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Found 8 results

  1. A man with Cushing’s disease — caused by an adrenocorticotrophic hormone (ACTH)-secreting pituitary adenoma — who later developed metastases in the central nervous system without Cushing’s recurrence, was successfully treated over eight years with radiation and chemotherapy, according to a case report. The report, “Long-term survival following transformation of an adrenocorticotropic hormone secreting pituitary macroadenoma to a silent corticotroph pituitary carcinoma: Case report,” was published in the journal World Neurosurgery. Pituitary carcinomas make up only 0.1-0.2% of all pituitary tumors and are characterized by a primary pituitary tumor that metastasizes into cranial, spinal, or systemic locations. Fewer than 200 cases have been reported in the literature. Most of these carcinomas secrete hormones, with ACTH being the most common. Though the majority of ACTH-secreting carcinomas present with Cushing’s disease, about one-third do not show symptoms of the condition and have normal serum cortisol and ACTH levels. These are called silent corticotroph adenomas and are considered more aggressive. A research team at the University of Alabama at Birmingham presented the case of a 51-year-old Caucasian man with ACTH-dependent Cushing’s disease. He had undergone an incomplete transsphenoidal (through the nose) resection of an ACTH-secreting pituitary macroadenoma – larger than 10 mm in size – and radiation therapy the year before. At referral in August 1997, the patient had persistent high cortisol levels and partial hypopituitarism, or pituitary insufficiency. He exhibited Cushing’s symptoms, including facial reddening, moon facies, weight gain above the collarbone, “buffalo hump,” and abdominal stretch marks. About two years later, the man was weaned off ketoconazole — a medication used to lower cortisol levels — and his cortisol levels had been effectively reduced. He also had no physical manifestations of Cushing’s apart from facial reddening. In May 2010, the patient reported two episodes of partial seizures, describing two spells of right arm tingling, followed by impaired peripheral vision. Imaging showed a 2.1-by-1-cm mass with an associated cyst within the brain’s right posterior temporal lobe, as well as a 1.8-by-1.2-cm mass at the cervicomedullary junction, which is the region where the brainstem continues as the spinal cord. His right temporal cystic mass was then removed by craniotomy. A histopathologic analysis was consistent with pituitary carcinoma. Cell morphology was generally similar to the primary pituitary tumor, but cell proliferation was higher. Physical exams showed no recurrence of Cushing’s disease and 24-hour free urinary cortisol was within the normal range. His cervicomedullary metastasis was treated with radiation therapy in July 2010. He took the oral chemotherapy temozolomide until August 2011, and Avastin (bevacizumab, by Genentech) was administered from September 2010 to November 2012. At present, the patient continues to undergo annual imaging and laboratory draws. He receives treatment with hydrocortisone, levothyroxine — synthetic thyroid hormone — and testosterone replacement with androgel. His most recent exam showed no progression over eight years of a small residual right temporal cyst, a residual mass along the pituitary stalk — the connection between the hypothalamus and the pituitary gland — and a small residual mass at the cervicomedullary junction. Lab results continue to show no Cushing’s recurrence. “Our case is the first to document a patient who initially presented with an endocrinologically active ACTH secreting pituitary adenoma and Cushing’s disease who later developed cranial and spinal metastases without recurrence of Cushing’s disease and transformation to a silent corticotroph pituitary carcinoma,” the scientists wrote. They added that the report is also the first documenting “8 years of progression-free survival in a patient with pituitary carcinoma treated with radiotherapy, [temozolomide] and bevacizumab.” Adapted from https://cushingsdiseasenews.com/2019/01/03/successful-treatment-pituitary-carcinoma-radiation-chemo-case-report/
