Evaluating seasonal influences on hormone responses to a diagnostic test advocated for early diagnosis of equine Cushing#s disease.

Rationale: Over the past decade the aged horse population has expanded significantly with 20-30% of the equine population comprised of geriatric horses (? 15 years). As a result there is a mounting demand for veterinary care and management of these aged horses. Unfortunately, one of the most common equine endocrinopathies, affecting 30% of older horses, is Equine Cushing's disease (ECD), also known as pituitary pars intermedia dysfunction (PPID). Clinical signs include hirsutism or now called hypertrichosis , muscle wasting, polyuria, polydipsia, abnormal sweating, laminitis, lethargy, pseudolactation, subfertility, and immunosuppression resulting in increased opportunistic infections. Early diagnosis of PPID is critical given the health risks associated with this condition. Horses with late-stage PPID are easier to diagnose, due to the presence of obvious clinical signs of generalized hypertrichosis however, early diagnosis of subclinical, suspect PPID horses requires sensitive diagnostic tests. A thyrotropin-releasing hormone (TRH) stimulation (stim) test was developed and is now considered to be the most sensitive test and is recommended for the assessment of horses if early PPID is suspected. However, the effects of season on the hormone responses to this dynamic test have not been evaluated in similarly managed groups of non-PPID, subclinical and clinical PPID horses in order to establish seasonal reference ranges for diagnosing PPID in subclinical horses. Hypothesis/Objectives: Our hypothesis is that season will affect hormone responses to the TRH stim test in non-PPID horses, subclinical and clinical PPID horses. Thus, the objective of this study is to evaluate the adrenocorticotropic hormone (ACTH) responses to the TRH stim test over a 12 month period in three different groups of horses: 1) non-PPID horses, 2) clinical PPID horses, and 3) subclinical, suspect PPID horses. Study Design: The TRH stim test, clinical evaluation, and a CBC/chemical profile will be performed once a month for a 12-month period using the same group of 60 horses, all of which are managed the same by the Gluck Center, and are currently characterized by one of the following: 1) non-PPID horses, both young adults (15 yrs) (n=15), 2) clinical PPID horses (>15 yrs) (n=22), and 3) subclinical, suspect PPID horses(>15 yrs) (n=23). The following defines each group of horses: group 1) non-PPID, defined by no classical signs of disease and normal endocrine tests (dexamethasone suppression test (DST), resting basal ACTH levels and low ACTH levels in response to the TRH stim test), group 2) clinical PPID horses, defined by one or more classical signs of disease and two or more abnormal endocrine test results (DST, basal ACTH or elevated ACTH in response to TRH), and group 3) subclinical, suspect PPID horses, defined by no hirsutism score and one or more abnormal endocrine test results ( basal ACTH or elevated ACTH in response to TRH). Classical signs of disease include: hirsutism and abnormal shedding, abnormal fat deposits over the tail head, lethargy, loss of epaxial muscle mass, pendulous abdomen, previous history of laminitis or recurrent infections. The TRH stim test will be performed during a three day period with random sampling of 20 horses each day from each of the three groups of horses. The TRH test will occur at the same time each day during each month and will consist of collecting plasma prior to administering TRH, followed by a single TRH i.v. injection (1mg) with plasma collected at 10 min and 30 min post TRH injection. Blood samples will be stored in the freezer (-80C) until analysis of ACTH. The clinical exam will performed by the same persons and will involve collecting temperature, heart rate, respiration and scoring of nasal discharge and signs of PPID. A Youden index value will be used to determine a cut-off value for each of the months being tested. Preliminary Data: We have recently collected data from the above PPID horses to begin evaluating the changes over time in ACTH responses to the TRH stim test. While we have just collected samples during the months of May and June, there was an overall trend for 'month' to have an impact on ACTH levels in response to the TRH stim test (P=0.269). Expected Results: We expect ACTH responses to the TRH stim to be influenced by the time of year in all groups of horses however we expect there to be significant changes in ACTH with season in subclinical and clinical PPID horses that will allow us to determine the range for PPID diagnosis. Budget & Timeline: $$95,167-Work will begin summer of 2014 and be completed in spring 2016.