MaryO

We have an opportunity for you to take part in a Cushing's Disease study(IPS_4636) for Patients. Our project number for this study is IPS_4636. Project Details: Web- Camera Interview There is a homework component Interview is 75-minutes long 125 Reward + 100 homework Things to Note: Patient study only, Caregivers please pass the link along Unique links, please do not pass along for 2nd use One Participant per household Want to share this opportunity? Let us know and we can provide a new link Preliminary questions are Mobile Friendly! Save this email to reference if you have any questions about the study! If you have any problems, email pm3@rarepatientvoice.com and reference the project number. If you hit reply, you will get an auto do-not-reply email. If you are interested in this study, please click the link below to answer a few questions to see if you qualify. Study Link: Link OR if the Study Hyperlink is not clickable above, please copy/paste this URL below. https://panel.rarepatientvoice.com/newdesign/site/rarepatientvoice/surveystart.php?surveyID=hld5jbejublj&panelMemberID=trfnbc7mvduh1gseff1h&invite=email Thanks as always for your participation! Please be aware that by entering this information you are not guaranteed that you will be selected to participate. As always, we do not share any of your contact information without your permission.

The treatment of adrenal insufficiency with hydrocortisone granules in children with congenital adrenal hyperplasia (CAH) was associated with an absence of adrenal crises and normal growth patterns over a 2-year period, according to study findings published in The Journal of Clinical Endocrinology and Metabolism. The study included a total of 17 children with CAH and 1 child with hypopituitarism. All included participants were <6 years old who were receiving current adrenocortical replacement therapy, including hydrocortisone with or without fludrocortisone. Hydrocortisone medications used in this population were converted from pharmacy compounded capsules to hydrocortisone granules without changing the dose. These study participants were followed by study investigators for 2 years. Glucocorticoid replacement therapy was given three times a day for a median treatment duration of 795 days. Treatment was adjusted by 3 monthly 17-hydroxyprogesterone (17-OHP) profiles in children with CAH. There were a 150 follow-up visits throughout the study. At each visit, participants underwent assessments that measured hydrocortisone dose, height, weight, pubertal status, adverse events, and incidence of adrenal crisis. A total of 40 follow-up visits had changes in hydrocortisone doses based on salivary measurements (n=32) and serum 17-OHP levels (n=8). At time of study entry, the median daily doses of hydrocortisone were 11.9 mg/m2 for children between the ages of 2 to 8 years, 9.9 mg/m2 for children between 1 month and 2 years, and 12.0 mg/m2 for children <28 days of age. At the end of the study, the respective doses for the 3 age groups were 10.2, 9.8, and 8.6. The investigators observed no trends in either accelerated growth or reduced growth; however, 1 patient with congenital renal hypoplasia and CAH did show reduced growth. While 193 treatment-emergent adverse events, including pyrexia, gastroenteritis, and viral upper respiratory tract infection, were reported in 14 patients, there were no observed adrenal crises. Limitations of this study included the small sample size as well as the relatively high drop-out rate of the initial sample. The researchers concluded that “hydrocortisone granules are an effective treatment for childhood adrenal insufficiency providing the ability to accurately prescribe pediatric appropriate doses.” Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures. Reference Neumann U, Braune K, Whitaker MJ, et al. A prospective study of children 0-7 years with CAH and adrenal insufficiency treated with hydrocortisone granules. Published online September 4, 2020. J Clin Endocrinol Metab. doi:10.1210/clinem/dgaa626

Generally overweight people have weight everywhere and don't get a buffalo hump. Please don't give up! I know it's hard to get a diagnosis but definitely worthwhile.

