Page 900 - Small Animal Internal Medicine, 6th Edition

872 PART VI Endocrine Disorders

Cholesterol electrolytes should be performed 4 weeks after initiation of
K,A 17-OH Pregnenolone Dehydroepiandrosterone treatment and approximately 4 hours after trilostane admin-
Pregnenolone
VetBooks.ir Progesterone 17-OH Progesterone Androstenedione istration. Results of ACTH stimulation tests started at
T
T
T
different times may yield significantly different results so
11-Deoxycorticosterone 11-Deoxycortisol subsequent ACTH stimulation tests should be started at or
about the same time (Bonadio et al., 2014). In addition, the
K,M K,M
Corticosterone Cortisol client should bring in a urine sample collected at home the
K morning of the ACTH stimulation test for a UCCR. The
Aldosterone goals of therapy include clinical improvement without devel-
FIG 50.15 opment of illness, a suppressed adrenocortical response to
Steroid biosynthetic pathways in the adrenal cortex. The ACTH, and a normal UCCR. Results of the ACTH stimula-
branching pathways for glucocorticoids, mineralocorticoids, tion test are used to adjust the dosage of trilostane, and
and adrenal androgens are shown. The site of blockade in serum electrolytes are monitored for changes consistent with
the steroid biosynthetic pathways by the enzyme inhibitors the onset of hypoaldosteronism. The goal of the ACTH stim-
trilostane (T), ketoconazole (K), metyrapone (M), and ulation test is a post-ACTH cortisol concentration between
aminoglutethimide (A) are also shown.
2 and 5 µg/dL (60 and 145 nmol/L). However, it may take
several weeks before maximum suppression of adrenocorti-
cal function is attained, and some dogs may need TID treat-
hyperadrenocorticism. Trilostane is effective in dogs with ment to attain control of hyperadrenocorticism. Frequent
PDH and ADH, the clinical efficacy of trilostane is excellent adjustments in the trilostane dose should be avoided, espe-
(~90%), and trilostane can control clinical signs of hyperad- cially if post-ACTH cortisol concentrations are between 5
renocorticism in dogs for prolonged periods (longer than 1 and 8 µg/dL (145 and 225 nmol/L), the owner is reporting
year). Trilostane is used as the primary treatment modality improvement in clinical signs, and the dog appears to be
for PDH in dogs, as an alternative in dogs in which mitotane doing well. Similarly, dogs that attain a post-ACTH cortisol
is ineffective or not usable because of problems with drug concentration between 2 and 5 µg/dL shortly after trilostane
sensitivity, as a means of reversing the metabolic derange- treatment is initiated should be watched closely for develop-
ments of hyperadrenocorticism before adrenalectomy in ment of clinical signs of hypoadrenocorticism. Once control
dogs with ADH, and as a medical option to control clinical of the hyperadrenal state is attained, an ACTH stimulation
signs in dogs with metastatic adrenocortical tumors causing test, serum electrolytes, and UCCR should be evaluated
ADH. every 3 to 4 months—sooner if clinical signs of hypercorti-
Trilostane is currently available as 5-, 10-, 30-, 60-, and solism or hypocortisolism develop.
120-mg capsules. Compounded trilostane products are not Adverse effects of trilostane include lethargy, vomit-
recommended because of documented variation in actual ing, and electrolyte shifts compatible with hypoadreno-
trilostane content in some compounded capsules versus the corticism. Trilostane should be discontinued until adverse
prescribed strength of the compounded capsule (Cook et al., effects dissipate and then trilolstane should be reinitiated
2012)—a variation that could influence the dog’s response to at a lower dose, frequency of administration, or both. Per-
treatment. Some dogs have problems with short duration of manent hypoadrenocorticism has been reported in a small
cortisol suppression (<10 hours) that may result in persis- number of dogs, presumably caused by trilostane-induced
tence of clinical signs, subsequent administration of large adrenocortical necrosis. Acute death has been reported
doses of trilostane, and greater likelihood of adverse reac- in a small number of dogs shortly after initiation of tri-
tions to the drug. In our experience, twice-daily dosing using lostane treatment. The reason for this is not known, but
a lower dose provides better control than once-daily dosing, it may be affiliated with concurrent disease such as a
and the occurrence and severity of adverse reactions are less hepatopathy.
frequent. We routinely use an initial dosage of approximately
1 mg/kg twice a day administered with food to increase MITOTANE
gastrointestinal absorption. Chemotherapy using mitotane (o,p′DDD; Lysodren) is an
Dosage adjustments are based on the history, findings on effective treatment for PDH and should be considered in
physical examination, and results of serum electrolytes, dogs that have a poor response to trilostane. Mitotane has
ACTH stimulation test, and UCCR. Baseline serum cortisol also been used to treat ADH (i.e., cortisol secreting adrenal
concentrations should not be used to monitor trilostane tumor) although our preference is to use trilostane (see
treatment. A history and physical examination should be section on adrenalectomy). Two treatment protocols have
performed 2 weeks after trilostane treatment is initiated to been used: the traditional approach, the goal of which is to
ensure that problems related to hypocortisolism (e.g., leth- control the hyperadrenal state without causing clinical signs
argy, loss of appetite, vomiting) have not developed and that of hypoadrenocorticism; and medical adrenalectomy, the
the dog is healthy. An ACTH stimulation test and serum goal of which is to destroy the adrenal cortex using mitotane
electrolytes should be performed if problems have developed to create permanent hypoadrenocorticism. We prefer the
at 2 weeks; otherwise an ACTH stimulation test and serum traditional approach, which involves two phases of mitotane