title: A Comparison of Salivary Steroid Levels during Diagnostic Tests for Adrenal Insufficiency.
abstract: 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.
authors.affiliation: Institute of Endocrinology, Prague, Czech Republic. mduskova@endo.cz.
authors.forename: Michaela
authors.initials: M
authors.lastname: Dušková
authors.affiliation: 3rd Department of Medicine - Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Šimůnková
authors.affiliation: Institute of Endocrinology, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Vítků
authors.affiliation: Institute of Endocrinology, Prague, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Sosvorová
authors.affiliation: Institute of Endocrinology, Prague, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Jandíková
authors.affiliation: Institute of Endocrinology, Prague, Czech Republic.
authors.forename: Hana
authors.initials: H
authors.lastname: Pospíšilová
authors.affiliation: Institute of Endocrinology, Prague, Czech Republic.
authors.forename: Monika
authors.initials: M
authors.lastname: Šrámková
authors.affiliation: 3rd Department of Medicine - Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Mikuláš
authors.initials: M
authors.lastname: Kosák
authors.affiliation: 3rd Department of Medicine - Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Kršek
authors.affiliation: 3rd Department of Medicine - Department of Endocrinology and Metabolism, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Václav
authors.initials: V
authors.lastname: Hána
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Magdaléna
authors.initials: M
authors.lastname: Žánová
authors.affiliation: Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
authors.forename: Drahomíra
authors.initials: D
authors.lastname: Springer
authors.affiliation: Institute of Endocrinology, Prague, Czech Republic.
authors.forename: Luboslav
authors.initials: L
authors.lastname: Stárka
mesh_terms: D000309:Adrenal Insufficiency / Q000175:diagnosis* / Q000378:metabolism; D000328:Adult; D002853:Chromatography, Liquid / Q000379:methods; D003366:Cosyntropin / Q000494:pharmacology*; D003687:Dehydroepiandrosterone / Q000032:analysis*; D003955:Diagnostic Tests, Routine / Q000379:methods; D064368:Healthy Volunteers; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism; D011284:Pregnenolone / Q000032:analysis*; D012463:Saliva / Q000378:metabolism*
chemical_list: D006728:Hormones; D003366:Cosyntropin; D003687:Dehydroepiandrosterone; D011284:Pregnenolone; D006854:Hydrocortisone
keywords: Cortisol; Cortisone; Dehydroepiandrosterone; Insulin tolerance test; Pregnenolone; Saliva; Synacthen test