ACTH Plasma Test

Description

What is the ACTH Plasma Test?

The ACTH Plasma Test from BiomarkersLabs.com measures Adrenocorticotrophic Hormone — the anterior pituitary hormone that drives cortisol production in the adrenal cortex and is the central regulator of the hypothalamic-pituitary-adrenal (HPA) axis. ACTH is secreted by corticotroph cells of the anterior pituitary in response to corticotrophin-releasing hormone (CRH) from the hypothalamus, and acts on the adrenal cortex to stimulate the synthesis and release of cortisol, DHEA, and other corticosteroids. The primary clinical utility of ACTH measurement is as a differential diagnostic tool — it determines the anatomical source of HPA axis pathology by identifying whether an adrenal disorder is being driven by excessive or deficient pituitary ACTH signalling, or whether the adrenal gland itself is the primary source of dysfunction. No other single investigation can discriminate ACTH-dependent from ACTH-independent adrenal disease as directly and efficiently as plasma ACTH measured alongside a concurrent cortisol. Specimens are processed through CLIA-certified partner laboratories (Quest Diagnostics and LabCorp) for USA orders, with IVDR-compliant partner laboratories serving EU and UK practitioners. Results are delivered to your secure BiomarkersLabs.com practitioner portal within 1–3 business days of confirmed specimen receipt.

ACTH follows a strict and reproducible diurnal secretion pattern — concentrations peak at approximately 6–8am as part of the circadian cortisol awakening response, then decline progressively throughout the day to reach nadir levels in the late evening and overnight. This diurnal variation is not incidental background noise — it is the physiological basis of the HPA axis rhythm, and derangement of this pattern is itself a diagnostic feature of Cushing’s syndrome. Critically, an ACTH result is only clinically interpretable if collected at the correct time of day. An ACTH measured at 2pm will produce a value in the lower half of the reference range in any healthy individual — a value that is indistinguishable from the ACTH suppression seen in adrenal Cushing’s syndrome or secondary adrenal insufficiency. Morning collection between 8:00 and 9:00am is therefore not a preference but a clinical requirement for this test. Beyond timing, ACTH is one of the most labile hormones in clinical laboratory practice — the intact peptide is rapidly degraded by plasma proteases at room temperature, requiring collection into an EDTA plasma tube, immediate placement on ice, centrifugation within 15 minutes of collection, and frozen transport to the processing laboratory. Failure at any step in this pre-analytical chain produces falsely low ACTH results that can lead to incorrect diagnosis.

The ACTH Plasma Test is available within the Thyroid & Endocrine and Adrenal & Stress categories at BiomarkersLabs.com. It is most informative when ordered alongside AM cortisol (BML-ADR-001) from a concurrent blood draw — the ACTH:cortisol relationship at 8–9am is the fundamental diagnostic pattern that drives all adrenal and HPA axis differential diagnosis. ACTH alone, without a concurrent cortisol, cannot be fully interpreted. CLIA-certified (USA) and IVDR-compliant (EU/UK). Licensed practitioners only.

What does this test measure?

ACTH (Adrenocorticotrophic Hormone — Plasma) — A 39-amino acid peptide hormone secreted by the anterior pituitary corticotroph cells, measured by chemiluminescent immunoassay in EDTA plasma and reported in pg/mL with laboratory-specific reference ranges applied according to collection time. Morning ACTH reference range is approximately 7–63 pg/mL — results above this range indicate excessive pituitary or ectopic ACTH drive; results below this range indicate pituitary suppression or failure. The ACTH:cortisol pattern at morning collection defines the four principal HPA axis diagnostic states: elevated ACTH with elevated cortisol indicates ACTH-dependent Cushing’s syndrome (Cushing’s disease from a pituitary adenoma, or ectopic ACTH syndrome from a tumour); markedly elevated ACTH with low cortisol indicates primary adrenal insufficiency (Addison’s disease — the pituitary is appropriately attempting to stimulate an adrenal gland that cannot respond); low or undetectable ACTH with low cortisol indicates secondary adrenal insufficiency (pituitary ACTH secretion is impaired, adrenal response is absent due to lack of stimulation); suppressed ACTH with elevated cortisol indicates ACTH-independent Cushing’s syndrome (an adrenal adenoma, carcinoma, or bilateral adrenal hyperplasia is producing cortisol autonomously, suppressing pituitary ACTH through negative feedback).

