Endocrine Abstracts

Recently, we demonstrated for adrenocortical carcinoma (ACC) promising antitumoural effects for LEDP-M (etoposide, liposomal doxorubicin, liposomal cisplatin, mitotane) a novel liposomal variant of the classical EDP-M protocol (etoposide, doxorubicin, cisplatin, mitotane). However, clinical translation of novel therapeutic regimens remains challenging due to high tumor heterogeneity. Thus, to obtain preclinical results with more clinically predictive power we investigated for ...

Only two human cell lines are available for adrenocortical carcinoma (ACC) which do not reflect the functional heterogeneity of individual patient tumors and metastases. To overcome the lack of preclinical models for testing of novel therapeutic options in recent years we aimed at the development of patient-individual tumor models for endocrine tumors. Therefore, pieces of surgically excised patient tumors were implanted subcutaneously in the neck of athymic nude mice. To inve...

The cardiovascular outcome of targeted treatment of primary aldosteronism (PA) has not been prospectively studied in large cohorts. Using the data of the prospective German Conn’s registry we evaluated the effect of adrenalectomy (ADX) vs mineralocorticoid-receptor-antagonists (MRA) treatment on blood pressure (BP), serum potassium, eGFR, pro-BNP, number and WHO DDD of antihypertensive drugs. Since 2008, 181 patients have been newly diagnosed with PA and underwent subtype...

ASA404 (Vadimezan) belongs to a class of agents with disrupting properties against tumor vasculature. Herein, putative therapeutic applicability was investigated in preclinical models for neuroendocrine tumors of the gastroenteropancreatic system (BON) and adrenocortical carcinoma (NCIh295). Upon treatment of tumor bearing mice we detected a significant disruption of microvessels, decrease in cell proliferation, increase of apoptotic cells and extensive necrosis in BON tumors ...

Scattered case reports have described patients who have been diagnosed with both primary hyperaldosteronism and prolactinoma. Prolactin receptor (PRLR) is known to be expressed in human adrenal cortex. Furthermore, PRLR mRNA and protein have both been detected in human adrenal tumors. It has also been shown that PRL treatment of adrenal cells is capable of stimulating aldosterone secretion. The contribution of PRL to the development of hyperaldosteronism is u...

Adrenal vein sampling (AVS) is a technically demanding procedure required for identification of suitable candidates for unilateral adrenalectomy in primary aldosteronism. Recently, somatic mutations in aldosterone producing adenomas (APA) have become a focus of research. We identified KCNJ5 K+-channel mutations in 34% of APAs, and more recently mutations in 2 ATPase family members in 11 and 6%. However, it is unclear whether steroid gradients during the AVS are infl...

Context: Primary aldosteronism (PA) represents the most frequent cause of a curable secondary arterial hypertension. Conflicting data have been published regarding the effect of aldosterone excess on glucose and lipid metabolism.Objective: Our aim was to analyze insulin sensitivity and beta cell function in a cohort of PA patients. Prospective follow-up investigations were performed in a subgroup of patients before and after adrenalectomy to assess the m...

Introduction: Rats carrying a germline loss-of-function mutation in p27 (MENX syndrome) develop bilateral pheochromcoytoma (PCC) with complete penetrance. Gene expression profiling of rat PCCs identified genes highly expressed in tumors vs normal adrenal medulla. Several of them were found up-regulated also in human PCCs (both sporadic and familial), including the BMP7 gene encoding a member of the bone morphogenic protein family. BMP7 has been shown to be involved in other hu...

In an attempt to amend the lack of preclinical models for endocrine tumors, we recently initiated establishment of patient-individual tumor models. Pieces from four adrenocortical carcinomas (ACC), one aldosterone producing adenoma (APA), one pheochromocytoma (pheo), one metastasis of a malignant pheo, one pheo and medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2 and 11 neuroendocrine tumors (NETs, nine NETs of the gastroenteropancreatic system i...

Potassium channels regulate the membrane voltage of aldosterone-producing glomerulosa cells in the adrenal glands. They are required for the unique K+ sensitivity of these cells and are targets of angiotensin II signaling. Several K+ channels show high levels of expression in the adrenal cortex and are believed to be important for the control of hormone secretion, e.g. KCNJ5, TASK1, TASK3, KCNMA1, and KCNQ1.In a pioneering study, Li...