Short Synacthen Test: Indication, Procedure, and Interpretation

Short Synacthen Test (SST) is a diagnostic test that is used to determine the function of adrenal gland by examining the hypothalamic-pituitary-adrenal (HPA) axis and the adrenal cortex ability to secrete cortisol.

Indications

To diagnose adrenal insufficiency:

• Primary adrenal insufficiency (Addison’s disease)
• Secondary adrenal insufficiency due to pituitary dysfunction
• Tertiary adrenal insufficiency from hypothalamic suppression (e.g., prolonged steroid therapy)

To check adrenal recovery following:

• Long-term corticosteroid therapy
• Pituitary surgery
• Treatment of Cushing’s syndrome

To evaluate unexplained symptoms such as:

• Fatigue
• Weight loss
• Hypotension
• Hyponatraemia
• Hypoglycaemia

Procedure of the Short Synacthen Test

Preparation

• The patient should be well-hydrated and fasting or lightly fed.
• Morning testing is preferred, preferably between 8:00 AM and 10:00 AM, due to the diurnal pattern of cortisol release.
• In case of exogenous corticosteroids, suppress as much as possible the day before testing (24 to 48 hours).

Test Procedure

1. Blood sample is collected to measure:
   • Serum cortisol
   • ACTH (nonessential), electrolytes, glucose
2. Administer 250 micrograms of synthetic ACTH (Synacthen) via intramuscular (IM) or intravenous (IV) injection.
3. Get a follow-up sample after 30 minutes and, optionally, after 60 minutes.
4. Measure serum cortisol levels in all samples.

Interpretation

Normal (adequate) response:

• Peak serum cortisol ≥ 500–550 nmol/L (varies by lab)
• Increase from baseline ≥ 200 nmol/L

Abnormal (inadequate) response:

Primary adrenal insufficiency (Addison’s disease):

• Low baseline cortisol
• Minimal or no rise in cortisol after Synacthen
• ACTH is elevated

Secondary/Tertiary adrenal insufficiency:

• Low baseline cortisol
• Blunted or delayed cortisol response
• ACTH is low or inappropriately normal

The levels of ACTH are normal or low in case of secondary insufficiency, depending on the stage of the disease Insulin Tolerance Test (ITT) or CRH stimulation test is usually necessary when the diagnosis is uncertain, especially in early-stage secondary insufficiency, at which time the adrenal glands may remain responsive to ACTH and, thus, cause false-negative result.

Clinical Considerations

• SST is safe and simple but not suitable for acute adrenal crisis. Treatment should not be delayed for testing.
• Patients on oral or inhaled corticosteroids must be carefully evaluated, as these can suppress the HPA axis.
• Interpret results in the context of clinical findings, ACTH levels, and time of day.