Endocrine Abstracts

Objectives: To determine if a single intra- or peri-articular injection of corticosteroid for post-traumatic or microtraumatic skeleton injuries in healthy young subjects would induce a suppression of hypothalamo-pituitary-adrenal axis activity and reactivity.Methods: 10 young healthy male sportsmen (28.8±2.5 years) received a single intra- or peri-articular injection of either cortivazol or betamethasone for post-traumatic or microtraumatic skeleto...

Introduction: As an alternative to cortisol assays in the serum or saliva to diagnose hypercorticisme we evaluated the ability of a commercial cortisol assay to assess capillary blood cortisol concentrations using routine procedures.Methods: Capillary blood was obtained using a device used by diabetics to routinely assess capillary glucose levels and deposited on Schleicher-Scheull 903 blotter paper (routinely used for neonatal diagnosis of hypothyroidis...

Cushing’s syndrome is rare in males. Hypercortisolic consequences on male gonadal function are unknown. The aim of our study is to research gonadal and sexual abnormalities in 17 male subjects with endogenous cortisol excess: 10 Cushing’s diseases, 5 paraneoplastic Cushing syndrome, 1 malignant corticosurrenaloma, 1 micronodular dysplasia. Their mean age=30.2 years (18–50). Our work is based an anamnestic, clinical and hormonal results. Our population is compare...

Glucocorticoid hormones play a key role in glucose, fat and protein metabolism and dampen immune and inflammatory reactions. Synthetic equivalents are widely used as therapeutic drugs. Upon hormone binding, the glucocorticoid receptor (GR) detaches from a cytoplasmic multiprotein complex, translocates to the nucleus and regulates the transcription of target genes either directly or indirectly through interference with other transcription regulators.While...

Aim: To assess hormonal function of cortex of adrenal glands in patients (pts) after cardiac arrest (CA) and its role for survival.Material: CA-pts- 52 pts after CA in the age 62±13 years. 26 pts died after CA (CA-D-pts), 26 pts survived and were discharged from hospital (CA-S-pts). H-pts- 22 pts in the age 60±11 years with stable coronary artery disease.Methods: In CA-pts concentrations(conc) of adrenocorticotropin (ACTH...

The aim of this publication is to address an attention to possible misdiagnosis in patients with 17-alpha-hydroxylase deficiency.A 24 year old woman was admitted to our Centre with diagnosis of aldosteroma (aldosterone – 486 pmol/l (22–478), hypertension, hypokaliemia, adrenal mass (d–2.2 sm) defined by ultra sound). At the age of 15 years the patient was diagnosed with testicular feminisation as the cause of absent puberty (karyotype &#15...

In order to evaluate hypothalamic-pituitary-adrenal activity in diabetic patients in relation to neuroautonomic balance, we studied 50 consecutive hospitalized T2D patients (22F, 28M) without symptoms of neuropathy or hypercortisolism. We measured: morning, midnight and post-dexamethasone suppression cortisol (F8, F24 and F-Dex respectively) 24-hours urinary free cortisol (UFC), morning ACTH, systolic and diastolic blood pressure levels (SBP, DBP) and performed deep-breathing ...

Androgens are increasingly known to play an important role in female health, development and well being. Alongside a controversial increase in androgen therapy there is a realisation that what actually constitutes androgen insufficiency is poorly understood. The aim of this study was to establish circadian profiles for salivary testosterone in healthy women from the age of 19 through 69 year old at 3 points during the menstrual cycle. Females were subdivided into these groups:...

The purpose: to study prevalence of classical forms of 21-hydroxylasae deficiency according to the results of neonatal screening on a congenital adrenal hyperplasia (CAH) in Tyumen, Russia.The analysis of neonatal screening on CAH results in Tyumen for the period of 2003–2004. For the period under research 20011 newborn have been tested on the 17-OHP level. Measurement of 17-hydroxyprogesterone in blood samples was done in the central laboratory by ...

Ion and fluid transport mechanisms within the eye are important for several key physiological processes including the maintenance of corneal transparency and the regulation of intraocular pressure (IOP). The mechanism involved in epithelial sodium transport in the eye is regulated by corticosteroids and at a pre-receptor level, by 11β-hydroxysteroid dehydrogenase (11β-HSD) activity. Recent studies localised type 1 (11β-HSD1), an oxo-reductase that activates cort...

Androgens play an important part in follicular development, sexual behavior, maintenance of skeletal homeostasis, normal affect and cognitive function. The negative influence of androgen deficiency is widely discussed in postmenopausal women. However, there is a cohort of young women with gonadal steroid deficit caused by the disorders of central regulation. It is well known that these patients are in lack of estrogens however their androgen status is not detailed.<p class...

