In 2001, trilostane, a synthetic steroid analogue, was licensed in the United Kingdom for treating canine pituitary-and adrenal-dependent
hyperadrenocorticism. Trilostane is currently undergoing Food and Drug Administration (FDA) review for the same purposes in
the United States. In this article, I briefly review the diagnosis and treatment of hyperadrenocorticism and then present
the current knowledge on trilostane, discuss therapeutic considerations, and address possible adverse effects.
HYPERADRENOCORTICISM
Hyperadrenocorticism is a clinical syndrome arising from chronic, excessive exposure to glucocorticoids. It is also referred
to as Cushing's syndrome in recognition of the work done by Dr. Harvey Cushing, a pioneering neurosurgeon, in the early 1900s. There are three types
of hyperadrenocorticism. >
Table 1 Clinical Signs of Hyperadrenocorticism
|
-
Pituitary-dependent hyperadrenocorticism (PDH) involves excessive cortisol secretion in response to an inappropriate release of adrenocorticotropic hormone (ACTH) by a
pituitary tumor (usually a benign adenoma). This form of hyperadrenocorticism is also called Cushing's disease.
-
Adrenal-dependent hyperadrenocorticism involves excessive cortisol secretion by an adrenocortical tumor and can be benign or malignant.
-
Iatrogenic hyperadrenocorticism is due to exogenous glucocorticoid administration—oral, parenteral, or topical. It resolves when glucocorticoids are discontinued.
Diagnosis
Table 2 Laboratory Abnormalities Associated with Hyperadrenocorticism
|
In patients with the clinical signs of hyperadrenocorticism (Table 1) and supportive findings on routine laboratory tests (Table 2), the diagnosis must be confirmed before therapy is considered.
Table 3 ACTH Stimulation Testing Methodology and Interpretation
|
The two screening tests commonly used to diagnose hyperadrenocorticism are the ACTH stimulation test and the low-dose dexamethasone
suppression test. The ACTH stimulation test (Table 3)1 is quicker and requires less venipuncture, but it may be less sensitive than the low-dose dexamethasone suppression test
is.2 However, it is the only way to identify a patient with iatrogenic hyperadrenocorticism, and it provides information for post-treatment
comparisons. The advantage of the low-dose dexamethasone suppression test (Table 4) is its potential for differentiating PDH from adrenocortical tumors.3
Table 4 Low-dose Dexamethasone Suppression Testing Methodology and Interpretation
|
It is important to determine whether a patient has PDH or an adrenocortical tumor. The easiest way to answer this question
is by performing an abdominal ultrasonographic examination. A competent scanner can easily identify both adrenal glands and
assess their size and shape. Bilaterally normal or enlarged glands support PDH; asymmetry with a mass on one gland and atrophy
of the other gland indicates an adrenocortical tumor. Other ways to differentiate between PDH and an adrenocortical tumor
include measuring endogenous ACTH concentrations (normal or elevated in patients with PDH, low in patients with hyperadrenocorticism
due to an adrenocortical tumor) and performing a high-dose dexamethasone suppression test (suppression supports a diagnosis
of PDH). Abdominal radiography may reveal calcification associated with an adrenal mass but is not a sensitive test for this
purpose.
Featuring Information from:
