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 addition to steroidogenic enzymes, ACTH also enhances transcription of the mitochondrial genes that encode for subunits of mitochondrial oxidative phosphorylation systems. These actions may actually be necessary to supply the enhanced energy needs of adrenocortical cells stimulated by ACTH.

ACTH stimulates the adrenal cortex to stimulate the production and release of glucocorticoids. Its 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.1,4

ACTH and Cushing’s Disease in Horses

Cushing’s Disease (also known as Equine Pituitary Pars Intermedia Dysfunction or PPID) is a condition involving the pituitary gland that usually affects that are 15 years of age or older. In Cushing’s, the pituitary gland becomes enlarged and produces too much ACTH. High levels of ACTH result in an over production of cortisol, which are secreted by the adrenal glands.1 

Clinical signs of Cushing’s typically include incomplete shedding, long curly hair along the jaw or back of the fetlocks, abnormal sweating, increased water intake and urination, decreased energy and muscle loss. Horses with this disease have a lowered immune response, are more at-risk for infections and have a more difficult time clearing infections once they’ve set in.1 There is a link between horses with Cushing’s and insulin resistance, predisposing horses to laminitis and other health problems.

PPID in older horses is obviously a major health concern for horse owners; as a result, veterinarians and equine researchers have made vigorous efforts to understand, diagnose and treat this disorder. While PPID is recognized to be a different form of pituitary-dependent hyperadrenocorticism than is seen in canine or human patients, relatively little is known about the pathophysiology and natural progression of the disease.2 Presently, any diagnosis is best supported by clinical signs and endocrinologics tests. 

In veterinary medicine, ACTH products have been FDA-approved for use in dogs, cats, and beef or dairy cattle for stimulation of the adrenal cortex when there is a deficiency of ACTH and as a therapeutic agent in primary bovine ketosis but apparently is no longer commercially available.2,4 ACTH is used most often in the diagnosis and treatment of hypoadrenocorticism (via the 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.4

When used for diagnostic purposes, it is unlikely that increases in serum cortisol levels induced by ACTH produce significant untoward effects on conditions where increased cortisol levels are contraindicated (such as systemic fungal infections, osteoporosis, peptic ulcer disease). Prolonged use of ACTH may result in fluid and electrolyte disturbances and other side effects.4 If using on a chronic basis, refer to the human literature for an extensive listing of potential adverse reactions.4,5

ACTH should only be used during pregnancy when the potential benefits outweigh the risks, as ACTH may be embryocidal. Neonates born from mothers receiving ACTH should be observed for signs of adrenocortical insufficiency.4 In humans, recent data has shown that multiple sclerosis (MS) patients experiencing an acute exacerbation and who previously had suboptimal response to standard high-dose methylprednisolone (MP) treatment showed positive clinical outcomes with fewer adverse events with ACTH.6 It has also been used in high doses for the rapid and complete elimination of infantile spasms (IS).7

For humans, the FDA categorizes this drug as category C for use during pregnancy. 

Dosing for ACTH varies depending upon the application. For the ACTH-stimulation test (extra-label use in horses), a predose cortisol level must be obtained, followed by 1 Unit/kg IM of ACTH between 8 and 10 AM with post-ACTH cortisol levels at 2 and 4 hours post dose. Horses with functional adrenal glands should have a 2- to 3-fold increase in plasma cortisol when compared with baseline.4,5 Your veterinarian should be consulted before beginning any treatment regimen.

Where to buy Adrenocorticotropic Hormone

Adrenocorticotropic hormone (ACTH) is available in the U.S. through several pharmaceutical manufacturers and through veterinary custom compounding companies. Adrenocorticotropic Hormone IM 80 IU injectable by NexGen Pharmaceuticals is a superior ACTH formulation that performs equally well for both diagnostic and therapeutic applications. 

FOR RX ONLY: A valid prescription from a licensed veterinarian is required for dispensing this medication.

1McCue PM. Equine Cushing's disease. Vet Clin North Am Equine Pract. 2002 Dec;18(3) 533-43, viii. doi:10.1016/s0749-0739(02)00038-x. PMID: 12516933.

2Hatazoe, Takashi et al. Pituitary pars intermedia dysfunction (equine Cushing's disease) in a Thoroughbred stallion: a single report. Journal of equine science vol. 26,4 (2015): 125-8. doi:10.1294/jes.26.125.

3Schott HC. Pituitary pars intermedia dysfunction: equine Cushing's disease. Vet Clin North Am Equine Pract. 2002 Aug;18(2) 237-270. doi:10.1016/s0749-0739(02)00018-4. PMID: 15635907.

4Plumb’s Veterinary Drugs.

5Toribio R. The adrenal glands. In: Reed M, Bayly W, Sellon D, eds. Equine Internal Medicine 2nd Edition. Phila: Saunders; 2004:1357-1361.

6Berkovich R, Agius MA. Mechanisms of action of ACTH in the management of relapsing forms of multiple sclerosis. Ther Adv Neurol Disord. 2014;7(2):83-96. doi:10.1177/1756285613518599.

7Brunson KL, Avishai-Eliner S, Baram TZ. ACTH treatment of infantile spasms: mechanisms of its effects in modulation of neuronal excitability. Int Rev Neurobiol. 2002;49:185-97.