Lack of association between clinical signs and laboratory parameters in dogs with hyperadrenocorticism before and during trilostane treatment

Abstract

INTRODUCTION Trilostane therapy, the treatment of choice for pituitary-dependent hyperadrenocorticism (HAC) in dogs, is monitored by assessing resolution of clinical signs and measuring adrenocortical reserve capacity with an ACTH-stimulation test. The aim of this prospective study was to evaluate agreement between clinical signs reported by owners and cortisol or ACTH concentrations before and during trilostane therapy (starting dose 1-2 mg/kg once daily). A questionnaire on signs of HAC was used and a clinical score calculated as the sum of the 9 questions. Eighteen questionnaires at diagnosis and 97 during therapy were filled out by owners of 32 dogs. An ACTH-stimulation test was performed at each reevaluation. There were weak correlations between abdominal girth, appetite or weight gain and cortisol concentrations during therapy. However, the clinical score did not correlate with cortisol or cACTH values. In 50% of dogs, trilostane application had to be changed from once daily to twice daily during the study. Clinical signs reported by owners matched poorly with cortisol or cACTH concentrations at any time point. If low-dose trilostane is used, treatment frequency often has to be increased. SummaryTrilostane therapy, the treatment of choice for pituitary-dependent hyperadrenocorticism (HAC) in dogs, is monitored by assessing resolution of clinical signs and measuring adrenocortical reserve capacity with an ACTH-stimulation test. The aim of this prospective study was to evaluate agreement between clinical signs reported by owners and cortisol or ACTH concentrations before and during trilostane therapy (starting dose 1-2 mg/kg once daily). A questionnaire on signs of HAC was used and a clinical score calculated as the sum of the 9 questions. Eighteen questionnaires at diagnosis and 97 during therapy were filled out by owners of 32 dogs. An ACTH-stimulation test was performed at each reevaluation. There were weak correlations between abdominal girth, appetite or weight gain and cortisol concentrations during therapy. However, the clinical score did not correlate with cortisol or cACTH values. In 50% of dogs, trilostane application had to be changed from once daily to twice daily during the study. Clinical signs reported by owners matched poorly with cortisol or cACTH concentrations at any time point. If low-dose trilostane is used, treatment frequency often has to be increased.

Comparison of methods to monitor dogs with hypercortisolism treated with trilostane

“…When only data of the first re‐evaluation were analyzed to assess the robustness of the results, prepill and day‐to‐re‐evaluation USG failed to significantly discriminate well and undercontrolled dogs. The limitation of these 2 possible monitoring tools has already been described in the literature, confirming the low reliability of these variables to correctly evaluate the trilostane treatment control of HC dogs 6,8,18 …”

“…For several years, the adrenocorticotropic hormone stimulation test (ACTHst) has been used to monitor trilostane treatment 5 . However, over time, concerns have been raised regarding the reliability of this test 6‐8 . The ACTHst has never been validated for trilostane monitoring purposes and the results strictly depend on the time of trilostane administration 2‐4,9‐12 .…”

“… 5 However, over time, concerns have been raised regarding the reliability of this test. 6 , 7 , 8 The ACTHst has never been validated for trilostane monitoring purposes and the results strictly depend on the time of trilostane administration. 2 , 3 , 4 , 9 , 10 , 11 , 12 Recent evidence has supported a lack of correlation between post‐ACTH administration serum cortisol concentration (post‐ACTH) and clinical signs.…”

Comparison of two prepill cortisol concentrations in dogs with hypercortisolism treated with trilostane

“…Blood was drawn approximately 11–12 h after the last trilostane application for prepill 1 and 12–13 h after the last trilostane application for prepill 2. The target ranges of both cortisol concentrations were defined as 1.5–5 μg/dl [16]. Every dog was assessed by a standardized owner questionnaire and by a clinical examination.…”

“…Although, low doses of ACTH (1 μg/kg) can be used in dogs receiving trilostane [10], a monitoring method not relaying on ACTH would be preferable. In several studies baseline cortisol, endogenous ACTH, cortisol/ACTH ratio, haptoglobin, urine corticoid:creatinine ratio (UCCR) and clinical signs reported by owners were evaluated, but none of them seemed convincingly superior to the ACTH stimulation test [11–16]. A recent study compared the pre-trilostane cortisol, the three-hour post-trilostane cortisol and the post-ACTH cortisol concentrations against the clinical signs reported by owners [17].…”