Background: - Glucocorticoids are primary stress response hormones released from the adrenal gland when an individual is under stress. Chronic or ongoing elevation of these hormones due to prolonged stress or medical treatments can have numerous harmful effects. Researchers are interested in learning more about how these hormones affect cell growth, development, and death. To study glucocorticoid hormones, researchers plan to use the medication dexamethasone, which affects the parts of cells that respond to glucocorticoid hormones. Objectives: - To study glucocorticoid stress hormones in healthy individuals before and after receiving dexamethasone. Eligibility: - Healthy individuals at least 18 years of age. - Participants must not be using certain medications that may affect the dexamethasone test, including hormonal contraception, steroid-based drugs, and some antidepressants. Design: - This study will require an initial screening visit and a second study visit. The visits are estimated to require about 1 to 2 hours of participation over a period of up to 14 days. - Participants will be screened at visit 1 with a full physical examination and medical history, and an initial blood sample for testing. - For visit 2, participants will be asked to abstain from all food and drinks except for water for 12 hours before the appointment, and will take one tablet of dexamethasone 9 hours before the appointment. - Participants will have a second blood sample taken during visit 2, and will receive a snack after the blood is drawn.

NCT01143493

Conditions

1. Glucose Homeostasis
2. Protein Metabolism
3. Lipid Metabolism
4. Respiratory Function
5. Connective Tissue Metabolism

MeSH:Metabolic Diseases

The two-sided alternative hypothesis is that there is a trend(homozygous wild-type to heterozygous to homozygous for the minor allele) in change from baseline.. Measure gene expression fold changes by microarray analysis after ex vivo glucocorticoid exposure of macrophages and lymphocytes; validation of affected RNA (elevated or decreased expression) through PCR analysis.. The secondary null hypotheses are that there are no differences among genotypes in fold-change for expression level (measured by RT-PCR for the genes selected by the microarray analysis as having differential expression), and the two-sided alternative is that there are trends.. - INCLUSION CRITERIA FOR PART 1 AND 2: - Male or female 18 years of age or older at the time of enrollment - Must be a participant in the EPR study - Are genotyped and determined to be heterozygote or homozygote carriers of one of the two hGR SNPs (hGR9B A3669G and hGR N363S) or are wild type at the SNP location - Able to understand and provide written informed consent to participate in the study - Able to travel to the CRU - Willing and able to fast for periods of up to 12 hours during the study - Healthy participants as defined by the International Red Cross guidelines (Healthy means that an individual feels well and can perform normal activities. --- A3669G --- --- N363S ---

- Active coronary artery disease (angina) or moderate to severe heart failure stage New York Heart Association III-IV - Renal failure - Glaucoma - Uncontrolled psychiatric disorders such as bipolar disorder or schizoaffective disorder - Active systemic fungal infection - Prior hypersensitivity reaction to Dexamethasone - Currently receiving treatment for cancer (certain cancers, like lung cancer make adrenocorticotropic hormone (ACTH), and all induce stress) - Any condition that, in the investigator's opinion, places the participant at undue risk for complications - INCLUSION CRITERIA FOR PART 1 AND 2: - Male or female 18 years of age or older at the time of enrollment - Must be a participant in the EPR study - Are genotyped and determined to be heterozygote or homozygote carriers of one of the two hGR SNPs (hGR9B A3669G and hGR N363S) or are wild type at the SNP location - Able to understand and provide written informed consent to participate in the study - Able to travel to the CRU - Willing and able to fast for periods of up to 12 hours during the study - Healthy participants as defined by the International Red Cross guidelines (Healthy means that an individual feels well and can perform normal activities. --- A3669G --- --- N363S ---

PRIMARY OBJECTIVE: Investigate in vivo the role of hGR SNPs (hGR9beta A3669B, hGR N363S) in steroid responsiveness by performing a modified dexamethasone suppression test and comparing responses by genotype. --- N363S ---

SECONDARY OBJECTIVE: Investigate the role of hGR SNPs (hGR9beta A3669B, hGR N363S) in human steroid responsiveness by comparing (across genotypes) gene expression profiles of isolated macrophages and lymphocytes exposed ex vivo to corticosteroids. --- N363S ---

Development of glucocorticoid (GC)-induced adrenal insufficiency is a serious adverse effect of GC treatment. It is today not possible to predict this adverse effect. The project aims at investigating a possible individual aspect, which may render subjects more or less sensitive to glucocorticoids, and thereby influence development of GC induced adrenal insufficiency. The hypothesis is that subjects with one or another of the polymorphisms in the GC receptor gene will either have increased or diminished GC sensitivity. This may be responsible for differences in development of GC induced adrenal insufficiency.

