal mucosa, and usually involves sphenoid drilling, which can result in aerosolization of contaminated tissues. The healthcare institution will invariably divert resources from elective services to support the care of patients with COVID-19, with a knock-on effect on the capacity to manage patients with pituitary disease (Table 1). Bernstein et al. [5] suggest that surgery is particularly affected in such reorganization, because of both the need for redeployment of anesthesiologists able to manage patient airways, and availability of protective physical resources such as masks, gowns, and gloves (personal protective equipment; PPE). Furthermore, in areas with high number of infections, several operating rooms (OR)s were converted into intensive care units (ICU) to treat patients with COVID-19, thus limiting patients’ access to elective surgery even more. Recommendations for pituitary surgery When the viral risk is decreasing in a specific geographic area, we would advocate a stepwise, but flexible normalization of activity, addressing each of the aforementioned factors. Burke et al. [6] proposed a staged volume limiting approach to scheduling surgical cases depending on the number of community cases and inpatients with COVID-19, and staffing shortages. In extreme cases, where significant assistance is required from outside institutions, only emergent cases can proceed. Until further data become available, all patients undergoing pituitary surgery should undergo screening for COVID-19, until a vaccine is developed or herd immunity is achieved by other means. At the least, we recommend screening patients for cough, fever, or other recognized symptoms of infection with SARS-CoV-2, and taking swab samples for testing if there is any clinical suspicion. Depending on the level of COVID-19 activity in the community, and available resources, a more exhaustive strategy may be appropriate, including isolation of patients for up to 2 weeks before surgery, paired swabs and/or serological tests for all patients irrespective of symptoms, and routine chest X-ray or chest computed tomography (CT), depending on local guidance. In patients with COVID-19 in whom surgery is indicated, in general we recommend delaying surgery if possible, ideally until patients no longer have symptoms and have a negative swab test result. The nature of the patient’s pituitary disease is an important consideration, and we propose stratifying cases as emergent, urgent, or elective. We recommend that patients continue to be operated on in an emergent fashion if they present with pituitary apoplexy, acute severe visual loss, or other significant mass effect, or if there is concern regarding malignant pathology. Selected patients with slowly progressive visual loss, functioning tumors with aggressive clinical features, and those with an unclear diagnosis, may also benefit from urgent (but not emergent) surgery, with decisions made on a case-by-case basis. Patients with incidental and asymptomatic tumors, known nonfunctioning adenomas [7] or functioning tumors, which are well controlled with medical therapy, can be scheduled as elective cases. In most cases, TSS remains the safest, most effective, and most efficient approach to pituitary tumors. In a series of 9 consecutive patients without COVID-19 undergoing pituitary and skull base surgery during the pandemic, Kolias et al. [8] reported that none of the patients or staff contracted COVID-19 following adoption of a standardized risk-mitigation strategy. In the rare instances where a patient with COVID-19 requires emergent surgery that cannot be deferred, alternative transcranial approaches may be considered (avoiding nasal mucosa). To replace high-speed drilling, the use of non-powered tools such as rongeurs and chisels has been recommended. If this is not possible large suction tubes can be used to aspirate as much particulate matter as possible [9]. In such cases, the availability and use of PPE, and in particular filtering facepiece (FFP3) respirators, is mandated. Depending on the level of COVID-19 activity in the community, and the availability and effectiveness of testing, PPE may be appropriate in all cases. At an institutional level, there must remain flexibility in anticipation of further waves of COVID-19. This necessitates a reduction in capacity, particularly in available ICU beds, that must be recognized when scheduling challenging surgical cases. In the long term, resumption of full elective workloads depends on wider national and international factors, including widespread testing, and widespread immunity through vaccination or other means. Pituitary diseases diagnosis and management Acromegaly Acromegaly, a condition that arises from growth hormone (GH) excess, generally occurs as a result of autonomous GH secretion from a somatotroph pituitary adenoma [10, 11], is associated with substantial morbidity and excess mortality, which can be mitigated by prompt and adequate treatment [12]. Diagnosis is often delayed because of the low prevalence of the disease, the frequently non-specific nature of presenting symptoms, and the typically subtle progression of clinical features [10, 11]. During the COVID-19 pandemic many outpatient clinics have closed or limited work hours. Patients are often reluctant to seek care out of fear of possible exposure to the coronavirus. Therefore, even longer diagnostic delays are anticipated. In addition, patients who present with vision loss and larger tumors encroaching upon the optic apparatus are at risk for experiencing persistent visual compromise unless the optic chiasm and nerves are promptly decompressed. To improve patient access to care and minimize potentially deleterious delays in diagnosis and treatment, clinicians may conduct virtual visits (VV) using secure, internet-based electronic medical record platforms. A detailed history can be obtained and a limited physical examination is possible, including inspection of the face, skin and extremities. Diagnosis Establishing the diagnosis of acromegaly requires testing of serum insulin-like growth factor-I (IGF-I) levels [11] (Box 1). Access to accurate IGF-I assays is critical in light of the substantial analytical and post-analytical problems that have plagued several IGF-I immunoassays. While the oral glucose tolerance test (OGTT) is considered the diagnostic “gold standard”, this test is not essential in many patients, including those with a clear-cut clinical picture and an unequivocally elevated serum IGF-I level. Deferring the lengthy (2-h) OGTT may minimize the risk of potential exposure to infectious agents. Given the over-representation of macroadenomas in patients with acromegaly, pituitary imaging is indicated, preferably by a pituitary-specific magnetic resonance imaging (MRI) protocol, although CT may be performed to rule out a large tumor if MRI is not feasible. Obtaining imaging at satellite sites detached from major hospitals may also decrease the risk of infection exposure. Management Transsphenoidal pituitary surgery remains the treatment of choice for most patients with acromegaly [10, 11], and patients with visual compromise as a result of a pituitary adenoma compressing the optic apparatus should still undergo pituitary surgery promptly. Other patients could be treated medically until the pandemic subsides. Medical treatment options are somatostatin receptor ligands (SRLs), octreotide long-acting release (LAR), lanreotide depot and pasireotide LAR, pegvisomant and cabergoline (used off-label) [13]. Medical therapies can be effective in providing symptomatic relief, control GH excess or action, and potentially reduce tumor size (except pegvisomant, which does not have direct