Identification of human glucocorticoid response markers using integrated multi-omic analysis from a randomized crossover trial.

Background: Glucocorticoids are among the most commonly prescribed drugs, but there is no biomarker that can quantify their action. The aim of the study was to identify and validate circulating biomarkers of glucocorticoid action.

Methods: In a randomized, crossover, single-blind, discovery study, 10 subjects with primary adrenal insufficiency (and no other endocrinopathies) were admitted at the in-patient clinic and studied during physiological glucocorticoid exposure and withdrawal.

Personalized approach to growth hormone replacement in adults.

Growth hormone (GH) deficiency (GHD) in adults is well-characterized and includes abnormal body composition, reduced bone mass, an adverse cardiovascular risk profile, and impaired quality of life. In the early 1990s, it was also shown that patients with hypopituitarism without GH replacement therapy (GHRT) had excess mortality. Today, GHRT has been shown to decrease or reverse the negative effects of GHD.

Expression of GHR and Downstream Signaling Genes in Human Adipose Tissue-Relation to Obesity and Weight Change.

Context: GH is a strong regulator of metabolism. In obesity, both GH secretion and adipose tissue GHR gene expression are decreased. More detailed information on the regulation of GHR, STAT3/5, and downstream-regulated genes in human adipose tissue during diet-induced weight loss and weight gain is lacking.

Pseudoacromegaly: A Differential Diagnostic Problem for Acromegaly With a Genetic Solution.

Acromegaly is usually not a difficult condition to diagnose once the possibility of this disease has been raised. However, a few conditions present with some aspects of acromegaly or gigantism but without growth hormone (GH) excess. Such cases are described as "pseudoacromegaly" or "acromegaloidism".

Visceral Fat and Novel Biomarkers of Cardiovascular Disease in Patients With Addison's Disease: A Case-Control Study.

Context: Patients with Addison's disease (AD) have increased cardiovascular mortality.

Objective: To study visceral fat and conventional and exploratory cardiovascular risk factors in patients with AD.

Design: A cross-sectional, single-center, case-control study.

MECHANISMS IN ENDOCRINOLOGY: Clinical and pharmacogenetic aspects of the growth hormone receptor polymorphism.

Pharmacogenetics aims to maximize the beneficial effects of a medical therapy by identifying genetic finger prints from responders and non-responders and, thereby improving safety and efficacy profile of the drug. Most subjects who are deficient in growth hormone (GHD) are candidates for recombinant human GH (rhGH) therapy. To date, it is well established that even after adjustments for several clinical variables, such as age, gender, body composition and the age at onset of the GHD, response to rhGH treatment is highly variable among individuals, part of which is believed to be due to genetic factors within the GH system.

A polymorphism in the CYP17A1 gene influences the therapeutic response to steroidogenesis inhibitors in Cushing's syndrome.

Context: Steroidogenesis inhibitors, such as ketoconazole (KTZ) and metyrapone (MTP), are used to lower hypercortisolism in patients with Cushing's syndrome (CS). Cortisol normalization is not reached in all patients taking these medications.

Objective: To test the hypothesis that variants in genes affecting steroidogenesis contribute to different responses to KTZ and/or MTP in patients with CS.

Reduced DNA methylation and psychopathology following endogenous hypercortisolism - a genome-wide study.

Patients with Cushing's Syndrome (CS) in remission were used as a model to test the hypothesis that long-standing excessive cortisol exposure induces changes in DNA methylation that are associated with persisting neuropsychological consequences. Genome-wide DNA methylation was assessed in 48 women with CS in long-term remission (cases) and 16 controls matched for age, gender and education. The Fatigue impact scale and the comprehensive psychopathological rating scale were used to evaluate fatigue, depression and anxiety.

Body composition and bone mineral density in women with Cushing's syndrome in remission and the association with common genetic variants influencing glucocorticoid sensitivity.

Objective: Adverse body compositional features and low bone mineral density (BMD) are the characteristic of patients with active Cushing's syndrome (CS). The aim of this study was to evaluate body composition and BMD in women with CS in long-term remission and the influence of polymorphisms in genes affecting glucocorticoid (GC) sensitivity on these end-points.

Design, Patients And Methods: This was a cross-sectional, case-controlled study, including 50 women previously treated for CS and 50 age and gender-matched controls.

The GH receptor exon 3 deleted/full-length polymorphism is associated with central adiposity in the general population.

Objective: To test the hypothesis that the GH receptor (GHR) exon 3 deleted (d3)/full-length (fl) polymorphism influences anthropometry and body composition in the general population.

Design And Setting: The Swedish Obese Subjects (SOS) reference study is a cross-sectional population-based study, randomly selected from a population registry. A subgroup of the population-based Malmö Diet and Cancer study (MDC-CC) was used as a replication cohort.

Extracellular water and blood pressure in adults with growth hormone (GH) deficiency: a genotype-phenotype association study.

