Low-Dose ACTH Stimulation Testing in Cats

Cortisol and Aldosterone Response to Various Doses of Cosyntropin in Healthy Cats

Amy E. DeClue, Linda G. Martin, Ellen N. Behrend, Leah A. Cohn, David I. Dismukes, and Hollie P. Lee

Journal of the American Veterinary Medical Association 2011;238:176-182. 

Adrenocorticotropic hormone (ACTH) stimulation testing is commonly used to evaluate adrenocortical function in both dogs and cats (1-3). In cats, ACTH stimulation testing has been used primarily to test adrenocortical production of cortisol (4-6), but has also been used to evaluate the adrenal sex steroid (progestins and androgens) response (7-10).

Although the primary regulators of aldosterone secretion are the renin-angiotensin system and extracellular potassium concentration (11,12), ACTH acts as an additional stimulant (13). In accord with that fact, administration of exogenous ACTH to cats has been reported to cause a reliable increase in aldosterone secretion. Therefore, ACTH stimulation testing can also be used for evaluation of adrenal mineralocorticoid function (14).

Traditionally, a standard dose of cosyntropin (125 μg/cat, IV) has been recommended for ACTH stimulation testing (5). A previous study (15) documented that lower doses of cosyntropin will stimulate maximal cortisol secretion in cats. However, that study used per-cat dosing as opposed to per-body-weight dosing and did not evaluate the serum aldosterone response to ACTH stimulation.

The purpose of the study reported here by DeClue et al (16) were to determine the lowest dose of cosyntropin (Cortrosyn) on a per-body-weight basis that would produce maximal cortisol and aldosterone secretion in cats.  A secondary purpose was to determine the ideal timing of blood sample collection for cortisol and aldosterone concentrations after ACTH injection in these healthy cats.

Objective—To determine the lowest dose of cosyntropin on a per body weight basis that would produce maximal cortisol and aldosterone secretion and the ideal timing of blood sample collection after ACTH stimulation in healthy cats.

Design—Randomized crossover trial.

Animals—7 adult sexually intact male purpose-bred cats.

Procedures—Each cat received saline (0.9% NaCl) solution (control) and 5 doses (125 μg/cat and 10, 5, 2.5, and 1 μg/kg) of cosyntropin IV with a 2-week washout period between treatments. Blood samples were obtained before (baseline) and at 15, 30, 45, 60, 75, and 90 minutes after administration of saline solution or cosyntropin.

Results—Serum cortisol and aldosterone concentration increased significantly, compared with baseline values, after administration of all cosyntropin doses. Lower doses of cosyntropin resulted in an adrenocortical response equivalent to the traditional dose of 125 μg/ cat.

The lowest doses of cosyntropin that stimulated a maximal cortisol and aldosterone response were 5 and 2.5 μg/kg, respectively. Lower doses of cosyntropin resulted in a shorter interval between IV administration of cosyntropin and peak serum cortisol and aldosterone concentrations.

Conclusions and Clinical Relevance—Low-dose ACTH stimulation testing with IV administration of cosyntropin at 5 μg/kg followed by blood sample collection at 60 to 75 minutes resulted in concurrent peak serum cortisol and aldosterone concentrations that were equivalent to those achieved following administration of cosyntropin at 125 μg/cat, the standard dose currently used.

My Bottom Line:

This study confirms our earlier work that low doses of ACTH (e.g., 5 μg/kg body weight of cosyntropin) will maximally stimulate cortisol secretion in cats (15). In the cats of this study, as in our previous study, lower doses of cosyntropin resulted in an adrenocortical response that was equivalent to the traditional dose of 125 μg/cat (15, 16). The efficacy of of this low-dose ACTH stimulation testing protocol is also well documented in dogs (17-19), and has become a widely used testing dosage in clinical practice for evaluation of both hyper- and hypoadrenocorticism.

Based on the results of these cat studies, the following test protocol can be recommended:

1. Collect blood sample for basal cortisol (± aldosterone or sex steroids).
2. Calculate the cosyntropin (Cortrosyn) dosage (5 μg/kg of cat's body weight). To draw up this amount, it's best to reconstitute and dilute the Cortrosyn powder and store the remaining ACTH product (20).
3. Administer the cosyntropin dose to the cat by the IV route.
4. Collect a post-ACTH blood sample at 60-75 minutes after cosyntropin injection.