antiproliferative effects). Preoperative medical therapy has been reported to improve surgical outcomes in some, but not all studies. Pasireotide, which potentially can induce QTc prolongation, should be used with caution in patients who are taking, either as prophylaxis or treatment, medications for COVID-19 (azithromycin, hydroxychloroquine), which can also have an effect on QTc interval. Furthermore, as hyperglycemia is very frequent in patients treated with pasireotide and needs close monitoring at start of the treatment, this treatment should be reserved for truly resistant cases, with large tumors and who cannot have surgery yet. Notably, lanreotide depot, cabergoline or pegvisomant can be administered by the patient or a family member and therefore an in-person visit to a clinic is not required. If SRLs that require health care professional administration are required, raising the dose may allow the interval between injections to be extended beyond 4 weeks while maintaining disease control. Virtual visits can be implemented to monitor the patient’s course and response to medical therapy during the pandemic. Careful management of comorbidities associated with acromegaly remains an essential part of patient care [14, 15]. Prolactinomas Hyperprolactinemia may be physiological in origin or arise because of an underlying pathophysiologic cause, medication use or laboratory artifact. Therefore, an initial evaluation for hyperprolactinemia should include a comprehensive medication history, a thorough evaluation for secondary causes, including primary hypothyroidism, and a careful assessment for clinical features of hyperprolactinemia, including hypogonadism and galactorrhea. Unless a secondary cause of hyperprolactinemia can be established definitively, further investigation is indicated to evaluate the etiology of hyperprolactinemia. Diagnosis The diagnosis of a lactotroph adenoma can be inferred in most patients based on the presence of a pituitary adenoma and an elevated prolactin level, which is typically proportionate in magnitude to adenoma size. Pituitary imaging (MRI or CT) is therefore a key step in the investigation of hyperprolactinemia. Evaluation for hypopituitarism is also necessary. Management Although observation and routine follow-up with serial prolactin levels and imaging is acceptable for patients who are asymptomatic and who have a microadenoma, most patients diagnosed with a prolactinoma will require treatment. Dopamine-agonists (DA) can normalize prolactin levels and lead to reduction in size of the lactotroph adenoma [16]. In patients who have a microadenoma and who are not seeking fertility, hormone-replacement therapy may also be appropriate if serum prolactin is routinely followed and imaging performed as necessary. Medical therapy can be managed effectively and efficiently via VVs coupled with laboratory/imaging studies as needed. However, in all patients in whom a DA will be initiated, it is critical that a comprehensive psychiatric history is obtained prior to commencing treatment. Patients may not readily volunteer their psychiatric history and may not appreciate the relevance of such information. For example, until specifically questioned about their psychiatric history, the patient described in the illustrative case (Box 2) did not report a history of severe depression, suicide attempt and prolonged psychiatric hospitalization 8 months prior to presentation with hyperprolactinemia. At the time of the visit, he was not taking any psychiatric medications and was not under the care of a mental health team. Given this patient’s significant psychiatric history, lack of ongoing psychiatric care, and the well-recognized adverse effects of DA therapy, including increased impulsivity, depression and psychosis [17], a DA was not initiated. Counseling on potential DA side-effects is crucial, as they may also present in individuals with no prior psychiatric history [17]. Furthermore, during the COVID-19 pandemic when there is reduced access to routine medical and mental health care, patients who develop symptoms of severe depression may not have ready access to mental health services, or may not seek care. Therefore, it is particularly important to make patients aware of these potential side effects and the critical importance of reporting them. In the small number of patients for whom medical therapy is not possible and where surveillance is not appropriate (e.g., macroprolactinoma with visual loss) the risks and benefits of surgical intervention will need to be carefully weighed. Cushing’s disease Left untreated, CD has significant morbidity and mortality, and delays in diagnosis (from a few months to even years) are common. Clinical presentation is also very variable with some patients having subtle symptoms while others present with more striking/classical features. Severe hypercortisolemia induces immunosuppression, which may place patients with untreated CD at particular risk from COVID-19. New patients referred for endocrinology evaluation with clinical suspicion of Cushing’s Diagnosis Screening for, and confirmation of Cushing’s syndrome (CS) and, furthermore, localization for CD is laborious and requires serial visits and testing procedures [18, 19]. If initial laboratory abnormalities are consistent with hypercortisolemia, a VV should allow for an estimate of the severity of clinical presentation and facilitate planning for further testing and treatment. Careful questioning for potential causes of exogenous CS (including, but not limited to, history of high-dose oral corticosteroids, intraarticular injections or topical preparations) is an important first step. Subsequently, establishing the likelihood and pretest probability of CS is more important than ever now, when testing may be delayed. While presentation varies significantly between patients, some features, although not all highly sensitive, are more specific, e.g. easy bruising, facial plethora, large wide > 1 cm violaceous striae, proximal weakness and hypokalemia. Diagnosis of CS is often challenging even under normal circumstances, however, a diagnosis by VV is more nuanced and difficult. Conversely, if a patient has a high likelihood of CS, we recommend limited laboratory evaluation (urinary free cortisol (UFC), adrenocorticotropic hormone (ACTH), liver panel, basic metabolic panel), preferably at a smaller local laboratory rather than a Pituitary Center, to reduce viral risk exposure. Salivary cortisol samples could represent a hazard for laboratory staff and they are prohibited in some countries [18, 19]. In the US, laboratories have continued to process salivary cortisol samples and salivary cortisol has higher sensitivity compared with UFC and has the convenience of mailing multiple specimens at a time, without travel [18, 19]. Though usually we strongly recommend sequential laboratory testing under normal circumstances, limiting trips to a laboratory is preferred during COVID-19. If preliminary assessment confirms ACTH-dependent CS [18, 19] and no visual symptoms are reported, imaging may be delayed. However, in the presence of any visual symptoms, and recognizing the challenges of undertaking a formal visual field assessment, proceeding directly with MRI or CT (shorter exam time and easier machine access) imaging, will allow confirmation or exclusion of a large pituitary adenoma compressing the optic chiasm. If the latter is confirmed, the patient will need to be evaluated by a neurosurgeon. In contrast, a small pituitary adenoma may not be visible on CT, but in such cases MRI may be deferred for a few months until COVID-19 restrictions limiting access to care are lifted. Another VV will help to decide, in conjunction