Frequent urination in dogs

Frequent urination in dogs: the role of adrenal corticoids in normal and hyperadrenal function.

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OBJECTIVE: To review the pathogenesis and current treatment strategies for hyperadrenocorticism (HAC), focusing on the role of adrenal corticosteroids in the maintenance of electrolyte and water balance in normal and hyperadrenal function.BACKGROUND: Hyperadrenocorticism (HAC) is the most common cause of hypercortisolism in dogs and most frequently is caused by a pituitary lesion (pituitary-dependent hyperadrenocorticism [PDH]) or an adrenal neoplasm (adrenal-dependent hyperadrenocorticism [ADH]). HAC is an important condition, with mortality rates up to 50%. METHODS: Relevant publications from 1977 to 2011 were identified through MEDLINE searches of MEDLINE(R) and Web of Science using the following key terms: (1) adrenal hormones and adrenocortical tumors, (2) adrenal hormones and hyperadrenocorticism, and (3) hyperadrenocorticism and corticosteroid, cortisol, and progestin. RESULTS: HAC results from excessive secretion of adrenocortical hormones from adrenocortical neoplasms or cortisol excess from nonpituitary ACTH-secreting adrenocortical tumors. These tumors may occur sporadically or as part of familial inheritance, although the mechanism remains uncertain. In addition to increased activity of the hypothalamic-pituitary-adrenal axis, aldosterone is also involved. In dogs, there are 4 types of HAC, 2 of which (ADH and PDH) are caused by a neoplasm of the adrenal cortex. Although there are no clear clinical and pathologic criteria to differentiate among types of HAC in humans, dogs, and cats, it is possible to make a diagnosis by history and physical examination alone if hypercortisolism is present. In dogs, the most common type of HAC is PDH, followed by ADH. In addition, Cushing's disease, which is a nonhyperadrenocorticoid, cortisol-secreting ACTH-secreting ACTH-producing tumor of the pituitary gland, is considered a subtype of PDH. The most common adrenocortical tumor associated with PDH is a benign adrenocortical adenoma, and the most common form of adrenocortical tumor associated with ADH is a pituitary-dependent corticoadenoma. Treatment of PDH is based on surgical removal of the tumor(s), with the goal of restoring glucocorticoid and mineralocorticoid homeostasis. Dogs with ADH have tumors that secrete both aldosterone and cortisol, and therefore are treated with both mineralocorticoid and glucocorticoid replacement. For most cats, HAC is a difficult diagnosis to make. There are no pathologic criteria to differentiate among the various forms of HAC in cats, although it is possible to differentiate among the types of HAC in dogs. Definitive diagnosis of HAC in cats is made only after clinical signs of hypercortisolism develop.


##### Hypercortisolism

In a dog with HAC, the ACTH and cortisol that are secreted by the tumor cells stimulate the glucocorticoid (e.g., cortisol) and mineralocorticoid (e.g., aldosterone) production of the adrenal gland. Glucocorticoid excess is most evident clinically as signs of hypercortisolism in the form of polyuria, polydipsia, and polyphagia, decreased physical activity, lethargy, weight gain, anemia, hypercalcemia, and hyperphosphatemia. An excessive urinary sodium excretion results in a secondary hyperaldosteronism, causing further retention of salt and water, which can lead to signs of polyuria, polydipsia, polyphagia, and weight gain. A high cortisol concentration inhibits the action of growth hormone and IGF‐1. This leads to an increased appetite and subsequent weight gain, which over time contributes to an increase in the size of the tumor. The hypercortisolism stimulates further production of IGF‐1, which stimulates growth of cancer cells in the adrenal gland.

###### Adrenocortical Tumors

In cats with HAC, the cause of the ACTH and cortisol secretion by the tumor cells is currently unknown. Although a hypersecretion of ACTH by the tumor cells may occur, in contrast to dogs, cats do not secrete cortisol at a normal basal concentration. ACTH secretion is often, but not always, present. The tumors are considered malignant because of their aggressive clinical behavior and tendency to metastasize.

The most common adrenal tumor in cats is the cortical adenoma, followed by the adenoma and carcinoma. Most often, adenomas are found incidentally. When HAC is found in a patient's medical history, the adrenal tumor is presumed to be malignant.

###### Cortical Adenoma

Cortical adenomas are usually solid masses, but occasionally they may be composed of a mix of solid and cystic areas. The tumors are generally larger than 1 cm.

###### Cortical Adenocarcinoma

Cortical adenocarcinomas are more common in dogs than in cats. Tumors with carcinoma cells have been reported to be found in the subcutis and along the periosteum. Cortical adenocarcinomas tend to be larger than 5 cm.

Tumors with malignant cells may invade the medullary part of the adrenal gland.

###### Medullary Adenoma

Medullary adenomas are rare. Their occurrence in dogs and cats is related to sex.

###### Medullary Carcinoma

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