A 12-Month Phase 3 Study of Pasireotide in Cushing's Disease

Colao, Annamaria; Petersenn, Stephan; Newell‐Price, John; Findling, James W.; Gu, Feng; Maldonado, Mario; Schoenherr, U; Mills, David; Salgado, Luiz Roberto; Biller, Beverly M. K.

doi:10.1056/nejmoa1105743

Cited by 571 publications

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“…In October 2008, the patient was enrolled in a prospective phase 3 trial (ClinicalTrials.gov identifier, NCT00434148) (8,11), completed the core study after 1 year, and entered into the extension phase of the study in October 2009, as per protocol. After 5 years (September 2013), the patient entered into a roll-over protocol, allowing access to pasireotide upon completing the initial phase 3 trial (ClinicalTrials.gov identifier, NCT01794793) (15).…”

Section: Methodsmentioning

confidence: 99%

“…Mean 24-hour UFC was calculated using three or four 24-hour urine samples collected within a 14-day period at months 3, 6, and 12 and using 2 consecutive-day samples at other time points (8). Monthly 24-hour UFC was assessed for 6 months and every 3 months thereafter.…”

Section: Methodsmentioning

confidence: 99%

“…In a phase 2 study, pasireotide reduced mean 24-hour urinary free cortisol (UFC), serum cortisol, and plasma ACTH in patients with CD (7). Subsequently, a phase 3 study (CSOM230B2305) in CD patients demonstrated that 12 months of pasireotide not only decreased 24-hour UFC, serum and salivary cortisol, and plasma ACTH levels but also improved clinical signs and symptoms (8). In this study, diarrhea (58%), nausea (52%), and hyperglycemia (40%) were the most commonly reported adverse events.…”

Section: Introductionmentioning

confidence: 99%

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Effective Medical Therapy for Cushing Disease Can Increase the Susceptibility to Relative Hypocortisolism

Yuen

Mercado

Moloney

et al. 2018

AACE Clinical Case Reports

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Objective: Pasireotide is approved for treatment of adults with Cushing disease (CD) with persistent hypercortisolism for whom surgery has failed or is not an option. Effective medical therapy for CD may increase the susceptibility of relative hypocortisolism during acute stress because of a patient's inability to compensate by increasing endogenous adrenocorticotropic hormone (ACTH) and cortisol secretion. We describe a patient with CD on pasireotide therapy for 7 years in whom biochemical eucortisolemia was achieved but subsequently experienced several distinct episodes of relative hypocortisolism during periods of acute illness.Methods: A 67-year-old man with biochemical confirmation of CD exhibited clinical and biochemical features of persistent hypercortisolism after transsphenoidal surgery despite pituitary magnetic resonance imaging showing no residual or recurrent tumor. He was enrolled into a phase 3 study (NCT00434148) and was initated on twice-daily subcutaneous pasireotide.Results: Long-term pasireotide therapy normalized 24-hour urinary free cortisol, serum cortisol, and ACTH levels. The patient subsequently developed type 2 diabetes mellitus and was managed effectively with oral hypoglycemic agents and insulin therapy. During a routine clinic assessment 79 months after study enrollment, he reported symptoms suggestive of relative hypocortisolism during three distinct substantially acute stressful health events in the preceding 18 months.Conclusion: Successful achievement of eucortisolemia with long-term medical therapy may increase susceptibility to relative hypocortisolism and precipitate symptoms of adrenal insufficiency during periods of acute stress in patients with CD. We recommend that such patients should be counseled on glucocorticoid stress dosing to prevent such events that could lead to adrenal crisis. (AACE Clinical Case Rep. 2018;4:e1-e6) Abbreviations: ACTH = adrenocorticotropic hormone; CD = Cushing disease; FPG = fasting plasma glucose; GH = growth hormone; HbA 1c = hemoglobin A 1c ; T2DM = type 2 diabetes mellitus; TSS = transsphenoidal surgery; UFC = urinary free cortisol

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effective Medical Therapy for Cushing Disease Can Increase the Susceptibility to Relative Hypocortisolism

Yuen

Mercado

Moloney

et al. 2018

AACE Clinical Case Reports

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“…Dessa forma, o LRS de nova geração, com maior afinidade ao SSTR5, podem apresentar maior eficácia (135) . Com os resultados do estudo de fase III de Colao et al (136) , no qual houve normalização dos níveis de cortisol urinário em 20% de 162 pacientes, a pasireotida foi liberada para o tratamento de DC (137) .…”

