Endocrine Abstracts

Cranial radiotherapy is widely used in combination with chemotherapy to treat patients with primary brain tumours. Increased survival has lead to the recognition of long term sequelae, including endocrine dysfunction due to radiation-induced hypothalamic–pituitary damage. Here we assessed health-related quality of life and endocrine function in 31 adult long term survivors (median age 45, range 29–65 years; 21M, 10F) of primary brain tumours outside the hypothalamic&...

Objective: There is evidence that current replacement regimens fail to restore well-being in patients with adrenal insufficiency (AI). No data is available on the effect of different therapeutical regimes (hydrocortisone, prednisolone and cortisone acetate) on the quality of life in these patients.Methods: Eight hundred and eighty three patients with adrenal insufficiency were contacted, 526 patients participated (60%) and received a disease specific que...

Adrenocortical carcinoma (ACC) is a rare and heterogeneous malignancy with incompletely understood pathogenesis and poor prognosis. Recent data from the German ACC Registry (n=377) demonstrate an overall 5-year survival of 46%. Survival is clearly stage-dependent (P<0.01) with a 5-year survival of 85% in stage 1, 56% in stage 2, 42% in stage 3, and 16% in stage 4, respectively.In stages I –III open surgery by an expert surgeon aimi...

Androgen excess is a key feature of polycystic ovarian syndrome (PCOS). Pre-receptor regulation contributes to this with increased activation of testosterone (T) to 5α-dihydrotesterone (DHT) by 5α-reductase type 1 (SRD5A1), as we have shown previously in PCOS (Lancet 1990,335:431; JCE&M 2003,88:2760). Peripheral blood mononuclear cells (PBMCs) are easily accessible and a useful model for studying pre-receptor regulation in the immune compartment. We have previous...

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...