Adrenocorticotropic Hormone (ACTH)
Adrenocorticotropic Hormone (ACTH)
Systemic Hormonal Diagnostic Agent (steroid hormone)
- Stimulates cortisol release; used primarily to test for hyper- or hypoadrenocorticism (ACTH-stimulation test); use as a screening test for naturally occurring Cushing’s disease (Cushing's Syndrome) is becoming less popular than in the past. Also used to test for iatrogenic Cushing’s and to monitor therapy when treating with antiadrenal drugs.
- Normally, ACTH levels increase when cortisol is low and fall when cortisol is high. In response to a fall in the blood cortisol level, the hypothalamus produces corticotropin-releasing hormone (CRH). Thus, there is an inverse relationship between the production of cortisol and levels of ACTH, and ACTH levels have a direct impact on levels of cortisol.
- Production of ACTH is regulated by corticotrophin-releasing hormone (CRH) from the hypothalamus and cortisol from the adrenal gland. 4
- Adverse effects: Unlikely unless using chronically.
- The ACTH blood test is involved in the diagnosis of Addison's disease in humans.
- Typically, levels of naturally-occurring ACTH is highest early in the morning and lowest in the evening.
- Issues include availability & expense; may need to obtain via a compounding pharmacy. Most have switched to using cosyntropin. 1
Naturally-occurring Adrenocorticotropic Hormone (ACTH) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. The hormone is an adrenal gland stimulant that is administered to secrete large amounts of cortisol into the bloodstream.
In veterinary medicine, ACTH tends to be used most often in the diagnosis of hypoadrenocorticism (ACTH-stimulation test), iatrogenic Cushing’s syndrome, and to monitor the response to mitotane or trilostane therapy in Cushing’s syndrome. It is less often recommended as a screening test for naturally occurring hyperadrenocorticism (Cushing’s syndrome) in dogs since the test is not as sensitive as the low-dose dexamethasone suppression test; thus test results may not be reliable.
One reference recommends using the ACTH-stimulation test if the dog has nonadrenal illness, received any form of exogenous glucocorticoids (including topicals) or phenobarbital. If the dog has no known nonadrenal illness and moderate to severe clinical signs of hyperadrenocorticism, use the low-dose dexamethasone suppression test. 1
The most well known function of the equine pituitary is the production of adrenocorticotropic hormone (ACTH) by the pars intermedia. ACTH acts directly on the adrenal glands to stimulate the production of steroids, most notably cortisol in response to stress. It is the dysfunction of this portion of the pituitary that causes Equine Cushing’s Disease, known in the veterinary community as Pituitary Pars Intermedia Dysfunction (PPID). 2
Adrenocorticotropic Hormone is approved for use in dogs, cats, horses and beef or dairy cattle.
ACTH stimulates the adrenal cortex (principally the zona fasciculata) to stimulate the production and release of glucocorticoids (primarily cortisol in mammals and corticosterone in birds). ACTH release is controlled by corticotropin-releasing factor (CRF), activated in the hypothalamus via a negative feedback pathway, whereby either endogenous or exogenous glucocorticoids suppress ACTH release. A 39-amino acid polypeptide, corticotropin is secreted from the anterior pituitary. The first 24 amino acids (from the N-terminal end of the chain) define its biologic activity. 1
Because it is rapidly degraded by proteolytic enzymes in the gut, ACTH cannot be administered PO. It is not effective if administered topically to the skin or eye. After IM injection in humans, repository corticotropin injection is absorbed over 8 to 16 hours. The elimination half-life of circulating ACTH is about 15 minutes, but because of the slow absorption after IM injection of the gel, effects may persist up to 24 hours. 1
Contraindications / Precautions:
When used for diagnostic purposes, it is unlikely that increases in serum cortisol levels induced by ACTH will have significant deleterious effects on conditions where increased cortisol levels are contraindicated (eg, systemic fungal infections, osteoporosis, peptic ulcer disease). ACTH gel should not be used in patients hypersensitive to porcine proteins. 1
Prolonged use may result in fluid and electrolyte disturbances and other adverse effects; if using on a chronic basis, refer to the human literature for an extensive listing of potential adverse reactions. Veterinary manufacturers suggest giving potassium supplementation with chronic therapy. 1
The following drug interactions have either been reported or are theoretical in humans or animals receiving corticotropin for diagnostic purposes and may be of significance in veterinary patients. Unless otherwise noted, use together is not necessarily contraindicated, but weigh the potential risks and perform additional monitoring when appropriate.
- ANTICHOLINESTERASES (eg, pyridostigmine): ACTH may antagonize effects in patients with myasthenia gravis.
- DIURETICS: ACTH (chronically administered) may increase electrolyte loss. 1
- ACTH may decrease I-131 uptake by the thyroid gland.
- ACTH may suppress skin test reactions.
- ACTH may interfere with urinary estrogen determinations.
- Obtain specific information from the laboratory on sample handling and laboratory normals for cortisol when doing ACTH stimulation tests. 1
Note: When using compounded ACTH products, it is recommended to get several post-ACTH samples, at a minimum one and two hours following injection. 3 Do not confuse these dosages/protocols with those for cosyntropin. 1
Dogs: ACTH-stimulation test (extra-label): Draw baseline blood sample for cortisol determination and administer 2.2 Units/kg of ACTH gel IM. Draw sample 120 minutes after injection. 3,4
Cats: ACTH-stimulation test (extra-label): Draw baseline blood sample for cortisol determination and administer 2.2 Units/kg of ACTH gel IM. Draw samples at 60 minutes and 120 minutes after injection. 4
Horses: ACTH-stimulation test (extra-label): Obtain predose level. Administer 1 Unit/kg IM of ACTH gel between 8 and 10 AM; take post ACTH cortisol levels at 2 and 4 hours post dose. Horses with a functional adrenal gland should have a 2- to 3-fold increase in plasma cortisol when compared with baseline. 5
Birds (extra-label): ACTH Stimulation Test: Draw baseline blood sample for corticosterone (not cortisol) determination and administer 16 – 25 Units IM. Draw second sample 1 to 2 hours later. Normal baseline corticosterone levels vary with regard to species but generally range from 1.5 – 7 mg/mL. After ACTH, corticosterone levels generally increase by 5 to 10 times those of baseline. Specific values are listed in the reference. 6
1Plumb's Veterinary Drugs.
3Feldman EC, Peterson ME. Hypoadrenocorticism. Vet Clin of North America: Small Anim Prac. 1984;14(4):751-766.
4Kemppainen RJ, Zerbe CA. Common Endocrine Diagnostic Tests: Normal Values and Interpretation. In: Kirk RW, ed. Current Veterinary Therapy X: Small Animal Practice. Philadelphia: WB Saunders; 1989:961-968.
5Toribio R. The adrenal glands. In: Reed M, Bayly W, Sellon D, eds. Equine Internal Medicine 2nd Edition. Phila: Saunders; 2004:1357-1361.
6Harrison G.J., et. al. Miscellaneous diagnostic tests. In: Harrison GJ, Harrison LR, eds. Clinical Avian Medicine and Surgery. Philadelphia: W.B. Saunders; 1986:293-297.