Pituitary pars intermedia dysfunction (PPID) is one of the most common equine endocrine disorders. It is caused by oxidative damage to dopaminergic neurons in the hypothalamus and results in loss of inhibition of the pituitary pars intermedia. This leads to increased circulating concentrations of adrenocorticotropic hormone (ACTH) and related peptides. Diagnosis is based on increased resting and/or thyrotropin releasing hormone-stimulated ACTH concentrations. Assessment of insulin regulation is also important, as insulin dysregulation occurs in at least one-third of PPID cases and is associated with laminitis risk. Management requires treatment with the dopamine agonist pergolide and an appropriate diet.
Magnesium (Mg) is a critical intracellular cation involved in energy metabolism, neuromuscular and cardiac stability, and endocrine regulation of calcium and potassium. In horses, Mg dysregulation is common in gastrointestinal disease, systemic inflammation and critical illness, yet often remains underdiagnosed. Hypomagnesemia contributes to ileus, cardiac arrhythmias, and refractory hypocalcemia or hypokalemia, whereas hypermagnesemia is rarely reported and typically iatrogenic. This review summarizes Mg physiology, regulation, clinical manifestations of Mg dysregulation, diagnostic approaches, and therapeutic strategies, with emphasis on equine-specific considerations.
Endocrinopathic laminitis is a consequence of persistent hyperinsulinemia, therefore insulin control is the key to prevention and effective treatment. This form of laminitis is commonly subclinical and therefore early diagnosis requires metabolic screening to establish risk and radiographic screening to detect early laminitic changes that may not yet be clinically apparent. Management changes can be used in conjunction with medication to control insulin and effectively prevent and treat endocrinopathic laminitis.
Dysregulation of energy metabolism occurs in horses and foals with transient systemic illness, malnutrition, or chronic metabolic diseases. The pathophysiologic processes resulting in energy dysregulation are important to interpret, understand, and appropriately monitor laboratory abnormalities associated with various disease states (hypoglycemia and hyperglycemia), as well as to aid in the management of energy dysregulation through nutritional and medical management.
Ultrasound is readily available to most practitioners and can be used in a straightforward manner to assess the liver. The liver can be assessed for size, shape, echogenicity, and architecture. Findings such as masses, cysts, granulomas, and biliary distention can be relatively specific as to suspected disease process. Other findings may be nonspecific but are useful to confirm concerns and aid in refining differential diagnosis. Findings should be interpreted considering the clinicopathologic picture and sampling performed when appropriate. Ultrasound can and should be used to identify optimal location for transcutaneous sampling.
Liver dysfunction may reduce the metabolism of drugs that undergo extensive hepatic processing. This will lead to reduced clearance and elimination, and can cause accumulation of the drug, increasing the risk of toxicity. Pentoxifylline and ursodeoxycholic acid are 2 pharmaceuticals that can provide benefits for a variety of equine hepatic diseases. Nutraceuticals are frequently used in horses with hepatopathy, targeting oxidative stress, inflammation, and hepatocellular injury. Neutraceuticals such as S-adenosylmethionine, silymarin and vitamin E are most commonly used although extensive research on their use is lacking. These therapies should be regarded as supportive rather than targeted treatments or cures.
Clinical signs associated with liver disease in horses are often a reflection of underlying hepatic dysfunction but typically vague rather than pathognomonic. Many observed clinical signs are subtle or not recognizable in the early stages of liver disease and thus may appear acute in onset despite an underlying chronic condition. Clinical signs reported in horses with liver disease include hyporexia or anorexia, weight loss, changes in demeanor, hepatic encephalopathy, colic signs, icterus, photosensitization, diarrhea, clinical coagulopathies, ascites, peripheral edema, steatorrhea, pruritus, polydipsia, and hemolysis. Here, we will review the reported incidence of clinical signs and their relevant pathophysiology.
Horses in racing and race training can develop high gamma-glutamyl transferase (GGT) syndrome (HGS), or increased GGT without overt evidence of primary liver disease. Current evidence points toward overtraining and a response to oxidative stress, but the etiology is incompletely understood. Evidence for an association of HGS with poor performance is mixed. Without a clear understanding of the etiology, the only evidence-based treatment option is rest or reduced training intensity. More research is needed to determine whether HGS is a physiologic adaptation, perhaps indicative of overtraining but not requiring direct intervention, versus a pathologic response that should be treated.
Liver disease in horses is primarily evaluated using the routine serum biochemical profile with a few additional specialty tests of liver function that are performed when indicated. Serum enzyme activities are evaluated to indicate hepatocellular damage and cholestasis. Liver function is evaluated using synthetic markers like BUN, albumin, bilirubin, and clotting times, while clearance function tests such as serum bile acids and ammonia are performed separately. Most equine liver disease is characterized by some degree of hepatocellular damage and cholestasis, while decreased liver function is less common because of the large reserve capacity of the organ.
Hepatic encephalopathy is a neurologic syndrome caused by hepatic insufficiency or portosystemic shunting, leading to the accumulation of ammonia and other neurotoxins. Clinical signs range from subtle behavioral changes to seizures and recumbency. Diagnosis relies on neurologic signs together with laboratory evidence of liver dysfunction, imaging, and sometimes biopsy. Importantly, hyperammonemia may occur without underlying hepatic dysfunction. Treatment focuses on addressing the underlying hepatic disease, reducing ammonia production and absorption, managing inflammation and cerebral edema, and providing supportive care. Prognosis varies widely and depends primarily on the underlying etiology, severity of hepatic damage, and response to therapy.
Since 2012, 2 viral causes of hepatitis have been identified in horses. Much remains to be discovered about their transmission, risk factors for clinical disease, diagnosis, and treatment approaches. Equine parvovirus-hepatitis has been identified as the cause of acute hepatic necrosis, previously known as Theiler's disease. Equine hepacivirus is recognized as a cause of chronic fibrosing hepatitis. Diagnosis relies on ruling out other causes of hepatitis and documenting infection by serum or liver polymerase chain reaction. There is no direct antiviral for either condition and treatments are symptomatic or aimed at ameliorating effects of liver failure and encephalopathy if present.
This review summarizes best practices for equine liver biopsy, including when to perform a biopsy, techniques for sample collection and handling, and strategies to optimize diagnostic yield. It discusses the interpretive framework used by pathologists, common diagnostic challenges, and prognostic scoring systems. Limitations such as sampling error and variability among observers are considered alongside ancillary testing, immunohistochemistry, and in situ hybridization. Emphasis is placed on the importance of communication between clinicians and pathologists to maximize diagnostic and prognostic value.
Equines are exposed to a variety of dietary phytotoxins, phytonutrients, pharmaceuticals, and other exogenous compounds (xenobiotics). The hepatobiliary system has major roles in xenobiotic metabolism and excretion and is of major importance in toxicology. Understanding possible sources of toxic compounds, circumstances of exposure, likely differentials, and diagnostic options can help practitioners arrive at a diagnosis in poisoning cases. Treatment of toxic hepatopathies is generally symptomatic and supportive. Antidotes and specific treatments rarely exist. Important exceptions are identification and removal of source material to prevent ongoing exposures and decontamination of recently exposed animals.
