Pasireotide for the treatment of Cushing’s disease

Posted on June 23, 2013 by MaryO

Posted online on June 17, 2013. (doi:10.1517/21678707.2013.807731)

Annamaria Colao †, Chiara Simeoli , Monica De Leo , Alessia Cozzolino , Rosario Pivonello

Department of Clinical Medicine and Surgery, Section of Endocrinology, Federico II University, Via Sergio Pansini 5,

80131 Naples

, Italy +39 0817462132; +39 0815465443; colao@unina.it

†Author for correspondence

Introduction: Pasireotide, a novel multireceptor targeted somatostatin analog is the first drug approved for treatment of adult patients with Cushing’s disease (CD) for whom pituitary surgery is not an option or has not been curative.

Areas covered: The review describes published data on efficacy and safety of pasireotide in CD patients. In particular, the review focuses on a Phase III study (CSOM230B2305) evaluating the outcomes of treatment with pasireotide at the doses of 600 and 900 µg twice daily for 12 months in 162 CD patients. This clinical trial reported a decrease in urinary free cortisol levels in the majority of patients, with a substantial reduction in nearly half and a normalization in > 25% of patients included in the study, accompanied by an improvement in clinical picture as well as a significant reduction in pituitary tumor size. Hyperglycemia appears as the most important side effect, requiring a careful monitoring and a prompt administration of glucose-lowering medications.

Expert opinion: Pasireotide seems to have a promising role as medical option for CD patients who experienced a failure or not candidate for neurosurgery; its employment will probably induce in the near future significant changes in the therapeutic approach to CD.

Read More: http://informahealthcare.com/doi/abs/10.1517/21678707.2013.807731

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Hypercortisolism Is Associated With Increased Coronary Arterial Atherosclerosis

Posted on May 21, 2013 by MaryO

Hypercortisolism Is Associated With Increased Coronary Arterial Atherosclerosis: Analysis of Noninvasive Coronary Angiography Using Multidetector Computerized Tomography

Journal of Clinical Endocrinology and Metabolism, 05/21/2013  Clinical Article

  1. Nicola M. Neary*,
  2. O. Julian Booker*,
  3. Brent S. Abel,
  4. Jatin R. Matta,
  5. Nancy Muldoon,
  6. Ninet Sinaii,
  7. Roderic I. Pettigrew,
  8. Lynnette K. Nieman and
  9. Ahmed M. Gharib

–Author Affiliations


  1. Program in Reproductive and Adult Endocrinology (N.M.N., L.K.N., B.S.A.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Laboratory of Cardiac Energetics (O.J.B.), National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; Integrative Cardiovascular Imaging Laboratory (J.R.M., R.I.P., A.M.G.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Critical Care Medicine (N.M.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892; and Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Center, National Institutes of Health, Bethesda, Maryland 20892
  1. Address all correspondence and requests for reprints to: Ahmed M. Gharib, MB, ChB, National Institutes of Health, Building 10, Room 3-5340, Mail Stop Code 1263, 10 Center Drive, Bethesda, MD 20892. E-mail: agharib@mail.nih.gov.

  1. ↵* N.M.N. and O.J.B. contributed equally to this work.

Abstract

Background: Observational studies show that glucocorticoid therapy and the endogenous hypercortisolism of Cushing’s syndrome (CS) are associated with increased rates of cardiovascular morbidity and mortality. However, the causes of these findings remain largely unknown.

Objective: To determine whether CS patients have increased coronary atherosclerosis.

Design: A prospective case-control study was performed.

Setting: Subjects were evaulated in a clinical research center.

Subjects: Fifteen consecutive patients with ACTH-dependent CS, 14 due to an ectopic source and 1 due to pituitary Cushing’s disease were recruited. Eleven patients were studied when hypercortisolemic; 4 patients were eucortisolemic due to medication (3) or cyclic hypercortisolism (1). Fifteen control subjects with at least one risk factor for cardiac disease were matched 1:1 for age, sex, and body mass index.

Primary outcome variables: Agatston score a measure of calcified plaque and non-calcified coronary plaque volume were quantified using a multidetector CT (MDCT) coronary angiogram scan. Additional variables included fasting lipids, blood pressure, history of hypertension or diabetes, and 24-hour urine free cortisol excretion.

Results: CS patients had significantly greater noncalcified plaque volume and Agatston score (noncalcified plaque volume [mm3] median [interquartile ranges]: CS 49.5 [31.4, 102.5], controls 17.9 [2.6, 25.3], P < .001; Agatston score: CS 70.6 [0, 253.1], controls 0 [0, 7.6]; P < .05). CS patients had higher systolic and diastolic blood pressures than controls (systolic: CS 143 mm Hg [135, 173]; controls, 134 [123, 136], P < .02; diastolic CS: 86 [80, 99], controls, 76 [72, 84], P < .05).

Conclusions: Increased coronary calcifications and noncalcified coronary plaque volumes are present in patients with active or previous hypercortisolism. Increased atherosclerosis may contribute to the increased rates of cardiovascular morbidity and mortality in patients with glucocorticoid excess.

  • Received October 29, 2012.
  • Accepted March 7, 2013.

From JCEM

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