Merck Manual

Please confirm that you are a health care professional

honeypot link
Professional Version

Cushing Syndrome (Hyperadrenocorticism)


David Bruyette

, DVM, DACVIM, Anivive Lifesciences, Inc.

Reviewed/Revised Apr 2019 | Modified Oct 2022
Topic Resources

Cushing syndrome refers to any cause of elevated cortisol concentrations. Pituitary-dependent hyperadrenocorticism (PDH; Cushing disease) is the most common form of hyperadrenocorticism and accounts for 80%-85% of reported cases. Adrenal-dependent hyperadrenocorticism occurs when a unilateral or bilateral adrenal tumor -secretes cortisol and accounts for 10%-15% of cases. Less common causes of hyperadrenocorticism include ectopic secretion of ACTH, episodic Cushing disease, meal induced, and "atypical" manifestations.

The most common clinical signs of hyperadrenocorticism include polyuria and polydipsia, weight gain. endocrine alopecia, muscle atrophy, and a "pot-bellied" appearance. Common laboratory abnormalities include elevations in serum alkaline phosphatase and decreased urine concentrating ability. Diabetes mellitus and/or insulin resistance can be seen in as many as 15% of canine cases. The initial steps in the diagnosis of hyperadrenocorticism include an accurate history, thorough physical examination, and screening laboratory tests (CBC, chemistry panel, urinalysis). Once other causes for the clinical signs have been ruled out, specific adrenal function tests are performed to confirm hyperadrenocorticism and differentiate between the various causes.

Cushing syndrome (hyperadrenocorticism) may be the most frequent endocrinopathy in adult to aged dogs but is infrequent in other domestic animals. More recently, publications have highlighted the incidence, clinical presentation, diagnostic approach, and treatment options for hyperadrenocorticism in cats as well. Hyperadrenocorticism is the second-leading cause of insulin resistance in diabetic cats after acromegaly. The clinical signs and biochemical abnormalities result primarily from chronic excess production of cortisol. Increased cortisol levels in dogs may result from one of several mechanisms. The most common is an adenoma or hyperplasia of the ACTH-containing cells of the pituitary gland (pars distalis or pars intermedia), which results in bilateral adrenal cortical hypertrophy and hyperplasia. This form of the disease is referred to as pituitary-dependent hyperadrenocorticism (Cushing disease) and is seen in ~90% of cases.

Functional adrenal tumors, a far less frequent cause of hyperadrenocorticism in dogs, may secrete cortisol or sex steroids, resulting in a variety of clinical signs. Many of the clinical signs and biochemical abnormalities seen with naturally occurring hyperadrenocorticism can be induced by longterm, daily administration of large doses of corticosteroids. Dogs develop a spectrum of clinical signs and laboratory abnormalities as a result of the combined gluconeogenic, lipolytic, protein catabolic, and anti-inflammatory effects of the glucocorticoid hormones on many organ systems. The disease is insidious and slowly progressive. (For discussion of the clinical signs, laboratory abnormalities, diagnosis, and treatment of hyperadrenocorticism, see The Pituitary Gland The Pituitary Gland .)

For More Information

quiz link

Test your knowledge

Take a Quiz!