with patient’s preference, the best next step, which in cases of more severe clinical Cushing’s, and in the absence of a large pituitary adenoma, would be medical therapy. The magnitude of 24 h-UFC elevation could also represent a criterion for primary therapy, since higher values have been associated with increased risk of infection. In parallel, it is also important to address comorbidities including diabetes mellitus, hypertension and hyperlipidemia. In light of the increased risk of venous thromboembolism, in discussion with primary care providers, plans for regular mobilization/exercise as permitted (including at home when orders to stay in are in place) and/or prophylactic low weight molecular heparin should be considered. Management First line medical therapy options vary, depending on country availability, regulatory approval and patient comorbidities. Ideally, an oral medication, which is easier to administer is preferred; options include ketoconazole, osilodrostat or metyrapone [20, 21]. Cabergoline therapy, which has lesser efficacy [20, 21] compared with adrenal steroidogenesis inhibitors, can be also attempted in very mild cases. The initial laboratory profile should be reviewed to exclude significant abnormalities of renal and/or liver function prior to commencing treatment. Starting doses of all medications should be the lowest possible to avoid adrenal insufficiency (AI) and up titration should be slow, with VVs weekly if possible. All patients with CS on any type of medical therapy should have prescribed glucocorticoids (GC) both in oral and injectable forms available at home and information regarding AI should be provided during a VV when starting therapy for CS. Down titration of other medications for diabetes and hypertension may also be needed over time. Pasireotide (both subcutaneous and LAR preparations) would be a second line option, reflecting higher risk of significant hyperglycemia that would require treatment [22]. If the clinical features of CS are mild and longstanding, with no acute deterioration, another possibility is to aggressively treat the associated comorbidities for a few months; depending on local circumstances, this may actually be less risky for the patient by avoiding the risk of AI/crisis and the need for an emergency department (ED) visit and/or admission. For patients with Cushing’s disease with endocrinology chronic care Patients in remission after surgery with adrenal insufficiency on glucocorticoid replacement These patients are likely to remain at slightly higher risk of COVID-19 infection due to immunosuppression from previous hypercortisolemia. Furthermore, GC doses should be adjusted to prevent adrenal crisis and visits to an ED. Lower GC daily doses (10–15 mg hydrocortisone/day) are now frequently used for replacement and virtual and/or phone visits are encouraged to evaluate an appropriate regimen and sufficient supplies of medication and injectable GC (at home) should be prescribed. Patients with potential symptoms of under replacement may require an increase in daily dose, while balancing any risk of GC over replacement and possible consequent immunosuppression. Patients in non-remission treated with medical therapy (dependent on country availability) Doses may need to be adjusted to reduce the risk of AI/crisis and reduce the need for serial laboratory work. Monthly or bimonthly VVs are appropriate for clinical evaluation and up titration should be slower than usual. Patients with CD on medical therapy need to have at home prescriptions for oral and injectable GC and instruction on AI surveillance. Patients should also be advised, that if they develop a fever, to stop Cushing’s medication for few days; if they develop AI symptoms, GC administration will be required. In some countries, block and replace regimens are also employed to avoid risk of AI. Of note, for mifepristone, a glucocorticoid receptor (GR) antagonist, patients will require much higher doses of GC to reverse the blockade (1 mg of dexamethasone approximately per 400 mg of mifepristone) and for several days, as drug metabolites also have GR antagonist effects. Furthermore, for all patients who have made dose changes or discontinued medications for Cushing’s, it is essential to follow very closely and consider adjustments in the doses of concomitant medications, especially insulin, other antidiabetic and antihypertensive medications, and potassium supplements. If patients have history of radiotherapy and are still on medications for CD, a VV every few months should be performed to determine if anti-Cushing’s treatment can be slowly down-titrated (to avoid AI). A morning serum cortisol would be ideal to rule out AI off medications, however, if laboratory testing cannot be undertaken safely, clinical evaluation by serial VVs can be helpful. While head-to-head data will never be available, in COVID-19 hotspots, given the higher risk of infection with laboratory testing or face to face visits, mild hypercortisolemia might be “better” than adrenal crisis, especially in the short term! Patients with CD have increased rates of depression, anxiety and can have decreased quality of life (QoL) even when in long-term remission, thus in the challenging circumstances of the current pandemic it is it even more important to focus on psychological evaluation during virtual endocrinology visits, with referral to virtual counseling as needed. From https://link.springer.com/article/10.1007/s11102-020-01059-7?utm_source=newsletter_370
  9. I think we always knew Cushing's and pregnancy were related... Abstract Cushing’s syndrome (CS) during pregnancy is very rare with a few cases reported in the literature. Of great interest, some cases of CS during pregnancy spontaneously resolve after delivery. Most studies suggest that aberrant luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor (LHCGR) seems to play a critical role in the pathogenesis of CS during pregnancy. However, not all women during pregnancy are observed cortisol hypersecretion. Moreover, some cases of adrenal tumors or macronodular hyperplasia with LHCGR expressed, have no response to hCG or LH. Therefore, alternative pathogenic mechanisms are indicated. It has been recently reported that estrogen binding to estrogen receptor α (ERα) could enhance the adrenocortical adenocarcinoma (ACC) cell proliferation. Herein, we hypothesize that ERα is probably involved in CS development during pregnancy. Better understanding of the possible mechanism of ERα on cortisol production and adrenocortical tumorigenesis will contribute to the diagnosis and treatment of CS during pregnancy. Read the entire article here: https://www.sciencedirect.com/science/article/pii/S0306987720303893?via%3Dihub
  10. 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 No Registration is Required. It will be webcast by Microsoft Teams. Click here to attend. Date: Friday, July 17, 2020 Time: 10:00 AM Pacific Daylight Time, 1:00 PM Eastern Daylight Time
  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 No Registration is Required. It will be webcast by Microsoft Teams. Click here to attend. Date: Friday, July 17, 2020 Time: 10:00 AM Pacific Daylight Time, 1:00 PM Eastern Daylight Time
  12. Thank you so much for sharing your dad's story, Andy. What a sad, difficult one it is. I know when Dr. Cushing was originally testing people for Cushing's disease, he found some of his early patients in the circus (bearded woman, etc) and other patients have been in mental wards before their diagnosis. This disease, especially untreated, can really cause havoc in all aspects of a person's life. I hope you and your family have been able to find some peace since the original article.