NCT01411046

Conditions

1. Rheumatoid Arthritis

Interventions

1. Diagnostic Test: Synacthen test

MeSH:Arthritis Arthritis, Rheumatoid Adrenal Insufficiency

HPO:Adrenal insufficiency Arthritis Polyarticular arthritis Rheumatoid arthritis

Patients with or without these polymorphisms were invited to a Synacthen® test, but patients with a mixed hetero- and homozygote genotype were not Exclusion Criteria: - Other major organ disease - Females pregnant - Females not willing to pause estrogen-containing medications 6 weeks prior to Synacthen® test - unable to give a written informed content Rheumatoid Arthritis Arthritis Arthritis, Rheumatoid Adrenal Insufficiency Blood is sampled from patients with rheumatoid arthritis (RA), fulfilling the inclusion criteria and patients are genotyped for the SNPs N363S, BclI, ER22/23EK and 9β and grouped according to haplotypes. --- N363S ---

The primary purpose of this study is to determine the prevalence of adrenal insufficiency in a population of patients with kidney transplants receiving low dose prednisone treatment. Development of glucocorticoid-induced adrenal insufficiency is a serious adverse effect to glucocorticoid treatment. The study includes a control group of patients with kidney failure currently treated in dialysis, who are not in glucocorticoid treatment. Individual genotyping is performed to determine the haplotype of glucocorticoid receptor polymorphisms: N363 S, BclI, ER23/23EK and 9β in all the patients with the purpose of investigating this as a risk factor for the development of adrenal insufficiency. The hypothesis is that subjects with one or another of the polymorphisms in the glucocorticoid receptor gene will either have increased or diminished glucocorticoid sensitivity. Using validated questionnaires assessing the quality of life and functional level of the patients enrolled in the study we aim to establish a link between functional level and biochemically proven adrenal insufficiency. Other secondary outcomes in the study includes bloodpressure, body composition, bone density, metabolic syndrome, inflammation and salivary cortisol profiles.

NCT03136562

Conditions

1. Adrenal Insufficiency

Interventions

1. Diagnostic Test: Synacthen test

MeSH:Adrenal Insufficiency

HPO:Adrenal insufficiency

The primary outcome measure of this study is the result of the Synacthen® test using primarily the level of P-cortisol 30 minutes after the injection of synacthen.. Cutoff for normal adrenal function: 30 min p-cortisol >/= 420 nmol/L.. Registration of history of treatment.. History of treatment with prednisone and other types of glucocorticoids to examine dosage and time of treatment as risk factors.. Quality of life and functional level.. Assessed in all patients enrolled in the study using validated questionnaires as a means to establish a link between functional level and biochemically proven adrenal insufficiency.. Determination of the specific type of glucocorticoid receptor using genotyping in all the patients with the purpose of investigating this as a risk factor for the development of adrenal insufficiency.. Patients are genotyped for 4 polymorphisms (9 beta, ER22/23EK, Bcl1 and N363S) of the glucocorticoid receptor.. Body composition. --- N363S ---

To investigate the correlation between four well-known polymorphisms of the glucocorticoid receptor gene (two with reduced sensitivity versus two with increased sensitivity) and the prevalence of secondary adrenal insufficiency in glucocorticoid-treated patients with exacerbation of COPD.

NCT03140761

Conditions

1. Adrenal Insufficiency

MeSH:Adrenal Insufficiency

HPO:Adrenal insufficiency

Inclusion Criteria: - Adult patients > 18 years - Caucasian classified with COPD - Patients with AECOPD being treated with at least 5 days of glucocorticoid (minimum of 180 mg) Exclusion Criteria: - Treated with estrogen-containing medications, including anticonceptiva 6 weeks prior to Synacthen® - Pregnancy or lactation - on regular systemic glucocorticoid therapy before admission to the hospital - People who are detained under the act on the use of coercion in psychiatry - Severe language problems or inability to provide written informed consent Inclusion Criteria: - Adult patients > 18 years - Caucasian classified with COPD - Patients with AECOPD being treated with at least 5 days of glucocorticoid (minimum of 180 mg) Exclusion Criteria: - Treated with estrogen-containing medications, including anticonceptiva 6 weeks prior to Synacthen® - Pregnancy or lactation - on regular systemic glucocorticoid therapy before admission to the hospital - People who are detained under the act on the use of coercion in psychiatry - Severe language problems or inability to provide written informed consent Adrenal Insufficiency Adrenal Insufficiency COPD patients who have received systemic glucocorticoid exceeding the equivalent of 180 mg prednisolone which are homo / heterozygous for the BclI and / or N363S polymorphisms (associated with increased glucocorticoid sensitivity) will have a lower cortisol response in a synacthen® test (greater suppression of adrenal corticosteroid) than the corresponding patients there are wild-type or homo- or heterozygous for the polymorphic ER22 / 23EK and / or 9β (associated with decreased sensitivity). --- N363S ---

Within this clinical study patients with chronic adrenal insufficiency will be investigated by clinical and biochemical examination as well as questionnaire to identify predisposing factors for adrenal crisis.

NCT03410160

Conditions

1. Adrenal Insufficiency

Interventions

1. Diagnostic Test: Clinical and biochemical examination.

MeSH:Adrenal Insufficiency

HPO:Adrenal insufficiency

Evaluation of glucocorticoid-receptor-polymorphisms (ER 22/23 EK, N363S, bcl1, 9beta, Tth3l). --- N363S ---