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Adrenal incidental adenomas
Published in Nadia Barghouthi, Jessica Perini, Endocrine Diseases in Pregnancy and the Postpartum Period, 2021
Cell typesAdrenal incidentalomas can arise from the adrenal cortex, adrenal medulla, or as metastatic disease from an extra-adrenal cancer.Tumors arising from the adrenal cortex include nonfunctional adrenocortical adenomas, cortisol-producing adenomas, aldosterone-producing adenomas, and adrenocortical carcinoma.A tumor arising from the adrenal medulla is a pheochromocytoma.5The most common etiology of an adrenal incidentaloma is a benign, non-hypersecreting adrenocortical adenoma.8
Primary adrenal malignancy
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Ayshea Hameeduddin, Anju Sahdev, Rodney H Reznek
Seventy percent of patients with adrenal cancer have either stage III or IV disease at the time of diagnosis (Figure 14.2). The most frequent sites of metastases are: Lymph nodes (25%–46%)Lungs (47%–97%)Liver (53%–96%)Abdomen (35%–43%)Bone (11%–33%)
Coincidental adrenal masses and adrenal cancer
Published in Philip E. Harris, Pierre-Marc G. Bouloux, Endocrinology in Clinical Practice, 2014
Marinella Tzanela, Dimitra Argyro Vassiliadi, Stylianos Tsagarakis
The size of the lesion used to be considered as a major predictor of malignancy, and surgery is usually recommended for lesions >4–6 cm. The prevalence of adrenocortical carcinoma (ACC) is thought to be 2% among tumors that are ≤4 cm, 6% among tumors that are 4.1–6.0 cm, and 25% among larger tumors.11 Size has both a low specificity and low sensitivity for the detection of cancer because 75% of tumors >6 cm are not malignant, and also small ACCs have been reported. In lesions of <4 cm, a repeat imaging evaluation at 3–6 months, depending on the size and imaging characteristics of the mass, is usually advocated. A rapid and significant (usually >5 mm) change in size may occasionally indicate malignancy, but again it is not an accurate predictor of adrenal cancer.7,12 The role of further repeat imaging has been challenged recently by Cawood et al.7 who raised concerns that the risk of inducing cancer from the ionizing radiation delivered from multiple computed tomography (CT) scans outweighs the possible benefits, given the substantially small probability of malignant transformation of these tumors.
Drug design strategies for Cushing’s syndrome
Published in Expert Opinion on Drug Discovery, 2019
S. A. Usanov, A. V. Kliuchenovich, N. V. Strushkevich
Cushing’s syndrome (CS) denotes a set of clinical signs that evolve due to pathological exposure to cortisol as a consequence of its endogenous overproduction or corticosteroid treatment. ACTH-dependent endogenous cortisol excess due to a pituitary adenoma is called Cushing disease and account for ~70% of cases [1]. The disease was first described by Harvey Cushing in 1932 [2] and the treatment is still challenging for endocrinologists worldwide due to diverse etiologies, leading to hypercortisolism. ACTH-independent autonomous adrenal overproduction of cortisol caused by an adrenal cancer or by an adrenal adenoma leads to CS. Cortisol is a steroid hormone of the glucocorticoid class produced by the adrenal cortex. It is released in response to stress and low blood-glucose concentration and regulates metabolism and immune response. As a result, CS is associated with hypertension, weight gain, truncal adiposity, impaired glucose tolerance or diabetes, insomnia, cognitive impairment, mood changes ranging from anxiety and depression to psychosis, infections, and fractures [3,4]. Uncontrolled CS and severe hypercortisolism could lead to life-threating conditions, including mortality mainly due to cardiovascular disease [5,6].
Cancer preventive and therapeutic effects of EGCG, the major polyphenol in green tea
Published in Egyptian Journal of Basic and Applied Sciences, 2018
Islam Rady, Hadir Mohamed, Mohamad Rady, Imtiaz A. Siddiqui, Hasan Mukhtar
EGCG induced cell apoptosis (Table 3) through intrinsic mitochondrial pathway via activation of Caspase-9 in PC3 prostate cancer cells [47], MCF-7 breast cancer cells [73] and PANC-1, MIA-Pa-Ca-2, Hs 766 T and AsPC-1 pancreatic cancer cells [48]. EGCG has also been shown to induce apoptosis through extrinsic death receptor pathway in MIA-Pa-Ca-2 pancreatic cancer cells via activation of Fas, DR5 and Caspase-8 [74]. In addition, EGCG downregulated the expression of anti-apoptotic proteins, such as BCL-2 in PANC-1, MIA-Pa-Ca-2, Hs 766 T and AsPC-1 pancreatic cancer cells [48], MDA-MB-231 breast cancer cells [75], NCI-H295 adrenal cancer cells [76] and PC-12 pheochromocytoma cells [77], BCL-XL in PANC-1, MIA-Pa-Ca-2, Hs 766 T and AsPC-1 cells pancreatic cancer cells [48] and NCI-H295 adrenal cancer cells [76], survivin in MCF-7 breast cancer cells [73] and NUGC-3 gastric cancer cells [78]; and XIAP in NCI-H295 adrenal cancer cells [76]. Also, EGCG was found to upregulate the expression of pro-apoptotic proteins, including Apaf-1 and BAD in NCI-H295 adrenal cancer cells [76] and BAK, BAX, BCL-XS and PUMA in PANC-1, MIA-Pa-Ca-2, Hs 766T and AsPC-1 pancreatic cancer cells [48]. Moreover, EGCG induced apoptosis through both intrinsic and extrinsic pathways, regulatory proteins and endoplasmic reticulum stress via activation of caspase-dependent, caspase-independent, death receptors, downregulation of anti-apoptotic proteins BCL-2, BCL-XL and XIAP and upregulation of pro-apoptotic BAD and BAX in NCI-H295 human adrenal cancer cells [76].
A patent review of anticancer glucocorticoid receptor modulators (2014-present)
Published in Expert Opinion on Therapeutic Patents, 2020
Marianna Lucafò, Martina Franzin, Giuliana Decorti, Gabriele Stocco
Of interest, two of the compounds included in the Corcept’s patent filings are already in advanced clinical development, in particular relacorilant (CORT 125134) is employed for the treatment of Cushing syndrome (phase III), fallopian tube cancer, ovarian cancer, peritoneal cancer (phase II), solid tumors (phase I/II) and prostate cancer (phase I). In addition, Corcept Therapeutics plans a phase Ib trial of relacorilant combined with an immunotherapeutic agent for adrenal cancer, and a phase III trial for pancreatic cancer in the second quarter of 2020; moreover, the company has announced the intention to submit new drug application to the FDA for Cushing syndrome in the fourth quarter of 2021 (https://adisinsight.springer.com/drugs/800041622).