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Bondronat

The Short Synacthen Test, to help diagnose primary adrenal insufficiency1

Would you recognise Primary Adrenal Insufficiency?

Primary Adrenal Insufficiency (PAI) is also known as Addison’s Disease.2 Its prevalence is about 1:250,000 per year in Western societies.2 Therefore its relative rarity and the fact that symptoms are rather non-specific, mean that diagnosis is frequently delayed, which may result in clinical presentation with an acute life-threatening adrenal crisis.2 So making a diagnosis as soon as possible can be vital in order to avoid such a potential consequence.

Recognising the symptoms of PAI is challenging

The symptoms of PAI are mostly non-specific, multiple and varied.2 They include, but may not be limited to:2-5

  • Fatigue
  • Skin hyperpigmentation – if this sign is present it's characteristic of PAI2
  • Weight loss
  • Hypotension
  • Postural dizziness
  • Anorexia
  • Abdominal discomfort
  • Muscle weakness
  • Nausea/vomiting
  • Depression
  • Salt craving
  • Loss of appetite
  • Loss of axillary and pubic hair (women)

An adrenal crisis is a medical emergency2

Undiagnosed, PAI may progress to an adrenal crisis. The signs and symptoms include, but may not be limited to the following:2

  • Severe weakness
  • Syncope/hypotension
  • Marked, acute abdominal symptoms, pain/tenderness/guarding
  • Nausea, vomiting
  • Back pain
  • Confusion
  • Reduced consciousness, delirium

A simple test can help you diagnose or rule out PAI

"To establish the diagnosis of adrenal insufficiency with confidence, a short synacthen test (SST) needs to be performed.” 6

The Short Synacthen Test (SST)1

The SST is a test to help diagnose primary adrenal insufficiency

Synacthen contains tetracosactide acetate, a synthetic ACTH analogue that stimulates the adrenal glands to produce cortisol. Comparing cortisol levels before and after injection of Synacthen gives an indication of how the adrenal glands are functioning.1

Carrying out the SST

Before the SST

Preparation should be made in advance to combat any anaphylactic reaction that may occur after an injection of Synacthen. In the event of a serious anaphylactic reaction, the patient should be treated appropriately with adrenaline and steroids.1

Synacthen Ampoules should not be used in the presence of active infectious or systemic diseases, when the use of live vaccine is contemplated or in the presence of a reduced immune response, unless adequate disease specific therapy is being given.1

Administration should be under the supervision of appropriate senior hospital medical staff with observation for 30 minutes after injection for signs of hypersensitivity.1

The SST involves four simple steps1

1

Patient's blood sample is collected

2

Synacthen is immediately administered via IM or IV injection

3

A second blood sample is taken exactly 30 minutes post Synacthen administration

4

In the hospital laboratory, plasma cortisol levels from both blood samples are measured and compared

Dosing: Adults: IV or IM, 250 μg (1 ml); Children: IV, 250 μg/1.73 m2 body surface area. Therefore for children aged 5 to 7 years, approximately half the adult dose will be adequate. For more accurate dosing of other ages, standard body surface area tables should be consulted1

ACTH = Adrenocorticotropic hormone     IV = Intravenous     IM = Intramuscular

Interpreting the SST results1

The difference between the two plasma cortisol levels needs to be assessed.1 As can be seen below, the absolute plasma cortisol level indicates normal adrenocortical function if the second sample level is >500 nmol/litre (180 μg/litre).

Alternatively, the plasma cortisol increment indicates normal adrenocortical function if the second cortisol level has increased by ≥200 nmol/litre (70 μg/litre) compared to the first.

OR

Any other response may be suggestive of Primary Adrenal Insufficiency1.

Accuracy

The predictive value of the SST in excluding PAI is approximately

97%7

The sensitivity of the SST is

91%7

Reassuring

In over 5,000 SSTs during 20 years8..."Our experience suggests that, for the purpose of clinical decision making, true false negative (false reassurance) results are rare." 8

(Agha A et al. J Clin Endocrinol Metab 2006)

"The corticotropin stimulation test is currently regarded as the diagnostic “gold standard” for the diagnosis of primary (but not secondary) adrenal insufficiency..." 2

(Bornstein SR et al. J Clin Endocrinol Metab 2016)

Why wait?

ACT
NOW!

If you suspect PAI, remember the SST for a fast diagnosis or to rule out PAI. REMEMBER: an adrenal crisis is a medical emergency

Tolerability

The use of the SST is contraindicated in patients1

  • With hypersensitivity to tetracosactide and/or ACTH or to any of the excipients
  • With allergic disorders (e.g. asthma), acute psychosis, infectious diseases, peptic ulcer, refractory heart failure, Cushing’s syndrome, treatment of primary adrenocortical insufficiency and adrenocongenital syndrome

Potential adverse events – related to tetracosactide

(frequency unknown)1

Endocrine disorders:1 Adrenal haemorrhage

Immune system disorders:1 Hypersensitivity

  • Tetracosactide can provoke hypersensitivity reactions, which tend to be more severe (anaphylactic shock) in patients susceptible to allergies (especially asthma). Hypersensitivity reactions may include skin reactions at the injection site, dizziness, nausea, vomiting, urticaria, pruritus, flushing, malaise, dyspnoea, angioneurotic oedema and Quincke's oedema
  • Preparation should be made in advance to combat any anaphylactic reaction that may occur after an injection of Synacthen. In the event of a serious anaphylactic reaction, the patient should be treated appropriately with adrenaline and steroids. Synacthen Ampoules should NOT be used in the presence of active infectious or systemic diseases, when the use of live vaccine is contemplated or in the presence of a reduced immune response, unless adequate disease specific therapy is being given
  • Administration should be under the supervision of appropriate senior hospital medical staff with observation for 30 minutes after injection for signs of hypersensitivity

Potential adverse events – related to glucocorticoid and mineralocorticoid effects

(frequency unknown)1

  • The undesirable effects related to glucocorticoid and mineralocorticoid effects are unlikely to be observed with short-term use of Synacthen as a diagnostic tool
  • Refer to the Summary of Product Characteristics for further information1
ACTH = Adrenocorticotropic hormone

References

  1. Synacthen Ampoules 250 mcg, Summary of Product Characteristics.
  2. Bornstein SR et al. J Clin Endocrinol Metab 2016;101(2): 364-389.
  3. Nicolaides NC et al. Adrenal Insufficiency. [Updated 2017 Oct 14]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279083/ [Last accessed July 2021].
  4. https://rarediseases.org/rare-diseases/acth-deficiency/ [Last accessed July 2021].
  1. https://pituitary.org/knowledge-base/disorders/adrenal-insuffieciency-addison-s-disease [Last accessed July 2021].
  2. Society for Endocrinology 2015, Adrenal Insufficiency Patient Booklet. Author: Professor Wiebke Arlt. Available from: https://www.endocrinology.org/media/1767/16-04_adrenalinsufficiency.pdf [Last accessed July 2021].
  3. Gleeson HK et al. J Clin Endocrinol Metab 2003; 88:2106-2111.
  4. Agha A et al. J Clin Endocrinol Metab 2006; 91(1):43-47.


Downloads

Prescribing Information
Patient Information Leaflet
Summary of Product
Characteristics – 250mcg Ampoule

Contact Us

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 Yellowcard in the Google Play or Apple App Store. Adverse events should also be reported to ATNAHS Pharma UK Ltd on 00 44 (0) 1279 406759, or by email to athnahspv@diamondpharmaservices.com

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