ABSTRACT
BACKGROUND: Severe muscle stiffness (SMS) in dogs with hypercortisolism (HC) is uncommon. OBJECTIVES: To evaluate signalment, presentation, treatments, and long-term outcomes of dogs with concurrent HC and SMS. ANIMALS: Thirty-seven dogs. METHODS: Medical records of dogs with HC and concurrent SMS were recruited from 10 institutions. Clinical information, test results, therapeutic responses, and survival times were reviewed. RESULTS: All 37 dogs with HC and SMS had pituitary-dependent hypercortisolism (PDH); 36/37 weighed <20 kg. Signs and test results were typical of PDH aside from SMS, initially diagnosed in all 4 limbs in 9, pelvic limbs of 22, and thoracic limbs of 6 dogs. Hypercortisolism and SMS were diagnosed together in 3 dogs; HC 1-36 months before SMS in 23; SMS 1-12 months before HC in 11. Mitotane or trilostane, given to control HC in 36/37 dogs, improved or resolved HC signs in 28; SMS did not resolve, remaining static or worsening in 31/36 dogs, mildly improving in 5/19 dogs given additional therapies. Progression of SMS included additional limbs in 10 dogs and the masticatory muscles of 2. The median survival time from diagnosis of SMS was 965 days (range, 8-1188). CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent SMS and HC is uncommon, possibly affecting only dogs with PDH. Development of SMS might occur before or after diagnosis of HC. Apart from SMS, the clinical picture and survival time of these dogs seem indistinguishable from those of dogs with HC in general. However, while muscle weakness usually resolves with HC treatment SMS does not.
Subject(s)
Cushing Syndrome , Dog Diseases , Pituitary ACTH Hypersecretion , Dogs , Animals , Cushing Syndrome/complications , Cushing Syndrome/diagnosis , Cushing Syndrome/drug therapy , Cushing Syndrome/veterinary , Dog Diseases/diagnosis , Dog Diseases/drug therapy , Pituitary ACTH Hypersecretion/complications , Pituitary ACTH Hypersecretion/diagnosis , Pituitary ACTH Hypersecretion/drug therapy , Pituitary ACTH Hypersecretion/veterinary , Mitotane/therapeutic use , MusclesABSTRACT
Hypercortisolism induces a state of insulin resistance that can occur concurrently with fasting hyperglycaemia, dyslipidaemia and diabetes mellitus. Metformin reduces hepatic glucose production and insulin resistance of the skeletal muscle and adipose tissue. The aim of this study was to evaluate the effects of metformin on the control of metabolic disorders of dogs with hyperadrenocorticism (HAC). Twenty-three dogs with HAC were randomly divided into two groups, consisting of a control group and a metformin group (10 mg metformin/kg/12 h). Both groups received the same treatment for HAC. At baseline and 3 months, blood glucose, total cholesterol, triglycerides and insulin concentrations, in addition to urinary cortisol:creatinine ratio, Homeostatic Model Assessment (HOMA) for insulin sensitivity and ß-cell function were measured. Dogs treated with metformin showed significantly reduced glycaemia, cholesterolaemia and triglyceridaemia. They also presented reduced hyperinsulinism and insulin resistance, as well as improved pancreatic ß-cell function. The implementation of metformin as an adjuvant therapy is effective for the normalisation of metabolic disorders of dogs with HAC.
ABSTRACT
11ß-Hydroxysteroid dehydrogenase 1 (11ß-HSD1) is an enzyme that activates cortisone into cortisol in tissues. Alterations in this enzyme are related to the development of metabolic syndrome, obesity and hyperadrenocorticism (HAC). Endothelial nitric oxide synthase (eNOS) produces nitric oxide and is related to the regulation of adrenal steroidogenesis. The aim of the study was to evaluate 11ß-HSD1 and eNOS expression in dogs with HAC. Visceral adipose tissue samples were taken to evaluate 11ß-HSD1 expression by immunohistochemistry and western blotting. In parallel, adrenal gland samples were collected to evaluate eNOS expression by immunohistochemistry. 11ß-HSD1 expression was significantly higher in the adipocytes of dogs with HAC than in those of the control dogs. eNOS expression in the adrenal cortex (zona fasciculata) was significantly lower in the dogs with HAC than in the control dogs. 11ß-HSD1 overexpression and eNOS underexpression could play a role in the maintenance of hypercortisolism in dogs with HAC.
