Endocrine Abstracts

For a long time it has been assumed that patients with adrenal insufficiency (AI) can live without any restriction when receiving standard hormone replacement therapy.However, recent evidence indicates that subjective health status (SHS) in patients with primary adrenal insufficiency is significantly impaired at least in a subgroup of patients and that mortality is increased compared to the general population.The observation of imp...

Molecular imaging technologies are emerging tools providing both researchers and clinicians with technologies for non invasive in vivo studies. Steroidogenic enzymes are abundantly and specifically expressed in steroidogenic tissue and represent an interesting target for tissue specific characterization. Iodometomidate is a highly potent inhibitor of cortisol and aldosterone synthesis due to specific and high affinity binding to both CYP11B1- and CYP11B2-enzymes. Our ai...

Quality of life (QoL) is significantly impaired in patients with primary and secondary adrenal insufficiency (AI) irrespective of the glucocorticoid dosing regimen or the currently available glucocorticoid preparation. The impairment of QoL has been particularly attributed to the unphysiological mode of glucocorticoid replacement, which only roughly resembles the physiological profile. In both congenital adrenal hyperplasia (CAH) and Addison's disease, failure in cortisol synt...

Introduction: Polymorphisms of the glucocorticoid (NR3C1) and mineralocorticoid receptor (NR3C2) have been linked to the regulation of HPA-axis and to glucocorticoid sensitivity. We investigated whether NR3C1 and NR3C2 polymorphisms correlate with the occurence of adrenal crises (AC) in patients with primary adrenal insufficiency (PAI).Material and methods: We investigated 100 patients with PAI (70% women, mean age 51±15 years). DNA was extracted fr...

Background: Mitotane is a strong inducer of hepatic CYP3A4 activity (cortisol metabolism) and increases cortisol-binding globulin (CBG). High hydrocortisone dosages are necessary in patients with adrenocortical cancer (ACC) on mitotane treatment. The newly modified release hydrocortisone has not been used in mitotane-treated ACC patients yet.Aim: To compare cortisol (serum and saliva), calculated free serum cortisol and ACTH levels in ACC patients on mit...

ACC is a rare, heterogeneous malignancy with poor prognosis. Data from the German ACC Registry (n=478) indicate a 5-year survival rate of 47%. In addition to mitotane, cytotoxic drugs are standard of care in advanced ACC. The best results have been reported by Berruti et al. for the combination of mitotane with etoposide, doxorubicin and cisplatin with an objective tumor response rate of 49% in 72 patients. A response rate of 36% was published for the combination...

Available glucocorticoid (GC) replacement regimens in adrenal insufficiency (AI) only roughly correspond to physiological steroid profiles. Control of substitution quality is therefore difficult but significant, as even mild chronic over- or under-replacement may be clinically relevant. FKBP5 regulates GC receptor sensitivity by reducing its affinity to cortisol when bound to the receptor complex. FKBP5 methylation has been inversely correlated with cortisol levels both in hea...

Background: Potentially fatal adrenal crises (AC) still occur in educated patients with adrenal insufficiency (AI). Identifying predisposing factors is necessary for prevention in this patient population.Objectives: Investigating clinical and biochemical fingerprints of increased susceptibility to AC.Material and methods: Our study population included 260 patients with chronic AI, classified as high and low risk according to the fr...

Background: The chemokine receptor CXCR4 and its associate receptor CXCR7, that modulates CXCR4 function, have been associated with tumor progression and metastasis in human cancers. In ACC, Ki67 index and ENSAT stage are the most important prognostic parameters.Objective: To assess expression of CXCR4 and CXCR7 in adrenal cancer and correlate results with clinical outcome.Methods: CR expression was assessed by immunohistochemistry...

Introduction: Although long-term complications such as nephrocalcinosis and renal insufficiency are well-known in chronic hypoparathyroidism (HPT), standardized investigations of their prevalence and causes are still lacking.Objective: To systematically investigate the prevalence of renal calcifications and dysfunction and their predictors in a well-characterized cohort of patients with HPT.Methods: Cross-sectional assessment of co...