VCA West Los Angeles Animal Hospital
By David Bruyette, DVM, DACVIM
Published: March 28, 2011

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As part of our ongoing studies of Cushing's Syndrome in the dog we are now offering transsphenoidal surgery for dogs and cats with functional (ACTH and growth hormone) and non-functional pituitary tumors.

Pituitary dependent hyperadrenocorticism (PDH) is caused by unregulated and excess production of cortisol in the adrenal glands, in response to excess ACTH production from pituitary tumors (adenoma). The resultant hypercortisolemia causes bodily changes such as severe polyuria and polydipsia, alopecia, weight gain, high blood pressure, diabetes, osteoporosis, and behavioral disturbance. PDH is progressive and may be fatal if untreated. In humans, PDH is a very rare disease, occurring in approximately 1 in every 1 million persons. Interestingly, while PDH is rare in humans, it is extremely common in dogs. It is estimated that PDH occurs in up to 100,000 dogs yearly in the US, making it one of the most common hormone-related disorders in dogs.

Several medical treatments are available for treatment of PDH in dogs with a far fewer number approved for treatment in humans. Medical treatment options in the dog include drugs that chemically destroy the adrenals (lysodren; op-DDD), inhibit enzymes in the adrenal leading to the synthesis of cortisol (ketoconazole, trilostane) or inhibit the release of ACTH from the pituitary gland (Anipryl or selegiline, cabergoline, retinoic acid). While these treatments can improve the clinical signs in 40-80% of patients they need to be chronically administered, necessitate frequent monitoring and do not cure or address the primary cause of the disease (the pituitary tumor). In humans, transsphenoidal surgery to remove the tumor is the most successful long-term therapy. Surgical cure rates for PDH are reported to be in the range of 65-85%, although more recent long-term follow up data suggest that the recurrence rate is as high as 25 % within 5 years. Transsphenoidal hypophysectomy has also been successfully employed in dogs, with long-term remission rates similar to humans. However, these surgeries have generally not been performed in the US due to a lack of expertise and the relative cost of surgery compared with medical therapy. Further, the techniques described by groups outside the US do not employ the use of surgical microscopes or other devices to improve illumination and magnification, making these surgeries technically challenging and difficult to be adopted on a large scale basis. Veterinarians at the VCAWLAAH, in collaboration with physicians and scientists at Cedars-Sinai, have recently developed the instrumentation and methods to perform these surgeries in dogs and cats using a high definition video camera and rigid telescope lens technology. These techniques should improve the safety and efficacy of these procedures.

A secondary but equally important aspect of this work is the opportunity to establish a repository for pituitary tumor tissue. In humans the tumors that cause PDH are usually very small, with over 70% being less than 10mm in size. MRI is non-diagnostic in up to 40% of cases. Due to the small size of the tumors in humans, very little tissue can be preserved for analysis, and this limitation has impeded knowledge about tumorigenesis and tumor behavior. In contrast, tumors in dogs and cats tend to be large in size and easily detected by MRI or CT.Therefore this tissue can be preserved in a repository following the surgery for subsequent analysis, and correlated with laboratory assessments and other clinical evaluations in the dogs and cats. This should prove invaluable to better understand the nature of pituitary disease and the development of alternate treatment strategies in humans, dogs and cats. This information will be used to develop new medical treatment options. Therapies being investigated by our group include dopaminergic agonists, retinoids, somatostatin receptor ligands (SRL's) and combination therapies. Such medical therapies may prove useful as first line therapeutics for pituitary tumors or as adjunct therapies in conjunction with hypophysectomy.

We are very excited about this trial and its potential impact on the care of both pets and humans with pituitary tumors. This is truly an example of the concept of One Medicine with veterinarians, physicians, and basic science researchers working together towards one common goal.

If you have any questions or potential cases you would like to discuss please feel free to contact us at any time.

Sincerely,

David Bruyette, DVM, DACVIM - David.Bruyette@vcahospitals.com
Tina Owen, DVM, DACVS - Tina.Owen@vcahospitals.com

David Bruyette, DVM, DACVIM
Medical Director
VCA West Los Angeles Animal Hospital

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