Endocrine Abstracts

Background: Adrenocortical tumours consist of frequent adrenocortical adenomas (ACA) and highly malignant (ACC) with a still incompletely understood pathogenesis. Dysregulation of Notch signalling pathway is implicated in several cancers with oncogenic or tumour suppressor functions. Copy number gains and over-expression of Jagged1, a ligand of Notch receptor, was reported in ACC. The aim of the study was to evaluate the expression of Jagged1 and other Notch-r...

Recently, mutations in the PRKACA (catalytic subunit α of the PKA) gene have been identified as causative in 35% of adrenocortical adenomas (ACA) with overt Cushing’s syndrome (Beuschlein et al. 2014). These mutations lead to constitutive activation of PKA signaling and subsequently to an excessive production of cortisol. Protein kinase A is a heterotetramer consisting of two catalytic and two regulatory subunits with several isoforms (Cα, β, &#947...

Background: Copeptin is the C-terminal portion of the precursor of vasopressin. In contrast to vasopressin copeptin is stable in vitro and easy to measure. Similar kinetics of both peptides have been described in different trials. However, the physiological area of normality of copeptin has never been evaluated.Methods: We measured plasma copeptin, sodium, and osmolality levels in 93 healthy volunteers at baseline, during/after i.v. infusion of ...

Objective: We have developed (123/131I)iodometomidate (IMTO) for specific adrenal imaging and radiotherapy of adrenocortical carcinoma. IMTO binds with high affinity and specificity to the two adrenocortical enzymes aldosterone synthase (CYP11B2) and 11β-hydroxylase (CYP11B1). Metabolic analysis has revealed very rapid metabolization of IMTO both in vitro and in vivo by hepatic esterases. Due to the low metabolic stability of (123/131</su...

Introduction: Current medical treatment of adrenocortical carcinoma (ACC) is based on mitotane alone or in combination with cytotoxic chemotherapy. However, very little is known about the pharmacokinetic properties of mitotane and dosing schedules are based on clinical experience only. The aim of this study was to investigate the relationship between mitotane dose and plasma concentration comparing two pre-defined treatment regimens. Secondary objectives were to evaluate safet...

Introduction: The syndrome of inappropriate antidiuresis (SIADH) is the most common cause of hypoosmolality. Ectopic AVP hypersecretion has long been considered as the primaryn mechanism of SIADH. But different types of osmoregulatory defect in AVP release have been described in this disorder. A comprehensive characterization of these different forms of SIADH in a large cohort of patients may provide important new insights into the still incompletely understood pathophysiology...

Background: Adrenal crisis (AC) is a life-threatening complication in patients with congenital adrenal hyperplasia due to classical 21-hydroxylase deficiency (21-OHD). AC was defined as an acute state of health impairment which required i.v. glucocorticoid administration and hospital admission. No data on AC over life-time in 21-OHD is available.Study design: In a retrospective study AC was studied following two approaches: a) questionnaire-based: 122 ad...

Background: No randomized trials have been conducted in adrenocortical carcinoma (ACC) patients. Treatment recommendations for this rare but aggressive disease have been based on data from small phase II trials. We have now performed the first randomized phase III trial, comparing etoposide, doxorubicin, cisplatin, plus mitotane (EDP-M) against streptozotocin plus mitotane (Sz-M).Methods: Three-hundred and four chemotherapy-naive patients with ACC not am...

Background: The water deprivation test (WDT) with direct or indirect measurement of plasma vasopressin (AVP) is the method of choice for the differential diagnosis of the polydipsia–polyuria syndrome. In theory, direct measurement of AVP is highly attractive but hampered by technical difficulties.Objective: To evaluate the utility of copeptin, a surrogate of AVP secretion, in the diagnostic work-up of the polyuria–polydipsia syndrome, and to co...

While bariatric surgery is the most effective treatment strategy to maintain long-term weight-loss and to improve survival, it has not been shown, that bariatric surgery is as effective in craniopharyngeoma patients with hypothalamic obesity. We retrospectively analyzed weight loss and metabolic parameters in 7 craniopharyngeoma patients and 14 controls who underwent gastric banding surgery in five centers in Germany and Austria. The last before and the first patient after the...