Cautions

Trilostane should be given with food. In dogs receiving trilostane, only minor side effects, such as mild lethargy and decreased appetite two to four days from the start of therapy (potentially due to hypocortisolemia) and mild electrolyte abnormalities, are commonly seen. Overt hypoadrenocorticism seems to be a rare event, despite the marked decrease in serum cortisol concentrations found shortly after trilostane dosing. While sporadic cases of acute adrenal necrosis have been reported, this side effect is rare with trilostane. Keep in mind that mitotane works by inducing adrenal necrosis.

Trilostane can cause hyperkalemia through its aldosterone-inhibiting effect, so use caution if you administer it to a patient receiving a potassium-sparing diuretic. Trilostane may also potentiate the effect of angiotensin-converting enzyme inhibitors (again because of its aldosterone inhibiting effect), but no studies have evaluated this. No adverse drug interactions have been seen in dogs receiving trilostane and several nonsteroidal anti-inflammatory drugs, various antibiotics, insulin, or levothyroxine.

It is important to regularly monitor the clinical and biochemical effects of therapy and to adjust the trilostane dose to achieve optimal control. All ACTH stimulation tests must be performed four to six hours after trilostane administration and interpreted in light of the history and the findings of a thorough physical examination.

The long view

We need to continue to enhance our understanding of the etiopathogenesis of canine hyperadrenocorticism and eventually move beyond drugs that attack the end organ through adrenal enzyme inhibition (trilostane) or adrenocorticolysis (mitotane). It is likely that soon we will be able to address the primary cause by administering medications that alter gene expression, induce apoptosis, or decrease hormonal hypersecretion of ACTH from the pituitary gland. Potential therapies would include medications that include ligands for the peroxisome proliferator-activated receptor and retinoic acid receptors as well as medications that bind to somatostatin receptors. However, until that time, in my opinion, trilostane offers us the best option to manage dogs with moderate to severe signs of hyperadrenocorticism. At our hospital, we have treated more than 300 dogs with trilostane over the past five years, and it is our drug of choice for initial therapy.

RADIOIODINE THERAPY

Radioiodine therapy appears to be the safest and most effective therapy for hyperthyroidism in cats. Radioiodine may be administered intravenously, subcutaneously, or orally. While all routes appear effective, oral administration is discouraged because of the risk of human exposure and environmental contamination.

The largest radioiodine treatment safety and efficacy study involved 524 cats.⁸ Serum T₄ concentrations remained high in 80 cats initially, but dropped within or below the reference range in all but eight cats by six months after radioiodine administration. Although many cats had low serum T₄ concentrations after radioiodine treatment, only 11 cats required L-thyroxine therapy. Thirteen cats had a relapse of hyperthyroidism. Overall, 94% of the cats showed a good treatment response, and their median survival time was two years. A year after treatment, 89% of the cats were alive, and two and three years after treatment, 72% and 52% were alive, respectively. These percentages are important because pet owners may find this information on the Internet and erroneously assume that the cats die because of hyperthyroidism or its treatments. In reality, the cats die of senior diseases unrelated to hyperthyroidism.

Also keep in mind that cats with thyroid carcinoma are candidates for radioiodine therapy, especially after surgical debulking of neoplastic tissue.⁹ However, a higher percentage of these cats may require L-thyroxine supplementation after radioiodine treatment.

Feline hyperthyroidism can be treated safely, simply, and effectively with radioiodine therapy. Availability continues to increase as more and more centers become licensed. In addition, the cost of therapy has decreased, as routine scintigraphy appears not to be necessary to determine an effective radioiodine dose.¹⁰

David S. Bruyette, DVM, DACVIM, VCA West Los Angeles Animal Hospital, 1818 S. Sepulveda Blvd, West Los Angeles, CA 90025.

REFERENCES

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3. Kintzer PP, Peterson ME. Mitotane (o,p'DDD) treatment of 200 dogs with pituitary-dependent hyperadrenocorticism. J Vet Intern Med 1991;5(3):182-190.

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8. Peterson ME, Becker DV. Radioiodine treatment of 524 cats with hyperthyroidism. J Am Vet Med Assoc 1995;207(11):1422-1428.

9. Guptill L, Scott-Moncrieff CR, Janovitz EB, et al. Response to high-dose radioactive iodine administration in cats with thyroid carcinoma that had previously undergone surgery. J Am Vet Med Assoc 1995;207(8):1055-1058.

10. Forrest LJ, Baty CJ, Metcalf MR, et al. Feline hyperthyroidism: efficacy of treatment with volumetric analysis for radioiodine dose calculation. Vet Radiol 1996;37:141-145.