ACTH Stimulation Test (Short Synacthen Test): What It Shows About Your Adrenal Glands

Ključni postupci

• The ACTH stimulation test tests the adrenal glands' capacity to respond, not the pituitary gland directly.
• A normal response makes primary adrenal insufficiency unlikely, but does not reliably exclude recent or partial pituitary (secondary) adrenal insufficiency.
• Cortisol cut-offs differ between laboratories because assays differ; your own laboratory's threshold applies.
• Steroid medicines, including inhalers, skin creams, joint injections and some ayurvedic or unlabelled "joint pain" powders, can alter the result.
• Never start, stop or reduce a prescribed steroid to prepare for the test. Speak to the prescriber first.

Na prvi pogled

Također poznat kao

In Indian labs and prescriptions you may see: Synacthen test, short Synacthen test (SST), ACTH stim test, cortisol stimulation test, cosyntropin test, ili jednostavno "adrenal function test". It is different from a plain morning cortisol or serum ACTH blood test, which are single samples with no injection.

What the ACTH stimulation test is

ACTH (adrenocorticotropic hormone) is made by the pituitary gland and tells the adrenal cortex to make cortisol. In the ACTH stimulation test, a synthetic version of ACTH is injected so the adrenal glands receive a strong, standardised signal. Blood cortisol is then measured to see whether the adrenal cortex can respond.

The standard version uses a 250 microgram dose. Some centres use a low-dose (1 microgram) variant, which is not standardised for preparation or interpretation and is used selectively. The test does not involve radiation and does not require sedation.

Why the ACTH stimulation test is done

• Suspected adrenal insufficiency: unexplained fatigue with low blood pressure, salt craving, weight loss, low sodium, high potassium, darkening of skin creases or repeated unexplained collapse.
• After long-term steroid therapy: to assess whether adrenal function has recovered, when the prescriber judges testing useful.
• Known or suspected pituitary disease: after pituitary surgery, radiotherapy, apoplexy, or in hypopituitarism, usually alongside other pituitary tests.
• Congenital adrenal hyperplasia: particularly non-classic CAH, where 17-hydroxyprogesterone is measured before and after ACTH.
• Follow-up of adrenal surgery when residual adrenal reserve is in question.

Tko bi trebao napraviti ovaj test

The ACTH stimulation test is not a screening test and is not useful for general tiredness on its own. It is appropriate when a doctor has a specific clinical suspicion, such as:

• A borderline or low early-morning cortisol already reported.
• Symptoms and biochemistry suggesting Addison's disease (hyponatraemia with hyperkalaemia, unexplained hypotension, hyperpigmentation).
• Planned withdrawal of long-term glucocorticoids, or symptoms on tapering.
• Structural pituitary disease, or previous pituitary surgery or radiotherapy.
• Infants and children with ambiguous genitalia, salt-losing crisis, early pubic hair or unexplained hypoglycaemia, assessed by a paediatric endocrinologist.
• Adults with suspected non-classic CAH presenting with hirsutism, irregular cycles or subfertility.

People already taking hydrocortisone replacement for confirmed adrenal insufficiency usually do not need repeat stimulation testing; monitoring is clinical.

What the ACTH stimulation test cannot detect or exclude

• It cannot localise the problem by itself. A poor response shows the adrenal cortex under-performed; it does not say whether the fault is adrenal, pituitary or hypothalamic. Baseline plasma ACTH, renin and aldosterone, adrenal antibodies and imaging are needed for that.
• It can miss recent secondary adrenal insufficiency. If pituitary ACTH has failed only in the past few weeks, the adrenal glands may not yet have atrophied and can still respond normally. A normal test in that setting does not exclude central adrenal insufficiency.
• It can miss partial or mild central deficiency. Insulin tolerance testing or other dynamic testing may be needed, decided by an endocrinologist.
• It does not diagnose Cushing syndrome or cortisol excess.
• It shows nothing about adrenal anatomy: no nodules, masses, haemorrhage, calcification or tuberculosis of the adrenals. That needs CT or MRI.
• It does not assess adrenal medulla function (adrenaline, noradrenaline) or phaeochromocytoma.
• It is not a thyroid, growth hormone or prolactin test, though these are often checked separately in pituitary disease.
• A normal result is "not identified", not "excluded". If your symptoms continue despite a normal ACTH stimulation test, return to your doctor rather than assuming the matter is settled.