Clinical indications

Suspected Cushing’s syndrome — ACTH-dependent versus ACTH-independent differential — the single most critical application of plasma ACTH; an elevated ACTH alongside elevated cortisol confirms ACTH-dependent disease (pituitary or ectopic source) and triggers imaging and further dynamic testing; a suppressed ACTH alongside elevated cortisol confirms ACTH-independent disease (primary adrenal source) and directs investigation toward adrenal imaging.

Suspected Addison’s disease (primary adrenal insufficiency) — a patient with fatigue, postural hypotension, hyperpigmentation, hyponatraemia, and hyperkalaemia where primary adrenal failure is suspected; markedly elevated ACTH alongside low morning cortisol confirms the diagnosis of primary adrenal insufficiency by demonstrating intact pituitary drive in the face of adrenal unresponsiveness.

Secondary adrenal insufficiency investigation — patients with features of adrenal insufficiency without the hyperpigmentation of Addison’s disease, or patients with known pituitary pathology, head trauma, or cranial irradiation where central ACTH deficiency is the suspected mechanism; low or undetectable ACTH alongside low cortisol confirms the pituitary origin of the adrenal insufficiency and directs the clinical workup toward pituitary imaging and broader pituitary function assessment.

Abnormal cortisol requiring HPA axis characterisation — a patient with an unexpectedly elevated or suppressed morning cortisol on initial assessment where ACTH measurement is required to determine whether the cortisol abnormality is pituitary-driven (ACTH-dependent) or adrenal-autonomous (ACTH-independent).

Pituitary function assessment — as part of a broader anterior pituitary hormone panel in patients with pituitary adenoma, pituitary surgery, pituitary irradiation, empty sella, or known pituitary disease where ACTH reserve and basal HPA axis function require characterisation.

Ectopic ACTH-secreting tumour investigation — patients with severe hypercortisolism, hypokalaemia, and markedly elevated ACTH where a non-pituitary ACTH-secreting tumour — most commonly a small cell lung carcinoma, bronchial carcinoid, pancreatic neuroendocrine tumour, or thymic carcinoid — is the suspected source; markedly elevated ACTH values (often above 200 pg/mL) with a clinical picture disproportionate to typical Cushing’s disease raise the index of suspicion for ectopic ACTH production.

Sample type and collection

Sample Type: Blood (plasma — EDTA)

Fasting Required: Yes — morning collection between 8:00 and 9:00am is required. ACTH follows a strict diurnal rhythm with peak secretion at 6–8am. Collection outside this window produces results that cannot be reliably compared to morning reference ranges and will lead to incorrect clinical interpretation. Fasting is preferred but the primary requirement is correct timing — a non-fasted 8am specimen is clinically acceptable and preferable to a fasted but late-collected specimen.

Collection Method: Venepuncture at an approved collection site. USA patients attend a Quest Diagnostics or LabCorp patient service centre using the requisition generated through your BiomarkersLabs.com portal. EU, UK, and Canada patients are directed to partner collection networks in their region.

Critical Pre-Analytical Requirements: ACTH is one of the most labile hormones in routine laboratory practice and has strict pre-analytical handling requirements that differ from all other tests in the BiomarkersLabs.com thyroid and endocrine range. Collection must be into an EDTA (lavender-top or purple-top) plasma tube — not a serum separator tube. Immediately after collection, the tube must be placed on ice and transported to the processing facility for centrifugation within 15 minutes. The separated plasma must be frozen at -20°C or below until analysis. Failure to follow these steps results in ACTH degradation by plasma proteases and produces falsely low results. Quest Diagnostics and LabCorp collection sites follow standardised ACTH handling protocols — patients attending these sites do not require special preparation beyond arriving for an 8:00–9:00am morning collection.

