Cushing's disease: a multidisciplinary overview of the clinical features, diagnosis, and treatment.

Cushing's disease is considered a rare condition characterized by the hypersecretion of the adrenocorticotropic hormone (ACTH) due to a pituitary adenoma that ultimately causes endogenous hypercortisolism by stimulating the adrenal glands. The clinical signs suggesting Cushing's disease, such as obesity, moon face, hirsutism, and facial plethora are already present on presentation. Endogenous hypercortisolism is associated with an increased risk of cardiovascular and metabolic manifestations, as well as respiratory disorders, psychiatric complications, osteoporosis and infections, leading to high rates of morbidity and mortality. It is vital to diagnose Cushing's disease as early as possible and to implement a treatment plan to lead to a successful prognosis and a low number of complications. The goal of this article was to review the clinical, diagnostic and treatment aspects of Cushing's disease using the most recent available guidelines.

The multimodal management of GH-secreting pituitary adenomas: predictive factors, strategies and outcomes.

Object. The aim of this study was to analyze a series of 28 patients with acromegaly who underwent a multimodal surgical, medical and radiosurgical therapy, with a special attention to the advantages, complications, and predictive factors of a successful outcome. Methods. 28 consecutive cases of GH-secreting pituitary adenomas, who underwent transsphenoidal endoscopic or microscopic surgery, between 1 January 2014 and 31 December 2014 were retrospectively reviewed. Tumors were classified according to the diameter, measured on MRI, as micro- or macroadenomas, and parasellar (cavernous sinus) tumor extension was analyzed based on the Knosp grading score. The mean follow-up period was of 18.4 months. Criteria justifying the complete hormonal remission were preoperative basal serum GH < 2.5 µg/ L, preoperative nadirGH < 1 ng/ L after OGTT and normal preoperative IGF-I levels age and sex-matched. Results. An overall complete hormonal remission rate was achieved in 64.3% of the patients. The remission rate was higher in patients with microadenomas (77.8%) than in those with macroadenomas (57.9%). A number of predictive factors, which might have interfered with the hormonal remission rate from a statistical, clinical and paraclinical point of view, were identified: tumor size (r = 0.625), preoperative GH serum levels (r = -0.517), cavernous sinus extension was quantified according to Knosp grading score (r = 0.469) and the degree of tumor subtotal resection (r = 0.598). Conclusions. Favorable hormonal and visual remission rates can be achieved after transsphenoidal resection of GH-secreting pituitary adenomas; however, the management remains challenging, the increased surgical experience being important for higher cure rates. If a biochemical hormonal cure is not achieved postoperatively, adjuvant medical or radio surgical therapy can be recommended.

Effect of VEGFR, PDGFR and PI3K/mTOR Targeting in Glioblastoma.

Resistance to targeted therapy is a well known obstacle in cancer therapy. The cross-talk between several growth factor receptors generates redundancy in their intracellular pathways that usually mediates resistance to receptor targeted therapy. Simultaneous inactivation of two or more growth factor receptors has been suggested to prevent the cross-talk between their signaling pathways and to better eliminate malignant cells. Here we found that targeted therapy against these receptors induced moderate cell death in glioblastoma cells. More important, dual PDGFR and VEGFR inactivation induced more pronounceable cell death compared to inactivation of each receptor alone but failed to induce synergistic cell death in glioblastoma. PI3K/mTOR dual targeting has been identified as an efficient therapeutic approach in several malignant diseases, including glioblastoma. Therefore, we also investigated the PI3K/mTOR pathways inhibition effect in glioblastoma cells. Our results showed that inactivation of PI3K/mTOR pathways were more efficient than PDGFR or VEGFR single targeting or their dual inhibition.