Cosyntropin

In plain language

Cosyntropin is a diagnostic injection, sold as Cortrosyn, used to test whether the adrenal glands can still make cortisol. It is a copy of the first 24 amino acids of ACTH, the pituitary hormone that drives the adrenal glands.

The test is simple: inject cosyntropin, measure cortisol in the blood 30 to 60 minutes later, and see if the adrenal glands responded. A failed response points to adrenal insufficiency, such as Addison's disease.

For students

Cosyntropin is synthetic ACTH(1-24) (about 2,933 Da), retaining the full corticotropic activity of the 39-residue parent hormone while losing the melanocyte-stimulating and opioid-like regions (ACTH shares its precursor, POMC, with MSH and beta-endorphin, a classic teaching point in prohormone processing).

The standard 250 mcg stimulation test (with a low-dose 1 mcg variant for milder deficiency) measures cortisol at 30 or 60 minutes; a peak below roughly 18 mcg/dL (500 nmol/L) at 60 minutes supports primary adrenal insufficiency when paired with a simultaneously high ACTH. The test distinguishes primary (adrenal) failure from secondary (pituitary) causes: in primary disease the adrenal cortex is destroyed and cannot respond, while in secondary disease prolonged ACTH deprivation causes atrophy that a single bolus may not fully overcome, an interpretive nuance that shapes guideline practice.

For researchers and instructors

Biochemistry. POMC (proopiomelanocortin) processing into ACTH, alpha-MSH and beta-endorphin is the structural lesson; the 1-24 truncation keeps the receptor-binding pharmacophore while dropping residues 25-39, which contribute to MSH-like activity and degradation.

Pharmacology. 250 mcg IV or IM bolus; cortisol sampled at 30 and/or 60 minutes; low-dose 1 mcg test has higher sensitivity for partial deficiency; rare hypersensitivity reactions occur with repeated use.

Human evidence. Decades of validation against insulin tolerance and metyrapone tests; large cohort performance data underpin guideline cutoffs (e.g., Endocrine Society 2016 adrenal insufficiency guideline).

Teaching point. The archetype of a diagnostic peptide drug: a hormone fragment repurposed as a functional test of an endocrine axis.