• Publikační typ
• abstrakt z konference MeSH

Testing of the adrenal function with ACTH 1-24 (Synacthen test) or insulin (insulin tolerance test-ITT) is commonly used. The question of ongoing debate is the dose of Synacthen. Moreover, it may be important from the physiological point of view besides measurement of cortisol levels and 17α-hydroxy-progesterone to know also the response of other steroids to these test. The plasma levels of 24 free steroids and their polar conjugates were followed after stimulation of 1 μg, 10 μg and 250 μg of ACTH 1-24 and after insulin administration in thirteen healthy subjects. The study aimed to describe a response of steroid metabolome to various doses of ACTH 1-24 and to find the equivalency of these tests. The additional ambition was to contribute to understanding of physiology of these stimulation tests and suggest an additional marker for HPA axis evaluation. No increase of most conjugated steroids and even decrease of some of them during all of the Synacthen tests and ITT at 60th min were observed. The levels of steroid conjugates decreased in ITT but did not during all of the Synacthen tests by 20 min of each test. Testosterone and estradiol did not increase during the Synacthen tests or ITT as expected. The results suggest that the conjugated steroids in the circulation can serve as reserve stock for rapid conversion into free steroids in the first minutes of the stress situation. Various doses of ACTH 1-24 used in the Synacthen tests implicate earlier or later occurrence of maximal response of stimulated steroids. The equivalent dose to ITT and standard 250 μg of ACTH 1-24 seemed to be dose of 10 μg ACTH 1-24 producing the similar response in all of the steroids in the 60th min of the test.

• MeSH
• dospělí MeSH
• estradiol krev   MeSH
• hydrokortison krev   MeSH
• inzulin aplikace a dávkování   MeSH
• kosyntropin aplikace a dávkování   MeSH
• lidé MeSH
• metabolom MeSH
• nadledviny metabolismus   patologie   MeSH
• steroidy metabolismus   MeSH
• systém hypofýza - nadledviny účinky léků   patologie   MeSH
• systém hypotalamus-hypofýza metabolismus   patologie   MeSH
• testosteron krev   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Criteria for the evaluation of the insulin tolerance test (ITT) and Synacthen test are still a matter of debate. The objective of the study was to make a comparison of serum and salivary cortisol during four stimulation tests. Sixty four healthy volunteers underwent the ITT, the Synacthen test with 1 (LDST), 10 (MDST) and 250 (HDST) microg dose of ACTH. Maximum serum cortisol response was observed at the 90 min of the ITT (49 %), HDST (89 %) and MDST (56 %) and at the 40 min of the LDST (44 %). Results expressed as 95 % confidence intervals: 408.0-843.6 and 289.5-868.1 nmol/l in the IIT at 60 and 90 min. In the HDST and the MDST serum cortisol reached the maximum at 90 min 542.6-1245.5 and 444.2-871.3 nmol/l. Levels of salivary cortisol followed the same pattern as serum cortisol. Salivary cortisol reached the maximum response in the HDST and the MDST at 90 min and at 40 min in the LDST. We confirmed good reliability of all tests with respect to timing of response and maximum response compared to the ITT. We proved that the MDST test can provide the similar response in serum cortisol to the HDST. Measuring either salivary cortisol or ACTH levels did not provide any additional benefit then measuring serum cortisol by itself.

• MeSH
• dospělí MeSH
• hydrokortison analýza   krev   MeSH
• inzulin aplikace a dávkování   normy   MeSH
• inzulinová rezistence fyziologie   MeSH
• kosyntropin aplikace a dávkování   normy   MeSH
• lidé MeSH
• referenční standardy MeSH
• reprodukovatelnost výsledků MeSH
• sliny chemie   metabolismus   MeSH
• systém hypofýza - nadledviny účinky léků   metabolismus   MeSH
• systém hypotalamus-hypofýza účinky léků   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• srovnávací studie MeSH