  2. Treatment with fluconazole after cabergoline eased symptoms and normalized cortisol levels in a patient with recurrent Cushing’s disease who failed to respond to ketoconazole, a case study reports. The case report, “Fluconazole as a Safe and Effective Alternative to Ketoconazole in Controlling Hypercortisolism of Recurrent Cushing’s Disease: A Case Report,” was published in the International Journal of Endocrinology Metabolism. Ketoconazole, (brand name Nizoral, among others) is an anti-fungal treatment used off-label for Cushing’s disease to prevent excess cortisol production, a distinct symptom of the disease. However, severe side effects associated with its use often result in treatment discontinuation and have led to its unavailability or restriction in many countries. Consequently, there is a need for alternative medications that help manage disease activity and clinical symptoms without causing adverse reactions, and that could be given to patients who do not respond to ketoconazole treatment. In this case report, researchers in Malaysia reported on a 50-year-old woman who fared well with fluconazole treatment after experiencing severe side effects with ketoconazole. The woman had been in remission for 16 years after a transsphenoidal surgery — a minimally invasive brain surgery to remove a pituitary tumor — but went to the clinic with a three-year history of high blood pressure and gradual weight gain. She also showed classic symptoms of Cushing’s disease: moon face, fragile skin that bruised easily, and purple stretch marks on her thighs. Blood and urine analysis confirmed high cortisol levels, consistent with a relapse of the pituitary tumor. Accordingly, magnetic resonance imaging (MRI) of her brain showed the presence of a small tumor on the right side of the pituitary gland, confirming the diagnosis of recurrent Cushing’s disease. Doctors performed another transsphenoidal surgery to remove the tumor, and a brain MRI then confirmed the success of the surgery. However, her blood and urine cortisol levels remained markedly high, indicating persistent disease activity. The patient refused radiation therapy or adrenal gland removal surgery, and was thus prescribed ketoconazole twice daily for managing the disease. But after one month on ketoconazole, she experienced low cortisol levels. Hydrocortisone — a synthetic cortisol hormone — was administered to maintain steady cortisol levels. However, she developed severe skin itching and peeling, which are known side effects of ketoconazole. She also suffered a brain bleeding episode, for which she had to have a craniotomy to remove the blood clot. Since she experienced adverse effects on ketoconazole, which also hadn’t decreased her disease activity, the doctors switched her to cabergoline. Cabergoline (marketed as Dostinex, among others) is a dopamine receptor agonist that has been shown to be effective in managing Cushing’s disease. But cabergoline treatment also did not lower the disease activity, and her symptoms persisted. The doctors then added fluconazole (marketed as Diflucan, among others), an anti-fungal medication, based on studies that showed promising results in managing Cushing’s syndrome. Three months after the addition of fluconazole to her treatment plan, the patient’s clinical symptoms and cortisol levels had responded favorably. At her next clinical visit 15 months later, her condition remained stable with no adverse events. “This case demonstrates the long-term efficacy of fluconazole in tandem with cabergoline for the control of recurrent Cushing’s disease,” the researchers wrote. The favorable outcome in this case also “supports the notion that fluconazole is a viable substitute for ketoconazole in the medical management of this rare but serious condition,” they concluded. From https://cushingsdiseasenews.com/2018/09/27/fluconazole-safe-effective-alternative-recurrent-cushings-patient-case-report/
  3. Ectopic Cushing’s syndrome can be challenging to diagnose, especially when it comes identifying the problem source. But appropriate hormone management protocols, used in combination with advanced imaging methods, may help physicians identify ectopic ACTH-producing tumors. The findings in a case report of a young man with ectopic Cushing’s syndrome were published in the International Journal of Surgery Case Reports, under the title “Case report: Ectopic Cushing’s syndrome in a young male with hidden lung carcinoid tumor.” Cushing’s syndrome is caused by high amounts of glucocoticosteroids in the blood. The most common cause is a malfunction of the glands that produce these hormones. In some cases, however, the disease may be caused by tumors elsewhere in the body that have the ability to produce adrenocorticotropic hormone (ACTH). In half of all Cushing’s patients, ectopic ACTH is produced by small lung cell carcinomas or lung carcinoids (a type of slow-growing lung cancer). But some tumors in the thymus and pancreas also have been found to produce ACTH. Researchers at Damascus University Hospital in Syria presented the case of a 26-year-old man who had ectopic Cushing’s