  13. Dexamethasone, a cheap and widely used steroid, has become the first drug shown to be able to save lives among Covid-19 patients in what scientists hailed as a “major breakthrough”. Results of trials announced on Tuesday showed dexamethasone, which is used to reduce inflammation in other diseases, reduced death rates by around a third among the most severely ill Covid-19 patients admitted to hospital. The results suggest the drug should immediately become standard care in patients with severe cases of the pandemic disease, said the researchers who led the trials. “This is a result that shows that if patients who have Covid-19 and are on ventilators or are on oxygen are given dexamethasone, it will save lives, and it will do so at a remarkably low cost,” said Martin Landray, an Oxford University professor co-leading the trial, known as the RECOVERY trial. “It’s going to be very hard for any drug really to replace this, given that for less than 50 pounds ($63.26), you can treat eight patients and save a life,” he told reporters in an online briefing. His co-lead investigator, Peter Horby, said dexamethasone was “the only drug that’s so far shown to reduce mortality - and it reduces it significantly.” “It is a major breakthrough,” he said. “Dexamethasone is inexpensive, on the shelf, and can be used immediately to save lives worldwide.” There are currently no approved treatments or vaccines for Covid-19, the disease caused by the new coronavirus which has killed more than 431,000 globally. Saving ‘countless lives’ The RECOVERY trial compared outcomes of around 2,100 patients who were randomly assigned to get the steroid, with those of around 4,300 patients who did not get it. The results suggest that one death would be prevented by treatment with dexamethasone among every eight ventilated Covid-19 patients, Landray said, and one death would be prevented among every 25 Covid-19 patients that received the drug and are on oxygen. Among patients with Covid-19 who did not require respiratory support, there was no benefit from treatment with dexamethasone. “The survival benefit is clear and large in those patients who are sick enough to require oxygen treatment, so dexamethasone should now become standard of care in these patients,” Horby said. Nick Cammack, a expert on Covid-19 at the Wellcome Trust global health charity, said the findings would “transform the impact of the Covid-19 pandemic on lives and economies across the world”. “Countless lives will be saved globally,” he said in a statement responding to the results. The RECOVERY trial was launched in April as a randomised clinical trial to test a range of potential treatments for Covid-19, including low-dose dexamethasone and the malaria drug hydoxycholoroquine. The hydroxychloroquine arm was halted earlier this month after Horby and Landray said results showed it was “useless” at treating Covid-19 patients. Global cases of infection with the novel coronavirus have reached over 8 million, according to a Reuters tally, and more than 434,000 people have died after contracting the virus, the first case if which was reported in China in early January. From https://www.cnbc.com/2020/06/16/steroid-dexamethasone-reduces-deaths-from-severe-covid-19-trial.html
  14. 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
  15. 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
  16. https://doi.org/10.1016/S2213-8587(20)30215-1 Over the past few months, COVID-19, the pandemic disease caused by severe acute respiratory syndrome coronavirus 2, has been associated with a high rate of infection and lethality, especially in patients with comorbidities such as obesity, hypertension, diabetes, and immunodeficiency syndromes.1 These cardiometabolic and immune impairments are common comorbidities of Cushing's syndrome, a condition characterised by excessive exposure to endogenous glucocorticoids. In patients with Cushing's syndrome, the increased cardiovascular risk factors, amplified by the increased thromboembolic risk, and the increased susceptibility to severe infections, are the two leading causes of death.2 In healthy individuals in the early phase of infection, at the physiological level, glucocorticoids exert immunoenhancing effects, priming danger sensor and cytokine receptor expression, thereby sensitising the immune system to external agents.3 However, over time and with sustained high concentrations, the principal effects of glucocorticoids are to produce profound immunosuppression, with depression of innate and adaptive immune responses. Therefore, chronic excessive glucocorticoids might hamper the initial response to external agents and the consequent activation of adaptive responses. Subsequently, a decrease in the number of B-lymphocytes and T-lymphocytes, as well as a reduction in T-helper cell activation might favour opportunistic and intracellular infection. As a result, an increased risk of infection is seen, with an estimated prevalence of 21–51% in patients with Cushing's syndrome.4 Therefore, despite the absence of data on the effects of COVID-19 in patients with Cushing's syndrome, one can make observations related to the compromised immune state in patients with Cushing's syndrome and provide expert advice for patients with a current or past history of Cushing's syndrome. Fever is one of the hallmarks of severe infections and is present in up to around 90% of patients with COVID-19, in addition to cough and dyspnoea.1 However, in active Cushing's syndrome, the low-grade chronic inflammation and the poor immune response might limit febrile response in the early phase of infection.2 Conversely, different symptoms might be enhanced in patients with Cushing's syndrome; for instance, dyspnoea might occur because of a combination of cardiac insufficiency or weakness of respiratory muscles.2 Therefore, during active Cushing's syndrome, physicians should seek different signs and symptoms when suspecting COVID-19, such as cough, together with dysgeusia, anosmia, and diarrhoea, and should be suspicious of any change in health status of their patients with Cushing's syndrome, rather than relying on fever and dyspnoea as typical features. The clinical course of COVID-19 might also be difficult to predict in patients with active Cushing's syndrome. Generally, patients with COVID-19 and a history of obesity, hypertension, or diabetes have a more severe course, leading to increased morbidity and mortality.1 Because these conditions are observed in most patients with active Cushing's syndrome,2 these patients might be at an increased risk of severe course, with progression to acute respiratory distress syndrome (ARDS), when developing COVID-19. However, a key element in the development of ARDS during COVID-19 is the exaggerated cellular response induced by the cytokine increase, leading to massive alveolar–capillary wall damage and a decline in gas exchange.5 Because patients with Cushing's syndrome might not mount a normal cytokine response,4 these patients might parodoxically be less prone to develop severe ARDS with COVID-19. Moreover, Cushing's syndrome and severe COVID-19 are associated with hypercoagulability, such that patients