Synacthen Test

• Synacthen (Tetracosactrin) is a synthetic analogue, comprising amino acids 1-24 of the 39 amino acid peptide Adenocorticotrophic Hormone (ACTH).
• This sequence retains the full biological activity of intact ACTH.
• Synacthen stimulates the normal adrenal cortex to secrete cortisol, which can then be measured in serum.

INDICATIONS

• The short Synacthen test is a simple procedure for investigating reduced adreno-cortical function and adrenocortical reserve.
• It is a screening test and abnormal responses need to be followed up with further tests and an endocrinology opinion
• Prednisolone and hydrocortisone cross react with cortisol assays, but the short synacthen test is suitable for patients that have recently started steroid replacement or are on low dose steroids. For these patients, the steroid dose should be omitted the evening before the test (if possible) and on the morning of the test.

CONTRAINDICATIONS

• Pregnancy, history of hypersensitivity to ACTH, Synacthen or Synacthen depot.
• Acute psychosis.
• Infectious diseases.
• Peptic ulcer.
• Refractory heart failure.
• Cushing's syndrome.
• Treatment of primary adrenocortical insufficiency.
• Adrenogenital syndrome.

NOT RECOMMENDED

• Gives unreliable results in the six weeks following pituitary surgery.
• Patients on the contraceptive pill or on hormone replacement therapy should stop this 6 weeks prior to the test.
• For the assessment of adrenal status in patients receiving long term steroid treatment who are having difficulty coming off steroids

SIDE EFFECTS

• Local or systemic hypersensitivity reactions have been reported very rarely following Synacthen injection, particularly in children with a history of allergic disorders.

PREPARATION

Availability	250 mcg/ 1 ml Ampoule
Time	should ideally be performed as near to 9am as possible (8-10am)	·         Cortisol levels decline throughout the day and cortisol responses between the morning and late afternoon may differ by as much as 100 nmol/L at 30 minutes post Synacthen, making interpretation of afternoon tests difficult if the response in cortisol is abnormal. ·         However, adequate response to synacthen is a valid result at any time of day
Patient	Stop HRT or oestrogen containing contraceptives 6 weeks before May eat and drink normaly Avoid stress	·           Prednisolone and hydrocortisone will cross react with the assay and need stopping at least 24hrs before. If this is not safe to do then switching to dexamethasone should be done 24hrs prior to SST. ·           (5mg prednisolone = 750mcg dexamethasone) ·           Take medications except steroids (for at least 8h, preferably 24h)
	Renal/Hepatic	·         No studies have been performed in patients
	Geriatric patients	·         If the 30-minute test gives inconclusive results, or if the aim is to determine the functional reserve of the adrenal cortex, the 5-hour test may be performed
Basal Sample	Cortisol [Plain /red top] ACTH (if required) [EDTA / purple top]	·         Place ACTH samples on ice and take to the laboratory within 10 min ·         Volume of blood recommended: 4-7ml
0 min	Inject 250 mcg of Synacthen i.m. or i.v. (Infant dose 36mcg/kg)	·         there is no difference in cortisol response between IV and IM administration ·         for IM: can dissolve in 1ml of sterile water or isotonic saline (usually into deltoid) ·         ·         for IV: given via cannula, and flush the line with 5ml NS 0.5%
30 min	Cortisol [Plain /red top]	·         Before taking sample, withdraw 2 ml from the IV line and discard
60 min	Cortisol [Plain /red top]	·         A further sample may be taken at 60 minutes postsynacthen when specifically requested by ·         a consultant endocrinologist: this sample is not usually required.

17OH-Progesterone with Synacthen Stimulation Test

• Synacthen test can be requested to diagnose a late onset congenital adrenal hyperplasia
• The above protocol is followed with blood samples taken for 17OH Progesterone at baseline (pre synacthen) and 60 minutes after ACTH injection (Post Synacthen)

Procedure Summary:

 Interpretation:

Sensitivity /  Specificity	·         does not exclude adrenal failure, since impending adrenal failure might be associated with a much greater loss of zona glomerulosa function. ·         The latter would be suggested by an elevated plasma renin activity. ·         If equivocal result and no urgency, repeat test after a few weeks
Basal Cortisol	·         greater than 180nmol/L
30min or 60min Cortisol	·         greater than 500-540 nmol/L(regardless basal level) ·         increment should be at least 170-200 nmol/L apart from in severely ill patients where adrenal output is already maximal
if taking oestrogens	·         greater than 640nmol/L
primary adrenal failure	·         If impaired cortisol response, and ACTH >200ng/l
secondary adrenal failure	·         If ACTH <10ng/l
normal result	·         excludes primary adrenocortical insufficiency, but does not necessarily exclude ACTH deficiency. ·         Partial ACTH deficiency may result in a normal or reduced response to Synacthen
decreased response	·         Primary adrenal failure (such as Addison’s disease). Results typically show a low baseline cortisol with little or no response to Synacthen. ·         Adrenal atrophy secondary to prolonged ACTH deficiency. ·         Adrenal atrophy secondary to long term steroid therapy (including topical, nasal or inhaled steroids).
Factors affecting
stressed patient	·         interpretation of results must take into account the stress level of the patient and the time of day of the test. For example, a stressed patient that is secreting all the cortisol that their adrenal gland can synthesise may have a basal cortisol >540 nmol/L with very little increment after 30 minutes but does not have adrenal insufficiency.
Females	·         show a small but significantly greater incremental and stimulated cortisol value than males. There are no age-related changes in adults ·         Values for baseline and post-Synacthen cortisol levels do not apply to women taking oral contraceptives
obesity	·         The response to Synacthen is not affected
drugs	·         particularly steroids (Hydrocortisone and Prednisolone) may interfere with cortisol estimation. Please note all drug therapy, including topical, nasal or inhaled steroids on the request form so this possibility can be checked

Reference:

1. Synacthen Information Leaflet
2. CHISCG : Short Synacthen Test for the Investigation of Adrenal Insufficiency CG-Path/2006/03
3. Canterbury District Health Board Hospital Services: Synacthen Test, 24 May 2010
4. http://www.homerton.nhs.uk/our-services/services-a-z/p/pathology/information-for-healthcare-professionals/dynamic-function-testing/synacthen-test-protocol/
5. https://www.rcpa.edu.au/Library/Practising-Pathology/RCPA-Manual/Items/Pathology-Tests/S/Synacthen-stimulation-test
6. Synacthen Test. County Durham and Darlington, NHS Foundation Trust, 2007.
7. ADRENAL HYPOFUNCTION:GUIDELINES FOR INVESTIGATION. East Kent Hospitals University, Feb 2014
8. Synacthen, New Zealand Data Sheet.
9. http://www.southend.nhs.uk/pathology-handbook/test-directory/test-directory-s-index/synacthen-test/