Dr. Friedman wants to update his patients about natural desiccated thyroid (NDT) recalls based on new information from the FDA. Dr. Friedman prescribes various thyroid hormone preparations to his patients with hypothyroidism. This includes natural desiccated thyroid (NDT) of which two preparations are WP Thyroid and Nature-Throid, both made by RLC Labs. On August 25, 2020, RLC Labs announced a voluntary, consumer-level recall of all lots of Nature-Throid and WP Thyroid tablets because some lots contain less than the required 90% of the active ingredient as determined by the FDA. The RLC spokesperson said to Dr. Friedman that one lot of WP Thyroid and 5 lots of Nature-Throid contained between 87% and 90% of the labeled amount of levothyroxine (T4) or liothyronine (T3). Recently the FDA announced which lots are recalled that are listed below. According to the recall, if a patient receives a sub-potent tablet, hypothyroid symptoms may not be controlled. To date, there have been no reports of adverse events related to this recall. Patients who have had an adverse event should contact RLC Labs. The lot numbers are listed on the bottles of Nature-Throid and WP Thyroid. With this information about which lots are recalled, Dr. Friedman is only recommended those taking the effective lots to discontinue them. Currently no lots of Nature-Throid and WP Thyroid tablets are commercially available, so a replacement with the same product is not an option. It is unknown how long it will be before Nature-Throid and WP Thyroid become commercially available. In September 2020, the FDA also announced that two lots (one of 15 mg and one of 120 mg) (see table) of NP Thyroid made by Acella Pharamceuticals were also recalled due to reduced potency between 87% and 90% of the labeled amount of levothyroxine (T4) or liothyronine (T3). Other lots are currently available. The lot numbers are not listed on the Acella product bottles, but the expiration dates are. If patient has one of the products with the expiration date listed, they can ask their pharmacy for the lot number. Dr. Friedman has several comments about these recalls. Dr. Friedman sees them as unfortunate, but still believes NDT is a good option for patients with hypothyroidism. The “subpotent” Nature-Throid, WP Thyroid and NP Thyroid pills are only slightly less potent than stated in that only the effective lots are between 87% and 90% of the T4 and T3 levels. For most patients, they will not have symptoms from these subpotent pills and if they are taking a lot that is subpotent, the dose can be adjusted based on laboratory levels at your next appointment with Dr. Friedman. According to Dr. Friedman, patients taking Nature-Throid and WP Thyroid with the subpotent lots have three options: 1) they can continue taking Nature-Throid and WP Thyroid knowing they may have a subpotent lot and knowing that they may not be able to get a refill at least temporarily. 2) patients can be switched to Armour thyroid, NP thyroid or have a compounding pharmacy compound the equivalent dose using USP grade porcine powder. Please let Dr. Friedman’s office know if you would like to go on a different desiccated thyroid product (and which one) and what pharmacy you would like to use, 3) Dr. Friedman has a small supply of desiccated thyroid with no reclled lots that is available at his clinic for those in Los Angeles on the last Tuesday night of each month. He will not be able to mail desiccated thyroid. Please contact his office about this option. Patients with a subpotent lot of NP thyroid can have their pharmacy switch them to an unaffected lot at no charge. Patients do not need to contact Dr. Friedman, but if you have any questions or need to schedule an appointment with Dr. Friedman, please email us at mail@goodhormonehealth.com or schedule an appointment on his website at www.goodhormonehealth.com.

Presented by Dr. Magge, Assistant Professor of Neurology at Weill Cornell Medical College and an Assistant Attending Neurologist at New York-Presbyterian Hospital. Dr. Ranakrishna, Chief of Neurological Surgery at NewYork-Presbyterian Brooklyn Methodist Hospital, Associate Professor of Neurological Surgery at Avina and Willis Murphy at Weill Cornell Medicine Click here to attend. Date: Tuesday, October 13, 2020 Time: 10:00 AM Eastern Daylight Time Learning objectives: - the basic characteristics of the different types of pituitary adenomas - the potential predictors of recurrence and aggressiveness in pituitary adenomas - the surgical and radiotherapy options for recurrent pituitary adenomas - the potential medical interventions, including chemotherapy, for recurrent pituitary adenomas

Health Condition: All Conditions Demographics: Ages 18+, United States Resident Special Request(s): Everyone who has taken part in a clinical trial is asked to share. We are interested in learning why you decided to take part in a clinical trial and how your experience went. Honoraria: Some respondents may be asked to participate in a clinical trial awareness network where there are paid opportunities to tell their stories. Apply to learn more.

