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pasireotide cushings disease

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
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; identifier, NCT00434148; study number, B2305)...
2017: Frontiers in Endocrinology
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
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
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
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
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
Mojtaba Malek, Fatemeh Esfehanian, Atieh Amouzegar, Farzaneh Sarvghadi, Zohreh Moossavi, Mohammad R Mohajeri-Tehrani, Mohammad E Khamseh, Alireza Amirbaigloo, Ameneh Ebrahim Valojerdi
BACKGROUND: Cushing's disease is the most prevalent cause of endogenous adrenocorticotrophic hormone hypersecretion. The aim of this study was to document the current clinical practice pattern in the management of Cushing's disease by Iranian Endocrinologists to determine their opinions and compare them with the current clinical practice guidelines. METHODS: An eight-item questionnaire dealing with diagnosis, treatment and follow up of patients with Cushing's disease was developed, piloted, and sent to the members of Iranian Endocrinology Society...
2016: Medical Journal of the Islamic Republic of Iran
James W Findling, Maria Fleseriu, John Newell-Price, Stephan Petersenn, Rosario Pivonello, Albert Kandra, Alberto M Pedroncelli, Beverly M K Biller
Measuring salivary cortisol is a simple, convenient and accurate technique with potential value in monitoring patients with hypercortisolism. This analysis reports changes in late-night salivary cortisol (LNSC) during a 12-month, multicentre, Phase III study of patients with Cushing's disease who were randomized to pasireotide 600 or 900 μg sc bid. LNSC assessment was an exploratory objective based on a single, optional measurement at midnight ± 1 h on the same day as one of the 24-h urinary free cortisol (UFC) measurements...
November 2016: Endocrine
L Trementino, G Michetti, A Angeletti, G Marcelli, C Concettoni, C Cardinaletti, B Polenta, M Boscaro, G Arnaldi
Pasireotide is the first pituitary-directed drug approved for treating patients with Cushing's disease (CD). Our 10-year experience with pasireotide in CD is reported here. Twenty patients with de novo, persistent, or recurrent CD after pituitary surgery were treated with pasireotide from December 2003 to December 2014. Twelve patients were treated with pasireotide in randomized trials and 8 patients with pasireotide sc (Signifor(®); Novartis AG, Basel, Switzerland) in clinical practice. The mean treatment duration was 20...
May 2016: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Chiara Simeoli, Renata Simona Auriemma, Fabio Tortora, Monica De Leo, Davide Iacuaniello, Alessia Cozzolino, Maria Cristina De Martino, Claudia Pivonello, Ciro Gabriele Mainolfi, Riccardo Rossi, Sossio Cirillo, Annamaria Colao, Rosario Pivonello
No abstract text is available yet for this article.
April 8, 2016: Endocrine
Antonio Stigliano, Vincenzo Toscano
The hypercortisolism is a rare endocrine disease characterized by an autonomous steroid secretion or excessive adrenal stimulation by ACTH. the Surgical removal of the lesion directly responsible hypercortisolism represents the treatment of choice. When neurosurgery for pituitary adenoma is contraindicated, radiotherapy is candidate as the second line of therapy. Currently, the recent advances in medical therapy provide a viable alternative to surgery and radiotherapy, when these are not feasible or followed by relapses (present in more than one third of cases) of the underlying disease...
March 2016: Recenti Progressi in Medicina
Lichun Sun, David H Coy
Somatostatin (SST) is a cyclic hormone-release inhibitory peptide that has high binding affinity to all of its five SST receptors (SSTRs). SST negatively regulates cell proliferation and the release of multiple hormones via activation of its cognate receptors. A variety of SST analogs, some with high affinity and selectivity of receptor subtypes, have been synthesized and developed. Certain long-acting SST analogs such as octreotide, lanreotide and pasireotide have been clinically applied to the treatment of human diseases such as those caused by excessive release of growth hormone (acromegaly), or adrenocorticotropic hormone (Cushing's syndrome), and for the treatment of carcinoid syndrome...
2016: Current Drug Targets
Jingyu Yu, Sang Chung, Immo Zadezensky, Ke Hu, Christelle Darstein, Jerry Nedelman, Nitin Mehrotra
No abstract text is available yet for this article.
