ACTH Stimulation Test

Adrenocorticotropic Hormone Stimulation (ACTH Stimulation Test) is performed on patients found to have adrenal insufficiency. An increase in plasma cortisol levels after the infusion of an ACTH-like drug indicates that the adrenal gland is normal and capable of functioning if stimulated. In that case the cause of adrenal insufficiency would lie within the pituitary gland (hypopituitarism, which is called secondary adrenal insufficiency). If little or no rise in cortisol levels occurs after the administration of the ACTH-like drug, the adrenal gland is the source of the problem and cannot secrete cortisol. This is called primary adrenal insufficiency (Addison disease), which may be caused by adrenal hemorrhage, infarction, autoimmunity, metastatic tumor, surgical removal of the adrenal glands, or congenital adrenal enzyme deficiency.

This test can also be used to evaluate patients with Cushing syndrome. Patients with Cushing syndrome caused by bilateral adrenal hyperplasia have an exaggerated cortisol elevation in response to the administration of the ACTH-like drug. Those experiencing Cushing syndrome as a result of hyperfunctioning adrenal tumors (which are usually autonomous and relatively insensitive to ACTH) have little or no increase in cortisol levels over baseline values.
Cosyntropin (Cortrosyn) is a synthetic subunit of ACTH that has the same corticosteroid-stimulating effect as endogenous ACTH in healthy persons. During this test, cosyntropin is administered to the patient, and the ability of the adrenal gland to respond is measured by plasma cortisol levels.


The rapid stimulation test is only a screening test. A normal response excludes adrenal insufficiency. An abnormal response, however, requires a 1- to 3-day prolonged ACTH stimulation test to differentiate primary insufficiency from secondary insufficiency. It should be noted that the adrenal gland can also be stimulated by insulin-induced hypoglycemia as a stressing agent. When insulin is the stimulant, cortisol and glucose levels are measured.




Normal Cortisol Levels using ACTH Stimulation

Rapid test: cortisol levels increase >7 mg/dL above baseline. Baseline is obtained 30 minutes before the test.

24-hour test: cortisol levels >40 mcg/dL.

3-day test: cortisol levels >40 mcg/dL.




Drugs that Cause False Indications

Drugs that may cause artificially increased cortisol levels include:

  • Prolonged Corticosteroid Administration.
  • Eestrogens
  • Spironolactone.




Causes of Exaggerated Cortisol Response

  • Cushing’s syndrome: Bilateral adrenal hyperplasia.
  • Adrenal Insufficiency: Secondary adrenal insufficiency caused by hypopituitarism, exogenous steroid ingestion, or endogenous steroid production from nonendocrine tumor.




Causes of Normal or Below-Normal Cortisol Response

  • Cushing syndrome: Adrenal Adenoma, Adrenal Carcinoma, ACTH-producing Tumor, Chronic Steroid Ingestion.
  • Adrenal Insufficiency: Primary Adrenal Insufficiency (Addison Disease) caused by Adrenal Infarction, Hemorrhage, Infection, or Metastatic Tumor to Adrenal Gland.
  • Congenital Enzyme Adrenal Insufficiency.
  • Surgical Removal of Adrenal Gland.


Drugs that cause Below-Normaol Coritsol Response include:

  • Mitotane.
  • Metyrapone.
  • Aminoglutethimide.