It is extremely important to point out that cosyntropin must be administered by the IV route in cats, especially when this low-dose protocol is used for ACTH stimulation testing. When given intramuscularly (IM) to cats, cosyntropin is not well absorbed and will not produce a maximal adrenocortical response (21). In cats, ACTH given by the IV route induces a greater and more prolonged adrenocortical stimu­lation than intramuscular administration.

This difference in the cortisol response between IV and IM administration is in contrast to the situation in dogs, in which IV or IM low-dose ACTH stimulation protocols produce similar adrenocortical responses (22). This difference between cats and dogs should not surprise us— we all know that cats are not just small dogs, especially when it comes down to endocrinology!

References:

1. Behrend EN, Kemppainen RJ. Diagnosis of canine hyperadrenocorticism. Vet Clin North Am Small Anim Pract 2001;31:985-1003.
2. Church DB. Canine hypoadrenocorticism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;156-166.
3. Herrtage ME, Ramsey IK. Canine hyperadrenocorticism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;167-189.
4. Peterson ME, Greco DS, Orth DN. Primary hypoadrenocorticism in ten cats. J Vet Intern Med 1989;3:55-58. 
5. Duesberg C, Peterson ME. Adrenal disorders in cats. Vet Clin North Am Small Anim Pract 1997;27:321-347. 
6. Peterson ME. Feline hyperadrenocorticism In: Mooney CT, Peterson ME, eds. BSAVA Manual of Canine and Feline Endocrinology. Fourth ed. Quedgeley, Gloucester: British Small Animal Veterinary Association, 2012;199-203.
7. DeClue AE, Breshears LA, Pardo ID, et al. Hyperaldosteronism and hyperprogesteronism in a cat with an adrenal cortical carcinoma. J Vet Intern Med 2005;19:355-358. 
8. Briscoe K, Barrs VR, Foster DF, et al. Hyperaldosteronism and hyperprogesteronism in a cat. J Feline Med Surg 2009;11:758-762. 
9. Quante S, Sieber-Ruckstuhl N, Wilhelm S, et al. Hyperprogesteronism due to bilateral adrenal carcinomas in a cat with diabetes mellitus. Schweiz Arch Tierheilkd 2009;151:437-442. 
10. Meler EN, Scott-Moncrieff JC, Peter AT, et al. Cyclic estrous-like behavior in a spayed cat associated with excessive sex-hormone production by an adrenocortical carcinoma. J Feline Med Surg 2011;13:473-478. 
11. Gogerly RL, Coghlan JP, Morgenroth P, et al. A compartmental model of acute stimulation of aldosterone secretion in vivo by potassium and ANG II. Am J Physiol 1993;265:E190-196. 
12. Pratt JH. Role of angiotensin II in potassium-mediated stimulation of aldosterone secretion in the dog. J Clin Invest 1982;70:667-672. 
13. Crabbe J, Reddy WJ, Ross EJ, et al. The stimulation of aldosterone secretion by adrenocorticotropic hormone (ACTH). J Clin Endocrinol Metab 1959;19:1185-1191. 
14. Zimmer C, Horauf A, Reusch C. Ultrasonographic examination of the adrenal gland and evaluation of the hypophyseal-adrenal axis in 20 cats. J Small Anim Pract 2000;41:156-160. 
15. Peterson ME, Kemppainen RJ. Dose-response relation between plasma concentrations of corticotropin and cortisol after administration of incremental doses of cosyntropin for corticotropin stimulation testing in cats. Am J Vet Res 1993;54:300-304. 
16. DeClue AE, Martin LG, Behrend EN, et al. Cortisol and aldosterone response to various doses of cosyntropin in healthy cats. J Am Vet Med Assoc 2011;238:176-182. 
17. 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. 
18. Kerl ME, Peterson ME, Wallace MS, et al. 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;214:1497-1501. 
19. 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. 
20. Peterson ME. How to extend your supply of cortrosyn and lower the cost of ACTH stimulation testing. Insights into Veterinary Endocrinology, Blog post, March 22, 2011.
21. Peterson ME, Kemppainen RJ. Comparison of intravenous and intramuscular routes of administering cosyntropin for corticotropin stimulation testing in cats. Am J Vet Res 1992;53:1392-1395. 
22. Behrend EN, Kemppainen RJ, Bruyette DS, et al. Intramuscular administration of a low dose of ACTH for ACTH stimulation testing in dogs. J Am Vet Med Assoc 2006;229:528-530. 

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