Adrenocorticotropic Hormone (ACTH) is a tropic hormone produced by the anterior pituitary gland. There is an elaborate feedback mechanism for cortisol coordinates the function of the hypothalamus, pituitary gland, and adrenal glands. Adrenocorticotropic Hormone is an important aspect of this mechanism. Corticotropin-releasing hormone (CRH) is made in the hypothalamus. This stimulates Adrenocorticotropic Hormone production in the anterior pituitary gland, which in turn stimulates the adrenal cortex to produce cortisol. The rising levels of cortisol act as negative feedback and curtail further production of CRH and Corticotropin.
In the patient with Cushing Syndrome, an elevated Adrenocorticotropic Hormone level can be caused by a pituitary ACTH-producing Tumor or a Nonpituitary (ectopic) ACTH-producing Tumor, which usually occur in the lung, pancreas, thymus, or ovary. Adrenocorticotropic Hormone levels greater than 200 pg/mL usually indicate ectopic Adrenocorticotropic Hormone production. If the Adrenocorticotropic Hormone level is below normal in a patient with Cushing syndrome, an adrenal adenoma or carcinoma is probably the cause of the hyperfunction.
In patients with Addison disease, an elevated Adrenocorticotropic Hormone level indicates primary adrenal gland failure, as in adrenal gland destruction caused by infarction, hemorrhage, or autoimmunity; surgical removal of the adrenal gland; congenital enzyme deficiency; or adrenal suppression after prolonged ingestion of exogenous steroids. If the Adrenocorticotropic Hormone level is below normal in a patient with adrenal insufficiency, hypopituitarism is most probably the cause of the hypofunction.
Adrenocorticotropic Hormone can be directly measured by immunoassay. Adrenocorticotropic Hormone levels exhibit diurnal variations that correspond to cortisol levels. Levels in evening (8PM to 10 PM) samples are usually one half to two thirds of morning (4AM to 8 AM) specimens. This diurnal variation is lost when disease (especially neoplasm) affects the pituitary or adrenal glands. Likewise, stress can blunt or eliminate this normal diurnal variation.
Adrenocorticotropic Hormone is measured in amniotic fluid when anencephaly is suspected. Decreased levels are noted in anencephalic fetuses.
Normal Adrenocorticotropic Hormone Levels
Morning: <80 pg/mL or <18 pmol/L (SI units).
Night: <50 pg/mL or <11 pmol/L (SI units).
Causes of Adrenocorticotropic Hormone False Indications:
- Stress (trauma, pyrogen, hypoglycemia), menses, and pregnancy cause increased levels of cortisol. This is accomplished through elevation of ACTH.
- Recently administered radioisotope scans can affect levels measured by radioimmunoassay or immunoradiometry.
- Drugs that may cause increased levels include Aminoglutethimide, Amphetamines, Estrogens, Ethanol, Insulin, Levodopa, Metyrapone, Spironolactone, and Vasopressin.
- Exogenously administered corticosteroids decrease ACTH levels.
- ACTH is a very unstable peptide in plasma and should be stored at -20° C (-4° F) to prevent artificially low values.
Causes of High Adrenocorticotropic Hormone Levels
- When the adrenal glands don’t not make enough cortisol for the body’s needs, the reduced serum cortisol level is a strong stimulus to pituitary production of ACTH which leads to High ACTH Levels. The adrenal glands may not produce sufficient cortisol when patients have Addison Disease (Primary Adrenal Insufficiency) or Adrenogenital Syndrome (Congenital Adrenal Hyperplasia).
- ACTH is overproduced as a result of neoplastic overproduction of ACTH in the pituitary or elsewhere in the body by an ACTH-producing cancer. Stress is a potent stimulus to ACTH production. Also ACTH overproduction is associated with Cushing Disease (Pituitary-dependent Adrenal Hyperplasia) and
Ectopic ACTH Syndrome.
Causes of Low Adrenocorticotropic Hormone Levels
When the pituitary gland is incapable of producing adequate ACTH which causes low Adrenocorticotropic Hormone Levels. The low production of ACTH can be an indication of:
- Secondary Adrenal Insufficiency (Pituitary Insufficiency).
Overproduction or high levels of cortisol is a strong inhibitor to Pituitary production of ACTH which causes Low Adrenocorticotropic Hormone Levels. This can be a result of:
- Adrenal Adenoma or Adrenal Carcinoma.
- Cushing Syndrome.
- Exogenous steroid administration.