ACTH Blood Test: High, Low & the Cortisol Connection

The ACTH blood test measures the pituitary hormone that drives cortisol. Learn normal levels, what high or low ACTH means, and why it's always read with cortisol.

Published July 20, 202611 min readWritten by the Blood Analysis Team · Reviewed and verified by Julien Priour

ACTH (adrenocorticotropic hormone, or corticotropin) is a hormone made by your pituitary gland, a small gland at the base of the brain. Its job is to tell your adrenal glands to make cortisol. It is the central link in the hypothalamic-pituitary-adrenal (HPA) axis — the body's stress axis. The single most important thing to understand: ACTH is never read alone. It is always interpreted together with cortisol, because it's the ACTH-plus-cortisol pair that shows where a problem sits (in the adrenal gland or in the pituitary). This guide covers normal ACTH levels, what a high or low result means, and how it's read alongside cortisol. ACTH is part of a broader hormone panel; see also our guides to cortisol, DHEA-S, and prolactin.

Key takeaways

ACTH is the pituitary hormone that stimulates the adrenal glands to make cortisol; together they form the hypothalamic-pituitary-adrenal (HPA) axis.¹²
It is never interpreted alone: it's the combination of ACTH and cortisol that tells whether the problem is in the adrenal gland (primary) or the pituitary (secondary).³²
High ACTH + low cortisol points to primary adrenal insufficiency (Addison's disease); low ACTH + low cortisol points to secondary (pituitary) insufficiency or exogenous steroids.³⁴⁵
High or normal ACTH + high cortisol suggests Cushing disease (a pituitary adenoma) or ectopic ACTH secretion; low ACTH + high cortisol suggests an adrenal Cushing syndrome or steroid use.²⁶⁷
ACTH is a fragile, pulsatile hormone with a morning peak: the sample is drawn in the morning, often in a chilled tube delivered quickly to the lab. Indicative morning values are ~7–63 pg/mL, and they vary widely by lab and time of day.⁸¹
It is not a first-line screening test and not a cancer marker: it belongs to a specialist work-up that includes dynamic tests (dexamethasone suppression, cosyntropin/Synacthen stimulation).⁹⁵

What is ACTH?

ACTH is a peptide hormone released by the anterior pituitary. Its full name — adrenocorticotropic hormone — describes its function: it acts on the cortex (outer layer) of the adrenal glands, two small glands sitting on top of the kidneys. In response to ACTH, the adrenals make and release cortisol, the key hormone for the stress response and for regulating blood sugar, blood pressure, and inflammation.¹²

The whole system works like a three-tier chain of command, the hypothalamic-pituitary-adrenal (HPA) axis:

the hypothalamus (in the brain) releases CRH;
CRH tells the pituitary to release ACTH;
ACTH tells the adrenal glands to make cortisol.

This loop is self-regulating through negative feedback: when cortisol rises, it suppresses the hypothalamus and pituitary, so ACTH falls. That feedback loop is exactly why ACTH and cortisol are always read together.³²

ACTH is not cortisol. ACTH is the signal sent by the brain; cortisol is the end hormone produced by the adrenal gland. Measuring both shows which tier of the chain is off.

Why the test is done

ACTH is not tested routinely. Your clinician orders it in targeted situations, almost always at the same time as cortisol, to find out where an excess or a shortage of cortisol is coming from:³²⁵

to work up suspected adrenal insufficiency (severe fatigue, weight loss, dizziness, low blood pressure, salt craving, sometimes skin that darkens abnormally);
to work up a cortisol excess (Cushing syndrome): weight gain in the face and trunk, purple stretch marks, high blood pressure and blood sugar, thin fragile skin;
to localize the source of a cortisol problem already found: adrenal gland, pituitary, or an ectopic source (a tumor elsewhere in the body making ACTH);
to follow a known disorder of the HPA axis or adjust treatment, on specialist advice.

Outside these indications, ACTH adds nothing: it is not a general screening test, and the result only makes sense with cortisol and, often, dynamic tests (see below).⁹⁵

How the test is done

A strict fast is not always required, but ACTH imposes other, more important constraints because of what it is. ACTH is a fragile hormone (it degrades fast) and a rhythmic one: secretion is pulsatile and follows a 24-hour cycle, with a peak in the early morning (around 6–8 a.m.) and a trough at night. So the draw is almost always done in the morning, at a fixed time, at rest, often in a chilled (iced) tube that must be delivered quickly to the lab and spun cold — otherwise the level collapses artificially. Follow your order exactly and note the precise draw time.⁸¹

Normal ranges

Below are indicative adult reference values for a morning draw. ACTH varies a lot by time of day (circadian rhythm), stress, assay, and lab — always compare against the range printed on your report.