Related but different examinations, and how they compare

These tests answer different questions. None is universally superior; which comes first depends on the clinical problem.

How to prepare for the ACTH stimulation test

Preparation is operational and differs between hospitals and laboratories. The instructions your own unit gives you take precedence over anything written here.

• Medicines list: bring every medicine and supplement, including inhalers, nasal sprays, eye drops, skin creams, joint injections, ayurvedic or homeopathic preparations and gym supplements. Several unlabelled pain and "strength" preparations sold in India contain steroids.
• Do not stop any prescribed steroid yourself. Only the prescriber can advise whether, when and how a dose is adjusted or switched before testing. Stopping steroids abruptly can be dangerous.
• Oestrogen-containing pills: oral contraceptives and hormone therapy raise cortisol-binding globulin and can raise measured total cortisol. Your doctor may advise a washout period, this is a clinical decision, not something to do on your own.
• Vremenski raspored: many units book the test in the morning; follow your appointment time.
• Post: the ACTH stimulation test itself does not usually require fasting, but some units fast patients if other tests are drawn at the same visit. Confirm with your unit.
• Time to allow: plan to be in the unit for roughly 60-90 minutes, sometimes longer if a 60-minute sample and observation are added.

If you are pregnant or breastfeeding

Cortisol and cortisol-binding globulin rise physiologically in pregnancy, so standard cut-offs do not apply and interpretation needs an endocrinologist. Tell the unit you are pregnant before any injection.

If you have diabetes on glucose-lowering treatment

If your unit asks you to fast, ask the prescriber how to handle insulin or sulfonylureas that morning, and carry glucose with you. Do not fast for long periods without that advice.

If you have heart failure, chronic kidney disease or a fluid restriction

Do not increase your fluid intake for this test. Any general "drink plenty of water" advice does not apply if you have been given a fluid limit.

Djeca

Paediatric testing uses weight-adjusted protocols and different reference expectations, and should be arranged through a paediatric endocrinology service. Bring a feed or snack, and a distraction for the cannula.

Older adults and people on multiple medicines

Review the full medicine list carefully; topical and inhaled steroids are commonly forgotten and commonly relevant.

What happens during the ACTH stimulation test

Baseline sample. Blood is drawn for cortisol, sometimes with ACTH, aldosterone, renin or 17-hydroxyprogesterone.

Injekcija. Synthetic ACTH is given into a vein or a muscle. Most people feel nothing beyond the needle; some notice brief flushing.

Repeat samples. Cortisol is measured at 30 minutes, 60 minutes, or both, depending on the protocol used.

Promatranje. Staff keep you in the unit between draws. You can usually read or sit quietly; strenuous activity is avoided.

Nakon toga. Normal activity and eating can resume unless told otherwise. There is no sedation, so you can drive yourself home unless your unit advises otherwise.

Razumijevanje vašeg izvješća

The report shows cortisol at baseline and after stimulation, usually in micrograms per decilitre (mcg/dL) or nanomoles per litre (nmol/L). Interpretation depends on:

• The peak cortisol value reached after the injection, this is the main figure.
• The specific assay used. Newer, more specific mass-spectrometry and second-generation immunoassays give lower cortisol values than older assays, so historic thresholds can over-diagnose adrenal insufficiency. Your laboratory's stated cut-off is the one that applies.
• Your clinical picture and other hormones, including baseline ACTH, sodium, potassium and any pituitary imaging.

Broadly: an adequate rise in cortisol argues against primary adrenal insufficiency; a blunted or absent rise supports it and prompts further testing to establish the cause. Because thresholds are assay-specific, this page does not quote a single numerical cut-off. No result should be self-interpreted, only the doctor who requested the test can interpret it in your clinical context.

When ACTH stimulation test results can be misleading

Falsely reassuring (cortisol appears adequate when the axis is impaired)

• Recent-onset pituitary ACTH deficiency: adrenal glands have not yet atrophied and still respond.
• Partial or mild central adrenal insufficiency, where a supraphysiological ACTH dose overwhelms a subtle defect.
• High cortisol-binding globulin from pregnancy, oral oestrogen or combined oral contraceptives, raising measured total cortisol.
• Recent exogenous hydrocortisone or prednisolone cross-reacting with some immunoassays and inflating measured cortisol. Dexamethasone does not cross-react in the same way.
• Older, less specific immunoassays reading higher than mass spectrometry.

