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

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