Context: Patients with adrenocortical carcinoma (ACC) frequently suffer from cortisol excess, which portends a negative prognosis. Rapid control of cortisol hypersecretion and tumor growth are the main goals of ACC therapy. Abiraterone acetate (AA) is a potent inhibitor of 17alpha-hydroxylase/17,20-lyase, a key enzyme of adrenal steroidogenesis.Objective: To investigate the therapeutic use of AA in preclinical models of ACC.Design: AA antisecretive and antiproliferative effects were investigated in vitro using NCI-H295R and SW13 ACC cell lines and human primary ACC cell cultures, as well as in vivo using immunodeficient mice.Methods: Steroid secretion, cell viability and proliferation were analyzed in untreated and AA-treated ACC cells. The ability of AA to affect the Wnt/beta-catenin pathway in NCI-H295R cells was also analyzed.Progesterone receptor (PgR) gene was silenced by the RNA interference approach. The antitumor efficacy of AA was confirmed in vivo in NCI-H295R cells xenografted in immunodeficient mice.Results: AA reduced the secretion of both cortisol and androgens, increased production of progesterone and induced a concentration-dependent decrease of cell viability in the NCI-H295R cells and primary secreting ACC cultures. AA also reduced beta-catenin nuclear accumulation in NCI-H295R cells. AA administration to NCI-H295R-bearing mice enhanced progesterone levels and inhibited tumor growth. The cytotoxic effect of AA was prevented by either blocking PgR or by gene silencing.Conclusion: AA is able to inhibit hormone secretion and growth of ACC both in vitro and in vivo. It also reduces beta-catenin nuclear accumulation. The cytotoxic effect of AA appears to require PgR.

Editor-in-Chief: A. Giustina ▶ Covers leading topics in endocrinology ▶ Includes Hormones of reproduction, metabolism, growth, and ion balance ▶ Offers the latest on insulin and diabetes ▶ Presents newly-emerging endocrine-related topics ▶ 94% of authors who answered a survey reported that they would definitely publish or probably publish in the journal againWell-established as a major journal in today's rapidly advancing experimental and clinical research, Endocrine publishes full-length original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical (including proof of concept studies and clinical trials) research in all the different fields of endocrinology and metabolism. Endocrine covers the following leading topics in Endocrinology such as: Neuroendocrinology, Pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, type 1 and type 2 diabetes, hormones of male and female reproduction, and of HPA axis, pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.

Background: The administration of abiraterone acetate (abiraterone) leads to an adrenocorticotropic hormone (ACTH)-driven increase in mineralocorticoid hormones, requiring glucocorticoid supplementation that may stimulate the growth of prostate cancer (PCa). Amiloride is a drug that selectively reduces the aldosterone-sensitive Na+/K+ exchange and could be effective in the management of mineralocorticoid excess syndrome (MCES). Methods: The efficacy of amiloride + hydrochlorothiazide (HCT) in the clinical management of abiraterone-induced MCES was assessed in 5 consecutive patients with castration-resistant PCa (CRPC). Then, using the in vitro experimental model of PCa cell lines, the possible effects of drugs usually used in the clinical management of CRPC patients on PCa cell viability were investigated. Results: Amiloride/HCT led to a complete disappearance of all clinical and biochemical signs of abiraterone-induced MCES in the 5 treated patients. The in vitro study showed that abiraterone treatment significantly decreased cell viability of both androgen receptor (AR)-expressing VCaP (vertebral-cancer of the prostate) and LNCaP (lymph node carcinoma of the prostate) cells, with no effect on AR-negative PC-3 cells. Prednisolone, spironolactone, and eplerenone increased LNCaP cell viability, while amiloride reduced it. The non-steroid aldosterone antagonist PF-03882845 did not modify PCa cell viability. Conclusions: The combination of amiloride/HCT was effective in the management of abiraterone-induced MCES. Amiloride did not negatively interfere with the abiraterone inhibition of PCa cell viability in vitro.

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Angioimmunoblastic T-cell lymphoma shows a high release of cytokines. Different blood purification techniques are employed to control hypercytokinemia. Here we investigated the effects of intermittent supra-hemodiafiltration with endogenous reinfusion on cytokine removal in a patient presenting with acute kidney injury. After the first day of chemotherapy for angioimmunoblastic T-cell lymphoma, a 78-year-old male patient developed acute kidney injury and systemic inflammatory response syndrome due to massive release of inflammatory cytokines. Three sessions of supra-hemodiafiltration were performed. Blood samples for evaluation of renal function and inflammatory mediators were collected at the beginning and the end of each dialytic session. A marked improvement of clinical state and renal function was associated to a significant reduction of inflammatory markers. Our results suggest that renal replacement therapy with supra-hemodiafiltration may remove a wide spectrum of inflammatory mediators and uremic toxins involved in acute kidney injury and systemic inflammatory response syndrome.