Michael P Catalino 1 2, David M Meredith 3 4, Umberto De Girolami 3 4, Sherwin Tavakol 1 5, Le Min 6, Edward R Laws 1 4 Affiliations expand PMID: 32886921 DOI: 10.3171/2020.5.JNS201514 Abstract Objective: This study was done to compare corticotroph hyperplasia and histopathologically proven adenomas in patients with Cushing disease by analyzing diagnostic features, surgical management, and clinical outcomes. Methods: Patients with suspected pituitary Cushing disease were included in a retrospective cohort study and were excluded if results of pathological analysis of the surgical specimen were nondiagnostic or normal. Cases were reviewed by two experienced neuropathologists. Total lesion removal was used as a dichotomized surgical variable; it was defined as an extracapsular resection (including a rim of normal gland) in patients with an adenoma, and for hyperplasia patients it was defined as removal of the presumed lesion plus a rim of surrounding normal gland. Bivariate and multivariate analyses were performed. Recurrence-free survival was compared between the two groups. Results: The final cohort consisted of 63 patients (15 with hyperplasia and 48 with adenoma). Normal pituitary acinar architecture was highly variable. Corticotroph hyperplasia was diagnosed based on the presence of expanded acini showing retained reticulin architecture and predominant staining for adrenocorticotropic hormone. Crooke's hyaline change was seen in 46.7% of specimens, and its frequency was equal in nonlesional tissue of both groups. The two groups differed only by MRI findings (equivocal/diffuse lesion in 46% of hyperplasia and 17% of adenoma; p = 0.03). Diagnostic uncertainty in the hyperplasia group resulted in additional confirmatory testing by 24-hour urinary free cortisol. Total lesion removal was infrequent in patients with hyperplasia compared to those with adenoma (33% vs 65%; p = 0.03). Initial biochemical remission was similar (67% in hyperplasia and 85% in adenoma; p = 0.11). There was no difference in hypothalamic-pituitary-adrenal axis recovery or disease recurrence. The median follow-up was 1.9 years (IQR 0.7-7.6 years) for the hyperplasia group and 1.2 years (IQR 0.4-2.4 years) for the adenoma group. Lack of a discrete lesion and diagnostic uncertainty were the only significant predictors of hyperplasia (sensitivity 53.3%, specificity 97.7%, positive predictive value 88.9%, negative predictive value 85.7%). An adjusted Cox proportional hazards model showed similar recurrence-free survival in the two groups. Conclusions: This study suggests an association between biochemically proven Cushing disease and histopathologically proven corticotroph hyperplasia. Imaging and operative findings can be ambiguous, and, compared to typical adenomas with a pseudocapsule, the surgical approach is more nuanced. Nevertheless, if treated appropriately, biochemical outcomes may be similar. Keywords: ACTH = adrenocorticotropic hormone; CRH = corticotropin-releasing hormone; Cushing disease; HPA = hypothalamic-pituitary-adrenal; HR = hazard ratio; IPSS = inferior petrosal sinus sampling; ROC = receiver operating characteristic; UFC = urinary free cortisol; corticotroph adenoma; corticotroph hyperplasia; diagnosis; pathology; pituitary surgery; surgical outcomes. From https://pubmed.ncbi.nlm.nih.gov/32886921/

Presented by Ahmad Sedaghat, MD, PhD - Associate Professor and Director of the Division of Rhinology, Allergy and Anterior Skull Base Surgery in the Department of Otolaryngology - Head and Neck Surgery at the University of Cincinnati College of Medicine and UC Health. Norberto Andaluz, MD, MBA, FACS - Professor of Neurosurgery and Otolaryngology/Head and Neck Surgery - Director, Division of Skull Base Surgery University of Cincinnati College of Medicine and University of Cincinnati Gardner Neuroscience Institute - UC Health Click here to attend Date: Wednesday, Sept 23, 2020 Time: 3:00 PM Eastern Daylight Time Learning objectives: 1. To understand the surgical steps of endoscopic pituitary surgery 2. To understand how the surgical steps of endoscopic pituitary surgery translate to post-operative outcomes 3. To understand surgical factors that can modify post-operative outcomes after endoscopic pituitary surgery 4. To understand post-operative care that can modify post-operative outcomes after endoscopic pituitary surgery

Adults with adrenal insufficiency who are adequately treated and trained display the same incidence of COVID-19-suggestive symptoms and disease severity as controls, according to a presenter. “Adrenal insufficiency is supposed to be associated with an increased risk for infections and complications,” Giulia Carosi, a doctoral student in the department of experimental medicine at Sapienza University of Rome, said during a presentation at the virtual European Congress of Endocrinology Annual Meeting. “Our aim was to evaluate the incidence of COVID symptoms and related complications in this group.” In a retrospective, case-control study, Carosi and colleagues evaluated the incidence of COVID-19 symptoms and complications among 279 adults with primary or secondary adrenal insufficiency (mean age, 57 years; 49.8% women) and 112 adults with benign pituitary nonfunctioning lesions without hormonal alterations, who served as controls (mean age, 58 years; 52.7% women). All participants lived in the Lombardy region of northern Italy. Participants completed a standardized questionnaire by phone on COVID-19-suggestive symptoms, such as fever, cough, myalgia, fatigue, dyspnea, gastrointestinal symptoms, conjunctivitis, loss of smell, loss of taste, upper respiratory tract symptoms, thoracic pain, headaches and ear pain. Patients with primary or secondary adrenal insufficiency were previously trained to modify their glucocorticoid replacement therapy when appropriate. From February through April, the prevalence of participants reporting at least one symptom of viral infection was similar between the adrenal insufficiency group and controls (24% vs. 22.3%; P = .788). Researchers observed “highly suggestive” symptoms among 12.5% of participants in both groups. No participant required hospitalization and no adrenal crisis was reported. Replacement therapy was correctly increased for about 30% of symptomatic participants with adrenal insufficiency. Carosi noted that few nasopharyngeal swabs were performed (n = 12), limiting conclusions on the exact infection rate (positive result in 0.7% among participants with adrenal insufficiency and 0% of controls; P = .515). “We can conclude that hypoadrenal patients who have regular follow-up and trained about risks for infection and sick day rules seem to present the same incidence of COVID-19 symptoms and the same disease severity as controls,” Carosi said. As Healio previously reported, there is no evidence that COVID-19 has a more severe course among individuals with primary and secondary adrenal insufficiency; however, those with adrenal insufficiency are at increased risk for respiratory and viral infections, and patients experiencing major inflammation and fever are at risk for life-threatening adrenal crisis. In a position statement issued by the American Association of Clinical Endocrinologists in March, researchers wrote that people with adrenal insufficiency or uncontrolled Cushing’s syndrome should continue to take their medications as prescribed and ensure they have appropriate supplies for oral and injectable steroids at home, with a 90-day preparation recommended. In the event of acute illness, those with adrenal insufficiency are instructed to increase their hydrocortisone dose per instructions and call their health care provider for more details. Standard “sick day” rules for increasing oral glucocorticoids or injectables would also apply, according to the statement. From https://www.healio.com/news/endocrinology/20200910/no-increased-covid19-risk-with-adequately-treated-adrenal-insufficiency