Background: A functioning Hypothalamo-pituitary-adrenal (HPA) axis is essential for life. Prolonged high circulating levels of glucocorticoids inhibit pituitary Pro-opiomelanocortin (POMC) gene expression. Repression continues even in the absence of continued glucocorticoid exposure. To date there are no molecular explanations for this observation.Hypothesis: Long-term exposure to glucocorticoids causes de-novo DNA methylation of the pituit...

Three siblings of Pakistani origin presented shortly after birth with failure to thrive and hyperkalemia and were found to have isolated hyperreninaemic hypoaldosteronism. They were all well controlled on fludrocortisone therapy during childhood and adolescence. When reassessed in adult life off fludrocortisone treatment, hyperreninaemic hypoaldosteronism was confirmed in all subjects, but with significant hyperkalemia in only one case. None of the subjects developed orthostat...

Tissue inflammation is usually transient but in diseases such as rheumatoid arthritis (RA) inflammation persists. It remains unclear why inflammation persists in some tissues and not in others. Recent studies have shown that stromal cells such as fibroblasts play a pivotal role in determining this persisitance. We have hypothesized that glucocorticoid (GC) activation via the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) within fibroblasts plays a key role in ...

Primary hyperaldosteronism secondary to bilateral adrenal hyperplasia (BAH) bears striking similarities pathophysiologically to essential hypertension. During stimulation studies to elucidate possible aberrant aldosterone responses in BAH we measured the aldosterone response to 250mcg iv synacthen after 30 and 60 minutes in 7 patients with BAH and in 20 healthy controls. Patients had diuretics withheld for at least 4 weeks and betablockers and calcium channel blockers withheld...

Tissue inflammation is usually transient but in diseases such as rheumatoid arthritis (RA) inflammation persists. It remains unclear why inflammation persists in some tissues and not in others. Recent studies have shown that stromal cells such as fibroblasts play a pivotal role in determining this persisitance. We have hypothesized that glucocorticoid (GC) activation via the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) within fibroblasts plays a key role in ...

Introduction: Paediatric Cushing’s disease is rare and up to 50% have incomplete cure.1 Besides hypopituitarism growth failure is particularly common and maybe due to GH deficiency, target tissue resistance2 or accelerated skeletal maturation 3. Our patient is an 18-year-old obese male who first presented at the age of 16 with delayed puberty and short stature.Results: His 24 hr urinary cortisol was 1472 nmol/l, ACTH...

Corticosteroids can be synthesised in tissues other than the adrenal cortex but the contribution of this extra-adrenal corticosteroidogenesis to circulating levels in man is not known. We studied this in a group 10 subjects taking chronic glucocorticoid replacement following bilateral adrenalectomy. In phase 1, they were maintained on cortisol alone (30 mg/day). In phase 2, cortisol was replaced by dexamethasone (2 mg/day) and in phase 3, they received both cortisol and dexame...

The pathological effects of glucocorticoids (GC) are exemplified by patients with Cushing’s syndrome who develop central obesity, insulin resistance and in some cases, type 2 diabetes mellitus. It is generally accepted that GC cause insulin resistance, however, both insulin and GC increase adipocyte differentiation. The question therefore arises as to how GC stimulate adipocyte differentiation whilst apparently making adipocytes insulin resistant. We have hypothesized tha...

BXL-628 is a non-hypercalcemic calcitriol analog successfully tested in a phase IIa trial for benign prostate hyperplasia therapy. Because part of low urinary tract symptoms (LUTS) are generated by overactive bladder (OAB) and bladder expresses the calcitriol receptor (VDR), we investigated the BXL-628 effects on bladder contractility and RhoA/ROK signalling activated in OAB, by in vivo (2-weeks; 30 mcg/Kg, Sprague-Dawley, SD, and spontaneously hypertensive rats, SHR) a...

Primary aldosteronism is diagnosed with increasing frequency, especially between patients with hypertension. Thus, a reliable screening test is necessary to avoid costly and demanding diagnostic procedures to this population. The aim of the present study is the evaluation of aldosterone to renine ratio (A/R) in the diagnostic algorithm of patients with hypertension with or without adrenal insidentaloma.A total of 115 subjects were studied: 13 patients wi...

Introduction: Unconjugated oestriol (uE3) is often measured in maternal serum during second trimester prenatal screening. While oestriol itself has little physiological importance, low values can indicate the presence of a disorder in feto-placental synthesis with potential health implications. Fetal steroids pass through the maternal circulation and into the urine so analysis of maternal fluids can be used for diagnosing causes of low oestriol.<p class="...

