Pasireotide in Cushing’s Disease

Posted on May 31, 2012 by MaryO

N Engl J Med 2012; 366:2134-2135 May 31, 2012

 

To the Editor:

In their study, Colao et al. (March 8 issue)1 examined the clinical efficacy and safety of two different doses of subcutaneous pasireotide in patients with newly diagnosed, persistent, or recurrent Cushing’s disease. Since alternative therapies (including bilateral adrenalectomy) are available for patients with persistent or recurrent Cushing’s disease, it would be important to consider all options before embarking on what might turn out to be many years of medication.

Giovanni Targher, M.D.
University of Verona, Verona, Italy 

No potential conflict of interest relevant to this letter was reported.

1 References

To the Editor:

The phase 3 trial by Colao et al. showed the efficacy of 12 months of treatment with subcutaneous pasireotide (600 or 900 μg twice daily) in patients with Cushing’s disease. We now report results after 7 years of treatment with pasireotide administered as part of a phase 2 study.1 In July 2004, a 43-year-old woman with Cushing’s disease, whose 24-hour urinary free cortisol level was 9.2 times the upper limit of normal, began 15 days of treatment with subcutaneous pasireotide (600 μg twice daily) that resulted in normalization of these levels (Figure 1AFIGURE 1Effects of Pasireotide Treatment on 24-Hour Urinary Free Cortisol Levels and on Adrenocorticotropin Hormone Levels during Desmopressin-Stimulation Testing.). When treatment was halted for 35 days, urinary free cortisol levels increased. In September 2004, she resumed treatment with pasireotide (600 μg twice daily), which led to clinical improvement (i.e., a weight loss of 13 kg, regular menstrual cycles, and reduced hirsutism). Hyperglycemia ensued (glycated hemoglobin, 5.7 to 7.7%), and weakness necessitated a temporary reduction in the dose to 450 μg twice daily (November 2004 to October 2005). Since November 2005, when the patient resumed taking the 600-μg dose twice daily, urinary free cortisol levels have remained in the normal range at most monthly assessments. Basal and desmopressin-stimulated adrenocorticotropin levels also decreased as a result of treatment with pasireotide (Figure 1B). To date, she has not had any serious adverse events. This case illustrates the long-term efficacy of pasireotide without the development of resistance to the drug’s effects.

Rossella Libé, M.D.
INSERM Unité 1016, Paris, France

Lionel Groussin, M.D., Ph.D.
Université Paris Descartes, Paris, France

Jérôme Bertherat, M.D., Ph.D.
Hôpital Cochin, Paris, France 

Drs. Libé and Bertherat report being investigators for studies of pasireotide in Cushing’s disease funded by Novartis. No other potential conflict of interest relevant to this letter was reported.

1 References

Author/Editor Response

We concur with Targher’s implication that the advantages and disadvantages of all management options should be considered for each patient before a specific treatment is advised.

Libé and colleagues present a very interesting case of a patient with Cushing’s disease in the extension of a phase 2 study of pasireotide. This patient was treated with pasireotide for a much longer duration than the 1 year reported in the phase 3 study.

Annamaria Colao, M.D., Ph.D.
University of Naples Federico II, Naples, Italy

Mario Maldonado, M.D.
Novartis Pharma, Basel, Switzerland

Since publication of their article, the authors report no further potential conflict of interest.

 

From http://www.nejm.org/doi/full/10.1056/NEJMc1204078

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Correlation Between Histological Subtypes and MRI Findings in Clinically Nonfunctioning Pituitary Adenomas

Posted on May 30, 2012 by MaryO

Hiroshi Nishioka, Naoko Inoshita, Toshiaki Sano, Noriaki Fukuhara and Shozo Yamada

Clinically nonfunctioning pituitary adenomas (CNFPAs) consist of several histological subtypes, including null cell adenoma (NCA), silent gonadotroph cell adenoma (SGA), silent corticotroph adenoma (SCA), and other silent adenomas (OSA) (i.e., GH, TSH, and prolactin adenomas).

To detect possible correlations between MRI findings and the subtypes, we retrospectively studied 390 consecutive patients with CNFPA who underwent surgery between 2008 and 2010. They were classified into three groups: NCA/SGA (313 cases), SCA (39 cases), and OSA (36 cases); in addition there were two unusual cases of plurihormonal adenoma.

Three MRI findings were less common in NCA/SGA than in the other groups (P < 0.0001): giant adenoma (>40 mm), marked cavernous sinus invasion (Knosp grade 4), and lobulated configuration of the suprasellar tumor. When these MRI findings were negative in patients older than 40 years old, 91.0 % (212/233) were NCA/SGA.