with active Cushing's syndrome might present an increased risk of thromboembolism with COVID-19. Consequently, because low molecular weight heparin seems to be associated with lower mortality and disease severity in patients with COVID-19,6 and because anticoagulation is also recommended in specific conditions in patients with active Cushing's syndrome,7 this treatment is strongly advised in hospitalised patients with Cushing's syndrome who have COVID-19. Furthermore, patients with active Cushing's syndrome are at increased risk of prolonged duration of viral infections, as well as opportunistic infections, particularly atypical bacterial and invasive fungal infections, leading to sepsis and an increased mortality risk,2 and COVID-19 patients are also at increased risk of secondary bacterial or fungal infections during hospitalisation.1 Therefore, in cases of COVID-19 during active Cushing's syndrome, prolonged antiviral treatment and empirical prophylaxis with broad-spectrum antibiotics1, 4 should be considered, especially for hospitalised patients (panel). Panel Risk factors and clinical suggestions for patients with Cushing's syndrome who have COVID-19 Reduction of febrile response and enhancement of dyspnoea Rely on different symptoms and signs suggestive of COVID-19, such as cough, dysgeusia, anosmia, and diarrhoea. Prolonged duration of viral infections and susceptibility to superimposed bacterial and fungal infections Consider prolonged antiviral and broad-spectrum antibiotic treatment. Impairment of glucose metabolism (negative prognostic factor) Optimise glycaemic control and select cortisol-lowering drugs that improve glucose metabolism. Hypertension (negative prognostic factor) Optimise blood pressure control and select cortisol-lowering drugs that improve blood pressure. Thrombosis diathesis (negative prognostic factor) Start antithrombotic prophylaxis, preferably with low-molecular-weight heparin treatment. Surgery represents the first-line treatment for all causes of Cushing's syndrome,8, 9 but during the pandemic a delay might be appropriate to reduce the hospital-associated risk of COVID-19, any post-surgical immunodepression, and thromboembolic risks.10 Because immunosuppression and thromboembolic diathesis are common Cushing's syndrome features,2, 4 during the COVID-19 pandemic, cortisol-lowering medical therapy, including the oral drugs ketoconazole, metyrapone, and the novel osilodrostat, which are usually effective within hours or days, or the parenteral drug etomidate when immediate cortisol control is required, should be temporarily used.9 Nevertheless, an expeditious definitive diagnosis and proper surgical resolution of hypercortisolism should be ensured in patients with malignant forms of Cushing's syndrome, not only to avoid disease progression risk but also for rapidly ameliorating hypercoagulability and immunospuppression;9 however, if diagnostic procedures cannot be easily secured or surgery cannot be done for limitations of hospital resources due to the pandemic, medical therapy should be preferred. Concomitantly, the optimisation of medical treatment for pre-existing comorbidities as well as the choice of cortisol-lowering drugs with potentially positive effects on obesity, hypertension, or diabates are crucial to improve the eventual clinical course of COVID-19. Once patients with Cushing's syndrome are in remission, the risk of infection is substantially decreased, but the comorbidities related to excess glucocorticoids might persist, including obesity, hypertension, and diabetes, together with thromboembolic diathesis.2 Because these are features associated with an increased death risk in patients with COVID-19,1 patients with Cushing's syndrome in remission should be considered a high-risk population and consequently adopt adequate self-protection strategies to minimise contagion risk. In conclusion, COVID-19 might have specific clinical presentation, clinical course, and clinical complications in patients who also have Cushing's syndrome during the active hypercortisolaemic phase, and therefore careful monitoring and specific consideration should be given to this special, susceptible population. Moreover, the use of medical therapy as a bridge treatment while waiting for the pandemic to abate should be considered. RP reports grants and personal fees from Novartis, Strongbridge, HRA Pharma, Ipsen, Shire, and Pfizer; grants from Corcept Therapeutics and IBSA Farmaceutici; and personal fees from Ferring and Italfarmaco. AMI reports non-financial support from Takeda and Ipsen; grants and non-financial support from Shire, Pfizer, and Corcept Therapeutics. BMKB reports grants from Novartis, Strongbridge, and Millendo; and personal fees from Novartis and Strongbridge. AC reports grants and personal fees from Novartis, Ipsen, Shire, and Pfizer; personal fees from Italfarmaco; and grants from Lilly, Merck, and Novo Nordisk. All other authors declare no competing interests. References 1 P Kakodkar, N Kaka, MN Baig A comprehensive literature review on the clinical presentation, and management of the pandemic coronavirus disease 2019 (COVID-19) Cureus, 12 (2020), Article e7560 View Record in ScopusGoogle Scholar 2 R Pivonello, AM Isidori, MC De Martino, J Newell-Price, BMK Biller, A Colao Complications of Cushing's syndrome: state of the art Lancet Diabetes Endocrinol, 4 (2016), pp. 611-629 ArticleDownload PDFView Record in ScopusGoogle Scholar 3 DW Cain, JA Cidlowski Immune regulation by glucocorticoids Nat Rev Immunol, 17 (2017), pp. 233-247 CrossRefView Record in ScopusGoogle Scholar 4 V Hasenmajer, E Sbardella, F Sciarra, M Minnetti, AM Isidori, MA Venneri The immune system in Cushing's syndrome Trends Endocrinol Metab (2020) published online May 6, 2020. DOI:10.1016/j.tem.2020.04.004 Google Scholar 5 Q Ye, B Wang, J Mao The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19 J Infect, 80 (2020), pp. 607-613 ArticleDownload PDFView Record in ScopusGoogle Scholar 6 N Tang, H Bai, X Chen, J Gong, D Li, Z Sun Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy J Thromb Haemost, 18 (2020), pp. 1094-1099 CrossRefView Record in ScopusGoogle Scholar 7 AM Isidori, M Minnetti, E Sbardella, C Graziadio, AB Grossman Mechanisms in endocrinology: the spectrum of haemostatic abnormalities in glucocorticoid excess and defect Eur J Endocrinol, 173 (2015), pp. R101-R113 View Record in ScopusGoogle Scholar 8 LK Nieman, BM Biller, JW Findling, et al.Treatment of Cushing's syndrome: an endocrine society clinical practice guideline J Clin Endocrinol Metab, 100 (2015), pp. 2807-2831 CrossRefView Record in ScopusGoogle Scholar 9 R Pivonello, M De Leo, A Cozzolino, A Colao The treatment of Cushing's disease Endocr Rev, 36 (2015), pp. 385-486 CrossRefView Record in ScopusGoogle Scholar 10 J Newell-Price, L Nieman, M Reincke, A Tabarin Endocrinology in the time of COVID-19: management of Cushing's syndrome Eur J Endocrinol (2020) published online April 1. DOI:10.1530/EJE-20-0352 Google Scholar View Abstract From https://www.thelancet.com/journals/landia/article/PIIS2213-8587(20)30215-1/fulltext
  17. MaryO

    Anxious

    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.
