Page 90 - WSAVA2018
P. 90

 25-28 September, 2018 | Singapore
The practitioner should determine whether the patient has pituitary or adrenal dependent disease. This will direct therapy choice as well as help predict cost of treatment, explain potential neurologic disease, predict time of resolution of signs, and mitigate owner frustration with therapy (hopefully). An endogenous ACTH concentration can be evaluated. Dogs with adrenal tumors have low endogenous ACTH levels (<10 pg/ml). Mishandling of the plasma sample will result in artificially low ACTH levels, leading the practitioner to erroneously conclude the presence of an adrenal tumor. Abdominal ultrasound can be very helpful in identification of an adrenal tumor or bilateral adrenal hyperplasia. The practitioner should be cautious in interpreting results
of an abdominal ultrasound in that adrenal masses may be nonfunctional, may be a pheochromocytoma, or the animal may have pituitary-dependent disease as well as an adrenal tumor. Bilateral adrenal hyperplasia may also occur in animals with concurrent non-adrenal disease.
Medical treatment of HAC includes trilostane (VetorylR) and mitotane (LysodrenR). Ketoconazole and deprenyl (AniprilR) have also been advocated, but are substantially less effective than trilostane or lysodren. Surgical options include adrenalectomy and hypophysectomy. Trilostane is a competitive 3B-OH steroid dehydrogenase
inhibitor that inhibits the conversion of pregnenolone
to progesterone in the adrenal gland. This blocks the formation of the end products of progesterone including cortisol and aldosterone. Trilostane can be compounded but a manufactured product is available (Vetoryl R, Dechra Pharmaceuticals). VetorylR is FDA approved for veterinary use so that the veterinarian is legally protected. VetrorylR is much more consistent in active ingredients than compounded trilostane and should be used when possible. The drug must be given daily or twice daily. The recommended dose is 1.5-3 mg/kg, with the lower dose given bid considered safer and more efficacious. Side effects of trilostane are similar to those of mitotane and prednisone should be sent home with the owner similarly to that done with mitotane therapy. Side effects of trilostane include glucocorticoid, mineralocorticoid or glucocorticoid + mineralocorticoid deficiency. Complete adrenal necrosis has been reported, although this a rare and idiosyncratic response. Over time adrenal glands
will get enlarged and irregular, but no problems with this have been noted. Investigators have reported elevations of 17 OH progesterone indicating that trilostane has
other actions that those expected based on just its pharmacology.
Trilostane therapy should be monitored 10-14 days after initiation. An ACTH-stimulation test measuring cortisol is performed 4-6 hours after the morning dose of trilostane is given. Results of the ACTH-stimulation are ideally a cortisol in the normal range pre- and post- ACTH with little stimulation, similar to what is desired with lysodren therapy. A sodium/potassium
level should be measured as well. This often decreases with trilostane treatment because of increasing K+
due to loss of aldosterone function.Mitotane is a DDT derivative. It kills adrenocortical cells with a preference for the cortisol producing ones (zonae fasciculata and reticularis). The induction phase consists of administering 35 (big dog)-50 (little dog) mg/kg PO q.d. x 5-7 d. The maintenance phase is 35-50 mg/kg PO divided twice per week. The practitioner may work with the 500 mg tablet size or may have it compounded. Owners should be discharged with instructions to call the veterinarian
if any of the danger signs including loss of appetite, lethargy, vomiting, diarrhea, or “just aint right” occur. The practitioner should also send home at least 2 doses of prednisone at 0.5 mg/kg to be given if the animal becomes ill from the mitotane. Side effects of mitotane include: adrenal cortical destruction producing a glucocorticoid-deficient addisonian or a full-blown addisonian. Often the adrenocortical deficiency is reversible. Another side effect is liver toxicity. This
often resolves once off Lysodren, but it cannot be
used again. Monitoring mitotane therapy should occur after the induction phase. An ACTH-stimulation test should be performed the morning after the last dose of mitotane during the induction phase. Ideally the cortisol should be within the normal range pre- and post- ACTH injection. ACTH should cause a minimal increase in
the cortisol level. The practitioner should also perform bloodwork to evaluate liver health. Clinical signs of the animal should be discussed with the owner. In cases where the ACTH-stimulation test results do not agree with the resolution (or non resolution) of clinical signs reported by the owner, the clinical signs should be believed. Which therapy should the practitioner choose to treat HAC. In comparing trilostane and mitotane, both are as efficacious in controlling clinical signs and in the longevity of the treated animals with PDH or adrenal dependent disease. Both are sold commercially and cost is approximately the same. Some considerations are that trilostane must be given every day while mitotane can be given 2-3 times per week in a stabilized animal. Mitotane should not be given to animals with liver disease. The effects of adrenal gland hyperplasia/metaplasia by trilostane have not been fully investigated but appear to be unproblematic. The author recommends the use of trilostane initially as it is easier and safer for owners to administer; mitotane tablets are not coated and owners can ingest excess drug power if they do not wash their hands frequently. The dosing schedule for trilostane is also easier for owners to manage. If dogs do not respond well to trilostane, mitotane therapy can be instituted.

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