IN-DEPTH: ENDOCRINOLOGY IN GERIATRICS


the conclusion that laminitis could occur without pro-inflammatory and intestinal conditions; fitting in with the term, endocrinopathic laminitis, that had been coined a few years earlier.17


Endocrinopathic Laminitis


There are two main conditions associated with en- docrinopathic laminitis, PPID and equine metabolic syndrome (EMS). Common to both these condi- tions appears to be the development of insulin dysregulation. Insulin dysregulation results in hyperinsulinemia (either basally, or in association with the ingestion of carbohydrates in forages and feeds).18 PPID is a disease of aged horses characterized by


loss of dopaminergic inhibition of the pituitary pars intermedia and resultant overproduction of pitu- itary hormones (adrenocorticotropin [ACTH], alpha melanocyte–stimulating hormone, beta endorphin, and corticotropin-like intermediate peptide [CLIP]). The resultant clinical syndrome is variably associ- ated with a wide array of clinical signs including hypertrichosis and abnormal hair-shedding patterns, laminitis, muscle wastage, abnormal fat distribution, polyuria and polydipsia, increased susceptibility to in- fections, and infertility.19 EMS has been defined in the 2010 American College of Veterinary Internal Medicine (ACVIM) consensus statement as a pheno- type of obesity (regional or generalized), insulin resistance (hyperinsulinemia or abnormal insulin and glucose regulation; now known as insulin dys- regulation18) and a predisposition to laminitis that has developed in the absence of recognized causes such as grain overload, colic, colitis, or retained placenta.20


Laminitis and PPID


Laminitis has been frequently diagnosed in horses with PPID and laboratory submissions suggest it is a common trigger for horse owners to request veter- inary investigation of cases of PPID.21 On pooled analysis from 13 studies, laminitis was the second most common clinical sign in horses with PPID (49%), second only to hypertrichosis (70%).22 Horses with PPID have 4.65 times the odds of developing laminitis compared with aged matched controls.23 Yet laminitis occurs variably in stud- ies from 8% to 82%.22 This finding may seem con- flicting, but can be explained by a number of factors. First, it seems that insulin dysregulation is key to development of laminitis in PPID-affected horses. This is supported by histological research that showed that laminar lesions only occurred in horses with PPID and hyperinsulinemia, and not in horses with PPID but normal basal insulin concentra- tions.24 An epidemiological study demonstrated that over a third of horses with PPID had hyperin- sulinemia, and 67% of horses with PPID and lami- nitis had basal hyperinsulinemia.23 Horses with PPID were 2.7 times more likely to have hyperinsu- linemia than aged matched controls.23 However,


184 2018  Vol. 64  AAEP PROCEEDINGS


when basal hyperinsulinemia occurred in PPID or non-PPID aged horses, they were equally at risk for developing laminitis.23 Secondly, even when horses are insulin dysregu-


lated, laminitis may not produce clinical lameness. Histological research in naturally occurring cases of endocrinopathic laminitis showed no relationship between the duration of clinical lameness and the degree of pathology found histologically, but did identify the consistent presence of hoof capsular changes in association with the histopathology such as divergent hoof rings.25 This was sup- ported by epidemiological research in aged horses where hoof abnormalities indicative of chronic lami- nitis (including dropped soles, laminitic rings, and separated white lines) were more prevalent than a history of laminitis.23,26 This implies that horses can have repeated subclinical bouts of laminitis without lameness, which may not be identified or may not be considered significant by horse owners. Third, the presentation of horses with PPID for veterinary attention requires the recognition of the clinical signs of PPID by their owners. Epidemio- logical research has shown that many of the clinical signs of PPID are considered normal signs of aging by horse owners, including hypertrichosis and mus- cle atrophy.27 Indeed, in one study, only 1.6% of horse owners reported their horses with PPID, yet 21.2% tested positive on seasonally adjusted basal ACTH measurements.23 This may well explain the large category of “unknown” laminitis cases back in the 1990s when horse owners were asked to identify the causes of laminitis in their horses.9 Laminitis, at least where it causes lameness, is more likely to result in horses being presented for veterinary at- tention; therefore, if research studies or case se- ries used owner-presented animals for inclusion in studies, the prevalence of laminitis is likely to be higher.21,22


Insulin Dysregulation and Laminitis


It is now well established that hyperinsulinemia associated with insulin dysregulation causes lamin- itis in affected horses, especially when challenged by dietary carbohydrates. Laminitis has been linked to insulin resistance and hyperinsulinemia in field studies since the 1980s.7,8,15,16,28 Experimental re- search has shown a direct link between hyperinsu- linemia and laminitis.12,13 Laminitis was induced in 100% of normal ponies12 or horses13 exposed to high concentrations of insulin ( 1000 IU/mL) while maintaining euglycemia of 5 mmol/L using a modified euglycemic-hyperinsulinemic clamp tech- nique. All treated ponies or horses were healthy, young, and non-obese, with no history of laminitis and no evidence of endocrine or other abnormalities on blood tests. Laminitis occurred slowly and in all 4 limbs, with the onset of lameness associated with laminitis (Obel grade 2) occurring by approximately 48 hours. There was no evidence of gastrointesti-


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