  18. J Clin Endocrinol Metab . 2003 Apr;88(4):1554-8. doi: 10.1210/jc.2002-021518. Francesca Pecori Giraldi 1, Mirella Moro, Francesco Cavagnini, Study Group on the Hypothalamo-Pituitary-Adrenal Axis of the Italian Society of Endocrinology Affiliations PMID: 12679438 DOI: 10.1210/jc.2002-021518 Abstract Cushing's disease (CD) presents a marked female preponderance, but whether this skewed gender distribution has any relevance to the presentation and outcome of CD is not known. The aim of the present study was the comparison of clinical features, biochemical indices of hypercortisolism, and surgical outcome among male and female patients with CD. The study population comprised 280 patients with CD (233 females, 47 males) collected by the Italian multicentre study. Epidemiological data, frequency of clinical signs and symptoms, urinary free cortisol (UFC), plasma ACTH and cortisol levels, responses to dynamic testing, and surgical outcome were compared in female and male patients. Male patients with CD presented at a younger age, compared with females (30.5 +/- 1.93 vs. 37.1 +/- 0.86 yr, P < 0.01), with higher UFC and ACTH levels (434.1 +/- 51.96 vs. 342.1 +/- 21.01% upper limit of the normal range for UFC, P < 0.05; 163.9 +/- 22.92 vs. 117.7 +/- 9.59% upper limit of the normal range for ACTH, P < 0.05). No difference in ACTH and cortisol responses to CRH, gradient at inferior petrosal sinus sampling, and cortisol inhibition after low-dose dexamethasone was recorded between sexes. In contrast, the sensitivity of the high-dose dexamethasone test was significantly lower in male than in female patients. Of particular interest, symptoms indicative of hypercatabolic state were more frequent in male patients; indeed, males presented a higher prevalence of osteoporosis, muscle wasting, striae, and nephrolitiasis. Conversely, no symptom was more frequent in female patients with CD. Patients with myopathy, hypokalemia, and purple striae presented significantly higher UFC levels, compared with patients without these symptoms. Lastly, in male patients, pituitary imaging was more frequently negative and immediate and late surgical outcome less favorable. In conclusion, CD appeared at a younger age and with a more severe clinical presentation in males, compared with females, together with more pronounced elevation of cortisol and ACTH levels. Furthermore, high-dose dexamethasone suppression test and pituitary imaging were less reliable in detecting the adenoma in male patients, further burdening the differential diagnosis with ectopic ACTH secretion. Lastly, the postsurgical course of the disease carried a worse prognosis in males. Altogether, these findings depict a different pattern for CD in males and females. From https://pubmed.ncbi.nlm.nih.gov/12679438/
  19. Sherry passed away this afternoon, naturally and peacefully in her sleep. She loved her community and we know how grateful she was to every one of her friends on here for the genuine love and support she’s received over the years. We (her family) are processing, but will share details about her celebration of life when we’ve worked it out. Sherry's bio: I have been very ill for many years now, since 1999 that I know of. But it had always come and gone, until 2004 when it decided to stay. At first it was a mystery as to what was wrong. I was seeing a psychiatrist that felt very strong that what I was dealing with was endocrine related. He mentioned a few things that it could be and one was Cushing’s, so I looked it up on the internet and sure enough I had many of the symptoms of Cushing’s disease, moon face, buffalo hump, weight gain, big round belly, red face, very ruddy complexion, acne, nausea, depression, fatigue, hirsutism, depression, anxiety, hypertension, unusual bruising, and highs and lows of energy. I found this support group on the internet at Cushings-help.com and they helped me find Dr.William Ludlam at OHSU. He told me I had a suddle case of Cushing’s and had a pituitary tumor on the right side displacing the pituitary to the left. Although Dr.Ludlam originally saw tumors on both sides, I had a pituitary tumor that seemed to be cyclic. When it turned on I had major Cortisol energy, when it turned off I got very achy, nausea, and very tired. In March of 2006 I was officially diagnosed after 1 long year of testing, and went on to have my first unsuccessful Transphenoidal pituitary surgery 3/23/2006 with Dr. Johnny Delashaw at OHSU. I had a second unsuccessful pituitary surgery 10/12/06 and finally a BLA 11/7/06. I am now cured of Cushing’s disease 2 1/2 years out from my BLA and I am still very sick, I traded Cushing’s disease for Addison’s disease, and my body does not like it. Cushing’s did a lot more damage than ever thought; I have permanent nerve damage to my lower back, damage to soft tissues throughout my body, Diabetes, High lipids, Fatty liver, I have no usable veins, I have permanent port-a-cath in now so they can access my veins for blood draws and any IV stuff I may need in emergency’s. I had my period for 1 year straight so I had a full hysterectomy 8/20/08. I am permanently panhypopituitary now, no working hormones any more. I am on all replacement hormones, except DDAVP. I ended up with a new doctor that gave me a severe case of steroid induced Cushing’s. I am still dealing with this aftermath; the details are in my timeline. My timeline will update you as to where I am at now. I will try to keep the timeline updated so you know where I am at as far as getting better. Please don’t let this scare you, most people are cured and go on to live lives as best they can, and a lot of people are doing very well. Towards the end of my Cushing’s I went full blown, Dr.Ludlam told me this was a progressive disease and in me this was the case. So if you believe you have Cushing’s, get to a specialist that knows Cushing’s disease, don’t waste time on doctors that do not know the disease, it is so worth it in the end to get to the right doctor. This disease is one of the hardest endocrine diseases to diagnose. Cushings_help.com/ founder MaryO has been a lifesaver for me and still is, I have met people from all over the country, over the years I have made many friends that have, had or are still in the diagnostic phase. I live in a small town of around 10,000 people and I hear all the time, oh I know so and so that had or has a pituitary tumor. What I am finding out is there are a lot of people in this town that have this disease, it is suppose to be rare, one in a million, my next goal is to get my story out and have local people contact me, then start a support group. Maybe get some accurate numbers of actual pituitary/brain tumors and find out why this is happening in this small town. It will be a big adventure but if it saved even one life it will be worth it. I know of 3 definite pituitary Cushing’s cases so far. My Timeline of illness to diagnosis 3rd pregnancy 1994 pre-term labor again, stopped, gestational diabetes, son born 3 weeks early and I got toxemia after my son was born, was told this is very rare. I should have known RARE would be a word I would hear a lot in my future. 