Patients with endogenous Cushing’s syndrome who stopped using Recorlev (levoketoconazole) and moved to a placebo in a study started having their urine cortisol levels rise in response to lack of treatment, compared with those who remained on Recorlev, according to top-line data from the Phase 3 LOGICS trial. Based on these findings and data from a previous Phase 3 trial of Recorlev called SONICS (NCT01838551), the therapy’s developer, Strongbridge Biopharma, is planning to submit a new drug application requesting its approval to the U.S. Food and Drug Administration (FDA) early next year. If approved, Recorlev could be available to patients in the U.S. in 2022. “We are delighted to announce the positive and statistically significant top-line results of the LOGICS study, which add to the growing body of evidence supporting the potential of Recorlev (levoketoconazole) as an effective and well tolerated cortisol synthesis inhibitor to treat Cushing’s syndrome,” Fredric Cohen, MD, chief medical officer of Strongbridge Biopharma, said in a press release. Recorlev, also known as COR-003, is an investigational oral treatment for endogenous Cushing’s syndrome that inhibits the production of cortisol, the glucocorticoid hormone that is overly produced in patients with the disorder. The safety, tolerability, effectiveness, and pharmacological properties of Recorlev in people with endogenous Cushing’s syndrome are currently being assessed in the LOGICS trial (NCT03277690). LOGICS enrolled patients who had never been treated with Recorlev, as well as those given the medication in SONICS. The study included an initial withdrawal phase, in which patients were assigned randomly to either Recorlev (up to a dose of 1,200 mg), or to a placebo for about 8 weeks. This was followed by a restoration phase, lasting approximately the same time, in which all patients received Recorlev in combination with a placebo. With this design, patients initially assigned to Recorlev continued treatment in the study’s second phase, while those originally assigned to a placebo switched to Recorlev. Before enrolling in the study’s initial randomized-withdrawal phase, patients completed an open-label titration and maintenance phase lasting 14 to 19 weeks, which determined the best dose of Recorlev they should receive later. Of the 79 patients who entered the open-label titration and maintenance phase, 44 enrolled in the randomized-withdrawal phase, and 43 completed this initial portion of the trial. Top-line data now announced by the company showed the proportion of patients having their urine cortisol levels rise by the end of the randomized-withdrawal phase was 54.5% higher among those on a placebo than among those treated with Recorlev (95.5% vs. 40.9%). All 21 patients who lost their initial treatment response in the open-label portion of the study, and saw their cortisol levels rise after moving to a placebo (withdrawal phase) were given early rescue treatment. Their cortisol levels started to drop after a median of 22 days. The percentage of patients whose urine cortisol levels were within normal range by the end of the withdrawal phase was 45.5% higher among those treated with Recorlev, compared with those given a placebo (50.0% vs. 4.5%). In addition to losing benefits related to cortisol control, patients receiving a withdrawal-phase placebo also lost the therapy’s positive cholesterol-lowering effects. “The Phase 3 LOGICS results complement the long-term efficacy and safety data supplied by the Phase 3 SONICS study, which was published in The Lancet Diabetes & Endocrinology, by confirming that the effects of Recorlev (levoketoconazole) were responsible for the therapeutic response when treatment was continued compared to withdrawing patients to placebo,” said Maria Fleseriu, MD, FACE, professor of Medicine and Neurological Surgery and director of the Oregon Health Sciences University Pituitary Center, and principal investigator of the study. “The LOGICS findings — which build upon the long-term benefit shown during open-label treatment in SONICS — provide robust evidence to support the use of RECORLEV as an important treatment option for this life-threatening rare endocrine disease,” Fleseriu added. Recorlev was found to be safe and well-tolerated in LOGICS. Of the 79 patients who entered in the study’s open-label titration and maintenance phase, 19% discontinued due to side effects in this phase, and none of the 44 who proceeded to the withdrawal phase stopped treatment for these reasons. The most common side effects observed during the first two parts of LOGICS included nausea (29%), low blood potassium levels (28%), headache (21%), high blood pressure (19%), and diarrhea (15%). Some patients saw the levels of their liver enzymes rise above normal levels — a sign of liver inflammation and damage — during the study. However, this and other side effects of special interest, including those associated with adrenal insufficiency, resolved by either lowering the dose or stopping treatment with Recorlev. The proportion of patients experiencing these side effects was similar to that seen in SONICS. These findings are part of a subset of data from a planned interim analysis of LOGICS. Final study data requires analyses of additional datasets. Adapted from https://www.globenewswire.com/news-release/2020/09/08/2089872/0/en/Strongbridge-Biopharma-plc-Announces-Positive-and-Statistically-Significant-Top-Line-Results-from-the-Pivotal-Phase-3-LOGICS-Study-of-RECORLEV-levoketoconazole-for-the-Treatment-of.html

