Recipient Organization
TUFTS UNIVERSITY
200 WESTBORO ROAD
N. GRAFTON,MA 01536
Performing Department
Clinical Sciences
Non Technical Summary
Equine Cushing's disease is one of the most common diseases of horses greater than 15 years of age. The clinical signs are associated with abnormally elevated hormone concentrations in the blood and along with other hormones, cortisol, plays an important role in this disease. This syndrome is better defined as Equine Pituitary Pars Intermedia Dysfunction (PPID) because it reflects the location within the brain that is abnormal. In humans, Cushing's disease affects a different location within the pituitary gland, thus the reason why veterinarians prefer to call this disease PPID. The pituitary gland is located at the base of the brain. In horses with PPID, the middle lobe of the pituitary gland (so called pars intermedia) becomes enlarged over time and results not only in overproduction of hormones but can compress the adjacent structures in the pituitary and hypothalamus resulting in loss of their function. One of the major limitations of diagnostic testing for PPID is the sensitivity of available diagnostic tests. Of the tests available, the thyrotropin-releasing hormone (TRH) stimulation test is the most likely to detect the disease in an early stage. Unfortunately, TRH is not commercially available. This project will examine the efficacy of a compounded TRH product for use in the field.
Animal Health Component
(N/A)
Research Effort Categories
Basic
(N/A)
Applied
(N/A)
Developmental
(N/A)
Goals / Objectives
One of the major limitations of diagnostic testing for pituitary pars intermedia dysfunction (PPID) is the sensitivity of available diagnostic tests. The two most commonly used diagnostic tests, resting adrenocorticotropin hormone (ACTH) concentrations and the dexamethasone suppression test, can yield negative results in horses with early PPID. Of the tests available, the thyrotropin-releasing hormone (TRH) response test is the most likely to detect early PPID. Unfortunately, TRH is not commercially available and has to be prepared in the laboratory using a chemical purchased from a laboratory reagent supplier. This problem has limited the use of the TRH response test and left many horses with early PPID undiagnosed. One solution to this problem is to identify a source of TRH that will be available to all practitioners. A compounding pharmacy has prepared syringes containing TRH for use in the field. The proposed study will examine the efficacy of this product. Hypothesis: we hypothesize that TRH produced by a commercial compounding pharmacy is effective in stimulating ACTH release in horses with PPID. Specific Aims: 1) To compare the efficacy of compounded TRH with regular TRH in PPID testing. 2) To measure the repeatability of the TRH response test when two tests are performed sequentially.
Project Methods
Study design: Owners of horses with suspected or previously diagnosed PPID will be offered free diagnostic testing. Each horse will undergo two TRH response tests. One test will be performed with regular TRH prepared in our laboratory and the other with TRH supplied by a commercial compounding pharmacy. We will also administer regular TRH for two sequential tests to assess the repeatability of the results. Our two specific aims will be examined concurrently by having three treatment protocols (n=10 per group; 30 horses total): 1. Compounded TRH and then regular TRH 2. Regular TRH and then compounded TRH 3. Regular TRH for both tests TRH response testing: a pre-injection (baseline) blood sample will be collected followed by injection of TRH intravenously and then a second blood sample later. After a delay, testing will be repeated.