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Cortisol Suppression Test (Dexamethasone Suppression) (ACTH suppression)

October 9, 2023Chemical pathologyLab Tests

Cortisol Suppression Test

Sample for a cortisol suppression test:

  1. Take fasting blood to prepare the serum.
  2. 24-hours urine sample. Take baseline 24-hour urine collection for corticosteroids (urine 17-OHCS) or urinary cortisol.

Rapid cortisol suppression test:

  1. This test is easy and quick to perform.
  2. This is used as a screening test for Cushing’s syndrome.
    1. Obtain 4 ml of fasting blood at 8 AM.
    2. Inject I/M or  I/V cortisone.
    3. Collect blood 5 ml after 30 and 60 minutes of injection.
    4. Serum or heparinized blood can be used.
  3. What is the normal value of rapid cortisol suppression test = Nearly 0 cortisol levels.

Prolonged suppression test:

  1. Obtain 24 hours of urine as a baseline sample.
  2. Collect blood for baseline cortisol level.
  3. Collect 24-hour urine samples daily for 6 days.
  4. On day 3, give a low dose of dexamethasone by mouth (with antacid or milk).
  5. On day 5, give a high dose of dexamethasone by mouth like above.
  6. Keep the urine refrigerated.
  7. What is the normal value of a prolonged cortisol suppression test:
    1. Low dose = >50% reduction of plasma cortisol and 17-hydroxycorticosteroid levels (17-OCHS).
    2. High dose = 50% reduction of plasma cortisol and 17-OCHS.

Protocol for an overnight low-dose dexamethasone suppression test:

  1. One mg of dexamethasone is given at night at 11 PM by mouth.
  2. Collect the blood at 8 AM.
  3. A normal person’s cortisol concentration is suppressed to 2  µg/dL or less.
  4. Cushing’s patient does not show suppression, and the level may be >10  µg/dL.

Purpose of the test (Indications) for cortisol suppression test:

  1. This test is done to diagnose adrenal hyperfunction (Cushing’s Syndrome).
  2. This also diagnoses adrenal hypofunction (Addison’s disease).

Precautions for cortisol suppression test:

  1. Physical and emotional stress can increase ACTH release and interfere with the interpretation of the test result.
  2. Drugs that will interfere with the results are barbiturates, oral contraceptives, estrogen, Dilantin, steroids, and tetracyclines.
  3. Explain the procedure to the patients.
  4. Take the patient weight as a baseline for evaluation of side effects of steroids.

Pathophysiology of Cortisol hormone

  1. Corticotropin-releasing hormone (CRH) is made in the hypothalamus.
  2. CRH stimulates the production of ACTH from the anterior pituitary gland.
  3. ACTH stimulates the adrenal gland cortex (zona fscicultra) to produce cortisol.
  4. The feedback mechanism is rising levels of negative cortisol feedback, stopping the further production of CRH and ACTH.
Cortisol control mechanism and negative feed back

Cortisol control mechanism and negative feedback

Cortisol feedback mechanism

Cortisol feedback mechanism

  1. Cortisol is a potent glucocorticoid released from the adrenal cortex (zona fasciculta)
  2. Cortisol hormone affects the metabolism of:
    1. Carbohydrates.
    2. Proteins.
    3. Fats.
    4. The main effect is on the glucose level.

Cushing’s syndrome:

  1. Cushing’s syndrome is due to bilateral adrenal hyperplasia.
    1. The pituitary gland only responds to the high level of cortisol (corticosteroids).
  2. Cushing’s syndrome due to adrenal adenoma or cancer, cortisol secretion continues despite a decrease in ACTH.
  3. Cushing’s syndrome due to ectopic ACTH-producing tumors, there is the secretion of ACTH despite high cortisol levels.
Cortisol secretion and control

Cortisol secretion and control

Interpretations of cortisol suppression test:

  1. Suppression occurs in patients with:
    1. Cushing’s syndrome where the level is >10 µg/dL.
    2. In 50% of the cases, the cause is endogenous.
  2. There is no suppression in patients with:
    1. Adrenal Adenoma.
    2. Adrenal carcinoma.
    3. In the case of ectopic ACTH-producing neoplasm.

Table showing the relation of Cushing’s syndrome with the dose of cortisone:

Disease Causative reason low dose High Dose
Cushing’s syndrome Bilat. adrenal hyperplasia No change >50 % reduction in cortisol
Cushing’s syndrome Adrenal adenoma or carcinoma No change No change
Cushing’s syndrome Ectopic ACTH tumors No change No change
  1. Absent or failure response to cortisol stimulation seen in:
    1. Addison’s disease (adrenal insufficiency).
    2. Hypopituitarism (secondary adrenal insufficiency).
    3. Adrenal adenoma and carcinoma.
  2. Respond to cortisol stimulation indicate adrenal hyperplasia (Cushing’s syndrome).

Adrenal hyperfunction is seen in the following conditions:

  1. Cushing’s Syndrome.
  2. Ectopic ACTH- producing tumors
  3. Adrenal adenoma or carcinoma.
  4. Bilateral adrenal hyperplasia.
  5. Mental depression.

Adrenal Hypofunction is seen in:

  1. Addison’s disease.
  2. Neoplastic infiltration.
  3. Granulomatous inflammation like TB, histoplasmosis, and sarcoidosis.
  4. After adrenalectomy.

Differential diagnosis of adrenal gland tumors:

Test Normal Cushing’s Syndrome Adrenal tumor Ectopic ACTH
Urinary free cortisol <100 µg/day >120 µg/day >120 µg/day >120µg/day
Serum cortisol <3 µg/dL >10 µg/dL >10 µg/dL >120 µg/dL
H.D Dexamethasone 50% supp. Most supp. Fail to supp. fail to supp

Supp = suppression.
H.D = high dose.

Questions and answers:

Question 1: What is the significance of cortisol suppression test?
Show answer
Suppression occurs in Cushing's syndrome.
Question 2: In what cases there is no suppression of cortisol?
Show answer
There is no suppression in the adrenal adenoma, adrenal carcinoma and ectopic ACTH production.

Possible References Used
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