Endocrine Abstracts

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...

Adrenal crisis (AC) is a life threatening condition in chronic adrenal insufficiency (AI). Furthermore, recent data demonstrate increased mortality in this patient group.Incidence and causes of adrenal crisis as well as general morbidity and hospitalization was assessed in 472 patients in a prospective trial. Patients were contacted via mail every 6 months and in case of AC additionally by phone to evaluate the exact circumstances of AC. Criteria for AC ...

Overexpression and aberrant activation of the insulin-like growth factor system plays a key role in tumor cell proliferation and tumorigenesis in many human tumors. Different therapies targeting IGF1-receptor (IGF1-R) have been developed and currently, some of these agents are evaluated in preclinical and early clinical trials with promising results. Moreover, recent studies have demonstrated that combined treatments with doxorubicin, enhance the efficiency of anti-IGF1-R ther...

To date, the in depth analysis of the key molecular mechanisms involved in functional autonomy and tumor formation in aldosterone producing adenomas has been hampered by the rarity of the disease and the lack of adequate tumor cell lines. Herein, we cultivated a primary cell culture of an aldosterone producing adenoma taken from a 40 year old male patient with a left sided adrenal tumor mass. The cells have been passaged 24 times and still continue to grow after nearly 11 mont...

Acromegalic patients under treatment with Octreotide LAR (Oct), 10, 20 or 30 mg were switched to Lanreotide Autogel 120 mg (Lan) at different dose intervals: 56, 42 and 28 days respectively. Just before the fourth Lan injection, IGF-I values were measured and the dose interval for the final three injections adjusted accordingly: if IGF-I values were between 1 and 2 standard deviations (S.D.) above the age and sex related mean value, no change in dose-interval wa...

Radioactive and transgenic tracing experiments indicate that in the adult adrenal stem cells persist in the periphery of the cortex, which migrate centripetally and populate the inner cortical zones upon differentiation. However, investigation of these cells has been hampered by the lack of known marker genes. Vital Hoechst dye exclusion has been described as a method for isolating a side population (SP) from mouse bone marrow, which was enriched with stem cells. Utilizing thi...

Introduction: Streptozotocin (SZ) is an active drug for the treatment of advanced adrenocortical carcinoma (ACC) in a minority of patients with an objective response rate of <10%. It has been reported that expression of glucose transporter-2 (GLUT-2) is essential for SZ to enter tumor cells and that high activity of O-6-methylguanine-DNA methyltransferase (MGMT) counteracts the alkylating effect of SZ. Therefore, we aimed to clarify the role of GLUT-2 and MGMT in the respo...