
Endocrine diseases can arise from several causes. Hormones can be overproduced or underproduced, receptors can malfunction, and normal pathways for hormone removal may be disrupted. Syndromes of hormone excess or deficiency can result from multiple mechanisms (see the table Common Endocrine Diseases in Small Animals Common Endocrine Diseases in Small Animals ).
In veterinary species, the most common reasons for hormone excess are manufacture of excessive amounts of hormone by either adenoma or hyperplasia involving the endocrine tissue itself (eg, adrenal-dependent hyperadrenocorticism Cushing Syndrome (Hyperadrenocorticism) Cushing syndrome refers to any cause of elevated cortisol concentrations. Pituitary-dependent hyperadrenocorticism (PDH; Cushing disease) is the most common form of hyperadrenocorticism and... read more in dogs or hyperthyroidism Hyperthyroidism in Animals Hyperthyroidism is characterized by hypermetabolism and high circulating thyroid hormone concentrations. Clinical features include weight loss despite a good appetite. Treatment depends on the... read more
in cats), or neoplasia at a secondary site that in turn stimulates excess hormone secretion (eg, pituitary-dependent hyperadrenocorticism [ Cushing disease Cushing Disease (Pituitary-dependent Hyperadrenocorticism) in Animals Cushing disease is hyperadrenocorticism caused by an ACTH-secreting tumor of the pituitary gland. Clinical signs include polyuria, polydipsia, alopecia, and muscle weakness. A low-dose dexamethasone... read more
] in dogs).
Syndromes involving hormone deficiency are usually a consequence of autoimmune attack and destruction of an endocrine organ.
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.
Pathogenesis of Endocrine Diseases in Animals
Often, abnormal endocrine tissue not only overproduces hormone but also fails to respond normally to feedback signals, contributing to inappropriate release of hormone. Hormone overproduction from an endocrine tissue can also be due to stimulation arising from a secondary source; eg, renal disease can result in parathyroid hyperplasia and oversecretion of parathyroid hormone (PTH).
Hyperphosphatemia Hyperphosphatemia in Animals Physiologically elevated serum and plasma phosphorus concentrations are seen in young and growing animals due to enhanced intestinal phosphorus uptake and decreased renal phosphorus excretion... read more results from some types of renal disease. It leads to decreased formation of the active form of vitamin D: 1,25-dihydroxycholecalciferol (calcitriol). In turn, low calcitriol concentrations contribute to low calcium concentrations in extracellular fluid, thereby stimulating PTH secretion.
Nonendocrine tissues can produce and secrete hormones in sufficient amounts to cause clinical signs. For example, certain tumors (apocrine gland tumors of the anal sac in dogs, lymphomas) can manufacture PTH-related protein (PTHrP) that can mimic PTH action, resulting in hypercalcemia (an example of a paraneoplastic syndrome Paraneoplastic Disorders of the Nervous System in Animals Paraneoplastic syndromes are nonmetastatic complications of cancer with effects distant from the primary tumor. They are unrelated to neurologic complications secondary to metabolic or nutritional... read more ).
Syndromes associated with deficient or absent hormone secretion also have multiple causes. Cell-mediated autoimmune destruction of endocrine tissue is often believed to be the cause. Examples of endocrine hypofunction resulting from primary tissue loss include canine hypothyroidism Hypothyroidism in Animals Hypothyroidism is thyroid hormone deficiency. It is diagnosed by clinical features such as lethargy, weight gain, obesity, haircoat changes, and low serum thyroid hormone concentrations. Management... read more , type I diabetes mellitus Diabetes Mellitus in Dogs and Cats Diabetes mellitus is a common endocrine disease in dogs and cats, occurring in about 1 of every 300 patients. Clinical signs reflect hyperglycemia with resultant glycosuria. Diagnosis is made... read more , primary hypoparathyroidism Hypoparathyroidism in Dogs Hypoparathyroidism of various causes is primarily recognized in dogs and is characterized by insufficient PTH secretion by parathyroid glands. Deficiency of PTH results in an inability to adequately... read more , and primary hypoadrenocorticism (Addison disease Addison Disease Addison disease (hypoadrenocorticism) results from the lack of glucocorticoids, mineralocorticoids, or both. Isolated aldosterone insufficiency appears to be very rare, whereas isolated glucocorticoid... read more ).