syndrome due to lung carcinoids. The patient presented with increased appetite and rapid weight gain for more than a year. These were associated with headache, fatigue, proximal muscle weakness, and easy bruising. He had no family history of hormonal disorder. Based on the initial physical and symptom evaluation, the clinical team suspected Cushing’s syndrome. Blood analysis revealed high levels of cortisol and ACTH hormones, which supported the diagnosis. Administration of dexamethasone, a treatment used to inhibit the production of glucocoticosteroids by the pituitary gland, reduced cortisol levels within normal range, but not ACTH levels. This led to the diagnosis of ectopic Cushing’s syndrome. The next step was to identify the tumor causing the syndrome. The team conducted imaging studies of the brain, chest, and abdomen, but found no tumor. Because ectopic ACTH is commonly produced by lung cancers, the team then analyzed the patient’s lungs. Again, they failed to detect a tumor. The patient was discharged with prescription of 200 mg of Nizoral (ketoconazole) once-daily, calcium, and vitamin D. After three months of treatment, he remained stable, with no evidence of symptom improvement. At this point, the team decided to surgically remove both adrenal glands in an attempt to reduce the hormone levels. Treatment with prednisolone 5 mg and fludrocortisone 0.1 mg once daily was initiated, along with calcium and vitamin D. Eighteen months later, the patient’s condition worsened and he required hospitalization. Imaging tests targeting the neck, chest, and abdomen were conducted again. This time, physicians detected a 2 cm mass in the middle lobe of the right lung, which was removed surgically. Detailed analysis of the small tumor confirmed that it was the source of the excessive ACTH. “ACTH secreting tumors can be very hard to detect,” the researchers stated. “Initial failed localization is common in ectopic ACTH syndrome and it is usually due to carcinoid.” Cases where the ectopic ACTH production is caused by a carcinoid tumor can be challenging to diagnose because tumors are small and relatively slow-growing. Imaging data is often hard to analyze and the tumors can be confused with pulmonary vessels, the researchers explained. “In such cases we should first aim to lower blood cortisol medically or through bilateral adrenalectomy to avoid Cushing’s complications,” which should then “be followed up through imaging studies (CT, MRI, scintigraphy or PET) to detect the tumor and resect it, which is the definitive treatment of these patients,” the researchers concluded. From https://cushingsdiseasenews.com/2017/12/12/case-report-ectopic-acth-producing-lung-tumors-can-hard-detect/
  4. Cushing disease is caused by tumour in the pituitary gland which leads to excessive secretion of a hormone called adrenocorticotrophic (ACTH), which in turn leads to increasing levels of cortisol in the body. Cortisol is a steroid hormone released by the adrenal glands and helps the body to deal with injury or infection. Increasing levels of cortisol increases the blood sugar and can even cause diabetes mellitus. However the disease is also caused due to excess production of hypothalamus corticotropin releasing hormone (CRH) which stimulates the synthesis of cortisol by the adrenal glands. The condition is named after Harvey Cushing, the doctor who first identified the disease in 1912. Cushing disease results in Cushing syndrome. Cushing syndrome is a group of signs and symptoms developed due to prolonged exposure to cortisol. Signs and symptoms of Cushing syndrome includes hypertension, abdominal obesity, muscle weakness, headache, fragile skin, acne, thin arms and legs, red stretch marks on stomach, fluid retention or swelling, excess body and facial hair, weight gain, acne, buffalo hump, tiredness, fatigue, brittle bones, low back pain, moon shaped face etc. Symptoms vary from individual to individual depending upon the disease duration, age and gender of the patient. Disease diagnosis is done by measuring levels of cortisol in patient’s urine, saliva or blood. For confirming the diagnosis, a blood test for ACTH is performed. The first-line treatment of the disease is through surgical resection of ACTH-secreting pituitary adenoma, however disease management is also done through medications, Cushing disease treatment market comprises of the drugs designed for lowering the level of cortisol in the body. Thus patients suffering from Cushing disease are prescribed medications such as ketoconazole, mitotane, aminoglutethimide metyrapone, mifepristone, etomidate and pasireotide. Request to View Tables of Content @ http://www.persistencemarketresearch.com/toc/14155 Cushing’s disease treatment market revenue is growing with a stable growth rate, this is attributed to increasing number of pipeline drugs. Also increasing interest of pharmaceutical companies to develop Cushing disease drugs is a major factor contributing to the revenue growth of Cushing disease treatment market over the forecast period. Current and emerging players’ focuses on physician education and awareness regarding availability of different drugs for curing Cushing disease, thus increasing the referral speeds, time to diagnosis and volume of diagnosed Cushing disease individuals. Growing healthcare expenditure and increasing awareness regarding Cushing syndrome aids in the revenue growth of Cushing’s disease treatment market. Increasing number of new product launches also drives the market for Cushing’s disease Treatment devices. However availability of alternative therapies for curing Cushing syndrome is expected to hamper the growth of the Cushing’s disease treatment market over the forecast period. The Cushing’s disease Treatment market is segment based on the product type, technology type and end user Cushing’s disease Treatment market is segmented into following types: By Drug Type Ketoconazole Mitotane Aminoglutethimide Metyrapone Mifepristone Etomidate Pasireotide By End User Hospital Pharmacies Retail Pharmacies Drug Stores Clinics e-Commerce/Online Pharmacies Cushing’s disease treatment market revenue is expected to grow at a good growth rate, over the forecast period. The market is anticipated to perform well in the near future due to increasing awareness regarding the condition. Also the market is anticipated to grow with a fastest CAGR over the forecast period, attributed to increasing investment in R&D and increasing number of new product launches which is estimated to drive the revenue growth of Cushing’s disease treatment market over the forecast period. Depending on geographic region, the Cushing’s disease treatment market is segmented into five key regions: North America, Latin America, Europe, Asia Pacific (APAC) and Middle East & Africa (MEA). North America is occupying the largest regional market share in the global Cushing’s disease treatment market owing to the presence of more number of market players, high awareness levels regarding Cushing syndrome. Healthcare expenditure and relatively larger number of R&D exercises pertaining to drug manufacturing and marketing activities in the region. Also Europe is expected to perform well in the near future due to increasing prevalence of the condition in the region. Asia Pacific is expected to grow at the fastest CAGR because of increase in the number of people showing the symptoms of Cushing syndrome, thus boosting the market growth of Cushing’s disease treatment market throughout the forecast period. Some players of Cushing’s disease Treatment market includes CORCEPT THERAPEUTICS, HRA Pharma, Strongbridge Biopharma plc, Novartis AG, etc. However there are numerous companies producing branded generics for Cushing disease. The companies in Cushing’s disease treatment market are increasingly engaged in strategic partnerships, collaborations and promotional activities to capture a greater pie of market share. Buy Now: You can now buy a single user license of the report at http://www.persistencemarketresearch.com/checkout/14155 The final report customized as per your specific requirement will be sent to your e-mail id within 7-20 days, depending on the scope of the report. The research report presents a comprehensive assessment of the market and contains thoughtful insights, facts, historical data, and statistically supported and industry-validated market data. It also contains projections using a suitable set of assumptions and methodologies. The research report provides analysis and information according to categories such as market segments, geographies, types, technology and applications. For more information, please e-mail us at sales@persistencemarketresearch.com About Us Persistence Market Research (PMR) is a U.S.-based full-service market intelligence firm specializing in syndicated research, custom research, and consulting services. PMR boasts market research expertise across the Healthcare, Chemicals and Materials, Technology and Media, Energy and Mining, Food and Beverages, Semiconductor and Electronics, Consumer Goods, and Shipping and Transportation industries. The company draws from its multi-disciplinary capabilities and high-pedigree team of analysts to share data that precisely corresponds to clients’ business needs. PMR stands committed to bringing more accuracy and speed to clients’ business decisions. From ready-to-purchase market research reports to customized research solutions, PMR’s engagement models are highly flexible without compromising on its deep-seated research values. Contact Persistence Market Research Pvt. Ltd 305 Broadway 7th Floor, New York City, NY 10007, United States, USA – Canada Toll Free: 800-961-0353 Email: sales@persistencemarketresearch.com media@persistencemarketresearch.com Web: http://www.persistencemarketresearch.com
