Endocrine Abstracts

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...

Introduction: Corticotroph pituitary adenomas that cause Cushing’s disease (CD) predominantly express the dopamine 2 receptor (D2) and somatostatin receptor subtype (sst) 5. The expression of sst2 is relatively low because of downregulating effects of high endogenous cortisol levels. This may explain why the sst2-preferring somatostatin analog octreotide is not effective in CD. To assess whether normalization of urinary free cortisol (UFC) excretion modulates the sst expr...

Introduction: Cushing’s disease (CD) is characterized by various symptoms, amongst which fatigue, muscle weakness and depression. The chronic state of hypercortisolism severely impairs quality of life (QoL). In addition, the physiological cortisol diurnal rhythm (CDR) is disturbed in CD. Transsphenoidal surgery is the primary treatment for CD, but long-term remission rates are disappointing. We performed a prospective trial in which stepwise medical treatment was applied ...

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...

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...

Background: Novel treatment options are required for patients with adrenocortical carcinomas (ACCs). mTOR-inhibitors are anti-neoplastic drugs that target the mTOR-pathway.Aim: To describe the expression of the mTOR-pathway in normal and pathological adrenocortical tissues.Methods: We evaluated mRNA expression levels of mTOR, S6K and 4EBP1 in 10 normal adrenals (NA), 11 adrenal hyperplasias (AH), 19 adrenal adenomas (ACA) and 26 AC...

Introduction: The diagnosis of Cushing’s Syndrome (CS) and in particular cyclic CS can be complicated. Standard screening tests for CS are the measurement of cortisol in 24-hours urine collections and in midnight saliva. In case of cyclic CS, results of these tests can be normal in between periods of hypercortisolism. The development of a method to measure cortisol in scalp hair provides the opportunity to investigate historical cortisol levels of months to years ago, wit...

Introduction: Neuroendocrine tumors (NET) are rare tumors originating from various types of neuroendocrine cells. The somatostatin receptor type 2 (sst2) is expressed in NET cells and is a target for therapy with somatostatin analogues.Epigenetic changes including methylation of DNA at CpG dinucleotides, and particularly in the promoter region of genes can inhibit transcription. Methylation can be inhibited by cytidine analogues such as 5-aza-...

Background: The mechanism underlying the spontaneous improvement of rheumatoid arthritis (RA) during pregnancy and the subsequent post-partum flare is incompletely understood. The glucocorticoid receptor (GR) polymorphisms Bcl1 and 9β are associated with an increased and decreased glucocorticoid sensitivity respectively. We examined the relation between carriership of these functional GR polymorphisms and disease course during pregnancy and post-partum in RA...