Fun with atypical Cushing's disease and extended adrenal panels (Proceedings) - Veterinary Healthcare
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Fun with atypical Cushing's disease and extended adrenal panels (Proceedings)


CVC IN BALTIMORE PROCEEDINGS

One of the most common endocrine disorders of dogs is hyperadrenocorticism (HAC). Clinical disease results from excess secretion of hormone from the adrenal cortex. Canine Cushing's Syndrome (CCS), refers to a collection of clinical signs and chemical abnormalities that stem from chronic exposure to excessive concentrations of glucocorticoids. Under the general category of naturally occurring HAC are pituitary dependent hyperadrenocorticism (PDH) and adrenal dependent hyperadrenocorticism (ADH). Regardless of the underlying cause of the HAC, there is an elevation of systemic adrenocortical hormones. The clinical signs most frequently seen in a Cushing's patient are: polydipsia, polyuria, alopecia, pendulous abdomen, hepatomegaly, polyphagia, muscle weakness, anestrus, muscle atrophy, comedones, panting, hyperpigmentation, testicular atrophy, calcinosis cutis, and facial nerve paralysis. Laboratory abnormalities associated with CCS include: mature leukocytosis, neutrophilia, lymphopenia, eosinopenia, increased alkaline phosphatase, alanine transferase, cholesterol, fasting blood glucose, abnormal bile acids, lipemia, and a urine specific gravity (USG) < 1.015 (Table 2). Diagnosis of CCS is generally made based on clinical signs, laboratory abnormalities, and results of one, or a combination of screening tests: adrenocorticotropic hormone (ACTH) stimulation test, low dose dexamethasone (LDDS) test, urine cortisol:creatinine ratio.

Patients sometimes present with the constellation of clinical signs compatible with CCS, without concurrent elevation of plasma cortisol levels. Instead, plasma levels of cortisol precursors or androgens are elevated. "Atypical Cushing's" has been used to describe the syndrome in these patients. It been hypothesized that these 'atypical' cases may involve a relative deficiency in some of the enzymes critical to the synthesis of cortisol. 21-β hydroxylase and 11-β hydroxylase have been investigated as enzymes that are deficient in the synthesis pathway. It has been suggested that without the requisite enzymes the steroid synthesis pathway is blocked, resulting in abnormal increases in plasma concentrations of active cortisol precursors or sex hormones. This has been seen in dogs with adrenal dysfunction, PDH, and non-cortisol secreting adrenal tumors (ATs). In these cases, neither ACTH stimulation, measuring cortisol, nor low dose dexamethasone tests will be diagnostic for CCS. Thus, a patient can present with clinical signs strongly suggestive of CCS, but without supportive diagnostic results on routine endocrine screening tests. These patients can be diagnosed using the extended adrenal panel. The results of these panels must be interpreted with caution. To make the diagnosis of atypical cushing's disease, there must be a significant increase of at least 2 precursor/sex hormones along with appropriate patient clinical signs.

A similar syndrome of excess adrenorcortical hormone secretion that does not involve cortisol has been described: Alopecia X. Many of these patients are seen by dermatologists for evaluation of alopecia. It should be noted that while Atypical CCS and Alopecia X are poorly understood and may share similar clinical signs of hair loss, they are not the same syndrome. The clinical signs of the latter are predominantly limited to changes in hair coat; the clinical signs of the former are far more similar to PDH or AT. The relationship of steroid hormones and Alopecia X as well as the treatment of this condition with trilostane, melatonin, and mitotane has been examined. However, to our knowledge, no detailed examination of treatment efficacy in atypical CCS has been made.

Trilostane is a hormonally inactive steroid competitive inhibitor 3β-hyydroxysteroid dehydrogenase. This enzyme mediates the conversion of pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, and androstenediol. Trilostane has been reported to be effective in the treatment of Alopecia X and CCS. Historically mitotane has been used to treat HAC, specifically PDH. Mitotane selectively and progressively destroys the adrenal cortex. This can be partial or complete, depending upon the treatment protocol selected. There are clear advantages to mitotane, including reported efficacy >80% in dogs with PDH. However, there are disadvantages that must be considered, including potential for development of adrenocortical insufficiency, relatively high relapse frequency, and drug intolerance. Melatonin alters gonadotropin release and sex hormone concentrations. While melatonin does impact the circadian and seasonal reproductive cycles, it does not appear to impact the glucocorticoids.

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Source: CVC IN BALTIMORE PROCEEDINGS,
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