  5. RESEARCH STUDY SUMMARY An Open Label Study to Assess the Safety and Efficacy of COR-003 (2S, 4R ketoconazole) in the Treatment of Endogenous Cushing's Syndrome PURPOSEThe primary objectives of this study are to evaluate the efficacy of ascending doses of COR-003 in subjects with elevated levels of cortisol due to endogenous Cushing's Syndrome by assessment of reduction in Urinary Free Cortisol (UFC) concentrations and to identify the range of safe and effective doses of COR-003 that reduce mean UFC concentrations ≤ULN (upper limit of normal) of the assay at month 6 of the maintenance phase of dosing without a prior dose increase in that phase. TO LEARN MORE Review research study eligibility criteria » Contact information for clinical study » CW ID: 208654 Date Last Changed: June 25, 2015 Inclusion Criteria: Subjects eligible for enrollment in the study must meet all the following criteria: Male or female, ≥18 year of age Confirmed diagnosis of persistent or recurrent CS (with or without therapy) or newly diagnosed disease, if they are not candidates for surgery. Subjects in whom surgery will be delayed beyond 5 months will be permitted to participate. CS will be defined according to the criteria in the guidelines for diagnosis of CS (Nieman 2008). Previous medical records will be collected and used to support the diagnosis. The diagnostic criteria for appropriateness of inclusion of each subject into the study will be reviewed by the Medical Monitor. Diagnosis of the disease will be based on the association of clinical features of endogenous CS (see Appendix G in clinical protocol), review of past medication history, excluding exogenous sources of glucocorticoids, and abnormal values from two of the three following tests: Elevated 24-hour UFC levels ≥1.5X ULN of assay based on a minimum of 4 measurements from adequately collected urine. Urine may be collected on sequential days. Abnormal DST: Elevated 8 AM serum cortisol ≥1.8 ug/dL (50 nmol/L) after 1 mg dexamethasone orally at 11 PM the evening prior (if not conducted already in the diagnostic workup of the subject within the previous 6 months; previous test results and details of conduct will need to be available; normal serum cortisol ≤ 1.4 ug/dL) Elevated late night salivary cortisol concentrations (at least 2 measurements) >ULN at screening [NOTE: For subjects with estimated glomerular filtration rate (eGFR as determined by MDRD equation >40 and <60 mL/min) a late night salivary cortisol test (≥2 measurements) MUST be conducted in addition to measuring UFC levels to demonstrate evidence of CS.] Previously irradiated subjects will be allowed as long as the radiation treatment occurred ≥2 years ago and they do have stable UFC levels based on 24-hour urine collections for at least 6 months. The total number of previously irradiated subjects will not exceed 10.In the vast majority of subjects treated with radiation, efficacy is observed in <2 years. Confirmed diagnosis of persistent or recurrent endogenous hypercortisolemia as defined by UFC concentrations on repeated determinations (described in Inclusion #2) caused by either ACTH-dependent or ACTH-independent etiologies. Subjects on treatment for CS for whom treatment has been inadequate or not well tolerated must agree to the following minimum washout periods as determined by the nature of their treatment before baseline assessments are performed for participation in this study: Inhibitors of steroidogenesis: 2weeks; subjects on ketoconazole will be considered inadequately treated if they had failed to normalize UFC with a dose lower than or equal to 600 mg/day (also see Exclusion 7 below). Dopamine agonists: bromocriptine (2 week), cabergoline (8 weeks) Octreotide acetate LAR and lanreotide Autogel®: 12 weeks Lanreotide SR/long-acting pasireotide: 8 weeks Octreotide acetate (immediate release formulation) or short-acting pasireotide: 1 week Mifepristone (RU 486): 4 weeks Subjects on megasterol acetate (medroxyprogesterone acetate) must agree to a wash out of ≥6 weeks prior to receiving the first dose of the study medication. Female subjects should be either post-menopausal, surgically sterile, or women of child-bearing potential (WOCP) with a negative serum beta human chorionic gonadotropin (ßhCG) pregnancy test prior to entering the study and who agree to use an acceptable method of contraception, for the duration of the study. Condoms will be considered an acceptable form of contraceptive. 