Short Synacthen Test 🧪

• Diagnose adrenal insufficiency. Under normal circumstances pituitary ACTH stimulates cortisol secretion from the adrenal gland; Synacthen (synthetic ACTH / tetracosactrin) has a similar effect. In adrenal insufficiency there is an inadequate response.
• In adrenal insufficiency there is reduced production of mineralocorticoids and glucocorticoids. Common causes: glucocorticoid treatment, autoimmune adrenal destruction, TB, and adrenalectomy.
• Addison's disease / adrenal failure may be primary (adrenal), secondary (pituitary ACTH synthesis), or tertiary (hypothalamic).

• If 8–10 am cortisol >350 nmol/L, SST is usually not required for assessment.
• Previous hypersensitivity reaction to ACTH.
• Severe atopic allergies (especially asthma): avoid SST.
• Pregnancy.

• Stop HRT or oestrogen-containing contraceptives 6 weeks before. If this is not appropriate, discuss with a clinical biochemist.
• Some steroids cross-react with the cortisol assay. If the patient is already taking steroids, discuss with endocrinology before starting the SST.
• Ideally perform the test between 08:00 and 10:00.
• Admission is only required if at risk of Addisonian crisis (virtually never). Synacthen is a "red" drug on some formularies; follow local referral/prescribing rules.

• Request on the local electronic system so correct labels and test codes are generated.
• Label all sample bottles with patient ID and time of collection.
• At baseline (0 min): take cortisol (serum tube).
• If an inpatient: also take ACTH (EDTA / purple tube) and send to the lab immediately, packed on ice.
• Give IM Synacthen 250 mcg (adult dose).
• At 30 and 60 minutes: take cortisol (serum tube).
• Send all serum tubes to the lab together; do not send them separately.

• Basal cortisol should be greater than 180 nmol/L.
• 30 min or 60 min cortisol should be greater than 420 nmol/L (whatever the basal level).
• The increment should be at least 170 nmol/L, apart from in severely ill patients where adrenal output is already maximal.
• If the patient is taking oestrogens, post-Synacthen cortisol should be greater than 640 nmol/L.
• These cut-offs reflect the North Bristol NHS Trust protocol for their Roche assay method. Confirm local laboratory reference limits before interpreting.

• If the cortisol response is suboptimal and ACTH was sent, it is measured to distinguish primary from secondary adrenal failure. ACTH cannot usually be sent from primary care because of sampling requirements (ice, prompt processing).
• A normal cortisol response does not exclude adrenal failure. Impending adrenal failure may be associated with greater loss of zona glomerulosa function, suggested by elevated plasma renin activity.
• If the result is equivocal and there is no urgency, repeat the test after a few weeks.

• SST can help diagnose and characterise 21-hydroxylase deficiency and other causes of adrenal hyperplasia.
• Perform SST in the follicular phase because 17-hydroxyprogesterone (17OHP) rises after ovulation.
• On the samples taken for cortisol, also request 17OHP.
• In suspected 21-hydroxylase deficiency, a marked rise in 17OHP after ACTH stimulation (>30 nmol/L) supports the diagnosis; response varies between homozygous and heterozygous states (New et al., JCEM 1983).

• Synacthen can rarely provoke hypersensitivity reactions, which tend to be more severe (anaphylactic shock) in patients with atopic allergies, especially asthma.
• Reactions may include injection-site skin reactions, dizziness, nausea, vomiting, urticaria, pruritus, flushing, malaise, dyspnoea, and angioneurotic oedema. They tend to set in within 30 minutes; keep the patient under observation during this time.
• In anaphylaxis: adrenaline 0.5 mg as 0.5 mL of 0.1% (1:1000) IM, repeat every 5 minutes as necessary; then hydrocortisone 200 mg IV and chlorphenamine 10 mg IV slowly over at least 1 minute. Follow local anaphylaxis / Resuscitation Council guidance.

• NBT cut-offs were agreed after literature review, discussion with endocrinology, and published cut-offs for their Roche assay.
• Patients taking oestrogens have a significant positive bias post-Synacthen due to increased cortisol-binding globulin (CBG) and assay interference; lower reference limits on the combined oral contraceptive pill around 643 nmol/L have been quoted with mass spectrometry.
• CBG is increased in pregnancy, combined oral contraceptive pill, and HRT, and may be decreased in liver and renal disease.

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