Cosyntropin (Monograph)

Drug class: Adrenocortical Insufficiency
VA class: DX900
Chemical name: α1–24-Corticotropin
CAS number: 16960-16-0

Medically reviewed by Drugs.com on Nov 21, 2024. Written by ASHP.

Introduction

Cosyntropin, a synthetic adrenocorticotropic hormone, is principally used in the diagnostic assessment of adrenocortical function.

Uses for Cosyntropin

Cosyntropin is used as an aid in the diagnosis of adrenocortical insufficiency. The 30-minute cosyntropin test (see Dosage and Administration: Dosage) provides a good method of screening for primary adrenocortical insufficiency (Addison’s disease) and is preferable to corticotropin for rapid screening since it is less likely to cause allergic reactions. When a greater stimulus to the adrenal cortex is desired, corticotropin or cosyntropin may be administered by IV infusion. If subnormal increases in plasma cortisol concentrations occur following administration of corticotropin or cosyntropin, additional tests providing prolonged stimulation of the adrenal cortex are required before impaired adrenocortical function can be diagnosed precisely and differentiation between primary and secondary adrenocortical insufficiency can be established.

Investigationally, long-acting IM depot cosyntropin preparations have been used as an aid in the diagnosis of adrenocortical insufficiency and, in patients with normal adrenocortical function, in the long-term management of chronic inflammatory and degenerative disorders that are responsive to glucocorticoids.

Cosyntropin Dosage and Administration

Reconstitution and Administration

Cosyntropin is administered by IM or IV injection or by IV infusion. Cosyntropin injection is reconstituted for IM or direct IV administration by adding 1 mL of 0.9% sodium chloride injection to a vial labeled as containing 0.25 mg to provide a solution containing 0.25 mg of cosyntropin per mL.

Dosage

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.

Cautions for Cosyntropin

Except for hypersensitivity reactions, short-term administration of cosyntropin, even in massive doses, is unlikely to produce harmful effects. When the drug is used for longer than brief periods, however, it can produce a variety of devastating effects.

Cosyntropin is less antigenic than corticotropin and is less likely to produce allergic reactions than is corticotropin; however, hypersensitivity reactions have occurred rarely. Patients known to be sensitized to corticotropin and who have markedly positive skin tests usually react negatively when tested intradermally with cosyntropin. Some patients who are hypersensitive to corticotropin preparations may be able to tolerate cosyntropin, but cross-sensitivity reactions may occur. The possibility of hypersensitivity reactions should be considered in all patients receiving cosyntropin, especially in those with preexisting allergic diseases and/or a history of allergic reactions to corticotropin. Patients should be carefully observed for hypersensitivity reactions during and after administration of cosyntropin. Appropriate agents (e.g., epinephrine, corticosteroids, oxygen) for the treatment of an acute hypersensitivity reaction and equipment for maintenance of an adequate airway should be readily available whenever cosyntropin is administered.

Cosyntropin is contraindicated in patients with a known hypersensitivity to cosyntropin.

Drug Interactions

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.

Pharmacology

Cosyntropin elicits all the pharmacologic responses usually produced by endogenous corticotropin; however, cosyntropin is immunologically much less active than corticotropin since most of the antigenic activity of corticotropin has been attributed to the C-terminal portion of the molecule (i.e., the 22–39 amino acid residues). In patients with normal adrenocortical function, cosyntropin stimulates the adrenal cortex to secrete cortisol (hydrocortisone), corticosterone, several weakly androgenic substances, and to a very limited extent aldosterone. When cosyntropin is used diagnostically, the effect of the drug is usually measured by determining plasma cortisol concentrations prior to and following administration of the drug. In patients with primary adrenocortical insufficiency (Addison’s disease), cosyntropin does not substantially increase plasma cortisol concentrations.

In healthy individuals, the rate of release of corticotropin from the anterior pituitary is determined by a balance of inhibitory effects of the secretions of the adrenal cortex on the pituitary (negative corticosteroid feedback mechanism) and the excitatory effects of the nervous system. In response to neurogenic stimuli, corticotropin-releasing factor (CRF) is released from neuronal endings in the median eminence of the hypothalamus and transported in the hypophyseal-portal vessels to the anterior pituitary, where corticotropin is released. Cosyntropin, via cyclic 3′,5′-adenosine monophosphate (cAMP), controls the initial rate-limiting step in steroidogenesis from cholesterol and leads to the synthesis of adrenocortical hormones.

Cosyntropin Pharmacokinetics

Absorption

Following oral administration, cosyntropin is inactivated by the proteolytic enzymes of the GI tract. Cosyntropin is rapidly absorbed following IM administration. More cortisol is secreted with a fixed dose of cosyntropin if the drug is given slowly IV rather than rapidly. Increasing the IM or IV dose of cosyntropin increases the duration of action. Repeated IV infusions of cosyntropin over an 8-hour period on successive days increase the responsiveness of the adrenal cortex to further stimulation by the drug.

Following rapid direct IV administration of 0.25 mg of cosyntropin in patients with normal adrenocortical function, plasma cortisol concentrations begin to increase within 5 minutes and are approximately doubled within 15–30 minutes. After IM or rapid direct IV administration of 0.25 mg of cosyntropin in patients with normal adrenocortical function, peak plasma cortisol concentrations are usually achieved within 1 hour and begin to decrease after 2–4 hours.

In healthy individuals who sleep at night, plasma concentrations of endogenous corticotropin undergo diurnal rhythm and are high in the morning and low in the evening. At rest, normal endogenous plasma concentrations of corticotropin in the morning are 5–95 pg/mL; with activity or stress in persons with normal HPA axis function, plasma concentrations may increase to 200–600 pg/mL.

Distribution and Elimination

The precise distribution and metabolic fate of cosyntropin is not known, but the drug is rapidly removed from the plasma by many tissues. Cosyntropin apparently does not cross the placenta.

Chemistry and Stability

Chemistry

Cosyntropin, α^1-24-corticotropin, is a synthetic polypeptide which is identical to the first 24 of the 39 amino acids in naturally occurring corticotropin.

Commercially available cosyntropin for injection occurs as a lyophilized white to off-white powder which contains mannitol. Each 0.25 mg of cosyntropin is equivalent to 25 units of corticotropin.

Stability

Following reconstitution with 1 mL of 0.9% sodium chloride injection, cosyntropin solutions have a pH of 5.5–7.5 and are stable for 24 hours when stored at room temperature or for 21 days at 2–8°C. After further dilution, the drug is stable for 12 hours at room temperature if the pH of the solution is 5.5–7.5. Cosyntropin is inactivated by enzymes and the drug should not be added to blood or plasma infusions.

Compatibility of cosyntropin for injection with other drugs depends on several factors (e.g., concentration of the drugs, specific diluents used, resulting pH, temperature). Specialized references should be consulted for specific compatibility information.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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