Section: Corticotropinomasunclassified

“…Na Tabela 4, a seguir, resume-se a freqüência de resistência às drogas utilizadas para cada subtipo tumoral. Redução tumoral 55-60% (75) AD 65% (72) ACNF Cirúrgico AD Redução tumoral 44-62% (153,155) Corticotropinoma Cirúrgico AD Fu normal 60-70% (124) LRS de nova geração Fu normal 74% (136) AD: agonista dopaminérgico; Fu: cortisol urinário; LRS: ligante de receptor de somatostatina; GH:…”

Section: Filamina a E Resistência Ao Tratamento Medicamentoso Nos Tumunclassified

Análise da expressão da filamina A nos tumores hipofisários e suas implicações clínicas e terapêuticas

Sickler¹

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Dedico esta tese:Aos meus pais, Marilena e Luciano, pelo apoio incondicional, ajuda e exemplo de boas pessoas.Aos meus filhos, Lucas e Rafael, por deixarem a vida doce, e repleta de alegrias em todos os seus momentos.À minha irmã Bruna, por ser sempre sincera e amiga. E principalmente ao Gabriel, pelo amor presente em cada dia que antecedeu a realização e finalização desse estudo; sem você, eu não conseguiria...

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Diagnosis and Treatment of Pituitary Adenomas

Molitch

2017

JAMA

817

578

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pproximately 10% of unselected pituitaries (meaning those from individuals without known pituitary disease) examined at autopsy contain pituitary adenomas. 1 Magnetic resonance imaging (MRI) scans of normal volunteers also show a 10% prevalence, 2 but other pathologic entities may have a similar appearance, such as Rathke cleft cysts and metastatic tumors. 3 Not all patients with pituitary tumors develop symptoms because most tumors remain small and most do not secrete hormones in excessive amounts. Clinical case-finding studies, in which all hospitals and practices in a geographic area were queried about cases with pituitary tumors over a defined period, have suggested a prevalence of pituitary adenoma ranging from 1 in 865 persons to 1 in 2688 persons (Table 1). 4,[6][7][8][9][10][11] Pituitary adenomas are classified into microadenomas (<10 mm), macroadenomas (Ն10 mm), and giant adenomas (Ն40 mm) (Figure 1). 12,13 Pituitary carcinomas with distant metastases are rare, occurring in 0.1% to 0.2% of cases. 12 If an MRI shows the tumor impinging on the optic chiasm, then formal visual field testing is indicated. 13 An evaluation for hypopituitarism should be carried out in all patients with macroadenomas and even large (6-9 mm) microadenomas. 1 Diabetes insipidus is rarely seen with pituitary adenomas. 1 About two-thirds of pituitary adenomas may secrete excess hormones. In the studies 4,6-11 that included 1718 patients, about 50% of cases were macroadenomas and 32% to 66% of tumors were secreting prolactin, 14% to 54% were clinically nonfunction-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 (Ն10 mm). Mass effects cause headache, hypopituitarism, and visual field defects. Treatments include transsphenoidal surgery, medical therapies, and radiotherapy. Prolactinomas account for 32% to 66% of adenomas and present with amenorrhea, loss of libido, galactorrhea, and infertility in women and loss of libido, erectile dysfunction, and infertility in men; they are generally treated with the dopamine agonists cabergoline and bromocriptine. Growth hormone-secreting tumors account for 8% to 16% of tumors and usually present with enlargement of the lips, tongue, nose, hands, and feet and are diagnosed by elevated insulin-like growth factor 1 levels and growth hormone levels; initial treatment is surgical. Medical therapy with somatostatin analogues, cabergoline, and pegvisomant is often also needed. Adrenocorticotropic hormone (ACTH)-secreting tumors account for 2% to 6% of adenomas and are associated with obesity, hypertension, diabetes, and other morbidity. Measurement of a late-night salivary cortisol level is the best screening test but petrosal sinus sampling for ACTH may be necessary to distinguish a pituitary from an ectopic source. The primary treatment of Cushin...

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A 12-Month Phase 3 Study of Pasireotide in Cushing's Disease

Abstract: The significant decrease in cortisol levels in patients with Cushing's disease who received pasireotide supports its potential use as a targeted treatment for corticotropin-secreting pituitary adenomas. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00434148.).

Cited by 571 publications

References 17 publications

Effective Medical Therapy for Cushing Disease Can Increase the Susceptibility to Relative Hypocortisolism

Effective Medical Therapy for Cushing Disease Can Increase the Susceptibility to Relative Hypocortisolism

Análise da expressão da filamina A nos tumores hipofisários e suas implicações clínicas e terapêuticas

Diagnosis and Treatment of Pituitary Adenomas

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