Time of draw	Plasma ACTH (indicative)	SI equivalent
Morning (6–10 a.m.)	~7 – 63 pg/mL	~1.5 – 13.9 pmol/L
Evening	Lower than morning	—

Units: the common unit is pg/mL; in SI units it's pmol/L (1 pg/mL ≈ 0.22 pmol/L). These cutoffs are only indicative — every lab sets its own range depending on the assay. An isolated ACTH number means almost nothing; what counts is how it matches the cortisol from the same draw. Only your clinician can interpret it in your context.¹²

Understanding your results

ACTH is interpreted together with cortisol from the same moment. Here's the reading grid clinicians use to locate the tier of the problem:³²⁵

ACTH	Cortisol	What it suggests
High	Low	Primary adrenal insufficiency (Addison's disease)
Low	Low	Secondary (pituitary) insufficiency or exogenous steroids
High / normal	High	Cushing disease (pituitary adenoma) or ectopic ACTH
Low	High	Adrenal Cushing syndrome (adrenal tumor) or steroids

High ACTH

A high ACTH means the pituitary is pushing hard. The meaning depends entirely on the cortisol:

High ACTH + low cortisol: the adrenal gland no longer responds despite maximal stimulation. This is the pattern of primary adrenal insufficiency, whose best-known cause is Addison's disease (often autoimmune). The excess ACTH explains the skin pigmentation (tanning) sometimes seen. Diagnosis is confirmed with a cosyntropin (Synacthen) stimulation test and a morning ACTH.³⁴⁵
High or normal ACTH + high cortisol: the pituitary is making too much ACTH, often from a small benign adenoma — this is Cushing disease. A deceptive variant is ectopic ACTH secretion, where a tumor elsewhere (lung, gut, and others) makes ACTH. Telling the two apart is specialist work combining imaging, dynamic tests, and sometimes inferior petrosal sinus sampling (below).²⁶⁷

Low ACTH

A low ACTH means the pituitary is no longer sending the command. Again, cortisol decides:

Low ACTH + low cortisol: this is secondary adrenal insufficiency, of pituitary origin (the pituitary isn't making enough ACTH). By far the most common cause overall is prolonged steroid (glucocorticoid) use, which quiets the axis through feedback. You never stop steroids abruptly — tapering is decided and supervised by a clinician.³⁴
Low ACTH + high cortisol: cortisol is coming from an autonomous adrenal gland (an adrenal tumor making cortisol), which suppresses ACTH. This is adrenal (ACTH-independent) Cushing syndrome. Taking steroids produces the same biochemical picture.²

The ACTH–cortisol pair (and dynamic tests)

ACTH only makes sense with cortisol, and often with dynamic tests that challenge the axis: the dexamethasone suppression test (a synthetic steroid that should normally crush cortisol) and the cosyntropin/Synacthen stimulation test (a synthetic ACTH that should normally push cortisol up). Other markers of the adrenal axis, such as DHEA-S and cortisol, and of the pituitary, such as prolactin, often round out the work-up.²⁵

ACTH and cancer? ACTH is not a screening tumor marker. Some tumors do make ACTH ectopically, but that is rare and is only chased in the setting of an already-identified Cushing syndrome — not on a routine blood draw.⁶

What affects your ACTH

Many things change ACTH: the time of day (morning peak, evening trough), physical or psychological stress, an acute illness, pregnancy, disrupted sleep (night-shift work), and above all many medications — chief among them steroids (which crash ACTH), but also drugs acting on the pituitary. Sample quality is decisive: the right tube, kept cold, delivered fast. Always report your medications (especially any form of cortisone, including creams or inhalers) and the exact draw time: they completely change the interpretation.⁸¹³

Recent research

According to recent PubMed-indexed publications:

Diagnosing Cushing syndrome: updated guidance. An international consensus (Pituitary Society, more than 50 experts) updated the algorithms for screening, diagnosis, and management of Cushing disease in 2021, clarifying the respective roles of ACTH, dynamic testing, and imaging.⁷ A recent review stresses that measuring ACTH is the pivotal step to separate ACTH-dependent Cushing (pituitary or ectopic source) from ACTH-independent (adrenal) forms.² (Reincke M & Fleseriu M, JAMA, 2023 — DOI.)
Measuring ectopic ACTH, a diagnostic challenge. An expert opinion on ectopic ACTH Cushing syndrome describes a genuine endocrine emergency: the hypercortisolism is often intense and the source tumor sometimes occult, demanding a multidisciplinary diagnostic and treatment strategy.⁶
Petrosal sinus sampling to localize the source. When ACTH is high but pituitary imaging is inconclusive, bilateral inferior petrosal sinus sampling (BIPSS) samples ACTH right next to the pituitary. A hospital series reported excellent accuracy for distinguishing Cushing disease from an ectopic source, with simultaneous prolactin measurement helping confirm correct catheter placement.¹⁰
Recognizing adrenal insufficiency earlier. Recent reviews note that a high morning ACTH with a low cortisol is often enough to raise primary adrenal insufficiency, and emphasize early recognition to prevent adrenal crisis, a life-threatening emergency.³⁴

These findings concern diagnosis and research; they do not authorize self-medication and do not replace your physician's advice.

Get your ACTH interpreted by AI DiagMe

An ACTH level is never read alone: its meaning depends entirely on your cortisol, the time of the draw, your medications (especially steroids), and your context. That cross-reading is what gives the result its real value.

