Ruleout Adrenal Insufficiency

Referral and diagnosis

What are my next steps as a GP?

In adults, if adrenal insufficiency is suspected on the basis of the patient’s symptoms or risk factors (and urgent treatment is not indicated), carrying out an early morning serum cortisol test is a simple way to confirm or rule out your suspicions.1

This test is usually available in standard bloods.* The procedure is quick and relatively simple and should not cause any significant side effects2

*When interpreting cortisol results, be aware that laboratories use many different assays, so check local reference ranges.

Early morning cortisol testing should be considered in Primary Care1

Secondary care will be less likely to accept a referral without bloods from early morning cortisol that must have been taken between 8:00am to 9:00am1

A random (e.g., non-9.00 a.m.) cortisol test (or a value taken when patient is on steroids) is uninterpretable.3

Early cortisol testing is the responsibility of the Primary Care Physician. Once done, the Short Synacthen Test (tetracosactide acetate) (SST) can confirm or rule out adrenal insufficiency

Professor Partha Kar – Consultant in Diabetes and Endocrinology

Interpreting the results of the cortisol test1,3

Cortisol reading
Interpretation
Action
Less than 100 nmol/L
Adrenal insufficiency is highly likely
Depending on the clinical situation of the patient, seek urgent specialist referral and assessment
Between 100 and 500 nmol/L1
Inconclusive
Consider referring for a Short Synacthen Test (tetracosactide acetate) (SST)
Greater than 400 nmol/L
Adrenal insufficiency unlikely
Explore other reasons for patient symptoms

Swipe for full table

A quick summary of key actions

1

You suspect adrenal insufficiency on the basis of patient symptoms or risk factors.

2

You carry out an early morning serum cortisol test.1,3

3

If the serum cortisol level is less than 100 nmol/L:
Admit the person to hospital, adrenal insufficiency is highly likely and there may be a danger of adrenal crisis.1,3

4

If the results are between 100
and 500 nmol/L:
Refer the patient to endocrinology for further investigations, including a Short Synacthen Test (tetracosactide acetate) (SST).1,3

5

If the cortisol result is greater
than 400 nmol/L:
Primary adrenal insufficiency unlikely.1,3

If steroid deficiency such as Addison’s disease is suspected clinically and not confirmed or refuted by a 9am cortisol, a Short Synacthen Test (tetracosactide acetate) should be undertaken which is usually arranged via referral to specialist care.

Professor Mike Cummings – Consultant Physician, Diabetes and Endocrinology

GP explainer video

Dr. Claire de Mortimer-Griffin

A practising GP and an adrenal insufficiency patient herself, gives her invaluable insight into the disease.

From first-hand experience, she shares critical insights with other GPs: what to be aware of when assessing a patient with adrenal insufficiency symptoms; the importance of speeding up the diagnosis; and when to refer a patient for a simple test, the gold standard for the differential diagnosis of adrenal insufficiency.

PREPARING THE PATIENT FOR THE CORTISOL TEST2

Because cortisol levels tend to be highest earlier in the day, make the patient aware of the importance of scheduling a test in the morning hours (8–9 am).1

The patient will not typically need to fast in preparation for the test. However, you may consider asking them to stop taking medications that might affect cortisol levels.2

Does the cortisol test carry any risks?2

  • Healthcare professionals consider the test to be generally well tolerated. There are some side effects of blood removal from the arm, including temporary scabbing and bruising or discoloration at the site of needle insertion2
  • In rare cases, a person may have more severe side effects, including: feeling lightheaded or faint; excessive bleeding; infection; haematoma, where blood pools under the skin by the injection site2
close more

The Short Synacthen Test (tetracosactide acetate)

The Short Synacthen Test (tetracosactide acetate), sometimes called the Synacthen Stimulation Test (SST) is the gold standard for a diagnosis of primary adrenal insufficiency.4

  • Usually given in hospital under the supervision of a trained healthcare professional, following referral from primary care5
  • Synacthen (tetracosactide acetate) is a synthetic form of the peptide adrenocorticotrophic hormone (ACTH). ACTH is naturally produced by the pituitary gland to encourage the adrenal glands to release cortisol and aldosterone6
  • When Synacthen (tetracosactide acetate) is given, the adrenal glands should respond in the same way they would to ACTH by releasing cortisol and other steroid hormones into the blood6
  • The SST is based on measurement of the plasma cortisol concentration immediately before and exactly 30 minutes after an intramuscular or intravenous injection of 250 micrograms (1 ml) Synacthen

The two plasma cortisol levels from each blood sample are compared5

Absolute plasma cortisol5

Plasma cortisol increment5

A level of >500 nmol/L (180 µg/L) in the second sample indicates normal adrenocortical function5

OR

An increase of >200 nmol/L (70 µg/L) between the first and second sample indicates normal adrenocortical function5

Any other response may be suggestive of primary adrenal insufficiency6

If the ACTH level is high but the cortisol and aldosterone levels are low, it’s usually confirmation of primary adrenal insufficiency.6

Adverse events should be reported. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at https://yellowcard.mhra.gov.uk/ or search for MHRA Yellow card in the Google Play or Apple App Store. Adverse events should also be reported to Atnahs Pharma UK Ltd on +44 (0) 1279 406759 or by email to atatnahspv@diamondpharmaservices.com

A guide to the Short Synacthen Test (tetracosactide acetate)

Dri Choa

Dri Choa is an endocrine nurse at St Mary's Hospital, London. In this video, she explains the aims of the SST, before carrying out the test on a patient and interpreting the results.

References: 

  1. NICE. https://cks.nice.org.uk/topics/addisons-disease/diagnosis/investigations-suspected-adrenal-insufficiency/ [Last accessed June 2023].
  2. Medical News Today. https://www.medicalnewstoday.com/articles/322330#preparing-for-the-test [Last accessed June 2023].
  3. NHS Oxford. https://www.ouh.nhs.uk/biochemistry/tests/tests-catalogue/cortisol.aspx [Last accessed June 2023].
  4. Bornstein SR, et al. J Clin Endocrinol Metab 2016;101(2): 364–389.
  5. Synacthen Ampoules 250 mcg. Summary of Product Characteristics. https://www.medicines.org.uk/emc/product/10822/smpc#gref [Last accessed June 2023].
  6. NHS. Diagnosis. Addison’s disease. https://www.nhs.uk/conditions/addisons-disease/diagnosis/ [Last accessed June 2023].

ACTH = Adrenocorticotrophic Hormone; SST = Short Synacthen Test

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