Although hydrocortisone is the standard replacement therapy for primary or secondary adrenal insufficiency (AI), there are limited data on dosage requirements and the value of salivary monitoring in this patient group. We assessed inter-individual variability in cortisol metabolism and relationships between plasma and salivary cortisol profiles in 27 patients. Ten (3 male) patients had primary AI and 17 (8 male) secondary AI. Salivary and plasma cortisol levels were measured a...

Increased dietary intake of polyunsaturated fatty acids (PUFAs) has been reported to be associated with a decreased incidence of cardiovascular disease. Increased dietary intake of polyunsaturated fatty acids (PUFAs) has been reported to be associated with a decreased incidence of cardiovascular disease. We have recently reported that ovarian steroid synthesis in ewes fed a diet high in n-3 PUFAs is significantly compromised1. Hence in this study we have assessed th...

The mineralocorticoid hormone aldosterone is secreted by the adrenal cortex. It plays a major role in maintaining water and electrolyte balance and hence blood pressure homeostasis by the kidneys. The aldosterone synthesizing zona glomerulosa of the adrenal cortex is a highly vascularized region. This allows a complex and articulated interaction between the steroidogenic cells and the vascular endothelial cells regulating the hormonal output.In this stud...

Bile acids inhibit glucocorticoid and mineralocorticoid metabolism. However bile acids may also influence hormone action by modulating steroidogenesis in the adrenal gland. In rodents adrenal cholesterol supply for steroidogenesis is derived from circulating HDL through the actions of scavenger receptor SR-B1. Since hepatic SR-B1 expression is known to be regulated by bile acids, we have investigated whether adrenal SR-B1 is similarly affected and, if so, whether adrenal lipid...

One microgram ACTH (adrenocorticotropin) test is considered to have higher sensitivity for early diagnosis of subclinical hypoadrenalism. In the test, the response of total serum cortisol concentration after ACTH application is evaluated. The concentration of total cortisol in serum is influenced by various diseases and drugs (containing oestrogens) that affect the concentration of cortisol binding proteins and subsequently measured cortisol levels. By routine laboratory metho...

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease resulting from adrenal unresponsiveness to ACTH. Patients present in early childhood with hyperpigmentation, hypoglycaemic episodes and seizures secondary to glucocorticoid deficiency. If left untreated this condition is fatal. Mineralocorticoid production is normal. Mutations in the ACTH receptor have been well described and account for approximately 25% of cases. We describe 3 additional novel mut...

Dehydroepiandrosterone (DHEA) and its sulphate ester DHEAS are neurosteroids with potential effects on neurogenesis, neuronal survival and neuronal stem cells proliferation. DHEA is produced by the inner adrenocortical zone, which is in direct contact to the adrenomedullary chromaffin. Unlike the closely related sympathetic neurons, chromaffin cells are able to proliferate throughout the life span. The aim of the present study was to examine in vitro the effect of DHEA ...

Glucocorticoid Receptor (GR) levels are increased in response to glucocorticoids (GC) in T-lymphoma cell lines susceptible to GC-induced cell death (GICD). The GR gene is transcribed from 5 promoters generating alternate first exons, 1A-1E, with 1A expression restricted to immune tissue and the cortex of the brain. Expression of the 1A-containing variant correlates with susceptibility to GICD in mouse thymocytes. Here we describe the time course of GC induction of total GR mRN...

The prevalence of obesity and its association with many health complications have evoked a high interest in adipose tissue metabolism. In man, glucocorticoid (GC) excess increases fat mass and the risk of developing Metabolic Syndrome. The enzyme responsible for modifying intracellular GC concentrations in adipose tissue is 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). The aim of this study was to characterise the novel human preadipocyte cell line (Chub-S7) an...

Oestrogens are capable of inducing rat prolactin gene transcription through liganded Oestrogen Receptor (ER) binding a degenerate oestrogen response element (ERE) sequence on the promoter 1440 bp upstream of the transcription start site. ER binding is thought to interact with DNA bound Pit-1 leading to chromatin looping bringing enhancer elements into proximity with the transcription start site. This ERE sequence, TGTCActaTGTCA, differs from the consensus GGTCAnnnTGACC by two ...

The melanocortin-2 receptor accessory protein (MRAP) is a type I integral membrane protein that is required for cell surface expression of the melanocortin 2 receptor (MC2R). Mutations in the N-terminal region of this protein are associated with familial glucocorticoid deficiency type II (OMIM#607398).Here we have investigated the expression and biochemical properties of MRAP using polyclonal antibodies to a conserved peptide sequence in the N-terminal r...