In early stages of tissue loss, compensatory mechanisms involving feedback pathways stimulate activity (hormone production) from the remaining tissue. In Addison disease, for example, the 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 hormone source.
Disorders resulting in clinical signs of endocrine hypoactivity may also arise as a result of disruption in tissues distant from the hormone source. Secondary hypothyroidism results from a deficiency in pituitary thyroid-stimulating hormone (TSH) that decreases the stimulus needed at the thyroid for the production and secretion of thyroxine (T4) and triiodothyronine (T3).
Glucocorticoid administration 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 or destructive growth of nonfunctional tumors.
Endocrine disease also results from alterations in tissue responsiveness to hormones (eg, insulin resistance, such as in diabetes mellitus Diabetes Mellitus in Dogs and Cats Diabetes mellitus is a common endocrine disease in dogs and cats, occurring in about 1 of every 300 patients. Clinical signs reflect hyperglycemia with resultant glycosuria. Diagnosis is made... read more type II).
Nephrogenic diabetes insipidus Diabetes Insipidus in Animals Diabetes insipidus is caused by a lack of antidiuretic hormone (ADH) or an inability of the kidneys to respond to ADH. It results in production of large volumes of dilute urine, which prompts... read more is due to renal insensitivity to the actions of vasopressin (antidiuretic hormone). The renal insensitivity to vasopressin may relate to congenital abnormalities in the vasopressin receptor. More often, however, this insensitivity is secondary to other diseases (eg, pyometra Cystic Endometrial Hyperplasia–Pyometra Complex in Small Animals Cystic endometrial hyperplasia (CEH) is a progressive pathological change of the uterine lining. CEH is associated with poor fertility. Pyometra may be an infection overlying CEH. CEH usually... read more , hyperadrenocorticism [ Cushing syndrome Cushing Syndrome (Hyperadrenocorticism) Cushing syndrome refers to any cause of elevated cortisol concentrations. Pituitary-dependent hyperadrenocorticism (PDH; Cushing disease) is the most common form of hyperadrenocorticism and... read more
]) or to abnormalities in ion concentrations (eg, hypokalemia, hypercalcemia).
Clinical Findings of Endocrine Diseases in Animals
Clinical findings coincident with endocrine disease vary.
Cats with hyperthyroidism Hyperthyroidism in Animals Hyperthyroidism is characterized by hypermetabolism and high circulating thyroid hormone concentrations. Clinical features include weight loss despite a good appetite. Treatment depends on the... read more show polyphagia in the face of weight loss. Dogs with hypothyroidism Hypothyroidism in Animals Hypothyroidism is thyroid hormone deficiency. It is diagnosed by clinical features such as lethargy, weight gain, obesity, haircoat changes, and low serum thyroid hormone concentrations. Management... read more may gain weight, be lethargic, and develop dermatologic abnormalities.
Dogs with hyperadrenocorticism Cushing Syndrome (Hyperadrenocorticism) Cushing syndrome refers to any cause of elevated cortisol concentrations. Pituitary-dependent hyperadrenocorticism (PDH; Cushing disease) is the most common form of hyperadrenocorticism and... read more (Cushing syndrome) typically show polyphagia, polyuria, and polydipsia, often accompanied by hair loss. Dogs with typical hypoadrenocorticism (Addison disease Addison Disease Addison disease (hypoadrenocorticism) results from the lack of glucocorticoids, mineralocorticoids, or both. Isolated aldosterone insufficiency appears to be very rare, whereas isolated glucocorticoid... read more ) show nonspecific signs such as lethargy, inappetance, and weight loss.
Diagnosis of Endocrine Diseases in Animals
Clinical evaluation
Clinicopathologic testing
Endocrinologic testing
A thorough history and a complete physical examination are critical elements in the diagnosis of endocrine disease. Routine biochemical and CBC tests are mandatory in the initial evaluation.
The results of examination and testing should lead to formulation of differential diagnoses. Specific hormone tests Measurement of Hormones in Animals Because hormones circulate in low quantities in blood, their accurate measurement requires sensitive assays, usually in the form of a competitive immunoassay. The original method is radioimmunoassay... read more (eg, thyroid, adrenal) that are based on the likelihood of possible differential diagnoses should then be performed to confirm (or reject) specific diagnoses.