Objectives: Growth hormone deficiency (GHD) in adults is associated with decreased extracellular water volume (ECW). In response to GH replacement therapy (GHRT), ECW increases and blood pressure (BP) reduces or remains unchanged. Our primary aim was to study the association between polymorphisms in genes related to renal tubular function with ECW and BP before and 1 year after GHRT.

Common genetic variants in the glucocorticoid receptor and the 11β-hydroxysteroid dehydrogenase type 1 genes influence long-term cognitive impairments in patients with Cushing's syndrome in remission.

Context: Cognitive function is impaired in patients with Cushing's syndrome (CS) in remission.

Objective: The objective of the investigation was to study the effects of polymorphisms in genes associated with glucocorticoid (GC) sensitivity on cognitive function in patients with CS in long-term remission.

Design: This was a cross-sectional, case-controlled, single-center study.

SNPs within the GH-signaling pathway are associated with the early IGF1 response to GH replacement therapy in GHD adults.

Objective: GH-deficient (GHD) adults have reduced serum concentrations of IGF1. GH replacement therapy increases serum IGF1 concentrations, but the interindividual variation in treatment response is large and likely influenced by genetic factors. This study was designed to test the hypothesis that single-nucleotide polymorphisms (SNPs) in genes within the GH signaling pathway influence the serum IGF1 response to GH replacement.

The GH/IGF-1 axis in obesity: pathophysiology and therapeutic considerations.

Obesity has become one of the most common medical problems in developed countries, and this disorder is associated with high incidences of hypertension, dyslipidaemia, cardiovascular disease, type 2 diabetes mellitus and specific cancers. Growth hormone (GH) stimulates the production of insulin-like growth factor 1 in most tissues, and together GH and insulin-like growth factor 1 exert powerful collective actions on fat, protein and glucose metabolism. Clinical trials assessing the effects of GH treatment in patients with obesity have shown consistent reductions in total adipose tissue mass, in particular abdominal and visceral adipose tissue depots.

Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy.

Objective: GH deficiency (GHD) in adults is associated with an altered serum lipid profile that responds to GH replacement therapy (GHRT). This study evaluated the influence of polymorphisms in genes related to lipid metabolism on serum lipid profile before and after 1 year of GHRT in adults.

Design And Methods: In 318 GHD patients, total cholesterol (TC) serum concentrations, LDL-C, HDL-C, and triglycerides (TG) were assessed.

Reverse feeding suppresses the activity of the GH axis in rats and induces a preobesogenic state.

Reversed feeding (RF) is known to disrupt hormone rhythmicity and metabolism. Although these effects may be mediated in part by phase inversion of glucocorticoid secretion, the precise mechanism is incompletely characterized. In this study, we demonstrate that acute nocturnal food deprivation in male rats suppressed the amplitude of spontaneous GH secretion during the dark phase by 62% (P < 0.

Detection of genetic hypopituitarism in an adult population of idiopathic pituitary insufficiency patients with growth hormone deficiency.

Idiopathic pituitary insufficiency (IPI) is diagnosed in 10% of all hypopituitary patients. There are several known and unknown aetiologies within the IPI group. The aim of this study was to investigate an adult IPI population for genetic cause according a screening schedule.

Identification of adipocyte genes regulated by caloric intake.

Context: Changes in energy intake have marked and rapid effects on metabolic functions, and some of these effects may be due to changes in adipocyte gene expression that precede alterations in body weight.

Objective: The aim of the study was to identify adipocyte genes regulated by changes in caloric intake independent of alterations in body weight.

Research Design And Methods: Obese subjects given a very low-caloric diet followed by gradual reintroduction of ordinary food and healthy subjects subjected to overfeeding were investigated.

Rapid and high throughput genotyping of the growth hormone receptor exon 3 deleted/full-length polymorphism using a tagSNP.

Objective: The growth hormone (GH) receptor (GHR) exon 3 deleted/full-length (d3/fl) polymorphism has been suggested to affect GH sensitivity. The conventional genotyping method used for this polymorphism (multiplex PCR with fragment detection by gel electrophoresis) is laborious and requires large amount of DNA template. This has restricted analysis of this polymorphism to small cohorts.

Influence of the exon 3-deleted/full-length growth hormone (GH) receptor polymorphism on the response to GH replacement therapy in adults with severe GH deficiency.

Context: There is considerable individual variation in the clinical response to GH replacement therapy in GH deficient (GHD) adults. Useful predictors of treatment response are lacking.

Objective: The aim of the study was to assess the influence of the exon 3-deleted (d3-GHR) and full-length (fl-GHR) GH receptor isoforms on the response to GH replacement therapy in adults with severe GHD.

Cell death-inducing DFF45-like effector C is reduced by caloric restriction and regulates adipocyte lipid metabolism.

Members of the cell death-inducing DFF45-like effector (CIDE) gene family have been shown to regulate lipid metabolism. In this article, we report that the third member of the human CIDE family, CIDEC, is down-regulated in response to a reduced caloric intake. The down-regulation was demonstrated by microarray and real-time polymerase chain reaction analysis of subcutaneous adipose tissue in 2 independent studies on obese patients undergoing treatment with a very low calorie diet.