Falsely worrying (cortisol appears low when the axis is adequate)

• Low binding proteins: nephrotic syndrome, chronic liver disease, severe malnutrition or critical illness lower total cortisol even when free cortisol is acceptable.
• Recent steroid exposure of any route suppressing the axis temporarily, including single joint injections and potent skin creams.
• Testing too soon after pituitary surgery or apoplexy.
• Interfering medicines such as mitotane, ketoconazole, metyrapone or etomidate, which block cortisol synthesis.
• Assay switch: a result that looks lower than an old report may simply reflect a newer, more specific assay, not deterioration.
• Sampling or handling errors, wrong timing, or injection not fully delivered.

Acute stress and illness generally raise cortisol rather than lower it, but severe illness changes binding proteins and makes interpretation unreliable. In acute severe illness, treatment decisions are usually made clinically rather than waiting for stimulation testing.

Rizici i sigurnost

Synthetic ACTH testing is generally well tolerated, but no injection is without risk. Results and reactions vary depending on individual clinical circumstances.

Uzorkovanje krvi

Bruising, brief pain, a small haematoma, and occasionally light-headedness or fainting. Rarely, local infection or nerve irritation at the puncture site.

Synthetic ACTH injection (cosyntropin/tetracosactide)

Flushing, mild nausea, headache or a transient rise in blood pressure can occur. Hypersensitivity reactions, including rare anaphylaxis, have been reported, risk is higher in people with a history of allergy to ACTH preparations, and units keep resuscitation facilities available. Depot (long-acting) tetracosactide has been more often associated with allergic reactions than the short-acting preparation and is not the standard agent for this test. Tell staff immediately about rash, swelling of lips or tongue, wheeze or faintness.

Low-dose variant

Side-effect profile is similar, but the dilution step introduces a risk of dosing error, which is one reason the low-dose test is not used everywhere.

Posebne situacije

Trudnoća

Physiological rises in cortisol and binding globulin mean non-pregnant cut-offs do not apply; trimester-specific interpretation by an endocrinologist is required. The test is performed in pregnancy when genuinely needed, with obstetric input.

Djeca i novorođenčad

Doses, sampling schedules and expected responses differ from adults. In suspected congenital adrenal hyperplasia, 17-hydroxyprogesterone rather than cortisol alone may be the key measurement. Paediatric endocrinology supervision is standard.

People taking long-term steroids

Prolonged oral, inhaled, topical or injected steroid use suppresses the HPA axis. Timing of the test relative to the last dose matters and is decided by the prescriber. Do not omit or reduce doses on your own initiative.

Chronic kidney disease and liver disease

Altered binding proteins and drug handling affect total cortisol. Results need interpretation alongside albumin and overall clinical state.

Kritično bolesni pacijenti

The stimulation test performs poorly in critical illness and is not recommended as the sole basis for steroid decisions in septic shock; management is clinical.

Starije odrasle osobe

Symptoms such as fatigue, low appetite and postural dizziness overlap with many other conditions and with medicine side effects, so results must be read against the whole picture.

ACTH stimulation testing in the Indian context

• Tuberculosis remains a relevant cause of primary adrenal insufficiency in India, alongside autoimmune Addison's disease. Adrenal imaging may be arranged if primary adrenal insufficiency is confirmed, and past or current TB is always asked about.
• Unregulated steroid exposure is common. Over-the-counter steroid skin creams, injectable steroids for joint pain, some proprietary "pain relief" powders, and steroid-containing gym supplements can suppress the adrenal axis. Disclosing these is important; the Drugs and Magic Remedies (Objectionable Advertisements) Act 1954 restricts advertising of such cure claims, but products still circulate.
• Dostupnost varira. Synthetic ACTH supply can be intermittent in some regions, so the test is usually performed at centres with endocrinology support and access to the injection.
• Assay variation between Indian laboratories is real. Comparing a cortisol value from one lab with a cut-off quoted by another can mislead. Where possible, use the same laboratory for serial testing.
• Privatnost podataka: personal health data collected for appointments and reports is handled under the Digital Personal Data Protection Act 2023.
• Steroid emergency information: if adrenal insufficiency is confirmed, ask for written sick-day rules, a steroid alert card, and training for an emergency hydrocortisone injection, particularly important where travel to hospital may take time.

