Tuesday, March 22, 2011

How to Extend Your Supply of Cortrosyn and Lower the Cost of ACTH Stimulation Testing

Cortrosyn is expensive. And once reconstituted, it has a limited shelf-life.

However, by following the protocol outlined below, you can easily dilute, aliquot and store Cortrosyn after reconstitution for up to 6 months. This makes each ACTH stimulation test much less expensive, because each vial of Cortrosyn can be used to perform as many as five ACTH stimulation tests.

Cortrosyn is supplied in vials each containing 0.25 mg (250 μg) of synthetic ACTH (cosyntropin) in powder form. Because the dose of Cortrosyn used to perform an ACTH stimulation test is only 5 μg/kg, small to medium sized dogs require only a fraction of the ACTH contained in each vial.  

For more information on how to perform an ACTH stimulation test, see my post entitled, What's the best protocol for ACTH stimulation testing in dogs and cats?

How to aliquot and store each vial of Cortrosyn for subsequent use? It's simple — just follow the directions outlined here:

1. Reconstitute the Cortrosyn power by adding exactly 2.5-ml of sterile saline solution to the vial. With this dilution, the resulting concentration of the Cortrosyn solution in the vial would be 100 μg /ml.

2. Once Cortrosyn is reconstituted, aspirate 50-μg doses (0.5 ml) into 5 plastic syringes.  Or, if smaller ACTH doses are desired, aspirate 25-μg doses (0.25 ml) into 10 syringes.  (For more accurate dosing, I use insulin or tuberculin syringes).

    DO NOT store reconstituted Cortrosyn in glass containers or vials. The reason that the Cortrosyn needs to be stored in plastic is that ACTH will stick to glass, thereby lowering the available amount of Cortrosyn that would be injected at time of testing.

3. The syringes containing the reconstituted, diluted Cortrosyn should be labeled with the product, dose in each syringe, and the date the Cortrosyn was reconstituted.  

4. Freeze each of the syringes at -20oC.  Avoid storing these syringes in a frost-free freezer, which must periodically warm up to de-frost. Repeated freezing and thawing cycles would compromise the integrity of the Cortrosyn.

    When frozen properly, aliquots can be stored for up to 6 months without loss of efficacy.

5.  Alternatively, the Cortrosyn solution can be stored refrigerated (4oC) where it has been shown to be bioactive and stable for at least 4 weeks.


Diluting the Cortrosyn and using a low-dose ACTH stimulation test protocol is very cost-effective. In this way, 1 vial of Cortrosyn can be used to test multiple patients without compromising the quality of the test results.

As an example, at the 5-µg/kg dose, 5 dogs weighing 10 kg (22 lbs) can be tested using a single vial, reducing the cost of the drug by 80%. By looking at the cost benefit, it is clear that the savings could be significant by using this testing protocol.


Unknown said...

I'd love to see some supporting documentation for this technique. Can you direct me towards some potency and stability studies?

Unknown said...

I'd love to see some supporting documentation for this technique, specifically studies verifying potency, stability and sterilty for the 6 month beyond-use date. Thanks in advance.

Dr. Mark E. Peterson said...

I'd love a study of the potency of diluted cortrosyn at 6 months. If you wish to do the study, I'd be happy to help you set up the study design (if you need me).

Here's some references:

Kerl ME, Peterson ME, Wallace MS, Melián C, Kemppainen RJ. Evaluation of a low-dose synthetic adrenocorticotropic hormone stimulation test in clinically normal dogs and dogs with naturally developing hyperadrenocorticism. J Am Vet Med Assoc 1999,214:1497-501.

Martin LG, Behrend EN, Mealey KL, Carpenter DM, Hickey KC. Effect of low doses of cosyntropin on serum cortisol concentrations in clinically normal dogs. Am J Vet Res 2007;68:555-60.

Frank LA, Oliver JW. Comparison of serum cortisol concentrations in clinically normal dogs after administration of freshly reconstituted versus reconstituted and stored frozen cosyntropin. J Am Vet Med Assoc 1998;212:1569-1571.

Lathan P, Moore GE, Zambon S, et al. Use of a low-dose ACTH stimulation test for diagnosis of hypoadrenocorticism in dogs. J Vet Intern Med 2008;22:1070-1073.

n Pomerantz said...

If cortrosyn were to be out dated or stored improperly after splitting the vial, causing impairment of potency, would post stimulated cortisol be higher or lower? I am asking because as an admin on a canine cushing's support group, this question came up in a dog whose ACTH stimulation tests appear to be low with a pre 0.9 µg/dL and post stimulated cortisol of 1.6 µg/dL yet dog has return of pu/pd and chronic UTI's. Dog is on BID Trilostane. Thank you for your time.

Dr. Mark E. Peterson said...

The serum cortisol results would be lower if the cortrosyn was outdated.