Numerous diagnostic tests are used to evaluate the hypothalamic-pituitary-adrenal axis (HPA axis). The gold standard is still considered the insulin tolerance test (ITT), but this test has many limitations. Current guidelines therefore recommend the Synacthen test first when an HPA axis insufficiency is suspected. However, the dose of Synacthen that is diagnostically most accurate and sensitive is still a matter of debate. We investigated 15 healthy men with mean/median age 27.4/26 (SD±4.8) years, and mean/median BMI (body mass index) 25.38/24.82 (SD±3.2) kg/m2. All subjects underwent 4 dynamic tests of the HPA axis, specifically 1 μg, 10 μg, and 250 μg Synacthen (ACTH) tests and an ITT. Salivary cortisol, cortisone, pregnenolone, and DHEA (dehydroepiandrosterone) were analysed using liquid chromatography-tandem mass spectrometry. During the ITT maximum salivary cortisol levels over 12.5 nmol/l were found at 60 minutes. Maximum cortisol levels in all of the Synacthen tests were higher than this; however, demonstrating that sufficient stimulation of the adrenal glands was achieved. Cortisone reacted similarly as cortisol, i.e. we did not find any change in the ratio of cortisol to cortisone. Pregnenolone and DHEA were higher during the ITT, and their peaks preceded the cortisol peak. There was no increase of pregnenolone or DHEA in any of the Synacthen tests. We demonstrate that the 10 μg Synacthen dose is sufficient stimulus for testing the HPA axis and is also a safe and cost-effective alternative. This dose also largely eliminates both false negative and false positive results.

• MeSH
• adrenální insuficience diagnóza   metabolismus   MeSH
• chromatografie kapalinová metody   MeSH
• dehydroepiandrosteron analýza   MeSH
• diagnostické testy rutinní metody   MeSH
• dospělí MeSH
• hormony farmakologie   MeSH
• hydrokortison analýza   MeSH
• kosyntropin farmakologie   MeSH
• lidé MeSH
• pregnenolon analýza   MeSH
• sliny metabolismus   MeSH
• systém hypofýza - nadledviny metabolismus   MeSH
• systém hypotalamus-hypofýza metabolismus   MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Studies on the time course of ACTH- or insulin-induced hypoglycemia stimulating adrenal androgens are usually limited to dehydroepiandrosterone and/or its sulphate. Our data on dehydroepiandrosterone (DHEA) and its hydroxylated metabolites clearly show that measurements of DHEA and its sulphate (DHEAS) are valuable markers of the integrity of the HPA (hypothalamus-pituitary-adrenal) axis. Assessments of HPA function should rely on measurements of baseline and/or stimulated serum cortisol concentrations, and C19 Δ5-steroids may provide additional information. The art of stimulation of 7- and 16-hydroxylated metabolites of DHEA can help our understanding of the formation sequence of these compounds.

• MeSH
• adenom hypofýzy vylučující ACTH krev   diagnóza   MeSH
• adrenální insuficience krev   diagnóza   MeSH
• dehydroepiandrosteron aplikace a dávkování   MeSH
• dehydroepiandrosteronsulfát krev   MeSH
• diagnostické techniky endokrinologické MeSH
• dospělí MeSH
• hydrokortison krev   MeSH
• hypoglykemie chemicky indukované   MeSH
• lidé středního věku MeSH
• lidé MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

• Klíčová slova
• doba odběru,
• MeSH
• časové faktory MeSH
• chromatografie kapalinová MeSH
• cirkadiánní rytmus * MeSH
• hmotnostní spektrometrie MeSH
• hydrokortison * krev   metabolismus   sekrece   MeSH
• imunoanalýza MeSH
• lidé MeSH
• odběr biologického vzorku metody   MeSH
• omezení příjmu potravy MeSH
• přijímání potravy MeSH
• psychický stres * komplikace   MeSH
• radioimunoanalýza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

