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https://www.readbyqxmd.com/read/29765354/pituitary-directed-therapies-for-cushing-s-disease
#1
REVIEW
Fabienne Langlois, Jennifer Chu, Maria Fleseriu
Cushing's disease (CD) is caused by a pituitary corticotroph neuroendocrine tumor inducing uncontrolled hypercortisolism. Transsphenoidal surgery is the first-line treatment in most cases. Nonetheless, some patients will not achieve cure even in expert hands, others may not be surgical candidates and a significant percentage will experience recurrence. Many patients will thus require medical therapy to achieve disease control. Pharmacologic options to treat CD have increased in recent years, with an explosion in knowledge related to pathophysiology at the molecular level...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29621813/cushing-s-syndrome-a-historic-review-of-the-treatment-strategies-and-corresponding-outcomes-in-a-single-tertiary-center-over-the-past-half-century
#2
Anelia Nankova, Maria Yaneva, Atanaska Elenkova, Dimitar Tcharaktchiev, Marin Marinov, Asen Hadzhiyanev, Tanyo Sechanov, Georgi Gantchev, Georgi Todorov, Georgi Kirilov, Krasimir Kalinov, Maria Andreeva, Sabina Zacharieva
Cushing's syndrome (CS) is associated with serious comorbidities and an increased mortality rate that could be reduced only if strict biochemical control is achieved. The aim of this study was to show the 50-year experience of a single tertiary center in the management of CS patients - the different treatment modalities used over the years and the corresponding outcomes. It was a retrospective study of a large cohort of patients from the Bulgarian CS database: 613 patients (374 with ACTH-dependent and 239 with ACTH-independent CS)...
April 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29595102/pasireotide-mechanism-of-action-and-clinical-applications
#3
Nadia Sawicka-Gutaj, Maciej Owecki, Marek Ruchala
Pasireotide (SOM230) is a multi-receptor ligand somatostatin analogue (SSA) developed as the successor of the first-generation SSAs. Currently, pasireotide is recommended for the treatment of patients with Cushing's disease in whom surgery was unsuccessful, and patients with acromegaly who either remain uncontrolled after surgical therapy or in whom tumor resection is not possible. Phase II and III clinical trials have shown pasireotide efficacy in these diseases, with a similar rate of adverse events when compared with first-line SSA, although higher incidence of hyperglycemia has been observed...
March 27, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29396758/insulin-sensitivity-and-secretion-and-adipokine-profile-in-patients-with-cushing-s-disease-treated-with-pasireotide
#4
V Guarnotta, G Pizzolanti, A Ciresi, C Giordano
PURPOSE: To evaluate the effect of pasireotide on β-cell and adipose function in patients with Cushing's disease (CD). METHODS: Clinical and hormonal parameters, insulin secretion evaluated by HOMA-β and by the area under the curve (AUC2h ) of C-peptide during a mixed meal tolerance test and insulin sensitivity, evaluated by the euglycaemic hyperinsulinaemic clamp, were evaluated in 12 patients with active CD, before and after 6 and 12 months of pasireotide. In addition, a panel of adipokines including leptin (Ob), leptin/leptin receptor ratio (Ob/Ob-R ratio), adiponectin, resistin, visfatin, adipocyte fatty acid binding protein (AFABP) and non-esterified fatty acids (NEFAs) was evaluated at baseline and after 12 months of pasireotide...
February 2, 2018: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29383677/pasireotide-treatment-reduces-cardiometabolic-risk-in-cushing-s-disease-patients-an-italian-multicenter-study
#5
A Albani, F Ferraù, A Ciresi, R Pivonello, C Scaroni, D Iacuaniello, M Zilio, V Guarnotta, A Alibrandi, E Messina, M Boscaro, C Giordano, A Colao, S Cannavo
PURPOSE: Patients with Cushing's disease (CD) experience metabolic alterations leading to increased cardiovascular mortality. Recently, the visceral adiposity index (VAI) has been proposed as a marker of visceral adipose tissue dysfunction (ATD) and of the related cardiometabolic risk. We aimed to evaluate the impact of 12-month pasireotide treatment on cardiometabolic risk in CD patients. METHODS: This is a multicentre, prospective, and observational study. Sixteen CD patients, referred to the Endocrine Units of the University Hospitals of Messina, Napoli, Padova, and Palermo (Italy), successfully treated with pasireotide for 12 month have been enrolled...
