Duration and magnitude of hypothalamic-pituitary-adrenal axis suppression caused by daily oral administration of a glucocorticoid was investigated, using an anti-inflammatory dose of prednisone. Twelve healthy adult male dogs were given prednisone orally for 35 days (0.55 mg/kg of body weight, q 12 h), and a control group of 6 dogs was given gelatin capsule vehicle. Plasma cortisol (baseline and 2-hour post-ACTH administration) and plasma ACTH and cortisol (baseline and 30-minutes post corticotropin-releasing hormone [CRH] administration) concentrations were monitored biweekly during and after the 35-day treatment period. Baseline plasma ACTH and cortisol and post-ACTH plasma cortisol concentrations were significantly (P < 0.05) reduced in treated vs control dogs after 14 days of oral prednisone administration. By day 28, baseline ACTH and cortisol concentrations remained significantly (P < 0.05) reduced and reserve function was markedly (P < 0.0001) reduced as evidenced by mean post-CRH ACTH, post-CRH cortisol, and post-ACTH cortisol concentrations in treated vs control dogs. Two weeks after termination of daily prednisone administration, significant difference between group means was not evident in baseline ACTH or cortisol values, post-CRH ACTH or cortisol values, or post-ACTH cortisol values, compared with values in controls. Results indicate complete hypothalamic-pituitary-adrenal axis recovery 2 weeks after oral administration of an anti-inflammatory regimen of prednisone given daily for 5 weeks.

Adrenocortical function was assessed in 27 Beagle pups at 2, 4, 6, 8, 10, and 12 weeks of age by determination of plasma sodium, potassium, and chloride concentrations; serum aldosterone and cortisol concentrations; and plasma ACTH concentrations. Serum cortisol concentration was measured before and 1 and 2 hours after IM administration of 2.2 IU of ACTH/kg of body weight. Serum progesterone concentration also was determined for all pups at 2, 4, and 6 weeks of age. Mean baseline cortisol concentration was lower for pups 8 weeks old or younger than for mature dogs. Nevertheless, mean serum ACTH-stimulated cortisol concentration in dogs of all age groups increased into the adult reference range after administration of ACTH. For pups 4 weeks old or younger, increase in cortisol concentration was maximal at 2 hours after ACTH administration. However, in pups between 6 and 12 weeks of age, the increase in cortisol concentration was maximal 1 hour after ACTH administration in about a third of the pups, whereas the remaining pups had peak values at 2 hours. Mean plasma sodium, potassium, and chloride concentrations for each age group were within the reference ranges established for mature dogs, with the exception of lower mean plasma sodium and chloride concentrations in pups 4 weeks old or younger. Mean serum aldosterone concentration in pups of each age group was substantially higher than the range of aldosterone concentrations for clinically normal mature dogs. Median progesterone concentration was uniformly less than 0.2 ng/ml for all pups 6 weeks old or younger. The normal endogenous ACTH concentration and adequate cortisol responses to exogenous ACTH seen in our pups would support functional pituitary gland and adrenal cortex for cortisol production. The low baseline cortisol concentration observed in the pups of this study may be related to reduced binding of cortisol to plasma proteins, as exists in human infants.

The hypothalamic-pituitary-adrenocortical (HPA) axis was studied in 8 healthy cats after administration of supraphysiologic doses of methylprednisolone (MP). Ovine corticotropin-releasing hormone (oCRH) administration increased cortisol and adrenocorticotropic hormone (ACTH) concentrations. Significant (P < 0.05) suppression of cortisol and a trend toward suppression of ACTH was observed after 1 week of MP administration. The HPA axis quickly recovered from suppressive effects of MP 1 week after administration of the steroid was discontinued. Side effects of oCRH administration were minimal in 7 cats; however, 1 cat had a severe hypotensive reaction. Clinical abnormalities were not associated with MP administration. The HPA axis was suppressed by supraphysiologic doses of MP in all treated cats that lacked clinical signs consistent with iatrogenic HPA axis suppression. Despite the relatively active pars intermedia in cats, compared with human beings and dogs, feedback of MP on the HPA axis resulted in similar trends in oCRH-stimulated ACTH and cortisol concentrations as observed in human beings and dogs. Lack of consistent correlation between ACTH and cortisol concentrations was observed in 3 cats and possibly was related to the active pars intermedia in the cat.

Objective—To determine whether trilostane or ketotrilostane is more potent in dogs and determine the trilostane and ketotrilostane concentrations that inhibit adrenal gland cortisol, corticosterone, and aldosterone secretion by 50%. Sample—24 adrenal glands from 18 mixed-breed dogs. Procedures—Adrenal gland tissues were sliced, placed in tissue culture, and stimulated with 100 pg of ACTH/mL alone or with 5 concentrations of trilostane or ketotrilostane. Trials were performed independently 4 times. In each trial, 6 samples (1 for each time point) were collected for each of the 5 concentrations of trilostane and ketotrilostane tested as well as a single negative control samples. At the end of 0, 1, 2, 3, 5, and 7 hours, tubes were harvested and media and tissue slices were assayed for cortisol, corticosterone, aldosterone, and potassium concentrations. Data were analyzed via pharmacodynamic modeling. One adrenal slice exposed to each concentration of trilostane or ketotrilostane was submitted for histologic examination to assess tissue viability. Results—Ketotrilostane was 4.9 and 2.4 times as potent in inhibiting cortisol and corticosterone secretion, respectively, as its parent compound trilostane. For trilostane and ketotrilostane, the concentrations that inhibited secretion of cortisol or corticosterone secretion by 50% were 480 and 98.4 ng/mL, respectively, and 95.0 and 39.6 ng/mL, respectively. Conclusions and Clinical Relevance—Ketotrilostane was more potent than trilostane with respect to inhibition of cortisol and corticosterone secretion. The data should be useful in developing future studies to evaluate in vivo serum concentrations of trilostane and ketotrilostane for efficacy in the treatment of hyperadrenocorticism.