Treatment of Endocrine Diseases in Animals
Surgical intervention
Medical treatment
Radiotherapy
Dietary therapy
Hormone replacement therapy
Hormone deficiency can be treated by replacement of the hormone (eg, insulin treatment in diabetes mellitus or thyroid hormone replacement therapy in hypothyroidism). Some protein and polypeptide hormone deficiency syndromes can be difficult to treat because of the cost and limited availability of the hormone.
Endocrine diseases involving hyperactivity may potentially be treated by surgical intervention (eg, tumor removal, as in thyroidectomy for feline hyperthyroidism Hyperthyroidism in Animals Hyperthyroidism is characterized by hypermetabolism and high circulating thyroid hormone concentrations. Clinical features include weight loss despite a good appetite. Treatment depends on the... read more ), by radiotherapy (eg, radioactive iodine [I 131] for feline hyperthyroidism), by medical intervention (eg, methimazole as an antithyroid drug), or by modifications in the diet (eg, iodine-deficient diet for feline hyperthyroidism).
Hormone replacement therapy for deficiencies related to protein and polypeptide hormones can present a challenge. Often, the species-specific version of the hormone is not available, the drug may need to be injected several times per day, or the possibility of antibody formation and anaphylaxis must be considered.
Steroid and thyroid hormones can usually be administered orally. Some protein and polypeptide hormones or analogues are effective when given by routes other than injection (eg, the antidiuretic hormone analogue desmopressin acetate is effective when administered by a variety of routes).
Hormone replacement therapy should be monitored by assessment of clinical response and other suitable measures, such as therapeutic blood monitoring (eg, postpill measurement of T4 concentrations, measurement of sodium and potassium in serum in patients with primary hypoadrenocorticism [Addison disease]).
Hormone replacement therapy is often required for a time after surgical removal of an endocrine tumor. However, remaining normal tissue that atrophied as a consequence of the disease often recovers activity fairly quickly, obviating the need for lifelong hormone replacement therapy. Animals show marked variation in drug bioavailability; thus, a proper dosing schedule should be tailored to each patient.
Glucocorticoids Corticosteroids in Animals Two classes of steroid hormones, mineralocorticoids and glucocorticoids, are naturally synthesized in the adrenal cortex from cholesterol. (Also see The Adrenal Glands.) Mineralocorticoids ... read more are commonly used therapeutic drugs, particularly because of their anti-inflammatory and anti-allergic activity. Proper use requires an understanding of their adverse effects, including the potential appearance of signs of hyperadrenocorticism resulting from longterm treatment or from the use of potent derivatives. The adverse effects of longterm (> 2 weeks) glucocorticoid treatment can be diminished by use of an alternate-day treatment regimen. Once inflammation has been controlled using daily treatment with a drug that has intermediate duration of activity (eg, orally administered prednisolone or prednisone), a gradual change to alternate-day treatment can be made.
Key Points
Diagnosis of endocrine disease is based on a thorough history and physical examination, followed by general and then specific laboratory tests. Diagnostic imaging (eg, ultrasonography, scintigraphy) may also be helpful.
Treatment may be surgical, medical, or dietary and is usually intended either to suppress excess hormone secretion or to replace a deficient hormone.
In most cases, treatment and regular monitoring can be successful and result in a good prognosis and expected lifespan.
For More Information
Behrend EN. Update on drugs used to treat endocrine diseases in small animals. Vet Clin North Am Small Anim Pract. 2006;36(5):1087-1105, vii. doi:10.1016/j.cvsm.2006.05.007
American Animal Hospital Association: 2023 AAHA Selected Endocrinopathies of Dogs and Cats Guidelines
Behrend EN, Kooistra HS, Nelson R, Reusch CE, Scott-Moncrieff JC. Diagnosis of spontaneous canine hyperadrenocorticism: 2012 ACVIM consensus statement (small animal). J Vet Intern Med. 2013;27(6):1292-1304. doi:10.1111/jvim.12192
Gilor C, Graves TK. Diabetes mellitus in cats and dogs. Vet Clin North Am Small Anim Pract. 2023;53(3):xiii-xiv. doi:10.1016/j.cvsm.2023.02.018
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