Oestrogens are essential regulators of fertility in women. They induce changes in uterine cell function by binding to oestrogen receptors (ERs) two of which (ERα and ERß) have been identified. ERα and ERß share significant sequence homology with three other steroid receptor superfamily members that are known as oestrogen related receptors alpha (ERRα), beta (ERRß) and gamma (ERRγ). ERRs bind as monomers to the sequence TNAAGGTCA and as dimers...

Background: Although it is well known that glucocorticosteroids induce insulin resistance, probably due to postreceptor defects, the exact time scale is still a matter of debate.Objective: The aim of the present study was to determine the time scale of effects of therapeutic doses of glucocorticoids on insulin sensitivity.Methods: Study group consisted of 20 patients with Graves ophtalmopathy who were treated with corticosteroids f...

Arachidonic acid (AA) metabolites derived from cytochrome P450 enzymes regulate vascular tone and renal tubular function. The cytochrome P450 4A (Cyp4A) enzymes are responsible for the synthesis of 20- hydroxyeicosatetraenoic (20-HETE), the most abundantly produced AA Cyp P450 metabolite in the kidney. Cyp4a expression and the production of 20-HETE, have been implicated in the development of hypertension. Here we have investigated the expression of various renal isoforms of Cy...

Glucocorticoids (Gcs) act via the glucocorticoid receptor (GR) to inhibit proliferation of many epithelial cell types, and induce apoptosis in others, notably lymphoblastic leukemia. Resistance to Gcs occurs in human small cell lung cancer (SCLC), manifest clinically as dysregulated secretion of ACTH-related peptides. Currently nothing is known of the biological consequences such resistance causes. We have previously shown that a panel of human SCLC cell lines secrete ACTH rel...

Mifepristone (RU38486) is a progesterone and glucocorticoid receptor antagonist which is used clinically to induce medical abortion, and as a research tool, e.g., in metabolic syndrome and depression. We aimed to develop a sensitive method to detect and quantify mifepristone in human plasma.Analyses were developed using a Surveyor HPLC system, with a mobile phase of methanol:ammonium acetate (5 mM) (70:30; 0.4 ml/min) and a C18 column (5 μm; 2.1&#21...

Introduction: The development of colorectal cancer is influenced by dietary as well as growth factors. Butyrate, (NaB) one of the metabolic by-products of bacterial fermentation of dietary fibre is a primary source of energy for colonic mucosa. It has growth-promoting effects on normal colonic epithelial cells, induces cell cycle arrest, differentiation and apoptosis in colorectal cancer cells. Since it has been suggested that the apoptotic effects of NaB may be due to its syn...

Decreased bone mineral density (BMD) and disturbances in glucose metabolism are common complications of Cushing’s disease. Many recent studies have shown that hyperinsulinemia in type 2 diabetes mellitus (DM) may lead to higher BMD as compared to healthy individuals. The aim of the present study was to investigate the possible relationships between BMD, serum markers of bone metabolism and plasma cortisol concentrations. The second objective was to determine whether the p...

Many previous studies have shown decreased bone mineral density (BMD) in patients with endogenous hypercortisolism, although data on the severity of bone disease are contradictory. There are very sparse data about the correlations between plasma cortisol concentrations and BMD.The study included 188 patients with clinically inactive adrenal adenomas (IAA) and 30 patients with ACTH-independent Cushing’s syndrome (CS) due to adrenocortical adenomas. A...

Without adequate treatment patients with acromegaly die prematurely from cardiovascular disease (CVD); however the contribution of atherosclerosis in this process is controversial. Increased carotid IMT is an early morphological marker of atherosclerosis and predictor of subsequent cardiovascular events. Contradictory data exist regarding IMT in patients with acromegaly.We measured carotid IMT in 79 patients with acromegaly (47 male, mean age 55±14 ...

Insulin-like factor 3 (INSL3), a member of the relaxin-insulin family, is produced in the Leydig cells and at reduced levels in ovarian thecal cells. As ovaries from most of PCOS are characterized by an hyperplasia of the theca interna, we hypothesized that INSL3 could be overproduced in PCOS women and therefore that circulating levels of this hormone could became a new marker for the syndrome. Forty lean and obese women with PCOS and 20 controls comparable for age and weight ...

The 5′ UTR of the glucocorticoid receptor plays a key role in determining tissue specific expression, and protein isoforms. Analysis of the 5′ UTR of the hGR has revealed 11 splice variants of the hGR exon 1, based on 7 exon 1 s, 4 of which (1-D to 1-F and 1-H) were previously unknown. All of the exon 1 variants have unique splice donor sites and share a common exon 2 splice acceptor site. Due to an upstream in-frame TGA stop codon the predicted translation from al...