Troškovi i osiguranje u Indiji

Charges differ widely between government hospitals, trust hospitals and private laboratories, and between cities. Costs are usually made up of:

• The synthetic ACTH injection: frequently the largest single component, and sensitive to supply and brand.
• Cortisol assays: charged per sample, so a three-sample protocol costs more than a two-sample one.
• Add-on hormones such as ACTH, aldosterone, renin or 17-hydroxyprogesterone.
• Day-care or observation charges, cannulation and nursing time.
• Naknade za konzultacije for the endocrinologist ordering and interpreting the test.
• Repeat or confirmatory testing, and any imaging that follows an abnormal result.

Insurance behaviour also varies: outpatient diagnostics are often excluded from basic indemnity policies but may be covered when the test is done during an admission or under an OPD benefit rider. Government schemes and hospital packages have their own rules. Ask the hospital billing desk for a written estimate and your insurer for pre-authorisation guidance before the appointment.

Mitovi i činjenice

Često postavljana pitanja

Koliko dugo traje ACTH stimulacijski test?

Most people are in the unit for about 60-90 minutes. That covers the baseline blood draw, the injection, a sample at 30 minutes and often another at 60 minutes, plus a short observation period. Registration, cannulation and waiting for the phlebotomy room can add time.

Trebam li gladovati prije ACTH stimulacijskog testa?

Fasting is usually not required for the ACTH stimulation test itself. Some units fast patients because other blood tests are collected at the same visit. Fasting rules are unit-specific, so confirm with the laboratory when booking, especially if you take insulin or sulfonylureas.

Is the injection painful?

The discomfort is that of a needle prick, plus one or two blood draws. Some people notice brief warmth or flushing after the injection. If needles make you anxious or faint, tell the staff beforehand so you can be positioned lying down and given extra time.

Can I take my hydrocortisone on the morning of the test?

Do not decide this yourself. Recent hydrocortisone or prednisolone can interfere with some cortisol assays and with the result's meaning. Ask the doctor who ordered the test how to handle your dose; some units switch patients temporarily to a non-interfering steroid under supervision.

What if my result is borderline?

Borderline results are common because assay cut-offs are not absolute. Your endocrinologist may repeat the test, measure baseline ACTH, renin and aldosterone, arrange imaging, or use a different dynamic test. Treatment may be started while investigation continues if symptoms are concerning.

How is this test different from a simple morning cortisol?

A morning cortisol is a single resting sample and often lands in an indeterminate range. The ACTH stimulation test challenges the adrenal glands with synthetic ACTH and measures the response, which is more informative about adrenal reserve, though still not a complete assessment of the pituitary.

Will I need the test repeated?

Often not. Once adrenal insufficiency is confirmed, monitoring is mainly clinical and dose-based. Repeat testing is mostly used when assessing recovery of the axis after long-term steroids or after pituitary surgery, and the timing is decided case by case.

Can children have this test?

Yes, with weight-adjusted dosing and paediatric protocols, arranged through a paediatric endocrinology team. In children, the test is often used to look at 17-hydroxyprogesterone for congenital adrenal hyperplasia as well as cortisol. Expected responses differ from adults.

Does the test diagnose "adrenal fatigue"?

No. "Adrenal fatigue" is not a recognised medical diagnosis, and no version of the ACTH stimulation test confirms it. The test looks for genuine adrenal insufficiency. If fatigue persists with a normal result, your doctor should look for other causes such as anaemia, thyroid disease, sleep disorders, diabetes or depression.

Izvori

• Bornstein SR, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. Časopis za kliničku endokrinologiju i metabolizam, 2016.
• Fleseriu M, et al. Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline, 2016.
• Speiser PW, et al. Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline, 2018.
• Society for Endocrinology (UK) guidance on the emergency management of adult adrenal crisis and short Synacthen testing.
• Manufacturer prescribing information for tetracosactide/cosyntropin preparations regarding hypersensitivity risk.
• Published analyses of cortisol assay-specific peak thresholds following standard-dose ACTH stimulation.