August 2016: Journal of Clinical Pharmacology
Kyohei Hayashi, Naoko Inoshita, Kohei Kawaguchi, Arif Ibrahim Ardisasmita, Hisanori Suzuki, Noriaki Fukuhara, Mitsuo Okada, Hiroshi Nishioka, Yasuhiro Takeuchi, Masayuki Komada, Akira Takeshita, Shozo Yamada
CONTEXT: Somatic mutations in the ubiquitin-specific peptidase USP8 gene were recently detected in one- to two-third(s) of corticotroph adenomas of Cushing's disease (CD). These mutations may lead to the deubiquitination of EGFR, thereby increasing EGFR signaling, which has been implicated in ACTH hypersecretion. OBJECTIVE: Our objective was to determine the impact of USP8 mutations on the clinicopathological features of CD. SUBJECTS AND METHODS: USP8 mutations as well as clinicopathological characteristics were examined in 60 corticotroph adenomas including 15 Crooke's cell adenomas (CCAs), a rare histological variant presenting with generally aggressive behavior, using qRT-PCR and/or immunohistochemistry...
February 2016: European Journal of Endocrinology
Erika Grossrubatscher, Benedetta Zampetti, Paolo Dalino Ciaramella, Paola Doneda, Paola Loli
This case shows efficacy of low-dose pasireotide in biochemical and clinical control of severe hypercortisolism and in tumor volume reduction in a patient with an ACTH-secreting macroadenoma. The drug may be an option for long-term treatment in some patients where control of tumor mass is an important clinical endpoint.
August 2015: Clinical Case Reports
Sara G Creemers, Leo J Hofland, Steven W J Lamberts, Richard A Feelders
INTRODUCTION: Endogenous Cushing's syndrome (CS) is characterized by chronic overproduction of cortisol and is associated with increased mortality and morbidity. It can be caused by a pituitary adenoma, ectopic adrenocorticotropic hormone (ACTH) production or primary adrenal disease. Successful tumor-directed surgery is the keystone treatment. When surgery is unsuccessful, contraindicated or in case of acute disease, pharmacotherapy is indicated to treat hypercortisolism. AREAS COVERED: In this review, pharmacotherapeutic options for CS will be covered discussing the different possible targets, that is: i) inhibition of ACTH secretion; ii) suppression of steroidogenesis; and iii) blockade of cortisol effects at tissue level...
2015: Expert Opinion on Pharmacotherapy
Rosario Pivonello, Monica De Leo, Alessia Cozzolino, Annamaria Colao
Cushing's disease (CD), or pituitary-dependent Cushing's syndrome, is a severe endocrine disease caused by a corticotroph pituitary tumor and associated with increased morbidity and mortality. The first-line treatment for CD is pituitary surgery, which is followed by disease remission in around 78% and relapse in around 13% of patients during the 10-year period after surgery, so that nearly one third of patients experience in the long-term a failure of surgery and require an additional second-line treatment...
August 2015: Endocrine Reviews
Daniela Guelho, Ashley B Grossman
INTRODUCTION: Considering the effects of uncontrolled hypercortisolism on morbidity and mortality, there is a clear need for effective medical therapy for patients with Cushing's disease (CD). Therefore, the search for new medical effective tools remains active, and already promising results have been obtained. AREAS COVERED: The importance of the design and conduct of trials to validate old drugs or to test new compounds is discussed. The results of the ongoing clinical trials, targeting the specific properties of drugs, such as ketoconazole, LCI699, mifepristone, etomidate and pasireotide, are also reported...
September 2015: Expert Opinion on Emerging Drugs
S Cannavo, E Messina, A Albani, F Ferrau, V Barresi, S Priola, F Esposito, F Angileri
The management of critically ill Cushing's disease (CD) patients is extremely challenging. Pasireotide is indicated for the treatment of CD patients when pituitary surgery is unfeasible or has not been curative, but no data are available about the use of this drug as pre-operative treatment in critically ill patients. We report the effects of presurgical pasireotide therapy in CD patients in whom hypercortisolism caused life-threatening hypokalemia, alkalosis, and cardio-respiratory complications precluding surgical approach...
June 2016: Endocrine
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