January 30, 2018: Endocrine
https://www.readbyqxmd.com/read/29313180/a-prospective-longitudinal-study-of-pasireotide-in-nelson-s-syndrome
#6
Eleni Daniel, Miguel Debono, Sharon Caunt, Constantine Girio-Fragkoulakis, Stephen J Walters, Scott A Akker, Ashley B Grossman, Peter J Trainer, John Newell-Price
PURPOSE: Nelson's syndrome is a challenging condition that can develop following bilateral adrenalectomy for Cushing's disease, with high circulating ACTH levels, pigmentation and an invasive pituitary tumor. There is no established medical therapy. The aim of the study was to assess the effects of pasireotide on plasma ACTH and tumor volume in Nelson's syndrome. METHODS: Open labeled multicenter longitudinal trial in three steps: (1) a placebo-controlled acute response test; (2) 1 month pasireotide 300-600 μg s...
January 8, 2018: Pituitary
https://www.readbyqxmd.com/read/29032486/population-pharmacokinetics-of-subcutaneous-pasireotide-in-healthy-volunteers-and-cushing-s-disease-patients
#7
Jerry Nedelman, Roland Fisch, Ke Hu, Ines Paule, Jocelyn Zhou
BACKGROUND AND OBJECTIVE: Pasireotide (SOM230, Signifor(®)) is a somatostatin analog approved in a subcutaneous formulation for the treatment of Cushing's disease. This analysis characterizes the population pharmacokinetics (PopPK) of subcutaneous pasireotide jointly in healthy volunteers (HVs) and Cushing's disease patients (CDPs), evaluating the effects of age, body size, and population on pasireotide pharmacokinetics. METHODS: The analysis dataset included five phase I studies and one each from phase II and phase III...
October 14, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29032078/efficacy-and-safety-of-once-monthly-pasireotide-in-cushing-s-disease-a-12-month-clinical-trial
#8
André Lacroix, Feng Gu, Wilson Gallardo, Rosario Pivonello, Yerong Yu, Przemysław Witek, Marco Boscaro, Roberto Salvatori, Masanobu Yamada, Libuse Tauchmanova, Michael Roughton, Shoba Ravichandran, Stephan Petersenn, Beverly M K Biller, John Newell-Price
BACKGROUND: Cushing's disease is a rare debilitating endocrine disorder for which few prospective interventional studies have been done. We report results of the first phase 3 trial assessing long-acting intramuscular pasireotide in patients with Cushing's disease. METHODS: In this phase 3 clinical trial we recruited patients aged 18 years or older with persistent, recurrent, or de-novo (non-surgical candidates) Cushing's disease who had a mean urinary free cortisol (mUFC) concentration (from three 24 h samples) of 1·5-5·0 times the upper limit of normal (ULN), a normal or greater than normal morning plasma adrenocorticotropic hormone concentration, and a pituitary source of Cushing's syndrome, from 57 sites across 19 countries...
January 2018: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28903425/pasireotide-is-more-effective-than-octreotide-alone-or-combined-with-everolimus-on-human-meningioma-in-vitro
#9
Thomas Graillon, David Romano, Céline Defilles, Christophe Lisbonis, Alexandru Saveanu, Dominique Figarella-Branger, Pierre-Hugues Roche, Stéphane Fuentes, Olivier Chinot, Henry Dufour, Anne Barlier
Pasireotide is a somatostatin analog (SSA) that targets somatostatin receptor subtype 1 (SST1), SST2, SST3, and SST5 with a high affinity. Pasireotide has a better antisecretory effect in acromegaly, Cushing's disease, and neuroendocrine tumors than octreotide. In this study, we compared the effects of pasireotide to those of octreotide in vitro on meningioma primary cell cultures, both alone and in combination with the mTOR inhibitor everolimus. Significant mRNA expression levels of SST1, SST2, and SST5 were observed in 40...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28762950/pasireotide-is-more-effective-than-octreotide-alone-or-combined-with-everolimus-on-human-meningioma-in-vitro
#10
Thomas Graillon, David Romano, Céline Defilles, Christophe Lisbonis, Alexandru Saveanu, Dominique Figarella-Branger, Pierre-Hugues Roche, Stéphane Fuentes, Olivier Chinot, Henry Dufour, Anne Barlier
Pasireotide is a somatostatin analog (SSA) that targets somatostatin receptor subtype 1 (SST1), SST2, SST3, and SST5 with a high affinity. Pasireotide has a better antisecretory effect in acromegaly, Cushing's disease, and neuroendocrine tumors than octreotide. In this study, we compared the effects of pasireotide to those of octreotide in vitro on meningioma primary cell cultures, both alone and in combination with the mTOR inhibitor everolimus. Significant mRNA expression levels of SST1, SST2, and SST5 were observed in 40...
