AAEP 2002: Thyroid Function in Horses with Peripheral Cushing's Syndrome

Peripheral Cushing's syndrome (PCS) is seen in middle-aged horses with obesity-associated laminitis. These horses tend to accumulate fat in the crest of the neck, over the rump, and in the sheath of male horses. Researchers are trying to understand this recently named syndrome. It was first proposed that classic Cushing's disease--a disorder of the pituitary gland that leads to excessive cortisol levels in the blood--was causing the obesity-associated laminitis. Cortisol is primarily produced by the adrenal gland, and some of its main effects include stimulation of conversion of amino acids to glucose in the liver, elevation of blood sugar levels, and promotion of glycogen storage in the liver.

As a brief description, under normal circumstances, cortisol production is regulated by corticotropin-releasing hormone (CRH) release from the hypothalamus, which then stimulates adrenocorticotropic hormone (ACTH) release from the pituitary gland. ACTH in turn normally stimulates the release of cortisol. When there is enough cortisol in the bloodstream, CRH and ACTH secretion "backs off” through a negative feedback system. A significant and sustained rise in the level of cortisol circulating in the blood can result in clinical signs of classic Cushing's disease, such as a long, curly hair coat and laminitis. However, when tested for classic Cushing’s disease using the overnight dexamethasone suppression test (DST), these overweight, laminitic horses/ponies tested normally, i.e., had normal pituitary gland function.

In a presentation on "Thyroid Function in Horses with Peripheral Cushing's Syndrome," Emily Graves, VMD, of Michigan State University, discussed what researchers have recently discovered about how this disease works. Graves said that based on detection of low serum thyroid hormone concentrations in horses with suspected PCS, hypothyroidism (a deficiency in thyroid gland activity) has been implicated as a cause of the syndrome. Graves also said that PCS appears  to be a syndrome of increased cortisol action in peripheral tissues, such as skin, fat, and laminar tissue.

In a recent study, researchers at Michigan State University evaluated thyroid gland function in horses with peripheral Cushing's syndrome to see if thyroid function was normal or abnormal. They compared thyroid hormone responses to administration of thyrotropin-releasing hormone (TRH) in horses with obesity-associated laminitis and control horses with other musculoskeletal disorders. They confirmed their hypothesis that the thyroid gland functions normally in PCS-affected horses. Graves said their findings helped to rule out hypothyroidism as a risk factor for development of obesity-associated laminitis.

In addition, preliminary data indicate that oxoreductase activity of 11-beta hydroxysteroid dehydrogenase (HSD) is increased. This is an enzyme that converts inactive cortisone into active cortisol in the peripheral tissues throughout the body. This is analogous to a human disorder called central obesity or metabolic syndrome, in which elevated HSD action is the root of the disease. The human disorder is serving as a model for further characterization of PCS in horses and ponies.

Additional endocrine testing of PCS-affected horses also found elevated serum insulin concentrations. Graves said that based on the study, serum insulin concentration should be measured and combined with an overnight DST to evaluate and monitor horses with obesity-associated laminitis. An additional goal is to develop a test that measures HSD activity in body tissues. She commented that it is still not known if peripheral Cushing's syndrome-affected horses might be at a greater risk for development of classic Cushing's syndrome, or if horses with classic Cushing's syndrome have an elevated oxoreductase activity of laminar tissue HSD.

Graves said that more research is needed since this disease is still not well understood in equine species, and added that there could be multiple metabolic/endocrine disorders involved. She recommends that peripheral Cushing's syndrome-affected horses be treated with appropriate corrective trimming and shoeing, non-steroidal anti-inflammatory drugs for laminitis-associated pain, and that weight should be reduced through diet and exercise once laminitic pain is better controlled. She said that several horses treated in this manner have clinically improved and have shown a reduction in serum insulin concentrations.

Continued work is being done at the University of Missouri’s School of Veterinary Medicine. Researchers there, led by Philip Johnson, BVSc, are developing methods to measure activity of 11-beta HSD. As both the human and veterinary medical communities gain further knowledge of this disorder, improved treatment options should become available. Until that time, laminitis management and weight reduction in appropriate cases will be the mainstays of therapy.

About the Author

Sarah Evers Conrad

Sarah Evers Conrad has a bachelor’s of arts in journalism and equine science from Western Kentucky University. As a lifelong horse lover and equestrian, Conrad started her career at The Horse: Your Guide to Equine Health Care magazine. She has also worked for the United States Equestrian Federation as the managing editor of Equestrian magazine and director of e-communications and served as content manager/travel writer for a Caribbean travel agency. When she isn’t freelancing, Conrad spends her free time enjoying her family, reading, practicing photography, traveling, crocheting, and being around animals in her Lexington, Kentucky, home.

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