The possibility exists that rabbit hemorrhagic disease virus (RHDV) can be transmitted to swine, through lapinized hog cholera virus (HCV) vaccine. To investigate the infectivity of RHDV in swine, 16 four- to six-week-old piglets were inoculated subcutaneously with RHDV, and samples of liver, lung, spleen, kidney, bile, adrenal gland, tonsil, mesenteric lymph node, thymus, urine, buffy coat, and feces were collected from each of 2 animals on Days 0, 1, 2, 3, 5, 7, 14, and 28 post infection. Using reverse transcription-polymerase chain reaction, viral RNA was detected in most tissues by Day 3 and was absent after Day 5, except in lung and liver tissues, in which viral RNA was detected up to Day 14. Viral RNA was not detected in kidney, urine, feces or bile. Antibody responses, as detected by hemagglutination inhibition, were of low titer and short duration, and were similar in animals inoculated with viable RHD and in those given formalin-inactivated RHDV (n = 2). Neither viral RNA nor antibody were detected in the negative control or in the uninfected, in-contact animals.

Dexamethasone pharmacokinetics was studied in 10 healthy dogs receiving high-dose administration of dexamethasone (dosage, 0.1 mg/kg of body weight, IV), alone or combined with ACTH dosage, 0.5 U/kg, IV), or low-dose administration of dexamethasone (dosage, 0.01 mg/kg, IV) in an incomplete cross-over design. Serum samples were obtained at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, 480, 720, 1,080, 1,440, 1,920, 2,400, and 2,880 minutes after dexamethasone administration; dexamethasone was measured by radioimmunoassay validated for use in dogs. Dexamethasone pharmacokinetics was adequately described by a two-compartment first-order open model. Comparison of pharmacokinetics for the low- and high-dose protocols revealed dose dependence; area under the curve, mean residence time, clearance, and volume of distribution increased significantly when dexamethasone dosage increased, The elimination rate constant was significantly (P < 0.05) less, and the elimination half-life significantly greater for the high-dose protocols; however, the distribution rate constant and distribution half-life were not significantly different when high-dose protocols were compared with the low-dose protocol. Dose-dependent increases in volume of distribution and clearance may be related to saturation of protein-binding sites. Concurrent administration of ACTH did not affect dexamethasone disposition.

To evaluate the effect of exogenous testosterone on the development of T-2 toxin-induced necrosis of adrenal glands, mice were allotted to 3 treatment groups. Each treatment group contained castrated male, and castrated and sexually intact female mice. Each mouse in group 1 was given 0.16 mg testosterone propionate at 48-hour intervals for a total of 12 infections, group-2 mice were given similar injections of only the vehicle, and group-3 mice were given no treatment. Twenty-four hours after the last injection, the mice in all 3 groups were exposed for 10 minutes to an aerosol of T-2 toxin. All mice alive at 24 hours after exposure were euthanatized and the adrenal glands and thymuses were examined histologically. Necrosis of the adrenal cortex was not found in any of the mice given preexposure treatment with exogenous testosterone, whereas all mice given vehicle only or no treatment had T-2 toxin-induced necrosis of the inner portion of the adrenal cortex. Lymphocytolysis in the cortex of the thymus confirmed that each mouse of all 3 treatment groups had experienced systemic mycotoxicosis. The uniform severity of the lesion in all mice suggests that the thymus was not protected by exogenous testosterone administration or by the castration status of the mice. We propose that T-2 toxin-induced adrenal necrosis in mice is prevented by the presence of testosterone.

OBJECTIVE To investigate systemic changes following low-dosage prednisolone administration in dogs. ANIMALS 4 healthy purpose-bred adult male Beagles. PROCEDURES Dogs were administered prednisolone PO at a dosage of 2 mg/kg/d for 2 weeks, 1 mg/kg/d for 4 weeks, and 0.5 mg/kg/d for 3 weeks. Body weight, blood pressure, hepatic size and echogenicity, percentage of vacuolated hepatocytes, serum hepatic enzyme activities and glucose concentration, adrenal gland size, and pancreatic echogenicity were evaluated weekly for 9 weeks. RESULTS The only significant change identified was an increase in hepatic echogenicity, assessed by measuring liver-kidney contrast on ultrasonographic images. Increases in hepatic size and percentage of vacuolated hepatocytes were identified, but values did not differ from baseline values. Similarly, serum hepatic enzyme activities increased, but changes were mild and not significantly different from baseline values. Body weight, pancreatic echogenicity, and serum glucose concentration did not show noticeable changes. Mild systemic hypertension was seen, but blood pressure was not significantly different from the baseline value. Similarly, adrenal gland size steadily decreased during the first 6 weeks and increased again after the prednisolone dosage was decreased to 0.5 mg/kg/d. However, mean adrenal gland size was not significantly different from the baseline value at any time. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that in dogs, administration of prednisolone at a low dosage was associated with minimal systemic effects.