Endocrine diseases can arise from many possible causes. Hormones can be over- or underproduced, receptors can malfunction, and normal pathways for hormone removal may be disrupted. Clinical signs consistent with malfunction in an endocrine tissue may develop because of a problem originating in the source of the hormone itself or may be due to disruption in another location that is secondarily affecting hormone secretion or action.

In veterinary medicine, the most common types of endocrine disease are hormonal overproduction associated with either a tumor or hyperplastic tissue manufacturing excessive amounts of hormone, and hormonal deficiency due to destruction of the endocrine tissue source. Common diseases associated with hormonal overproduction are hyperthyroidism in cats and hyperadrenocorticism (Cushing's disease) in dogs. Often the abnormal endocrine tissue not only overproduces hormone, it also fails to respond normally to feedback signals, contributing to inappropriate release of hormone. Hormonal overproduction from an endocrine tissue can also result from stimulation arising from a secondary source; eg, renal disease can result in parathyroid hyperplasia and oversecretion of PTH. Hyperphosphatemia occurs as a consequence of some types of renal disease. This leads to decreased formation of the active form of vitamin D, 1,25-dihydroxycholecalciferol (calcitriol). In turn, low calcitriol concentrations contribute to low calcium levels in extracellular fluid, which act as a stimulus for PTH secretion. Nonendocrine tissues can produce and secrete hormones in sufficient amounts to cause clinical signs; eg, certain tumors (apocrine gland tumors of the anal sac in dogs, lymphoma) can manufacture PTH-related protein that can mimic PTH action, resulting in hypercalcemia.

Syndromes associated with deficient or absent hormone secretion also have multiple causes. Endocrine tissue destruction secondary to cell-mediated autoimmune attack is often believed to be the cause. Examples of endocrine hypofunction resulting from primary tissue loss include canine hypothyroidism, type 1 diabetes mellitus, primary hypoparathyroidism, and primary hypoadrenocorticism. In early stages of tissue loss, compensatory mechanisms involving feedback pathways stimulate activity (hormone production) from the remaining tissue. For example, in primary hypoadre-nocorticism (Addison's disease), secretion of pituitary ACTH increases as the adrenal cortex disappears. The increased trophic support results in full activation of the remaining tissue and often provides sufficient hormone secretion to delay signs of deficiency until tissue loss simply eliminates the hormonal source. Disorders resulting in clinical signs of endocrine hypoactivity may also occur due to disruption in tissues distant from the hormone source. Secondary hypothyroidism results from pituitary thyroid-stimulating hormone insufficiency that reduces the stimulus needed at the thyroid for T₄ and T₃ production and secretion. Patients receiving glucocorticoid therapy may experience atrophy of the cortisol-producing zones in the adrenal cortex. The exogenous steroid initiates negative feedback on the pituitary gland, suppressing ACTH secretion and leading to adrenal cortical atrophy. Another potential cause for endocrine hypofunction relates to tissue loss secondary to compressive and/or destruc-tive growth of nonfunctional tumors.

Endocrine disease and related maladies also result from alterations in tissue res-ponsiveness to hormones. An important example is type 2 or non-insulin-dependent diabetes mellitus, in which relative insensitivity to insulin is observed, often associated with obesity. Nephrogenic diabetes insipidus is due to renal insensitivity to the actions of vasopressin (antidiuretic hormone). The renal insensitivity to vasopressin in this syndrome may relate to congenital abnormalities in the vasopressin receptor but more often is secondary to other diseases (eg, pyometra, hyperadrenocorticism) or abnormalities in ion concentrations (eg, hypokalemia, hypercalcemia).

Last full review/revision July 2011 by Robert J. Kemppainen, DVM, PhD