ACTH
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ACTH (ACTH).
ACTH (corticotropin) stimulates the adrenal cortex to release cortisol, corticosterone, aldosterone, and androgenic steroids. It binds to the melanocortin 2 receptor (MC2R) in the adrenal gland, activating adenylyl cyclase and increasing intracellular cAMP.
| Metabolism | Metabolized primarily by proteolytic cleavage in plasma and tissues; not significantly hepatic. |
| Excretion | Renal: <5% unchanged; hepatic metabolism via proteolysis; <1% biliary/fecal |
| Half-life | 15 minutes (intravenous); rapid clearance due to enzymatic degradation; clinical effect persists 2-4 hours due to steroidogenesis |
| Protein binding | 25-30% bound to albumin and transcortin (corticosteroid-binding globulin) |
| Volume of Distribution | 0.4 L/kg; primarily extracellular fluid; negligible tissue binding |
| Bioavailability | Intramuscular: ~70-80%; Subcutaneous: ~60-70%; Oral: <1% due to gastrointestinal degradation |
| Onset of Action | Intravenous: rapid, within minutes; Intramuscular: 15-30 minutes; Subcutaneous: 30-60 minutes |
| Duration of Action | Intravenous: 2-4 hours; Intramuscular: 4-6 hours; Subcutaneous: 6-12 hours; based on cortisol elevation |
40-80 units intramuscularly or subcutaneously every 24-72 hours for chronic conditions; 25 units intravenously over 8 hours for diagnostic use.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended; use with caution in severe renal impairment (GFR <30 mL/min) due to potential fluid retention. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment (Child-Pugh class C) due to altered corticosteroid metabolism. |
| Pediatric use | 0.25-0.5 units/kg intramuscularly or subcutaneously every 12-24 hours; for diagnostic ACTH stimulation test: 0.125-0.25 mg cosyntropin intravenously. |
| Geriatric use | Start at lower end of dosing range (e.g., 40 units every 72 hours); monitor for fluid retention, hypertension, and hyperglycemia due to age-related decreased renal function and increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ACTH (ACTH).
| Breastfeeding | Excreted in breast milk in low amounts; M/P ratio unknown. Use caution, especially with high maternal doses, due to potential for infant adrenal suppression. |
| Teratogenic Risk | First trimester: Limited human data; animal studies show increased risk of cleft palate at supraphysiologic doses. Second/third trimester: Fetal adrenal suppression, growth restriction, and premature labor with chronic high-dose use. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to ACTH or any component; administration of live or live-attenuated vaccines; systemic fungal infections; scleroderma; osteoporosis; peptic ulcer disease; recent intestinal anastomosis; uncontrolled hypertension; congestive heart failure; diabetes mellitus; myasthenia gravis; tuberculosis; ocular herpes simplex; pregnancy (relative).
| Precautions | Suppression of hypothalamic-pituitary-adrenal (HPA) axis with prolonged use; increased risk of infections; masking signs of infection; electrolyte disturbances; increased blood pressure; behavioral changes; gastrointestinal perforation; osteoporosis; ocular effects (cataracts, glaucoma); vaccination risk with live vaccines. |
| Food/Dietary | Grapefruit juice may increase ACTH levels; avoid concomitant consumption. Sodium restriction may be necessary if fluid retention occurs. Maintain adequate potassium intake (e.g., bananas, oranges) as ACTH can cause hypokalemia. Avoid excessive licorice consumption (can potentiate mineralocorticoid effects). |
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| Monitor maternal blood pressure, blood glucose, and signs of infection. Fetal ultrasound for growth restriction. Neonatal assessment for adrenal suppression after delivery if used chronically in third trimester. |
| Fertility Effects | May suppress endogenous gonadotropins and adrenal androgens, potentially impairing ovulation. Reversible upon discontinuation. |
| Clinical Pearls | ACTH (cosyntropin) is used for diagnostic testing of adrenal insufficiency; a normal response is a rise in serum cortisol >18-20 mcg/dL at 30 or 60 min post-IV/IM dose. It can also be used therapeutically for infantile spasms (West syndrome) and multiple sclerosis exacerbations. Monitor for hypersensitivity reactions, anaphylaxis, and adrenal suppression with prolonged use. Avoid in patients with scleroderma, osteoporosis, congestive heart failure, or recent surgery. Corticosteroids and ACTH can mask signs of infection. |
| Patient Advice | ACTH may cause mood changes, insomnia, or fluid retention; report severe mental health changes or swelling. · Avoid live vaccines during treatment (e.g., MMR, varicella, nasal flu). · Do not stop medication abruptly; taper under medical supervision to prevent adrenal crisis. · Carry medical ID indicating ACTH use and risk of adrenal insufficiency. · Report signs of infection (fever, sore throat) as ACTH can suppress immune response. |