FDA (US): Approved (Cortrosyn and generics) as a diagnostic agent to detect adrenal insufficiency in adults and children
EMA (EU): No centralized authorization; authorized through national procedures in European countries (Synacthen and other presentations), for diagnosis and, in depot form, with therapeutic uses
Dose
Diagnostic test: 0.25 mg intravenously or intramuscularly in adults and children aged 2 years or older (0.125 mg from 0 to 2 years), with baseline cortisol and at 30 and 60 minutes; a stimulated value below 18 µg/dL suggests insufficiency (FDA label Cortrosyn). A low-dose test (1 µg) is also used in studies.
Safety
Well tolerated as a single dose. Rare allergic reactions, including anaphylaxis, more likely in people with allergies or asthma. Changes in heart rate, high blood pressure, and edema have also been described. Given in a healthcare setting.
Interactions
Corticosteroids and spironolactone can falsely raise cortisol; stop them on the day of the test or before (FDA label).
Differences between women and men
Estrogen-containing drugs (contraceptives, hormone therapy) raise cortisol-binding globulin and total cortisol, which can give falsely normal results. The FDA label advises stopping them 4–6 weeks before the test or measuring that protein. In pregnancy, no increase in risks has been seen and diagnosis should not be delayed.
Effect by goal · level of evidence
Diagnostic accuracy in adrenal insufficiency
improvesLow-moderatemeta-analysis (AAA)in people
Sensitivity 92% (primary)
Meta-analysis of 30 studies in secondary adrenal insufficiency (1,209 adults and 228 children) and 5 in primary. High-dose (250 µg) and low-dose (1 µg) tests had similar accuracy: they are useful to confirm, but not to rule out, secondary insufficiency. In primary insufficiency, the sensitivity of the high dose was 92%.
It activates the ACTH receptor of the adrenal glands and causes a rapid rise in cortisol. If cortisol does not rise enough at 30–60 minutes, it suggests that the adrenal glands are not responding well (adrenal insufficiency).
What the evidence says
In people
Diagnostic accuracy in adrenal insufficiency. Meta-analysis of 30 studies in secondary adrenal insufficiency (1,209 adults and 228 children) and 5 in primary. The high-dose (250 µg) and low-dose (1 µg) tests had similar accuracy: they are useful to confirm, but not to rule out, secondary insufficiency. In primary insufficiency, the sensitivity of the high dose was 92%. PubMed 26649617