Cosyntropin (cosyntropin)

For rapid screening for adrenocortical insufficiency, plasma cortisol concentrations are determined prior to and 30 minutes after administration of 0.25 mg of cosyntropin IM or by direct IV injection over a 2-minute period. In children younger than 2 years of age, a dose of 0.125 mg may be adequate. In one study, neonates were given cosyntropin 0.015 mg/kg IM. Since peak plasma cortisol concentrations usually occur 45-60 minutes after cosyntropin administration, some clinicians prefer to determine plasma cortisol concentrations at 60 minutes following injection of the drug. Although the 60-minute values are usually somewhat higher than the 30-minute values, the difference in most patients is probably not enough to outweigh the disadvantages of a longer testing period.

In patients with normal adrenocortical function, baseline plasma cortisol concentrations are greater than 5 mcg/dL, and 30-minute plasma cortisol concentrations are greater than 18 mcg/dL, with an increase of at least 7 mcg/dL above the control value. If the 60-minute test is used, a normal response is indicated by doubling of the baseline plasma cortisol concentration with an increase of 11 mcg/dL above the baseline value. Baseline plasma cortisol concentration and the degree of increase above the baseline concentration exhibit marked diurnal variation. However, the cortisol plasma concentration at 30 minutes following cosyntropin administration is constant, regardless of the time of the day, and the 30-minute plasma concentration (i.e., greater than 18 mcg/dL) should be the only criterion when tests are performed at various times during the day.

When a greater stimulus to the adrenal cortex is desired, 0.25 mg of cosyntropin may be added to dextrose or sodium chloride infusions and administered over a 4- to 8-hour period. Usually the drug is administered at a rate of approximately 0.04 mg per hour over a 6-hour period. The adrenal response may be measured by determining plasma cortisol concentrations or 24-hour urinary 17-OHCS and 17-KS excretion prior to and at the end of the infusion; plasma cortisol concentrations are usually better indicators of adrenal function than is urinary steroid excretion.

When subnormal cosyntropin test results are obtained, the patient is assumed to have adrenocortical insufficiency and further testing is required to determine if the insufficiency is primary or secondary and to determine the etiology of the insufficiency. The manufacturer of cosyntropin recommends that patients with subnormal cosyntropin test results be given 40 units of repository corticotropin injection IM twice daily for 4 days or 60 units twice daily for 3 days, followed by a second cosyntropin test. However, most clinicians recommend an 8-hour corticotropin infusion on each of 4-5 successive days, followed by a second rapid-screening cosyntropin test. In patients with primary adrenocortical insufficiency, there will be little or no increase in plasma cortisol concentrations following the second cosyntropin test; patients with secondary adrenocortical insufficiency will have higher or even normal plasma cortisol concentrations.

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Patients receiving cortisone or hydrocortisone on the test day may exhibit abnormally high baseline plasma cortisol concentrations and a paradoxical decrease in plasma cortisol concentrations following administration of cosyntropin. Patients receiving estrogens may have abnormally elevated plasma cortisol concentrations before and after cosyntropin administration, but a normal incremental response to cosyntropin still occurs. Because spironolactone metabolites fluoresce, erroneously high plasma cortisol concentrations may be reported in patients receiving spironolactone when fluorometric analysis is used but not when radioimmunoassay or competitive protein binding methods are used. Patients should not receive pretest doses of cortisone, hydrocortisone, or spironolactone on the day of testing when the fluorometric method is used; pretest doses of spironolactone can be given on the day of testing when radioimmunoassay or competitive protein binding methods are used. Since prednisone, dexamethasone, and betamethasone are not detectable by the fluorometric method, therapy with these drugs can be maintained. In patients with increased plasma bilirubin concentrations or with free hemoglobin in the plasma, falsely elevated fluorescence measurements may occur.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Cosyntropin/Agents Affecting Plasma Cortisol Levels

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Agents affecting plasma cortisol levels may impact the accuracy of the cosyntropin diagnostic test.(1)

CLINICAL EFFECTS: Concurrent use of agents affecting plasma cortisol levels may impact the accuracy of the cosyntropin diagnostic test.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of cosyntropin states accuracy of diagnosis using the cosyntropin diagnostic test may be complicated by concomitant medications affecting plasma cortisol levels.(1) Agents affecting plasma cortisol levels and recommendation to stop prior to cosyntropin diagnostic test include: - Glucocorticoids: May elevate plasma cortisol levels. Stop these drugs on the day of testing. Long-acting glucocorticoids may need to be stopped for a longer period before testing. - Spironolactone: May elevate plasma cortisol levels. Stop spironolactone on the day of testing. - Estrogen: May elevate plasma total cortisol levels. Discontinue estrogen containing drugs 4 to 6 weeks prior to testing to allow cortisol binding globulin levels to return to levels within the reference range. Alternatively, concomitant measurement of cortisol binding globulin at the time of testing can be done; if cortisol binding globulin levels are elevated, plasma total cortisol levels are considered inaccurate.(1)

DISCUSSION: Concurrent use of agents affecting plasma cortisol levels may impact the accuracy of the cosyntropin diagnostic test.(1)

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

There is no enhanced messaging for this drug.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

• No disease contraindications

There is no enhanced messaging for this drug.

Less Frequent

• Anaphylaxis

Rare or Very Rare

• Bradycardia
• Hypersensitivity drug reaction
• Hypertension

Less Frequent

• Injection site sequelae

Rare or Very Rare

• Peripheral edema
• Skin rash
• Tachycardia

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