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Summary

Pituitary pars intermedia dysfunction is a slowly progressive disorder that afflicts most breeds of horses. Because it shares features with human Cushing disease, it has been referred to as equine Cushing disease. A variety of tests of pituitary-adrenocortical function were performed on horses with evidence of pituitary pars intermedia dysfunction, and results were compared with those in healthy control horses. Diurnal variations in plasma cortisol concentration were not statistically different between control horses and those with pituitary pars intermedia dysfunction. An ACTH stimulation (1 U of natural ACTH gel/kg of body weight, IM) test or a combined dexamethasone suppression test (10 mg, IM) and ACTH stimulation (100 mg of synthetic ACTH, IV) test also failed to distinguish horses with pituitary pars intermedia dysfunction from control horses. A significant (P < 0.001) dose-related suppression of cortisol concentration in response to increasing doses (5, 10, 20, and 40 μg/kg) of dexamethasone was observed in control horses but not in those with pituitary pars intermedia dysfunction. On the basis of plasma cortisol concentration, the dexamethasone suppression test, using 40 μg/kg, whether initiated at 5 PM with sample collection at 15 (8 AM) and 19 (12 PM) hours after dexamethasone administration, or initiated at 12 AM with sample collection at 8 (8 AM), 12 (12 PM), 16 (4 PM), 20 (8 PM), and 24 (12 AM) hours after dexamethasone administration, reliably distinguished between control horses and those with pituitary pars intermedia dysfunction. Several horses did not have clinical evidence of pituitary pars intermedia dysfunction, but did have abnormal dexamethasone suppression test results. In these horses, adenomatous hypertrophy and hyperplasia of the pars intermedia of the pituitary gland was confirmed at necropsy.

Free access
in Journal of the American Veterinary Medical Association

SUMMARY

The role of prostaglandin F (pgf ) in embryonic loss following induced endotoxemia was studied in mares that were 21 to 44 days pregnant. Thirteen pregnant mares were treated with a nonsteroidal anti-inflammatory drug, flunixin meglumine, to inhibit the synthesis of pgf caused by Salmonella typhimurium endotoxin given iv. Flunixin meglumine was administered either before injection of the endotoxin (group 1, -10 min; n = 7), or after endotoxin injection into the mares (group 2, 1 hour, n = 3; group 3, 2 hours, n = 3); 12 pregnant mares (group 4) were given only S typhimurium endotoxin.

In group 4, the secretion of pgf , as determined by plasma 15-keto-13,14-dihydro-pgf concentrations, was biphasic, initially peaking at 30 minutes followed by a second, larger peak approximately 105 minutes after the endotoxin was given iv. When flunixin meglumine was administered at −10 minutes, synthesis of pgf was inhibited for several hours, after administration of flunixin meglumine at 1 hour, the second secretory surge of pgf was blocked, and administration of the drug at 2 hours did not substantially modify the secretion of pgf .

Plasma progesterone concentrations were unchanged after endotoxin injections were given in group 1. In group 2, progesterone values decreased < 2 ng/ml and remained low for several days. In group 3 and group 4, progesterone concentrations decreased to values < 0.5 ng/ml by 48 hours after endotoxin injections were given. Pregnancy continued in all 7 mares in group 1; in group 2, pregnancy continued in 2 of 3 mares; and in group 3, none of the 3 mares was pregnant by 4 days after endotoxin administration.

The abortifacient effect of endotoxemia in mares < 2 months pregnant is mediated indirectly through the secretion of pgf ; compromised luteal activity and inadequate progesterone secretion are the primary causes of fetal death. Although flunixin meglumine administration can be used to prevent loss of pregnancy in cases of endotoxemia, it must be initiated at an early stage of the endotoxemia, that is, when clinical signs are often not yet apparent.

Free access
in American Journal of Veterinary Research

SUMMARY

The role of decreased luteal activity in embryonic loss after induced endotoxemia was studied in mares 21 to 35 days pregnant. Fourteen pregnant mares were treated daily with 44 mg of altrenogest to compensate for the loss of endogenous progesterone secretion caused by prostaglandin F (pgf ) synthesis and release following intravenous administration of Salmonella typhimurium endotoxin. Altrenogest was administered daily from the day of endotoxin injection until day 40 of gestation (group 1; n = 7), until day 70 (group 2; n = 5), or until day 50 (group 3; n = 2).

In all mares, secretion of pgf , as determined by the plasma 15-keto-13,14-dihydro-pgf concentrations, followed a biphasic pattern, with an initial peak at 30 minutes followed by a second, larger peak at 105 minutes after endotoxin injection. Plasma progesterone concentrations decreased in all mares to values < 1 ng/ml within 24 hours after endotoxin injection.

In group 1, progesterone concentrations for all mares were < 1 ng/ml until the final day of altrenogest treatment. In 6 of 7 mares in group 1, the fetuses died within 4 days after the end of treatment, with progesterone concentrations < than 1 ng/ml at that time. In the mare that remained pregnant after the end of treatment, plasma progesterone concentration was 1.6 ng/ml on day 41 and increased to 4.4 ng/ml on day 44.

In group 2, all mares remained pregnant, even though plasma progesterone concentrations were < 1 ng/ml in 4 of 5 mares from the day after endotoxin injection until after the end of altrenogest treatment. One group-2 mare appeared to develop a secondary corpus luteum before day 70, with progesterone concentrations greater than 1 ng/ml from day 36 through day 70.

Daily altrenogest administration consistently prevented pregnancy loss, which usually follows induced endotoxemia. Altrenogest administration offers a reliable and practical treatment for the prevention of fetal loss following endotoxemia in mares < 2 months pregnant.

One group-3 mare remained pregnant, and in the other mare, fetal death was diagnosed 8 days after endotoxin administration, although this mare was still being treated with altrenogest. In that case fetal death was believed to be unrelated to the treatment.

Free access
in American Journal of Veterinary Research