The first ever prospective study to test the safety and efficacy of metyrapone in patients with Cushing’s Syndrome in a real-life setting has shown successful results. HRA Pharma Rare Diseases SAS, of Paris, has presented data from PROMPT, the first ever prospective study designed to confirm metyrapone efficacy and good tolerance in patients with endogenous Cushing’s Syndrome, with results confirming that metyrapone controlled 80% of the patients at week 12 with either normalisation or at least 50% decrease of urinary free cortisol. These initial results are being published to coincide with HRA Pharma Rare Diseases’ participation in the e-ECE conference 2020. Cushing’s Syndrome is a rare condition where patients have too much cortisol in their blood. Endogenous Cushing’s Syndrome is most often caused by hormone-releasing tumours of the adrenal or the pituitary glands. To manage this condition, controlling high cortisol levels in patients is important. Successful results with metyrapone Metyrapone is an inhibitor of the 11-beta-hydroxylase enzyme, which majorly contributes to cortisol synthesis and is approved in Europe for the treatment of endogenous Cushing’s Syndrome based on observational retrospective studies published over more than 50 years. As this prospective study took place over five years from April 2015 to April 2020, the longitudinal format reduced potential sources of bias and helped determine the risk factors of metyrapone when compared to the previous retrospective studies. The first results of this study showed that at the end of the 12 weeks, metyrapone therapy is a rapid-onset, effective and safe medical treatment in patients living with the syndrome. Evelina Paberze, COO of HRA Pharma Rare Diseases, said: “At HRA Pharma Rare Diseases, we are dedicated to building comprehensive evidence of our products. The first results of this prospective study clearly demonstrate the effectiveness of metyrapone in treating Cushing’s Syndrome.” The next set of data on the six-month optional extension is awaiting confirmation and the full study with the final results will be published next year. Frederique Welgryn, Managing Director of HRA Pharma Rare Diseases, added: “Cushing’s Syndrome is a chronic disease that can lead to deterioration in patients’ conditions if not treated appropriately. We are thrilled to announce that this first prospective study verifies that metyrapone is both an effective and safe way to treat endogenous Cushing’s Syndrome. This is a big step given the high unmet medical need for patients with endogenous Cushing’s Syndrome.” From https://www.healtheuropa.eu/study-shows-metyrapone-effective-for-treating-rare-cushings-syndrome/102584/

Abnormally high levels of cortisol in the urine — one of the hallmarks of Cushing’s syndrome — seem to be associated with alterations in blood sugar metabolism in obese patients, a study found. The study, “Hypercortisolism and altered glucose homeostasis in obese patients in the pre-bariatric surgery assessment,” was published in the journal Diabetes/Metabolism Research and Reviews.

Carma, I removed the links from your post. I suggest you try spamming elsewhere.