1995-Left breast discharge, surgical biopsy done, lump removal of marble size, this should have signaled a full hormonal work-up, but didn’t. No cancer. 1997-1999 Depression and severe anxiety with panic attacks…Diagnosis of Fibromyalgia. Weight 130# 1999- First occurrence of unknown mystery illness. Hypertension, fatigue, flushing, swelling of face, hives, and much more that lasted several months. Sick on and off with mystery illness. Tumor was turning on and off. April 1999-2004-Severe nausea and vomiting, extreme fatigue, weight gain of 50# in about 1 years time, headaches, dizziness, hypertension, tachycardia, muscle and bone pain, malor rash, other rashes, IBS, occasional unexplained low grade fevers, anxiety and depression much worse, increased hirsutism, almost constant mouth sores, memory loss, cognitive difficulties, loss of coordination, syncope, excessive energy spurts, insomnia. **Off work for 3 months April-June due to symptoms…Saw PCP, Gastroenterologist, Rheumatologist and Cardiologist… diagnosis Peptic ulcer/Chronis Gastritis and Chronic pain Syndrome and Tachycardia/Hypertension. Abdominal/Pelvic Cat scan done and fatty liver noted. High Cholesterol and Triglycerides discovered. Nov-2004 My Psychiatrist was the first to mention Cushing’s or a Pheochromocytoma; he felt all my symptoms where due to endocrinology. He did not want to see me again until I was seen at OHSU. I have never seen him again due to insurance change. I really need to thank him. Dec-2004 10# weight gain in 1 week with severe abdominal distention….another Cat scan done, lymph nodes around vena cava where enlarged. Jan-2005 Went to OHSU for diagnosis….First saw an endocrinologist that was not experienced with Cushing’s, she ordered 1 UFC and 2 midnight saliva tests, and told me to test when I felt my worst; Tests where low so she felt my symptoms where not due to my endocrine system. Boy was she wrong. I needed to test when I felt good, or high. Feb-2005 Went to the Pituitary Unit at OHSU and saw Dr.Ludlam, he believed that I had Cushing’s but we needed to prove it. MRI saw adenoma on right side displacing pituitary to the left. He originally thought he saw tumors on both sides, he was right. Lot’s of testing done. Testing did not prove it yet. Dr believes I am Cyclic. It took 1 year for diagnoses from Dr.Ludlam. April-2005 Peripheral vision test done by local optometrist, showed some peripheral loss in left eye. May 2005-Lot’s more Cushing’s testing, PICC line in all month. Major dizziness, passed out and fell this month. Diagnosed with Type 2 Diabetes but cannot treat due to extreme highs and lows, trying to control glucose with diet. I have very high and low Cortisol days. I am very cyclic at this point. June/July 2005-Three TIA like event’s… left sided weakness and numbness. Saw Neurologist that sent me to Neurologist at OHSU. Found three new white matter lesions seen on my brain MRI. Unknown cause. 5 in all now. August 2005-Had to leave my beloved job teaching Medical Assistants due to symptoms. I had one more TIA like event. Sep-2005 Neurologist at OHSU ran several tests and came to the conclusion that if in fact we could prove Cushing’s, all of my symptoms where due to this disease. I stopped all medications by choice. Nov-2005 I went back for extensive testing at OHSU with Dr.Ludlam and sure enough the numbers started proving my case. Very high midnight serum Cortisol’s among other high tests. Jan/Feb 2006-PICC line in and extensive Cushing’s testing done with CSS in Feb. CSS showed left sided gradient strongly. Cortisol numbers have proven my case, finally…. I had a midnight serum Cortisol of 34.1, the Midnight Salivaries, Midnight Serum Cortisol, UFC’s and CSS all positive for Cushing’s disease. March 23, 2006 I finally had Pituitary surgery at OHSU, they found the tumor on the left side bigger than originally though and removed the whole left half of my Pituitary gland. I was in the hospital for 6-days due to complications of Diabetes Insipitus and Adrenal Insuffiency. April-2006 Seen in the ER 3 times. Hospitalized for 4 days again due to complications, Blood cultures showed infection. I am on very high doses of Hydrocortisone and also taking DDAVP for the Diabetes Insipitus. April 2006- I am finally getting better somewhat…..This has been one heck of a roller coaster ride. I am now on Hydrocortisone 40/40/30. I am told we won’t know if I am cured for 3-6 month’s. June 5, 2006- Off Hydrocortisone stimulated my Cortisol to 24 on the ACTH stim test. August, 2006- Not cured, testing again!!! I had that gut feeling when I woke from the first surgery. I just knew… October 12, 2006- Second Pituitary surgery, more tumor on right side, most of my pituitary gland removed. Surgery unsuccessful, still have Cushing’s disease. November 7, 2006- BLA ...soon to be cured of Cushing's. Dec 2006/Jan 2007- Very sick due to another blood infection. Lot’s of adrenal crises due to infections. 3 blood infections to date. November 2008- 2 years out from my BLA and I am still very sick, I traded Cushing’s disease for Addison’s disease, and my body does not like it. Towards the end of my Cushing’s I went full blown, Dr.Ludlam told me this was a progressive disease and in me this was the case. Cushing’s did a lot more damage than ever thought; I have permanent nerve damage to my lower back requiring permanent narcotic pain relief through a pain center, damage to soft tissues throughout my body, diabetes, high lipids, fatty liver (NASH), Osteopenia, I have no usable veins, they are destroyed due to the high Cortisol, I have permanent port-a-cath in now so they can access my veins for blood draws and any IV stuff I may need, I had my period for 1 year straight because of lack of appropriate hormones after my surgeries so I had a full hysterectomy 8/20/08. I am permanently panhypopituitary now, no working pituitary hormones any more at all. I must replace all pituitary hormones, except DDAVP. Please don’t let this scare you, most people are cured and go on to live lives as best they can, and a lot of people are doing very well. June 21, 2009-Since writing in November I sat on the couch in severe AI until around September when I was put with a doctor that has been seeing Cushing’s patients for 38 years, he put me a on a very high dose of Dexamthasone and Florinef and forgot about me, he ended up with cancer and is no longer seeing patients. In the meantime, I got severe steroid induced Cushing’s and have had severe complications from it. I started falling from atrophied muscles and broke both hips, I ended up in a wheelchair, which I am happy to say I am out of now, had to have surgery on my left hip to pin it, it is still not healing, I am having absorption issues with