12-lead ECGs show no acute ischemia or clinically significant abnormality needing medical intervention Ability to comprehend and comply with procedures Agree to commit to participate in the current protocol Subjects provide written informed consent prior to any study procedures being performed (all subjects should be able to understand the informed consent form and any other documents that subjects are required to read) Exclusion Criteria: Subjects will be excluded from the study if any of the following criteria are met: De novo Cushing´s disease AND a candidate for pituitary surgeryIf surgery is to be delayed for >5 months, subjects may be allowed to participate in the trial while awaiting surgery, but must agree to complete this study prior to surgery. Subjects treated with radiation within the previous 2 years.In the vast majority of subjects treated with radiation, efficacy is observed in <2 years. Characteristics of pseudo-CS (see Appendix H in clinical protocol) Subjects with adrenal carcinoma Body Mass Index (BMI) exceeding 50 kg/m2 Body habitus preventing repeated venipuncture as required by protocol Subject is currently in another study or has received any investigational treatment (drug, biological agent or device) within 30 days or 5 half lives of screening, whichever is longer History of significant abnormalities in liver function tests on ketoconazole; history of therapeutic response failure to ketoconazole as defined by lack of normalization of UFC at a dose greater than 800 mg/day; lack of therapeutic response failure at maximum dose of mitotane Male and female subjects with QTc interval of >470 msec History of Torsades des Pointes or ventricular tachycardia or ventricular fibrillation Subjects with a non-endogenous source of hypercortisolemia such as exogenous source of glucocorticoids or therapeutic use of ACTH History of malignancy, other than thyroid, early stage prostate, squamous cell and basal cell carcinoma, within 3 years prior to the initial dose of the study medication. Subjects with history of carcinoma must have a life expectancy of >1 year and must be on stable doses of their specific therapies. Subjects with early stage prostate cancer undergoing no treatment due to low grade potential may be enrolled. Diagnosis of HIV History of persistent uncontrolled hypertension (>210/110 mmHg) despite medical intervention Subjects with hypercholesterolemia who are on current atorvastatin or simvistatin and not willing or unable to change to alternative therapies as noted (pravastatin, fluvastatin, and rosuvastatin) with 2 weeks of study screening Subjects with T2DM or with a history of hyperglycemic episodes requiring repeated, frequent hospitalizations Subjects with decreased renal function as defined by eGFR ≤40 mL/min, using Modified Diet in Renal Disease (MDRD) equation for estimating renal function (eGFR). Any other clinically significant medical condition, as determined by the Investigator that precludes enrollment and participation in the study through completion (for example, New York Heart Association (NYHA) class III or IV congestive heart failure). Known hepatic disease, other than mild to moderate hepatic steatosis consistent with fatty infiltration (non-alcoholic steatohepatitis [NASH]), with ongoing sustained biochemical activity (subjects with CS would be at risk for NASH) History of recurrent gall stone attacks or pancreatitis Positive for hepatitis B surface antigen (HbsAg) or positive hepatitis C test Liver function tests (LFT) must not be above the following cut-offs at screening: ALT and/or AST >3.0X ULN, alkaline phosphatase (AP) >1.5X ULN and total bilirubin >ULN. If all LFTs are within normal limits (WNL) and total bilirubin is elevated, examination of direct and indirect bilirubin may be conducted. Subjects with indirect total bilirubin up to 3X ULN are presumed to have Gilbert's syndrome and may be enrolled if all other LFTs are WNL. Presence of any other clinically significant medical condition, as determined by the Investigator that would preclude the subject from being able to follow instructions or to perform the necessary procedures (for example, psychiatric instability or severe disability) Compression of the optic chiasm Abnormal free T4. Subjects with TSH Excessive alcohol intake (>20 g per day for females (1.5 standard alcohol drinks) or >30 g per day for males (2.0 standard alcohol drinks) (a