Endocrine diseases are common in animals. They are more frequently diagnosed and treated in companion animals (dogs or cats) than in large animal species. Clinical signs and treatments vary substantially, depending on which organ system is affected and whether the etiology is an excess or a deficiency of hormone.
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).
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 in dogs or hyperthyroidism in cats), or neoplasia at a secondary site that in turn stimulates excess hormone secretion (eg, pituitary-dependent hyperadrenocorticism [Cushing disease] 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 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).
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, type I diabetes mellitus, primary hypoparathyroidism, and primary hypoadrenocorticism (Addison disease).
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 type II).
Nephrogenic diabetes insipidus 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, hyperadrenocorticism [Cushing syndrome]) 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 show polyphagia in the face of weight loss. Dogs with hypothyroidism may gain weight, be lethargic, and develop dermatologic abnormalities.
Dogs with hyperadrenocorticism (Cushing syndrome) typically show polyphagia, polyuria, and polydipsia, often accompanied by hair loss. Dogs with typical hypoadrenocorticism (Addison disease) 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 (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), 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 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
Also see pet health content regarding hormonal disorders in dogs, cats, and horses.
