Diagnosis and treatment of confirmed and suspected primary hyperparathyroidism in equids: 17 cases (1999-2016).

BACKGROUND: Primary hyperparathyroidism is uncommon in equids. OBJECTIVES: To describe the diagnostic findings and efficacy of treatment in equids with primary hyperparathyroidism. STUDY DESIGN: Retrospective case series describing 16 horses and one mule. METHODS: Cases were identified by retrospective review of records at Cornell University and via an ACVIM listserv query. Inclusion criteria were an equid with hypercalcemia, normal renal function and high parathyroid hormone (PTH) or histopathological diagnosis of a parathyroid adenoma. Equids with normal PTH and PTH-related protein (PTHrP) in the face of hypercalcemia were included as suspect cases. RESULTS: The most common presenting complaints were weight loss (12/17) and hypercalcemia (10/17). PTH was above reference range in 12/17 cases. Suspected parathyroid tumours were localised in 12/14 equids imaged using ultrasonography alone (2/3), technetium 99m Tc sestamibi scintigraphy alone (1/1) or both modalities (9/10). Three horses did not have imaging performed. Surgical exploration successfully excised tumours in six of 10 cases. Five were located at the thoracic inlet, and surgery resulted in complete cure. One tumour was excised from the thyroid lobe, and the horse remained hypercalcemic. Four other cases explored surgically, four treated medically and three that were not treated also remained hypercalcemic. MAIN LIMITATIONS: The small study size prohibited statistical analysis. CONCLUSIONS: Parathyroid adenomas in equids can be successfully localised with ultrasonography and scintigraphy. Surgical excision appears more likely to be successful for single gland disease at the thoracic inlet.

Presumed Neuroglycopenia Caused by Severe Hypoglycemia in Horses.

BACKGROUND: Neuroglycopenia refers to a shortage of glucose in the brain resulting in neuronal dysfunction and death if left untreated. Presumed neuroglycopenia has not been described in horses. OBJECTIVE: To report neurological signs in horses with presumed neuroglycopenia as the result of severe hypoglycemia. ANIMALS: Ninety horses (hours to 28 years of age) diagnosed with hypoglycemia (blood glucose concentration < 75 mg/dL [< 4.2 mmol/L]). METHODS: Retrospective study. Electronic medical records were searched. Signalment, history, complaint, clinical signs, laboratory findings including CSF analysis, electroencephalogram, clinical or definitive diagnosis, and outcome were recorded. Kruskal-Wallis analysis of variance and logistic regression were used to investigate association between blood glucose concentration and data extracted. Statistical significance was set at P < 0.05. RESULTS: Thirty-eight and 52 horses had mild (50-74 mg/dL [2.8-4.1 mmol/L]), and severe hypoglycemia (< 50 mg/dL [< 2.8 mmol/L]), respectively. Most common causes of hypoglycemia included liver and gastrointestinal (40%) disease, sepsis (33%), neoplasia (7%), and insulin-induced (4%). Most common neurologic deficits included obtundation (100%), seizures (42%), and disorientation (22%). CSF-glucose was severely low (mean 2.5 mg/dL [0.1 mmol/L], median 0 mg/dL). Paroxysmal discharges in support of seizures were identified in the occipital (visual) and parietal (closest to temporal-auditory) cortical regions upon EEG examination (8/8 horses). CONCLUSIONS AND CLINICAL IMPORTANCE: Neuroglycopenia is presumed to occur in horses as the result of severe hypoglycemia. Subclinical seizures, and intermittent blindness and deafness of cortical origin can occur. Severe altered state of consciousness and seizures can be observed at a blood glucose cut-off value of < 42 mg/dL (< 2.3 mmol/L).

Functional modelling of an equine bronchoalveolar lavage fluid proteome provides experimental confirmation and functional annotation of equine genome sequences.

The equine genome sequence enables the use of high-throughput genomic technologies in equine research, but accurate identification of expressed gene products and interpreting their biological relevance require additional structural and functional genome annotation. Here, we employ the equine genome sequence to identify predicted and known proteins using proteomics and model these proteins into biological pathways, identifying 582 proteins in normal cell-free equine bronchoalveolar lavage fluid (BALF). We improved structural and functional annotation by directly confirming the in vivo expression of 558 (96%) proteins, which were computationally predicted previously, and adding Gene Ontology (GO) annotations for 174 proteins, 108 of which lacked functional annotation. Bronchoalveolar lavage is commonly used to investigate equine respiratory disease, leading us to model the associated proteome and its biological functions. Modelling of protein functions using Ingenuity Pathway Analysis identified carbohydrate metabolism, cell-to-cell signalling, cellular function, inflammatory response, organ morphology, lipid metabolism and cellular movement as key biological processes in normal equine BALF. Comparative modelling of protein functions in normal cell-free bronchoalveolar lavage proteomes from horse, human, and mouse, performed by grouping GO terms sharing common ancestor terms, confirms conservation of functions across species. Ninety-one of 92 human GO categories and 105 of 109 mouse GO categories were conserved in the horse. Our approach confirms the utility of the equine genome sequence to characterize protein networks without antibodies or mRNA quantification, highlights the need for continued structural and functional annotation of the equine genome and provides a framework for equine researchers to aid in the annotation effort.

Plasma and pulmonary fluid endothelin in horses with seasonal recurrent airway obstruction.

BACKGROUND: Summer pasture-associated recurrent airway obstruction (SPA-RAO), a seasonal airway obstructive disease of horses, is characterized by clinical exacerbation after exposure to pasture during warm months of the year. Endothelin (ET)-1, potent bronchoconstrictor, mitogen, secretagogue, and proinflammatory mediator, has been implicated in the pathogenesis of asthma and equine heaves. HYPOTHESIS: Immunoreactive ET-1 concentrations increase during clinical exacerbation and return to basal values during periods of disease remission. ANIMALS: Twelve horses, 6 affected with SPA-RAO and 6 nonaffected. METHODS: Prospective, observational study. Bronchoalveolar lavage fluid (BALF), arterial and venous plasma samples, and clinical variables were obtained from affected horses during clinical exacerbation and remission. Samples and data of nonaffected horses were collected during the summer and winter on dates similar to affected horses. Immunoreactive ET-1 was determined using a commercial ELISA. RESULTS: The median and range ET-1 concentrations (pg/ml) in arterial (1.3, 0.7-1.8) and venous (1.3, 1.2-1.7) plasma and in BALF (0.3, 0.2-0.4), and pulmonary epithelial lining fluid (PELF) (25.5, 21-50) were greater in affected horses during clinical exacerbation compared with remission (P < .01). The concentrations of immunoreactive ET-1 were greater in affected horses during clinical exacerbation compared with nonaffected horses (P < .05). CONCLUSIONS AND CLINICAL IMPORTANCE: During clinical exacerbation of SPA-RAO, ET-1 is increased in circulation and pulmonary secretions. Intervention with ET receptor antagonists should provide further information on the role of ET-1 in SPA-RAO.