These MRI findings were frequently noted despite a low MIB-1 index in SCA. OSA showed a high MIB-1 index and a preponderance in younger patients. In conclusion, although SCA and OSA consisted of only 20 % of CNFPAs, their frequency significantly increased when the tumor was large, invasive, and lobulated, and the patient was younger than 40 years old.

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Adrenal cavernous hemangioma with subclinical Cushing’s syndrome: report of a case

Posted on May 30, 2012 by MaryO

Masaharu Oishi, Shugo Ueda, Sachiko Honjo, Hiroyuki Koshiyama, Yoshiaki Yuba and Arimichi Takabayashi

 

Cavernous hemangioma of the adrenal gland is a rare tumor, which does not usually have endocrinological function. We report to our knowledge, the third documented case of a functioning adrenal hemangioma.

Interestingly, this tumor indicated glucocorticoid hypersecretion, whereas the two previous cases showed mineralocorticoid hypersecretion. The tumor was 5 cm in diameter with typical computed tomography and magnetic resonance imaging findings.

Subclinical Cushing’s syndrome was diagnosed preoperatively, as there was insufficient suppression of cortisol by low-dose dexamethasone, a low adrenocorticotropic hormone (ACTH) concentration, and diminished ACTH and cortisol circadian rhythms without the typical clinical manifestation and symptoms of hypercortisolism.

Intraoperative hypotension occurred immediately after tumor removal and following postoperative adrenal insufficiency, which support that the tumor was hyperfunctioning. The postoperative adrenal insufficiency had recovered completely by 12 months after the operation.

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Read more at http://www.springerlink.com/content/5mv23480j870462m/

 

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Course of pregnancies in women with Cushing’s disease treated by gamma-knife

Posted on May 16, 2012 by MaryO

(doi:10.3109/09513590.2012.683057)

Francesco Ferraù1, Marco Losa2, Oana Ruxandra Cotta1, Maria Luisa Torre1, Marta Ragonese1, Francesco Trimarchi1, Salvatore Cannavò1

1Department of Medicine and Pharmacology, Section of Endocrinology, University of Messina, Messina, Italy

2Department of Neurosurgery, Istituto Scientifico San Raffaele, Milan, Italy

Correspondence: Francesco Ferraù, MD, Department of Medicine and Pharmacology, Section of Endocrinology, University of Messina, AOU Policlinico “G. Martino” (Pad. H, floor 4), Via Consolare Valeria 1, 98125 Messina, Italy. Tel: +39 090 2213507. Fax: +39 090 2213945. E-mail: ferrau1@interfree.it

 

Data concerning pregnancy in women with Cushing’s disease treated by gamma-knife (GK) are scanty. We present and discuss the course and outcome of five pregnancies in two women with Cushing’s disease (CD), the first of whom was treated only by GK, and the second one treated by surgery, GK and ketoconazole.

In the first patient, pregnancy was uneventful and full-term. During gestation, plasma ACTH, serum cortisol and 24-h urinary free cortisol (UFC) levels were steady, and always in the normal range for healthy non-pregnant individuals. The newborn was healthy and normal-weight.

In the second woman, two pregnancies, occurring 3 years after GK and few months after ketoconazole withdrawal, were interrupted by spontaneous abortion or placental disruption despite normal cortisol levels. This patient became again pregnant 3 years later and delivered vaginally a healthy full-term infant.

Seven months after the delivery, the patient became pregnant again and at the 39th week of gestation delivered vaginally a healthy male. Hypoprolactinemia and/or central hypothyroidism occurred in both cases. In women with CD treated by GK, pregnancy can occur. However, pregnancy is at risk even when ACTH and cortisol levels are normalized by treatment. After GK, evaluation of pituitary function is mandatory due to the risk of hypopituitarism.

Read More: http://informahealthcare.com/doi/abs/10.3109/09513590.2012.683057

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Have You Learned About Cushing’s At a Health Fair?

Posted on May 16, 2012 by MaryO

I cannot imagine this myself, since Cushing’s is so hard to diagnose but an article at yourdailyjournal.com claims: 

The blood profiles provide a comprehensive look at several physiological systems in the body at a cost that is very reasonable for the patients, all in one panel,” Laboratory Manager Rhonda Outlaw said. “The cost savings would amount to anywhere from $185 to $1,100, depending on the tests done and whether they were drawn at a physician’s office or on an outpatient basis.

 

“The panel itself will give indication of possible problems with kidney functions, hematological functions, like anemia, platelet function and infection; cardiovascular disease, thyroid functions, diabetes detection, liver functions and electrolyte function, like Cushings Syndrome, potassium regulation and dehydration detection.”

What do you think about this?


 

 

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