Turnaround time

1–3 business days from confirmed specimen receipt at the processing laboratory. Turnaround begins upon confirmed specimen receipt — not from the date of patient collection. The ordering practitioner receives an automated email notification when results are available in their BiomarkersLabs.com practitioner portal. Results are never sent to the patient and are not accessible outside the verified practitioner portal.

Availability

USA · EU · UK · Canada

Available to licensed practitioners ordering for patients in all US states. This test does not carry a New York state restriction — it can be ordered for patients in New York without limitation. For EU, UK, and Canadian practitioners, ordering and collection logistics are managed through your BiomarkersLabs.com portal on registration.

Compliance and certifications

CLIA Certified — All USA specimens processed by CLIA-certified Quest Diagnostics and LabCorp partner laboratories meeting federal standards for clinical laboratory quality.

IVDR Compliant — EU and UK specimens processed in compliance with the EU In Vitro Diagnostic Regulation (EU) 2017/746.

CE Marked — All diagnostic assays used for EU and UK specimens carry CE marking confirming conformity with applicable European IVD standards.

HIPAA Compliant — All USA patient data handled in full compliance with HIPAA. Results delivered to the ordering practitioner’s portal only — never to the patient.

GDPR Compliant — All EU and UK practitioner and patient data processed in accordance with the General Data Protection Regulation.

PIPEDA Compliant — Canadian data handled in compliance with the Personal Information Protection and Electronic Documents Act.

How to order

This test is available exclusively to licensed healthcare practitioners. Register free at BiomarkersLabs.com — licence verification takes 1–2 business days. USA practitioners with a valid NPI number are verified automatically. Once your account is active, search for the ACTH Plasma Test in your portal, enter patient details, and submit the order. Your patient receives a requisition with instructions for an 8:00–9:00am morning collection at their nearest approved collection site. Results are returned to your portal within 1–3 business days of specimen receipt. All pricing is visible after login — no subscription required, pay per test.

This test is available exclusively to licensed healthcare practitioners. Results are delivered to the ordering practitioner’s secure portal only — never directly to patients. Licence verification required (1–2 business days). BiomarkersLabs.com does not accept patient self-referrals.

Frequently Asked Questions — ACTH Plasma Test

What does the ACTH test measure and why must it always be interpreted alongside cortisol?

The ACTH test measures the plasma concentration of adrenocorticotrophic hormone — the pituitary signal that drives cortisol production in the adrenal cortex. ACTH alone tells you whether the pituitary is generating a cortisol stimulus that is high, normal, or low. It does not tell you whether the adrenal gland is responding appropriately to that stimulus. The diagnostic power of ACTH emerges entirely from its relationship with concurrent cortisol — the ACTH:cortisol pattern identifies the anatomical source of the disorder. High ACTH with high cortisol points to pituitary or ectopic ACTH-driven disease. High ACTH with low cortisol points to primary adrenal failure where the pituitary is working correctly but the adrenal gland cannot respond. Low ACTH with low cortisol points to pituitary failure where the adrenal gland has no stimulus to produce cortisol. Low ACTH with high cortisol points to autonomous adrenal cortisol production that is suppressing pituitary ACTH through negative feedback. Without a concurrent cortisol, an ACTH number in isolation cannot be interpreted.

Why is morning collection between 8:00 and 9:00am so critical for this test?

ACTH follows a strict circadian rhythm driven by the suprachiasmatic nucleus of the hypothalamus — it peaks at approximately 6–8am as part of the cortisol awakening response that prepares the body for the physiological demands of the day, then declines progressively to its nadir in the late evening and overnight. The reference ranges applied to ACTH results are calibrated to morning peak collections between 8:00 and 9:00am. A specimen collected at 2pm in a healthy individual will produce an ACTH in the lower half of the reference range or even below it — a value that is clinically indistinguishable from the ACTH suppression seen in adrenal Cushing’s syndrome or secondary adrenal insufficiency. Ordering a late-afternoon ACTH and receiving a low result is a diagnostic pitfall that leads directly to unnecessary further investigation of a healthy HPA axis. Morning collection is not a recommendation — it is the only collection time that produces a clinically interpretable result.

