Trilostane: A therapeutic consideration for canine hyperadrenocorticism - Veterinary Medicine
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Trilostane: A therapeutic consideration for canine hyperadrenocorticism
Choices in medical therapy for dogs with hyperadrenocorticism can be limited. Studies have shown that trilostane provides another option for treating this disease—as well as alopecia X.


VETERINARY MEDICINE


Treating alopecia-X

Alopecia-X is a dermatologic disorder usually described in Pomeranian, poodle, and husky breeds. It is related to an arrest in the normal hair growth cycle and has been associated with deregulation of both growth hormone and adrenal androgen synthesis.23 In classic cases, nonpruritic truncal alopecia occurs; no other signs or changes are noted.

Many of these dogs have elevated concentrations of the precursors to cortisol, particularly 17-hydroxyprogesterone. A recent study evaluating trilostane's effectiveness in 24 affected dogs (Pomeranians and miniature poodles) reported a 90% response rate within eight weeks.24 Trilostane was given once or twice daily, with a mean dose of 10.85 mg/kg/day. No adverse effects were noted, and it was concluded that the hair growth was related to downregulation of adrenal steroid synthesis or inhibition of estrogen receptors within the hair follicles themselves.24 Three affected Alaskan malamutes showed similar positive responses when given 3 mg/kg trilostane twice daily.25

Treating atypical hyperadrenocorticism

Atypical hyperadrenocorticism is a recently described disorder in which patients manifest clinical signs suggesting hyperadrenocorticism, but the diagnosis is not supported by the results of standard screening tests (an ACTH stimulation test and a low-dose dexamethasone suppression test).26 If detailed steroid profiles are performed (e.g. University of Tennessee College of Veterinary Medicine Clinical Endocrinology Service adrenal panel: cortisol, estradiol, androstenedione, 17-hydroxyprogesterone, progesterone, and aldosterone), affected patients have abnormal resting and post-ACTH concentrations of one or more of the cortisol precursors or adrenal androgens or estrogens. Many of these patients have adrenal tumors, so abdominal ultrasonography is always warranted before starting medical therapy.

A detailed discussion of these cases is beyond the scope of this review. However, depending on the particular steroid deregulation identified, trilostane may be an appropriate choice for some of these cases unless a surgical lesion is identified. A thorough understanding of the adrenocortical biochemical pathways is necessary to make an appropriate medical plan (Figure 1), and consultation with an endocrinologist may be helpful. If either mitotane or trilostane is used, careful monitoring for signs of hypocortisolemia is still warranted.

CONCLUSION

Dogs with hyperadrenocorticism that do not respond to mitotane or other forms of medical therapy may benefit from trilostane therapy. Any practitioner using trilostane should be familiar with the likely side effects and be able to adequately monitor patients during therapy. Prompt recognition of potentially life-threatening complications is imperative, and appropriate supportive care must be available. Clients must be informed that trilostane is not approved in the United States, educated on the warning signs of adrenal insufficiency, and given clear instructions about when to discontinue therapy and seek veterinary care.

Editors' note: Dr. Cook is an educational and marketing consultant for Dechra Pharmaceuticals, PLC.

Audrey K. Cook, BVM&S, MRCVS, DACVIM, DECVIM-CA
Department of Small Animal Clinical Sciences
College of Veterinary Medicine & Biomedical Sciences
Texas A&M University
College Station, TX 77843

REFERENCES

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15. Barker EN, Campbell S, Tebb AJ, et al. A comparison of the survival times of dogs treated with mitotane or trilostane for pituitary-dependent hyperadrenocorticism. J Vet Intern Med 2005;19(6):810-815.

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17. Reusch CE, Sieber-Ruckstuhl N, Wenger M, et al. Histological evaluation of the adrenal glands of seven dogs with hyperadrenocorticism treated with trilostane. Vet Rec 2007;160(7):219-224.

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26. Ristic JME, Ramsey IK, Heath EM, et al. The use of 17-hydroxyprogesterone in the diagnosis of canine hyperadrenocorticism. J Vet Intern Med 2002;16(4):433-439.


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