July 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28597198/long-term-treatment-of-cushing-s-disease-with-pasireotide-5-year-results-from-an-open-label-extension-study-of-a-phase-iii-trial
#11
S Petersenn, L R Salgado, J Schopohl, L Portocarrero-Ortiz, G Arnaldi, A Lacroix, C Scaroni, S Ravichandran, A Kandra, B M K Biller
BACKGROUND: Treating hypercortisolism in patients with Cushing's disease after failed surgery often requires chronic medication, underlining the need for therapies with favourable long-term efficacy and safety profiles. METHODS: In a randomised, double-blind study, 162 adult patients with persistent/recurrent or de novo Cushing's disease received pasireotide. Patients with mean urinary free cortisol at/below the upper limit of normal or clinical benefit at month 12 could continue receiving pasireotide during an open-ended, open-label phase, the outcomes of which are described herein...
July 2017: Endocrine
https://www.readbyqxmd.com/read/28579289/effects-of-anti-somatostatin-agents-on-glucose-metabolism
#12
REVIEW
B Vergès
The anti-somatostatin agents used to treat acromegaly, Cushing's disease and neuroendocrine tumours also have hyperglycaemic effects. This is particularly true for pasireotide. Hyperglycaemic events are seen in 57-73% of patients with Cushing's treated with pasireotide, with a need to initiate antidiabetic treatment in about 50% of these patients. In acromegaly, treatment with pasireotide induces hyperglycaemia in 29-61% of patients. Pasireotide-induced hyperglycemia occurs early, within the first 3 months of treatment, due to a decrease in insulin secretion secondary to a fall in secretion of GLP-1 and GIP, and potentially also due to a direct inhibitory effect of pasireotide on beta cells...
June 1, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28458898/efficacy-of-pasireotide-in-controlling-severe-hypercortisolism-until-cardiac-transplantation
#13
Roberto Attanasio, Liana Cortesi, Daniela Gianola, Claudia Vettori, Fulvio Sileo, Roberto Trevisan
SUMMARY: Cushing's syndrome is associated with increased morbidity and mortality. Although surgery is the first-line treatment, drugs can still play a role as an ancillary treatment to be employed while waiting for surgery, after unsuccessful operation or in patients unsuitable for surgery. We were asked to evaluate a 32-year-old male waiting for cardiac transplantation. Idiopathic hypokinetic cardiomyopathy had been diagnosed since 6 years. He was on treatment with multiple drugs, had a pacemaker, an implantable cardioverter and an external device for the support of systolic function...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28364356/diabetes-in-cushing-disease
#14
REVIEW
G Mazziotti, A M Formenti, S Frara, F Maffezzoni, M Doga, A Giustina
PURPOSE OF REVIEW: This review focuses on the pathophysiological and clinical aspects of diabetes mellitus occurring in patients with Cushing disease (CD). RECENT FINDINGS: Insulin resistance and impairment in insulin secretion are both involved in the pathogenesis of glucocorticoid-induced diabetes. Correction of glucocorticoid excess does not always resolve abnormalities of glucose homeostasis, and correction of hyperglycaemia is specifically required. In fact, insulin resistance may persist even after correction of glucocorticoid excess and diabetes needs to be treated for long term...
