Endocrine Abstracts

SWJ Lamberts, Erasmus MC, Rotterdam, Netherlands. AbstractSteven Lamberts is Professor of Medicine at Erasmus Medical Center in Rotterdam, The Netherlands. He has a special interest in endocrinology, notably pituitary diseases, the endocrinology of aging, glucocorticoid sensitivity and neuroendocrine tumours.He serves as an editorial board member on a number of endocrine and medical journals and ...

Generalized Glucocorticoid Resistance (GR) is rare. Only about 30 patients and (asymptomatic) family members with GR have been described. The molecular basis of GR has been elucidated in nine patients and affected family members: mutations in the hormone binding domain of the glucocorticoid receptor gene were responsible for the clinical manifestations of GR, while in one individual a mutation in the DNA-binding domain was observed. Clinical presentation varied, including hypo...

Dent’s disease is a renal proximal tubular Fanconi disorder characterised by generalised loss of solutes incuding insulin, glucose, PTH, amino acids and vitamin-D binding protein and is associated with rickets in 25% and phosphaturia in ~40% of patients. Dent’s disease is caused by mutations in the chloride/proton antiporter CLC-5, which, with megalin and cubilin has a role in receptor-mediated endocytosis and vesicle trafficking. To further elucidate the role of CLC...

Studies on the distribution of Somatostatin Receptor (sst)-subtypes on endocrine tumors, the development of sst-subtype specific analogues, the elucidation of phenomena like receptor desensitization and ligand-receptor internalization, and the potential consequences (and reversal) of the epigenetic silencing of sst offer new diagnostic and therapeutic modalities in endocrine diseases:1. apart from sst2 activation, Somatostatin analogues target...

Dent’s disease, due to mutations in the chloride/proton antiporter, CLC-5, represents one form of familial hypophosphataemic rickets. Dent’s disease patients also have: low-molecular-weight-proteinuria; hypercalciuria with nephrolithiasis and renal failure; and urinary loss of parathyroid hormone and vitamin D-binding protein, due to defective receptor-mediated endocytosis within the renal proximal tubule. However, there is variability in these clinical phenotypes su...

Receptor-mediated endocytosis (RME), involving megalin and cubilin, mediates renal proximal-tubular reabsorption of glucose, proteins and hormones including insulin, parathyroid-hormone and vitamin D. RME disruption occurs in Dent’s disease patients with mutations of the chloride/proton antiporter, CLC-5, who suffer from low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis and renal failure. To further investigate the RME role of CLC-5 we established conditio...

Dent’s disease is a renal proximal tubular disorder characterised by low-molecular-weight proteinuria, glycosuria, hypercalciuria, phosphaturia, nephrolithiasis and abnormal urinary loss of other proteins which include insulin, parathyroid hormone (PTH) and vitamin D-binding protein, due to defective receptor-mediated endocytosis (RME). Mutations in CLC-5 cause Dent’s disease-1 whilst mutations in OCRL1 cause Dent’s disease-2 and the oculocerebrorenal syndrome o...

Considerable overlap in IGF-I levels exists between normal and severely GHD subjects; the mechanisms underlying this observation remain poorly understood. Under various clinical circumstances therefore, IGF-I estimation is an unreliable marker of GH status. A polymorphism in the IGF-I gene influences IGF-I levels in normal populations; a higher IGF-I is associated with the presence of 2 wild type alleles of the IGF-I gene (WTG). The possibility that an IGF-I gene polymorphism ...

Introduction: The incidence of obesity and other features of the metabolic syndrome is increased in shift workers. This may be due to a misalignment between the internal circadian rhythm and the behavioral rhythm. The stress hormone cortisol could play a role in this phenomenon, because it is secreted in a circadian rhythm, and long-term elevated cortisol levels leads to components of the metabolic syndrome. Our aim was to study changes in long-term cortisol levels due to shif...

Preliminary data suggested an increased mortality in a French cohort after childhood somatropin treatment compared to the French reference population1. This cohort included patients (pts) with idiopathic-isolated GH-deficiency (GHD), and a similar cohort is also under follow-up for adult GH-replacement in HypoCCS.We therefore assessed all-cause mortality rates (n/1000 person-years (PY), (95% CI), standardized to the age/gender structure...