Cortisol Concentrations in Well‐Regulated Dogs with Hyperadrenocorticism Treated with Trilostane

Background

There are no clear treatment guidelines for dogs with clinically well‐regulated hyperadrenocorticism in which serum cortisol concentrations before and after an ACTH stimulation test performed 3–6 hours after trilostane administration are < 2.0 μg/dL.

Objective

To determine if serum cortisol concentrations measured before (Pre1) and after (Post1) ACTH stimulation at 3–6 hours after trilostane administration are significantly lower than cortisol concentrations measured before (Pre2) and after (Post2) ACTH stimulation 9–12 hours after trilostane administration, in a specific population of dogs with clinically well‐regulated hyperadrenocorticism and Pre1 and Post1 <2 μg/dL.

Animals

Thirteen client‐owned dogs with clinically well‐regulated hyperadrenocorticism and Pre1 and Post1 serum cortisol concentrations <2.0 μg/dL 3–6 hours after trilostane administration.

Methods

Prospective study. Dogs had a second ACTH stimulation test performed 9–12 hours after trilostane administration, on the same day of the first ACTH stimulation test. Cortisol concentrations before and after ACTH stimulation were compared using a paired t‐test.

Results

Cortisol concentrations before (1.4 ± 0.3 μg/dL) and after the first stimulation (1.5 ± 0.3 μg/dL, mean ± SD) were significantly lower than cortisol concentration before the second stimulation (3.3 ± 1.6 μg/dL, P = .0012 each). Cortisol concentration before the first stimulation was also significantly lower than cortisol concentration after the second stimulation (5.3 ± 2.4 μg/dL, P = .0001).

Conclusions and clinical importance

In dogs with clinically well‐regulated, trilostane‐treated, hyperadrenocorticism, and cortisol concentrations <2 μg/dL before and after the first stimulation, a second ACTH stimulation test performed 9–12 hours after treatment can result in higher cortisol concentrations that could support continued trilostane treatment.     

A case of chronic lymphocytic leukemia masked by Cushing’s disease in a dog

A 12-year-old, 3.5-kg, intact female dog was presented with polyuria, polydipsia, and a pendulous abdomen. Laboratory examinations showed elevated hepatobiliary enzyme levels and neutrophilic leukocytosis. The adrenocorticotropic hormone stimulation test confirmed hyperadrenocorticism (HAC). Trilostane therapy managed the clinical condition and cortisol concentration. However, lymphocytosis and nonregenerative anemia developed after HAC remission. Bone marrow aspiration analysis revealed a lymphoproliferative disorder with a clonal T-cell population. Accordingly, the patient was diagnosed with T-cell chronic lymphocytic leukemia (CLL) and concurrent HAC. Thereafter, chemotherapy was initiated, which improved the lymphocytosis. However, euthanasia was performed because of worsening quality of life at 45 weeks after the first presentation. These results suggested that CLL could be masked by excessive endogenous cortisol and discovered after HAC remission.     

Chronic lymphocytic leukaemia in the cat: 18 cases (2000–2010)

There is little information regarding the presentation, biologic behaviour, treatment and prognosis in cats with chronic lymphocytic leukaemia (CLL), and further investigation is needed to characterize this disease in cats. The goal of this study was to describe the clinical presentation, response to treatment and prognosis of feline CLL. A multi‐institutional retrospective study of 18 cats diagnosed with CLL between 2000 and 2010 was performed. CLL was defined as the presence of a mature lymphocytosis (> 9000 lymphocytes µL^?1) and confirmation of an immunophenotypically monomorphic or clonal lymphoid population. Each patient was required to also have at least one of the two following criteria: (1) concurrent cytopenia of at least one cell line and/or (2) >15% mature lymphocytes in the bone marrow. Data on signalment, history, clinical signs, clinicopathologic features and response to treatment were reviewed. Median age of the cats at initial presentation was 12.5 years (range: 5–20 years). The most common presenting complaint was chronic weight loss, which was present in 8/18 (44%) cats. Sixteen of 18 (89%) cats were treated with chlorambucil and prednisolone; four of these cats also received vincristine. Two (11%) cats were treated with multi‐agent injectable chemotherapy (L‐CHOP, l ‐asparaginase, cyclophosphamide, doxorubicin, vincristine, prednisolone). Eighty‐eight percent of cats evaluable for response achieved a complete (nine cats) or partial (six cats) remission. Median overall remission was 15.7 months (range: 1.3–22.8 months). The median overall survival in the 17 cats with follow‐up data was 14.4 months (range: 0.9–25.3 months). Results of this study suggest that CLL affects older‐aged cats and responds favourably to treatment with oral chlorambucil and prednisolone.     