Předmětem řešení projektu je podrobná analýza a porovnání testů osy hypotalamus-hypofýza-nadledviny a analýza metabolitů kortizolu v průběhu těchto testů. Na základě širokého zastoupení steroidů simultánně měřených v jednotlivých vzorcích v průběhu testů zhodnotíme klíčové prvky podílející se na patofyziologii adrenální insuficience.Tento přístup nám umožní vytvoření novějších diagnostických algoritmů hypokortikalismu a norem pro kortizol ve slinách. Získáme racionální podklady pro časnou diagnostiku nemocných s postižením osy hypotalamus- hypofýza – nadledviny a také možnost včasně odhalit poruchu nadledvin u žen užívajících estrogenní terapii nebo u pacientů se změněnými koncentracemi vazebných proteinů pro kortizol, u kterých je stále hodnocení poruchy osy hypotalamus- hypofýza – nadledviny problematické. Objasnění této problematiky umožní navržení nových diagnostických a terapeutických postupů těchto onemocnění, a tím zkvalitnění péče o pacienty.; A subject of solution of the project is a detailed analysis and a comparison of hypothalamic-pituitary-adrenal axis tests and cortisol metabolites analysis during these tests. Based on a wide range of steroids simulateously measured in each sample, we will evaluate key elements contributing to the pathophysiology of adrenal insufficiency. This procedure will enable to design new diagnostic algorithms of hypocorticalism and standards for salivary cortisol. Rational supporting data for early diagnostic of patients with hypothalamic-pituitary-adrenal axis disorder will be acquired as well as a possibility to reveal adrenal disorder in patients on estrogen therapy or with altered levels of cortisol-binding proteins whose hypothalamic-pituitary-adrenal axis evaluation is always problematic. Clarifying these issues will propose new diagnostic and therapeutic procedures of such disorders resulting in enhancing quality of patient care.

• MeSH
• Addisonova nemoc diagnóza   MeSH
• adrenální insuficience MeSH
• adrenokortikotropní hormon analýza   MeSH
• časná diagnóza MeSH
• estrogenní substituční terapie MeSH
• hydrokortison MeSH
• hypoglykemie MeSH
• neurotransmiterové látky MeSH
• systém hypofýza - nadledviny MeSH
• systém hypotalamus-hypofýza MeSH
• transkortin MeSH

• Konspekt
• Fyziologie člověka a srovnávací fyziologie
• NLK Obory
• endokrinologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

Determination of response of cortisol and its metabolites to different stimuli may be important for adrenal gland disorders. To date, only one metabolite, cortisone, has been followed in stimulation tests of the adrenal gland. We aimed to describe a response of cortisol metabolites to the standard short Synacthen test (HDST), insulin tolerance test (ITT), low dose Synacthen test (LDST) and medium dose Synacthen test (MDST). Sixty healthy subjects were investigated: 30 men and 30 women. Plasma for measurements of cortisol and its metabolites was obtained before and 30th and 60th min after Synacthen and insulin administration. The cut-off 500 nmol/l of cortisol was reached after stimulation in all of tests, the maximal stimulation level was reached in 60th min in all of the tests except for LDST. The response of cortisol and its metabolites at 30th and 60th min strongly correlated in all of the tests except for LDST. Cortisol and its metabolites increased after stimulation; in contrast, cortisone and its metabolites decreased. We showed that the response of the cortisol metabolites during the Synacthen tests and ITT well correlated, and the MDST showed similar response compared to HDST. The decrease in cortisone metabolites may correspond to the regeneration of cortisol from cortisone in response to stimulation test.

• MeSH
• dospělí MeSH
• hydrokortison agonisté   krev   MeSH
• inzulin agonisté   krev   MeSH
• inzulinová rezistence fyziologie   MeSH
• kortison agonisté   krev   MeSH
• kosyntropin farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Addiction to tobacco results in an imbalance of endocrine homeostasis in both sexes. This can also have impacts on fertility problems. The male reproductive system is less susceptible than that of females, with a worsening spermiogram in smokers, the most cited effect in the literature. However, the literature is inconsistent as to the effects of smoking on steroid hormone levels in men, and there is very little data on the effects of quitting smoking in men. In this study we followed 76 men before quitting smoking, and then after 6, 12, and 24 weeks and 1 year of abstinence. We measured basic anthropomorphic data and steroid hormone levels along with steroid neuroactive metabolites using GC-MS. We demonstrate lower androgen levels in men who smoke, and these changes worsened after quitting smoking. There was a drop in SHBG already in the first week of non-smoking, and levels continued to remain low. Male smokers have lower androgen levels compared to non-smokers. The lower the initial level of androgen, the lower the likelihood of success in quitting smoking. Changes in steroid hormones proved to be a promising marker for the prediction of success in quitting smoking.

• MeSH
• dospělí MeSH
• globulin vázající pohlavní hormony metabolismus   MeSH
• kouření krev   epidemiologie   trendy   MeSH
• lidé středního věku MeSH
• lidé MeSH
• odvykání kouření * MeSH
• prospektivní studie MeSH
• testosteron krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH