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Pronunciation
(koe sin TROE pin)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Diagnostic test to differentiate primary adrenal from secondary (pituitary) adrenocortical insufficiency
Pregnancy Risk Factor
C
Pregnancy Considerations
Animal reproduction studies have not been conducted.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to cosyntropin or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Corticotropin allergy: Use with caution in patients with a history of allergic reactions to corticotropin or pre-existing allergic disease.
Adverse Reactions
Frequency not defined.
Cardiovascular: Bradycardia, hypertension, peripheral edema, tachycardia
Dermatologic: Rash
Local: Whealing with redness at the injection site
Miscellaneous: Anaphylaxis, hypersensitivity reaction
Metabolism/Transport Effects
None known.
Drug Interactions
There are no known significant interactions.
Storage
Powder for injection: Store at controlled room temperature of 15°C to 30°C (59°F to 86°F).
Solution for injection: Store refrigerated between 2°C to 8°C (36°F to 46°F). Protect from light and freezing.
I.V. infusion: Stable for 12 hours at room temperature; stable for 21 days under refrigeration.
Reconstitution
I.M.: Reconstitute cosyntropin 0.25 mg with NS 1 mL.
I.V. push: Reconstitute cosyntropin 0.25 mg with NS 2-5 mL.
I.V. infusion: Mix in NS or D5W.
Mechanism of Action
Stimulates the adrenal cortex to secrete adrenal steroids (including hydrocortisone, cortisone), androgenic substances, and a small amount of aldosterone
Pharmacodynamics/Kinetics
Time to peak, serum: I.M., IVP: ~1 hour; plasma cortisol levels rise in healthy individuals within 5 minutes
Dosage
Diagnosis of adrenocortical insufficiency: I.M., I.V.: Note: Cosyntropin injection solution is not recommended for I.M. administration (manufacturer recommendation).
Children ≤2 years: 0.125 mg
Children >2 years and Adults:
Conventional dose: 0.25 mg
Note: Doses in the range of 0.25-0.75 mg have been used in clinical studies; however, maximal response is seen with 0.25 mg dose. When greater cortisol stimulation is needed, an I.V. infusion may be used: 0.25 mg administered at 0.04 mg/hour over 6 hours
Low-dose protocol (unlabeled dose): 1 mcg (Abdu, 1999)
Note: The use of the low-dose protocol has been advocated by some clinicians, particularly in mild or secondary adrenal insufficiency. The low-dose protocol is not recommended in critically-ill patients (Marik, 2008).
Administration: I.M.
May administer I.M. (reconstituted powder for injection only); cosyntropin injection solution is not recommended for I.M. administration (manufacturer recommendation).
Administration: I.V.
May administer by I.V. injection over 2 minutes or as an I.V. infusion over 4-8 hours.
Reference Range
Normal baseline cortisol >5 mcg/dL; normal response 30 minutes after cosyntropin injection: increase in serum cortisol concentration of >7 mcg/dL or peak response >18 mcg/dL; plasma cortisol concentrations should be measured immediately before and exactly 30 minutes after a dose. If increase in plasma cortisol levels at 30 minutes is equivocal, consider repeat cortisol sampling at 60 and/or 90 minutes.
Test Interactions
Concurrent or recent use of spironolactone, hydrocortisone, cortisone, etomidate, estrogens
Additional Information
Each 0.25 mg of cosyntropin is equivalent to 25 units of corticotropin.
Patient should not receive corticosteroids or spironolactone the day of the test.
Anesthesia and Critical Care Concerns/Other Considerations
Evidence-Based Information:
Septic Shock: Annane, et al (2002) randomized 300 septic shock patients to either hydrocortisone (50 mg I.V. push every 6 hours) and fludrocortisone (50 mcg tablet daily via nasogastric tube) or matching placebos for 7 days. The mean Simplified Acute Physiology Score II (SAPS II) was 57 ± 19 in the placebo group and 60 ± 19 in the active treatment group. The Logistic Organ Dysfunction score was 9 ± 3 in the placebo group and 9 ± 3 in the active treatment group. In patients who did not appropriately respond to cosyntropin (nonresponders), there were significantly fewer deaths in the active treatment group. Vasopressor therapy was withdrawn more frequently in this subset of the active treatment group. Adverse events were similar in both groups.
In the CORTICUS trial (Sprung, 2008), 484 septic shock patients were randomized within 72 hours of onset to receive either hydrocortisone (50 mg I.V. push every 6 hours) or placebo for 5 days followed by a 6-day taper. The primary endpoint was 28 day mortality in patients who did not respond to cosyntropin. The SAPS II score in the treatment group was 49.5 ± 17.8 and 48.6 ± 16.7 in the placebo group. The Sequential Organ Failure Assessment scores were 10.6 ± 3.4 in the treatment group and 10.6 ± 3.2 in the placebo group. Different than the Annane study, in the patients who did not respond to cosyntropin, there was no mortality difference at 28 days; 39.2% (95% CI 30.5-47.9) mortality in the hydrocortisone group and 36.1 % (95% CI 26.9-45.3, P=0.69) mortality in the placebo group. A trend towards increased incidence of superinfection was noted in hydrocortisone patients. New septic shock episodes, hyperglycemia, and hypernatremia were more frequent in the hydrocortisone group. Hydrocortisone did not improve survival in this population of septic shock patients regardless of corticotropin response.
Per the 2008 recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients (Marik, 2008), a diagnosis of critical illness-related corticosteroid insufficiency (CIRCI) is made with either a random total cortisol concentration of <10 mcg/dL or a delta cortisol concentration (30-60 minutes after administration of 0.25 mg I.V. cosyntropin) of <9 mcg/dL (Grade 2B). Although the cosyntropin 1 mcg test dose has demonstrated greater sensitivity in diagnosing adrenal insufficiency, it is currently not recommended due to limited data in the critically ill patient. Upon diagnosis of CIRCI, initiation of moderate-dose hydrocortisone in patients with poor response to fluid resuscitation and vasopressors should be considered; concomitant use of fludrocortisone is optional (Grade 2B). Of note, the use of etomidate for induction will suppress the hypothalamic-pituitary-adrenal axis and reduce cortisol production and blunt response to cosyntropin. Dexamethasone will reduce cortisol production and peak response to ACTH stimulation test may be reduced. Therefore, if hydrocortisone is not available and dexamethasone becomes necessary, initiation after the ACTH stimulation test is complete is recommended (Marik, 2009).
The 2008 Surviving Sepsis Campaign Guidelines suggest the following: Intravenous hydrocortisone be given only to adult septic shock patients after blood pressure is identified to be poorly responsive to fluid resuscitation and vasopressor therapy (Grade 2C); ACTH stimulation test not be used to identify the subset of adults with septic shock who should receive hydrocortisone (Grade 2B); patients with septic shock should not receive dexamethasone if hydrocortisone is available (Grade 2B); the addition of fludrocortisone if hydrocortisone is not available and the steroid that is substituted does not have significant mineralocorticoid activity (Grade 2C); doses of corticosteroids comparable to >300 mg hydrocortisone daily not be used in severe sepsis or septic shock for the purpose of treating septic shock (Grade 1A). They also recommend corticosteroids not be administered for the treatment of sepsis in the absence of shock. There is, however, no contraindication to continuing maintenance steroid therapy or to using stress dose steroids if the patient's endocrine or corticosteroid administration history warrants (Grade 1D).
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
None reported
Mental Health: Effects on Psychiatric Treatment
Barbiturates may decrease the levels of cosyntropin
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 0.25 mg
Cortrosyn®: 0.25 mg
Injection, solution [preservative free]: 0.25 mg/mL (1 mL)
References
Abdu TAM, Elhadd TA, Neary R, et al, “Comparison of the Low Dose Short Synacthen Test (1 μg), the Conventional Dose Short Synacthen Test (250 μg), and the Insulin Tolerance Test for Assessment of the Hypothalamo-Pituitary-Adrenal Axis in Patients With Pituitary Disease,” J Clin Endocrinol Metab, 1999, 84(3):838-43.
Annane D, Sebille V, Charpentier C, et al, “Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock,” JAMA, 2002, 288(7):862-71.
Broide J, Soferman R, Kivity S, et al, “Low-Dose Adrenocorticotropin Test Reveals Impaired Adrenal Function in Patients Taking Inhaled Corticosteroids,” J Clin Endocrinol Metab, 1995, 80(4):1243-6.
Dellinger RP, Levy MM, Carlet JM, et al, “Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2008,” Intensive Care Med, 2008, 34(1):17-60. Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2249616/pdf/134_2007_Article_934.pdf
Marik PE, “Critical Illness-Related Corticosteroid Insufficiency,” Chest, 2009, 135(1):181-93.
Marik PE, Pastores SM, Annane D, et al, “Recommendations for the Diagnosis and Management of Corticosteroid Insufficiency in Critically Ill Adult Patients: Consensus Statements From an International Task Force by the American College of Critical Care Medicine,” Crit Care Med, 2008, 36(6):1937-49.
Sprung CL, Annane D, Keh D, et al, “Hydrocortisone Therapy for Patients With Septic Shock,” N Engl J Med, 2008, 358(2):111-24.
Thaler LM and Blevins LS, “The Low Dose (1-μg) Adrenocorticotropin Stimulation Test in the Evaluation of Patients With Suspected Central Adrenal Insufficiency,” J Clin Endocrinol Metab, 1998, 83(8):2726-9.
Tordjman K, Jaffe A, Grazas N, et al, “The Role of the Low Dose (1 microgram) Adrenocorticotropin Test in the Evaluation of Patients With Pituitary Diseases,” J Clin Endocrinol Metab, 1995, 80(4):1301-5.
International Brand Names
Lexi-Comp.com
Last full review/revision February 2012
Content last modified February 2012
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