Clinical, morphological and immunohistochemical characterization of cutaneous lymphocytosis in 23 cats

Abstract   Clinical, morphological and immunohistochemical features of cutaneous lymphocytosis, an uncommon disease histologically resembling well-differentiated malignant lymphoma, were characterized in 23 cats. Clinical outcome was correlated with histomorphology and immunophenotype in an attempt to predict benign vs. malignant behaviour. The disease mainly affected older cats. Lesions were solitary in 61% of cats and often characterized by alopecia (73.9%), as well as erythema, scaling and ulceration. The lateral thorax was most commonly affected (43.5%). Pruritus was frequent (65.2%). Systemic signs included anorexia and weight loss. Morphologically, lesions were characterized by dermal infiltrations of well-differentiated CD3⁺ T-cells (100%) and aggregates of CD79⁺ B-cells (64.3%). Cutaneous lymphocytosis is slowly progressive and relatively benign, although in some cats systemic signs led to euthanasia. Four of 12 euthanized cats and one live cat also had lymphoid infiltrates in internal organs. Unfortunately, we were unable to predict clinical outcome by histological and immunohistochemical evaluations of skin lesions.     

Differentiating benign and malignant causes of lymphocytosis in feline bone marrow

Differentiation of benign and malignant causes of lymphocytosis in blood or bone marrow can be problematic. In the present study, reports of examinations of bone marrow from cats, submitted over an 8-year period, were reviewed to identify cats with increased numbers of small lymphocytes. Of 203 reports reviewed, 12 (5.9%) indicated increased numbers of small lymphocytes. Diagnoses for these cats included chronic lymphocytic leukemia (CLL; n = 2), pure red cell aplasia (PRCA; n = 4), immune-mediated hemolytic anemia (IMHA; n = 3), thymoma (n = 1), cholangiohepatitis (n = 1), and fever of unknown origin (n = 1). Several factors were identified that could be used to differentiate reactive lymphocytosis from CLL. Cats with CLL tended to be older, and lymphocytes were slightly larger and had cleaved or lobulated nuclei. Reactive lymphocytosis was associated with immune-mediated anemias and inflammatory diseases. In reactive lymphocytosis, the proliferating lymphocytes were organized into lymphoid aggregates in bone marrow and were predominately B cells. Alternatively, in CLL and thymoma, the proliferating lymphocytes were diffusely distributed and were predominately T cells. Therefore, differentiation of the causes of lymphocytosis should include evaluation of signalment, concurrent disease conditions, lymphocyte morphology, lymphocyte distribution in bone marrow, and immunophenotype. Cat age, presence of severe anemia, and evidence of inflammatory disease also should be considered.     

A case-controlled retrospective study of the causes and implications of moderate to severe leukocytosis in dogs in South Africa

BACKGROUND: Previous studies showed that dogs with extreme leukocytosis had specific types of diseases, long hospitalization times, and high mortality rates. Objectives: The aim of this study was to determine whether dogs with moderate to severe leukocytosis are likely to have similar results compared with age-matched control dogs. METHODS: Records at the Onderstepoort Veterinary Academic Hospital, University of Pretoria, were examined retrospectively from dogs with > or =35 x 10(9) WBC/L (Leukocytosis Group) and dogs with < or =30 x 10(9) WBC/L and < or =0.5 x 10(9) band neutrophils/L (Control Group). Hematologic and serum protein data, final diagnosis, and effect of glucocorticoid treatment were compared between groups. RESULTS: One hundred eighty-two dogs were included in the Leukocytosis Group and 179 in the Control Group. Compared with dogs in the Control Group, significantly more dogs in the Leukocytosis Group had infections, babesiosis, immune-mediated hematologic disease, and necrosis. Hospitalization time and neutrophil, lymphocyte, and monocyte counts were significantly higher and HCT, eosinophil count, platelet count, and serum albumin concentration were lower in dogs in the Leukocytosis Group (P<.0001). There was no difference in leukocyte counts between glucocorticoid-treated and non-glucocorticoid-treated dogs. Survival did not differ between Leukocytosis and Control Groups; however, a significant relationship was found between total neutrophil (mature+band) count and survival (P=.01). CONCLUSIONS: Dogs with leukocytosis of > or =35 x 10(9)/L are more likely to have bacterial and fungal infections, complicated babesiosis, immune-mediated hematologic disease, and necrosis. The total neutrophil count has a significant impact on outcome.     

Abnormal clonalities of B-lymphocytes in bovine leukemia virus-infected cattle with persistent lymphocytosis

Peripheral B-lymphocyte clonality of 274 bovine leukemia virus-infected cattle with lymphocytosis was analyzed using clonality PCR based on sequences of the variable region of the bovine immunoglobulin H chain. None of the cattle showed monoclonal proliferation, while 10, 31, and 233 showed minor-clonal, oligoclonal, and polyclonal proliferation, respectively. A total of 163 cattle were analyzable the following year, and lymphocytosis was maintained in 157, indicating persistent lymphocytosis (PL). B-lymphocyte clonality of the 157 PL cattle was minor-clonal in 6 (3.8%), oligoclonal in 8 (5.1%), and polyclonal in 143 (91.1%). A higher rate of enzootic bovine leukosis (EBL) onset within a year was observed in PL cattle with minor-clonal (50.0% (3/6)) and oligoclonal (25.0% (2/8)) proliferation compared to those with polyclonal (5.6% (8/143)) proliferation. Minor-clonal and oligoclonal proliferation in PL cattle may be a prognosis factor for developing EBL.