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

Dr. Friedman prescribes various thyroid hormone preparations to his patients with hypothyroidism. This includes natural desiccated thyroid (NDT) of which two preparations are WP Thyroid and Nature-Throid, both made by RLC Labs. On August 25, 2020, RLC Labs announced a voluntary, consumer-level recall of all lots of Nature-Throid and WP Thyroid tablets because some lots contain less than the required 90% of the active ingredient as determined by the FDA. The RLC spokesperson said to Dr. Friedman that one lot of WP Thyroid and 5 lots of Nature-Throid contained between 87% and 90% of the labeled amount of levothyroxine (T4) or liothyronine (T3). The recall did not disclose which of the lots were affected and all lots are recalled, not just the affected lots. According to the recall, if a patient receives a sub-potent tablet, hypothyroid symptoms may not be controlled. To date, there have been no reports of adverse events related to this recall. Patients who have had an adverse event should contact RLC Labs. RLC Labs advised that patients should talk to their healthcare professional before they stop taking their Nature-Throid and WP Thyroid medicine. Consumers with questions about the recall can email RLC at recall@rlclabs.com or RLC Customer Service (877) 797-7997. Patients may return unexpired Nature-Throid and WP Thyroid tablets to their pharmacy who are legally required to refund the cost of the tablets. Currently no lots of Nature-Throid and WP Thyroid tablets are commercially available, so a replacement with the same product is not an option. It is unknown how long it will be before Nature-Throid and WP Thyroid become commercially available. Dr. Friedman has several comments about this recall. This is the second recall of desiccated thyroid as some lots of NP thyroid were recalled in May 2020. Dr. Friedman sees this as unfortunate, but still believes desiccated thyroid is a good option for patients with hypothyroidism. Secondly, the “subpotent” Nature-Throid and WP Thyroid pills are only slightly less potent than stated in that only a few lots are between 87% and 90% of the T4 and T3 levels. For most patients, they will not have symptoms from these subpotent pills and if they are taking a lot that is subpotent, the dose can be adjusted based on laboratory levels at your next appointment with Dr. Friedman. According to Dr. Friedman, patients taking Nature-Throid and WP Thyroid have three options: 1) they can continue taking Nature-Throid and WP Thyroid knowing they may have a subpotent lot and knowing that they may not be able to get a refill at least temporarily. 2) patients can be switched to Armour thyroid, NP thyroid or have a compounding pharmacy compound the equivalent dose using USP grade porcine powder. Please let Dr. Friedman’s office know if you would like to go on a different desiccated thyroid product (and which one) and what pharmacy you would like to use, 3) Dr. Friedman has a small supply of desiccated thyroid that is available at his clinic for those in Los Angeles on the last Tuesday night of each month. He will not be able to mail desiccated thyroid. Please contact his office about this option. Patients do not need to contact Dr. Friedman, but if you have any questions or need to schedule an appointment with Dr. Friedman, please email us at mail@goodhormonehealth.com or schedule an appointment on his website at goodhormonehealth.com.

Thanks for being a member of Rare Patient Voice, LLC. We have an opportunity for you to take part in a Cushing Syndrome interview (NEON_4470) for Patients. Our project number for this study is NEON_4470. Project Details: Telephone interview Interview is 60-minutes long One Hundred Dollar Reward Looking for Patients diagnosed with Endogenous Cushing Syndrome Things to Note: Patient study only, Caregivers please pass the link along Unique links, please do not pass along for 2nd use Want to share this opportunity? Let us know and we can provide a new link Please use a laptop/computer ONLY. No smartphones or tablets - Preliminary questions are Mobile Friendly! Save this email to reference if you have any questions about the study! If you have any problems, email michael.taylor@rarepatientvoice.com and reference the project number. If you hit reply, you will get an auto do-not-reply email. If you are interested in this study, please click the link below to answer a few questions to see if you qualify. Study Link: Link OR if the Study Hyperlink is not clickable above, please copy/paste this URL below. https://panel.rarepatientvoice.com/newdesign/site/rarepatientvoice/surveystart.php?surveyID=9mth6d868qpc&panelMemberID=trfnbc7mvduh1gseff1h&invite=email Thanks as always for your participation! Please be aware that by entering this information you are not guaranteed that you will be selected to participate. As always, we do not share any of your contact information without your permission. Not Interested in this study? (Click link below so we do not send you any reminders for this study) Study Reminder Opt Out Link: Link We truly appreciate the time you set aside to interact with our company and don’t take it for granted. Receive a $5 gift card for referring others who may want to participate in this or future studies. Invite them to join Rare Patient Voice: https://www.rarepatientvoice.com/sign-up. They, too, receive a gift card. Our Privacy Policy Regards, Michael Taylor Project Manager Rare Patient Voice Helping Patients with Rare Diseases Voice Their Opinions Phone: + 1 609-462-5519 Email: michael.taylor@rarepatientvoice.com Websites: www.rarepatientvoice.com