Which laboratory processes the ACTH Plasma Test on BiomarkersLabs.com?

For USA practitioners, ACTH plasma specimens are processed by Quest Diagnostics or LabCorp — CLIA-certified national reference laboratories with standardised ACTH handling protocols including EDTA collection, immediate ice placement, prompt centrifugation, and frozen plasma transport. Your patient attends their nearest Quest or LabCorp patient service centre for an 8:00–9:00am morning collection using the requisition generated through your BiomarkersLabs.com portal. For EU, UK, and Canadian practitioners, specimens are processed by IVDR-compliant regional partner laboratories. All processing details are confirmed in your portal at the point of ordering.

What is the difference between Cushing’s disease, Cushing’s syndrome, and ectopic ACTH syndrome?

Cushing’s syndrome is the clinical syndrome of glucocorticoid excess — centripetal obesity, proximal myopathy, purple striae, easy bruising, hypertension, glucose intolerance, and osteoporosis — regardless of the underlying cause. Cushing’s disease is a specific subtype of Cushing’s syndrome caused by a pituitary corticotroph adenoma that secretes ACTH autonomously, driving bilateral adrenal hyperplasia and cortisol excess — it accounts for approximately 70% of endogenous Cushing’s syndrome. In Cushing’s disease, ACTH is elevated but typically only modestly — the pituitary adenoma retains partial feedback sensitivity. Ectopic ACTH syndrome occurs when a non-pituitary tumour — most commonly a small cell lung carcinoma, bronchial carcinoid, or pancreatic neuroendocrine tumour — secretes ACTH completely autonomously without feedback sensitivity, producing markedly elevated ACTH (often above 200 pg/mL) and very high cortisol, frequently accompanied by profound hypokalaemia. ACTH-independent Cushing’s syndrome occurs when the adrenal gland itself produces cortisol autonomously through an adenoma, carcinoma, or bilateral hyperplasia — in this scenario, ACTH is suppressed by the high cortisol through negative feedback. Plasma ACTH is the first discriminating test that separates ACTH-dependent (pituitary or ectopic) from ACTH-independent (adrenal) disease.

What is Addison’s disease and how does ACTH confirm the diagnosis?

Addison’s disease is primary adrenal insufficiency — destruction or dysfunction of the adrenal cortex resulting in deficient production of cortisol and aldosterone. The most common cause in developed countries is autoimmune adrenal destruction, followed by granulomatous infiltration, adrenal haemorrhage, metastatic malignancy, and genetic disorders. In primary adrenal insufficiency, the adrenal gland cannot produce cortisol despite receiving a normal or increased pituitary ACTH signal — the result is low morning cortisol alongside markedly elevated ACTH, as the pituitary appropriately attempts to compensate for the cortisol deficit by dramatically increasing ACTH secretion. Morning ACTH values in untreated Addison’s disease are typically well above the upper limit of normal — often in the range of 200–1000 pg/mL. A markedly elevated morning ACTH alongside a low or borderline morning cortisol, in a patient with the clinical features of adrenal insufficiency, is the defining biochemical pattern of Addison’s disease. The short Synacthen stimulation test is typically then performed to confirm the adrenal cortex’s inability to respond to exogenous ACTH.

Is the ACTH Plasma Test available for patients in New York state?

Yes. The ACTH Plasma Test does not carry a New York state restriction. Licensed practitioners in New York can order this test for their patients without limitation through BiomarkersLabs.com.

How quickly will ACTH results be available in my practitioner portal?

Results are available in your BiomarkersLabs.com practitioner portal within 1–3 business days from confirmed specimen receipt at the processing laboratory. You receive an automated email notification when results are ready. Results are accessible only through your secure verified portal — they are never sent to the patient, never shared in plain text, and not accessible to anyone outside your practitioner account.