Recent developments in canine Cushing`s syndrome

Abstract

Cushing`s syndrome or hypercortisolism is one of the most common endocrinopathies in dogs. Besides the ACTH or pituitary-dependent and adrenal or ACTH-independent hypercortisolism, ectopic ACTH secretion and food-dependent hypercortisolism are described in the dog for the very first time. Ectopic ACTH secretion has been diagnosed in a dog in which initially pituitary microadenoma was diagnosed and since the hypophysectomy was not curative, further diagnostic has been performed. CRH stimulation test revealed no respons of plasma ACTH and cortisol concentrations, which was strongly indicative of ectopic ACTH secretion syndrome. Total body CT scan revealed a mass in the pancreas and during the celiotomy, also some nodular changes in the liver were noted. Pathohistological examination confirmed pancreatic neuroendocrine tumor, which is a common origin of the ectopic ACTH secretion syndrome in men. Food-dependent hypercortisolism has been diagnosed in a dog with mild clinical signs of hypercortisolism, suppressed plasma ACTH concentrations and bilateral enlarged adrenal glands. UCCR increased after ingestion of the meal. Treatment with ocreotide, which suppresses release of gastric-inhibitory polypeptide (GIP), blocked cortisol secretion, while plasma ACTH concentration remained suppressed. Treatment with trilostane was successful only when trilostane was administered before ingestion of the meal, which provided an additional information for food-dependent hypercortisolism in this dog. The differentiation between ACTH-dependent and ACTH-independent hypercortisolism can be done by the measurements of the urinary corticoid:creatinine ratio (UCCR) combined with the high dose dexamethasone suppression test. The generally-accepted criterion of 50% suppression of plasma cortisol concentration in the differentiation between pituitary or adrenal hypercortisolism is also applicable to the UCCR. Although the UCCR is very reliable in the diagnostics of hypercortisolism, it cannot be used to detect the optimal dose of trilostane. However, the measurement of the UCCR could be useful to detect dogs at risk of developing hypocortisolism. Similar holds true for the basal ACTH concentration, which significantly increased in dogs which received trilostane overdose when compared to dogs receiving the optimal dose. There was no overlap in plasma ACTH concentration in dogs on the optimal dose when compared to dogs which received an overdose. Obviously, trilostane affected the pituitary-adrenal axis. In addition, also an effect at renin-aldosterone system has been detected, since the aldosterone:renin ratio significantly decreased during treatment with trilostane. The pathogenesis of the adrenocortical tumors in dogs is poorly understood. In humans, cortisol-secreting adenomas could be initiated by the aberrant expression of hormonal receptors. In the dog, the overexpression of the genes coding for luteinizing hormone receptor (LHR), gastric-inhibitory polypeptide receptor (GIPR) and three vasopressine receptors (V1aR, V1bR and V2R) was not responsible for the hypersecretion of cortisol by the adrenocortical tumor. However, ectopic expression of GIPR and V2R protein, and eutopic expression of LHR protein in tumorous ZF tissue, may play a role in the pathogenesis of canine cortisol-secreting ATs. Hypercortisolemia in dogs with cortisol-secreting ATs cannot be ascribed to upregulation of the genes encoding for steroidogenic enzymes. In adrenocortical carcinomas, there was a significant downregulation of ACTH-R, which may contribute to the malignant character of cortisol-secreting carcinomas