Comparison of methods to monitor dogs with hypercortisolism treated with trilostane

Abstract

Background The use of adrenocorticotropic hormone stimulation test as method to monitor efficacy of trilostane treatment of hypercortisolism (HC) in dogs has been questioned. Objectives To evaluate and compare 12 methods with which to monitor efficacy of trilostane treatment in dogs with HC. Animals Forty‐five client‐owned dogs with HC treated with trilostane q12h. Methods Prospective cross‐sectional observational study. The dogs were categorized as well‐controlled, undercontrolled, and unwell through a clinical score obtained from an owner questionnaire. The ability to correctly identify trilostane‐treatment control of dogs with HC with the following variables was evaluated: before trilostane serum cortisol (prepill), before‐ACTH serum cortisol, post‐ACTH serum cortisol, plasma endogenous ACTH concentrations, prepill/eACTH ratio, serum haptoglobin (Hp) concentration, serum alanine aminotransferase (ALT), gamma‐glutamyl transferase (γGT) and alkaline phosphatase activity, urine specific gravity, and urinary cortisol : creatinine ratio. Results Ninety‐four re‐evaluations of 44 dogs were included; 5 re‐evaluations of 5 unwell dogs were excluded. Haptoglobin was significantly associated with the clinical score (P < .001) and in the receiver operating characteristic analysis, Hp cutoff of 151 mg/dL correctly identified 90.0% of well‐controlled dogs (specificity) and 65.6% of undercontrolled dogs (sensitivity). Alanine aminotransferase (P = .01) and γGT (P = .009) were significantly higher in undercontrolled dogs. Cutoff of ALT and γGT greater than or equal to 86 U/L and 5.8 U/L, respectively, were significantly associated with poor control of HC by trilostane. Conclusions and Clinical Importance Of all the 12 variables, Hp, and to a lesser degree ALT and γGT, could be considered additional tools to the clinical picture to identify well‐controlled and undercontrolled trilostane‐treated dogs.

Increases in serum carbonylated protein levels of dogs with hypercortisolism

“…However, the haptoglobin level has been reported to decrease during trilostane treatment [27][28][29]. Another recent study of dogs with HC reported that haptoglobin is significantly associated with clinical scores [21]. During this study, the immune intensity of haptoglobin did not clearly alter based on the HC conditions, but the carbonylated haptoglobin ratio was low in well-managed HC patients treated with trilostane.…”

“…Our data suggest that protein carbonylation, which is one of the oxidative stress reactions, could be influenced by the medical control of HC. Although various methods have been considered for monitoring the health status after starting trilostane therapy, the gold standard has not yet been established for dogs with HC [19][20][21][22][23]. Additionally, the present results suggest that the carbonylation level of a 40-kDa protein could be a new factor used to monitor the medical condition of dogs with HC.…”

Urinary cortisol‐creatinine ratio in dogs with hypoadrenocorticism

“…The UCCR is currently routinely used as a screening test for dogs with spontaneous hypercortisolism, 20 and few studies have investigated its performance in monitoring dogs with hypercortisolism on a trilostane or mitotane regimen. 21 , 22 , 23 , 24 , 25 , 26 However, the use of the UCCR has not been evaluated in diagnosing spontaneous HA.…”

Ultrasonographic Changes of Adrenal Glands Size under Trilostane Therapy, Their Correlation with Clinical Signs and Endocrine Tests and Possibility of Introducing Ultrasound as Additional Monitoring Modality of Cushing’s Syndrome

“…It is important to be mentioned that adrenal gland enlargement is not only observed in patients with cushing's syndrome, but as well in patients with primary hyperaldosteronism, pheochromocytoma, incidentaloma, acromegaly and sometimes in patients with severe chronic or acute diseases (pyometra, severe gastro-enteritis, glomerulonephritis, etc.). Because in this study low dose of trilostane was used as initial dosage, no dog showed any sign of hypoadrenocorticism and therefore no data is available on adrenal gland enlargement in alanine aminotransferase-ALT, gamma-glutamyl transferase-γGT) [16] with assessment of adrenal gland enlargement (together with clinical examination and endocrine tests) could as well be considered. Limitation of using abdominal ultrasound as a monitoring tool could be: demand for skilled sonographer and difficulties in obtaining measurements at the same position every time.…”