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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Research and Markets: Pituitary ACTH Hypersecretion (Cushing’s Disease) – Pipeline Review Report, H1 2013 Edition

Posted on June 18, 2013 by MaryO

Research and Markets(http://www.researchandmarkets.com/research/rdf6gm/pituitary_acth) has announced the addition of the “Pituitary ACTH Hypersecretion (Cushing’s Disease) – Pipeline Review, H1 2013” report to their offering.

‘Pituitary ACTH Hypersecretion (Cushing’s Disease) – Pipeline Review, H2 2013’, provides an overview of the indication’s therapeutic pipeline. This report provides information on the therapeutic development for Pituitary ACTH Hypersecretion (Cushing’s Disease), complete with latest updates, and special features on late-stage and discontinued projects. It also reviews key players involved in the therapeutic development for Pituitary ACTH Hypersecretion (Cushing’s Disease).

Scope

– A snapshot of the global therapeutic scenario for Pituitary ACTH Hypersecretion (Cushing’s Disease).

– A review of the Pituitary ACTH Hypersecretion (Cushing’s Disease) products under development by companies and universities/research institutes based on information derived from company and industry-specific sources.

– Coverage of products based on various stages of development ranging from discovery till registration stages.

– A feature on pipeline projects on the basis of monotherapy and combined therapeutics.

– Coverage of the Pituitary ACTH Hypersecretion (Cushing’s Disease) pipeline on the basis of route of administration and molecule type.

– Key discontinued pipeline projects.

– Latest news and deals relating to the products.

Companies Involved in Pituitary ACTH Hypersecretion (Cushing’s Disease) Therapeutics Development

 

  • Isis Pharmaceuticals, Inc.
  • Ipsen S.A.
  • Novartis AG
  • HRA Pharma, SA
  • Cortendo Invest AB

 

Drug Profiles: Product Description, Mechanism of Action and R&D Progress

 

  • LCI-699
  • mifepristone
  • ISIS-GCCRRx
  • Inhibitors of ACTH receptor
  • ketoconazole
  • Next Generation Cortisol Inhibitor
  • pasireotide Long Acting Release

 

For more information visit http://www.researchandmarkets.com/research/rdf6gm/pituitary_acth

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Researchers May Have Found the Cause of Cushing’s Disease

Posted on June 3, 2013 by MaryO

A team of researchers may have zeroed in on the cause of Cushing’s disease, a condition that leads to diabetes, obesity and the risk of premature death.

Location of the pituitary gland in the human brain

Location of the pituitary gland in the human brain (Photo credit: Wikipedia)(TR4). By reducing the TR4 in lab mice, they were able to reverse tumor growth and excess ACTH production.

More women than men get the disease, which begins usually between 20 and 50 with mostly benign tumors in the pituitary gland. It’s known that that condition results in excess production of adrenocorticotrophic hormone (ACTH). But until now, scientists haven’t been sure what drives the production of ACTH.

Now, UCLA researchers and their colleagues have zeroed in on the culprit: excessive production of testicular orphan nuclear receptor (TR4). By reducing the TR4 in lab mice, they were able to reverse tumor growth and excess ACTH production.

The findings, published in the journal Proceedings of the National Academy of Sciences, could point the way to targeted treatment of Cushing’s.

From http://www.thirdage.com/medical-care/researchers-find-the-cause-of-cushing-s-disease

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Hyperthyroidism due to thyroid stimulating hormone secretion after surgery for Cushing’s syndrome: A novel cause of the syndrome of inappropriate secretion of thyroid stimulating hormone

Posted on May 14, 2013 by MaryO
Overview of the thyroid system (See Wikipedia:...

Overview of the thyroid system (See Wikipedia:Thyroid). To discuss image, please see Talk:Human body diagrams (Photo credit: Wikipedia)

  1. Daisuke Tamada, MD1,
  2. Toshiharu Onodera, MD1,
  3. Tetsuhiro Kitamura, MD, PhD1,
  4. Yuichi Yamamoto, MD1,
  5. Yoshitaka Hayashi, MD, PhD2,
  6. Yoshiharu Murata, MD, PhD2,
  7. Michio Otsuki, MD, PhD1 and
  8. Iichiro Shimomura, MD, PhD1

Author Affiliations


  1. 1Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan

  2. 2Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
  1. Address all correspondence and requests for reprints to: Michio Otsuki, MD, PhD, Department of Metabolic Medicine, Osaka University Graduate School of Medicine, 2–2 Yamada-oka, Suita, Osaka 565-0871, Japan, Telephone: +81-6-6879-3732. Fax: +81-6-6879-3739, E-mail: otsuki@endmet.med.osaka-u.ac.jp.

Abstract

Context: Hyperthyroidism with the syndrome of inappropriate secretion of thyroid stimulating hormone (TSH) (SITSH) occurred by a decrease in hydrocortisone dose after surgery for Cushing’s syndrome. This is a novel cause of SITSH.

Objective: The aim of this study was to describe and discuss the two cases of SITSH patients who were found after surgery for Cushing’s syndrome. We also checked whether SITSH occurred in the consecutive 7 patients with Cushing’s syndrome after surgery.

Patients and Methods: A 45-year-old Japanese woman with adrenocorticotropin (ACTH)-independent Cushing’s syndrome and a 37-year-old Japanese man with ACTH-dependent Cushing’s syndrome presented SITSH caused by insufficient replacement of hydrocortisone for postoperative adrenal insufficiency. When the dose of hydrocortisone was reduced to less than 20 mg/day within 18 days after operation, SITSH occurred in both cases. We examined whether the change of the hydrocortisone dose induced the secretion of TSH. Free T3 and TSH were normalized by the hydrocortisone dose increase of 30 mg/day and these were elevated by the dose decrease of 10 mg/day. We also checked TSH and thyroid hormone the consecutive 7 patients with Cushing’s syndrome after surgery. Six (66.6 %) of nine patients showed SITSH.

Conclusions: This is the first report that insufficient replacement of hydrocortisone after the surgery of Cushing’s syndrome caused SITSH. Hyperthyroidism by SITSH as well as adrenal insufficiency can contribute to withdrawal symptoms of hydrocortisone replacement. So we need to consider the possibility of SITSH for the pathological evaluation of withdrawal syndrome of hydrocortisone replacement.

  • Received May 4, 2013.
  • Accepted May 8, 2013.

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