Cortisol Suppression Test (Dexamethasone Suppression) (ACTH suppression)

Sample

• Rapid cortisol suppression test:
  1. This test is easy and quick to perform.
  2. This is used as a screening for Cushing’s syndrome.
     1. Obtain 4 ml of fasting blood at 8 AM.
     2. Inject I/M or  /V cortisone.
     3. Collect blood 5 ml after 30 and 60 min. of injection.
     4. Serum or heparinized blood can be used.
• Prolonged suppression test:
  1. Obtain 24 hours of urine as a baseline sample.
  2. Collect blood for baseline cortisol level.
  3. Collect 24 hours urine sample 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.
• Protocol for an overnight low-dose dexamethasone suppression test:
  1. One mg of dexamethasone given at night at 11 PM.
  2. Collect the blood in the morning at 8 AM.
  3. In a normal person, 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)

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

Pathophysiology

1. Corticotropin-releasing hormone (CRH) 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 cortisol negative feedback, stop further production of CRH and ACTH.

5. Cortisol is a potent glucocorticoid released from the adrenal cortex (zona fasciculta)
6. Cortisol hormone affects the metabolism of:
   1. Carbohydrates.
   2. Proteins.
   3. Fats.
   4. The main effect on the glucose level.
7. Cushing’s syndrome due to bilateral adrenal hyperplasia.
   1. The pituitary gland only responds to the high level of cortisol (corticosteroids).
8. Cushing’s syndrome due to adrenal adenoma or cancer, cortisol secretion continues despite a decrease in ACTH.
9. Cushing’s syndrome due to ectopic ACTH-producing tumors, there is the secretion of ACTH despite high cortisol levels.

Normal interpretations

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

3. 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.
4. Respond to cortisol stimulation indicate adrenal hyperplasia (Cushing’s syndrome).

Adrenal hyperfunction is seen in:

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.

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.

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