👉 AI DiagMe interprets your lab results — blood, urine, or stool — in plain language, taking your whole profile into account. An informational service that does not provide a diagnosis and complements, never replaces, your physician.

Frequently asked questions

What is an ACTH blood test?

It measures adrenocorticotropic hormone (ACTH), the pituitary hormone that tells your adrenal glands to make cortisol. ACTH is the central link in the hypothalamic-pituitary-adrenal (HPA) axis, the stress axis.

What is a normal ACTH level?

In the morning, indicatively about 7–63 pg/mL (roughly 1.5–13.9 pmol/L). The level is lower in the evening and varies a lot with time of day, stress, and the assay used. Values vary by lab — read the one on your report.

Why is ACTH always tested with cortisol?

Because ACTH is the signal (from the brain) and cortisol the end hormone (from the adrenal gland). It's their combination that shows which tier is off: adrenal (primary) or pituitary (secondary). ACTH on its own is nearly uninterpretable.

What does high ACTH mean?

With a low cortisol, it points to primary adrenal insufficiency (Addison's disease). With a high cortisol, it suggests Cushing disease (a pituitary adenoma) or ectopic ACTH secretion. Only your clinician concludes, usually after dynamic tests.

What does low ACTH mean?

With a low cortisol, it suggests secondary (pituitary) insufficiency or, very often, treatment with steroids. With a high cortisol, it points to an adrenal Cushing syndrome or, again, steroids.

What symptoms might prompt this test?

For a cortisol shortage: deep fatigue, weight loss, dizziness, low blood pressure, salt craving, sometimes darkening skin. For an excess: weight gain in the face/trunk, purple stretch marks, high blood pressure and sugar, fragile skin. These deserve medical review, not self-testing.

Do I need to fast for an ACTH test?

A strict fast is not always required, but the draw must be done in the morning, at rest, often in a chilled tube delivered quickly to the lab, because ACTH is fragile. Follow your order's exact instructions, and see our guide to fasting before a blood test.

Does high ACTH mean cancer?

No. ACTH is not a cancer screening test. Some tumors do make ACTH ectopically, but that is rare and is only investigated in the setting of an already-identified Cushing syndrome, in specialist care.

Do steroids affect ACTH?

Yes, a lot. Steroids/cortisone (tablets, but also creams or prolonged inhalers) lower ACTH through feedback. That's why you should always report any steroid treatment — and why you never stop steroids abruptly without medical advice.

Bottom line

ACTH is the pituitary hormone that commands cortisol from the adrenal glands, at the heart of the stress axis. The golden rule: it is never read alone, but with cortisol — it's their pair that places a problem in the adrenal gland (primary) or the pituitary (secondary). Keep the main patterns in mind (high ACTH + low cortisol = Addison's; low ACTH + low cortisol = secondary or steroids; high/normal ACTH + high cortisol = pituitary or ectopic Cushing; low ACTH + high cortisol = adrenal Cushing), remember it's a fragile hormone (morning draw, chilled tube), and that ranges vary by lab. It is not a cancer marker. No value is read alone — it's your whole set of markers and your context that counts, which is what AI DiagMe provides, alongside your physician.

Sources

Official sources and peer-reviewed publications (PubMed) used for this guide:

Mayo Clinic Laboratories — Corticotropin (ACTH), Plasma: test overview and reference values. mayocliniclabs.com ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶
Reincke M, Fleseriu M. Cushing Syndrome: A Review. JAMA, 2023. PubMed · DOI ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰ ↩¹¹ ↩¹²
Lewis A, Thant AA, Aslam A, et al. Diagnosis and management of adrenal insufficiency. Clin Med (Lond), 2023. PubMed · DOI ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹
Husebye ES, Pearce SH, Krone NP, Kämpe O. Adrenal insufficiency. Lancet, 2021. PubMed · DOI ↩ ↩² ↩³ ↩⁴
Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 2016. PubMed · DOI ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷
Young J, Haissaguerre M, Viera-Pinto O, et al. Cushing's syndrome due to ectopic ACTH secretion: an expert operational opinion. Eur J Endocrinol, 2020. PubMed · DOI ↩ ↩² ↩³ ↩⁴
Fleseriu M, Auchus R, Bancos I, et al. Consensus on diagnosis and management of Cushing's disease: a guideline update. Lancet Diabetes Endocrinol, 2021. PubMed · DOI ↩ ↩² ↩³
MedlinePlus (U.S. National Library of Medicine, NIH) — ACTH (Adrenocorticotropic Hormone) Blood Test. medlineplus.gov ↩ ↩² ↩³
Testing.com — ACTH Test (Adrenocorticotropic Hormone). testing.com ↩ ↩²
Moreno Parro I, Ortiz Sánchez D, García Moreno R, et al. Bilateral inferior petrosal sinus sampling in the diagnosis of ACTH-dependent Cushing's syndrome: experience in a tertiary hospital. Adv Lab Med, 2022. PubMed · DOI ↩