calcium, iron, vitamins, minerals and meds. So I have to do my DEX by injections. We are now trying to find out why I am having absorption issues. I have a new endo at OHSU Dr.V and he is wonderful. He has brought my steroids down to a safe level and did it slow. He really seems to know his stuff as far as after care. I do not think he does the diagnosis process for Cushing’s. I would definitely go back to Dr.Ludlam if I had to go through it again. But I know there are many other great Cushing’s experts out there, this was just my experience. I know I will get better, but it may be a while. I am still at home handicapped, can barely go to the grocery store and I do not drive as I am on a high dose of Morphine. My goal is to get my pain under a 5 and be able to drive myself around. That is a good goal for now. Then on to finding out why my small town has so many tumors and starting a support group. I just need to get to a point where I feel I can be a good advocate for Cushing’s and right now I can’t. But that is the goal. Nov 16, 2009 I am still not well, I have broken my ankle, have no idea how, woke up one morning and it was broken. I am almost down to my 1/2 mg of DEX and am happy about that. had 2 surgeries in Sep and Oct on both elbows for ulnar nerve decompression. The first surgery got infected and a week later I had sepsis, which they think I had a small bowel preferation that healed itself. I was ambulanced up to OHSU and was in AI. It was a very rare bowel bacteria running through my blood stream, I was very sick. I just want to get well, but for some reason I am going through one thing after another. I am praying that 2010 will be my year of healing and I will have a good quaility of life then.That is what I am counting on. UPDATE January 23, 2016 2016: wow has the past few years have been a roller coaster. I don't know dates because I'm having memory issues at 47 years old. I have had 5 port-a-caths. I kept getting sepsis and every time they would take me to surgery and remove my port. Then place another when I was better. I have no veins that work. So I received IV port fluids 2-3x a week. I just recently had sepsis, when I get it I have a 50/50 % chance of survival. They removed my port and did not place another. So no more fluids which was for Pots. I had labs done through my port every 2 weeks. Now everything stopped. I am producing small amounts of cortisol. After a BLA. Intermittently. I am just now starting to feel good for 2 weeks now. I have started the exercise program called T-Tapp. I love it. No jumping or hard moves. 15 min and that's it. I am a grandma of 2 and one due any day. So for now I hope I'm on the road to recovery at least the best I can. HOME | Sitemap | Abbreviations | Adrenal Crisis! | Glossary | Forums | Bios | Add Your Bio | Add Your Doctor | MemberMap | CushieWiki
  20. Braun LT, Fazel J, Zopp S Journal of Bone and Mineral Research | May 22, 2020 This study was attempted to assess bone mineral density and fracture rates in 89 patients with confirmed Cushing's syndrome at the time of diagnosis and 2 years after successful tumor resection. Researchers ascertained five bone turnover markers at the time of diagnosis, 1 and 2 years postoperatively. Via chemiluminescent immunoassays, they assessed bone turnover markers osteocalcin, intact procollagen‐IN‐propeptide, alkaline bone phosphatase, CrossLaps, and TrAcP 5b in plasma or serum. For comparison, they studied 71 gender‐, age‐, and BMI‐matched patients in whom Cushing's syndrome had been excluded. The outcomes of this research exhibit that the phase immediately after surgical remission from endogenous CS is defined by a high rate of bone turnover resulting in a striking net increase in bone mineral density in the majority of patients. Read the full article on Journal of Bone and Mineral Research.
  21. 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
  22. 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?
  23. Those are all definitely symptoms of Cushing's...and excess cortisol. I think I had every one of them while I was being diagnosed. Have you taken steroids, especially often? They can cause these symptoms. Definitely mention these symptoms to your doctor. Please keep us posted.
  24. MaryO

    Naturopath

    Heidi, my first instinct was to say no but I did a search of the boards and found 177 posts on this topic so some people have actually gone this route. If you join the boards, you can read those responses. My reasoning for saying no was that if you have Cushing's, it is generally caused by a tumor and surgery is the only way to deal with the tumor. If Cushing's is caused by taking steroids, weaning off the steroids can sometimes help. Have you been diagnosed with Cushing's? If so, do you know what type? Best of luck to you!
  25. First published:03 May 2020 Read the entire article at https://doi.org/10.1002/alr.22540 Potential conflict of interest: None disclosed. Presented at the 65th Annual Meeting of the American Rhinologic Society, on September 14, 2019, in New Orleans, LA. Abstract Background Endoscopic transsphenoidal surgery (ETS) for the resection of pituitary adenoma has become more common throughout the past decade. Although most patients have a short postoperative hospitalization, others require a more prolonged stay. We aimed to identify predictors for prolonged hospitalization in the setting of ETS for pituitary adenomas. Methods A retrospective chart review as performed on 658 patients undergoing ETS for pituitary adenoma at a single tertiary care academic center from 2005 to 2019. Length of stay (LoS) was defined as date of surgery to date of discharge. Patients with LoS in the top 10th percentile (prolonged LoS [PLS] >4 days, N = 72) were compared with the remainder (standard LoS [SLS], N = 586). Results The average age was 54 years and 52.5% were male. The mean LoS was 2.1 days vs 7.5 days (SLS vs PLS). On univariate analysis, atrial fibrillation (p = 0.002), hypertension (p = 0.033), partial tumor resection (p < 0.001), apoplexy (p = 0.020), intraoperative cerebrospinal fluid (ioCSF) leak (p = 0.001), nasoseptal flap (p = 0.049), postoperative diabetes insipidus (DI) (p = 0.010), and readmission within 30 days (p = 0.025) were significantly associated with PLS. Preoperative continuous positive airway pressure (CPAP) (odds ratio, 15.144; 95% confidence interval, 2.596‐88.346; p = 0.003) and presence of an ioCSF leak (OR, 10.362; 95% CI, 2.143‐50.104; p = 0.004) remained significant on multivariable analysis. Conclusion For patients undergoing ETS for pituitary adenomas, an ioCSF leak or preoperative use of CPAP predicted PLS. Additional common reasons for PLS included postoperative CSF leak (10 of 72), management of DI or hypopituitarism (15 of 72), or reoperation due to surgical or medical complications (14 of 72). From https://onlinelibrary.wiley.com/doi/abs/10.1002/alr.22540?af=R
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