Osilodrostat treatment was found to be associated with a rapid and sustained reduction in mean concentration of urinary free cortisol (UFC) and improved clinical symptoms in patients with Cushing’s disease, according to the results of a prospective, multicenter, open-label, phase 3 study published in the Lancet Diabetes Endocrinology. Osilodrostat is an oral inhibitor of 11-β hydroxylase cytochrome P450. Adults aged 18 to 75 years of age with diagnosed persistent or recurrent Cushing’s disease were recruited between 2014 and 2017 at 66 hospitals in 19 countries. Cushing’s disease was defined by a mean UFC concentration over a 24-hour period >1.5 times greater than the upper limit of normal (ULN) and morning plasma adrenocorticotropic hormone level above normal limits. Participants (n=137) received 30 mg osilodrostat twice daily, dose which was adjusted every 2 weeks until week 12 on the basis of mean 24-hour UFC concentration. The determined maintenance dose was continued until week 24. At week 26, participants who had achieved 24-hour UFC concentration ≤ ULN and did not need titration after week 12 were randomly assigned in an equal ratio to maintain osilodrostat treatment or were switched to a placebo for 8 weeks. This 8-week period of the study was double-blinded. During weeks 35 to 48, all patients were returned to osilodrostat treatment. In this cohort, mean age was 40.0 years (range, 19.0-70.0 years), 77% of participants were women, the average time since diagnosis was 47.2 months (interquartile range [IQR], 19.0-88.3), 88% had previous pituitary surgery, 16% had pituitary radiation therapy, and 74% had medicinal therapy. At baseline, the mean 24-hour UFC concentration was 1006±1590 nmol/24 h. At week 24, 53% of participants achieved a mean 24-hour UFC concentration ≤ULN without increases in dose after week 12 and were eligible for randomization (osilodrostat, n=36; placebo, n=35). At week 34, more patients receiving osilodrostat vs placebo maintained a complete response (86% vs 29%, respectively; odds ratio [OR], 13.7; 95% CI, 3.7-53.4; P <.0001). Improvements in cardiovascular-related metabolic parameters associated with hypercortisolism and overall measures of well-being were observed. Levels of high-density lipoprotein decreased by week 48 (-0.3 mmol/L; 95% CI, .0.3 to -0.2), mean Cushing’s quality of life score increased by 52.4% (95% CI, 32.3-72.7), and Beck Depression Inventory score decreased by 31.8% (95% CI, -44.3 to -19.3). Adverse events were hypocortisolism (51%), adverse events related with adrenal hormone precursors (42%), nausea (42%), headache (34%), fatigue (28%), and adrenal insufficiency (28%). A total of 18% of participants dropped out of the study due to adverse events. The major limitation of this study was the short withdrawal period (8 weeks) which may not have permitted to observe symptoms of hypercortisolism. “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,” concluded the study authors. Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures. Reference Pivonello R, Fleseriu M, Newell-Price J, et al. Efficacy and safety of osilodrostat in patients with Cushing’s disease (LINC 3): a multicentre phase III study with a doubleblind, randomised withdrawal phase. Lancet Diabetes Endocrinol. 2020;S2213-8587(20)30240-0. doi:10.1016/S2213-8587(29)30240-0 From https://www.endocrinologyadvisor.com/home/topics/general-endocrinology/osilodrostat-sustained-reduction-mean-ufc-concentration-cushings-disease/

Susanne, this is not a blog. It is a message board about Cushing's Syndrome and Disease. I would suggest you do a google search for how to write blog posts.

