Mifepristone, a Glucocorticoid Receptor Antagonist, Produces Clinical and Metabolic Benefits in Patients with Cushing's Syndrome

Fleseriu, Maria; Biller, Beverly M. K.; Findling, James W.; Molitch, Mark E.; Schteingart, D.E.; Gross, Coleman

doi:10.1210/jc.2011-3350

Cited by 419 publications

(386 citation statements)

References 35 publications

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“…Results from the SEISMIC (Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing Syndrome) trial reported significant improvements in glycemia in 60% (15/25) of patients with baseline diabetes or glucose intolerance following 24 weeks of mifepristone therapy (23). In addition, the majority of patients with hypertension in this study had either a ≥5 mm Hg decrease in diastolic blood pressure or a reduction in the number of antihypertensive medications following mifepristone treatment.…”

Section: Introductionmentioning

confidence: 58%

“…Centrally acting agents that target excessive pituitary adrenocorticotropic hormone (ACTH) secretion, inhibitors of See accompanying article, p. 1175. steroidogenesis, or glucocorticoid receptor antagonists have been utilized depending on the underlying cause of CS. Prospective clinical trials, however, are limited (22), and there have not been any head-to-head studies comparing the efficacy, tolerability, and safety of the U.S. Food and Drug Administration (FDA)-and non-FDA approved drugs (14,17,23,24).…”

Section: Introductionmentioning

confidence: 99%

“…In addition, the majority of patients with hypertension in this study had either a ≥5 mm Hg decrease in diastolic blood pressure or a reduction in the number of antihypertensive medications following mifepristone treatment. However, the most common adverse events (AEs) (≥20%) reported during the SEISMIC trial were nausea, fatigue, headache, hypokalemia, arthralgia, vomiting, peripheral edema, hypertension, dizziness, decreased appetite, and endometrial thickening in females (23).…”

Section: Introductionmentioning

confidence: 99%

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Association Between Mifepristone Dose, Efficacy, and Tolerability in Patients With Cushing Syndrome

Yuen

Williams

Kushner³

et al. 2015

Endocrine Practice

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Section: Introductionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association Between Mifepristone Dose, Efficacy, and Tolerability in Patients With Cushing Syndrome

Yuen

Williams

Kushner³

et al. 2015

Endocrine Practice

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“…Reimbursement values for each CPT code (50th percentile) for physician services or outpatient services/procedures/labs were obtained from the MAG Mutual Physicians' Fee and Coding Guide 2012, and were summed separately to generate costs of surgery or radiation therapy. Costs for drug therapies in both scenarios are calculated based on the mean recommended daily dosage for each treatment (obtained from published literature) 2,28,[36][37][38] . Daily drug costs are estimated by multiplying mean daily dose (in mg) with the lowest drug cost per mg that was obtained using the wholesale acquisition cost (WAC) from the 2013 Drug Topics Redbook 39 .…”

Section: Treatment Durationmentioning

confidence: 99%

“…A literature review was conducted and eight studies identified as the most appropriate clinical studies for inclusion in the total budget impact model 37,38,[40][41][42][43][44][45] . Fourteen unique AEs were identified, of which hypopituitarism was associated with TSS, RS, and RT.…”

Section: Surgical Complications and Adverse Eventsmentioning

confidence: 99%

Budget impact of pasireotide for the treatment of Cushing’s disease, a rare endocrine disorder associated with considerable comorbidities

Truong

Nellesen

Ludlam

et al. 2014

Journal of Medical Economics

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Vol. 17, No. 4, 2014, 288-295 Cushing's disease (CD) is a rare condition with a prevalence of roughly 39 cases per million in the general population. Healthcare costs are substantial for CD patients with either untreated or inadequately controlled disease. This study assesses the 3-year budget impact of pasireotide on a US managed care health plan following pasireotide (Signifor*) availability. Methods:Two scenarios were evaluated to understand the differences in costs associated with the introduction of pasireotide. The first scenario evaluates the budget impact of pasireotide from the perspective of an entire health plan (total budget impact) and the second from the perspective of the pharmacy budget (pharmacy budget impact). Both scenarios evaluate the annual incremental budget impact with and without pasireotide. Scenario 1 includes costs for medical procedures, drug therapies, monitoring, surgical complications, comorbidities for patients with controlled or uncontrolled CD, and adverse events. Procedures include transsphenoidal surgery, bilateral adrenalectomy, radiotherapy and radiosurgery. Drugs include pasireotide (indicated for CD), mifepristone (indicated to control hyperglycemia secondary to hypercortisolism in patients with Cushing's syndrome) as well as several off-label treatments (ketoconazole, cabergoline, mitotane). Scenario 2 considers costs solely from the perspective of a health plan pharmacy. Costs are in $2013. Results:The estimated total budget impact is $0.0115 per-member per-month (PMPM) in the first year following FDA approval, $0.0184 in the second year, and $0.0194 in the third year. Introduction of pasireotide is expected to increase the pharmacy budget by $0.0257 PMPM in the first year, $0.0363 in the second year, and $0.0360 in the third year. Limitations:Model inputs rely on the small body of literature available for Cushing's disease. Conclusions:Cushing's disease is severe disease with debilitating comorbidities and substantial healthcare costs when untreated or inadequately controlled. The inclusion of pasireotide in a health plan formulary appears to have only a small impact on the total health plan or pharmacy budget.

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Diagnosis and Treatment of Pituitary Adenomas

Molitch

2017

JAMA

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811

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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Mifepristone, a Glucocorticoid Receptor Antagonist, Produces Clinical and Metabolic Benefits in Patients with Cushing's Syndrome

Abstract: Mifepristone produced significant clinical and metabolic improvement in patients with CS with an acceptable risk-benefit profile during 6 months of treatment.

Cited by 419 publications

References 35 publications

Association Between Mifepristone Dose, Efficacy, and Tolerability in Patients With Cushing Syndrome

Association Between Mifepristone Dose, Efficacy, and Tolerability in Patients With Cushing Syndrome

Budget impact of pasireotide for the treatment of Cushing’s disease, a rare endocrine disorder associated with considerable comorbidities

Diagnosis and Treatment of Pituitary Adenomas

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