standard drink contains 14 g of alcohol: 12 oz of beer, 5 oz of wine or 1.5 oz of spirits) or drug abuse. (1.0 fluid oz (US) = 29.57 ml) The subject is currently taking any H2 receptor antagonists or proton-pump inhibitors (which inhibit absorption of COR-003). Only over-the- counter liquid and tablet antacids are allowed which should be used in moderation and taken a minimum of 2 hours after dosing of COR-003. The subject is receiving the following concomitant therapies: Weight loss medications (prescription or over the counter) Coadministration of COR-003 and drugs primarily metabolized by the cytochrome P450 3A4 enzyme system may result in increased plasma concentrations of the drugs that could increase or prolong both therapeutic and/or adverse effects. Therefore, appropriate dosage adjustments may be necessary. Medications with metabolism largely mediated by CYP3A4 and a narrow therapeutic margin include: cyclosporine, midazolam, triazolam, alprazolam, digoxin, coumarin-derivatives, phenytoin, rifampin, erythromycin, clarithromycin, loratadine, astemizole, terfenadine, nicotinic acids, resins, orlistat, sibutramine, HIV protease inhibitors, thiazolidinodiones, aliskiren, and spironolactone. A complete list of medications metabolized by or with an effect on cytochrome P450 3A4 is provided in Appendix K. Also see Section 10.2. Coadministration of strong inducers or inhibitors of CYP3A4 enzyme system that may interfere with COR-003 and cannot be discontinued prior to the start of the study (see Appendix K for the list) Statins other than pravastatin, fluvastatin and rosuvastatin Following herbal medicines should be avoided: St John's Wort, yohimbe and red rice yeast Potent topical steroids, containing urea or salicylic acid, which are applied over 20% of the body Inhaled steroid medications that exceed minimal to moderate use Carbamazipine, fenofibrate, carbenoxolone Excessive ingestion of genuine licorice Pregnant or lactating women Any other condition which would increase the risk of participation in the trial in the opinion of the Investigator ContactAdrine Gdakian UCLA School of Medicine 700 Tiverton Avenue, Factor Building Rm 9-240 Los Angeles, CA 90095 Phone: 310-825-5874 Fax: 310-206-5553 Jessica Rios-Santiago Coastal Metabolic Research Center University Medical Center, Dept. of Endocrinology 3454 Loma Vista Rd. Ventura, CA 93003 Phone: 805-658-8460 Fax: 805-658-8462 Betsy Parrott, RN, CCRC Rhode Island Hospital, Hallett Center for Diabetes and Endocrinology 900 Warren Avenue, Suite 300 East Providence, RI 02914 Phone: 401-444-2091 Fax: 401-444-4921 Becky Wood, CCRP Swedish Neuroscience Research 500 17th Ave Professional Bldg 303 Seattle, WA 98122 Phone: 206-320-7115
  6. This book just hit the shelves. It's intended for investor institutions in the Pharma industry. You can buy it for the low low price of $2000, but a lot of info can be gleaned just by reading the table of contents. http://www.researchandmarkets.com/research/rdf6gm/pituitary_acth It's a 47 page analysis of all the drugs currently in the development pipeline for Cushing's disease. In particular, it discusses one that I was not aware of called Normocort (COR-003) - it is a modified version of Ketoconazole that is intended to work more effectively against cortisol synthesis and less effectively against the metabolic enzyme CYP7A, which is what causes all the common side effects of Keto. This is a very good drug because if everything pans out it will: 1. Be more effective in reducing cortisol than Ketoconazole with fewer side effects 2. Unlike Korlym, it will actually lower serum cortisol, not just block it 3. Unlike Signifor, it will not require an injection or cause hyperglycemia 4. Unlike Signifor, it should work on patients with Adrenal cushing's Possible downsides are: It may still be less effective than Korlym or Signifor at achieving clinical relief of symptoms As such a powerful cortisol inhibitor, in cyclical patients it may induce occasional AI incidents or may be difficult to dose Unlike Signifor, it does not act on the tumor and therefore does not reduce tumor size or ACTH production. http://www.cortendo.com/pipelines/normocort-cushings-disease/
