Required section · Section 2 of 6
The HPA axis and its clock
The hypothalamic-pituitary-adrenal (HPA) axis is a feedback loop. The hypothalamus releases corticotropin-releasing hormone (CRH), which drives the anterior pituitary to release ACTH, which drives the adrenal cortex to produce cortisol. Cortisol then feeds back on the hypothalamus and pituitary to restrain further CRH and ACTH release. That feedback loop is what keeps cortisol from rising without limit.
Layered on top of the feedback loop is a strong circadian rhythm. Cortisol, and ACTH with it, typically peaks near the time of waking, commonly cited as roughly 6 to 8 AM, and falls toward a nadir near midnight. A single cortisol value means something different at 7 AM than the identical number would mean at 11 PM. A patient's wake or shift schedule shifts the whole curve, so the collection clock time and the patient's schedule both have to travel with the result.
Because ACTH and cortisol are a negative-feedback pair, they are only interpretable together, drawn at the same venipuncture, at the same clock time. The paired pattern is what carries the diagnostic information: high ACTH with low cortisol points toward a primary adrenal problem, because the adrenal gland is not responding to an appropriately elevated signal. Low or inappropriately normal ACTH with low cortisol points toward a central, pituitary-driven problem, because the signal itself is deficient. A cortisol result reported without its ACTH partner, or an ACTH drawn at a different time than the cortisol, cannot support that distinction.
Treat a cortisol or ACTH order as incomplete until the requisition or the result carries a clock time, and treat an ACTH result as incomplete until its paired cortisol, drawn at the same time, is available to read alongside it.
Illustrative drawing — this picture was drawn rather than captured.
How a single ACTH/cortisol result reaches the bench, and where it can fail.
Order placed with intent
A clinician orders a basal screen, a stimulation test, or a suppression test. Each answers a different question, so the ordered test type has to be known before the result is read.
Paired collection at a documented time
ACTH and cortisol are drawn at the same venipuncture, with the clock time recorded, because their paired pattern is the diagnostic signal.
Analyte-specific handling
The ACTH plasma tube follows the chilled or ambient path required by the cited assay manufacturer, reference laboratory, or local controlled procedure; the cortisol serum tube follows its validated path. Requirements cannot be copied between systems, and a specimen that misses its applicable path is unsuitable.
Result reviewed against timing and context
Before release, the laboratory professional confirms the collection time, the handling history, and whether medication or illness could explain an unexpected value.
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