Version May 2024
Note: Acthrel has been discontinued in the United States for >1 year.
Cushing syndrome, differential diagnosis: IV: 1 mcg/kg.
Interpretation of results: Note: Basal and peak responses differ depending on AM or PM administration; therefore, any repeat evaluations on the same patient are recommended to be done at the same time of day as the initial testing.
Increased plasma ACTH and cortisol concentrations following administration: Patients with Cushing disease will exhibit high basal plasma ACTH plus high basal plasma cortisol (20 to 40 mcg/dL). Corticorelin administration will result in increased plasma ACTH and cortisol concentrations. This response pattern indicates an impairment of the negative feedback of cortisol on the pituitary.
Little or no response of plasma ACTH and cortisol concentrations following administration: Patients with ectopic production of ACTH will exhibit high basal plasma ACTH (may be very high) plus high basal plasma cortisol (20 to 40 mcg/dL). Corticorelin administration will result in little or no response of plasma ACTH and cortisol concentrations. Clinicians should note that there have been rare instances of patients with ectopic sources of ACTH that have responded to the corticorelin test.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
Refer to adult dosing.
Cushing syndrome, differential diagnosis: Children and Adolescents: Refer to adult dosing.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not always defined. Incidence of adverse effects is dependent upon dose.
Cardiovascular: Decreased blood pressure (7%), asystole, flushing (face, neck, and upper chest), palpitations (Corticorelin 2004)
Central nervous system: Tonic-clonic seizures (1%), dizziness, (Corticorelin 2004), metallic taste (Corticorelin 2004)
Gastrointestinal: Vomiting (Corticorelin 2004), xerostomia (Corticorelin 2004)
Respiratory: Dyspnea (urge to inspire)
<1%, postmarketing, and/or case reports: Angioedema, chest tightness, hypotension (severe), increased heart rate, loss of consciousness, tachycardia (severe), wheezing
Hypersensitivity to ovine corticorelin or any component of the formulation
Concerns related to adverse effects:
• Cardiovascular effects: High doses (>1 mcg/kg or >100 mcg) have been associated with asystole, hypotension, transient tachycardia, and syncope; cardiovascular effects occur 2 to 3 minutes after injection and may last 30 to 60 minutes. Do not exceed the recommended dose or rate of administration.
• Hypersensitivity: Use may result in hypersensitivity reactions, including urticaria, flushing of the face, neck and upper chest; dyspnea, wheezing, urticaria and angioedema; high doses (>3 mcg/kg) are associated with more prolonged flushing (up to 4 hours), dyspnea, and chest tightness. Discontinue use if hypersensitivity occurs.
Other warnings/precautions:
• False-negative responses: May occur in 5% to 10% of patients with Cushing disease, which may lead to an incorrect diagnosis of ectopic production of ACTH.
Acthrel has been discontinued in the United States for >1 year.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Reconstituted, Intravenous, as trifluoroacetate:
Acthrel: 100 mcg (1 ea [DSC]) [contains lactose]
No
Solution (reconstituted) (Acthrel Intravenous)
100 mcg (per each): $1,095.07
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IV: Prior to administration, obtain venous blood samples 15 minutes before and immediately prior to injection to determine baseline ACTH and cortisol concentrations. Administer over 30 to 60 seconds. Concurrent heparin (even to maintain IV patency) is not recommended. Obtain venous blood samples at 15, 30, and 60 minutes after administration to evaluate ACTH and cortisol response.
IV: Prior to administration, obtain venous blood samples 15 minutes before and immediately prior to injection to determine baseline ACTH and cortisol concentrations. Administer over 30 to 60 seconds. Concurrent heparin (even to maintain IV patency) is not recommended. Obtain venous blood samples at 15, 30, and 60 minutes after administration to evaluate ACTH and cortisol response.
Cushing syndrome, differential diagnosis: Used as a diagnostic aid to differentiate between pituitary and ectopic production of ACTH in patients with ACTH-dependent disease
Acthrel may be confused with Acthar
Corticorelin may be confused with corticotropin, cosyntropin, or Cortrosyn
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Corticosteroids (Systemic): May diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Risk C: Monitor therapy
Heparin: May enhance the adverse/toxic effect of Corticorelin. Significant hypotension and bradycardia have been previously attributed to this combination. Risk X: Avoid combination
Animal reproduction studies have not been conducted.
It is not known if corticorelin is excreted in breast milk. The manufacturer recommends that caution be exercised when administering corticorelin to nursing women.
ACTH and cortisol concentrations at 15 minutes prior to administration, at administration, and at 15, 30, and 60 minutes postinjection; blood pressure, heart rate, signs and symptoms of hypersensitivity reaction.
High basal plasma ACTH and cortisol (20 to 40 mcg/dL [SI: 551.8 to 1,103.6 nmol/L]) resulting in increased plasma ACTH and cortisol after administration of test indicates ACTH-dependent disease of pituitary origin (eg, Cushing disease).
High basal plasma ACTH (may be very high) and cortisol (20 to 40 mcg/dL [SI: 551.8 to 1,103.6 nmol/L]) resulting in little to no change in plasma ACTH and cortisol after administration of test indicates ACTH-dependent syndrome of ectopic origin.
Corticorelin ovine, a peptide of ovine corticotropin-releasing hormone (oCRH) and an analogue of human CRH (hCRH), stimulates adrenocorticotropic hormone (ACTH) release from the anterior pituitary. ACTH stimulates the adrenal cortex to produce cortisol. Depending on the plasma ACTH and cortisol response following the corticorelin stimulation test, the results aid the clinician in the differentiation between the source of ACTH-dependent hypercortisolism (pituitary vs ectopic).
Onset of action: IV:
Plasma ACTH concentration: Increases 2 minutes after injection
Plasma cortisol concentration: Increases within 10 minutes after injection
Peak effect: Response to injection is biphasic with a second lower peak 2 to 3 hours postinjection; basal and peak response levels vary depending on AM or PM administration. In general, baseline ACTH and cortisol concentrations are higher in the AM.
Plasma ACTH concentration: Initial peak: 15 to 60 minutes after injection
Plasma cortisol concentration: Initial peak at 30 to 120 minutes after injection
Duration: IV: Plasma ACTH and cortisol concentrations remain elevated for up to 2 hours after injection
Distribution: Vd: 6.2 ± 0.5 L
Protein binding: Does not appear to be bound by circulating plasma protein
Half-life elimination: t1/2: Exhibits biexponential decay; Fast component: 11.6 ± 1.5 minutes; slow component: 73 ± 8 minutes
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