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Pathogenesis of Endocrine Disease in Animals

By

Robert J. Kemppainen

, DVM, PhD, Department of Anatomy, Physiology & Pharmacology, College of Veterinary Medicine, Auburn University

Last full review/revision Apr 2019 | Content last modified Apr 2019
Topic Resources

Syndromes of hormone excess or deficiency can result from multiple mechanisms, In veterinary species, the most common reasons for hormone excess are either adenoma or hyperplasia involving the endocrine tissue itself or neoplasia at a secondary site that in turn stimulates excess hormone secretion. Syndromes involving hormone deficiency are usually a consequence of autoimmune attack and destruction of an endocrine organ.

Endocrine diseases can arise from several causes. Hormones can be over- or under-produced, 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 1) hormonal overproduction associated with either a tumor or hyperplastic tissue manufacturing excessive amounts of hormone, and 2) hormonal deficiency due to destruction of the endocrine tissue source. Common diseases associated with hormonal overproduction are hyperthyroidism in cats and hyperadrenocorticism (Cushing disease) in dogs.

Often, the abnormal endocrine tissue not only overproduces hormone but 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 parathyroid hormone (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 (paraneoplastic syndrome).

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.

Table
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Common Endocrine Diseases in Small Animals

Endocrine System Involved

Site of Disease Origin

Hypofunction

Hyperfunction

Adrenal

Adrenal

(primary)

Addison disease, loss of cortisol and aldosterone

Occasional in dogs or cats

Functional adrenal tumor

Occasional in dogs, common in ferrets but involves secretion of excessive sex steroids

Adrenal

Pituitary

(secondary)

Secondary hypoadrenocorticism

low cortisol only

Very occasional in dogs or cats

Cushing disease

Common in dogs

Thyroid

Thyroid

(primary)

Common in dogs

Hyperthyroidism

Very common in cats

Thyroid

Pituitary

(secondary)

Low TSH

Rare in dogs or cats

Secondary hyperthyroidism

High TSH

Very rare in dogs or cats

Parathyroid

Parathyroid

(primary)

Low PTH

Rare in dogs or cats

High PTH

Occasional in dogs or cats

Parathyroid

Kidney or diet

(secondary)

Not seen

Sometimes associated with kidney disease in dogs or cats

Pancreas

Pancreas

(primary)

Low insulin

Common in dogs

Insulinoma

High insulin

Occasional in dogs, common in ferrets

Pancreas

Multiple sites, including pancreas

Normal or high insulin

Common in cats

Not seen

TSH, thyroid-stimulating hormone. PTH, parathyroid hormone.

In early stages of tissue loss, compensatory mechanisms involving feedback pathways stimulate activity (hormone production) from the remaining tissue. For example, in primary hypoadrenocorticism (Addison disease), secretion of pituitary adrenocorticotropic hormone (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 (TSH) insufficiency that reduces the stimulus needed at the thyroid for T4 and T3 production and secretion. Glucocorticoid therapy may cause 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 of endocrine hypofunction relates to tissue loss secondary to compressive and/or destructive growth of nonfunctional tumors.

Endocrine disease and related maladies also result from alterations in tissue responsiveness 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).

Key Points

  • Diseases involving hormone excess or deficiency are common in veterinary medicine.

  • The most common endocrine diseases in dogs are Cushing disease, hypothyroidism, and diabetes mellitus.

  • The most common endocrine diseases in cats are hyperthyroidism and diabetes mellitus.

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