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Diagnosis and Medical Management of Endocrine Disorders in Aged Horses
N. Frank
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Aged horses are at risk for pituitary pars intermedia dysfunction (PPID), and insulin dysregulation (hyperinsulinemia and insulin resistance) is an underlying problem in some animals. Hyperinsulinemia and insulin resistance are exacerbated by PPID, and this increases the risk of laminitis. It is therefore recommended that all aged horses be screened for PPID and hyperinsulinemia and the magnitude of these problems be assessed. Endocrine disorders can be successfully managed in aged horses through appropriate husbandry and medical treatment. Author’s address: Department of Clinical Sciences, Tufts Cummings School of Veterinary Medicine, North Grafton, MA 01536 and School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, United Kingdom; e-mail: Nicholas.Frank@tufts.edu.
1. Introduction
Pituitary pars intermedia dysfunction (PPID) is the most important endocrine disorder of aged horses, with a prevalence rate of 21% recently reported for horses more than 15 years of age.1 Hyperinsulinemia and insulin resistance (IR), which can be collectively referred to as insulin dysregulation, are also concerns in aged horses and can occur concurrently with PPID. Hyperinsulinemia and IR are components of equine metabolic syndrome (EMS) and can remain an underlying problem for the life of the horse or pony. It is likely that EMS has a genetic basis, with the phenotype expressed in the younger animal if obesity is allowed to develop and/or later in life when PPID exacerbates the underlying condition. Equids with PPID can therefore either have lower insulin concentrations and normal insulin sensitivity or hyperinsulinemia and IR, and this can only be determined through diagnostic testing. Testing is highly recommended because hyperinsulinemia and laminitis are associated in equids, with evidence provided by epidemiological studies2,3 and experimental models.4,5 In this presentation, diagnostic testing for PPID, hyperinsulinemia, and IR are reviewed as well as medical treatments for these endocrine disorders.
2. Diagnostic Testing for PPID
When selecting a diagnostic test for PPID, the first question to ask is whether early or advanced disease is suspected. If the horse has advanced PPID, the disorder can be diagnosed on the basis of clinical signs alone. Hirsutism had 71% sensitivity and 95% specificity as a diagnostic test for PPID in horses with postmortem evidence of pituitary disease.6 Although hirsutism is considered pathognomonic for PPID in aged horses, care should be taken to consider the differential diagnoses of chronic systemic disease and malnutrition. Advanced PPID prolongs the anagen phase of hair growth and increases hair length, and the long haircoat of affected horses is better referred to as hypertrichosis rather than hirsutism.7 Although advanced PPID can be diagnosed on the basis of clinical examination alone, it is still advisable to measure adrenocorticotropic hormone (ACTH), glucose, and insulin concentrations before making treatment and diet recommendations.
Early PPID is more challenging to diagnose, and there are two tiers of testing. A plasma ACTH concentration can be measured as a screening test for early PPID.8 This is the simplest approach to diagnosing PPID, but clinicians are cautioned that some horses with early disease have normal results. To perform this test, a blood sample is drawn and submitted for measurement of ACTH. Plasma ACTH concentrations increase in the late summer and autumn9,10; therefore season-specific reference ranges have been established. It is also important to consider the assay used by the laboratory to measure ACTH and the familiarity of laboratory personnel with equine samples.
Blood is collected by means of jugular venipuncture into plastic tubes containing ethylenediaminetetraacetic acid. Tubes should be placed in a cooler with ice packs or refrigerated and centrifuged the same morning or afternoon of collection.
Interpretation: From November to July, a plasma ACTH concentration >35 pg/mL by chemiluminescent assay confirms the diagnosis of PPID. During the August to October period, an ACTH concentration >100 pg/mL strongly indicates that the horse has PPID, whereas a concentration of 50 to 100 pg/mL is a weak indication of disease. If clinical signs of PPID are present, this equivocal result should be interpreted as positive, and treatment is recommended. However, treatment should not be initiated in horses with ACTH concentrations within this range if there is no historical or clinical evidence of PPID. These horses should be monitored and rechecked in 3 to 6 months.
Because hormone concentrations naturally increase in the late summer and autumn, this time of year should be selected so that the physiological alterations serve as a natural stimulation test. Plasma ACTH concentrations increase in healthy horses during this period, and even higher peaks are detected in those with PPID. It should be noted that this is a new recommendation and reflects a shift in our approach to diagnosing PPID.
The thyrotropin-releasing hormone (TRH) stimulation test 11,12 is the second tier test for detecting early PPID. This test was developed by Dr Jill Beech at the University of Pennsylvania and is thought to be the most sensitive diagnostic test for PPID available at present. Although it is referred to as a second-tier test, it is also appropriate to perform this test as a first-tier approach. This is likely to become the recommended approach in the future because protirelin (synthetic TRH) is made available to practitioners by pharmacies. Testing is not recommended during the August-to-October period at present because season-specific cutoff values have not been established.
Fasting is not required for this test. A baseline (time = 0) blood sample is collected, and 1.0 mg (total dose) TRH is then administered IV as a bolus. A second blood sample is then collected 30 minutes later. Blood samples are handled as described above, and plasma is submitted for the measurement of ACTH concentrations.
Interpretation
- Baseline ACTH concentrations are interpreted as described above.
- Results are negative if ACTH concentration is < 35 pg/mL (chemiluminescent assay) at 30 minutes.
There is a strong indication of PPID if the ACTH concentration is > 75 pg/mL at 30 minutes when testing is performed from November through July. There is a weak indication of PPID if the ACTH concentration is between 35 and 75 pg/mL at 30 minutes when testing is performed from November through July.
- If accompanied by clinical signs, treatment is recommended.
- If there is no historical or clinical evidence of PPID, testing is repeated after 3 to 6 months.
Some clinicians prefer to collect the second blood sample at 10 minutes and interpret the results (November through July) as follows: Negative if <85 pg/mL, weak indication if 85 to 100 pg/mL, and strong indication if >100 pg/mL. Research to establish reference intervals is ongoing.
3. Diagnostic Testing for Hyperinsulinemia
Testing for hyperinsulinemia is recommended for all aged horses with clinical signs of endocrine disorders or laminitis. The author also recommends screening horses for hyperinsulinemia as part of routine health checks in the same way that humans are screened for hypercholesterolemia. High-risk populations for hyperinsulinemia include pony, Morgan horse, Paso Fino, and Arabian breed groups, as well as any horse with generalized obesity or obvious regional adiposity. Aged horses are placed in the high-risk category if PPID is developing or there is a history of EMS.
Fasting insulin concentrations were previously recommended as the diagnostic test for hyperinsulinemia in horses,13 but this recommendation has changed recently. When fasting insulin concentrations are measured, a cutoff value of 20 µU/mL is recommended for the general population if the radioimmunoassay is used. Breed-specific reference ranges are also being developed. [...]
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About
Affiliation of the authors at the time of publication
Department of Clinical Sciences, Tufts Cummings School of Veterinary Medicine, North Grafton, MA 01536 and School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, United Kingdom
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