Intravenous Diagnostic test in differentiating pituitary and ectopic production of ACTH in patients with ACTH-dependent Cushing's syndrome
Adult: 1 mcg/kg via inj or infusion over 30-60 seconds. Obtain venous blood samples 15 minutes before administration and immediately before inj to determine baseline ACTH and cortisol levels, and at 15, 30, and 60 minutes after inj to evaluate ACTH and cortisol response. After administration, patients with high basal plasma ACTH and cortisol (20-40 mcg/dL) will have an increase in plasma ACTH and cortisol levels indicating pituitary production of ACTH (Cushing's syndrome), while patients with high basal plasma ACTH (may be very high) and high basal plasma cortisol (20-40 mcg/dL) will have little or no response of plasma ACTH or cortisol levels indicating ectopic ACTH syndrome. Basal and peak responses may differ depending on the time of inj (AM or PM); if a repeat evaluation is needed, repeat tests must be done at the same time of day as the initial testing. Child: Same as adult dose.
Reconstitution
Reconstitute with 2 mL of 0.9% NaCl solution for inj to provide a solution containing 50 mcg/mL. Roll the vial to dissolve. Do not shake.
Contraindications
Hypersensitivity to ovine corticorelin.
Special Precautions
False-negative results may occur in 5-10% of patients with Cushing's disease. Concurrent administration of heparin (even to maintain IV patency) is not recommended. Children. Pregnancy and lactation.
Adverse Reactions
Significant: Hypotension, transient tachycardia, syncope, and asystole (high doses [>1 mcg/kg or >100 mcg]). Hypersensitivity reactions, including urticaria, flushing of the face, neck and upper chest; mild dyspnoea, wheezing, angioedema; more prolonged flushing, chest tightness, and dyspnoea (high doses [>3 mcg/kg]). Cardiac disorders: Palpitation. Gastrointestinal disorders: Vomiting, xerostomia, metallic taste. Nervous system disorders: Tonic-clonic seizures, dizziness.
Obtain ACTH and cortisol concentrations (15 minutes before administration, immediately before inj, and at 15, 30, and 60 minutes post-inj). Monitor blood pressure and heart rate. Assess for signs and symptoms of hypersensitivity reactions.
Overdosage
Symptoms: CV changes, severe facial flushing, and dyspnoea. Management: Symptomatic treatment.
Drug Interactions
Recent or current corticosteroid therapy (e.g. dexamethasone) may diminish the therapeutic efficacy of corticorelin, particularly by inhibiting the plasma ACTH response. May increase the risk of adverse effects (e.g. significant hypotension) with heparin.
Action
Description: Mechanism of Action: Corticorelin is a peptide of ovine corticotropin-releasing hormone (oCRH) and an analogue of human CRH (hCRH). It stimulates the adrenocorticotropic hormone (ACTH) release from the anterior pituitary, then ACTH causes the production of cortisol in the adrenal cortex. The plasma ACTH and cortisol response following the corticorelin stimulation test is used as an aid in the differentiation between the source of ACTH-dependent hypercortisolism (pituitary vs ectopic). Onset: Elevation of plasma ACTH level: 2 minutes. Elevation of plasma cortisol level: Within 10 minutes. Duration: Plasma ACTH and cortisol level elevation: Up to 2 hours. Pharmacokinetics: Absorption: Time to peak plasma concentration: Biphasic: Initial: 15-60 minutes (ACTH); 30-120 minutes (cortisol). 2nd lower peak: 2-3 hours. Distribution: Volume of distribution: 6.2 ± 0.5 L. Excretion: Elimination half-life: 73 ± 8 minutes (slow component); 11.6 ± 1.5 minutes (fast component).
Chemical Structure
Corticorelin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 16132344, Corticorelin ovine triflutate. https://pubchem.ncbi.nlm.nih.gov/compound/Corticorelin-ovine-triflutate. Accessed Feb. 24, 2022.
Storage
Intact vials: Store between 2-8°C. Protect from light. Reconstituted solution: Stable for 8 hours in the refrigerator.
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