CushieBlog

Fleseriu M, Petersenn S.

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Departments of Medicine and Neurological Surgery, Northwest Pituitary Center, Oregon Health & Science University, Portland, OR, USA.

Abstract

Cushing’s disease (CD) is caused by a corticotroph, adrenocorticotropic-hormone (ACTH)-secreting pituitary adenoma resulting in significant morbidity and mortality. Transsphenoidal surgery is the initial treatment of choice in almost all cases.

Remission rates for microadenomas are good at 65-90 % (with an experienced neurosurgeon) but remission rates are much lower for macroadenomas. However, even after postoperative remission, recurrence rates are high and can be seen up to decades after an initial diagnosis. Repeat surgery or radiation can be useful in these cases, although both have clear limitations with respect to efficacy and/or side effects.

Hence, there is a clear unmet need for an effective medical treatment. Currently, most drugs act by inhibiting steroidogenesis in the adrenal glands. Most is known about the effects of ketoconazole and metyrapone. While effective, access to ketoconazole and metyrapone is limited in many countries, experience with long-term use is limited, and side effects can be significant. Recent studies have suggested a role for a pituitary-directed therapy with new multireceptor ligand somatostatin analogs (e.g., pasireotide, recently approved in Europe for treatment of CD), second-generation dopamine agonists, or a combination of both.

Mifepristone (a glucocorticoid receptor antagonist) is another promising drug, recently approved by the FDA for treatment of hyperglycemia associated with Cushing’s syndrome. We review available medical treatments for CD with a focus on the two most recent compounds referenced above.

Our aim is to expand awareness of current research, and the possibilities afforded by available medical treatments for this mesmerizing, but often frightful disease.

PMID: 22674211 [PubMed – as supplied by publisher]

From http://www.ncbi.nlm.nih.gov/pubmed/22674211

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

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

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

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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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• From http://www.springerlink.com/content/4r466139264616q2/

(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