  7. LA JOLLA, CA—Scientists at the Salk Institute for Biological Studies have identified a protein that drives the formation of pituitary tumors in Cushing’s disease, a development that may give clinicians a therapeutic target to treat this potentially life-threatening disorder. The protein, called TR4 (testicular orphan nuclear receptor 4), is one of the human body’s 48 nuclear receptors, a class of proteins found in cells that are responsible for sensing hormones and, in response, regulating the expression of specific genes. Using a genome scan, the Salk team discovered that TR4 regulates a gene that produces adrenocorticotropic hormone (ACTH), which is overproduced by pituitary tumors in Cushing’s disease (CD). The findings were published in the May 6 early online edition of Proceedings of the National Academy of Sciences. “We were surprised by the scan, as TR4 and ACTH were not known to be functionally linked,” says senior author Ronald M. Evans, a professor in Salk’s Gene Expression Laboratory and a lead researcher in the Institute’s Helmsley Center for Genomic Medicine. “TR4 is driving the growth and overexpression of ACTH. Targeting this pathway could therapeutically benefit treatment of CD.” In their study, Evans and his colleagues discovered that forced overexpression of TR4 in both human and mouse cells increased production of ACTH, cellular proliferation and tumor invasion rates. All of these events were reversed when TR4 expression was reduced. First described more than 80 years ago, Cushing’s disease is a rare disorder that is caused by pituitary tumors or excess growth of the pituitary gland located at the base of the brain. People with CD have too much ACTH, which stimulates the production and release of cortisol, a hormone that is normally produced during stressful situations. While these pituitary tumors are almost always benign, they result in excess ACTH and cortisol secretion, which can result in various disabling symptoms, including diabetes, hypertension, osteoporosis, obesity and psychological disturbances. Surgical removal of the tumors is the first-line therapy, with remission rates of approximately 80 percent; however, the disease recurs in up to 25 percent of cases. Drugs such as cabergoline, which is used to treat certain pituitary tumors, alone or in combination with ketoconazole, a drug normally used to treat fungal infections, have been shown to be effective in some patients with Cushing’s disease. More recently, mefipristone-best known as the abortion pill RU-486-was approved by the FDA to treat CD. Despite these advances in medical therapy, the Salk scientists say additional therapeutic approaches are needed for CD. “Pituitary tumors are extremely difficult to control,” says Michael Downes, a senior staff scientist in the Gene Expression Laboratory and a co-author of the study. “To control them, you have to kill cells in the pituitary gland that are proliferating, which could prevent the production of a vital hormone.” Previous studies have found that, by itself, TR4 is a natural target for other signaling molecules in the pituitary. Small-molecule inhibitors that have been developed for other cancers could be potentially applied to disrupt this signaling cascade. “Our discovery,” says Evans, a Howard Hughes Medical Institute investigator and holder of the March of Dimes Chair in Molecular and Developmental Biology, “might lead clinicians to an existing drug that could be used to treat Cushing’s disease.” Source: Salk Institute
  8. Have questions about the new Korlym? How about Korlym vs ketoconazole? About medical vs surgical treatment for Cushing's. Ask Dr. Theodore F.. Theodore C. F., M.D., Ph.D. has opened a private practice, specializing in treating patients with adrenal, pituitary, thyroid and fatigue disorders. Dr. F. has privileges at Cedars-Sinai Medical Center and Martin Luther King Medical Center. His practice includes detecting and treating hormone imbalances, including hormone replacement therapy. Dr. F. is also an expert in diagnosing and treating pituitary disorders, including Cushings disease and syndrome. Dr. F.'s career reflects his ongoing quest to better understand and treat endocrine problems. With both medical and research doctoral degrees, he has conducted studies and cared for patients at some of the country's most prestigious institutions, including the University of Michigan, the National Institutes of Health, Cedars-Sinai Medical Center, and UCLA's Charles Drew University of Medicine and Science. Read Dr. F.'s First Guest Chat, November 11, 2003. Read Dr. F.'s Second Guest Chat, March 2, 2004. Listen to Dr. F. First Live Voice Interview, January 29, 2009. Listen to Dr. F. Second Live Voice Interview, March 12, 2009. Listen to Dr. F. Third Live Voice Interview, February 13, 2011. Listen live at http://www.blogtalkradio.com/cushingshelp/2012/03/13/questions-about-medical-therapies-for-cushings Call in to ask your question at (646) 200-0162 This interview will be archived afterwards at the same link and on iTunes Cushie Podcasts This post has been promoted to an article
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