May 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28289402/medical-therapy-with-pasireotide-in-recurrent-cushing-s-disease-experience-of-patients-treated-for-at-least-1-year-at-a-single-center
#15
Chris G Yedinak, Sarah Hopkins, Jessica Williams, Aly Ibrahim, Justin Schultz Cetas, Maria Fleseriu
Subcutaneous (SC) injection of pasireotide, a somatostatin analog, is approved for the treatment of adults with Cushing's disease (CD) for whom pituitary surgery was unsuccessful or is not an option. We highlight the symptomatic and biochemical improvement of six patients with recurrent CD treated with pasireotide SC at a single center for at least 1 year. Patients were treated either through commercial use ( n  = 5) or through the Phase 3 trial ( n  = 1; http://ClinicalTrials.gov identifier, NCT00434148; study number, B2305)...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28191290/loss-of-efficacy-of-pasireotide-after-its-re-administration-is-there-a-reason-why
#16
Stylianos Mandanas, Lemonia Mathiopoulou, Maria Boudina, Alexandra Chrisoulidou, Kalliopi Pazaitou-Panayiotou
Pasireotide is a recently approved medical treatment for persistent or recurrent Cushing's disease (CD). However, an escape from the initial successful response has not yet been described. A 42-year-old female presented with several symptoms indicative of hypercortisolism. Biochemical evaluation and imaging were consistent with CD due to a pituitary adenoma. Surgical excision of the adenoma was unsuccessful and gamma-knife radiosurgery was followed. Our patient remained hypercortisolemic thus treatment with pasireotide (900 mg subcutaneously twice daily) was decided...
November 17, 2016: Rare Tumors
https://www.readbyqxmd.com/read/28170483/diagnosis-and-treatment-of-pituitary-adenomas-a-review
#17
REVIEW
Mark E Molitch
Importance: Pituitary adenomas may hypersecrete hormones or cause mass effects. Therefore, early diagnosis and treatment are important. Observations: Prevalence of pituitary adenomas ranges from 1 in 865 adults to 1 in 2688 adults. Approximately 50% are microadenomas (<10 mm); the remainder are macroadenomas (≥10 mm). Mass effects cause headache, hypopituitarism, and visual field defects. Treatments include transsphenoidal surgery, medical therapies, and radiotherapy...
February 7, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/27894193/currently-used-and-investigational-drugs-for-cushing%C3%A2-s-disease
#18
REVIEW
Denis Ciato, Aizhar G Mumbach, Marcelo Paez-Pereda, Günter K Stalla
Cushing's disease (CD) is caused by a corticotroph adenoma of the pituitary gland that secretes excess adrenocorticotropic hormone (ACTH) causing increased morbidity and mortality. Surgery is the treatment of choice, but is not always successful. Alternatives include radiotherapy, adrenal surgery, and pharmaceutical therapy. The latter is increasingly gaining momentum due to the recent development of compounds that reduce hypercortisolaemia or its symptoms, acting through different mechanisms. Areas covered: In this article, the authors provide a complete overview of the treatment options for Cushing´s disease, including adrenal-directed, tumor-targeted, and peripheral therapies that are currently used or in development, and discuss their potential advantages and limitations...
January 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/27639583/paradoxical-and-atypical-responses-to-pasireotide-in-aggressive-acth-secreting-pituitary-tumors
#19
Yona Greenman, Naftali Stern
PURPOSE: Pasireotide is the only pituitary targeted medication registered for the treatment of Cushing's disease. Drug efficacy data are largely based on a major prospective study in which the vast majority of patients had microadenomas. The purpose of this study was to summarize results of pasireotide treatment of ACTH secreting macroadenomas from our center. METHODS: Retrospective review of data extracted from clinical files. RESULTS: Three patients presented with large and invasive macroadenomas that required several surgical interventions and radiotherapy treatments...
December 2016: Pituitary
https://www.readbyqxmd.com/read/27405306/hyperglycemia-induced-by-pasireotide-in-patients-with-cushing-s-disease-or-acromegaly
#20
REVIEW
Julie M Silverstein
PURPOSE: Cushing's disease (CD) and acromegaly are characterized by excessive hormone secretion resulting in comorbidities such as impaired glucose metabolism, diabetes and hypertension. Pasireotide is a new-generation, multireceptor-targeted somatostatin receptor ligand approved for CD (subcutaneous [SC] injection formulation) and acromegaly (long-acting release [LAR] formulation). In clinical studies of pasireotide, hyperglycemia-related adverse events (AEs) were frequently observed...
October 2016: Pituitary
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