Study Authors: Tsung-Chieh Yao, Ya-Wen Huang, et al.; Beth I. Wallace, Akbar K. Waljee Target Audience and Goal Statement: Primary care physicians, rheumatologists, pulmonologists, dermatologists, gastroenterologists, cardiologists The goal of this study was to examine the associations between oral corticosteroid bursts and severe adverse events among adults in Taiwan. Question Addressed: What were the associations between steroid bursts and severe adverse events, specifically gastrointestinal (GI) bleeding, sepsis, and heart failure? Study Synopsis and Perspective: It has long been known that long-term use of corticosteroids can be both effective and toxic. Long-term use is associated with adverse effects such as infections, GI bleeding/ulcers, cardiovascular disease (CVD), Cushing syndrome, diabetes and metabolic syndromes, cataracts, glaucoma, and osteoporosis. Most clinical practice guidelines caution against long-term steroid use unless medically necessary. Action Points In a retrospective cohort study and self-controlled case series, prescriptions for oral steroid bursts were found to be associated with increased risks for gastrointestinal bleeding, sepsis, and heart failure within the first month after initiation, despite a median exposure of just 3 days. Note that the risks were highest 5 to 30 days after exposure, and attenuated during the subsequent 31 to 90 days. Instead, clinical practice guidelines recommend steroid bursts for inflammatory ailments such as asthma, inflammatory bowel disease, and rheumatoid arthritis. Waljee and colleagues noted in 2017 that they are most commonly used for upper respiratory infections, suggesting that many people are receiving steroids in the real world. In a retrospective cohort study and self-controlled case series, prescriptions for oral steroid bursts -- defined as short courses of oral corticosteroids for 14 or fewer days -- were found to be associated with increased risks for GI bleeding, sepsis, and heart failure within the first month after initiation, despite a median exposure of just 3 days, according to Tsung-Chieh Yao, MD, PhD, of Chang Gung Memorial Hospital in Taoyuan, and colleagues. The risks were highest 5 to 30 days after exposure, and attenuated during the subsequent 31 to 90 days, they reported in Annals of Internal Medicine. The self-controlled case series was based on national medical claims records. Included were adults, ages 20-64, covered by Taiwan's National Health Insurance in 2013-2015. Out of a population of more than 15.8 million, study authors identified 2,623,327 people who received a steroid burst during the study period. These individuals were age 38 on average, and 55.3% were women. About 85% had no baseline comorbid conditions. The most common indications for the steroid burst were skin disorders and respiratory tract infections. The incidence rates among patients prescribed steroid bursts were 27.1 per 1,000 person-years for GI bleeding (incidence rate ratio [IRR] 1.80, 95% CI 1.75-1.84), 1.5 per 1,000 person-years for sepsis (IRR 1.99, 95% CI 1.70-2.32), and 1.3 per 1,000 person-years for heart failure (IRR 2.37, 95% CI 2.13-2.63). Absolute risk elevations were similar in patients with and without comorbid conditions, meaning that the potential for harm was not limited to those at high risk for these adverse events. The study authors acknowledged that they could not adjust for disease severity and major lifestyle factors such as alcohol use, smoking, and body mass index; because these factors were static, the effect could be eliminated using the self-controlled case series design. Their reliance on prescription data also meant they could not tell if patients actually complied with oral corticosteroid therapy. Furthermore, the exclusion of the elderly and younger populations also left room for underestimation of the risks of steroid bursts, they said. Source References: Annals of Internal Medicine 2020; DOI: 10.7326/M20-0432 Editorial: Annals of Internal Medicine 2020; DOI: 10.7326/M20-4234 Study Highlights and Explanation of Findings: Over the 3-year study period, steroid bursts were commonly prescribed to adults. Such prescriptions were written for common conditions, including skin disorders and upper respiratory tract infections. The highest risks for GI bleeding, sepsis, and heart failure occurred within the first month after receipt of the steroid burst, and this risk was attenuated during the subsequent 31 to 90 days. "Our findings are important for physicians and guideline developers because short-term use of oral corticosteroids is common and the real-world safety of this approach remains unclear," the researchers wrote. Notably, one corticosteroid that fits the bill is dexamethasone -- a medication that holds promise for the treatment of critically ill COVID-19 patients, although it is not generally prescribed orally for these patients. Based on preliminary results, the NIH's COVID-19 treatment guidelines panel recommended the use of "dexamethasone (at a dose of 6 mg per day for up to 10 days) in patients with COVID-19 who are mechanically ventilated and in patients with COVID-19 who require supplemental oxygen but who are not mechanically ventilated." In addition, they recommend "against using dexamethasone in patients with COVID-19 who do not require supplemental oxygen." "We are now learning that bursts as short as 3 days may increase risk for serious AEs [adverse events], even in young and healthy people. As providers, we must reflect on how and why we prescribe corticosteroids to develop strategies that prevent avoidable harms," wrote Beth Wallace, MD, and Akbar Waljee, MD, both of the VA Ann Arbor Healthcare System and Michigan Medicine. On the basis of the reported risk differences in the study, Wallace and Waljee calculated that one million patients exposed to corticosteroid bursts experienced 41,200 GI bleeding events, 400 cases of sepsis, and 4,000 cases of new heart failure per year that were directly attributed to this brief treatment. "Although many providers already avoid corticosteroids in elderly patients and those with comorbid conditions, prescribing short bursts to 'low-risk' patients has generally been viewed as innocuous, even in cases where the benefit is unclear. However, Yao and colleagues provide evidence that this practice may risk serious harm, making it difficult to justify in cases where corticosteroid use lacks evidence of meaningful benefit," they wrote in an accompanying editorial. "Medication-related risks for AEs can, of course, be outweighed by major treatment benefit. However, this study and prior work show that corticosteroid bursts are frequently prescribed for self-limited conditions, where evidence of benefit is lacking," Wallace and Waljee noted. "As we reflect on how to respond to these findings, it is useful to note the many parallels between use of corticosteroid bursts and that of other short-term medications, such as antibiotics and opiates. All of these treatments have well-defined indications but can cause net harm when used -- as they frequently are -- when evidence of benefit is low," they emphasized. Last Updated August 07, 2020 Reviewed by Dori F. Zaleznik, MD Associate Clinical Professor of Medicine (Retired), Harvard Medical School, Boston Primary Source Annals of Internal Medicine Source Reference: Yao TC, et al "Association between oral corticosteroid bursts and severe adverse events: a nationwide population-based cohort study" Ann Intern Med 2020; DOI: 10.7326/M20-0432. Secondary Source Annals of Internal Medicine Source Reference: Wallace BI, Waljee AK "Burst case scenario: why shorter may not be any better when it comes to corticosteroids" Ann Intern Med 2020; DOI: 10.7326/M20-4234. Additional Source MedPage Today Source Reference: Lou N "Sobering Data on Risks of Short-Term Oral Corticosteroids" 2020. From https://www.medpagetoday.org/primarycare/generalprimarycare/87959?xid=nl_mpt_DHE_2020-08-08&eun=g1406328d0r&utm_term=NL_Daily_DHE_dual-gmail-definition&vpass=1

I hope your phone appointment went well and- you got some answers! Please keep us posted!

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